![Genetic history of western European populations. All European populations derived from European hunter and gatherers, Anatolian farmers and Yamnaya pastoralists [77]. Pie charts indicate the respective percentages of the founding populations (A). A time axis of the past 10,000 years indicates the arrival of the different founding populations and schematically illustrates changes in the average percentage of SNPs rs12785878 and rs7940244 representing DHCR7 enzyme activity and skin lightening rs1426654 and rs16891982 (SLC24A5 and SLC24A2), respectively, in the European population [72,76] (B).](https://www.researchgate.net/publication/334851051/figure/fig8/AS:789691091656709@1565288436910/Genetic-history-of-western-European-populations-All-European-populations-derived-from_Q320.jpg)
![Evolutionary history of VDR. Anatomically modern human (homo sapiens) is compared with ten species (representing important steps in evolution [38,40,93]) for the homology of the respective VDR LBD. Axes on the right indicate, which of the species have bone metabolism, adaptive and innate immune system as well as energy metabolism. Please note that zebrafish (danio rerio) has two genes for VDR. The jawless fish sea lamprey (petromyzon marinus) exists since 550 million years and is the oldest known species expressing a VDR, which binds with high affinity 1,25(OH)2 D3 .](https://www.researchgate.net/publication/334851051/figure/fig11/AS:789693931220992@1565289113527/Evolutionary-history-of-VDR-Anatomically-modern-human-homo-sapiens-is-compared-with_Q320.jpg)
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Vitamin D and evolution: Pharmacologic implications
Abstract and Figures
Vitamin D3 is produced non-enzymatically when the cholesterol precursor 7-dehydrocholesterol is exposed to UV-B, i.e., evolutionary the first function of the molecule was that of an UV-B radiation scavenging end product. Vitamin D endocrinology started when some 550 million years ago first species developed a vitamin D receptor (VDR) that binds with high affinity the vitamin D metabolite 1α,25-dihydroxyvitamin D3. VDR evolved from a subfamily of nuclear receptors sensing the levels of cholesterol derivatives, such as bile acids, and controlling metabolic genes supporting cellular processes, such as innate and adaptive immunity. During vertebrate evolution, the skeletal and adaptive immune system showed in part interesting synchronous development although adaptive immunity is evolutionary older. There are bidirectional osteoimmune interactions between the immune system and bone metabolism, the regulation of both is under control of vitamin D. This diversity of physiological functions explains the pleiotropy of vitamin D signaling and opens the potential for various pharmacological applications of vitamin D as well as of its natural and synthetic derivatives. The overall impact of vitamin D on human health is demonstrated by the fact that the need for its efficient synthesis served in European hunter and gatherers as an evolutionary driver for increased 7-dehydrocholesterol levels, while light skin was established far later via populations from Anatolia and the northern Caucasus entering Europe 9000 and 5000 years ago, respectively. The later population settled preferentially in northern Europe and we hypothesize that the introduction of high vitamin D responsiveness was an essential trait for surviving dark winters without suffering from the detrimental consequences of vitamin D deficiency.
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... The vitamin D molecule has been synthesized by organisms since early in the evolutionary history of animals. This capability might have appeared about 1.2 billion years ago [40]. In early marine species, such as zooplankton and phytoplankton, sunlight mediated the production of vitamin D, which probably protected against DNA damage from ultraviolet B (UVB) exposure [41,42]. ...
... Next, the hydroxylation of 25OHD 3 in the kidneys leads to the production of biologically active 1α,25(OH) 2 D 3 (1α,25-dihydroxyvitamin D 3 ; calcitriol). This process is induced by 1α-hydroxylase (CYP27B1) [40], which was also found in several non-renal tissues in mammals, i.e., intestine, lung, skin, thyroid, osteoblasts and chondrocytes, immune system cells, and reproductive organs [48]. There are some differences in vitamin D 3 metabolism in fish. ...
... The first known species to express VDR with a high affinity to 1α,25(OH) 2 D 3 was a sea lamprey (Petromyzon marinus). In fact, since VDR appeared in this basal vertebrate species about 550 million years ago, other vertebrates from bony fish to mammals have also expressed VDR with the ability to interact with 1α,25(OH) 2 D 3 [40]. Despite the free hormone hypothesis that steroids enter target cells by passive diffusion, transmembrane proteins such as cubilin [57] and megalin/LRP2 (LDL receptor-related protein 2) [58] were suggested as participating in the endocytosis of 25OHD 3 bound with DBP, affecting its cellular uptake. ...
Recent studies have clearly shown that vitamin D3 is a crucial regulator of the female reproductive process in humans and animals. Knowledge of the expression of vitamin D3 receptors and related molecules in the female reproductive organs such as ovaries, uterus, oviduct, or placenta under physiological and pathological conditions highlights its contribution to the proper function of the reproductive system in females. Furthermore, vitamin D3 deficiency leads to serious reproductive disturbances and pathologies including ovarian cysts. Although the influence of vitamin D3 on the reproductive processes of humans and rodents has been extensively described, the association between vitamin D3 and female reproductive function in farm animals, birds, and fish has rarely been summarized. In this review, we provide an overview of the role of vitamin D3 in the reproductive system of those animals, with special attention paid to the expression of vitamin D3 receptors and its metabolic molecules. This updated information could be essential for better understanding animal physiology and overcoming the incidence of infertility, which is crucial for optimizing reproductive outcomes in female livestock.
... Vitamin D acts on the VDR in various tissues and cells of the human body. Many studies have shown that vitamin D not only participates in the traditional calcium and phosphorus metabolism, but also participates in immune regulation through a variety of mechanisms [1]. Their roles in many human diseases such as cancer, diabetes, hypertension, cardiovascular disease, autoimmune and skin diseases have also been widely studied [2]. ...
... VDR in addition to the kidney cells, intestinal epithelial cells, thyroid cells, bone cells and other traditional cells, but also exists in macrophages, NK cells, T cells, B-cells, and other immune cells [6][7][8]. Vitamin D not only participates in the metabolism of calcium, phosphorus and parathyroid hormone, but also regulates the innate immune response and adaptive immunity by various mechanisms [1,[9][10][11]. ...
... According to studies such as Zhang Yuanda [1], the level of 25-(OH) D3 in children with K D is significantly lower than that of healthy children. Considering that the decline in the level of 25-(OH) D3 is involved in the pathological process of KD. ...
Kawasaki Disease (KD), also known as mucocutaneous lymph node syndrome, is a kind of fever rash pediatric disease with systemic vasculitis as the main lesion. Its pathogenesis is not yet completely clear, the main pathological changes is systemic vasculitis, involving the small and medium-sized blood vessels of the body, especially coronary artery lesions are more obvious, can lead to coronary artery aneurysm, even serious sudden death. Because the disease can appear serious cardiovascular complications, has gradually attracted attention, in recent years, its incidence has gradually increased trend, has become one of the common pediatric acquired heart disease etiology. Vitamin D acts on the VDR in various tissues and cells of the human body. Many studies have shown that vitamin D not only participates in the traditional calcium and phosphorus metabolism, but also participates in immune regulation through a variety of mechanisms.
... Ця реакція є оборотною, а PreD 3 і VitD 3 співіснують. З еволюційної точки зору, спостереження про те, що виробництво VitD 3 суворо залежить від УФВ, проливає світло на стародавнє походження гормону, щонайменше 1,2 мільярда років тому, коли водорості почали виробляти холестерин [5]. Цей процес, ймовірно, розвинувся як механізм поглинання для захисту від УФВ-випромінювання, яке поглинається і розсіюється при перегрупуванні подвійних зв'язків [6]. ...
... У селективному епідермісі експериментальних тварин без VDR спостерігалась схильність до розвитку раку і порушення загоєння ран [15]. Крім того, дефіцит вітаміну D пов'язаний із запальними захворюваннями шкіри, а аналоги вітаміну D є ефективними при псоріазі -проліферативному запальному захворюванні шкіри [4,5]. ...
... Окрім відомої ролі вітаміну D у метаболізмі кальцію та кісток, за останні десять років були описані додаткові ефекти, особливо на імунну систему. З еволюційної точки зору, конкретні дослідження та дослідження всього генома продемонстрували, що стародавня і початкова роль вітаміну D полягала в регуляції генів, що беруть участь в енергетичному обміні [5]. Під час еволюції хребетних скелетна та імунна системи розвивалися одночасно, а вітамін D був центральною ланкою остеоімунних двонаправлених взаємодій [22]. ...
Vitamin D is a steroid hormone that plays a crucial role in maintaining normal bone condition and calcium homeostasis. In recent years, vitamin D has become a hot topic of endocrinological research, largely Due to the COVID-19 pandemic and the likely correlation between hypovitaminosis D and a high risk of chronic lung disease and associated mortality. Recent studies have shown that vitamin D exhibits a complex multistage metabolism and acts as a hormone on many extracellular targets. This review examines some new intriguing and as yet unclear aspects of vitamin D metabolism, such as new concepts of enzyme regulation, new pleiotropic effects of vitamin D receptor activation (VDR), and epigenetic effects. The mechanisms of vitamin D synthesis in the skin, its metabolism in the hepatic cytochrome P450 system, catabolism, metabolites and transport, gene control and epigenetic modulation are considered in Detail. In addition to the well-known role of vitamin D in calcium and bone metabolism, it has many pleiotropic extraskeletal effects, including potent effects on the immune system, cardiovascular system, adipose tissue and glucose/lipid metabolism, muscle and more. Experimental studies have shown that VDRs are expressed by cancer cell lines. Recent studies have shown a link between low levels of vitamin D and almost all aspects of the metabolic syndrome, such as type 2 diabetes, fasting blood glucose, hypertension, dyslipidemia, obesity and insulin resistance. Several studies have focused on the role of vitamin D in adipose tissue biology. In particular, a negative correlation between vitamin D and leptin or resistin is shown, as well as an inverse correlation with adiponectin. Recent studies in vitamin D-deficient mice have shown impaired secretion of glucose-stimulated insulin by pancreatic islets. Vitamin D is thought to play a role in the pathogenesis and progression of cancer, and vitamin D analogues can slow cancer progression and metastasis. It is concluded that vitamin D is a molecule with several endocrine, paracrine and autocrine effects on many tissues and organs, in addition to maintaining skeletal homeostasis. Research in this area, which aims to clarify the pleiotropy of many effects of vitamin D and its metabolites, continues.
... Vitamin D, a lipid-soluble secosteroid hormone, significantly influences the human body's metabolism and bone mineralization. 1,2 Vitamin D made in the skin (cholecalciferol) during ultraviolet-B (UVB) exposure of 7-dehydrocholesterol or vitamin D ingested in the diet (ergocalciferol) is biologically inactive and requires two sequential steps of hydroxylations. It is converted to its physiologically active form, 1,25OHD, after being hydroxylated in the liver to generate 25OHD. ...
... When 7-dehydrocholesterol in the skin is exposed to UV-B (290-320 nm), it will absorb the energy of the UV-B radiation resulting in previtamin D3, a molecule with unstable thermodynamics. Pre-vitamin D3 then rapidly isomerizes into vitamin D3. 1 Given the abundance of sunshine, it makes sense that those who live in tropical and subtropical regions would have higher vitamin D levels than those who reside in the fourseason areas. Nevertheless, several studies have reported a lack of vitamin D even in nations where people can obtain enough sun exposure, like China, Korea, Thailand, and India. ...
Background: Vitamin D (25(OH)D) is a fat-soluble secosteroid hormone that plays a major role in bone mineralization and other metabolic processes in the human body. A complex between biologically active vitamin D (1,25(OH)2D) and its receptor serves as a transcription factor for various genes involves in bone homeostasis. Several studies have been link vitamin D deficiency with a reduction in Bone Mineral Density (BMD), but the result was still conflicting. However, data regarding vitamin D deficiency in the Indonesian population are rarely available.Objective: The study aims to assess vitamin D status and its correlation with Bone Mineral Density (BMD) among Javanese elderly women.Methods: A cross-sectional study was conducted in 75 healthy Javanese elderly women aged 60-84 years old. Serum Vitamin D was measured by enzyme link immunoassay using 25(OH)D ELISA kit. BMD was measured by dual-energy X-ray absorptiometry (DXA).Results: Mean±SD serum 25(OH)D level of the study population was 14.97±6.6ng/mL, we found that 73.3% were vitamin D deficient and 26.7% did not. There is no correlation between vitamin D and BMD lumbar, femoral neck or T-score (p=0.064, -0.215; p=0.443, -0.090; and p=0.109, -0.187 respectively). Lower BMD lumbar, femoral neck and T-score was correlated with increased age (r=-0.238, p=0.040; r=-0.377, p=0.001; and r=-0.295, p=0.010 respectively) and decreased BMI (r=0.525, p=0.000; r=0.516, p=0.000; and r=0.520, p=0.000 respectively).Conclusion: From this study, we concluded that vitamin D deficiency was prevalent among Javanese elderly women. However, there is no correlation has been found between vitamin D status and bone mineral density in this population.
... Asimismo, más de 200 tipos de fitoesteroles han sido reportados (Uddin et al., 2015), y son el colesterol, el β-sitosterol, el campesterol y el estigmasterol los de más abundancia en el APC OxG. El colesterol es precursor de moléculas bioquímicamente activas como hormonas (Šošić-Jurjević et al., 2017), vitamina D (Prabhu et al., 2016;Hanel & Carlberg, 2020) y ácidos biliares (Hanel & Carlberg, 2020;Nuno et al., 2016;Zerbinati & Iuliano, 2017 APC OxG, llevada a cabo por Cenipalma, se determinaron concentraciones promedio de fitoesteroles desde 498,9 mg·kg -1 en el aceite del cultivar MxC (mínimo: 369,3 mg·kg -1; máximo: 654,2 mg·kg -1), hasta 710,2 mg·kg -1 en el aceite del híbrido CxD (mínimo: 500,2 mg·kg -1; máximo: 965,3 mg·kg -1) (Figura 17.4). No obstante, en el aceite del cultivar OxG BxD se han encontrado valores máximos de concentración de fitoesteroles cercanos a 2.085,7 mg·kg -1 (Tabla 17.1). ...
... Asimismo, más de 200 tipos de fitoesteroles han sido reportados (Uddin et al., 2015), y son el colesterol, el β-sitosterol, el campesterol y el estigmasterol los de más abundancia en el APC OxG. El colesterol es precursor de moléculas bioquímicamente activas como hormonas (Šošić-Jurjević et al., 2017), vitamina D (Prabhu et al., 2016;Hanel & Carlberg, 2020) y ácidos biliares (Hanel & Carlberg, 2020;Nuno et al., 2016;Zerbinati & Iuliano, 2017 APC OxG, llevada a cabo por Cenipalma, se determinaron concentraciones promedio de fitoesteroles desde 498,9 mg·kg -1 en el aceite del cultivar MxC (mínimo: 369,3 mg·kg -1; máximo: 654,2 mg·kg -1), hasta 710,2 mg·kg -1 en el aceite del híbrido CxD (mínimo: 500,2 mg·kg -1; máximo: 965,3 mg·kg -1) (Figura 17.4). No obstante, en el aceite del cultivar OxG BxD se han encontrado valores máximos de concentración de fitoesteroles cercanos a 2.085,7 mg·kg -1 (Tabla 17.1). ...
Este libro es fruto de más de una década de trabajo mancomunado entre investigadores y técnicos de Cenipalma y del gremio, y se presenta como un compendio de diferentes temáticas sobre este nuevo cultivo, que durante los últimos años se ha posicionado por su rápido crecimiento y adopción no solo en Colombia, sino también en países de Latinoamérica. El libro contiene una variada información sobre los híbridos OxG, su agronomía, procesamiento y usos. Esta publicación es propiedad del Centro de Investigación en Palma de Aceite, Cenipalma, por tanto, ninguna parte del material ni su contenido, ni ninguna copia del mismo puede ser alterada en forma alguna, transmitida, copiada o distribuida a terceros sin el consentimiento expreso de Cenipalma.
... Most likely, the first function of VDR was the regulation of energy metabolism [31]. Energy is essential for basically all biological processes, but particularly for the function of innate and adaptive immunity [32]. Vitamin D and its receptor obtained via the control of immunometabolism a modulatory role on immunity [33] (Figure 2). ...
... Most likely, the first function of VDR was the regulation of energy metabolism [32]. Energy is essential for basically all biological processes, but particularly for the function of innate and adaptive immunity [33]. ...
This year we are celebrating 100 years of the naming of vitamin D, but the molecule is, in fact, more than one billion years old [...]
... Before regulating the calcium endocrine system, ancient VDR functioned as a xenobiotic receptor mediating the degradation of marine biotoxins 2 . Evolutionary pressures led to the functional repurposing of the receptor with the acquisition of new roles including detoxification of endogeneous compounds, lipid metabolism, immunity and calcium homeostasis [13][14] . In humans, VDR retains the ability to detoxify toxic compounds such as the secondary bile acid, lithocholic acid (LCA) that binds and activate hVDR in the micromolar range 15 . ...
... The jawless fishes whose modern lampreys are descendants were first to diverge after the 1R WGD event and lampreys are considered to be the most basal vertebrates among extant organisms. As revealed by VDR gene repertoire analysis [33][34] , its function has evolved along with more complex animal species from detoxification response in the basal vertebrates to lipid metabolism, immunity and calcium homeostasis in higher vertebrates 14 . ...
... Previtamin D 3 is synthesized by solar exposure in the stratum Malpighii, which is composed of the stratum Basale and stratum Spinosum of the epidermis [64]. This region is principally where the epidermal 7-dehydrocholesterol reservoir is located ( Figure 2) [65]. This thermally unstable previtamin undergoes temperature-dependent isomerization over the course of three days after formation to become vitamin D 3 [66]. ...
Vitamin D is one significant prohormone substance in human organ systems. It is a steroidal hormone produced in the skin upon exposure to UVB rays. This paper presents a systematic review of the utilization of topical vitamin D, specifically cholecalciferol, calcipotriol, and tacalcitol, in the treatment of vitiligo. It considers the role of vitamin D in stimulating the synthesis of melanin and melanogenesis, which can help with the process of repigmentation. The inclusion of calcipotriol or tacalcitol in Narrowband Ultraviolet Phototherapy (NB-UVB) has shown the potential to enhance therapeutic outcomes for vitiligo. However, their effectiveness in combination with Psoralens Long Wave Ultraviolet Radiation (PUVA) and Monochromatic Excimer Light (MEL) treatment for vitiligo is limited. In contrast, combining topical corticosteroids with vitamin D analogues has demonstrated superior efficacy in treating vitiligo compared to using vitamin D analogues alone, while also providing the added benefit of reducing corticosteroid-related adverse effects. In addition, treating stable vitiligo with topical cholecalciferol and microneedling has shown success. Future studies are needed to ascertain an efficient method of administering vitamin D topically as an anti-vitiligo agent.
... Vitamin D is a lipid-soluble vitamin, acting as a pleiotropic hormone in most human tissues by regulating mineral homeostasis and various other biological functions, including effects on immunity. 18 The number of fractures, the number of people who get sick or die from them, and the cost to the community all come from the large number of people who have risk factors that only put them at a small risk. For example, most fragility fractures in the community happen to women with osteopenia (bone mineral density T score -2.5 to -1 SD) because they make up the biggest part of the community. ...
Introduction: Hip fractures are among the most common types of fractures that patients report with to emergency departments and orthopaedic trauma teams. Study showed association vitamin D and bone intensity. The aim: This article discusses association about hip fractures and vitamin D. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 218 articles, whereas the results of our search on SagePub brought up 109 articles. The results of the search conducted for the last year of 2013 yielded a total 88 articles for PubMed and 27 articles for SagePub. In the end, we compiled a total of 32 papers, 23 of which came from PubMed and nine of which came from SagePub. We included seven research that met the criteria. Conclusion: Research consistently shows a link between vitamin D and bone strength. This is related to the incidence of hip fractures.
... Vitamin D 3 was identified more than 100 years ago as the essential molecule preventing the bone malformation disorder rickets and was therefore termed a vitamin [1]. Since vitamin D 3 can be synthesized endogenously in UV-B exposed skin [2,3], the need for this vitamin classification is in part due to human migration from Africa to Northern latitudes in Europe, Asia and America over the past 50,000 years [4]. Above a latitude of 38 • N during winter, there is a period of 1-5 months in which no or insufficient amounts of UV-B reach the surface for vitamin D 3 synthesis. ...
Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D3 on health and disease. The appropriate design of studies is essential for their quality, successful execution, and interpretation. Randomized controlled trials (RCTs) are considered the “gold standard” for intervention studies. However, the most recent large-scale (up to 25,000 participants), long-term RCTs involving vitamin D3 did not provide any statistically significant primary results. This may be because they are designed similarly to RCTs of a therapeutic drug but not of a nutritional compound and that only a limited set of parameters per individual were determined. We propose an alternative concept using the segregation of study participants into different groups of responsiveness to vitamin D3 supplementation and in parallel measuring a larger set of genome-wide parameters over multiple time points. This is in accordance with recently developed mechanistic modeling approaches that do not require a large number of study participants, as in the case of statistical modeling of the results of a RCT. Our experience is based on the vitamin D intervention trials VitDmet, VitDbol, and VitDHiD, which allowed us to distinguish the study participants into high, mid, and low vitamin D responders. In particular, investigating the vulnerable group of low vitamin D responders will provide future studies with more conclusive results both on the clinical and molecular benefits of vitamin D3 supplementation. In conclusion, our approach suggests a paradigm shift towards detailed investigations of transcriptome and epigenome-wide parameters of a limited set of individuals, who, due to a longitudinal design, can act as their own controls.
... he different effects of vitamin D on physiological processes, metabolism, and immune system function have been well discussed [1]. Vitamin D 3 (cholecalciferol) and vitamin D 2 (ergocalciferol) are 2 major forms of vitamin D. At first, cholecalciferol is hydroxylated into 25-hydroxy cholecalciferol (25(OH) D 3 ) in the liver and then into the activated form of vitamin D 3 (1,25(OH) 2 D 3 ) in the kidneys [2]. ...
Background: The effects of vitamin D on the skeletal system, biological metabolism, and immune system function are well shown. Cholecalciferol (vitamin D2) and ergocalciferol (vitamin) are 2 major types of vitamin D. Vitamin D3 deficiency is worldwide and the intoxication induced by it is very rare.
Conclusion: Vitamin D3 is involved in calcium hemostasis. The effects of acute hypercalcemia on blood pressure were established. Hypercalcemia can elevate the blood pressure, and renal failure may predispose the individual to a hypertensive response. The clinical symptoms often associated with vitamin D3 intoxication are related to acute renal failure. Hypertension without acute renal failure symptoms can emphasize the relationship between acute hypercalcemia and hypertension.
... As an essential factor of bone metabolism [6,7], vitamin D (VD) is a necessary micronutrient for human physiological processes [8,9], which is mainly synthesized by human skin cells under the effect of ultraviolet radiation [10,11]. Furthermore, 7-dehydrocholesterol can convert to vitamin D3 (VD3) in the skin by ultraviolet light [12]. ...
Objectives
Periodontitis is accompanied by attachment loss and alveolar bone resorption. Vitamin D (VD) deficiency was closely associated with bone loss or osteoporosis. The study aims to investigate the potential relationship between different VD levels and severe periodontal attachment loss in American adults.
Methods
A cross-sectional analysis was conducted including 5749 participants in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. The association of periodontal attachment loss progression with total VD, vitamin D3 (VD3), and vitamin D2 (VD2) levels was assessed using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models.
Results
Based on the indicators of 5749 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by less total VD levels, or VD3 levels, as well as a lower poverty-income ratio (PIR). Total VD (below the inflection point: 111 nmol/L) or VD3 were negatively associated with the progression of attachment loss in each multivariable regression model. In threshold analysis, VD3 is linearly correlated with the progression of attachment loss (β = − 0.0183, 95% CI: − 0.0230 to − 0.0136). The relationship between VD2 and attachment loss progression was an S-shaped curve (inflection point: 5.07 nmol/L).
Conclusion
Increasing total VD (below 111 nmol/L) and VD3 levels may be beneficial to periodontal health. VD2 levels above 5.07 nmol/L were a risk factor for severe periodontitis.
Clinical relevance
The present study reports that different vitamin D levels may serve as different associations with periodontal attachment loss progression.
... The continual availability of sufficient D3 in conjunction with the pleiotropic distribution of VDRs, co-factors, and the associated signaling systems enables a healthy life [43,144]. The vitamin D control system-CYP450 enzymes that activate and degrade vitamin D and metabolites, PTH and FGF23-associated feedback mechanisms, and VDRs have evolved over millions of years [145]. This complex system has been fine-tuned through vertebrate evolution, resulting in genetic variants and nucleotide polymorphisms in modern humans [146,147]. ...
Vitamin D is essential for life—its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. Vitamin D deficiency increases the vulnerability and severity of type 2 diabetes, metabolic syndrome, cancer, obesity, and infections. The active enzyme that generates vitamin D [calcitriol: 1,25(OH)2D], CYP27B1 (1a-hydoxylase), and its receptors (VDRs) are distributed ubiquitously in cells. Once calcitriol binds with VDRs, the complexes are translocated to the nucleus and interact with responsive elements, up- or down-regulating the expression of over 1200 genes and modulating metabolic and physiological functions. Administration of vitamin D3 or correct metabolites at proper doses and frequency for longer periods would achieve the intended benefits. While various tissues have different thresholds for 25(OH)D concentrations, levels above 50 ng/mL are necessary to mitigate conditions such as infections/sepsis, cancer, and reduce premature deaths. Cholecalciferol (D3) (not its metabolites) should be used to correct vitamin D deficiency and raise serum 25(OH)D to the target concentration. In contrast, calcifediol [25(OH)D] raises serum 25(OH)D concentrations rapidly and is the agent of choice in emergencies such as infections, for those who are in ICUs, and for insufficient hepatic 25-hydroxylase (CYP2R1) activity. In contrast, calcitriol is necessary to maintain serum-ionized calcium concentration in persons with advanced renal failure and hypoparathyroidism. Calcitriol is, however, ineffective in most other conditions, including infections, and as vitamin D replacement therapy. Considering the high costs and higher incidence of adverse effects due to narrow therapeutic margins (ED50), 1α-vitamin D analogs, such as 1α-(OH)D and 1,25(OH)2D, should not be used for other conditions. Calcifediol analogs cost 20 times more than D3—thus, they are not indicated as a routine vitamin D supplement for hypovitaminosis D, osteoporosis, or renal failure. Healthcare workers should resist accepting inappropriate promotions, such as calcifediol for chronic renal failure and calcitriol for osteoporosis or infections—there is no physiological rationale for doing so. Maintaining the population’s vitamin D sufficiency (above 40 ng/mL) with vitamin D3 supplements and/or daily sun exposure is the most cost-effective way to reduce chronic diseases and sepsis, overcome viral epidemics and pandemics, and reduce healthcare costs. Furthermore, vitamin D sufficiency improves overall health (hence reducing absenteeism), reduces the severity of chronic diseases such as metabolic and cardiovascular diseases and cancer, decreases all-cause mortality, and minimizes infection-related complications such as sepsis and COVID-19-related hospitalizations and deaths. Properly using vitamin D is the most cost-effective way to reduce chronic illnesses and healthcare costs: thus, it should be a part of routine clinical care.
... Of note, in the absence of vitamin D, S. typhimurium infection of epithelial cells was sufficient to increase VDR protein expression and subsequent transcriptional activity. While the specific mechanisms involved are not clear, VDR activation by non-vitamin D ligands is not unprecedented; cholesterol derivatives (e.g., bile acids) can activate VDR [17]. ...
Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body’s first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.
... VDR evolved some 550 million years ago in a boneless vertebrate where, at that time, its evolutionary function was to control the metabolism in order to support the immune system of ancestral vertebrates with energy [74]. This was confirmed based on the genome-wide analysis of vitamin D signaling on the most investigated cell types of the immune system, i.e., THP-1/monocyte/ and PBMCs. ...
The importance of the prevention and control of non-communicable diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer, is increasing as a requirement of the aging population in developed countries and the sustainability of healthcare. Similarly, the 2013–2030 action plan of the WHO for the prevention and control of non-communicable diseases seeks these achievements. Adequate lifestyle changes, alone or with the necessary treatments, could reduce the risk of mortality or the deterioration of quality of life. In our recent work, we summarized the role of two central factors, i.e., appropriate levels of vitamin D and SIRT1, which are connected to adequate lifestyles with beneficial effects on the prevention and control of non-communicable diseases. Both of these factors have received increased attention in relation to the COVID-19 pandemic as they both take part in regulation of the main metabolic processes, i.e., lipid/glucose/energy homeostasis, oxidative stress, redox balance, and cell fate, as well as in the healthy regulation of the immune system. Vitamin D and SIRT1 have direct and indirect influence of the regulation of transcription and epigenetic changes and are related to cytoplasmic signaling pathways such as PLC/DAG/IP3/PKC/MAPK, MEK/Erk, insulin/mTOR/cell growth, proliferation; leptin/PI3K-Akt-mTORC1, Akt/NFĸB/COX-2, NFĸB/TNFα, IL-6, IL-8, IL-1β, and AMPK/PGC-1α/GLUT4, among others. Through their proper regulation, they maintain normal body weight, lipid profile, insulin secretion and sensitivity, balance between the pro- and anti-inflammatory processes under normal conditions and infections, maintain endothelial health; balance cell differentiation, proliferation, and fate; and balance the circadian rhythm of the cellular metabolism. The role of these two molecules is interconnected in the molecular network, and they regulate each other in several layers of the homeostasis of energy and the cellular metabolism. Both have a central role in the maintenance of healthy and balanced immune regulation and redox reactions; therefore, they could constitute promising targets either for prevention or as complementary therapies to achieve a better quality of life, at any age, for healthy people and patients under chronic conditions.
... Vitamin D is first transformed into 25-hydroxyvitamin D in the liver by the enzyme vitamin D-25-hydroxylase, and then into the active form 1,25-dihydroxyvitamin D [1,25(OH)2D] in the kidney by 25-hydroxyvitamin D-1-hydroxylase [59]. 1,25(OH)2D performs its physiological function in target tissues by attaching to the vitamin D receptor, resulting in the up-or down-regulation of a vast number of genes [60,61]. ...
Nutritional biomarkers can be used as important indicators of nutritional status and play crucial roles in the prevention as well as prognosis optimization of various metabolism-related diseases. Measuring dietary with the deployment of biomarker assessments provides quantitative nutritional information that can better predict the health outcomes. With the increased availability of nutritional biomarkers and the development of assessment tools, the specificity and sensitivity of nutritional biomarkers have been greatly improved. This enables efficient disease surveillance in nutrition research. A wide range of biomarkers have been used in different types of studies, including clinical trials, observational studies, and qualitative studies, to reflect the relationship between diet and health. Through a comprehensive literature search, we reviewed the well-established nutritional biomarkers of vitamins, minerals, and phytonutrients, and their association with epidemiological studies, to better understand the role of nutrition in health and disease.
... Vitamin D deficiency is common in certain regions of the globe because of climatic conditions (low sunlight), lifestyle (clothing or sunscreen), and improper diet (Aparna et al., 2018;Sizar et al., 2021). This oil-soluble vitamin plays multiple roles in human health and wellbeing, which have been discussed in detail elsewhere (Gil et al., 2018;Glade, 2013;Hanel & Carlberg, 2020;Hii & Ferrante, 2016;Holick, 2008;Hossein-nezhad & Holick, 2013;Lappe, 2011;Nair & Maseeh, 2012;Reichrath et al., 2008;H. Wang et al., 2017;White, 2013;Zmijewski, 2019). ...
Over the past few decades, vitamin D deficiency has been recognized as a serious global public health challenge. The World Health Organization has recommended fortification of foods with vitamin D, but this is often challenging because of its low water solubility, poor chemical stability, and low bioavailability. Studies have shown that these challenges can be overcome by encapsulating vitamin D within well‐designed delivery systems containing nanoscale or microscale particles. The characteristics of these particles, such as their composition, size, structure, interfacial properties, and charge, can be controlled to attain desired functionality for specific applications. Recently, there has been great interest in the design, production, and application of vitamin‐D loaded delivery systems. Many of the delivery systems reported in the literature are unsuitable for widespread application due to the complexity and high costs of the processing operations required to fabricate them, or because they are incompatible with food matrices. In this article, the concept of “Fortification by Design” is introduced, which involves a systematic approach to the design, production, and testing of colloidal delivery systems for the encapsulation and fortification of oil‐soluble vitamins, using vitamin D as a model. Initially, the challenges associated with the incorporation of vitamin D into foods and beverages are reviewed. The Fortification by Design concept is then described, which involves several steps: (i) selection of appropriate vitamin D form; (ii) selection of appropriate food matrix; (iii) identification of appropriate delivery system; (iv) identification of appropriate production method; (vii) establishment of appropriate testing procedures; and (viii) system optimization. This article is protected by copyright. All rights reserved
... Vitamin D is present in almost forms of life, from phytoplankton to humans, and is considered one of the oldest hormones on Earth [1][2][3]. In humans, the classic endocrine function of this powerful secosteroid is regulation of calcium-phosphorus homeostasis in order to maintain proper function of the body [4]. ...
Vitamin D shows a variety of pleiotropic activities which cannot be fully explained by the stimulation of classic pathway- and vitamin D receptor (VDR)-dependent transcriptional modulation. Thus, existence of rapid and nongenomic responses to vitamin D was suggested. An active form of vitamin D (calcitriol, 1,25(OH)2D3) is an essential regulator of calcium–phosphate homeostasis, and this process is tightly regulated by VDR genomic activity. However, it seems that early in evolution, the production of secosteroids (vitamin-D-like steroids) and their subsequent photodegradation served as a protective mechanism against ultraviolet radiation and oxidative stress. Consequently, direct cell-protective activities of vitamin D were proven. Furthermore, calcitriol triggers rapid calcium influx through epithelia and its uptake by a variety of cells. Subsequently, protein disulfide-isomerase A3 (PDIA3) was described as a membrane vitamin D receptor responsible for rapid nongenomic responses. Vitamin D was also found to stimulate a release of secondary massagers and modulate several intracellular processes—including cell cycle, proliferation, or immune responses—through wingless (WNT), sonic hedgehog (SSH), STAT1-3, or NF-kappaB pathways. Megalin and its coreceptor, cubilin, facilitate the import of vitamin D complex with vitamin-D-binding protein (DBP), and its involvement in rapid membrane responses was suggested. Vitamin D also directly and indirectly influences mitochondrial function, including fusion–fission, energy production, mitochondrial membrane potential, activity of ion channels, and apoptosis. Although mechanisms of the nongenomic responses to vitamin D are still not fully understood, in this review, their impact on physiology, pathology, and potential clinical applications will be discussed.
... Currently, other factors that alter the innate immune response and facilitate the infection and replication of the virus are being investigated. Some of these factors are environmental temperature and vitamin D3 defi ciency, as they affect highaffi nity nuclear receptors such as the Vitamin D Receptor (VDR) [29]. These receptors, when stimulated, favor cellular stress in response to an infection by microorganisms. ...
At the end of 2019, in Wuhan, China, an outbreak of cases of respiratory tract infection emerged and its progressive infection mainly affects adults, generating many cases of pneumonia. A type of coronavirus named SARS-CoV-2, with genomic similarity to SARS-CoV and MERS-CoV, was identified as the etiological agent. The evolution of this pandemic has made it possible to verify the similarity in the pathophysiological mechanisms between these three viruses, identifying the Angiotensin-Converting protein-Enzyme 2 (ACE2) as the primary receptor for SARS-CoV-2. This age group is more prone to developing extrapulmonary complications from SARS-CoV-2 since the clinical and pathological findings suggest a particular relationship between greater expression of ACE2 and the comorbidities of chronic degenerative diseases and the greater expression of ACE2 at the level of the respiratory tract. It has also revealed the mechanisms by which the virus evades the innate immune response and the Th1-type adaptive response. The objective of this work was to analyze immunosenescence and its relationship with SARS-CoV-2 infection, through the review of the most recent articles (2021-2022), which describes the senescent state of the elderly. In addition, it intends to highlight the probable causes for which the most vulnerable population group (adults over 60 years of age) is more prone to presenting complications during the infection.
... For most people, the synthesis of Vit D in the skin after exposure to UV-B radiation [290-315nm] is the main source of Vit D, which converts 7-dehydrocholesterol to provitamin D3. The molecule is pushed into the extracellular space and drawn to the capillary bed, where it binds to Vit D binding protein (DBP) and is delivered to the liver due to these structural modifications [14], Then, vitamin D3 is converted into 25-hydroxycholecalciferol (25OHD) by 25hydroxylase (CYP2R1). This process mainly occurs in the liver, The final stage of the formation of active 1,25dihydroxycholecalciferol (1,25 (OH) 2 D) is mediated by the enzyme 25-hydroxyvitamin D1α-hydroxylase (CYP27B1), which is found in proximal tubular cells [15], the active form 1,25(OH)2 D3 enter the cells and bind to Vit D receptor (VDR) and react with the Vit D response elements [16,17]. ...
... For example, evidence suggests that the vitamin D receptor in the sea lamprey (Petromyzon marinus) may function to induce cytochrome P450 enzymes for xenobiotic detoxification [32]. Due to its evolutionary relationship to modern vertebrates, this insight allows us to speculate that the early function of the VDR receptor was detoxification [33]. With that in mind, it is interesting to note that C. elegans mounted a transcriptional response highly associated with the metabolism of xenobiotics, with vitamin D 3 treatment inducing the expression of many CYP and glutathione S-transferase (GST) proteins. ...
Vitamin D deficiency is associated with a variety of age-related diseases and is becoming increasingly more prevalent in the population over time. Some diseases associated with deficiency are cardiovascular disease, cancer, and neurodegeneration. This association, as well as the fact that vitamin D has been demonstrated to play an important role in a variety of extraskeletal processes, has led some to claim that vitamin D is an essential longevity vitamin. However, the role of vitamin D in healthy aging has been difficult to determine. In order to study vitamin D in the context of aging, the model organism, Caenorhabditis elegans (C. elegans), was employed. To study vitamin D’s impact on aging and age-related disease, lifespan and health span were measured across three different genetic strains of C. elegans. Strains investigated were wildtype (N2), worms with a mutant vitamin D receptor ortholog (nhr-8), and worms engineered to represent Alzheimer disease (gnals2). Bioinformatic analysis of available public data was also performed in order to identify the transcriptional response produced in N2 worms treated with vitamin D3. Treatment with vitamin D3 significantly extended the lifespan of N2 worms and rescued nhr-8 worms, which typically have decreased lifespans compared to N2. Treatment with vitamin D3 minimally extended the lifespan of gnals2 worms. Similar results were obtained for measures of health span, quantified as motility through time. Differentially expressed genes upon treatment with vitamin D3 were largely associated with biological processes such as the innate immune response and metabolism of xenobiotic compounds in the worms, which may explain the observed increase in lifespan and health span.
... This indicates that VDR and its five relatives have a common ancestor and that the individual receptor genes developed by whole genome duplications in early vertebrate evolution [28]. Interestingly, the six NRs function as sensors for cholesterol derivatives, such as 1,25(OH) 2 D 3 , oxysterols and bile acids [29]. Moreover, FXR, VDR, CAR and PXR detect toxic secondary bile acids, such as lithocholic acid, and get activated by them [30][31][32][33]. ...
For at least 1.2 billion years, eukaryotes have been able to synthesize sterols and, therefore, can produce vitamin D when exposed to UV-B. Vitamin D endocrinology was established some 550 million years ago in animals, when the high-affinity nuclear receptor VDR (vitamin D receptor), transport proteins and enzymes for vitamin D metabolism evolved. This enabled vitamin D to regulate, via its target genes, physiological process, the first of which were detoxification and energy metabolism. In this way, vitamin D was enabled to modulate the energy-consuming processes of the innate immune system in its fight against microbes. In the evolving adaptive immune system, vitamin D started to act as a negative regulator of growth, which prevents overboarding reactions of T cells in the context of autoimmune diseases. When, some 400 million years ago, species left the ocean and were exposed to gravitation, vitamin D endocrinology took over the additional role as a major regulator of calcium homeostasis, being important for a stable skeleton. Homo sapiens evolved approximately 300,000 years ago in East Africa and had adapted vitamin D endocrinology to the intensive exposure of the equatorial sun. However, when some 75,000 years ago, when anatomically modern humans started to populate all continents, they also reached regions with seasonally low or no UV-B, i.e., and under these conditions vitamin D became a vitamin.
... The idea that less melanization facilitates vitamin D photosynthesis in the skin has been challenged. Bogh et al. (2010) (Hanel & Carlberg, 2020b). These are interesting ideas, and are not inconsistent with the suggestion above that a secondary adaptive biochemical/ metabolic phenotype supports the primary adaptive pigmentation phenotype. ...
This review examines putative, yet likely critical evolutionary pressures contributing to human skin pigmentation and subsequently, depigmentation phenotypes. To achieve this, it provides a synthesis of ideas that frame contemporary thinking, without limiting the narrative to pigmentation genes alone. It examines how geography and hence the quality and quantity of UV exposure, pigmentation genes, diet-related genes, vitamins, anti-oxidant nutrients, and cultural practices intersect and interact to facilitate the evolution of human skin color. The article has a strong focus on the vitamin D-folate evolutionary model, with updates on the latest biophysical research findings to support this paradigm. This model is examined within a broad canvas that takes human expansion out of Africa and genetic architecture into account. A thorough discourse on the biology of melanization is provided (includes relationship to BH4 and DNA damage repair), with the relevance of this to the UV sensitivity of folate and UV photosynthesis of vitamin D explained in detail, including the relevance of these vitamins to reproductive success. It explores whether we might be able to predict vitamin-related gene polymorphisms that pivot metabolism to the prevailing UVR exposome within the vitamin D-folate evolutionary hypothesis context. This is discussed in terms of a primary adaptive phenotype (pigmentation/depigmentation), a secondary adaptive phenotype (flexible metabolic phenotype based on vitamin-related gene polymorphism profile), and a tertiary adaptive strategy (dietary anti-oxidants to support the secondary adaptive phenotype). Finally, alternative evolutionary models for pigmentation are discussed, as are challenges to future research in this area.
... Vitamin D deficiency (VDD) is known as a major health issue and affects the normal functions of many organs (1). It is believed that the effect of VDD is more profound in organs in which vitamin D metabolizing enzymes and vitamin D receptors (VDRs) are present (2,3). Given the presence of VDRs as well as its metabolizing enzymes in male and female reproductive systems, VDD is also likely to affect human fertility (4). ...
Background:
Today, vitamin D deficiency (VDD) is one of the major health issues around the world and VDD is associated with several diseases. This study was conducted to find the relationship between vitamin D status in male's serum with sperm function and clinical outcomes in infertile men candidate for intracytoplasmic sperm injection (ICSI).
Materials and methods:
In this cohort study, different parameters of male fertility such as sperm parameters, oxidative stress, and sperm chromatin status were evaluated in sperm samples of 30 infertile couples candidate for ICSI. Clinical outcomes like fertilization, embryo quality, and implantation were also assessed. Data were analyzed using SPSS Statistics 25.0 software. Besides, assessment of the correlation between aforementioned parameters with the level of serum vitamin D, in this study, ICSI candidates were divided into three groups [individuals with sufficient vitamin D levels (>30 ng/ml), insufficient vitamin D levels (between 20-29 ng/ml), and VDD (<20 ng/ml)]. The aforementioned parametesr were also compared between these study groups.
Results:
Analysis of all the data revealed a significant correlation between the level of vitamin D with sperm concentration (P=0.000, r=0.5), sperm count (P=0.03, r=0.31) and sperm reactive oxygen species (ROS) level (P=0.000, r=-0.77). Moreover, comparing clinical outcomes within study groups showed a significant difference in implantation rate between sufficient and other groups (insufficient and deficient) (P=0.02).
Conclusion:
Considering the association between sperm concentration and level of ROS with vitamin D and, higher implantation rate in individuals with vitamin D sufficient group compared to other two groups, our data call for vitamin D supplementation as part of male infertility treatment. But considering our sample size, further research is needed to verify these findings.
... VDR is a nuclear transcription factor that regulates bone metabolism and the inflammatory process by binding with specific ligands (31,32), such as steroid hormone 1alpha,25(OH)2-vitamin D3 (1,25(OH)2-D3) (33,34). VDR gene polymorphsim confers increased risk of AS in Chinese Han population (35,36). ...
Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-β1 (TGF-β1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.
... Початковою функцією вітаміну Д3 була регуляція енергетичного обміну, однак, через еволюційний розвиток імунної системи, остання потребувала більшої кількості енергії для свого функціонування, що сприяло глибшому залученню кальцитріолу у роботу імунітету [15]. Формування цього зв'язку вважають відправною точкою у розвитку імуномодулюючого впливу вітаміну, що здійснюється за рахунок контролю апоптозу, проліферації та диференціації імунокомпетентних клітин [6,22]. ...
Annotation. Breast cancer is the most common cancer diagnosed in women. In the last 5 years, it has been diagnosed in 7.8 million women, and in 2020, 685,000 deaths from breast cancer were registered. The growing number of patients with this pathology and the cost of therapy creates a need to study new methods of diagnosis and treatment. Therefore, detailed attention is paid to genetic risk factors for cancer, in particular, the VDR gene and its polymorphisms ApaI, TaqI, BsmI and FokI. Therefore, the purpose of this review is to collect and analyze currently known information about these SNPs and their relationship to the development, course and effectiveness of breast cancer treatment. To do this, an extensive literature review was conducted using basic databases, which described the effect of vitamin D3 on the tumor process and found that VDR receptor dysfunction increases the risk of breast cancer and affects the sensitivity of patients to treatment, which proves the effect of polymorphisms. ApaI, TaqI, BsmI and FokI on the development of pathology. Therefore, the prospects for further research are to study the prognostic value of each polymorphism and develop new treatments for the disease.
... Its target receptors, i.e., vitamin D receptors (VDRs), are expressed in almost all human tissues [4]. In general, vitamin D can exert endocrine, paracrine, and autocrine effects as part of a complex regulation and interactions of vitamin D metabolism [4,5]. ...
As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.
... Interestingly, the UVB fraction of sunlight is also required for skin formation of vitamin D, and the skin cells also possess fully functional enzymatic machinery to convert vitamin D to its active metabolite-calcitriol [25,[132][133][134]. The skin cells (keratinocytes) also express vitamin D receptor (VDR), and the skin is a very important target for vitamin D metabolite activity [135]. Alternative nuclear receptors for vitamin D metabolites have recently been reported to be expressed in the skin. ...
Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.
... VDR evolves from a nuclear receptor subfamily, and it can sense the level of sterol derivatives and control metabolic genes that support cellular processes, such as innate immunity and adaptive immunity (Hanel and Carlberg 2020). In the present study, we identified a functional VDR in Pacific abalone with the phylogenetic tree analysis, which showed that the cloned sequence was clustered with the confirmed VDR of gastropod. ...
Vitamin D3 is believed to be a contributing factor to innate immunity. Vitamin D receptor (VDR) has a positive effect on inhibiting nuclear factor κB (NF-κB)-mediated inflammation. The underlying molecular mechanisms remain unclear, particularly in mollusks. Consequently, this study will investigate the process of vitamin D3/VDR regulating NF-κB pathway and further explore their functions on inflammation, autophagy, and apoptosis in abalone Haliotis discus hannai. Results showed that knockdown of VDR by using siRNA and dsRNA of VDR in vitro and in vivo led to more intense response of NF-κB signaling to lipopolysaccharide and higher level of apoptosis and autophagy. In addition, 1,25(OH)2D3 stimulation after VDR silencing could partially alleviate apoptosis and induce autophagy. Overexpression of VDR restricted the K48-polyubiquitin chain-dependent inhibitor of κB (IκB) ubiquitination and apoptosis-associated speck-like protein containing CARD (ASC) oligomerization. Besides, VDR silencing resulted in increase of ASC speck formation. In further mechanistic studies, we showed that VDR can directly bind to IκB and IKK1 in vitro and in vivo. In the feeding trial, H&E staining, TUNEL, and electron microscope results showed that vitamin D3 deficiency (0 IU/kg) could recruit more basophilic cells and increase more TUNEL-positive apoptotic cells and lipid droplets (LDs) than vitamin D3 supplement (1000 IU/kg and 5000 IU/kg). In summary, abalone VDR plays a negative regulator role in NF-κB-mediated inflammation via interacting with IκB and inhibiting ubiquitin-dependent degradation of IκB. Vitamin D3 in combination with VDR is essential to establish a delicate balance between autophagy and apoptosis in response to inflammation.
... A weakness is the lack of data on melanized skin types because photobiological responses are affected by skin type (48)(49)(50)(51). The quantitative impact of melanin on vitamin D synthesis remains controversial with recent studies casting doubt on the need for vitamin D as a driver for the evolution of light skin with Homo sapiens' migration from Africa (52,53). The results from this study only apply to FST I/II, and it will be important to assess the effect of skin melanin on the action spectrum for 25(OH)D 3 . ...
Significance
Solar UV radiation (UVR) causes sunburn but initiates the first step of vitamin D synthesis, which is the formation of previtamin D 3 (pre-D 3 ) in skin. The gold standard for assessing vitamin D is serum 25-hydroxyvitamin D 3 [25(OH)D 3 ]. Public health advice for optimal solar exposure requires UVR wavelength-dependence (action spectrum) data on risks and benefits. An action spectrum for pre-D 3 in human ex vivo skin was established over 30 y ago, but its validity has been questioned. We tested this action spectrum in healthy volunteers using serum 25(OH)D 3 as the endpoint. Our analysis shows that the pre-D 3 action spectrum can be improved with a systematic correction. This will result in better risk–benefit calculations for public health advice on solar exposure.
... Calcium and phosphorous homeostasis is considered as one of the main functions of vitamin. It promotes the bone resorption by increasing the calcium absorption resulting the better bone structure and physiology (Hanel and carlberg, 2020). supplementary intake of vitamin D has been reported to decrease the chances of many diseases including hypertension, osteoporosis, cancer, and many autoimmune diseases. ...
... Vitamin D 3 (cholecalciferol) is produced in the skin when 7-dehydrocholesterol is exposed to solar ultraviolet radiation. In the liver cholecalciferol is converted into calcifediol (25-OH-cholecalciferol or 25(OH)D 3 ) and in the kidneys into calcitriol (1,25(OH) 2 -cholecalciferol or 1α,25-dihydroxyvitamin D 3 or 1,25(OH) 2 D 3 ) which is the high-affinity ligand to the nuclear receptor vitamin D receptor (VDR) [10,11]. The active form of vitamin D 3 , 1,25(OH) 2 D 3 , is endowed with anti-inflammatory and immunomodulatory properties. ...
Background
Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH) 2 D 3 (1α,25-dihydroxyvitamin D 3 , calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice).
Methods
DBA/2J mice were randomized to 1,25(OH) 2 D 3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t -test, and one-way ANOVA.
Results
DBA/2J mice treated with 1,25(OH) 2 D 3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH) 2 D 3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 ( p < 0.05). Moreover, 1,25(OH) 2 D 3 -treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors ( p < 0.05), such as BDNF.
Conclusions
1,25(OH) 2 D 3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH) 2 D 3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.
Colorectal cancer (CRC) is one of the most life‐threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH) 2 D 3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH) 2 D 3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D 3 supplementation conducted in both healthy individuals and CRC patients.
Steroids are a unique family of tetracyclic terpenoids that fulfill multiple functions vital to metazoan life. From unicellular fungi to higher plants and mammals, all eukaryotes depend on steroids to orchestrate multiple aspects of their growth, development, and reproduction. The wide array of biological activity of naturally occurring steroids has been exploited in developing therapeutic agents such as antihormones, anesthetics, immunomodulators, contraceptives, and antitumor agents. Nowadays, steroid pharmaceuticals are placed among the most marketed medical products and represent the second largest category next to antibiotics. Therefore, several industrial syntheses were developed for the efficient manufacture of structurally and stereochemically complex pharmaceuticals.
Vitamin D3 (VD3) plays a vital role in various physiological processes in addition to its role in regulating the homeostasis of calcium and phosphorus. The present study was conducted to investigate the effects of dietary VD3 on growth performance, immune status and the metabolism of calcium and phosphorus in Litopenaeus vannamei under the optimal salinity (25) and high salinity (35) conditions. Shrimp (2.1 g ± 0.1 g) were fed with experimental diets containing 0, 1500, 6000 and 12000 IU kg−1 VD3 for 30 days under two salinity conditions respectively. The results showed that the growth performance and intestinal health were reduced, while oxidative stress was induced in the shrimp cultured at salinity 35 compared to those in the shrimp cultured at salinity 25. Interestingly, dietary supplementation of 1500 IU kg−1 VD3 at salinity 35 promoted the growth performance, improved the intestinal health, and enhanced the antioxidant capacity and non-specific immunity in shrimp. In addition, the content of inorganic phosphorus in shrimp serum was affected by dietary VD3 independent of salinity. In contrast, the expressions of calcium transport-related genes, including calmodulin and Ca2+-ATPase, were regulated by salinity, instead of dietary VD3. In conclusion, an appropriate supplementation of dietary VD3 under high-salt condition can promote the growth, alleviate intestinal inflammation, enhance antioxidant capacity and immunity, and contribute to phosphorus metabolism in L. vannamei.
Nutrigenomics attempts to characterize and integrate the relation between dietary molecules and gene expression on a genome-wide level. One of the biologically active nutritional compounds is vitamin D3, which activates via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) the nuclear receptor VDR (vitamin D receptor). Vitamin D3 can be synthesized endogenously in our skin, but since we spend long times indoors and often live at higher latitudes where for many winter months UV-B radiation is too low, it became a true vitamin. The ligand-inducible transcription factor VDR is expressed in the majority of human tissues and cell types, where it modulates the epigenome at thousands of genomic sites. In a tissue-specific fashion this results in the up- and downregulation of primary vitamin D target genes, some of which are involved in attenuating oxidative stress. Vitamin D affects a wide range of physiological functions including the control of metabolism, bone formation and immunity. In this review, we will discuss how the epigenome- and transcriptome-wide effects of 1,25(OH)2D3 and its receptor VDR serve as a master example in nutrigenomics. In this context, we will outline the basis of a mechanistic understanding for personalized nutrition with vitamin D3.
Interest in cholesterol has grown significantly, especially in recent years, as it has become clear that cholesterol is a substance necessary for the normal functioning of the body: it regulates the properties of cell membranes; participates in the synthesis of vitamin D, which maintains the proper level of calcium and phosphorus in the body and determines the development and maintenance of bones; stimulates the production of antibodies; participates in the synthesis of bile acids and steroid hormones. Purpose: The aim of this study was to analyze the opinions of women and men of all ages on the knowledge of the role of cholesterol in physiological processes. Methodology. The research was conducted in 2017-2019 among the inhabitants of Słupsk, Bytów, Miastko, Sławno, the commune of Potęgowo and Czarna Dąbrówka (Pomeranian and West-Pomeranian voivodeships). Overall, 330 respondents took part in the study, including 274 women (83%) and 56 men (17%). Scientific novelty. The respondents largely knew which group of chemical compounds cholesterol belongs to. Less than half of the respondents knew the cholesterol fractions. Most of the respondents correctly answered the question about the general functions of cholesterol. More than half of the respondents knew that the liver is the organ responsible for the production of cholesterol. Regarding the prevention of cardiovascular diseases, respondents knew that there are many factors influencing the prevention of cardiovascular diseases. The respondents did not know products that have a high cholesterol content. The respondents identify the elevated level of cholesterol mainly with problems with the cardiovascular system. Unfortunately, almost the entire group of respondents believes that elevated cholesterol should be reduced as soon as possible, regardless of the reason for its increase. Conclusions. The respondents associated cholesterol with something bad and suggested that its elevated level should be reduced in all situations. Cholesterol was also considered by the respondents as a factor that is very important in the development of cardiovascular diseases.
Hypercholesterolemia is one of the major health concerns in today’s time. Bioactive compounds from various sources have been implicated in managing the conditions of Hypercholesterolemia. With advancements in research, several edible seeds have been explored in managing the disease. This study employs in silico approach to gain insights into the binding interactions of the bioactive compounds which are reportedly present in Edible seeds, against the protein HMG-CoA reductase, which plays a crucial role in cholesterol metabolism. The bioactive compounds were virtually screened and selected based on molecular docking studies which revealed the strong binding interactions of HMG-CoA reductase with Acacetin (-7.6 kcal/mol), Irilone (-7.5 kcal/mol), Orobanchol (-7.5 kcal/mol), Diadzein (-7.4 kcal/mol) and Malvidin (-7.4 kcal/mol). These compounds largely conformed to drug likeliness criteria and ADME properties with lesser mutagenic, hepatotoxic effects and higher absorption percentage in human intestine. Moreover, we performed molecular dynamics simulation studies for docked complexes to explore their stability under simulated conditions. Data gathered from this study will support the future in vitro and in vivo research in development of potential medicaments using the bioactive compounds from edible seeds for management of hypercholesterolemia.
Communicated by Ramaswamy H. Sarma
Background
Vitamin D has been extensively studied for its role in immune modulation, especially in the process of tolerance induction. The loss of tolerance towards self-antigens is the basis of several autoimmune disorders, this seems to be related to lower levels of Vitamin D. A neurological autoimmune disorder due to the loss of tolerance to compounds at the neuromuscular junction is known as Myasthenia Gravis (MG).
Objective
To assess the possible correlation between altered Vitamin D levels and MG. Methods: In this systematic review, all recruited studies compared Vitamin D levels in MG patients and healthy controls. Five studies fulfilled selection criteria and were included for the quantitative synthesis.
Methods
The meta-analysis involved data of a total population size of 450 individuals, quite equally divided in 219 cases and 231 controls, respectively.
Results
The results showed a statistically significant mean difference between cases and controls. The overall mean Vitamin D levels in MG patients were 4.69 ng/ml lower than control levels (95%CI -6.17; -3.22), by applying a random-effects model this mean difference was estimated at -3.79 (95%CI -7.24; -0.33), after exclusion of data source of heterogeneity and through applying a fixed-effect model, resulted in a mean difference -5.39 (95%CI -6.91; -3.88). The p-value was lower than 0.05.
Conclusion
Based on the current data, there are statically significant lower levels of Vitamin D in MG patients, so routine checking and possible correction should be advised in MG patients.
Background
Type 1 diabetes (T1D) is accompanied by numerous side effects, including renal dysfunction. Mounting evidence suggests that overactivation of nuclear factor ĸB (NF-κB) is one of the key triggers of diabetes-associated chronic kidney disease. Vitamin D3 is considered as a strong modulator of a number of transcription factors, including NF-κB. The purpose of our study was to assess the contribution of NF-κB to type 1 diabetes (T1D)-induced kidney dysfunction and to determine if vitamin D3 supplementation can correct the changes associated with T1D.
Methods
The following animal groups were used: control, diabetic (induced by single i.p. injection of streptozocin at dose 55 mg/kg b.w.), T1D group treated with vitamin D3 (600 IU/kg b.w.), T1D group treated with NF-κB inhibitor – BAY 11–7082.
Results
Diabetes led to a decrease in serum 25(OH)D that was accompanied by down-regulation of vitamin D receptor (VDR) expression and up-regulation of hydroxylases CYP24A1 and CYP27B1 synthesis in the kidneys. Diabetes activated the transcription factor NF-κB and increased cleaved (p17) caspase-3 level in renal tissue. Restoration of vitamin D status normalized vitamin D-endocrine system, decreased NF-κB activation and caspase-3 protein level in the kidneys of diabetic animals. BAY 11–7082 partially mimicked the effects of vitamin D3.
General significance
Vitamin D3 supplementation counteracts diabetes-induced kidney damage, most likely through VDR-mediated inhibition of NF-κB activation.
This study was designed to investigate the ameliorating effect of methanolic extract of green walnut husk (GWH) in hypercholesterolemic rats. A total of thirty male Albino Wistar rats (Rattus norvegicus domestica) were divided randomly into six equal groups. Group 1, negative control, fed on a standard rat diet whereas groups 2–6, hypercholesterolemic rats, fed a high-fat diet (1% cholesterol in a standard diet). Group 2, positive control, was left untreated, whereas the groups 3–5 treated orally with methanolic extract of GWH at 200, 400, and 800 mg/kg/day BW, respectively. Group 6, treatment control, received atorvastatin intraperitoneally at a dosage rate of 0.8 mg/kg/day. The treatment lasted for 84 days. Lipid profiles, biomarkers for liver and kidney functions, some hematological parameters, and liver histopathological assessment were performed. No significant variation was observed on lipid profile values after 42 days of GWH intake; while after 84 days, there was significant reduction (P
Background
Vitamin D deficiency is a global phenomenon and causes serious morbidities in people via fluctuation in ions homeostasis, oxidative and inflammatory stress. The fundamental goal of this review was to comprehend the growing awareness, biological impact, fortification and different resources of Vitamin D.
Methods
The purpose of the present study was to explore the biological impact, fortification and different ethnobotanicals and food resources of Vitamin D. The information was gathered from different published national and international articles, book chapters, etc using Google Scholar, Science Direct, Elsevier, PubMed, Springer, etc databases for a comprehensive understanding and perspective associated with Vitamin D.
Result
There is a growing awareness of Vitamin D as a requirement for optimal health. Unfortunately, there are very few food sources that naturally contain Vitamin D such as fish, milk, eggs, microalgae, mushrooms, and some ethnomedicines. However, the common population could not get sufficient Vitamin D and results fail to meet the requirements even leads senescence. Increasing awareness about Vitamin D, their rich foods and the fortification of foods can help in getting rid of the serious morbidities associated with Vitamin D deficiency.
Conclusion
The review elucidates the biological impact and the existing knowledge of natural sources to overtake the optimal requirements Vitamin D found in foods and ethnomedicine. It has been demonstrated that Vitamin D exhibits an essential role in calcium homeostasis and senescence due to oxidative and inflammatory damage. To maintain the biological applicability concerning Vitamin D for calcium homeostasis and senescence, it can be an active area of future research that has the potential to reveal new therapeutic strategies.
Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of calcium and phosphorus metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes, and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot ( Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD 3 (0, 200, 400, 800 and 1600 IU VD 3 /kg diet). According to our results, the optimal VD 3 level in the feed for turbot growth was estimated to be around 400 IU/kg, whereas VD 3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota, and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH) 2 D 3 , the active metabolite of VD 3 , reached a peak value in the turbot serum in the 400 IU group, although the concentrations of calcium and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD 3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD 3 for turbot, and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD 3 in fish.
Bal arıları meyve, sebze ve tohum oluşumu için çok önemli hayvanlardır.
Arılar, çiçekli bitkilerin erkek yapılarındaki polenleri dişi kısımlarına
aktararak bitkilerde meyve ve tohum oluşumunu sağlar. Ayrıca bal
yapmaları nedeniyle de tarih boyunca bu böceklere çok önem verilmiştir.
Biz insanlar her zaman bal arısına hayran olmuşuzdur. Afrika, Avrupa
ve Asya’daki en eski atalarımız, yüz binlerce yıl boyunca, bu arının bal
depolama ve balmumu yapma konusundaki şaşırtıcı endüstrisine, çok
değerli iki maddeye kesinlikle hayran kaldılar. Daha yakın zamanlarda,
son 10.000 yılda, karmaşık arıcılık zanaatını icat ettik ve bal arıları
üzerine bilimsel çalışmalarımıza başladık. Örneğin, bu arının «çiçek
değişmezliği» uygulamasını ilk kez tanımlayan antik filozof Aristotales’ti:
Bir işçi arı, yiyecek toplamanın verimliliğini artırmak için yiyecek
arama gezisi boyunca genellikle bir tür çiçeğe yapışır. Bal arısının
doğal dünyasında nasıl yaşadığını bilmek, geniş bir bilimsel araştırma
yelpazesi gerekmektedir. Bunun nedeni, Apis mellifera’nın biyolojideki,
özellikle davranışla ilgili temel soruları araştırmak için model sistemlerden
biri haline gelmesidir. Bu arıları ister hayvan bilişindeki, ister
davranışsal genetikteki veya sosyal davranışlardaki bazı gizemleri çözmek
için çalışıyor olun, birinin deneysel araştırmalarını tasarlamadan
önce doğal biyolojilerine aşina olmak kritik derecede önemlidir.
The biological active form of vitamin D3, 1α,25-dehydroxyvitamin D3 [1α,25(OH)2D3], exerts pleiotropic effects including bone mineralization, anti-tumor, as well as immunomodulator. This study aimed to explore the potential impact of 1α,25(OH)2D3 on tumor-associated macrophages (TAMs) infiltration in ovarian cancer. Firstly, human monocytic THP-1 cells were differentiated into macrophages (M0) in the presence of phorbol 12-myristate 13-acetate (PMA). In Vivo, 1α,25(OH)2D3 not only reversed the polarization of M2 macrophages, but also decreased the proliferation and migration abilities of ovarian cancer cells induced by M2 macrophages supernatant. Furthermore, 1α,25(OH)2D3 dramatically decreased the secretion of TGF-β1 and MMP-9 in M2 macrophages. However, no significant effect was observed in 1α,25(OH)2D3 treated M1 macrophages. In Vivo, vitamin D3 had an inhibitive effect of 1α,25(OH)2D3-treated M2 macrophages on tumorigenesis. In addition, we conducted the association of TAMs with the poor prognosis of patients with ovarian cancer by meta-analysis, which suggested the higher proportion of M2 macrophages was related to the poorer prognosis in ovarian cancer. Collectively, these results identified distinct roles of 1α,25(OH)2D3 treated M1 and M2 macrophages on cell proliferation and migration abilities in ovarian cancer.
A nivel mundial, los productores de aceite de palma crudo (APC) se han visto en la necesidad de adaptarse a las más recientes exigencias de calidad de los distintos mercados, al igual que a los requisitos normativos pedidos por los países en donde se comercializa este tipo de aceite. Ac-tualmente, más y nuevos parámetros de calidad conforman el grupo de requerimientos exigi-dos por los compradores durante las negociaciones del APC, materia prima indispensable para la producción de distintos alimentos. Hoy por hoy, los metales pesados, trazas de hidrocarburos aromáticos y alifáticos, cloropropanoles y compuestos de cloro y fósforo son monitoreados con mayor frecuencia durante la evaluación de las propiedades y características del aceite de palma 65 Baena S. María A.., K. (2021). La calidad del aceite de palma como un nuevo reto para la palmicultura mundial. Palmas, 42(1), 65-80. Palabras clave: Aceite de palma, Calidad, Comercialización, Fitonutrientes, Precursores de contaminantes, Contaminantes del aceite de palma.
Chronic fluorosis is an endemic disease that severely impairs human health. Studies have proved that the change of various receptors in the body is attributed to excessive fluoride intake. For instance, it will reduce the expression of acetylcholine receptor that affects the release of neurotransmitters and will cause changes of N-methyl-D-aspartic acid receptor that impacts cellular Ca²⁺ influx and of advanced glycation end product receptor, augmenting the inflammatory response of the body, etc. These changes are the key mechanism of multi-system injuries caused by fluorosis. With the increased attention on more and more receptors in recent years, the role they played in the pathogenesis of chronic fluorosis is becoming ever more essential. Therefore, an in-depth study of its mechanism of action is possibly vital to uncover the injury of chronic fluorosis and can also provide a theoretical basis for prevention and clinical treatments.
Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a group of rare neoplasms with unfavorable prognosis. So far, not much is known about the role of vitamin D and oxidative stress in the pathogenesis of LOCP in the European population. The aim of the study was to determine the concentrations of vitamin D, osteopontin, melatonin, and malondialdehyde (MDA) as markers of oxidative stress and/or inflammation, as well as the activities of antioxidant enzymes in the course of LOCP. The vitamin D, melatonin, and osteopontin concentrations in blood serum, the MDA levels in erythrocytes and blood plasma, and the activities of superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes were measured in blood samples taken from 25 LOCP patients of middle age (YCG), 20 LOCP elderly patients (OCG), and 25 healthy middle-aged volunteers. In both cancer groups, decreases in vitamin D and CAT, as well as increases in osteopontin and blood plasma MDA, were observed. An increase in GPx activity in YCG and a decrease in melatonin level in OCG were found. The results indicate the vitamin D deficiency and disturbed oxidant-antioxidant homeostasis in LOCP patients. Osteopontin seems to be associated with LOCP carcinogenesis and requires further research.
The term osteoimmunology was coined many years ago to describe the research field that deals with the cross-regulation between bone cells and the immune system. As a matter of fact, many factors that are classically considered immune-related, such as InterLeukins (i.e., IL-6, -11, -17, and -23), Tumor Necrosis Factor (TNF)-α, Receptor-Activator of Nuclear factor Kappa B (RANK), and its Ligand (RANKL), Nuclear Factor of Activated T-cell, cytoplasmatic-1 (NFATc1), and others have all been found to be crucial in osteoclast and osteoblast biology. Conversely, bone cells, which we used to think would only regulate each other and take care of remodeling bone, actually regulate immune cells, by creating the so-called “endosteal niche.” Both osteoblasts and osteoclasts participate to this niche, either by favoring engraftment, or mobilization of Hematopoietic Stem Cells (HSCs). In this review, we will describe the main milestones at the base of the osteoimmunology and present the key cellular players of the bone-immune system cross-talk, including HSCs, osteoblasts, osteoclasts, bone marrow macrophages, osteomacs, T- and B-lymphocytes, dendritic cells, and neutrophils. We will also briefly describe some pathological conditions in which the bone-immune system cross-talk plays a crucial role, with the final aim to portray the state of the art in the mechanisms regulating the bone-immune system interplay, and some of the latest molecular players in the field. This is important to encourage investigation in this field, to identify new targets in the treatment of bone and immune diseases.
The roles of migration, admixture and acculturation in the European transition to farming have been debated for over 100 years. Genome-wide ancient DNA studies indicate predominantly Aegean ancestry for continental Neolithic farmers, but also variable admixture with local Mesolithic hunter-gatherers. Neolithic cultures first appear in Britain circa 4000 bc, a millennium after they appeared in adjacent areas of continental Europe. The pattern and process of this delayed British Neolithic transition remain unclear. We assembled genome-wide data from 6 Mesolithic and 67 Neolithic individuals found in Britain, dating 8500–2500 bc. Our analyses reveal persistent genetic affinities between Mesolithic British and Western European hunter-gatherers. We find overwhelming support for agriculture being introduced to Britain by incoming continental farmers, with small, geographically structured levels of hunter-gatherer ancestry. Unlike other European Neolithic populations, we detect no resurgence of hunter-gatherer ancestry at any time during the Neolithic in Britain. Genetic affinities with Iberian Neolithic individuals indicate that British Neolithic people were mostly descended from Aegean farmers who followed the Mediterranean route of dispersal. We also infer considerable variation in pigmentation levels in Europe by circa 6000 bc.
Genetic variation in contemporary South Asian populations follows a northwest to southeast decreasing cline of shared West Eurasian ancestry. A growing body of ancient DNA evidence is being used to build increasingly more realistic models of demographic changes in the last few thousand years. Through high-quality modern genomes, these models can be tested for gene and genome level deviations. Using local ancestry deconvolution and masking, we reconstructed population-specific surrogates of the two main ancestral components for more than 500 samples from 25 South Asian populations and showed our approach to be robust via coalescent simulations.
Our f3 and f4 statistics–based estimates reveal that the reconstructed haplotypes are good proxies for the source populations that admixed in the area and point to complex interpopulation relationships within the West Eurasian component, compatible with multiple waves of arrival, as opposed to a simpler one wave scenario. Our approach also provides reliable local haplotypes for future downstream analyses. As one such example, the local ancestry deconvolution in South Asians reveals opposite selective pressures on two pigmentation genes (SLC45A2 and SLC24A5) that are common or fixed in West Eurasians, suggesting post-admixture purifying and positive selection signals, respectively.
For many individuals, in particular during winter, supplementation with the secosteroid vitamin D3 is essential for the prevention of bone disorders, muscle weakness, autoimmune diseases, and possibly also different types of cancer. Vitamin D3 acts via its metabolite 1α,25-dihydroxyvitamin D3 [1,25(OH)
2
D
3
] as potent agonist of the transcription factor vitamin D receptor (VDR). Thus, vitamin D directly affects chromatin structure and gene regulation at thousands of genomic loci, i.e., the epigenome and transcriptome of its target tissues. Modifications of 1,25(OH)
2
D
3
at its side-chain, A-ring, triene system, or C-ring, alone and in combination, as well as nonsteroidal mimics provided numerous potent VDR agonists and some antagonists. The nearly 150 crystal structures of VDR's ligand-binding domain with various vitamin D compounds allow a detailed molecular understanding of their action. This review discusses the most important vitamin D analogs presented during the past 10 years and molecular insight derived from new structural information on the VDR protein.
Tolerogenic dendritic cells (tolDCs) instruct regulatory T cells (Tregs) to dampen autoimmunity. Active vitamin D3 (1α,25-dihydroxyvitamin D3; 1α,25(OH)2D3) imprints human monocyte-derived DCs with tolerogenic properties by reprogramming their glucose metabolism. Here we identify the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) as a critical checkpoint and direct transcriptional target of 1α,25(OH)2D3 in determining the tolDC profile. Using tracer metabolomics, we show that PFKFB4 activity is essential for glucose metabolism, especially for glucose oxidation, which is elevated upon 1α,25(OH)2D3 exposure. Pharmacological inhibition of PFKFB4 reversed the 1α,25(OH)2D3-mediated shift in metabolism, DC profile and function, as determined by expression of inhibitory surface markers and secretion of regulatory cytokines and factors. Moreover, PFKFB4 inhibition in 1α,25(OH)2D3-treated DCs blocked their hallmark capacity to induce suppressive Tregs. This work demonstrates that alterations in the bioenergetic metabolism of immune cells are central to the immunomodulatory effects induced by 1α,25(OH)2D3.
For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1× average coverage), covering a period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers. Later, Scythians admixed with the eastern steppe nomads who formed the Xiongnu confederations, and moved westward in about the second or third century bc, forming the Hun traditions in the fourth–fifth century ad, and carrying with them plague that was basal to the Justinian plague. These nomads were further admixed with East Asian groups during several short- term khanates in the Medieval period. These historical events transformed the Eurasian steppes from being inhabited by Indo-European speakers of largely West Eurasian ancestry to the mostly Turkic-speaking groups of the present day, who are primarily of East Asian ancestry.
Fossil evidence points to an African origin of Homo sapiens from a group called either H. heidelbergensis or H. rhodesiensis. However, the exact place and time of emergence of H. sapiens remain obscure because the fossil record is scarce and the chronological age of many key specimens remains uncertain. In particular, it is unclear whether the present day 'modern' morphology rapidly emerged approximately 200 thousand years ago (ka) among earlier representatives of H. sapiens1 or evolved gradually over the last 400 thousand years2. Here we report newly discovered human fossils from Jebel Irhoud, Morocco, and interpret the affinities of the hominins from this site with other archaic and recent human groups. We identified a mosaic of features including facial, mandibular and dental morphology that aligns the Jebel Irhoud material with early or recent anatomically modern humans and more primitive neurocranial and endocranial morphology. In combination with an age of 315 ± 34 thousand years (as determined by thermoluminescence dating)3, this evidence makes Jebel Irhoud the oldest and richest African Middle Stone Age hominin site that documents early stages of the H. sapiens clade in which key features of modern morphology were established. Furthermore, it shows that the evolutionary processes behind the emergence of H. sapiens involved the whole African continent.
Farming was first introduced to southeastern Europe in the mid-7th millennium BCE - brought by migrants from Anatolia who settled in the region before spreading throughout Europe. However, the dynamics of the interaction between the first farmers and the indigenous hunter-gatherers remain poorly understood because of the near absence of ancient DNA from the region. We report new genome-wide ancient DNA data from 204 individuals-65 Paleolithic and Mesolithic, 93 Neolithic, and 46 Copper, Bronze and Iron Age-who lived in southeastern Europe and surrounding regions between about 12,000 and 500 BCE. We document that the hunter-gatherer populations of southeastern Europe, the Baltic, and the North Pontic Steppe were distinctive from those of western Europe, with a West-East cline of ancestry. We show that the people who brought farming to Europe were not part of a single population, as early farmers from southern Greece are not descended from the Neolithic population of northwestern Anatolia that was ancest
The effects of vitamin D3 dietary administration on certain innate immune parameters on the expression of immune-related genes in head-kidney (HK) and gut were investigated in European sea bass Dicentrarchus labrax. Vitamin D3 (vD3) was orally administered to fish in a commercial pellet food supplemented with 0 (control); 3750; 18,750; or 37,500?U?kg(-1). Furthermore, gut histology was considered. This study showed a modulation in the activities examined in fish fed with the addition of vD3. After just 2?weeks of administration, diet supplementation with the vitamin resulted in increased phagocytic ability, while serum peroxidase content was increased in fish fed with all experimental diets after 4?weeks, no significant differences were observed in protease, anti-protease, natural haemolytic complement activities and total IgM level. At gene level, fbl and rbl transcripts were up-regulated in HK in fish fed with the highest concentration of vD3-supplemented diets after 4?weeks, while in the gut, an up-regulation of hep gene was observed in fish fed with the different doses of vD3. These results suggest that vD3 may be of great interest for immunostimulatory purposes in fish farms.
Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1+cMyb+ HSPC numbers. Selective modulation in vivo and in vitro in zebrafish indicated that vitamin D3 acts directly on HSPCs, independent of calcium regulation, to increase proliferation. Notably, ex vivo treatment of human HSPCs with 1,25(OH)D3 also enhanced hematopoietic colony numbers, illustrating conservation across species. Finally, gene expression and epistasis analysis indicated that CXCL8 (IL-8) was a functional target of vitamin D3-mediated HSPC regulation. Together, these findings highlight the relevance of developmental 1,25(OH)D3 availability for definitive hematopoiesis and suggest potential therapeutic utility in HSPC expansion.
Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure,often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been,indeed,reversed following the identification of the Vitamin D molecule’s important role in the function of the immune system. Although traditionally considered limited to osteopathology,Vitamin D deficiency is now known to be linked to infection,inflammation,and carcinogenesis. In this review,we consider the key historical (Whistler,pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract,stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region.
The lamprey belongs to the phylogenetically oldest group of vertebrates that diverged from the mammalian evolutionary line 560 million years ago. A comparison between the lamprey and mammalian basal ganglia establishes a detailed similarity regarding its input from cortex/pallium and thalamus, as well as its intrinsic organisation and projections of the output nuclei. This means that the basal ganglia circuits now present in rodents and primates most likely had evolved already at the dawn of vertebrate evolution. This includes the 'direct pathway' with striatal projection neurons (SPNs) expressing dopamine D1 receptors, which act to inhibit the tonically active GABAergic output neurons in globus pallidus interne and substantia nigra pars reticulate that at rest keep the brainstem motor centres under tonic inhibition. The 'indirect pathway' with dopamine D2 receptor-expressing SPNs and intrinsic basal ganglia nuclei is also conserved. The net effect of the direct pathway is to disinhibit brainstem motor centres and release motor programs, while the indirect pathway instead will suppress motor activity. Transmitters, connectivity and membrane properties are virtually identical in lamprey and rodent basal ganglia. We predict that the basal ganglia contains a series of modules each controlling a given pattern of behaviour including locomotion, eye-movements, posture, and chewing that contain both the direct pathway to release a motor program and the indirect pathway to inhibit competing behaviours. The phasic dopamine input serves value-based decisions and motor learning. During vertebrate evolution with a progressively more diverse motor behaviour, the number of modules will have increased progressively. These new modules with a similar design will be used to control newly developed patterns of behaviour a process referred to as exaptation.
Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.
Vitamin D (VD3) has been linked to immunologic processes, and its supplementation may have a role in treatment or prevention of diseases with underlying autoimmune or proinflammatory states. As initiators of the immune responses, Dendritic Cells (DC) are a potential target of VD3 to dampen autoimmunity and inflammation, but the role of DC in VD3-mediated immunomodulation in vivo is not understood. In addition to being targets of VD3, DC can provide a local source of bioactive VD3 for regulation of T cell responses. Here we review existing studies that describe the tolerogenic potential of VD3 on DC, and discuss them in the context of current understanding of DC development and function. We speculate on mechanisms that might account for the potent but poorly understood tolerogenic activities of VD3 and the role of DC as both targets and sources of this hormone. This article is protected by copyright. All rights reserved.
Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe's first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.
The ability of nuclear receptors (NRs) to activate transcription of target genes requires the binding of cognate ligands to their ligand-binding domains (LBDs). Information provided by the three-dimensional structures of the unliganded RXR alpha and the liganded RAR gamma LBDs has been incorporated into a general alignment of the LBDs of all NRs. A twenty amino-acid region constitutes a NR-specific signature and contains most of the conserved residues that stabilize the core of the canonical fold of NR LBDs. A common ligand-binding pocket, involving predominantly hydrophobic residues, is inferred by homology modelling of the human RXR alpha and glucocorticoid receptor ligand-binding sites according to the RAR gamma holo-LBD structure. Mutant studies support these models, as well as a general mechanism for ligand-induced activation deduced from the comparison of the transcriptionally active RAR gamma holo- and inactive RXR alpha apo-LBD structures.
Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1(+)/cmyb(+) HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl(+) hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.
© 2015 Jing et al.
The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been driven by changes in protein-protein interactions between VDR and essential coregulators.
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000
years ago by enriching ancient DNA libraries for a target set of almost four
hundred thousand polymorphisms. Enrichment of these positions decreases the
sequencing required for genome-wide ancient DNA analysis by a median of around
250-fold, allowing us to study an order of magnitude more individuals than
previous studies and to obtain new insights about the past. We show that the
populations of western and far eastern Europe followed opposite trajectories
between 8,000-5,000 years ago. At the beginning of the Neolithic period in
Europe, ~8,000-7,000 years ago, closely related groups of early farmers
appeared in Germany, Hungary, and Spain, different from indigenous
hunter-gatherers, whereas Russia was inhabited by a distinctive population of
hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By
~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred
throughout much of Europe, but in Russia, the Yamnaya steppe herders of this
time were descended not only from the preceding eastern European
hunter-gatherers, but from a population of Near Eastern ancestry. Western and
Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded
Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya,
documenting a massive migration into the heartland of Europe from its eastern
periphery. This steppe ancestry persisted in all sampled central Europeans
until at least ~3,000 years ago, and is ubiquitous in present-day Europeans.
These results provide support for the theory of a steppe origin of at least
some of the Indo-European languages of Europe.
Metabolic switches in various immune cell subsets enforce phenotype and function. In the present study, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces human monocyte-derived tolerogenic dendritic cells (DC) by metabolic reprogramming. Microarray analysis demonstrated that 1,25(OH)2D3 upregulated several genes directly related to glucose metabolism, tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). Although OXPHOS was promoted by 1,25(OH)2D3, hypoxia did not change the tolerogenic function of 1,25(OH)2D3-treated DCs. Instead, glucose availability and glycolysis, controlled by the PI3K/Akt/mTOR pathway, dictate the induction and maintenance of the 1,25(OH)2D3-conditioned tolerogenic DC phenotype and function. This metabolic reprogramming is unique for 1,25(OH)2D3, because the tolerogenic DC phenotype induced by other immune modulators did not depend on similar metabolic changes. We put forward that these metabolic insights in tolerogenic DC biology can be used to advance DC-based immunotherapies, influencing DC longevity and their resistance to environmental metabolic stress.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Bone formation is indirectly influenced by 1,25-dihydroxyvitamin D3 (1,25D3) through the stimulation of calcium uptake in the intestine and re-absorption in the kidneys. Direct effects on osteoblasts and bone formation have also been established. The vitamin D receptor (VDR) is expressed in osteoblasts and 1,25D3 modifies gene expression of various osteoblast differentiation and mineralization-related genes, such as alkaline phosphatase (ALPL), osteocalcin (BGLAP), and osteopontin (SPP1). 1,25D3 is known to stimulate mineralization of human osteoblasts in vitro, and recently it was shown that 1,25D3 induces mineralization via effects in the period preceding mineralization during the pre-mineralization period. For a full understanding of the action of 1,25D3 in osteoblasts it is important to get an integrated network view of the 1,25D3-regulated genes during osteoblast differentiation and mineralization. The current data will be presented and discussed alluding to future studies to fully delineate the 1,25D3 action in osteoblast. Describing and understanding the vitamin D regulatory networks and identifying the dominant players in these networks may help develop novel (personalized) vitamin D-based treatments. The following topics will be discussed in this overview: (1) Bone metabolism and osteoblasts, (2) Vitamin D, bone metabolism and osteoblast function, (3) Vitamin D induced transcriptional networks in the context of osteoblast differentiation and bone formation.
Melanin provides a crucial filter for solar UV radiation and its genetically determined variation influences both skin pigmentation and risk of cancer. Genetic evidence suggests that the acquisition of a highly stable melanocortin 1 receptor allele promoting black pigmentation arose around the time of savannah colonization by hominins at some 1-2 Ma. The adaptive significance of dark skin is generally believed to be protection from UV damage but the pathologies that might have had a deleterious impact on survival and/or reproductive fitness, though much debated, are uncertain. Here, I suggest that data on age-associated cancer incidence and lethality in albinos living at low latitudes in both Africa and Central America support the contention that skin cancer could have provided a potent selective force for the emergence of black skin in early hominins.
Vitamin D is the sunshine vitamin that has been produced on this earth for more than 500 million years. During exposure to sunlight 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to previtamin D3 which in turn isomerizes into vitamin D3. Previtamin D3 and vitamin D3 also absorb UV B radiation and are converted into a variety of photoproducts some of which have unique biologic properties. Sun induced vitamin D synthesis is greatly influenced by season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, passing through glass and plastic, and aging. Vitamin D is metabolized sequentially in the liver and kidneys into 25-hydroxyvitamin D which is a major circulating form and 1,25-dihydroxyvitamin D which is the biologically active form respectively. 1,25-dihydroxyvitamin D plays an important role in regulating calcium and phosphate metabolism for maintenance of metabolic functions and for skeletal health. Most cells and organs in the body have a vitamin D receptor and many cells and organs are able to produce 1,25-dihydroxyvitamin D. As a result 1,25-dihydroxyvitamin D influences a large number of biologic pathways which may help explain association studies relating vitamin D deficiency and living at higher latitudes with increased risk for many chronic diseases including autoimmune diseases, some cancers, cardiovascular disease, infectious disease, schizophrenia and type 2 diabetes. A three-part strategy of increasing food fortification programs with vitamin D, sensible sun exposure recommendations and encouraging ingestion of a vitamin D supplement when needed should be implemented to prevent global vitamin D deficiency and its negative health consequences.
The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates was accompanied by major morphological and physiological innovations, such as hinged jaws, paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups, the cartilaginous fishes and the bony vertebrates. Here we report the whole-genome analysis of a cartilaginous fish, the elephant shark (Callorhinchus milii). We find that the C. milii genome is the slowest evolving of all known vertebrates, including the 'living fossil' coelacanth, and features extensive synteny conservation with tetrapod genomes, making it a good model for comparative analyses of gnathostome genomes. Our functional studies suggest that the lack of genes encoding secreted calcium-binding phosphoproteins in cartilaginous fishes explains the absence of bone in their endoskeleton. Furthermore, the adaptive immune system of cartilaginous fishes is unusual: it lacks the canonical CD4 co-receptor and most transcription factors, cytokines and cytokine receptors related to the CD4 lineage, despite the presence of polymorphic major histocompatibility complex class II molecules. It thus presents a new model for understanding the origin of adaptive immunity.
Genome-wide analysis of vitamin D receptor (VDR) binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 (CXCL8). CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the CXCL8 gene are insulated from neighboring genes by CCCTC-binding factor (CTCF) binding sites. Only CXCL8, CXCL6 and CXCL1 are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH)2D3-dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the CXCL8 gene showed a 33-fold higher basal expression, but is together with CXCL6 and CXCL1 still a primary 1,25(OH)2D3 target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes CXCL8, CXCL6 and CXCL1 are under the primary control of 1,25(OH)2D3 and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D.
Divergent natural selection caused by differences in solar exposure has resulted in distinctive variations in skin color between human populations. The derived light skin color allele of the SLC24A5 gene, A111T, predominates in populations of Western Eurasian ancestry. To gain insight into when and where this mutation arose, we defined common haplotypes in the genomic region around SLC24A5 across diverse human populations, and deduced phylogenetic relationships between them. Virtually all chromosomes carrying the A111T allele share a single 78 kb haplotype that we call C11, indicating that all instances of this mutation in human populations share a common origin. The C11 haplotype was most likely created by a crossover between two haplotypes, followed by the A111T mutation. The two parental precursor haplotypes are found from East Asia to the Americas, but are nearly absent in Africa. The distributions of C11 and its parental haplotypes make it most likely that these two last steps occurred between the Middle East and the Indian subcontinent, with the A111T mutation occurring after the split between the ancestors of Europeans and East Asians.
Vitamin D is essential for a wide range of physiological processes including immune function and calcium homeostasis. Recent investigations have identified candidate genes which are strongly linked to concentrations of 25-hydroxyvitamin D. Since there is insufficient UVB radiation to induce year-round cutaneous synthesis of vitamin D at latitudes distant from the equator it is likely that these genes were subject to forces of natural selection. We used the fixation index (FST) to measure differences in allele frequencies in 993 individuals from ten populations to identify the presence of evolutionary selection in genes in the vitamin D pathway. We then explored the length of haplotypes in chromosomes to confirm recent positive selection.
We find evidence of positive selection for DHCR7, which governs availability of 7-dehydrocholesterol for conversion to vitamin D3 by the action of sunlight on the skin. We show that extended haplotypes related to vitamin D status are highly prevalent at Northern latitudes (Europe 0.72, Northeast Asia 0.41). The common DHCR7 haplotype underwent a recent selective sweep in Northeast Asia, with relative extended haplotype homozygosity of 5.03 (99th percentile). In contrast, CYP2R1, which 25-hydroxylates vitamin D, is under balancing selection and we found no evidence of recent selection pressure on GC, which is responsible for vitamin D transport.
Our results suggest that genetic variation in DHCR7 is the major adaptation affecting vitamin D metabolism in recent evolutionary history which helped early humans to avoid severe vitamin D deficiency and enabled them to inhabit areas further from the equator.
Life on earth can be dated back to some 3.8 billion years, and several lines of evidence suggest that the level of atmospheric oxygen was very low even 2.45 billion years ago, but then started to accumulate rapidly. However only for the past 500 million years has the atmosphere been "fully oxygenated", i.e. with an O2-concentration close to the present 20 %, which coincides with the development of large and complex life forms. The sun emits short-wave ultraviolet radiation (UVR) that is potentially harmful to life. While the present atmosphere absorbs all UV-C (< 280 nm), also the present biota face harmful levels of UV-B (280 - 320 nm) and UV-A (320 - 400 nm). It has been assumed that the evolution of higher life forms was linked with the establishment of a stratospheric ozone layer and thus a screening of UVR. This may not necessarily have been the case since also methane-derived organic hazes, sulfur vapour or aldehydes could have UV-screening properties. It is nevertheless reasonable to assume that early life for periods may have been at the edge of "mutation meltdown" partly due to high levels of mutagenic UV. On the other hand, low levels of atmospheric O2 would mean reduced likelihood of photo-oxidative damage. It is remarkably, however, that diversification of higher life during the "Cambrian explosion" coincided with establishment of a modern atmosphere, and that the subsequent colonization of land took place after the ozone layer was established. This presentation will discuss the development of early life in parallel with the development of an oxygenated atmosphere and changed levels of UVR, and also demonstrate how present life is evolutionary adapted to cope with UVR and thus reflects "the ghost of UV in the past". These adaptations allow organisms to tolerate fairly high levels of UV, but place a heavy toll on metabolism and productivity in terms of costs associated with synthesis of pigments, antioxidants, gene-repair mechanisms as well as metabolic and behavioural adaptations.
In terrestrial vertebrates, bone tissue constitutes the ‘osteoimmune’ system, which functions as a locomotor organ and a mineral reservoir as well as a primary lymphoid organ where haematopoietic stem cells are maintained. Bone and mineral metabolism is maintained by the balanced action of bone cells such as osteoclasts, osteoblasts and osteocytes, yet subverted by aberrant and/or prolonged immune responses under pathological conditions. However, osteoimmune interactions are not restricted to the unidirectional effect of the immune system on bone metabolism. In recent years, we have witnessed the discovery of effects of bone cells on immune regulation, including the function of osteoprogenitor cells in haematopoietic stem cell regulation and osteoblast-mediated suppression of haematopoietic malignancies. Moreover, the dynamic reciprocal interactions between bone and malignancies in remote organs have attracted attention, extending the horizon of osteoimmunology. Here, we discuss emerging concepts in the osteoimmune dialogue in health and disease. It is well known that immune cells can have profound effects on bone cells, but this interaction is not unidirectional. In this review, Tsukasaki and Takayanagi explore the reciprocal dialogue between bone cells and immune cells during health and disease.
Human skin and hair color are visible traits that can vary dramatically within and across ethnic populations. The genetic makeup of these traits—including polymorphisms in the enzymes and signaling proteins involved in melanogenesis, and the vital role of ion transport mechanisms operating during the maturation and distribution of the melanosome—has provided new insights into the regulation of pigmentation. A large number of novel loci involved in the process have been recently discovered through four large-scale genome-wide association studies in Europeans, two large genetic studies of skin color in Africans, one study in Latin Americans, and functional testing in animal models. The responsible polymorphisms within these pigmentation genes appear at different population frequencies, can be used as ancestry-informative markers, and provide insight into the evolutionary selective forces that have acted to create this human diversity.
Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 30, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.