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Immunohistochemical staining of caspase-1 expression in human scalp and hair. Normal scalp (A, E), balding men with androgenetic alopecia (AGA) (B, F); men with AGA responding poorly to finasteride (C, G), and men with AGA responding well to finasteride (D, H). Caspase-1 expression in the epidermis (A–D) and inner and outer root sheath (E–H). Negative controls without primary antibody and controls using an irrelevant antibody of the same isotype were included in each experiment.
Source publication
Inflammasomes that activate caspase-1 govern the innate immune inflammatory response. Whether hair loss associated with androgenetic alopecia (AGA) involves caspase-1 activation is not known.
Immunohistochemical staining for caspase-1 was performed on scalp tissue sections, and protein lysates were analyzed from individuals with AGA (no treatment),...
Contexts in source publication
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... statistically significant differences. Figure 1 shows the pattern of expression of caspase-1 staining within human hair and the scalp ...
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... balding men and in balding men who responded well (+ hair growth) or did not respond (À hair growth) to finasteride treatment. In normal controls, caspase-1 was expressed weakly throughout all levels of the epidermis ( Figure 1A), and more-intense staining was consistently observed in basal keratinocytes. In men with AGA ( Figure 1B) and men with AGA who were nonresponders to finasteride ( Figure 1C), caspase-1 was highly expressed throughout all levels of the epidermis, including the basal keratinocytes. ...
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... normal controls, caspase-1 was expressed weakly throughout all levels of the epidermis ( Figure 1A), and more-intense staining was consistently observed in basal keratinocytes. In men with AGA ( Figure 1B) and men with AGA who were nonresponders to finasteride ( Figure 1C), caspase-1 was highly expressed throughout all levels of the epidermis, including the basal keratinocytes. Men with AGA who responded well (+ hair growth) to the treatment ( Figure 1D) demonstrated a similar pattern of immunostaining as observed in normal controls ( Figure 1A). ...
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... normal controls, caspase-1 was expressed weakly throughout all levels of the epidermis ( Figure 1A), and more-intense staining was consistently observed in basal keratinocytes. In men with AGA ( Figure 1B) and men with AGA who were nonresponders to finasteride ( Figure 1C), caspase-1 was highly expressed throughout all levels of the epidermis, including the basal keratinocytes. Men with AGA who responded well (+ hair growth) to the treatment ( Figure 1D) demonstrated a similar pattern of immunostaining as observed in normal controls ( Figure 1A). ...
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... men with AGA ( Figure 1B) and men with AGA who were nonresponders to finasteride ( Figure 1C), caspase-1 was highly expressed throughout all levels of the epidermis, including the basal keratinocytes. Men with AGA who responded well (+ hair growth) to the treatment ( Figure 1D) demonstrated a similar pattern of immunostaining as observed in normal controls ( Figure 1A). Weak immunoreactivity was consistently observed in basal keratinocytes, whereas little expression was detected within the superficial layers of the epidermis. ...
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... men with AGA ( Figure 1B) and men with AGA who were nonresponders to finasteride ( Figure 1C), caspase-1 was highly expressed throughout all levels of the epidermis, including the basal keratinocytes. Men with AGA who responded well (+ hair growth) to the treatment ( Figure 1D) demonstrated a similar pattern of immunostaining as observed in normal controls ( Figure 1A). Weak immunoreactivity was consistently observed in basal keratinocytes, whereas little expression was detected within the superficial layers of the epidermis. ...
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... immunoreactivity was consistently observed in basal keratinocytes, whereas little expression was detected within the superficial layers of the epidermis. In addition to the positive staining of the epidermis, caspase-1 expression was found within cells of the outer root sheath immediately above the hair bulb ( Figure 1E, F), but little or no positive staining was observed in hair structures in normal scalp ( Figure 1E) of men with AGA who responded well (+ hair growth) to finasteride treatment ( Figure 1G). ...
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... immunoreactivity was consistently observed in basal keratinocytes, whereas little expression was detected within the superficial layers of the epidermis. In addition to the positive staining of the epidermis, caspase-1 expression was found within cells of the outer root sheath immediately above the hair bulb ( Figure 1E, F), but little or no positive staining was observed in hair structures in normal scalp ( Figure 1E) of men with AGA who responded well (+ hair growth) to finasteride treatment ( Figure 1G). ...
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... immunoreactivity was consistently observed in basal keratinocytes, whereas little expression was detected within the superficial layers of the epidermis. In addition to the positive staining of the epidermis, caspase-1 expression was found within cells of the outer root sheath immediately above the hair bulb ( Figure 1E, F), but little or no positive staining was observed in hair structures in normal scalp ( Figure 1E) of men with AGA who responded well (+ hair growth) to finasteride treatment ( Figure 1G). ...
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Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. Dihydrotestosterone (DHT) and androgen receptor (AR) levels are increased in patients with AGA, and DHT-AR signaling correlates strongly with AGA pathogenesis. In this study, treatment with self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticle-type siRNA selec...
Introduction: Since the early 1970s, Platelet-rich plasma (PRP) has been used in many fields as a potential remedy for having regenerative properties. In dermatology, its use is extended to different hair diseases: alopecia areata, traction alopecia, androgenetic alopecia (AGA), and even cicatricial alopecia. Despite its increasing use in the clini...
Finasteride is an orally active testosterone 5-alpha-reductase inhibitor that is used for the treatment of benign prostatic hyperplasia as a surgical alternative. The aim of this work was to improve finasteride levels in plasma and prostate through the formulation of biodegradable finasteride nanoparticles and to quantify finasteride levels using n...
Citations
... Inflammasome proteins have been previously shown to be good indicators of the inflammatory response in a variety of CNS injuries and diseases, such as traumatic brain injury [36,37], stroke [38][39][40], or Parkinson's disease [41]. In addition, inflammasome proteins have been shown to be reliable biomarkers of the inflammation in indications outside the CNS, such as in non-alcoholic steatohepatitis [42], male pattern baldness [43], and dry eye disease. In this study, we have extended these studies to the role of inflammasome in aSAH in patients. ...
Aneurysmal subarachnoid hemorrhage (aSAH) is caused by abnormal blood vessel dilation and subsequent rupture, resulting in blood pooling in the subarachnoid space. This neurological insult results in the activation of the inflammasome, a multiprotein complex that processes pro-inflammatory interleukin (IL)-1 cytokines leading to morbidity and mortality. Moreover, increases in inflammasome proteins are associated with clinical deterioration in many neurological diseases. Limited studies have investigated inflammasome protein expression following aSAH. Reliable markers of the inflammatory response associated with aSAH may allow for earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. Here, we investigated whether inflammasome signaling proteins may serve as potential biomarkers of the inflammatory response in aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls and hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of inflammasome signaling proteins and downstream pro-inflammatory cytokines. Protein measurements were carried out using Simple Plex and Single-Molecule Array (Simoa) technology. The area under the curve (AUC) was calculated using receiver operating characteristics (ROCs) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, a Spearman r correlation matrix was performed to determine the correlation between inflammasome protein levels and clinical outcome measures. aSAH subjects demonstrated elevated caspase-1, apoptosis-associated speck-like protein with a caspase recruiting domain (ASC), IL-18 and IL-1β levels in serum, and CSF when compared to controls. Each of these proteins was found to be a promising biomarker of inflammation in aSAH in the CSF. In addition, ASC, caspase-1, and IL-1β were found to be promising biomarkers of inflammation in aSAH in serum. Furthermore, we found that elevated levels of inflammasome proteins in serum are useful to predict worse functional outcomes following aSAH. Thus, the determination of inflammasome protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes.
... Caspase-1, ASC, and IL-18 levels are increased in patients with PD, suggesting that inflammasome proteins play a role in the inflammatory response. This finding is consistent with previous studies showing that inflammasome proteins are promising biomarkers of the inflammatory response associated with traumatic brain injury [53][54][55][56][57][58], stroke [59], Alzheimer's disease [60], multiple sclero- [62], ocular surface damage [63], male pattern baldness [64], psoriasis [65], depression [66], renal diseases [67], and non-alcoholic steatohepatitis [68]. ...
Parkinson’s disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain, the accumulation of α-synuclein aggregates, and motor deficits. A major contributor to dopaminergic neuronal loss is neuroinflammation. The inflammasome is a multiprotein complex that perpetuates neuroinflammation in neurodegenerative disorders including PD. Increases in inflammasome proteins are associated with worsened pathology. Thus, the inhibition of inflammatory mediators has the potential to aid in PD treatment. Here, we investigated inflammasome signaling proteins as potential biomarkers of the inflammatory response in PD. Plasma from PD subjects and healthy age-matched controls were evaluated for levels of the inflammasome protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin (IL)-18. This was carried out using Simple Plex technology to identify changes in inflammasome proteins in the blood of PD subjects. The area under the curve (AUC) was obtained through calculation of the receiver operating characteristics (ROC) to obtain information on biomarker reliability and traits. Additionally, we completed a stepwise regression selected from the lowest Akaike information criterion (AIC) to assess how the inflammasome proteins caspase-1 and ASC contribute to IL-18 levels in people with PD. PD subjects demonstrated elevated caspase-1, ASC, and IL-18 levels when compared to controls; each of these proteins were found to be promising biomarkers of inflammation in PD. Furthermore, inflammasome proteins were determined to significantly contribute to and predict IL-18 levels in subjects with PD. Thus, we demonstrated that inflammasome proteins serve as reliable biomarkers of inflammation in PD and that inflammasome proteins provide significant contributions to IL-18 levels in PD.
... [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Twenty-four studies investigated gene expression profiling [18][19][20][21][22][23][24][25][26][27][28] and markers for AGA. [29][30][31][32][33][34][35][36][37][38][39][40][41] Fourteen studies focused on the action of 5-alpha reductase (5AR), which converts the androgen (testosterone) into dihydrotestosterone (DHT) and the inhibition of this enzyme 42-55 using enzymatic, radiochemical and cell proliferation assays. Thirteen studies used the same techniques to investigate the role of other enzymes in the mediation of AGA. ...
Background
Androgenetic alopecia (AGA) is the most common form of non‐scarring alopecia in humans. Several studies have used different laboratory models to study the pathogenesis and interventions for AGA. These study models have proved beneficial and have led to the approval of two drugs. However, the need to build on existing knowledge remains by examining the relevance of study models to the disease.
Objective
We sought to appraise laboratory or pre‐clinical models of AGA.
Method
We searched through databases (PubMed, ScienceDirect, Web of Science, World CAT, Scopus and Google Scholar) for articles on AGA‐related studies from 1942 to March 2019 with a focus on study models.
Results
The search rendered 101 studies after screening and deduplication. Several studies (70) used in vitro models, mostly consisting of two‐dimensional monolayer cells for experiments involving the characterization of androgen and 5‐alpha reductase (5AR) and inhibition thereof, the effects of dihydrotestosterone (DHT) and biomarker(s) of AGA. Twenty‐seven studies used in vivo models of mice and monkeys to investigate DHT synthesis, the expression and inhibition of 5AR and hair growth. Only four studies used AGA‐related or healthy excisional/punch biopsy explants as ex vivo models to study the action of 5AR inhibitors and AGA‐associated genes. No study used three‐dimensional [3‐D] organoids or organotypic human skin culture models.
Conclusion
We recommend clinically relevant laboratory models like human or patient‐derived 3‐D organoids or organotypic skin in AGA‐related studies. These models are closer to human scalp tissue and minimize the use of laboratory animals and could ultimately facilitate novel therapeutics.
... 4 Minoxidil promotes the survival of dermal papilla cells by increasing Bcl-2/Bax ratio and by activating ERK and Akt. 5 Oral finasteride induces the prolongation of anagen phase of hairs, which results in gradual thickening and elongation of the hairs. 6 Finasteride reduces the pattern hair loss associated with increased expression of caspases 7 and apoptosis inhibitors and for this reason it is suggested to activate anagen hair growth. 8 Both of these two drugs can be used alone or in combination. ...
Background Androgenetic alopecia (AGA) is a common hair loss disorder affecting both men and women. Despite multiple therapeutic options, treatment of AGA remains unsatisfactory. Platelet rich plasma (PRP) is an autologous concentrate of plasma with a greater count of platelets than that of whole blood and is effective in promoting hair regrowth.
Objective This randomized controlled clinical trial was conducted to evaluate the efficacy and safety of PRP therapy in male androgenetic alopecia (AGA).
Materials and Methods This study was conducted at the Department of Dermatology &
Venereology, Bangabandhu Sheikh Mujib Medical University from October 2016 to October 2017. Fifty four male patients with AGA diagnosed by dermatologist were enrolled by consecutive sampling. The participants were divided into two groups by odd (group- A) and even numbering (Group-B). Group-A patients were treated with PRP injections on their scalp at 4 weeks interval for 3 sessions and group-B patients were treated with topical 5% minoxidil lotion for the same duration. All patients were followed up at 8th and 12th week. At each follow-up hair was counted in prefixed area of treatment, history was taken and clinical examinations were performed to detect any adverse effects of these therapies.
Results Among 54 male AGA patients, there was no significant difference (P>0.05) in mean age. Positive family history of AGA was found in 74.04% and 70.37% patients in group-A and group-B respectively. According to Norwood- Hamilton classification, in group-A 29.63% patients were in Stage II and in group-B 25.93% patients were in stage II. At the beginning, in group-A and group-B mean hair count/sq.cm was 15.41±1.16 and 15.56±1.88 respectively. At 8th week, mean hair count/sq.cm of group-A and group-B was 17.42±1.10 and 16.15±1.87 and at 12th week, the hair growth of group-A was increased to 19.14±1.06/sq.cm which was significantly higher (P<0.05) compared to group-B (17.62±2.07/sq.cm). 81.48% patient complaints mild pain followed by erythema at the injection site in group-A and 66.66% patient complaints of transient hair fall at the
beginning in group-B.
Conclusion PRP was more efficacious than topical 5% minoxidil lotion in male AGA.
... Oral Finasteride ® also prolongs anagen, with a gradual improvement of HT [38]. Finasteride ® has been shown to reduce the pattern of hair loss associated with an increased expression of caspase and apoptosis inhibitors, stimulating HG [39,40]. ...
The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.
... Oral Finasteride® also prolongs hairs anagen phase, with the gradual improvement of hair thickness [17]. Finasteride® has been shown to reduce the pattern HL associated with increased expression of caspases and apoptosis inhibitors, stimulating anagen phase which resulting in HG [18,19]. ...
Objectives: A retrospective case-series study comparing autologous activated platelet-rich plasma (AA-PRP) versus autologous non-activated platelet-rich plasma (A-PRP) in hair re-growth was reported.
Methods: 90 patients, 63 males showing AGA in stage I–V by the Norwood–Hamilton scale and 27 females with AGA in stage I–III by the Ludwig scale, treated since 2013, were analyzed. 57 patients were treated with A-PRP injections and 33 patients were treated with AA-PRP in three sessions spaced 30 days average. Assessment of hair re-growth was evaluated in different weeks (Ws) after the treatment, summarized in four phases: T0, before the first infusion, T1 - 12 Ws, T2 - 23 Ws, T3 - 44 Ws, T4 - 58 Ws after the last treatment.
Results: 12 Ws, 23 Ws, 44 Ws, and 58Ws after the last treatment, hair density measurements for patients treated with A-PRP and AA-PRP were 65 ± 5 and 28 ± 4 hairs/cm2 at T1, 28 ± 2 and 15 ± 3 hairs/cm2 at T2, 25 ± 3 and 14 ± 3 hairs/cm2 at T3, 23 ± 3 and 13 ± 3 hairs/cm² at T4.
Conclusion: The effects of A-PRP and AA-PRP in hair re-growth during a long-term follow-up, was demonstrated.
... Oral finasteride also prolongs the hairs' anagen phase, with the gradual improvement of hair thickness [14]. Finasteride reduces the thinning, increasing the expression of caspase and apoptosis inhibitors, stimulating the anagen phase resulting in HG [15,16]. ...
Tissue engineering in hair regrowth aims to develop innovative and not-invasive procedures to advance the hair regrowth. A placebo-controlled, randomized, evaluator-blinded, half-head group study to compare hair regrowth with micrografts containing human hair follicle mesenchymal stem cells (HF-MSCs) vs. placebo was reported. After 58 weeks, 27 patients displayed in the targeted area an increase of hair count and hair density, respectively, of 18.0 hairs per 0.65 cm2 and 23.3 hairs per cm2 compared with baseline, while the control area displayed a mean decrease of 1.1 hairs per 0.65 cm2 and 0.7 hairs per cm2 (control vs. treatment: P
... effects. These male hormones reduce cell division activity and suppress hair growth activity [17]. ...
... This concept applies to cells as diverse as neurons [10][11][12][13] sperm cells [14,15] or keratinocytes [16,17]. Importantly, targeting inflammation in these cells has been shown to offer an important therapeutic potential. ...
Background
Interleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored. Methods
Here we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture. ResultsIn this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL-1β. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1β. Conclusions
Taken together, these findings suggest that the inflammatory response through IL-1β experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification.
... Oral finasteride also induces the prolongation of anagen hairs, which results in gradual thickening and elongation of the hairs [21]. In addition, finasteride has been shown to reduce the pattern hair loss associated with increased expression of caspases and apoptosis inhibitors; therefore, it is ultimately suggested to activate anagen hair growth [22,23]. ...
Significance:
Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, the results of a randomized, placebo-controlled, half-head group study to compare the hair regrowth with PRP versus placebo are reported. Hair regrowth was quantified by a blinded evaluator using computerized trichograms. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area and a mean increase in total hair density of 45.9 hairs per cm(2) compared with baseline values. No side effects were noted during treatment. The data clearly highlight the positive effects of PRP injections on male pattern hair loss and absence of major side effects.
