Life sciences

Publisher: Elsevier

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  • Impact factor
    2.56
  • 5-year impact
    2.67
  • Cited half-life
    8.20
  • Immediacy index
    0.37
  • Eigenfactor
    0.04
  • Article influence
    0.69
  • ISSN
    1879-0631

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Elsevier

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase, an enzyme responsible for the generation of NO. Plasma concentrations of ADMA increase in the elderly and in postmenopausal women. In fact, an elevated ADMA level is a risk factor of cardiovascular disease. Aerobic exercise has a beneficial effect on cardiovascular disease. However, the relationship between ADMA and aerobic fitness is unknown. The aim of this study was to determine whether plasma ADMA concentrations correlate with aerobic fitness levels in postmenopausal women. Thirty healthy postmenopausal women aged 50-76 years participated in this study. We measured plasma concentrations of ADMA and oxygen consumption at the ventilatory threshold (VO2VT) as an index of aerobic fitness. Subjects were divided into the low aerobic fitness (Low fitness) and high aerobic fitness (High fitness) groups, and the dividing line was set at the median VO2VT value. VO2VT was significantly higher in the High fitness group than in the Low fitness group (P<0.01). The plasma ADMA concentrations in the High fitness group were significantly lower than those in the Low fitness group (P<0.05). There was a negative correlation between plasma ADMA concentrations and VO2VT (r=-0.532, P<0.01). We found that plasma ADMA concentrations were associated with aerobic fitness in postmenopausal women. The results of this study suggest that habitual aerobic exercise may decrease plasma ADMA concentrations.
    Life sciences 05/2014;
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    ABSTRACT: Inflammation and cancer are the two major disorders in the gastrointestinal tract. They are causally related in their pathogenesis. Animal models are important to study their causal relationship and in particular to discover new therapeutic agents for these diseases. There are several criteria for these models in order to make them useful to better understand the etiology and treatment of these diseases in man. In this regard, animal models should be similar as possible to human diseases and also be easy to produce and reproducible and also economic to allow a continuous replication in different laboratories. In this review, we summarize the various animal models for inflammatory and cancerous disorders in the upper and lower gastrointestinal tract. Experimental approaches are as simple as by giving a single oral dose of alcohol or other noxious agents or by injections of multiple dosages of ulcer inducing agents or by parenteral administration or in drinking water of carcinogens or by modifying the genetic makeups of animals to produce relatively long-term pathological changes in particular organs. With these methods they could induce consistent inflammatory responses or tumorigenesis in the gastrointestinal mucosa. These animal models are widely used in laboratories in understanding the pathogenesis as well as the mechanisms of action for therapeutic agents in the treatment of gastrointestinal inflammation and cancer.
    Life sciences 05/2014;
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    ABSTRACT: Preventive and/or therapeutic interventions using natural products for ischemic heart disease have gained considerable attention worldwide. This study investigated the cardioprotective effect and possible mechanism of embelin, a major constituent of Embelia ribes Burm, using isoproterenol (ISO)-induced myocardial infarction model in rats. Rats were pretreated for three days with embelin (50mg/kg, p.o) before inducing myocardial injury by administration of ISO (85mg/kg) subcutaneously at an interval of 24h for 2 consecutive days. Serum was analyzed for cardiac specific injury biomarkers, lipids and lipoproteins content. Heart tissues were isolated and were used for histopathology, antioxidant and mitochondrial respiratory enzyme activity assays and western blot analysis. Results showed that pretreatment with embelin significantly decreased the elevated levels of serum specific cardiac injury biomarkers (CK-MB, LDH and AST), serum levels of lipids and lipoproteins and histopathological changes when compared to ISO-induced controls. Exploration of the underlying mechanisms of embelin action revealed that embelin pretreatment restored the myocardial mitochondrial respiratory enzyme activities (NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity), strengthened antioxidant status and attenuated ISO-induced myocardial lipid peroxidation. Immunoblot analysis revealed that embelin interrupted mitochondria dependent apoptotic damage by increasing the myocardial expression of Bcl-2 and down regulating the expression of Bax, cytochrome c, cleaved-caspase-3 & 9 and PARP. Histopathology findings further strengthened the cardioprotective findings of embelin. Result suggested that embelin may have a potential benefit in preventing ischemic heart disease like myocardial infarction.
    Life sciences 05/2014;
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    ABSTRACT: Occupational exposure to organophosphate pesticides is becoming a common and increasingly alarming world-wide phenomenon. The present study is designed to investigate the preventive effect of N-acetylcysteine on malathion-induced hepatic injury and inflammation in rats. Adult male Wistar rats of body weight 200-230g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2g/l) in drinking water for 28days. Rats were sacrificed on the 28th day, 2hours after the last administration. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate desyhdogenase), inflammation (leukocyte counts, myeloperoxidase, immunophenotyping of CD4+ and CD8+, interleukin-1β, interleukin-6 and interferon-γ expression) and oxidative stress (lipid peroxidation, reduced glutathione and antioxidant status) were assessed. Malathion induced an increase in activities of hepatocellular enzymes in plasma, lipid peroxidation index, CD3+/CD4+ and CD3+/CD4+ percent and pro-inflammatory cytokines, when decreased antioxidant status in liver was noted. When malathion-treated rats were compared to NAC supplemented rats, leukocytosis, T cell count and IL-1β, IL-6, INF-γ expression were reduced. Furthermore, NAC restored liver enzyme activities and oxidative stress markers. Malathion induces hepatotoxicity, oxidative stress and liver inflammation. N-acetylcysteine showed therapeutic effects against malathion toxicity.
    Life sciences 05/2014;
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    ABSTRACT: We previously reported anti-dyslipidemic effects of a farnesoid X receptor antagonist in monkeys. In this study, we compared the cholesterol-lowering effects of single and combined administration of a farnesoid X receptor antagonist, compound-T8, and the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor atorvastatin in guinea pig model. Plasma levels of 7α-hydroxy-4-cholesten-3-one, a marker of hepatic cholesterol 7α-hydroxylase activity, were measured after a single administration of compound-T8. The effects of compound-T8 or atorvastatin on plasma cholesterol levels and low-density lipoprotein (LDL) clearance were investigated after 14 or 16days of repeated dosing, respectively. Fractional catabolic rate of plasma LDL was estimated by intravenous injection of DiI-labeled human LDL. The cholesterol-lowering effects of combination therapy were investigated after 7days of repeated treatment. Compound-T8 (10 and 30mg/kg) increased plasma 7α-hydroxy-4-cholesten-3-one levels in a dose-dependent manner. Single administration of compound-T8 (30mg/kg) and atorvastatin (30mg/kg) reduced plasma non-high-density lipoprotein (non-HDL) cholesterol levels by 48% and 46%, respectively, and increased clearance of plasma DiI-labeled LDL by 29% and 35%, respectively. Compound-T8 (10mg/kg) or atorvastatin (10mg/kg) reduced non-HDL cholesterol levels by 19% and 25%, respectively, and combination therapy showed an additive effect and lowered cholesterol levels by 48%. Similar to atorvastatin, compound-T8 reduced plasma non-HDL cholesterol levels accompanied with accelerated LDL clearance in guinea pigs. Combination therapy additively decreased plasma non-HDL cholesterol levels. Therefore, monotherapy with a farnesoid X receptor antagonist and combination therapy of a farnesoid X receptor antagonist with atorvastatin would be attractive dyslipidemia treatment options.
    Life sciences 05/2014;
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    ABSTRACT: Obesity and insulin resistance are associated with increased oxidant stress. However, treatments of obese subjects with different types of antioxidants often give mixed outcomes. In this work, we sought to determine if long-term supplementation of a thiol antioxidant, β-mercaptoethanol, to diet-induced obese mice may improve their health conditions. Middle-age mice with pre-existing diet-induced obesity were provided with low concentration β-mercaptoethanol (BME) in drinking water for six months. Animals were assessed for body composition, gripping strength, spontaneous physical and metabolic activities, as well as insulin and pyruvate tolerance tests. Markers of inflammation were assessed in plasma, fat tissue, and liver. BME-treated mice gained less fat mass and more lean mass than the control animals. They also showed increased nocturnal locomotion and respiration, as well as greater gripping strength. BME reduced plasma lipid peroxidation, decreased abdominal fat tissue inflammation, reduced fat infiltration into muscle and liver, and reduced liver and plasma C-reactive protein. However, BME was found to desensitize insulin signaling in vivo, an effect also confirmed by in vitro experiments. Long-term supplementation of low dose thiol antioxidant BME improved functional outcomes in animals with pre-existing obesity. Additional studies are needed to address the treatment impact on insulin sensitivity if a therapeutic value is to be explored.
    Life sciences 05/2014;
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    ABSTRACT: Compound K (CK) is known to possess anti-diabetic activities but the mechanism for this action is unknown. The present study observed the protective effect of CK on islet cell apoptosis through the AMP-activated protein kinase (AMPK) mediated C-Jun N-terminal kinase (JNK) pathway. Treatment effect of CK on type 2 diabetic (T2D) mice and palmitate-induced MIN6 β-cells injury were observed. Fasting plasma glucose, triacylglycerol, total cholesterol, insulin levels and glucose tolerance test were evaluated. The expression of AMPK and JNK was detected in islet and MIN6 cells. CK treatment (30mg/kg) decreased fasting plasma glucose, triacylglycerol, total cholesterol, elevated plasma insulin levels and improved glucose tolerance in T2D mice. CK treatment attenuated islet cell apoptosis, caspase-3 activity accompanied by a decrease in AMPK and JNK activation. Meanwhile, CK treatment attenuated the palmitate-induced reduction in MIN6 β-cells viability, apoptosis and caspase-3 activity and activation of AMPK and JNK. The AMPK activator AICAR attenuated the CK-mediated inhibition of palmitate-induced apoptosis. These data suggest that CK treatment provides a beneficial anti-diabetic effect in mice with T2D and this protective effect may be mediated through prevention of β-cell apoptosis via inhibition of the AMPK-JNK pathway.
    Life sciences 05/2014;
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    ABSTRACT: Cardiac fibrosis is a final outcome of many clinical conditions that lead to cardiac failure and is characterized by a progressive substitution of cellular elements by extracellular-matrix proteins, such as collagen type I, collagen type II, connective tissue growth factor (CTGF), etc. AIM: : The aim of this study was to identify the mechanisms responsible for angiotensin II (Ang II)-stimulated cardiac fibrosis using rat neonatal cardiac fibroblasts. Neonatal fibroblasts were transfected with IκBα mutant, constitutively active (ca) integrin-linked kinase (ILK), dominant negative of ILK and small interfering RNA (siRNA) of ILK in the presence and absence of Ang-II stimulation. The pro-fibrotic gene expression and protein levels were determined by quantitative real time PCR and western blotting using their specific probes and antibodies. NF-κB translocation was determined by immunocytochemistry and confocal microscopy images were analyzed. Our results indicate that overexpression of ILK promotes a pro-fibrotic process by upregulating collagen type I and CTGF genes via activation of nuclear factor-κB (NF-κB) in cardiac fibroblasts. Inactivation of either NF-κB by the super-repressor IκBα or ILK by siRNA significantly attenuates the pro-fibrotic process. Moreover, ILK overexpression triggers NF-κB-p65 translocation to the nucleus, and ILK inhibition prevents the translocation in cardiac fibroblasts stimulated with Ang II. Our data suggest that the Ang II-stimulated pro-fibrotic process is regulated by a complex mechanism involving crosstalk between ILK and NF-κB activation. This dual mechanism may play a critical role in the progression of cardiac fibrosis.
    Life sciences 05/2014;
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    ABSTRACT: Aim Jaundice, potentially fatal encephalopathy, is common in approximately two-thirds of all well term infants. It is largely due to low expression of constitutive androstane receptor (CAR) in newborns; however, the mechanisms for this low expression were poorly understood. Expression of miR-137 and CAR was compared between neonatal and adult mice and between healthy and a mouse model of obstructive jaundice (OJ) using real-time RT-PCR and Western blot methods. Rate of bilirubin clearance was measured. DNA methylation of miR-137 was analyzed. Inverse expressions of miR-137 and CAR were consistently observed between newborn and adult mice, with significantly higher miR-137 level and lower CAR protein and mRNA levels in neonatal liver than in adult liver. Similar reciprocal relationship was found existing between adult OJ mice and healthy control animals with higher miR-137 level and lower CAR protein and mRNA levels in OJ than in healthy mice. Forced expression of miR-137 in primary hepatocytes repressed CAR protein levels, which was prevented by the inhibitor of miR-137. Knockdown of endogenous miR-137 by its inhibitor increased the rate of bilirubin clearance in OJ mice. Finally, we found that miR-137 was epigenetically over-activated due to hypomethylation in neonatal mice and in adult OJ mice, relative to adult healthy animals. Our findings indicate that miR-137 is a repressor of CAR thus a critical determinant of bilirubin clearance and may be considered a molecular target for the treatment of neonatal hyperbilirubinaemia.
    Life sciences 05/2014;
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    ABSTRACT: Aim This study was aimed to exploit the role of heme oxygenase Hmx1 and the potential miRNA mechanisms in the kidney injuries induced by urinary tract infection by Candida species/Candidemia. Materials & Methods We employed a mouse model of systemic Candidiasis by injection of the C. albicans strain SC5314 into C57BL/6 mice. Kidney injuries were assessed by measuring serum cystain C (CysC), serum β2-microglobulin (β2-MG) and blood urea nitrogen (BUN). Validation of miRNA target gene was conducted by luciferase reporter gene assay, Western blot analysis and real-time RT-PCR. Key Findings We showed here that Candidemia caused significant downregulation of microRNAs miR-204 and miR-211. In sharp contrast, Hmx1 expression was remarkably upregulated, particularly at the protein level. Computational analysis predicted Hmx1 as a target gene for both miR-204 and miR-211 that share the same seed site sequence. We then experimentally validated the targeting relationship between miR-204/miR-211 and Hmx1, which explains the reciprocal changes of expression of miR-204/miR-211 and Hmx1 in Candidemia. Administration of miR-204/miR-211 mimics substantially downregulated Hmx1 and mitigated the severity of the kidney injuries induced by Candidemia, as reflected by improved renal glomerular filtration rate (GFR) determined by serum cystain C (CysC), serum β2-microglobulin (β2-MG) and blood urea nitrogen (BUN). Knockdown of miR-204/miR-211 worsened whilst forced expression of miR-204/miR-211 ameliorated kidney injuries in mice with systemic Candidiasis. Significance Our findings indicate that miR-204/miR-211 downregulation accounts at least partially for the Hmx1 upregulation and the miR-204/miR-211–Hmx1 signaling axis may contribute to immune-suppression in the host thereby the Candidemia-induced kidney dysfunction.
    Life sciences 05/2014;
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    ABSTRACT: Aims Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. Main methods Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10 hours). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for three hours to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. Key findings An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1 hour of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. Significance The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.
    Life sciences 05/2014;
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    ABSTRACT: Aims : Endoplasmic reticulum (ER) stress is involved in the pathogenesis of atherosclerosis (AS). Endothelial cell (EC) dysfunction and monocyte migration to the subendothelium are considered to be essential manifestations of AS. We conducted this study to determine whether ER stress was involved in uremic serum-induced EC dysfunction and whether the regulation of ER stress using a chemical chaperone 4-phenylbutyric acid (4-PBA) had a preventative effect. Main methods : Human umbilical vein endothelial cells (HUVECs) were divided into 4groups: a control serum group (C.S), a uremic serum group (U.S), a uremic serum plus 4-PBA (5 mM) treatment group (4-PBA), and a uremic serum plus pyrrolidine dithiocarbamate (PDTC:50 μM) treatment group (PDTC). Key findings : Lower concentrations of uremic serum (< 10%) facilitated the proliferation of HUVECs. In contrast, the proliferative capability of HUVECs was gradually decreased when we continuously increased the concentration of uremic serum. Compared with C.S, HUVECs incubation with uremic serum had high expression levels of GRP78, p-PERK, NF-κB, MCP-1, and VEGF. THP-1 migration was markedly higher than C.S over the indicated time. These alterations were inhibited by the administration of 4-PBA. Significance : These findings suggest regulation of ER stress coupled with inflammatory activation by 4-PBA would be a promising therapy to reverse the process and development of uremic serum-induced EC dysfunction.
    Life sciences 05/2014;
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    ABSTRACT: This study was aimed to determine whether microRNA1(miR1) plays a role in the activation of myosin light chain kinase (MLCK) mediated by oxLDL in Human umbilical vein endothelial cells (HUVECs). HUVECs were treated with oxLDL along with a control miR or miR1 mimic. MiR1 expression was assayed by miRNA plate assay kit and mirVana(TM) miRNA isolation kit. The MLCK protein, transcript, and kinase activity were measured by Western blot, real-time-polymerase chain reaction and γ-(32)P-ATP phosphate incorporation, respectively. In addition, phosphorylation of MLC, ERK and p38 were analyzed by Western blot. The results showed that upon treatment with oxLDL, miR1 expression was decreased, whereas MLCK expression was increased, in a time- and dose-dependent manner. Consistnet with this, MiR1 mimic prevented MLCK expression and activation and attenuated the phosphorylation of MLC and ERK/p38 in oxLDL-treated HUVECs. Furthermore, we showed that miR1 was able to bind a site located at the 3'un-translational region of MLCK mRNA and inhibited its expression. Taken together, this study demonstrated that the effect of miR1 on hyperlipidemia is mediated through down-regulation of MLCK and the ERK/p38 MAPK pathway.
    Life sciences 05/2014;