Protective effects of alpha-lipoic acid on bleomycin-induced skin fibrosis through the repression of NADPH Oxidase 4 and TGF-ß1/Smad3 signaling pathways.

The aim of this study was to determine the protective effects of alpha-lipoic acid (ALA), which is known as a powerful antioxidant, and the possible related molecular mechanisms that mediate its favorable action on skin fibrosis in the bleomycin (BLM)-induced scleroderma (SSc) model in mice. The experimental design was established with four groups of eight mice: Control, ALA (100 mg/kg), BLM (5 µg/kg), and BLM + ALA group. BLM was administered via subcutaneous (sc) once a day while ALA was injected intraperitoneally (ip) twice a week for 21 days. Histopathological and biochemical analyses showed that ALA significantly reduced BLM-induced dermal thickness, inflammation score, and mRNA expression of tumor necrosis factor-alpha (TNF-α) in the skin. Besides, the mRNA expressions of the subunits of NADPH oxidase, which are Nox4 and p22phox, were found to be significantly induced in the BLM group. However, ALA significantly reduced their mRNA expression, which were in parallel to its decreasing effect on serum total oxidant status (TOS) level. Moreover, it was found that ALA downregulated the mRNA expressions of alpha-smooth muscle actin (α-SMA), collagen type I and fibronectin in the skin tissue of the BLM group. Additionally, it was shown that ALA reduced significantly the TGF-ß1 and p-Smad3 protein expressions in the BLM + ALA group. On the other hand, ALA did not exhibit any significant effect on the p38 mitogen-activated kinase (MAPK) activation induced by BLM. All these findings point out that ALA may be a promising treatment for the attenuation of skin fibrosis in SSc patients.

Insights from the new horizons in biochemistry and molecular biology education conference. September 6-8, 2017, Rehovot, Israel.

The New Horizons in Biochemistry and Molecular Biology Education Conference was organized by the International Union of Biochemistry and Molecular Biology (IUBMB) in collaboration with the Federation of European Biochemical Societies (FEBS), and the Weizmann Institute of Science (Israel) and held in Rehovot, Israel, on September 6-8, 2017. The program covered the entire lifespan of students/scientists from the school level to undergraduate, graduate, and post-doctoral levels and brought together 130 international participants. This article provides an overview of the major issues and topics discussed at the conference and suggestions for the way forward.

Role of the microRNA-29 family in fibrotic skin diseases.

Fibrotic skin diseases are characterized by the accumulation of collagen. The hallmarks of fibrotic skin diseases are unbalanced fibroblast proliferation and differentiation, extracellular matrix production and transforming growth factor-ß signalling. Numerous studies have investigated the possibility that microRNAs (miRNAs or miRs) are involved in the pathogenesis of certain fibrotic diseases, including skin, heart, lung and liver diseases. miRNAs are a class of small non-coding RNAs, which modify gene expression by binding to target messenger RNA (mRNA) and blocking the translation or inducing the degradation of target mRNA. The biological relevance of miRNAs has been investigated in physiological and pathological conditions, and there is increasing evidence that the miR-29 family is associated with fibrotic diseases. The aim of the present review is to provide an up-to-date summary of current knowledge on the latest developments associated with the miR-29 family and fibrotic skin diseases.

Evaluation of serum neopterin levels and its relationship with adipokines in pediatric obesity-related nonalcoholic fatty liver disease and healthy adolescents.

AIM: Nonalcoholic fatty liver disease (NAFLD) is associated with inflammation and increased risk of atherosclerosis. Neopterin is regarded as a biochemical marker of cell-mediated immunity, which is secreted by monocytes and macrophages, mainly in response to interferon-gamma. The aim of the present study was to investigate the serum neopterin levels in obese adolescents and compare the neopterin levels in patients with and without NAFLD and also with healthy controls. The second aim of the study was to research the possible relationship between neopterin levels and adipokines (leptin, adiponectin, resistin, and ghrelin). METHODS: Ninety-three obese adolescents (39 with NAFLD, 54 without NAFLD) and 55 healthy controls were enrolled in the study. Serum levels of neopterin and adipokines were measured with high-performance liquid chromatography and sandwich enzyme-linked immunosorbent assay, respectively. RESULTS: Serum neopterin levels were significantly higher in patients with NAFLD (3.20 ± 0.09 nmol/L) than in their healthy peers (2.91 ± 0.08 nmol/L) (p=0.020). Neopterin levels were positively correlated with leptin levels in obese patients (r=0.380, p<0.001) and in the group comprising all individuals (r=0.206, p<0.05). There was no correlation between neopterin concentrations and relative weight, alanin aminotransferase, adiponectin, resistin, and ghrelin levels. CONCLUSION: The serum neopterin levels were significantly higher in obese adolescents with fatty liver disease compared to controls, and this may be related to increased cell-mediated immunity in fatty liver disease.

Effects of lipoic acid in an experimentally induced hypertensive and diabetic rat model.

In this study, experimental diabetes and nephrectomy have been applied separately and together in order to investigate the possible therapeutic effects of lipoic acid (LA) on hypertensive and diabetic rat kidneys. Wistar rats were divided into eight groups: control, diabetes mellitus (DM), 5/6 nephrectomy, DM + 5/6 nephrectomy, LA administration, DM + LA treated, 5/6 nephrectomy + LA treated, and DM + 5/6 nephrectomy + LA-treated groups, respectively. Renal damage was evaluated histomorphometrically, ultrastructurally, and biochemically. Our findings supported that diabetes and hypertension together increased the rate of renal injury, and LA had therapeutic effects on hypertensive and diabetic rat kidneys.

Resveratrol reduces matrix metalloproteinase-2 activity induced by oxygen-glucose deprivation and reoxygenation in human cerebral microvascular endothelial cells.

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 µM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.