Glycerol fermentation by skin bacteria generates lactic acid and upregulates the expression levels of genes associated with the skin barrier function.

Commensal bacteria play a major role in multiple skin functions by providing the first layer of defense against pathogens and maintaining the skin barrier. Staphylococcus epidermidis is one of the most common skin commensals. In this study, we showed that S. epidermidis ferments glycerol and uses it as a nutrient, while producing short-chain and organic fatty acids, with the most notable being lactic acid. Lactic acid is an alpha-hydroxy acid that inhibits the growth of pathogenic bacteria, without any negative effect on the commensal bacteria itself. Using in vivo experiments, we validated our in vitro results, showing that the skin microbiome is also capable of doing this. Finally, using 2D and 3D skin culture models, we showed that the fermentation of glycerol, mainly lactic acid, as determined by analytical methods, upregulates the expression levels of several key genes that are associated with the barrier properties of the skin. While the hydration effect of glycerol on the skin is well known, our study shows the overall benefits of glycerol on the skin microbiome, while revealing an alternate mode of action of glycerol for multiple skin benefits.

Circulatory miR-98-5p levels are deregulated during diabetes and it inhibits proliferation and promotes apoptosis by targeting PPP1R15B in keratinocytes.

Although deregulated circulatory miRNA signatures during diabetes have been identified for some years now, the effects of such miRNAs on several target tissues are not yet thoroughly investigated. The skin that is nourished by components present in the circulation exhibits several notable abnormal features during diabetes. We, therefore, hypothesized that such altered circulatory miRNA levels might be critical in the onset and progression of impaired skin health during diabetes. RNA sequencing from blood samples of normal and type 2 diabetic human subjects identified 9 upregulated and 19 downregulated miRNAs. miR-98-5p was significantly downregulated and its overexpression down-regulated PPP1R15B levels in HaCaT cells and this was prevented by the miR-98-5p inhibitor. This was validated in human primary epidermal keratinocytes and further supported by a dual reporter luciferase assay of the PPP1R15B 3'UTR where miR-98-5p significantly decreased the luciferase activity which was prevented in the presence of the miRNA inhibitor and by mutation in the miRNA binding site. By targeting PPP1R15B, miR-98-5p increases levels of p-eIF2α, BiP and CHOP. Consequently, there was induction of apoptosis accompanied with decreased proliferation in the presence of miR-98-5p. Conversely, miR-98-5p inhibition alone inhibited apoptosis and promoted proliferation. Taken together, our data suggest that by targeting PPP1R15B, miR-98-5p induces apoptosis and decreases proliferation. As opposed to this since circulatory miR-98-5p levels are decreased in diabetes, we believe that this decrease in the circulation that feeds the skin layers might be a major contributor of hyperproliferation as seen in the skin during diabetes.Abbreviations: miRNAs: MicroRNAs; PPP1R15B: PPP1R15B: Protein Phosphatase 1 Regulatory Subunit 15B; TGFßR1: Transforming Growth Factor Beta Receptor 1; ER: Endoplasmic Reticulum; Bip: Binding Immunoglobulin Protein; Chop: CCAAT-enhancer-binding protein homologous protein; p-eIF2α: Eukaryotic Translation Initiation Factor 2a; Bax: Bcl2-associated X protein; Bcl-2: B-cell CLL/lymphoma 2; PCNA: Proliferating Cell Nuclear Antigen; K5: Cytokeratin 5; qRT-PCR: Quantitative Real-Time PCR; ESCC: Oesophageal squamous cell carcinoma; HCC: Hepatocellular carcinoma; CTHRC1: Collagen triple helix repeat containing 1; SALL4: Sal-like protein 4; TNFα: Tumour Necrosis Factor alpha; PGC-1ß: Peroxisome Profilerator-activated receptor-γ coactivator-1ß; IGF2BP1: Insulin-like growth factor 2 mRNA binding protein 1.

Micro RNA: an epigenetic regulator of type 2 diabetes.

Type 2 Diabetes is a complex disease with multifactorial pathogenesis. The interplay between genes and lifestyle changes complicates the etiology of the disease. In spite of growing number of attempts to unravel the mechanism of this metabolic disease, the molecular nature of type 2 Diabetes is not fully understood. The discovery of a new class of non-coding RNAs, micro RNAs and their role in regulation of gene expression have paved the way for better understanding of disease pathogenesis. Increasing number of evidences suggest crucial role of miRNAs in insulin resistance and ß cell dysfunction, which are the two main features of type 2 Diabetes. This review summarizes the role of miRNA in elicitation and progression of type 2 Diabetes.

Adiponectin and IL-6: Mediators of inflammation in progression of healthy to type 2 diabetes in Indian population.

Aim The objective of the study was to identify the association if any, of inflammatory markers (adiponectin and IL-6) with fasting glucose in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) people in Indian population. Methods Total 162 volunteers were distributed into 3 groups (normoglycemic, individuals with impaired fasting glucose, and hyperglycemic) as per ADA criterion. The blood chemistry parameters were analyzed and serum adiponectin and IL-6 levels were measured by ELISA. Results Significant reduction was observed in serum adiponectin level in hyperglycemic and impaired fasting glucose population compared with normoglycemic population. Significant reduction in adiponectin was also observed in impaired fasting glucose group compared with hyperglycemic group. Similarly significant increase was also observed in IL-6 level in hyperglycemic and impaired fasting glucose groups compared with normoglycemic group. Conclusions From our data it can be summarized that there is a significant change in both adiponectin (reduction) and IL-6 (increase) levels in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) population in Indian population. There is a significant but gradual change during the progression of healthy toward diabetic population via pre-diabetic condition.