Sirtuin‐6 deficiency exacerbates diabetes‐induced impairment of wound healing

Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However, the role of sirtuin 6 (SIRT6), a NAD+‐dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyse the role of SIRT6 in cutaneous wound healing, paired 6‐mm stented wound was created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and nonsense siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6‐siRNA‐treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31‐staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor‐κB (NF‐κB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, tumor necrosis factor‐α and interleukin‐1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF‐κB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that the activation of SIRT6 signalling might be a potential therapeutic approach for promoting wound healing in diabetics.     

Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance

Background

Metabolic syndrome over the years have structured definitions to classify an individual with the disease. Literature review suggests insulin résistance is hallmark of these metabolic clustering. While measuring insulin resistance directly or indirectly remains technically difficult in general practice, along with multiple stability issues for insulin, various indirect measures have been suggested by authorities. Fasting triglycerides-glucose (TyG) index is one such marker, which is recently been suggested as a useful diagnostic marker to predict metabolic syndrome. However, limited data is available on the subject with almost no literature from our region on the subject.

Objective

1. To correlate TyG index with insulin resistance, anthropometric indices, small dense LDLc, HbA1c and nephropathy. 2. To evaluate TyG index as a marker to diagnose metabolic syndrome in comparison to other available markers.

Design-cross-sectional analysis

Place and duration of study-From Jun-2016 to July-2017 at PSS HAFEEZ hospital Islamabad.

Subjects and methods

From a finally selected sample size of 227 male and female subjects we evaluated their anthropometric data, HbA1c, lipid profile including calculated sdLDLc, urine albumin creatinine raito(UACR) and insulin resistance (HOMAIR). TyG index was calculated using formula of Simental-Mendía LE et al. Aforementioned parameters were correlated with TyG index, differences between subjects with and without metabolic syndrome were calculated using Independent sample t-test. Finally ROC curve analysis was carried out to measure AUC for candidate parameters including TyG Index for comparison.

Results

TyG index in comparison to other markers like fasting triglycerides, HOMAIR, HDLc and non-HDLc demonstrated higher positive linear correlation with BMI, atherogenic dyslipidemia (sdLDLc), nephropathy (UACR), HbA1c and insulin resistance. TyG index showed significant differences between various markers among subjects with and without metabolic syndrome as per IDF criteria. AUC (Area Under Curve) demonstrated highest AUC for TyG as [(0.764, 95% CI 0.700–0.828, p-value?≤?0.001)] followed by fasting triglycerides [(0.724, 95% CI 0.656–0.791, p-value?≤?0.001)], sdLDLc [(0.695, 95% CI 0.626–0.763, p-value?≤?0.001)], fasting plasma glucose [(0.686, 95% CI 0.616–0.756, p-value?≤?0.001)], Non-HDLc [(0.640, 95% CI 0.626–0.763, p-value?≤?0.001)] and HOMAIR [(0.619, 95% CI 0.545–0.694, p-value?≤?0.001)].

Conclusion

TyG index, having the highest AUC in comparison to fasting glucose, triglycerides, sdLDLc, non-HDLc and HOMAIR can act as better marker for diagnosing metabolic syndrome.

     

Descriptive epidemiology of metabolic syndrome among obese adolescent population

Aims

The study was done to assess the magnitude of problems of metabolic syndrome among obese adolescents.

Biological,nutritional, and therapeutic significance of Moringa oleifera Lam

The genus Moringa Adans. comprises 13 species, of which Moringa oleifera Lam. native to India and cultivated across the world owing to its drought and frost resistance habit is widely used in traditional phytomedicine and as rich source of essential nutrients. Wide spectrum of phytochemical ingredients among leaf, flower, fruit, seed, seed oil, bark, and root depend on cultivar, season, and locality. The scientific studies provide insights on the use of M. oleifera with different aqueous, hydroalcoholic, alcoholic, and other organic solvent preparations of different parts for therapeutic activities, that is, antibiocidal, antitumor, antioxidant, anti‐inflammatory, cardio‐protective, hepato‐protective, neuro‐protective, tissue‐protective, and other biological activities with a high degree of safety. A wide variety of alkaloid and sterol, polyphenols and phenolic acids, fatty acids, flavanoids and flavanol glycosides, glucosinolate and isothiocyanate, terpene, anthocyanins etc. are believed to be responsible for the pragmatic effects. Seeds are used with a view of low‐cost biosorbent and coagulant agent for the removal of metals and microbial contamination from waste water. Thus, the present review explores the use of M. oleifera across disciplines for its prominent bioactive ingredients, nutraceutical, therapeutic uses and deals with agricultural, veterinarian, biosorbent, coagulation, biodiesel, and other industrial properties of this “Miracle Tree.”     

Cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is a disorder that affects mostly those bones which derived from endochrondal and intramembranous ossification, such as the cranium and the clavicles. CCD is present at a frequency of one in one million individuals. Over 500 cases have been reported. A 13 years old boy reported in the Paediatric Endocrinology outpatient department, Bangladesh Institute of Research and Rehabilitation on Diabetes, Endocrine and Metabolic Disorders (BIRDEM) on 6th April 2006 with complaints of not growing according to his age, a wide gap over the head since birth and delayed shedding of primary teeth and also eruption of secondary teeth. The boy had elongated facies with midfacial hypoplasia, depressed nasal bridge with hypertelorism. His anterior fontanelle was open about 3/1.5 cm. He had short clavicle and his shoulders could be easily apposed. Radiological findings showed anterior fontanellle and sutures were open and widened, all decidual teeth were intact and all secondary teeth were impacted beneath the primary teeth and hypoplastic clavicle. He was diagnosed as a case of Cleidocranial Dysplasia on the basis of history, clinical examination and investigation.