Determination of G and P genotypes of bovine group A rotavirus with emergence of unusual G- and P-type combinations from neonatal calf diarrhea in Kashmir, India.

A total of 490 diarrhoeic samples from calves aged between 0 and 6 months were screened for the presence of different G- and P-genotypes of rotavirus circulating in bovines in the Kashmir Valley. Of the 490 diarrhoeic samples, Group A rotavirus was detected in 68 (13.87%) samples by polymerase chain reaction (PCR) followed by RNA-PAGE. Genotyping analysis revealed G10, G6, G3, P[11] and P[5] to be the predominant types. The most common types of combinations detected were G10P[11] (27.90%) and G6P[11] (20.60%). The prevalence rate of G10 and P[11] decreased from 60% to 36.76% and 100%-69.11%, respectively. Genotypes G6, G3, P[1] and P[5], which were not previously reported, were detected and unusual combinations such as G6P[11], G3P[11], G10P[5], G3P[5], G6P[1], G6P[5], G6+G8P[11] were also observed for the first time. Fluctuations in the predominant types, emergence of new types and possible genetic reassortment events suggest an unstable epidemiological situation and the need for continuous surveillance of the circulating types to ensure the suitability of the vaccination programme. The present data suggests G10, G6, P[11] and P[5] genotypes could be incorporated in the polyvalent vaccine to offer increased protection against bovine rotavirus infection in India.

Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model.

Regeneration is a rare occurrence in the animal kingdom, but the earthworm stands out as a remarkable example of this phenomenon. Recent research has highlighted the promising wound healing properties of extracts derived from earthworms. Therefore, we propose that earthworm granulation tissue extract (EGTE) may facilitate wound healing by regulating immune responses in a rabbit diabetic wound model. Electron microscopy reveals that 70 % EGTE possesses noteworthy porosity with spherical to irregularly oval configuration. Gas chromatography-mass spectrometry (GC-MS) Characterization of EGTE revealed higher levels of ergosta-5,7,22-trien-3-ol, (3. beta.,22E). In-Vitro studies revealed significant anti-oxidant, anti-inflammatory and anti-bacterial properties in dose dependent manner. Likewise, cytotoxicity assessments reveal that 70 % EGTE exhibits minimal harm to cells while displaying substantial antioxidant and anti-inflammatory activities. For In-Vivo studies excision wounds were created on the dorsal regions of the experimental animals and were divided as Group I (50 % EGTE), Group II (70 % EGTE), Group III (vehicle) and Group IV (distilled water). Over a 21-day observation period 70 % EGTE facilitated the early healing of wounds in the experimental animals, evident through prompt wound closure, granulation tissue formation, increased DNA content, enhanced tensile strength of the wound area and enhanced the expression/synthesis of wound healing markers/proteins. From these results it can be postulated that EGTE accelerates wound healing by immune modulation, dampening of inflammatory pathway and enhanced expression of growth markers. Henceforth making it promising candidate for therapeutic use in diabetic wound healing.

Novel Therapeutic Agents for Management of Diabetes Mellitus: A Hope for Drug Designing against Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM.

Aged garlic extract preserves beta-cell functioning via modulation of nuclear factor kappa-B (NF-κB)/Toll-like receptor (TLR)-4 and sarco endoplasmic reticulum calcium ATPase (SERCA)/Ca2+ in diabetes mellitus.

BACKGROUND: Peripheral insulin resistance and compromised insulin secretion from pancreatic ß-cells are significant factors and pathogenic hallmarks of diabetes mellitus (DM). NF-κß/TLR-4 and SERCA/Ca2+ pathways have been identified as potential pathways regulating insulin synthesis by preserving pancreatic ß-cell functioning. The current study aimed to evaluate the therapeutic effect of aged garlic extract (AGE) against DM in a streptozotocin (STZ)-induced rat model with particular emphasis on pancreatic ß-cell functioning. METHODS: AGE was characterized by gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to evaluate its physio-chemical characteristics followed by in-vitro anti-diabetic and antioxidant potential. This was followed by the induction of DM in laboratory animals for investigating the therapeutic action of AGE by evaluating the role of NF-κß/TLR-4 and the SERCA/Ca2+ pathway. The parameters assessed in the present experimental setup encompassed antioxidant parameters, metabolic indicators, insulin concentration, intracellular calcium levels, apoptotic markers (CCK-8 and Caspase Glo-8), and protein expression (P-62 and APACHE-II). RESULTS: AGE characterization by SEM, GC-MS, and X-ray diffraction (XRD) revealed the presence of phenylalanine, alliin, S-allylmercaptocysteine (SAMC), tryptophan, 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid as major bioactive constituents of AGE. Metabolic studies, including intraperitoneal glucose tolerance test (IPGTT), revealed significantly lower blood glucose levels in the AGE group compared to the disease control group. In contrast, the intraperitoneal insulin tolerance test (ITT) exhibited no significant difference in insulin sensitivity between the AGE supplementation group and the DM control group. Interestingly, AGE was found to have no significant effect on fasting glucose and serum insulin levels. In contrast, AGE supplementation was found to cause significant hypoglycaemia in postprandial blood glucose and insulin levels. Importantly, AGE causes restoration of intracellular Ca2+ levels by modulation of SERCA/Ca2 functioning and inhibition NF-κB/TLR-4 pathway. AGE was found to interact with and inhibit the DR-5/ caspase-8/3 apoptotic complex. Furthermore, microscopic studies revealed degeneration and apoptotic changes in pancreatic ß-cells of the DM control group, while supplementation of AGE resulted in inhibition of apoptotic pathway and regeneration of pancreatic ß-cells. CONCLUSION: The current study suggests that AGE enhance glucose homeostasis by exerting their effects on pancreatic ß-cells, without ameliorating peripheral sensitivity. Moreover, AGEs promote an increase in ß-cell mass by mitigating the apoptosis of pancreatic ß-cells. These findings suggest that AGE could aid in developing a viable alternative therapy for diabetes mellitus (DM).