Current Insights into miRNA and lncRNA Dysregulation in Diabetes: Signal Transduction, Clinical Trials and Biomarker Discovery.

Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Despite advances in antihyperglycemic therapeutics, the management of diabetes is limited due to its complexity and associated comorbidities, including diabetic neuropathy, diabetic nephropathy and diabetic retinopathy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the 'symptom complex' in diabetes. We review various miRNAs and lncRNAs implicated in diabetes and delineate ncRNA biological networks as well as key ncRNA targets in diabetes. Further, we discuss the spatial regulation of ncRNAs and their role(s) as prognostic markers in diabetes. We also shed light on the molecular mechanisms of signal transduction with diabetes-associated ncRNAs and ncRNA-mediated epigenetic events. Lastly, we summarize clinical trials on diabetes-associated ncRNAs and discuss the functional relevance of the dysregulated ncRNA interactome in diabetes. This knowledge will facilitate the identification of putative biomarkers for the therapeutic management of diabetes and its comorbidities. Taken together, the elucidation of the architecture of signature ncRNA regulatory networks in diabetes may enable the identification of novel biomarkers in the discovery pipeline for diabetes, which may lead to better management of this metabolic disorder.

Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities.

Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer's disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer's disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1ß and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.

Impact of COVID-19 on Indian Pharmaceutical Industry and Way Forward.

BACKGROUND: As countries and industries continue to cope with the unparalleled challenges presented by the novel coronavirus (COVID-19), a specific area of concern has been the uncertainty surrounding the impact of the COVID-19 pandemic on the global and Indian supply chains of the pharmaceutical industry. The COVID-19 crisis has demonstrated the importance of establishing a risk management system that focuses on assessing future risks resulting from the loss of a supply chain among countries. OBJECTIVE: This review focuses on the role of the Indian pharmaceutical industry towards the pandemic. This review investigates the economic effect of COVID-19 across segments and what it implies for the Indian economy. METHODS: The COVID 19 flare-up has additionally commenced the Indian pharmaceutical organizations an opportunity to transform into a supported trade place point for gathering drugs and intermediates. RESULTS: An enormous pharmaceutical industry in India has consistently been a foundation of reasonable human services, and this pattern would now be able to be required to heighten further. CONCLUSION: The activities from COVID-19 are with a need to change the overall impression of Indian pharmaceutical associations and even more altogether, reduce the dependence of the private pharma associations on alone suppliers like China.

New Vistas in microRNA Regulatory Interactome in Neuropathic Pain.

Neuropathic pain is a chronic pain condition seen in patients with diabetic neuropathy, cancer chemotherapy-induced neuropathy, idiopathic neuropathy as well as other diseases affecting the nervous system. Only a small percentage of people with neuropathic pain benefit from current medications. The complexity of the disease, poor identification/lack of diagnostic and prognostic markers limit current strategies for the management of neuropathic pain. Multiple genes and pathways involved in human diseases can be regulated by microRNA (miRNA) which are small non-coding RNA. Several miRNAs are found to be dysregulated in neuropathic pain. These miRNAs regulate expression of various genes associated with neuroinflammation and pain, thus, regulating neuropathic pain. Some of these key players include adenylate cyclase (Ac9), toll-like receptor 8 (Tlr8), suppressor of cytokine signaling 3 (Socs3), signal transducer and activator of transcription 3 (Stat3) and RAS p21 protein activator 1 (Rasa1). With advancements in high-throughput technology and better computational power available for research in present-day pharmacology, biomarker discovery has entered a very exciting phase. We dissect the architecture of miRNA biological networks encompassing both human and rodent microRNAs involved in the development of neuropathic pain. We delineate various microRNAs, and their targets, that may likely serve as potential biomarkers for diagnosis, prognosis, and therapeutic intervention in neuropathic pain. miRNAs mediate their effects in neuropathic pain by signal transduction through IRAK/TRAF6, TLR4/NF-κB, TXIP/NLRP3 inflammasome, MAP Kinase, TGFß and TLR5 signaling pathways. Taken together, the elucidation of the landscape of signature miRNA regulatory networks in neuropathic pain will facilitate the discovery of novel miRNA/target biomarkers for more effective management of neuropathic pain.

A Study on the Association of Psoriasis with Metabolic Disorders.

BACKGROUND: Psoriasis is a chronic inflammatory and hyper-proliferative skin disorder which is chronically relapsing with high morbidity and impaired quality of life, characterized by erythematous scaly patches affecting skin, joints and nails. It is a disorder of immune system involving genetic, immunologic and environtmental factors. Metabolic syndrome (also known as metabolic syndrome X) is a grouping of interrelated medical traits that, when present, indicate an increased risk of developing noninsulin-dependent diabetes mellitus and/or cardiovascular disease. AIMS AND OBJECTIVES: An attempt to find out the association between psoriasis and metabolic disorders by measuring height, weight, body mass index, hip circumference,waist circumference and its ratio, blood pressure and severity of psoriasis patients by PASI (Baseline psoriasis and severity index) score. Further, to investigate each and every patient with complete blood count, fasting and post-prandial blood glucose levels, thyroid profile,lipid profile. MATERIALS: It is a hospital based Case-control study conducted at Department of Dermatology, Venereology and Leprology at Dr.D.Y. Patil Hopsital Nerul, Navi Mumbai for a duration of October 2015 -October 2016 with sample size of 100 patients of Psoriasis along with 100 patients of controls. Informed consent was taken from patients to satisfy the inclusion criteria with patients clinically diagnosed as psoriasis, above 18 years and those who participated in the study not having psoriasis as the controls with no exclusion criteria. An information sheet was given to all the participating patients. METHODS: Ethical committee approval, informed Consent were taken from the patients. Severity of psoriasis by PASI score (Baseline psoriasis and severity index) along with height, weight, waist circumference: hip circumference, body mass index were measured. Investigations carried out in all patients were CBC, FBS, PLBS, Thyroid profile, Lipid profile and results were statistically analyzed at the end of study. RESULTS: Out of 200 patients, The observation was in accordance of psoriasis being associated with metabolic syndrome in 71% cases as compared to 37% controls. CONCLUSION: The blood pressure, sr. triglycerides, sr. high density lipids, fasting blood sugar were significant in cases as compared to controls satisfying the criteria of Adult Panel Treatment III (ATP III) of Metabolic Disorders.