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Curr Diabetes Rev ; 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359340


BACKGROUND: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies, are essential. INTRODUCTION: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic post-transcriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). METHODS: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. RESULT: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as the low-grade inflammation. CONCLUSION: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.

Crit Rev Clin Lab Sci ; : 1-14, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32306805


Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that antagonizes the proto-oncogenic phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and governs basic cellular metabolic processes. Recently, its role in cell growth, metabolism, architecture, and motility as an intramolecular and regulatory mediator has gained widespread research interest as it applies to non-tumorous diseases, such as insulin resistance (IR) and diabetic nephropathy (DN). DN is characterized by renal tubulointerstitial fibrosis (TIF) and epithelial-mesenchymal transition (EMT), and PTEN plays a significant role in the regulation of both. Epigenetics and microRNAs (miRNAs) are novel players in post-transcriptional regulation and research evidence demonstrates that they reduce the expression of PTEN by acting as key regulators of autophagy and TIF through activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway. These regulatory processes might play an important role in solving the complexities of DN pathogenesis and IR, as well as the therapeutic management of DN with the help of PTEN K27-linked polyubiquitination. Currently, there are no comprehensive reviews citing the role PTEN plays in the development of DN and its regulation via miRNA and epigenetic modifications. The present review explores these facets of PTEN in the pathogenesis of IR and DN.

Growth Factors ; 37(3-4): 190-207, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31693861


Growth differentiation factor-15 (GDF-15) is a novel cytokine secreted by a variety of cells like macrophages, adipocytes, normally expressed in high amounts by placenta. It is also highly expressed in multiple carcinomas like Colon, Breast, Pancreas, Liver, and Ovarian. Several reports on serum GDF-15 as a potential biomarker for diagnosis and prognosis of cancer are hampered by the lack of robust data, with large sample size and critical patient recruitment. However, experimental accounts on cancer tumors, cell lines, and animal models suggest GDF-15's role in cancer progression via endothelial mesenchymal transition, angiogenesis, metastasis, drug resistance and even stemness of various cancers. GDF-15 could be the point of amalgamation for the various hallmarks of cancer and can prove a useful therapeutic target in cancer. The current review was conceptualized with a thought of critically appraising the existing information of GDF-15 in carcinogenesis.

Nanoscale ; 10(35): 16822-16829, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30167606


Graphene-based van der Waals (vdW) heterostructures can facilitate exciting charge transfer dynamics in between structural layers with the emission of excitonic quasi-particles. However, the chemical formation of such heterostructures has been elusive thus far. In this work, a simple chemical approach is described to form such van der Waals (vdW) heterostructures using few layer MoS2 sheet embedded quantum dots (QDs) and amine-functionalized graphene quantum dots (GQDs) to probe the energy transfer mechanism for tunable photoluminescence (PL). Our findings reveal an interesting non-radiative Förster-type energy transfer with the quenching of functional GQD PL intensity after GQD/MoS2 composite formation, which validates the existing charge transfer dynamics analogous to 0D and 2D systems. The non-radiative type of energy transfer characteristic from GQD into the MoS2 layer through vdW interactions has been confirmed by photoluminescence, time decay analyses and ab initio calculations with the shifting of the Fermi level in the density of states towards the conduction band in the stacked configuration. These results are encouraging for the fundamental exploration of optical properties in other chemically prepared QD/2D based heterostructures to understand the charge transfer mechanism and fingerprint luminescence quenching for future optoelectronic device and optical sensing applications.

J Psychopharmacol ; 19(4): 426-8, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15983000


Clozapine has shown superior efficacy in treatment of refractory schizophrenia, but its use is limited by emergent side-effects. Among other adverse effects, sialorrhea is a troublesome side-effect, its stigmatizing nature results in poor treatment compliance. Several hypotheses have been put forward in the etiology of clozapine-induced sialorrhea. 2 adrenergic antagonism is hypothesized to be involved in its pathophysiology, based on the response to clonidine and lofexidine. Oral clonidine (50 to 100 g/day) was tried on 12 stable outpatients of schizophrenia maintained on clozapine. Wet area over the pillow as reported by the patients was recorded at baseline and at 4 weeks of treatment along with the subjective response after the treatment. Most of the patients reported a decrease in sialorrhea without any adverse events. We describe encouraging results in an open case series of oral clonidine for clozapine-induced sialorrhea.

Agonistas alfa-Adrenérgicos/uso terapêutico , Antipsicóticos/efeitos adversos , Clonidina/uso terapêutico , Clozapina/efeitos adversos , Sialorreia/induzido quimicamente , Sialorreia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico
Indian J Psychiatry ; 47(3): 167-8, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20814462


Paroxetine is a commonly used antidepressant with a safe side-effect profile. A case of paroxetine overdose (560 mg) is reported in an 18-year-old female who attempted suicide and recovered without any sequelae, requiring only supportive treatment. This report highlights a case of pure paroxetine overdose and the safety profile of paroxetine in overdose.