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81.
Tanuj Joshi Amit Kumar Singh Pouya Haratipour Archana Negi Sah Abhay K. Pandey Rozita Naseri Vijay Juyal Mohammad H. Farzaei 《Journal of cellular physiology》2019,234(10):17212-17231
Diabetes affects a large population of the world. Lifestyle, obesity, dietary habits, and genetic factors contribute to this metabolic disease. A target pathway to control diabetes is the 5′-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is a heterotrimeric protein with α, β, and γ subunits. In several studies, AMPK activation enhanced glucose uptake into cells and inhibited intracellular glucose production. Impairment of AMPK activity is present in diabetes, according to some studies. Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK. Thus, drugs that activate and regulate AMPK are potential candidates for the treatment of diabetes. In addition, many patients encounter important adverse effects, like hypoglycemia, while using allopathic drugs. As a result, the investigation of plant-derived natural drugs that lack adverse side effects and treat diabetes is necessary. Natural products like berberine, quercetin, resveratrol, and so forth have shown significant potential in regulating and activating the AMPK pathway which can lead to manage diabetes mellitus and its complications. 相似文献
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Aditya Sharma Chandan K. Maurya Deepti Arha Amit K. Rai Sushmita Singh Salil Varshney Jonathan D. Schertzer Akhilesh K. Tamrakar 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):136-146
Chronic inflammation contributes to obesity mediated metabolic disturbances, including insulin resistance. Obesity is associated with altered microbial load in metabolic tissues that can contribute to metabolic inflammation. Different bacterial components such as, LPS, peptidoglycans have been shown to underpin metabolic disturbances through interaction with host innate immune receptors. Activation of Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) with specific peptidoglycan moieties promotes insulin resistance, inflammation and lipolysis in adipocytes. However, it was not clear how Nod1-mediated lipolysis and inflammation is linked. Here, we tested if Nod1-mediated lipolysis caused accumulation of lipid intermediates and promoted cell autonomous inflammation in adipocytes. We showed that Nod1-mediated lipolysis caused accumulation of diacylglycerol (DAG) and activation of PKCδ in 3T3-L1 adipocytes, which was prevented with a Nod1 inhibitor. Nod1-activated PKCδ caused downstream stimulation of IRAK1/4 and was associated with increased expression of proinflammatory cytokines such as, IL-1β, IL-18, IL-6, TNFα and MCP-1. Pharmacological inhibition or siRNA mediated knockdown of IRAK1/4 attenuated Nod1-mediated activation of NF-κB, JNK, and the expression of proinflammatory cytokines. These results reveal that Nod1-mediated lipolysis promoted accumulation of DAG, which engaged PKCδ and IRAK1/4 to augment inflammation in 3T3-L1 adipocytes. 相似文献
84.
Maninder Kaur Yogesh Vikal Harleen Kaur Lalit Pal Kirandeep Kaur Jasbir Singh Chawla 《Journal of Phytopathology》2019,167(10):591-600
Southern leaf blight (SLB) caused by the fungus Cochliobolus heterostrophus (Drechs.) Drechs. is a major foliar disease of maize worldwide. Our objectives were to identify quantitative trait loci (QTL) for resistance to SLB and flowering traits in recombinant inbred line (RIL) population derived from the cross of inbred lines LM5 (resistant) and CM140 (susceptible). A set of 207 RILs were phenotyped for resistance to SLB at three time intervals for two consecutive years. Four putative QTL for SLB resistance were detected on chromosomes 3, 8 and 9 that accounted for 54% of the total phenotypic variation. Days to silking and anthesis–silking interval (ASI) QTL were located on chromosomes 6, 7 and 9. A comparison of the obtained results with the published SLB resistance QTL studies suggested that the detected bins 9.03/02 and 8.03/8.02 are the hot spots for SLB resistance whereas novel QTL were identified in bins 3.08 and 8.01/8.04. The linked markers are being utilized for marker‐assisted mobilization of QTL conferring resistance to SLB in elite maize backgrounds. Fine mapping of identified QTL will facilitate identification of candidate genes underlying SLB resistance. 相似文献
85.
Yogavel Manickam Nipun Malhotra Siddhartha Mishra Palak Babbar Abhishek Dusane Benoît Laleu Valeria Bellini Mohamed-Ali Hakimi Alexandre Bougdour Amit Sharma 《PLoS pathogens》2022,18(3)
Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins. 相似文献
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Pradeep Kumar Yadalam Santhiya Rengaraj Maryam H. Mugri Mohammed Sayed Amit Porwal Nasser Mesfer Alahmari Khaled M. Alzahrani Ali Robaian Hosam Ali Baeshen Shankargouda Patil 《Saudi Journal of Biological Sciences》2022,29(1):622-629
ObjectivesPeri-implantitis is a destructive inflammatory process that affects the soft and hard tissues around dental implants. porphyromonas gingivalis, an anaerobic gram-negative bacterium, appears to be the main culprit. Since there is no efficient and specific vaccine to treat peri-implantitis, the goal of our research has been to develop a multi-epitope vaccination utilizing an immunoinformatics approach that targeted P. gingivalis type I fim A.Materials and methodsP. gingivalis peptides 6JKZ and 6KMF are suitable for vaccine development. B- and T-cell epitopes from 6KMF and 6JKZ were detected and evaluated based on critical factors to produce a multi-epitope vaccine construct. It was assessed based on allergenicity, antigenicity, stability. The vaccine's dual major histocompatibility complex (MHC-I and MHC-II) binding epitopes allowed it to reach a larger population. P. gingivalis fimbriae induce immune subversion through TLR -CXCR4 receptor complex pathway. The ClusPro 2.0 server was used to do the molecular docking using TLR2 - CXCR4 and vaccine epitopes as receptor and ligand respectively.ResultsThe designed vaccine was non-allergenic and had a high antigenicity, solubility, and stability. The 3D structure of the vaccine revealed strong interaction with CXCR4(TLR2) using molecular docking. The vaccine-CXCR4 interface was more consistent, possibly because the vaccination has a higher affinity for the CXCR4-TLR2 complex.ConclusionThis study details the vaccine's distinct and sustained interaction with the CXCR4(TLR2) immunological receptor and its consistent and effective utterance in the bacterial system. As a result, our vaccine formulation will evoke a significant memory response and induce an adaptive immune response against P. gingivalis. 相似文献
88.
Amit Kumar Solanki Abhishek Acharya Himani Kaushik Bharti Bhatia Lalit C Garg 《Bioinformation》2021,17(6):628
Beta toxin from Clostridium perfringens after being secreted in gut is capable of causing necrotic enteritis in humans and several other animal species and does not respond to routinely used antibiotics. Therefore, there is a need to design an effective inhibitor for the Clostridium perfringens beta toxin (CPB) using cutting edge drug discovery technologies. Hence, potential CPB inhibitors were identified using computer aided screening of compounds from the ZINC database. Further, we document the molecular docking analysis of Clostridium perfringens beta toxin model (that revealed 4 binding pockets, A-D) with the identified potential inhibitors. We show that ZINC291192 [N-[(1-methylindol-3-yl) methyl eneamino]-7,10-dioxabicyclo[4.4.0]deca-2,4,11-triene-8- carboxamide] has optimal binding features with calculated binding energy of -10.38 kcal/mol and inhibition constant of 24.76 nM for further consideration. 相似文献
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90.
Stephan T. Koev Amit Agrawal Henri J. Lezec Vladimir A. Aksyuk 《Plasmonics (Norwell, Mass.)》2012,7(2):269-277
We report the design, fabrication, and characterization of a periodic grating of shallow rectangular grooves in a metallic film with the goal of maximizing the coupling efficiency of an extended plane wave (PW) of visible or near-infrared light into a single surface plasmon polariton (SPP) mode on a flat metal surface. A PW-to-SPP power conversion factor >45% is demonstrated at a wavelength of 780?nm, which exceeds by an order of magnitude the experimental performance of SPP grating couplers reported to date at any wavelength. Conversion efficiency is maximized by matching the dissipative SPP losses along the grating surface to the local coupling strength. This critical coupling condition is experimentally achieved by tailoring the groove depth and width using a focused ion beam. 相似文献