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971.
Zhigang Liu Ishan Y. Patil Tianyi Jiang Harsh Sancheti John P. Walsh Bangyan L. Stiles Fei Yin Enrique Cadenas 《PloS one》2015,10(5)
High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group) or a HFD (60% of calorie from fat; HFD group) for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a) a significant decrease of insulin receptor substrate (IRS-1) phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b) these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c) primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment); this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a) an inactivation of the IRS-1 and, consequentially, (b) a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c) a suppression of the ERK/CREB pathway, and (d) a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity). It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts profoundly on brain activity, i.e., synaptic plasticity. 相似文献
972.
Patil Basanagoud S. Vasanthakumar Ganga-Ramu Suresh Babu Vommina V. 《International journal of peptide research and therapeutics》2002,9(4-5):231-233
Summary The Wolff rearrangement of α-diazoketones, derived from Fmoc-α-amino acids, under no base conditions on exposure to microwave
irradiation for 40 to 60 sec to Fmoc-β-amino acids with retention of configuration in good yield (91–95%) is described. 相似文献
973.
Babasaheb P. Bandgar Sachin A. Patil Jalinder V. Totre Balaji L. Korbad Rajesh N. Gacche Baliram S. Hote Shivkumar S. Jalde Hemant V. Chavan 《Bioorganic & medicinal chemistry letters》2010,20(7):2292-2296
A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and evaluated for the inhibition of pro-inflammatory cytokines, TNF-α and IL-6. DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant potential of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a range of 81–89%, 09–42% at 10 and 1 μM, respectively, concentration. Exceptionally, the compound 20e was observed to be an effective inhibitor of TNF-α (54%) and IL-6 (97%), (47%) at 10 and 1 μM concentrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF-α, however the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity. 相似文献
974.
975.
976.
Anley Teferra Kiddane Min-Jae Kang Truc Cong Ho Adane Tilahun Getachew Maheshkumar Prakash Patil Byung-Soo Chun Gun-Do Kim 《Current issues in molecular biology》2022,44(3):1012
Cancer is currently one of the foremost health challenges and a leading cause of death worldwide. Cervical cancer is caused by cofactors, including oral contraceptive use, smoking, multiparity, and HIV infection. One of the major and considerable etiologies is the persistent infection of the oncogenic human papilloma virus. G. applanatum is a valuable medicinal mushroom that has been widely used as a folk medicine for the treatment and prevention of various diseases. In this study, we obtained crude extract from G. applanatum mushroom with a subcritical water extraction method; cell viability assay was carried out and the crude extract showed an antiproliferative effect in HeLa cells with IC50 of 1.55 ± 0.01 mg/mL; however, it did not show any sign of toxicity in HaCaT. Protein expression was detected by Western blot, stability of IκBα and downregulation of NFκB, IKKα, IKKβ, p-NFκB-65(Ser 536) and p-IKKα/β(Ser 176/180), suggesting loss of survival in a dose-dependent manner. RT-qPCR revealed RNA/mRNA expression; fold changes of gene expression in Apaf-1, caspase-3, cytochrome-c, caspase-9, Bax and Bak were increased, which implies apoptosis, and NFκB was decreased in a dose-dependent manner. DNA fragmentation was seen in the treatment groups as compared to the control group using gel electrophoresis. Identification and quantification of compounds were carried out by GC–MS and HPLC, respectively; 2(5H)furanone with IC50 of 1.99 ± 0.01 μg/mL could be the responsible anticancer compound. In conclusion, these findings suggest the potential use of the crude extract of G. applanatum as a natural source with anticancer activity against cervical cancer. 相似文献
977.
T L Brown S Patil C D Cianci J S Morrow P H Howe 《The Journal of biological chemistry》1999,274(33):23256-23262
Transforming growth factor beta (TGF-beta) is a potent growth inhibitor and inducer of cell death in B-lymphocytes and is essential for immune regulation and maintenance of self-tolerance. In this report the mouse immature B cell line, WEHI 231, was used to examine the mechanisms involved in TGF-beta-mediated apoptosis. Induction of apoptosis is detected as early as 8 h after TGF-beta administration. Coincident with the onset of apoptosis, the cytoskeletal actin-binding protein, alphaII-spectrin (alpha-fodrin) is cleaved into 150-, 115-, and 110-kDa fragments. The broad spectrum caspase inhibitor (Boc-D-fmk (BD-fmk)) completely abolished TGF-beta-induced apoptosis and alphaII-spectrin cleavage. Caspase 3, although present in WEH1 231 cells, was not activated by TGF-beta, nor was its substrate, poly(ADP-ribose) polymerase. These results identify alphaII-spectrin as a novel substrate that is cleaved during TGF-beta-induced apoptosis. Our data provide the first evidence of calpain and caspase 3-independent cleavage of alphaII-spectrin during apoptosis and suggests that TGF-beta induces apoptosis and alphaII-spectrin cleavage via a potentially novel caspase. This report also provides the first direct evidence of caspase 3 activation in WEH1 231 cells and indicates that at least two distinct apoptotic pathways exist. 相似文献
978.
S Patil A Jedsadayanmata J D Wencel-Drake W Wang I Knezevic S C Lam 《The Journal of biological chemistry》1999,274(40):28575-28583
Following platelet aggregation, integrin alpha(IIb)beta(3) becomes associated with the platelet cytoskeleton. The conserved NPLY sequence represents a potential beta-turn motif in the beta(3) cytoplasmic tail and has been suggested to mediate the interaction of beta(3) integrins with talin. In the present study, we performed a double mutation (N744Q/P745A) in the integrin beta(3) subunit to test the functional significance of this beta-turn motif. Chinese hamster ovary cells were co-transfected with cDNA constructs encoding mutant beta(3) and wild type alpha(IIb). Cells expressing either wild type (A5) or mutant (D4) alpha(IIb)beta(3) adhered to fibrinogen; however, as opposed to control A5 cells, adherent D4 cells failed to spread, form focal adhesions, or initiate protein tyrosine phosphorylation. To investigate the role of the NPLY motif in talin binding, we examined the ability of the mutant alpha(IIb)beta(3) to interact with talin in a solid phase binding assay. Both wild type and mutant alpha(IIb)beta(3), purified by RGD affinity chromatography, bound to a similar extent to immobilized talin. Additionally, purified talin failed to interact with peptides containing the AKWDTANNPLYK sequence indicating that the talin binding domain in the integrin beta(3) subunit does not reside in the NPLY motif. In contrast, specific binding of talin to peptides containing the membrane-proximal HDRKEFAKFEEERARAK sequence of the beta(3) cytoplasmic tail was observed, and this interaction was blocked by a recombinant protein fragment corresponding to the 47-kDa N-terminal head domain of talin (rTalin-N). In addition, RGD affinity purified platelet alpha(IIb)beta(3) bound dose-dependently to immobilized rTalin-N, indicating that an integrin-binding site is present in the talin N-terminal head domain. Collectively, these studies demonstrate that the NPLY beta-turn motif regulates post-ligand binding functions of alpha(IIb)beta(3) in a manner independent of talin interaction. Moreover, talin was shown to bind through its N-terminal head domain to the membrane-proximal sequence of the beta(3) cytoplasmic tail. 相似文献
979.
Ponnulakshmi Rajagopal Selvaraj Jayaraman Shazia Fathima JH Saravanan Radhakrishnan Patil Ashlesh Laxman Vijaya Prakash Krishnan Muthaiah Satyendra Chandra Tripathi TS Gugapriya Aaditya Madhusudan Tarnekar Gayatri Girish Muthiyan Vishwajit Ravindra Deshmukh Bharat Ramrao Sontakke Kirubhanand Chandrashekar 《Bioinformation》2021,17(11):928
980.
Mallikarjun S Beelagi Manoj Manjunath Bongale Anisha S Jain Kollur Shiva Prasad Sharanagouda S Patil Govindappa Mellappa Chandan Dharmashekar P Ashwini R Triveni Chandan Shivamallu Chandrashekar Srinivasa 《Bioinformation》2021,17(5):557
Acute bronchitis is a lower respiratory tract lung infection that causes bronchial inflammation. The known protein drug targets are peptidoglycan D, D-transpeptidase, and DNA topoisomerase 4 subunit A for bronchitis linked infections. These are the membrane associated macromolecules which takes a major role in the formation of cell wall membrane by synthesising the cross-linked peptidoglycan. Therefore, it is of interest to design molecules with improved binding features with these protein targets. Hence, we document the molecular docking analysis data of four phytocompounds from Acacia farnesiana having optimal binding features with these targets linked to bronchitis for further consideration. 相似文献