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61.
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Nibedita Das Mst. Shahnaj Parvin Mahadi Hasan Masuma Akter Md. Sanowar Hossain G.M.Masud Parvez Ashish Kumar Sarker Md. Aziz Abdur Rahman Al Mamun Md. Ekramul Islam 《Biochemistry and Biophysics Reports》2022
Among the major constituents of Leea rubra (Family Vitaceae) leaves, phenolic and flavonoind compounds are most important for therapeutic purposes and the plant parts have been used in traditional medicine to treat several diseases for long. Thus, in order to scientifically confirm the traditional uses of the L. rubra leaves, the present study was designed to investigate the efficacy of the isolated flavones against AAPH induced oxidative damage to pUC19 DNA by gel electrophoresis and antineoplastic activity was evaluated on Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice by evaluating percentage inhibition of cell growth, morphological changes of EAC cells and hematological parameters of the mice. The isolation was carried out by column chromatography and structure was revealed by 1H-NMR and 13C NMR. The result shows that, the isolated compound was identified as myricetin 4'-methoxy-3-O-α-l-rhamnopyranoside based on previously reported data. The isolated flavone effectively inhibited AAPH-induced oxidative damage to DNA; because it could inhibit the formation of circular and linear forms of the DNA. In anti-proliferative assay, 76% growth inhibition of EAC cells was observed as compare to the control mice (p<0.05) at a dose 100 mg/kg body weight. Thus the isolated flavone showed great importance as a possible therapeutic agent in preventing oxidative damage to DNA and the chronic diseases caused by such DNA damage, and can also become important in cancer chemotherapy. 相似文献
63.
Determination of community structure through deconvolution of PLFA-FAME signature of mixed population 总被引:1,自引:0,他引:1
Phospholipid fatty acids (PLFAs) as biomarkers are well established in the literature. A general method based on least square approximation (LSA) was developed for the estimation of community structure from the PLFA signature of a mixed population where biomarker PLFA signatures of the component species were known. Fatty acid methyl ester (FAME) standards were used as species analogs and mixture of the standards as representative of the mixed population. The PLFA/FAME signatures were analyzed by gas chromatographic separation, followed by detection in flame ionization detector (GC-FID). The PLFAs in the signature were quantified as relative weight percent of the total PLFA. The PLFA signatures were analyzed by the models to predict community structure of the mixture. The LSA model results were compared with the existing "functional group" approach. Both successfully predicted community structure of mixed population containing completely unrelated species with uncommon PLFAs. For slightest intersection in PLFA signatures of component species, the LSA model produced better results. This was mainly due to inability of the "functional group" approach to distinguish the relative amounts of the common PLFA coming from more than one species. The performance of the LSA model was influenced by errors in the chromatographic analyses. Suppression (or enhancement) of a component's PLFA signature in chromatographic analysis of the mixture, led to underestimation (or overestimation) of the component's proportion in the mixture by the model. In mixtures of closely related species with common PLFAs, the errors in the common components were adjusted across the species by the model. 相似文献
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Current chemotherapy focuses on the use of genotoxic drugs that may induce general DNA damage in cancer cells but also high levels of toxicity in normal tissues. Nongenotoxic activation of p53 by targeting specific molecular pathways therefore provides an attractive therapeutic strategy in cancers with wild-type p53. Here, we explored the antitumor potential of cyclin-dependent kinase (CDK) inhibitors in combination with a small molecule inhibitor of p53-murine double minute 2 (MDM2) interaction. We show that low doses of CDK inhibitors roscovitine and DRB synergize with the MDM2 antagonist nutlin-3a in the induction of p53 activity and promote p53-dependent apoptosis in a dose- and time-dependent manner. Statistical measurement of the combination effects shows that the drug combination is additive on the reduction of cell viability and synergistic on inducing apoptosis, a critical end point of cytotoxic drugs. The degree of apoptosis observed 24 to 48 h after drug treatment correlated with the accumulation of p53 protein and concomitant induction of proapoptotic proteins Puma and PIG3. The antiproliferative and cytotoxic effects of this drug combination are validated in a range of tumor-derived cells including melanoma, colon carcinoma, breast adenocarcinoma, and hepatocarcinoma cells. Furthermore, this drug combination does not induce phosphorylation of Ser(15) on p53 and does not induce genotoxic stress in the cell. Given that many cytotoxic drugs rely on their ability to induce apoptosis via DNA damage-mediated activation of p53, the data presented here may provide a new therapeutic approach for the use of CDK inhibitors and MDM2 antagonists in combinatorial drug therapy. 相似文献
66.
Myosin VI has been studied in both a monomeric and a dimeric form in vitro. Because the functional characteristics of the motor are dramatically different for these two forms, it is important to understand whether myosin VI heavy chains are brought together on endocytic vesicles. We have used fluorescence anisotropy measurements to detect fluorescence resonance energy transfer between identical fluorophores (homoFRET) resulting from myosin VI heavy chains being brought into close proximity. We observed that, when associated with clathrin-mediated endocytic vesicles, myosin VI heavy chains are precisely positioned to bring their tail domains in close proximity. Our data show that on endocytic vesicles, myosin VI heavy chains are brought together in an orientation that previous in vitro studies have shown causes dimerization of the motor. Our results are therefore consistent with vesicle-associated myosin VI existing as a processive dimer, capable of its known trafficking function. 相似文献
67.
Husemann Martin Dey Lara-Sophie Sadílek David Ueshima Norihiro Hawlitschek Oliver Song Hojun Weissman David B. 《Organisms Diversity & Evolution》2022,22(3):649-657
Organisms Diversity & Evolution - Orthoptera have some of the largest genomes of all insects. At the same time, the architecture of their genomes remains poorly understood. Comparative... 相似文献
68.
Jong Han Lee Mithun Kumer Sarker Hojung Choi Dongyun Shin Donghee Kim Hee-Sook Jun 《生物化学与生物物理学报:疾病的分子基础》2019,1865(6):1332-1340
Diabetic nephropathy (DN) is one of the major long-term complications of diabetes. Lysophosphatidic acid (LPA) signaling has been implicated in renal fibrosis. In our previous study, we found that the LPA receptor 1/3 (LPAR1/3) antagonist, ki16425, protected against DN in diabetic db/db mice. Here, we investigated the effects of a specific pharmacological inhibitor of LPA receptor 1 (LPA1), AM095, on DN in streptozotocin (STZ)-induced diabetic mice to exclude a possible contribution of LPAR3 inhibition. AM095 treatment significantly reduced albuminuria and the albumin to creatinine ratio and significantly decreased the glomerular volume and tuft area in the treated group compared with the STZ-vehicle group. In the kidney of STZ-induced diabetic mice, the expression of LPAR1 mRNA and protein was positively correlated with oxidative stress. AM095 treatment inhibited LPA-induced reactive oxygen species production and NADPH oxidase expression as well as LPA-induced toll like receptor 4 (TLR4) expression in mesangial cells and in the kidney of STZ-induced diabetic mice. In addition, AM095 treatment suppressed LPA-induced pro-inflammatory cytokines and fibrotic factors expression through downregulation of phosphorylated NFκBp65 and c-Jun N-terminal kinases (JNK) in vitro and in the kidney of STZ-induced diabetic mice. Pharmacological or siRNA inhibition of TLR4 and NADPH oxidase mimicked the effects of AM095 in vitro. In conclusion, AM095 is effective in preventing the pathogenesis of DN by inhibiting TLR4/NF-κB and the NADPH oxidase system, consequently inhibiting the inflammatory signaling cascade in renal tissue of diabetic mice, suggesting that LPAR1 antagonism might provide a potential therapeutic target for DN. 相似文献
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70.
Pierre-Yves Jean-Charles Vishwaesh Rajiv Subhodeep Sarker Sangoh Han Yushi Bai Ali Masoudi Sudha K. Shenoy 《The Journal of biological chemistry》2022,298(5)
Arrestins and their yeast homologs, arrestin-related trafficking adaptors (ARTs), share a stretch of 29 amino acids called the ART motif. However, the functionality of that motif is unknown. We now report that deleting this motif prevents agonist-induced ubiquitination of β-arrestin2 (β-arr2) and blocks its association with activated G protein–coupled receptors (GPCRs). Within the ART motif, we have identified a conserved phenylalanine residue, Phe116, that is critical for the formation of β-arr2–GPCR complexes. β-arr2 Phe116Ala mutant has negligible effect on blunting β2-adrenergic receptor–induced cAMP generation unlike β-arr2, which promotes rapid desensitization. Furthermore, available structures for inactive and inositol hexakisphosphate 6–activated forms of bovine β-arr2 revealed that Phe116 is ensconced in a hydrophobic pocket, whereas the adjacent Phe117 and Phe118 residues are not. Mutagenesis of Phe117 and Phe118, but not Phe116, preserves GPCR interaction of β-arr2. Surprisingly, Phe116 is dispensable for the association of β-arr2 with its non-GPCR partners. β-arr2 Phe116Ala mutant presents a significantly reduced protein half-life compared with β-arr2 and undergoes constitutive Lys-48-linked polyubiquitination, which tags proteins for proteasomal degradation. We also found that Phe116 is critical for agonist-dependent β-arr2 ubiquitination with Lys-63-polyubiquitin linkages that are known mediators of protein scaffolding and signal transduction. Finally, we have shown that β-arr2 Phe116Ala interaction with activated β2-adrenergic receptor can be rescued with an in-frame fusion of ubiquitin. Taken together, we conclude that Phe116 preserves structural stability of β-arr2, regulates the formation of β-arr2–GPCR complexes that inhibit G protein signaling, and promotes subsequent ubiquitin-dependent β-arr2 localization and trafficking. 相似文献