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61.
Sudipta Hazra Subhalakshmi Ghosh Madhushree Das Sarma Smriti Sharma Mousumi Das Prakash Saudagar Vijay Kumar Prajapati Vikash Kumar Dubey Shyam Sundar Banasri Hazra 《Experimental parasitology》2013
World health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. Diospyrin, a bis-naphthoquinone isolated from Diospyros montana Roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including Leishmania. Presently, we have investigated the antileishmanial effect of a di-epoxide derivative of diospyrin (D17), both in vitro and in vivo. Further, the safety profile of D17 was established by testing its toxicity against normal macrophage cells (IC50 ∼ 20.7 μM), and also against normal BALB/c mice in vivo. The compound showed enhanced activity (IC50 ∼ 7.2 μM) as compared to diospyrin (IC50 ∼ 12.6 μM) against Leishmania donovani promastigotes. Again, D17 was tested on L. donovani BHU1216 isolated from a sodium stibogluconate-unresponsive patient, and exhibited selective inhibition of the intracellular amastigotes (IC50 ∼ 0.18 μM). Also, treatment of infected BALB/c mice with D17 at 2 mg/kg/day reduced the hepatic parasite load by about 38%. Subsequently, computational docking studies were undertaken on selected enzymes of trypanothione metabolism, viz. trypanothione reductase (TryR) and ornithine decarboxylase (ODC), followed by the enzyme kinetics, where D17 demonstrated non-competitive inhibition of the L. donovani ODC, but could not inhibit TryR. 相似文献
62.
Ramachandran Prakasam Mitsuaki Fujimoto Ryosuke Takii Naoki Hayashida Eiichi Takaki Ke Tan Fangxu Wu Sachiye Inouye Akira Nakai 《FEBS letters》2013
The febrile response is elicited by pyrogenic cytokines including IL-6 in response to microorganism infections and diseases in vertebrates. Mammalian HSF1, which senses elevations in temperature, negatively regulates the response by suppressing pyrogenic cytokine expression. We here showed that HSF3, an avian ortholog of mammalian HSF1, directly binds to and activates IL-6 during heat shock in chicken cells. Other components of the febrile response mechanism, such as IL-1β and ATF3, were also differently regulated in mammalian and chicken cells. These results suggest that the febrile response is exacerbated by a feed-forward circuit composed of the HSF3-IL-6 pathway in birds. 相似文献
63.
Sellappan Selvamurugan Rangasamy Ramachandran Periasamy Viswanathamurthi 《Biometals》2013,26(5):741-753
A series of hexa-coordinated ruthenium(II) complexes of the type [Ru(CO)(B)L n ] (n = 1–4; B = PPh3, AsPh3 or Py) have been synthesized by reacting dibasic quadridentate Schiff base ligands H2L n (n = 1–4) with starting complexes [RuHCl(CO)(EPh3)2(B)] (E = P or As; B = PPh3, AsPh3 or Py). The synthesized complexes were characterized using elemental and various spectral studies including UV–Vis, FT-IR, NMR (1H, 13C and 31P) and mass spectroscopy. An octahedral geometry was tentatively proposed for all the complexes based on the spectral data obtained. The experiments on antioxidant activity showed that the ruthenium(II) S-methylisothiosemicarbazone Schiff base complexes exhibited good scavenging activity against various free radicals (DPPH, OH and NO). The in vitro cytotoxicity of these complexes has been evaluated by MTT assay. The results demonstrate that the complexes have good anticancer activities against selected cancer cell line, human breast cancer cell line (MCF-7) and human skin carcinoma cell line (A431). The DNA cleavage studies showed that the complexes have better cleavage of pBR 322 DNA. 相似文献
64.
Peter Bellstedt Thomas Seiboth Sabine Häfner Henriette Kutscha Ramadurai Ramachandran Matthias Görlach 《Journal of biomolecular NMR》2013,57(1):65-72
NMR-based structure determination of a protein requires the assignment of resonances as indispensable first step. Even though heteronuclear through-bond correlation methods are available for that purpose, challenging situations arise in cases where the protein in question only yields samples of limited concentration and/or stability. Here we present a strategy based upon specific individual unlabeling of all 20 standard amino acids to complement standard NMR experiments and to achieve unambiguous backbone assignments for the fast precipitating 23 kDa catalytic domain of human aprataxin of which only incomplete standard NMR data sets could be obtained. Together with the validation of this approach utilizing the protein GB1 as a model, a comprehensive insight into metabolic interconversion ("scrambling”) of NH and CO groups in a standard Escherichia coli expression host is provided. 相似文献
65.
Wen-Jie Mu Wen-Jing Zhong Ji-Yi Yao Lu-Jing Li Yu-lan Peng Yi Wang Li-sha Liu Ying Xiao Shou-jun Liu Chang-jun Wu Yu-xin Jiang Shyam Sundar Parajuly Ping Xu Yi Hao Jing Li Bao-Ming Luo Hui Zhi 《PloS one》2016,11(2)
Background
This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ultrasonographic elastography(UE).Materials and Methods
From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.Results
The strain ratios of benign lesions (mean, 2.6±2.0) and malignant lesions (mean,7.9±5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4.Conclusions
Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4. 相似文献66.
Angiopoietin‐2, its soluble receptor Tie‐2, and metabolic syndrome components in a population‐based sample
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67.
Poulami Das Akanksha Bansal Sudha Narayan Rao Kedar Deodhar Umesh Mahantshetty Shyam K. Shrivastava Karthikeyan Sivaraman Rita Mulherkar 《PloS one》2016,11(11)
There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer. 相似文献
68.
Cesar Meleza Bobbie Thomasson Chidambaram Ramachandran Jason W. O'Neill Klaus Michelsen Mei-Chu Lo 《Analytical biochemistry》2016
Prostaglandin D2 synthase (PGDS) catalyzes the isomerization of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2). PGD2 produced by hematopoietic prostaglandin D2 synthase (H-PGDS) in mast cells and Th2 cells is proposed to be a mediator of allergic and inflammatory responses. Consequently, inhibitors of H-PGDS represent potential therapeutic agents for the treatment of inflammatory diseases such as asthma. Due to the instability of the PGDS substrate PGH2, an in-vitro enzymatic assay is not feasible for large-scale screening of H-PGDS inhibitors. Herein, we report the development of a competition binding assay amenable to high-throughput screening (HTS) in a scintillation proximity assay (SPA) format. This assay was used to screen an in-house compound library of approximately 280,000 compounds for novel H-PGDS inhibitors. The hit rate of the H-PGDS primary screen was found to be 4%. This high hit rate suggests that the active site of H-PGDS can accommodate a large diversity of chemical scaffolds. For hit prioritization, these initial hits were rescreened at a lower concentration in SPA and tested in the LAD2 cell assay. 116 compounds were active in both assays with IC50s ranging from 6 to 807 nM in SPA and 82 nM to 10 μM in the LAD2 cell assay. 相似文献
69.
70.
Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology 总被引:1,自引:0,他引:1
Marcela Montes de Oca Rajiv Kumar Fabian de Labastida Rivera Fiona H Amante Meru Sheel Rebecca J. Faleiro Patrick T. Bunn Shannon E. Best Lynette Beattie Susanna S. Ng Chelsea L. Edwards Werner Muller Erika Cretney Stephen L. Nutt Mark J. Smyth Ashraful Haque Geoffrey R. Hill Shyam Sundar Axel Kallies Christian R. Engwerda 《PLoS pathogens》2016,12(1)
Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation. 相似文献