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101.
Gangwei Ou Pramod Kumar Rompikuntal Aziz Bitar Barbro Lindmark Karolis Vaitkevicius Sun Nyunt Wai Marie-Louise Hammarstr?m 《PloS one》2009,4(11)
Background
Vibrio cholerae is the causal intestinal pathogen of the diarrheal disease cholera. It secretes the protease PrtV, which protects the bacterium from invertebrate predators but reduces the ability of Vibrio-secreted factor(s) to induce interleukin-8 (IL-8) production by human intestinal epithelial cells. The aim was to identify the secreted component(s) of V. cholerae that induces an epithelial inflammatory response and to define whether it is a substrate for PrtV.Methodology/Principal Findings
Culture supernatants of wild type V. cholerae O1 strain C6706, its derivatives and pure V. cholerae cytolysin (VCC) were analyzed for the capacity to induce changes in cytokine mRNA expression levels, IL-8 and tumor necrosis factor-α (TNF-α) secretion, permeability and cell viability when added to the apical side of polarized tight monolayer T84 cells used as an in vitro model for human intestinal epithelium. Culture supernatants were also analyzed for hemolytic activity and for the presence of PrtV and VCC by immunoblot analysis.Conclusions/Significance
We suggest that VCC is capable of causing an inflammatory response characterized by increased permeability and production of IL-8 and TNF-α in tight monolayers. Pure VCC at a concentration of 160 ng/ml caused an inflammatory response that reached the magnitude of that caused by Vibrio-secreted factors, while higher concentrations caused epithelial cell death. The inflammatory response was totally abolished by treatment with PrtV. The findings suggest that low doses of VCC initiate a local immune defense reaction while high doses lead to intestinal epithelial lesions. Furthermore, VCC is indeed a substrate for PrtV and PrtV seems to execute an environment-dependent modulation of the activity of VCC that may be the cause of V. cholerae reactogenicity. 相似文献102.
Sharma-Walia N Raghu H Sadagopan S Sivakumar R Veettil MV Naranatt PP Smith MM Chandran B 《Journal of virology》2006,80(13):6534-6552
103.
Dong Young Kang Nipin S.P. Pramod Darvin Youn Hee Joung Hyo Joo Byun Chang Hee Do 《Animal biotechnology》2017,28(3):189-197
Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression. 相似文献
104.
Informed Consent in Health Research: Challenges and Barriers in Low‐and Middle‐Income Countries with Specific Reference to Nepal
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Pramod R. Regmi Nirmal Aryal Om Kurmi Puspa Raj Pant Edwin van Teijlingen Sharada P. Wasti 《Developing world bioethics》2017,17(2):84-89
Obtaining ‘informed consent’ from every individual participant involved in health research is a mandatory ethical practice. Informed consent is a process whereby potential participants are genuinely informed about their role, risk and rights before they are enrolled in the study. Thus, ethics committees in most countries require ‘informed consent form’ as part of an ethics application which is reviewed before granting research ethics approval. Despite a significant increase in health research activity in low‐and middle‐income countries (LMICs) in recent years, only limited work has been done to address ethical concerns. Most ethics committees in LMICs lack the authority and/or the capacity to monitor research in the field. This is important since not all research, particularly in LMICs region, complies with ethical principles, sometimes this is inadvertently or due to a lack of awareness of their importance in assuring proper research governance. With several examples from Nepal, this paper reflects on the steps required to obtain informed consents and highlights some of the major challenges and barriers to seeking informed consent from research participants. At the end of this paper, we also offer some recommendations around how can we can promote and implement optimal informed consent taking process. We believe that paper is useful for researchers and members of ethical review boards in highlighting key issues around informed consent. 相似文献
105.
Nagarani Thotakura Mukesh Dadarwal Pramod Kumar Gajanand Sharma Santosh Kumar Guru Shashi Bhushan Kaisar Raza Om Prakash Katare 《AAPS PharmSciTech》2017,18(3):759-768
Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells. The conjugate was characterized by FT-IR and NMR, and the nanocarrier was characterized for micromeritics, surface charge, drug loading, and morphological attributes. The efficacy was evaluated by in vitro MTT studies, safety by erythrocyte compatibility, and biodistribution by in vivo pharmacokinetic studies. Despite better drug loading and sustained drug release, cytotoxicity on MCF-7 breast cancer cells was substantially enhanced and the pharmacokinetic profile was significantly modified. The AUC was enhanced manifolds along with reduced clearance. The findings are unique and provide an alternative to the conventional lipid-based nanocarriers for better dose delivery, tissue adhesion, and desired pharmacokinetic modulation. 相似文献
106.
107.
Development of highly efficient and reproducible plant regeneration system has tremendous potential to provide improved technology to assist in genetic transformation of indica rice cultivars for their further exploitation in selection. For the development of a highly reproducible regeneration system through somatic embryogenesis, mature embryos of highly popular rice cultivars i.e., Govind (for rainfed areas), Pusa Basmati-1 (aromatic basmati) and Jaya (for irrigated areas) were used. Optimum callus formation (%) to MS medium supplemented with 2, 4-D was obtained at 12.0 microM in Govind, 14.0 microM in Jaya and 15.0 microM in Pusa Basmati-1. All the cultivars showed good proliferation on MS medium without hormone. In Govind, highest embryogenic response was observed in MS medium supplemented with 2, 4-D (0.4 microM) + kinetin (0.4 microM), while in Pusa Basmati-1 with 2, 4-D (0.4 microM) + kinetin (2.0 microM) and in Jaya on hormone-free MS medium. Excellent embryo regeneration in Govind was observed on MS medium supplemented with low concentrations (1.1 microM) of BAP or hormone-free MS medium, while in Pusa Basmati-1 and Jaya embryogenesis was observed on MS medium supplemented with higher concentration of BAP (2.2 microM). Similarly, maximum plantlets with proliferated roots were observed in Govind on hormone-free MS medium, while in Pusa Basmati-1 and Jaya on MS medium supplemented with high concentration of NAA (4.0 microM). Developed plantlets were further successfully acclimatized and grown under pot culture up to maturity. Further the yield potential of in vitro developed plants was accessed at par to the direct seeded one under pot culture. Present, protocol standardizes somatic embryogenesis and efficient regeneration of agronomically important, high yielding and diverse indica rice cultivars which can be utilized as an efficient tool for molecular studies and genetic transformation in future. 相似文献
108.
A new family of mononuclear Zn(II) complexes [Zn(Pyimpy)2](ClO4)2 (1), [Zn(Pyimpy)(Cl)2] (2), [Zn(Pyimpy)(SCN)2] (3) and [Zn(Pyimpy)(N3)2] (4) were synthesized using designed tridentate ligand Pyimpy having NNN donors (Pyimpy: (2-((2-phenyl-2-(pyridin-2-l)hydazono)methyl)pyridine)). Complexes were characterized by different spectroscopic studies and it has been found out that all complexes exhibited strong fluorescent emission at room temperature. Molecular structures of [Zn(Pyimpy)2](ClO4)2·C6H5CH3·0.5H2O (1·C6H5CH3·0.5H2O) and [Zn(Pyimpy)(Cl)2]·CH3CN (2·CH3CN) were determined by X-ray crystallography and ligand coordinated Zn(II) ions was described as distorted octahedral and distorted square pyramidal, respectively. DNA binding properties of these complexes were investigated by absorption spectral, fluorescence quenching and circular dichroism spectral studies. 相似文献
109.
Identification of potential drug targets is the first step in the process of modern drug discovery, subjected to their validation
and drug development. Whole genome sequences of a number of organisms allow prediction of potential drug targets using sequence
comparison approaches. Here, we present a subtractive approach exploiting the knowledge of global gene expression along with
sequence comparisons to predict the potential drug targets more efficiently. Based on the knowledge of 155 known virulence
and their coexpressed genes mined from microarray database in the public domain, 357 coexpressed probable virulence genes
for Vibrio cholerae were predicted. Based on screening of Database of Essential Genes using blastn, a total of 102 genes out of these 357 were
enlisted as vitally essential genes, and hence good putative drug targets. As the effective drug target is a protein which
is only present in the pathogen, similarity search of these 102 essential genes against human genome sequence led to subtraction
of 66 genes, thus leaving behind a subset of 36 genes whose products have been called as potential drug targets. The gene
ontology analysis using Blast2GO of these 36 genes revealed their roles in important metabolic pathways of V. cholerae or on the surface of the pathogen. Thus, we propose that the products of these genes be evaluated as target sites of drugs
against V. cholerae in future investigations. 相似文献
110.
Heat shock proteins and immune response: methods to madness 总被引:3,自引:0,他引:3
Srivastava P 《Methods (San Diego, Calif.)》2004,32(1):1-2