SYNTHESIS AND BIOLOGICAL EVALUATION OF 2-(2'/3'/4'/6'-SUBSTITUTED PHENYL)-1H-INDOLES

Objective: Indole derivatives were reported to a wide range of biological activities. Thus it was our aim to synthesize a series of 2-(2'/3'/4'/6'-substituted phenyl) -1H-indoles using clayzic catalyst and screen for their in vitro anti-inflammatory, antioxidant and antimicrobial activities.Methods: Various substituted acetophenones were reacted with phenylhydrazine in the presence of modified clayzic catalyst and obtained 2-(2'/3'/4'/6'-substituted phenyl)-1H-indoles in a one pot reaction. The cyclized compounds were characterized by FT-IR, NMR, UV-Vis and mass spectral analyses and screened for anti-inflammatory activity against cytokines tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) by measuring cytokine production by performing sandwich ELISA model, antioxidant activity by DPPH assay method and antimicrobial activity by well-diffusion method.Results: An eco-friendly route with better yields for the synthesis of 2-(2'/3'/4'/6'-substituted phenyl)-1H-indoles in the presence of clayzic catalyst was achieved. The biological activity results suggested that compounds (2d, 2e and 2i) have excellent anti-inflammatory activity, compounds (2a-2d and 2j) possessing better antioxidant property and compounds (2b, 2i, 2k and 2m) have promising antibacterial and antifungal activities when compared to the standard drugs.Conclusion: Synthesis of 2-(2'/3'/4'/6'-substituted phenyl)-1H-indoles was successfully achieved in the presence of clayzic catalyst. Compounds bearing amino, methyl, methoxy, hydroxyl and fluoro groups have shown better anti-inflammatory, antioxidant and antimicrobial activities when compared to the other compounds and 1H-indole.Â

Asymptomatic cardiac manifestations in CKD

Background: Chronic kidney disease is recognised as health concern globally with more than 40 percent of morbididty and mortality. CKD is one of the independent risk factor for cardiovascular diseases and its unfavourable health outcomes. The risk factors like smoking, hypertension, dyslipidemia and diabetes which are highly prevalent in CKD. The therapeutic interventions in CKD patients to reduce CVD events does not hold a desired effect and has bad prognosis in end stage renal disease. The initial evidence indicating a relationship between CKD and CVD is more apparent in patient with dialysis. The aim of the study was to evaluate the asymptomatic cardiac manifestations in 2-4 stages of CKD through non-invasive methods like ECG and Echocardiography.Methods: It is a cross sectional study investigated on 250 CKD patients receiving care in JSS hospital, Mysore. For the primary objective, correlational analysis were performed to evaluate the association of renalfunctional parameters like serum creatinine, urine albumin, eGFR with cardiac parameters through ECG and Echocardiographic changes.Results: ECG revealed LVH with pressure overload pattern in 36%. 25% patients had ST-T changes. Echocardiography revealed LVH and diastolic dysfunction as abnormalities. LVH has significant p value.Conclusions: CVD is a leading cause of morbidity and mortality in patients of CKD who succumb to Cardio vascular deaths before reaching the end stage renal disease. Thus, focus of patient care in early CKD stages should be directed to prevention of cardiovascular complications through early ECG and Echocardiography

Activation of Epithelial-Mesenchymal Transition and Altered β-Catenin Signaling in a Novel Indian Colorectal Carcinoma Cell Line

Colorectal cancer is the third major cause of cancer-related mortality worldwide. The upward trend in incidence and mortality rates, poor sensitivity to conventional therapies and a dearth of early diagnostic parameters pose a huge challenge in the management of colorectal cancer in India. Due to the high level of genetic diversity present in the Indian population, unraveling the genetic contributions toward pathogenesis is key for understanding the etiology of colorectal cancer and in reversing this trend. We have established a novel cell line, MBC02, from an Indian colorectal cancer patient and have carried out extensive molecular characterization to unravel the pathological alterations in this cell line. In-depth molecular analysis of MBC02 revealed suppression of E-cadherin expression, concomitant with overexpression of EMT related molecules, which manifested in the form of highly migratory and invasive cells. Loss of membrane-tethered E-cadherin released β-catenin from the adherens junction resulting in its cytoplasmic and nuclear accumulation and consequently, upregulation of c-Myc. MBC02 also showed dramatic transcriptional upregulation of β-catenin. Remarkably, we observed significantly elevated proteasome activity that perhaps co-evolved to compensate for the unnaturally high mRNA level of β-catenin to regulate the increased protein load. In addition, there was substantial misregulation of other clinically relevant signaling pathways that have clinical relevance in the pathogenesis of colorectal cancer. Our findings pave the way toward understanding the molecular differences that could define pathogenesis in cancers originating in the Indian population

An efficient system for the generation of marked genetic mutants in members of the genus Burkholderia

To elucidate the function of a gene in bacteria it is vital that targeted gene inactivation (allelic replacement) can be achieved. Allelic replacement is often carried out by disruption of the gene of interest by insertion of an antibiotic-resistance marker followed by subsequent transfer of the mutant allele to the genome of the host organism in place of the wild-type gene. However, due to their intrinsic resistance to many antibiotics only selected antibiotic-resistance markers can be used in members of the genus Burkholderia, including the Burkholderia cepacia complex (Bcc). Here we describe the construction of improved antibiotic-resistance cassettes that specify resistance to kanamycin, chloramphenicol or trimethoprim effectively in the Bcc and related species. These were then used in combination with and/or to construct a series enhanced suicide vectors, pSHAFT2, pSHAFT3 and pSHAFT-GFP to facilitate effective allelic replacement in the Bcc. Validation of these improved suicide vectors was demonstrated by the genetic inactivation of selected genes in the Bcc species Burkholderia cenocepacia and B. lata, and in the non-Bcc species, B. thailandensis

Significance of Thymosin β4 and Implication of PINCH-1-ILK-α-Parvin (PIP) Complex in Human Dilated Cardiomyopathy

Myocardial remodeling is a major contributor in the development of heart failure (HF) after myocardial infarction (MI). Integrin-linked kinase (ILK), LIM-only adaptor PINCH-1, and α-parvin are essential components of focal adhesions (FAs), which are highly expressed in the heart. ILK binds tightly to PINCH-1 and α-parvin, which regulates FA assembly and promotes cell survival via the activation of the kinase Akt. Mice lacking ILK, PINCH or α-parvin have been shown to develop severe defects in the heart, suggesting that these proteins play a critical role in heart function. Utilizing failing human heart tissues (dilated cardiomyopathy, DCM), we found a 2.27-fold (p<0.001) enhanced expression of PINCH, 4 fold for α-parvin, and 10.5 fold (p<0.001) for ILK as compared to non-failing (NF) counterparts. No significant enhancements were found for the PINCH isoform PINCH-2 and parvin isoform β-parvin. Using a co-immunoprecipitation method, we also found that the PINCH-1-ILK-α-parvin (PIP) complex and Akt activation were significantly up-regulated. These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model. Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression—the hallmarks of cardiac fibrosis. In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI. These data suggest that the PIP complex and activation of Akt play critical roles in HF development. Tβ4 treatment likely improves cardiac function by enhancing PIP mediated Akt activation and suppressing NF-κB activation and collagen-mediated fibrosis. These data provide significant insight into the role of the PIP-Akt pathway and its regulation by Tβ4 treatment in post-MI

Big Data Analytics for Wireless and Wired Network Design: A Survey

Currently, the world is witnessing a mounting avalanche of data due to the increasing number of mobile network subscribers, Internet websites, and online services. This trend is continuing to develop in a quick and diverse manner in the form of big data. Big data analytics can process large amounts of raw data and extract useful, smaller-sized information, which can be used by different parties to make reliable decisions. In this paper, we conduct a survey on the role that big data analytics can play in the design of data communication networks. Integrating the latest advances that employ big data analytics with the networks’ control/traffic layers might be the best way to build robust data communication networks with refined performance and intelligent features. First, the survey starts with the introduction of the big data basic concepts, framework, and characteristics. Second, we illustrate the main network design cycle employing big data analytics. This cycle represents the umbrella concept that unifies the surveyed topics. Third, there is a detailed review of the current academic and industrial efforts toward network design using big data analytics. Forth, we identify the challenges confronting the utilization of big data analytics in network design. Finally, we highlight several future research directions. To the best of our knowledge, this is the first survey that addresses the use of big data analytics techniques for the design of a broad range of networks

Asymptomatic cardiac manifestations in CKD

Background: Chronic kidney disease is recognised as health concern globally with more than 40 percent of morbididty and mortality. CKD is one of the independent risk factor for cardiovascular diseases and its unfavourable health outcomes. The risk factors like smoking, hypertension, dyslipidemia and diabetes which are highly prevalent in CKD. The therapeutic interventions in CKD patients to reduce CVD events does not hold a desired effect and has bad prognosis in end stage renal disease. The initial evidence indicating a relationship between CKD and CVD is more apparent in patient with dialysis. The aim of the study was to evaluate the asymptomatic cardiac manifestations in 2-4 stages of CKD through non-invasive methods like ECG and Echocardiography.Methods: It is a cross sectional study investigated on 250 CKD patients receiving care in JSS hospital, Mysore. For the primary objective, correlational analysis were performed to evaluate the association of renalfunctional parameters like serum creatinine, urine albumin, eGFR with cardiac parameters through ECG and Echocardiographic changes.Results: ECG revealed LVH with pressure overload pattern in 36%. 25% patients had ST-T changes. Echocardiography revealed LVH and diastolic dysfunction as abnormalities. LVH has significant p value.Conclusions: CVD is a leading cause of morbidity and mortality in patients of CKD who succumb to Cardio vascular deaths before reaching the end stage renal disease. Thus, focus of patient care in early CKD stages should be directed to prevention of cardiovascular complications through early ECG and Echocardiography

Synthesis and characterization of urea nitrate and nitrourea

Urea nitrate (UN) has not found use as a legitimate explosive but is commonly used as an improvised explosive. The dehydration product of UN is nitrourea (NU). Visually both UN and NU are white solids that both melt around 1608C. Other properties differ markedly as might be expected from an inorganic salt (UN) and an organic molecular compound (NU). An extensive physical characterization of NU and UN is reported. Two reported routes to the NU product are compared and a decomposition mechanism of UN proposed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Metabolic abnormalities, liver and body fat in American versus Chinese patients with non-alcoholic fatty liver disease

Background and AimNon-alcoholic fatty liver disease (NAFLD) is common in the United States and China. We compared prevalence of metabolic syndrome (MS), hepatic steatosis and fibrosis, and quantity and quality of body fat between American versus Chinese patients with NAFLD.MethodsNAFLD patients were prospectively recruited from the University of Michigan Health System (UMHS) in the United States and Peking University Health Sciences Center (PUHSC) in China. All patients had baseline computed tomography (CT), laboratory tests and Fibroscan® controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Comparisons were made for overall cohorts and matched cohorts (matched for sex, age, and body mass index [BMI] category). Logistic regression was performed to identify independent predictors of moderate and severe steatosis and lack of advanced fibrosis.ResultsOne-hundred and one American and One-hundred and sixty Chinese patients were included. UMHS patients were older, with higher prevalence of MS, had higher LSM and CAP scores, and more fat in liver, visceral, subcutaneous, and muscle compartments than PUHSC patients. Differences in LSM, visceral fat Hounsfield unit, and subcutaneous fat area (SFA) persisted in the matched cohort. NAFLD patients with MS had significantly higher LSM, and more fat in liver, visceral, subcutaneous and muscle compartments than those without. Moderate or severe steatosis was independently associated with MS, visceral fat quality, and SFA, while the absence of advanced fibrosis was associated with Asian race and not having MS.ConclusionAmerican patients with NAFLD had more liver fibrosis than Chinese patients despite having better quality visceral fat and after matching for age, sex, and BMI category.One-hundred and one American (University of Michigan Health System) and one-hundred and sixty Chinese (Peking University Health Sciences Center) patients with non-alcoholic fatty liver disease were included in this study and 64 in each cohort were matched for sex, age, and body mass index category.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/173140/1/jgh312756_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173140/2/jgh312756.pd