Anti-bacterial activity of neoandrographolide derivatives: In silico interaction with the bacterial target

157-164Natural products and their semi synthesized molecules have been used as efficient antibiotics since a long time. The present global health scenario has raised the demand for novel antimicrobial agents and drug targets that are effective against drug resistant pathogens, emerging infections etc. The current study has promoted the antibacterial activity of the glucoside labdane ‘neoandrographolide’, isolated from the methanolic extract of the medicinal plant Andrographis paniculata. Further modification at its glucoside hydroxyl groups to generate ester and acetonide derivatives was done and the antibacterial potential of these compounds was screened against common bacterial pathogens. Among various derivatives, 4,6-O-(4-methoxybenzylidene) neoandrographolide exhibited promising results. In addition, molecular modeling study of the active compound was also explored to identify its probable binding mode on the bacterial target. The present study reported antibacterial activity of neoandrographolide derivatives for first time and also the bioactive molecule, 4,6-O-(4-methoxybenzylidene) neoandrographolide was examined as a potent antibacterial agent against different strains

Bioinformatics Tools and Genomic Resources Available in Understanding the Structure and Function of Gossypium

Cotton is economically and evolutionarily important crop for its fiber. In order to improve fiber quality and yield, and to exploit the natural genetic potential inherent in genotypes, understanding genome structure and function of cultivated cotton is important. In order to achieve this, a functional understanding of bioinformatics resources such as databases, software solutions, and analysis tools is required. But currently, there are very few unified reports on bioinformatics tools and even fewer repositories to access cotton genomic information. Also, resourceful developers and bioinformatics scientists actively addressing complex genomic challenges in cotton genomes are much in need. The primary goal of this chapter is to provide a review of such tools and resources for analyzing the structure and function of the cotton genome with preferential emphasis on this complex and economically important plant species. This discourse begins with a description of concurrent advances in high‐throughput genome sequencing and bioinformatics analyses and focuses on four major sections covering bioinformatics tools and resources for analysis of: (1) genomes; (2) transcriptomes; (3) small RNAs; and (4) epigenomes. In each section, recent advances in cotton have been discussed. Cotton genome sequencing and annotation efforts are outlined within these sections. This review discusses the availability of genome information of both diploid and tetraploid species that have impelled cotton genome research into the post‐genomics era, opening new avenues for exploring regulatory mechanisms associated with fine‐tuning of gene expression of fiber‐related genes. Finally, the potential impacts of these rapid advances, especially the challenges in handling and analyzing the large datasets are discussed

Biliary Strictures after Liver Transplantation

Biliary strictures are one of the most common complications following liver transplantation, representing an important cause of morbidity and mortality in transplant recipients. The reported incidence of biliary stricture is 5% to 15% following deceased donor liver transplantations and 28% to 32% following living donor liver transplantations. Bile duct strictures following liver transplantation are easily and conveniently classified as anastomotic strictures (AS) or non-anastomotic strictures (NAS). NAS are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and the need for retransplantation. Current endoscopic strategies to correct biliary strictures following liver transplantation include repeated balloon dilatations and the placement of multiple side-by-side plastic stents. Endoscopic balloon dilatation with stent placement is successful in the majority of AS patients. In patients for whom gaining biliary access is technically difficult, a combined endoscopic and percutaneous/surgical approach proves quite useful. Future directions, including novel endoscopic retrograde cholangiopancreatography techniques, advanced endoscopy, and improved stents could allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. The aim of this review is to detail the present status of endoscopy in the diagnosis, treatment, outcome, and future directions of biliary strictures related to orthotopic liver transplantation from the viewpoint of a clinical gastroenterologists

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Anti-bacterial activity of neoandrographolide derivatives: In silico interaction with the bacterial target

Natural products and their semi synthesized molecules have been used as efficient antibiotics since a long time. The present global health scenario has raised the demand for novel antimicrobial agents and drug targets that are effective against drug resistant pathogens, emerging infections etc. The current study has promoted the antibacterial activity of the glucoside labdane ‘neoandrographolide’, isolated from the methanolic extract of the medicinal plant Andrographis paniculata. Further modification at its glucoside hydroxyl groups to generate ester and acetonide derivatives was done and the antibacterial potential of these compounds was screened against common bacterial pathogens. Among various derivatives, 4,6-O-(4-methoxybenzylidene) neoandrographolide exhibited promising results. In addition, molecular modeling study of the active compound was also explored to identify its probable binding mode on the bacterial target. The present study reported antibacterial activity of neoandrographolide derivatives for first time and also the bioactive molecule, 4,6-O-(4-methoxybenzylidene) neoandrographolide was examined as a potent antibacterial agent against different strains

Life cycle assessment of buildings: A review

Sustainable development requires methods and tools to measure and compare the environmental impacts of human activities for various products (goods and services). Providing society with goods and services contribute to a wide range of environmental impacts. Environmental impacts include emissions into the environment and the consumption of resources as well as other inventions such as land use etc. In order to create an environmentally-conscious building, the environmental impacts of entire service life must be known. The aim of this study is to review various buildings at different places, whose LCA has been performed and to see that which phase of the life cycle of building and which type of building consumes more energy and have more greenhouse gas (GHG) emissions. It has been observed that operational phase alone contributes more than 50% to GHG emissions and is highest energy consumer (80-85%) which is a matter of concern and cannot be ignored. Now there is a need for some alternative ways to design buildings for a sustainable future.

Identification of TBK1 inhibitors using a combination of pharmacophore- and machine learning-based approaches

The CHEMBL File containing RAW data of TBK-1 inhibition has been added to the github repository in asset folder. The code for making binary predictions has been deployed in the github link below: https://github.com/tanush84/TBK1-Binary_classification_Model.git The Link for the KCB database is https://chembank.org

Iodate induced toxic retinopathy: a case report

Abstract Background Iodine deficiency is a common preventable cause of intellectual and developmental disabilities. Iodine in the form of potassium iodate is added to the common salt under the National Iodine Deficiency Disorder Control Program in India. Overdose of iodate can lead to retinal toxicity. Case presentation We hereby present a case of a 34 year old male patient who presented to us 10 years following iodate ingestion. There was widespread outer retinal atrophy, foveal atrophy and sub-retinal fibrosis noted on fundus evaluation. The fundus fluorescein angiogram was suggestive of window defects while the scotopic electroretinogram showed diminished amplitude pointing towards a grave prognosis. Conclusions Excessive ingestion of potassium iodate can lead to outer retinal atrophy due to its toxicity to the retinal pigment epithelium and photo-receptors. The degree of damage is dependent on the ingested dose

A Simple Method for Fabrication of Self-sharpened Silicon Tips for Atomic Force Microscopy Applications

A simple and high yield method is presented for the bulk generation of atomic force microscopy (AFM) probes with self-sharpened silicon tips. The experimental setup includes a controlled chemical etching environment at a constant temperature with continuous recirculation and filtration. A KOH solution is considered cost-effective as the etchant and stabilized to the required concentration (55%, v/v) and temperature (40 degrees C), so as to provide an etch rate of 40 nm min(-1) and yield a smooth etch profile. A high density of silicon tips is fabricated, with yield up to 90%, and a consistent tip radius of approximate to 12.73 +/- 1.51 nm. These tips can be successfully integrated with AFM cantilevers, resulting in AFM probes. Further, such AFM-probes are well characterized using laser Doppler vibrometry and scanning electron microscopy. The result shows a resonance frequency of 1.2-1.4 MHz and a high-quality factor of approximate to 708.8. In addition, the AFM probes produced images are comparable in quality to those obtained from commercially available probes