Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Angiotensin-II down-regulates cardiac natriuretic peptide receptor-A mediated anti-hypertrophic signaling in experimental rat hearts

48-55Atrial natriuretic peptide (ANP) exerts anti-hypertrophic effects in the heart via natriuretic peptide receptor-A (NPR-A). However, ANP mediated anti-hypertrophic activity is decreased in the cardiomyopathic conditions. In the present investigation the <i style="mso-bidi-font-style: normal">in vivo effects of angiotensin II (Ang II), a hypertrophic agonist have been studied on the ventricular expression level of NPR-A in Wistar rat hearts. NPR-A expression at the protein and mRNA levels were found to be markedly reduced by 5-fold respectively in Ang II infused rats heart as compared with sham rat hearts. Moreover, cGMP production in response to ANP was reduced by 77% in the isolated cardiac membrane preparation from the Ang II infused rat hearts. Losartan treatment reversed NPR-A expression and responsiveness to ANP. This study suggests that Ang II down regulates cardiac NPR-A activity by suppressing Npr1 gene transcription

An In Silico Approach towards the Prediction of Druglikeness Properties of Inhibitors of Plasminogen Activator Inhibitor1

Diabetic retinopathy is the leading cause of blindness worldwide. It is caused by the abnormal growth of the retinal blood vessels. Plasminogen activator inhibitor1 (PAI1) is the key growth factor and the inhibition of PAI1 can reduce the angiogenesis. In this study, currently available inhibitors are taken and tested for the toxicity, binding affinity, and bioactivities of the compounds by in silico approach. Five toxic free inhibitors were identified, among which N-acetyl-D-glucosamine shows the significant binding affinity and two of the molecules are having the better bioactivity properties. The molecular optimization of 2-(acetylamino)-2-deoxy-A-D-glucopyranose and alpha-L-fucose can be used for the treatment of diabetic retinopathy

Antiobiotic Resistance in Catheterised Patients

Background Microbial biofilms pose a public health problem for persons requiring indwelling medical devices, as micro-organisms in biofilms are difficult to treat with antimicrobial agents. Thus the present study includes biofilm formation and antibiotic resistance pattern of uropathogens in hospitalised patients with catheter associated urinary tract infections (UTI). Method This prospective analysis included 100 urine samples from catheterised patients with symptoms of UTI over a period of six months. Following identification, all isolates were subjected to antibiotic sensitivity using modified Kirby-Bauer disc diffusion method. Detection of biofilms was done by tube adherence method and Congo red agar method. Results E.coli was found to be the most frequently isolated uropathogen 70%, followed by Klebsiella pneumoniae 16%, Pseudomonas aeruginosa 4%, Acinetobacter spp 2%, coagulase negative Staphylococci 6% and Enterococci spp 2%. In the current study 60% of strains were in vitro positive for biofilm production. Biofilm positive isolates showed 93.3%, 83.3%, 73.3% and 80% resistance to nalidixic acid, ampicillin, cephotaxime and cotrimoxazole, respectively, compared to 70%, 60%, 35%, 60% resistance showed by biofilm non-producers for the respective antibiotics. Approximately 80% of the biofilm producing strains showed multidrug resistant phenotype ConclusionE.coli was the most frequent isolate, of which 63% were biofilm producers. The antibiotic susceptibility pattern in the present study showed quinolones were the least active drug against uropathogens. The uropathogens showed the highest sensitivity to carbapenems. The next best alternatives were aminoglycosides. Significant correlation between biofilm production and multi-drug resistance was observed in our study

Impact of Copper Oxide Nanoparticles on Enhancement of Bioactive Compounds Using Cell Suspension Cultures of <i>Gymnema sylvestre</i> (Retz.) R. Br

Gymnema sylvestre is a plant that is enriched in bioactive compounds. In particular, gymnemic acids (GA) and phenolic compounds (PC) are pharmaceutically important. There is a commercial demand for naturally occurring bioactive compounds, but their availability is limited due to geographical and seasonal variations. The elicitation approach can enhance the biosynthesis of phytochemicals during in vitro culture of G. sylvestre. Here, to further improve gymnemic acid II (GA II) and phenolic compounds (PC) production by G. sylvestre, cell suspension cultures (CSC), which has attracted attention for the production of essential phytochemicals, was explored using copper oxide nanoparticles (CuO NPs). Callus was obtained on MS medium containing 2,4-dichlorophenoxyacetic acid, kinetin, phytoagar, and sucrose. Agar-free MS medium was used to initiate CSC, which was treated with three concentrations of CuO NPs (1, 3 or 5 mg/L). Treatment for 48 h with 3 mg/L CuO NPs resulted in the greatest yields of GA II, total phenolics, and flavonoids. The cultures also displayed pronounced antioxidant, antidiabetic, anti-inflammatory, antibacterial, antifungal, and anticancer activities. The use of CuO NPs (3 mg/L) significantly increased the production of GA II (nine-fold) and PC compared to unamended CSC. We propose that CSC and use of nanoparticles (NPs) as a new generation of elicitors, offer a suitable prospect for the production of bioactive compounds

Marine algal secondary metabolites promising anti-angiogenesis factor against retinal neovascularization in CAM model

Retinal angiogenesis is an angle of new blood vessels on retinal surface. This neovascularization condition within the eye contributes to visual loss. Commonest cause of this condition includes diabetes, retinopathy of prematurity, retinal vein occlusion, etc. A variety of endothelial cell growth factors have been identified as a responsible factor and previous studies report that marine metabolites are promising molecules against retinal angiogenesis. Based on the background information collected, the present study focused to insight the anti-angiogenesis effect of metabolites present in marine algae. Findings of CAM assay suggested that the extract obtained from the marine algae Dictayota dichotoma are effective against angiogenesis

Genetic Disruption of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Triggers Differential Cardiac Fibrosis and Disorders in Male and Female Mutant Mice: Role of TGF-&beta;1/SMAD Signaling Pathway

The global targeted disruption of the natriuretic peptide receptor-A (NPRA) gene (Npr1) in mice provokes hypertension and cardiovascular dysfunction. The objective of this study was to determine the mechanisms regulating the development of cardiac fibrosis and dysfunction in Npr1 mutant mice. Npr1 knockout (Npr1&minus;/&minus;, 0-copy), heterozygous (Npr1+/&minus;, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were treated with the transforming growth factor (TGF)-&beta;1 receptor (TGF-&beta;1R) antagonist GW788388 (2 &micro;g/g body weight/day; ip) for 28 days. Hearts were isolated and used for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analyses. The Npr1&minus;/&minus; (0-copy) mice showed a 6-fold induction of cardiac fibrosis and dysfunction with markedly induced expressions of collagen-1&alpha; (3.8-fold), monocyte chemoattractant protein (3.7-fold), connective tissue growth factor (CTGF, 5.3-fold), &alpha;-smooth muscle actin (&alpha;-SMA, 6.1-fold), TGF-&beta;RI (4.3-fold), TGF-&beta;RII (4.7-fold), and phosphorylated small mothers against decapentaplegic (pSMAD) proteins, including pSMAD-2 (3.2-fold) and pSMAD-3 (3.7-fold), compared with wild-type mice. The expressions of phosphorylated extracellular-regulated kinase ERK1/2 (pERK1/2), matrix metalloproteinases-2, -9, (MMP-2, -9), and proliferating cell nuclear antigen (PCNA) were also significantly upregulated in Npr1 0-copy mice. The treatment of mutant mice with GW788388 significantly blocked the expression of fibrotic markers, SMAD proteins, MMPs, and PCNA compared with the vehicle-treated control mice. The treatment with GW788388 significantly prevented cardiac dysfunctions in a sex-dependent manner in Npr1 0-copy and 1-copy mutant mice. The results suggest that the development of cardiac fibrosis and dysfunction in mutant mice is predominantly regulated through the TGF-&beta;1-mediated SMAD-dependent pathway

Inhibitory Effect of Ursolic Acid on Ultraviolet B Radiation-Induced Oxidative Stress and Proinflammatory Response-Mediated Senescence in Human Skin Dermal Fibroblasts

Ultraviolet radiation is an environmental carcinogenic agent that enhances inflammation and immunological reactions in the exposed human skin cells leading to oxidative photoaging of the epidermal and dermal segment. In the present study, we investigated the protective role of ursolic acid (UA) against ultraviolet B (UVB) radiation- induced photoaging an in vitro model of human skin dermal fibroblasts. UA-pretreated human skin dermal fibroblast (HDF) cells were exposed to UVB radiation to evaluated cell viability, reactive oxygen species (ROS), mitochondrial membrane potential, lipid peroxidation, antioxidant status, DNA damage, proinflammatory response, apoptotic induction, and matrix metalloproteinase (MMP) alteration. The UA pretreatment of HDFs mitigated the UVB irradiation-induced cytotoxicity, ROS generation, and mitochondrial membrane potential alteration and lipid peroxidation, depletion of antioxidant status, DNA damage, and apoptotic induction. UA pretreatment of HDFs also attenuated the UVB-induced expression of inflammatory (TNF-α and NF-κB) and apoptotic (p53, Bax, and caspase-3) and MMPs (MMP-2 and MMP-9) and enhanced the Bcl-2 protein levels in 20 μM UA treatment, when compared to concentrations. Hence, these results revealed that UA has the potential to mitigate UVB-induced extracellular damage by interfering with the ROS-mediated apoptotic induction and photoaging senescence and thus is a potential therapeutic agent to protect the skin against UVB-irradiation induced photooxidative damage

Resveratrol Nanoparticles: A Promising Therapeutic Advancement over Native Resveratrol

The importance of fruit-derived resveratrol (RES) in the treatment of various diseases has been discussed in various research publications. Those research findings have indicated the ability of the molecule as therapeutic in the context of in vitro and in vivo conditions. Mostly, the application of RES in in vivo conditions, encapsulation processes have been carried out using various nanoparticles that are made of biocompatible biomaterials, which are easily digested or metabolized, and RES is absorbed effectively. These biomaterials are non-toxic and are safe to be used as components in the biotherapeutics. They are made from naturally available by-products of food materials like zein or corn or components of the physiological system as with lipids. The versatility of the RES nanoparticles in their different materials, working range sizes, specificity in their targeting in various human diseases, and the mechanisms associated with them are discussed in this review