Evaluation of anti-inflammatory activity of Vernonia cinerea Less. extract in rats.

The methanol extract of the whole plant of Vernonia cinerea Less. was evaluated for its anti-inflammatory activity in acute (carrageenin, histamine and serotonin induced rat paw edema) and a chronic model (cotton pouch induced granuloma). The methanol extract (250 and 500 mg/kg(-1) p.o.) exhibited significant activity (p < 0.001) against all phlogistic agents used in a dose dependant manner. In the chronic model (cotton pouch granuloma method) the methanol extract exhibited significant anti-inflammatory activity. All these effects were compared with standard drug phenylbutazone (100 mg/kg(-1) p.o.).     

Design,Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940’s. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2‐(2‐bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4‐oxadiazole derivatives 4a – 4j have been synthesized and described by spectroscopic method. 2‐(2‐Bromo‐6‐nitrophenyl)‐5‐(4‐bromophenyl)‐1,3,4‐oxadiazole ( 4c ) was reconfirmed by single‐crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF‐7, MDA‐MB‐453 and MCF‐10A non‐cancer cell lines. The compounds with the methoxy (in 4c ) and methyl (in 4j ) substitution were shown to have significant cytotoxicity, with 4c showing dose‐dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein?ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.     

Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging

Recent genome‐wide association studies have linked type‐2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up‐regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type‐2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age‐dependent alterations of insulin and glucose homeostasis using Super‐Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age‐matched wild‐type controls, Super‐Ink4/Arf mice do not develop glucose intolerance with aging. Insulin tolerance tests demonstrated increased insulin sensitivity in Super‐Ink4/Arf compared with wild‐type mice, which was accompanied by higher activation of the insulin receptor substrate (IRS)‐PI3K‐AKT pathway in liver, skeletal muscle and heart. Glucose uptake studies in Super‐Ink4/Arf mice showed a tendency toward increased ¹⁸F‐fluorodeoxyglucose uptake in skeletal muscle compared with wild‐type mice (P = 0.079). Furthermore, a positive correlation between glucose uptake and baseline glucose levels was observed in Super‐Ink4/Arf mice (P < 0.008) but not in wild‐type mice. Our studies reveal a protective role of the Ink4/Arf locus against the development of age‐dependent insulin resistance and glucose intolerance.     

Metallic silver nanoparticle: a therapeutic agent in combination with antifungal drug against human fungal pathogen

Silver nanoparticles (Ag-NPs) are known to have inhibitory and fungicidal effects. Resistance against fungal infection has emerged as a major health problem in recent years, which needs great and immediate concern. Here, we report the extracellular biological synthesis of silver nanoparticles through a simple green route approach using a marine mangrove (Rhizophora mucronata) and silver nitrate. Aqueous extract of marine mangrove helped in reduction and was used as capping agent in biological synthesis. Nanoparticles were characterized using microscopy and spectroscopy techniques such as HRTEM, UV–Vis absorption spectroscopy and FTIR spectroscopy. X-ray diffraction analysis showed that the nanoparticles had face centered cubic structure with crystalline nature. FTIR spectroscopy showed the presence of different functional groups, such as hydroxyl and carbonyl, involved in the synthesis of nanoparticles. The antifungal activity of fluconazole and itraconazole was enhanced against the tested pathogenic fungi in the presence of Ag-NP and confirmed from increase in fold area of inhibition. This environmentally friendly method of biological synthesis can be easily integrated for various medical applications.     

Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling

Quantifying heterogeneity in gene expression among single cells can reveal information inaccessible to cell-population averaged measurements. However, the expression level of many genes in single cells fall below the detection limit of even the most sensitive technologies currently available. One proposed approach to overcome this challenge is to measure random pools of k cells (e.g., 10) to increase sensitivity, followed by computational “deconvolution” of cellular heterogeneity parameters (CHPs), such as the biological variance of single-cell expression levels. Existing approaches infer CHPs using either single-cell or k-cell data alone, and typically within a single population of cells. However, integrating both single- and k-cell data may reap additional benefits, and quantifying differences in CHPs across cell populations or conditions could reveal novel biological information. Here we present a Bayesian approach that can utilize single-cell, k-cell, or both simultaneously to infer CHPs within a single condition or their differences across two conditions. Using simulated as well as experimentally generated single- and k-cell data, we found situations where each data type would offer advantages, but using both together can improve precision and better reconcile CHP information contained in single- and k-cell data. We illustrate the utility of our approach by applying it to jointly generated single- and k-cell data to reveal CHP differences in several key inflammatory genes between resting and inflammatory cytokine-activated human macrophages, delineating differences in the distribution of ‘ON’ versus ‘OFF’ cells and in continuous variation of expression level among cells. Our approach thus offers a practical and robust framework to assess and compare cellular heterogeneity within and across biological conditions using modern multiplexed technologies.     

The contribution of endophytic bacteria to Albizia lebbeck-mediated phytoremediation of tannery effluent contaminated soil

Toxicity of chromium often impairs the remediation capacity of plants used in phytoremediation of polluted soils. In this study, we have identified Albizia lebbeck as a prospective chromium hyperaccumulator and examined cultivable diversity of endophytes present in chromium-treated and control saplings. High numbers (22–100%) of endophytic bacteria, isolated from root, stem, and leaf tissues, could tolerate elevated (1–3 mM) concentrations of K₂CrO₇. 16S rRNA gene sequence-based phylogenetic analysis showed that the 118 isolates obtained comprised of 17 operational taxonomic units affiliated with the proteobacterial genera Rhizobium (18%), Marinomonas (1%), Pseudomonas (16%), and Xanthomonas (7%) but also with members of Firmicutes genera, such as Bacillus (35%) and Salinococcus (3%). The novel isolates belonging to Salinococcus and Bacillus could tolerate high K₂CrO₇ concentrations (3 mM) and also showed elevated activity of chromate reductase. In addition, majority (%) of the endophytic isolates also showed production of indole-3-acetic acid. Taken together, our results indicate that the innate endophytic bacterial community assists plants in reducing heavy metal toxicity.     

Identification,functional characterization,assembly and structure of ToxIN type III toxin–antitoxin complex from E. coli

Toxin–antitoxin (TA) systems are proposed to play crucial roles in bacterial growth under stress conditions such as phage infection. The type III TA systems consist of a protein toxin whose activity is inhibited by a noncoding RNA antitoxin. The toxin is an endoribonuclease, while the antitoxin consists of multiple repeats of RNA. The toxin assembles with the individual antitoxin repeats into a cyclic complex in which the antitoxin forms a pseudoknot structure. While structure and functions of some type III TA systems are characterized, the complex assembly process is not well understood. Using bioinformatics analysis, we have identified type III TA systems belonging to the ToxIN family across different Escherichia coli strains and found them to be clustered into at least five distinct clusters. Furthermore, we report a 2.097 Å resolution crystal structure of the first E. coli ToxIN complex that revealed the overall assembly of the protein-RNA complex. Isothermal titration calorimetry experiments showed that toxin forms a high-affinity complex with antitoxin RNA resulting from two independent (5′ and 3′ sides of RNA) RNA binding sites on the protein. These results further our understanding of the assembly of type III TA complexes in bacteria.