Plasma lipid peroxidation and erythrocyte antioxidants status in workers exposed to nickel

The objectives were to investigate the plasma lipid peroxidation and erythrocyte antioxidants status in workers exposed to nickel. The study groups comprised 69 nickel plating workers and 50 office workers residing in the same city, but away from the place of work of the study group subjects, considered as control group. Urinary nickel concentration was determined by graphite furnace atomic absorption spectrophotometry. The plasma lipid peroxidation and erythrocyte antioxidants were measured by spectrophotmetric methods. The plasma lipid peroxidation level was significantly increased in nickel-platers and their helpers as compared with controls. Erythrocyte antioxidants were significantly decreased in the nickel-platers compared with the controls. The level of plasma lipid peroxidation was positively and erythrocyte antioxidants were negatively and significantly correlated with the urine nickel levels. Multiple regression analysis assessed the oxidative stress associated with nickel and other potential confounding factors such as body mass index, the consumption of green vegetables, coffee, tea, smoking and alcohol consumption. Analysis showed that the lifestyle confounding factors: the consumption of green vegetables, smoking and alcohol, were not significantly associated with oxidative stress. The exposure to nickel, body mass index and coffee consumption were significantly associated with oxidative stress. The results show that the increased plasma lipid peroxidation and decreased erythrocyte antioxidants levels observed in nickel-exposed workers could be used as biomarkers of oxidative stress.     

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.     

Esterase activity and interaction of human hemoglobin with diclofenac sodium: A spectroscopic and molecular docking study

To get an idea about the pharmacokinetics and pharmacodynamics, it is important to study the drug‐protein interaction. Therefore, herein, we studied the interaction of diclofenac sodium (DIC) with human hemoglobin. The binding study of nonsteroidal antiinflammatory drug, DIC with human hemoglobin (HHB) was done by utilizing fluorescence, UV–visible, time‐resolved fluorescence and far‐UV circular dichroism spectroscopy (CD). Various thermodynamic parameters such as enthalpy change (ΔH), entropy change (ΔS), and Gibbs free energy change (ΔG) were also calculated. CD results showed that DIC induces secondary structure change in HHB. Fluorescence resonance energy transfer was also performed. Additionally, it was also observed that DIC inhibits the esterase‐like enzymatic activity of HHB via competitive inhibition.     

Purification, Spectroscopic Characterization and o-Diphenoloxidase Activity of Hemocyanin from a Freshwater Gastropod: Pila globosa

Hemocyanins are multi-subunit oxygen carrier proteins, found in select species of arthropoda and mollusca. Here, we have purified native hemocyanin from Pila globosa, a freshwater gastropod, verified using mass spectrometry and determined its molecular weight, secondary structure and the spectral properties, using Ultraviolet/visible, Fourier transform infra-red and Circular dichroism spectroscopy. Our results reveal the oligomeric and glycosylated nature of the protein, comprising of 400 kDa subunits, organized predominantly into a thermo-stable, alpha-helical conformation. Further, biochemical assays confirm catecholoxidase-like activity in hemocyanin, which has been used to develop a first-generation optical sensor, for the detection of phenols.     

Lgr5 Identifies Progenitor Cells Capable of Taste Bud Regeneration after Injury

Taste buds are composed of a variety of taste receptor cell types that develop from tongue epithelium and are regularly replenished under normal homeostatic conditions as well as after injury. The characteristics of cells that give rise to regenerating taste buds are poorly understood. Recent studies have suggested that Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) identifies taste bud stem cells that contribute to homeostatic regeneration in adult circumvallate and foliate taste papillae, which are located in the posterior region of the tongue. Taste papillae in the adult anterior region of the tongue do not express Lgr5. Here, we confirm and extend these studies by demonstrating that Lgr5 cells give rise to both anterior and posterior taste buds during development, and are capable of regenerating posterior taste buds after injury induced by glossopharyngeal nerve transection.     

Infection process of Colletotrichum dematium on mulberry leaves: An unusual method of sporulation

Abstract

The pre-penetration and infection process of Colletotrichum dematium on mulberry leaf was investigated by scanning electron microscope. Conidia produced on germination appressoria directly or at the end of short germ tubes. Appressoria were formed mostly over cuticle, but sometimes over stomata also. At 72 h post-inoculation, an extensive network of sub-cuticular runner hyphae (RH) was produced. The RH were traceable by the cuticular bulgings on leaf surface. The RH emerged to leaf surface through ruptured cuticle to form secondary infection hyphae (SIH). The SIH re-entered the leaf tissue by sending penetration branches through stomata. Conidia were formed singly on short conidiophores from the RH and SIH, at short intervals. The conidia developed on RH were exposed to leaf surface through ruptured cuticle. Some times conidia were released through stomata also. The RH and SIH had thick knots from which hyphal branches and conidia were developed. Definite acervuli were not developed.     

Developing imidazole analogues as potential inhibitor for Leishmania donovani trypanothione reductase: virtual screening,molecular docking,dynamics and ADMET approach

Visceral leishmaniasis (VL) affects Indian subcontinent, African and South American continent, and it covers 70 countries worldwide. Visceral form of leishmaniasis is caused by Leishmania donovani in Indian subcontinent which is lethal if left untreated. Extensive resistance to antileishmanial drugs such as sodium stibogluconate, pentamidine and miltefosine and their decreased efficacy has been reported in the endemic region. Amphotericin B drug has shown good antileishmanial activity with significant toxicity, but its cost of treatment has limited the outreach of this treatment to affected people living in endemic zone. So, there is an urgent need to identify new antileishmanial drugs with excellent activity and minimal toxicity issues. Trypanothione reductase, a component of antioxidant system, is necessary for parasite growth and survival to raise infection. To develop potential inhibitor, we docked nine hundred and eighty-four 5-nitroimidazole analogues along with clomipramine which is a well-known inhibitor for TR. Total one hundred and forty-seven 5-nitroimidazole analogues with better docking score than clomipramine were chosen for ADMET and QikProp studies. Among these imidazole analogues, total twenty-four imidazole analogues and clomipramine were chosen on the basis of their ADMET, QikProp, and prime MM-GBSA study. Later on, two analogues with best MM-GBSA dG bind were undergone molecular dynamic simulation to ensure protein–ligand interactions. Using above approach, we confirm that ethyl 2-acetyl-5-[4-butyl-2-(3-hydroxypentyl)-5-nitro-1H-imidazol-1-yl]pent-2-enoate can be a drug candidate against L. donovani for the treatment of VL in the Indian subcontinent.     

The Chemical Nature of the Polar Functional Group of Oxidized Acyl Chain Uniquely Modifies the Physicochemical Properties of Oxidized Phospholipid-Containing Lipid Particles

Oxidative modification of phospholipids generates a variety of oxidized phospholipid (Ox-PL) species which differ considerably in their chemical compositions and molecular structures. Recent results suggest that even closely related Ox-PL species can have considerably different biological effects. However, the molecular mechanism for this is not yet clear. In truncated Ox-PLs (tOx-PLs) the fatty acyl chain is shorter in length than the parent nonoxidized phospholipid molecules and contains a polar functional group(s). In a previous study we showed that two closely related tOx-PL species having a similar polar functional group and differing only in the length of the oxidized fatty acyl chain exerts significantly different effects on the physicochemical properties of the nonoxidized phospholipid particles containing these lipids (Kar et al., Chem Phys Lipids 164:54–61, 2011). In this study we have characterized the effect of polar functional groups of oxidized fatty acyl chain on the physicochemical properties of the nonoxidized phospholipid particles containing these lipids. Our results show that Ox-PL species differing only in the chemical nature of polar functional groups in their oxidized fatty acyl chain modify the properties of nonoxidized phospholipid particles containing them in a distinctive way. These results indicate that different species of Ox-PLs induce unique changes in the physicochemical properties of lipid particles/membranes containing them and that this may lead to their different biological effects.