Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol

Pharmacologically increased estrogen levels have been shown to lower hepatic and plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in animals and humans. We hypothesized that physiological changes in estrogen levels influence circulating PCSK9, thereby contributing to the known wide inter-individual variation in its plasma levels, as well as to the established increase in LDL cholesterol (LDL-C) with normal aging. Circulating PCSK9, estradiol, and other metabolic factors were determined in fasting samples from 206 female and 189 male healthy volunteers (age 20–85 years), The mean levels of PCSK9 were 10% higher in females than in males (P < 0.05). PCSK9 levels were 22% higher in postmenopausal than in premenopausal (P < 0.001) females. Within the group of premenopausal females, circulating PCSK9 correlated inversely to estrogen levels, and PCSK9 was higher (305 ng/ml) in the follicular phase than in the ovulatory (234 ng/ml) or the luteal (252 ng/ml) phases (P < 0.05). Changes in endogenous estrogen levels during the menstrual cycle likely contribute to the broad inter-individual variation in PCSK9 and LDL-C in normal females. PCSK9 levels increase in females after menopause but not in men during this phase in life. This likely contributes to why LDL-C in women increases in this period.     

Synthesis and reactivity of azobenzene-based bispropargyl sulfones: interesting comparison between cyclic and acyclic systems

Azobenzene-based bispropargyl bissulfone 3 containing stable E-azo moiety has been synthesized. Upon irradiation with long wavelength UV it isomerized to the Z-form 4, which can be thermally reisomerized to the E-isomer. Reactivity towards isomerization to the allenic system as well as DNA-cleaving efficiency under basic conditions was found to be significantly lower as compared to the previously synthesized cyclic sulfones 1 and 2. This lowering of reactivity can be explained in terms of low conversion to the allenic form and hence the lower extent of alkylation of DNA-bases, the only possible DNA-cleavage pathway for 3 and 4.     

Novel piperazines: potent melanocortin-4 receptor antagonists with anxiolytic-like activity

In the present study, we found that a novel piperazine compound, 11a, showed a moderate affinity (IC(50)=333nM) for the MC4 receptor. We developed the new type of piperazine compounds and found that mono-piperazine 11b exhibited a high-affinity (IC(50)=40.3nM) for the MC4 receptor. We also found that a series of biphenyl analogues exhibited a high-affinity for the receptor, and in particular, compound 11j exhibited the highest affinity for the MC4 receptor with an IC(50) value of 14.5nM. Furthermore, some of these compounds, when administered orally, significantly reversed the stress-induced anxiety-like behavior in rats. In this paper, we report the synthesis, structure-activity relationships, and oral activity of the novel mono-piperazines as MC4 receptor antagonists.     

Involvement of Reactive Nitrogen and Oxygen Species (RNS and ROS) in Sunflower-Mildew Interaction

Nitric oxide (·NO) has been shown to participate in plantresponse against pathogen infection; however, less is knownof the participation of other NO-derived molecules designatedas reactive nitrogen species (RNS). Using two sunflower (Helianthusannuus L.) cultivars with different sensitivity to infectionby the pathogen Plasmopara halstedii, we studied key componentsinvolved in RNS and ROS metabolism. We analyzed the superoxideradical production, hydrogen peroxide content, L-arginine-dependentnitric oxide synthase (NOS) and S-nitrosoglutathione reductase(GSNOR) activities. Furthermore, we examined the location andcontents of ·NO, S-nitrosothiols (RSNOs), S-nitrosoglutathione(GSNO) and protein 3-nitrotyrosine (NO₂-Tyr) by confocal laserscanning microscopy (CLSM) and biochemical analyses. In thesusceptible cultivar, the pathogen induces an increase in proteinsthat undergo tyrosine nitration accompanied by an augmentationin RSNOs. This rise of RSNOs seems to be independent of theenzymatic generation of ·NO because the L-arginine-dependentNOS activity is reduced after infection. These results suggestthat pathogens induce nitrosative stress in susceptible cultivars.In contrast, in the resistant cultivar, no increase of RSNOsor tyrosine nitration of proteins was observed, implying anabsence of nitrosative stress. Therefore, it is proposed thatthe increase of tyrosine nitration of proteins can be considereda general biological marker of nitrosative stress in plantsunder biotic conditions.     

Nitric oxide imbalance provokes a nitrosative response in plants under abiotic stress

Nitric oxide (NO), a free radical generated in plant cells, belongs to a family of related molecules designated as reactive nitrogen species (RNS). When an imbalance of RNS takes place for any adverse environmental circumstances, some of these molecules can cause direct or indirect damage at the cellular or molecular level, promoting a phenomenon of nitrosative stress. Thus, this review will emphasize the recent progress in understanding the function of NO and its production under adverse environmental conditions.     

Tracheal Dysplasia Precedes Bronchial Dysplasia in Mouse Model of N-Nitroso Trischloroethylurea Induced Squamous Cell Lung Cancer

Squamous cell lung cancer (SCC) is the second leading cause of lung cancer death in the US and has a 5-year survival rate of only 16%. Histological changes in the bronchial epithelium termed dysplasia are precursors to invasive SCC. However, the cellular mechanisms that cause dysplasia are unknown. To fill this knowledge gap, we used topical application of N-nitroso-tris chloroethylurea (NTCU) for 32 weeks to induce squamous dysplasia and SCC in mice. At 32 weeks the predominant cell type in the dysplastic airways was Keratin (K) 5 and K14 expressing basal cells. Notably, basal cells are extremely rare in the normal mouse bronchial epithelium but are abundant in the trachea. We therefore evaluated time-dependent changes in tracheal and bronchial histopathology after NTCU exposure (4, 8, 12, 16, 25 and 32 weeks). We show that tracheal dysplasia occurs significantly earlier than that of the bronchial epithelium (12 weeks vs. 25 weeks). This was associated with increased numbers of K5⁺/K14⁺ tracheal basal cells and a complete loss of secretory (Club cell secretory protein expressing CCSP⁺) and ciliated cells. TUNEL staining of NTCU treated tissues confirmed that the loss of CCSP⁺ and ciliated cells was not due to apoptosis. However, mitotic index (measured by bromodeoxyuridine incorporation) showed that NTCU treatment increased proliferation of K5⁺ basal cells in the trachea, and altered bronchial mitotic population from CCSP⁺ to K5⁺ basal cells. Thus, we demonstrate that NTCU-induced lung epithelial dysplasia starts in the tracheal epithelium, and is followed by basal cell metaplasia of the bronchial epithelium. This analysis extends our knowledge of the NTCU-SCC model by defining the early changes in epithelial cell phenotypes in distinct airway locations, and this may assist in identifying new targets for future chemoprevention studies.     

Anti-ulcer and antioxidant activity of GutGard

The present study was undertaken to determine the anti-ulcer and antioxidant potential of GutGard, a standardized extract of Glycyrrhiza glabra commonly known as licorice. Effect of various doses (12.5, 25, and 50 mg/kg, po) of GutGard was studied on gastric ulcers in pylorus ligation-, cold-restraint stress- and indomethacin induced gastric mucosal injury in rats. Anti-ulcer activity was evaluated by measuring the ulcer index, gastric content, total acidity, and pH of gastric fluid. GutGard dose dependently decreased gastric content, total acidity, ulcer index and increased pH of gastric fluid in pylorus ligation ulcer model. In cold-restraint stress- and indomethacin induced ulcer models all the doses of GutGard decreased the ulcer index and increased the pH of gastric fluid. The antioxidant activity was evaluated by the oxygen radical absorbance capacity (ORAC) assay. GutGardT exhibited potent antioxidant activity with high hydrophilic and lipophilic ORAC value. GutGard possessed anti-ulcerogenic properties that might be afforded via cytoprotective mechanism by virtue of its antioxidant properties. These results supported the ethnomedical uses of licorice in the treatment of gastric ulcer.     

Income and nutritional status of the fishing community residing in coastal bay of Bengal: a case study

This is part of a project on the disadvantaged, marginalized, vulnerable/weaker section of the population and their survival strategy. The paper presents the results of a survey carried out during 2006-07 with the objective of throwing light on the life and living conditions of an economically weaker community such as 'fishing community' residing in the coastal area of Bay of Bengal in West Bengal and Orissa, India, in the context of global scenario. Various scientists have conducted quite a large number of studies to ascertain the income and nutritional status of people in rural India. Very few attempts, however, have been made to investigate in detail regarding the living standards of some specific communities, which are very often referred to, as the 'weaker section' of the people. The people belonging to fishing community are, by and large, not only economically weak in terms of earning and availability of work, the majority of them are not able to procure the minimum nourishment. The present study shows that some notable elements of living conditions such as food, shelter, health etc. matters much more than the conventional income or calorie deficiency. Commonly, the social scientists equate poverty with income or calorie deficiency which may not be the case as is evident from this study. We have hinted some measures to be undertaken to ameliorate the sufferings of the fishing community.