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Strategic and competitive use of foodstuff laws in order to bar electronic cigarettes and tobacco products throughout Of india: any qualitative analysis associated with litigation.
INTRODUCTION During pregnancy, maternal stressors cause changes in both maternal and fetal HPA axes. We therefore investigated the impact of maternal non chronic and chronic stress on fetal glucose metabolism and growth, and serum levels of cortisol in the fetus. MATERIALS AND METHODS Normal weight pregnant women (n = 192; mean ± SD 27.9 ± 4.2 years old, and; 26.9 ± 2.4 kg/m²) were assessed during the 2nd and 3rd trimester with anthropometry, fetal ultrasound, blood samples for serum CRH, cortisol and IL6, and STAI trait and state stress questionnaires. We measured serum cortisol, insulin and c-peptide, and plasma glucose from cord blood. Neonates underwent anthropometry at the 3rd post-delivery day. RESULTS In both 2nd and 3rd trimesters, women with STAI trait scores ≥40 had significantly greater levels of fasting serum CRH and cortisol than those with STAI trait scores less then 40. 2nd trimester STAI trait scores correlated positively with cord blood glucose and c-peptide. Maternal serum CRH correlated negf both CRH and cortisol correlated positively with cord blood c-peptide, glucose, and insulin. STAI trait was the best positive predictor of cord blood cortisol, glucose and c-peptide, whilst STAI state was the best positive and negative predictor, respectively of fetal abdominal circumference and fetal head circumference or biparietal diameter. CONCLUSIONS Increased maternal chronic stress (reflected by the STAI trait score) associates with increased fetal cortisol, glucose, c-peptide secretion and thus, insulin resistance. Maternal non chronic stress (STAI state) in the 3rd trimester associates with changes in fetal growth pattern, including increased and decreased measurements of fetal abdominal and head growth respectively. Second generation antipsychotics, particularly olanzapine, induce severe obesity, which is associated with their antagonistic effect on the histamine H1 receptor (H1R). We have previously demonstrated that oral administration of olanzapine increases the concentration of neuropeptide Y (NPY) in the hypothalamus of rats, accompanied by hyperphagia and weight gain. However, it is unclear if the increased NPY after olanzapine administration is due to its direct effect on hypothalamic neurons and its H1R antagonistic property. In the present study, we showed that with an inverted U-shape dose-response curve, olanzapine increased NPY expression in the NPY-GFP hypothalamic neurons; however, this was not the case in the hypothalamic neurons of H1R knockout mice. Olanzapine inhibited the interaction of H1R and GHSR1a (ghrelin receptor) in the primary mouse hypothalamic neurons and NPY-GFP neurons examined by confocal fluorescence resonance energy transfer (FRET) technology. Furthermore, an H1R agonist, FMPH inhibited olanzapine activation of GHSR1a downstream signaling pAMPK and transcription factors of NPY (pFOXO1 and pCREB) in the hypothalamic NPY-GFP cell. However, an olanzapine analogue (E-Olan) with lower affinity to H1R presented negligible enhancement of pCREB within the nucleus of NPY neurons. These findings suggest that the H1R antagonist property of olanzapine inhibits the interaction of H1R and GHSR1a, activates GHSR1a downstream signaling pAMPK-FOXO1/pCREB and increases hypothalamic NPY this could be one of the important molecular mechanisms of H1R antagonism of olanzapine-induced obesity in antipsychotic management of psychiatric disorders. In this study, a series of thieno [2,3-d]pyrimidine derivatives were designed, synthesized and evaluated as novel AKT1 inhibitors. In vitro antitumor assay results showed that compounds 9d-g and 9i potently suppressed the enzymatic activities of AKT1 and potently inhibited the proliferation of HepG2, Hep3B, Huh-7 and SMMC-7721 cancer cell lines. GF120918 Among these derivatives, the compound 9f demonstrated the best inhibitory activities on AKT1 (IC50 = 0.034 μM) and Huh-7 cell (IC50 = 0.076 μM). A panel of biological assays showed that compound 9f suppressed the cellular proliferation of Huh-7 through Akt/mTOR signaling pathway mediated autophagy mechanism. Furthermore, the antitumor capacity of 9f was validated in the subcutaneous Huh-7 xenograft models. Together, our results demonstrate that a novel small-molecule Akt1 inhibitor induces autophagy associated death in hepatocellular carcinoma, which may afford a potential drug candidate for targeted cancer therapy. Based on the definite therapeutic benefits, such as neuroprotective, cardioprotective, anticancer, anti-diabetic and so on, the Panax genus which contains many valuable plants, including ginseng (Panax ginseng C.A. Meyer), notoginseng (Panax notoginseng) and American ginseng (Panax quinquefolius L.), attracts research focus. Actually, the biological and pharmacological effects of the Panax genus are mainly attributed to the abundant ginsenosides. However, the low membrane permeability and the gastrointestinal tract influence seriously limit the absorption and bioavailability of ginsenosides. The acid or base hydrolysates of ginsenosides, 20 (R,S)-panaxadiol and 20 (R,S)-protopanaxadiol showed improved bioavailability and diverse pharmacological activities. Moreover, relative stable skeletons and active hydroxyl group at C-3 position and other reactive sites are suitable for structural modification to improve biological activities. In this review, the pharmacological activities of panaxadiol, protopanaxadiol and their structurally modified derivatives are comprehensively summarized. A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 μM, and 0.29-12.2 μM, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results might be explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK. Mycophenolic acid (MPA) was coupled with amino acids and biologically active peptides including derivatives of tuftsin to modify its immunosuppressive properties. Both amino acid unit in the case of simple MPA amides and modifications within peptide moiety of MPA - tuftsin conjugates influenced the observed activity. Antiproliferative potential of the obtained conjugates was investigated in vitro and MPA amides with threonine methyl ester and conjugate of MPA with retro-tuftisin occurred to be more selective against PBMC in comparison to parent MPA. link2 Both amino acid and peptide derivatives of MPA acted as inosine-5'-monophosphate dehydrogenaze (IMPDH) inhibitors. Pathological cardiac hypertrophy is a classical hallmark of heart failure. At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection. However, it is not known if the cardio-protective actions for emodin are mediated through HDAC-dependent regulation of gene expression. Therefore, we hypothesized that emodin would attenuate pathological cardiac hypertrophy via inhibition of HDACs, and that these actions would be reflected in an emodin-rich food like rhubarb. In this study, we demonstrate that emodin and Turkish rhubarb containing emodin inhibit HDAC activity in vitro, with fast-on, slow-off kinetics. Moreover, we show that emodin increased histone acetylation in cardiomyocytes concomitant to global changes in gene expression; gene expression changes were similar to the well-established pan-HDAC inhibitor trichostatin A (TSA). We additionally present evidence that emodin inhibited phenylephrine (PE) and phorbol myristate acetate (PMA)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs). Lastly, we demonstrate that the cardioprotective actions of emodin are translated to an angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition. These data suggest that emodin blocked pathological cardiac hypertrophy, in part, by inhibiting HDAC-dependent gene expression changes. Milk sphingomyelin (SM), a polar lipid (PL) component of milk fat globule membranes, is protective against dyslipidemia. However, it is unclear whether ingestion of milk PLs protect against atherosclerosis. To determine this, male LDLr-/- mice (age 6 weeks) were fed ad libitum either a high-fat, added-cholesterol diet (CTL; 45% kcal from fat, 0.2% cholesterol by weight; n=15) or the same diet supplemented with 1% milk PL (1% MPL; n=15) or 2% milk PL (2% MPL; n=15) added by weight from butter serum. After 14 weeks on diets, mice fed 2% MPL had significantly lower serum cholesterol (-51%) compared to CTL (P less then .01), with dose-dependent effects in lowering VLDL- and LDL-cholesterol. Mice fed 2% MPL displayed lower inflammatory markers in the serum, liver, adipose and aorta. Notably, milk PLs reduced atherosclerosis development in both the thoracic aorta and the aortic root, with 2% MPL-fed mice having significantly lower neutral lipid plaque size by 59% (P less then .01) and 71% (P less then .02) compared to CTL, respectively. Additionally, the 2% MPL-fed mice had greater relative abundance of Bacteroidetes, Actinobacteria and Bifidobacterium, and lower Firmicutes in cecal feces compared to CTL. Milk PL feeding resulted in significantly different microbial communities as demonstrated by altered beta diversity indices. link3 In summary, 2% MPL strongly reduced atherogenic lipoprotein cholesterol, modulated gut microbiota, lowered inflammation and attenuated atherosclerosis development. Thus, milk PL content may be important to consider when choosing dairy products as foods for cardiovascular disease prevention. The aim was to compare the antiobesity efficacy of different concentrations of a phenolic-rich water extract from purple maize pericarp (PPE) in a murine model of obesity for 12 weeks. Forty C57BL/6 mice (n=10/group) were randomized standard diet (SD), high-fat diet (HFD), HFD+200 mg PPE/kg (200 PPE) and HFD+500 mg PPE/kg (500 PPE). PPE contained mainly ferulic acid, anthocyanins and other phenolics (total phenolics 448.5 μg/mg dry weight, DW). Body weight (-27.9%), blood glucose (-26.5%) and blood triglycerides (-22.1%) were most attenuated (P less then .05) in 500 PPE group compared to HFD group. Also, 500 PPE group had reduced (P less then .05) plasma levels of TNF-α, MCP-1, resistin and leptin compared to HFD group. Fatty liver disease scores were highest for HFD (8.4), followed by 200 PPE (6.1), 500 PPE (2.7) and SD (0.4) groups. Relative adipose tissue was lower (P less then .05) in 200 PPE (7.6%), 500 PPE (8.0%) and SD (0.8%) compared to HFD (12.1%) group. In 500 PPE group, compared to HFD group, important genes were modulated related to adipogenesis (Mmp3, fold-change [FC]=7.
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