Rapid,non-genomic actions of progesterone and estradiol on steady-state calcium and resting calcium influx in lens epithelial cells

The effects of steroids on the steady-state intracellular [Ca(2+)] ([Ca(2+)](i)) and resting Ca(2+) influx in Fura-2-loaded bovine lens epithelial cells were examined to identify potential rapid, non-genomic actions. When administered in the presence of 1-2 mM extracellular Ca(2+) ([Ca(2+)](o)), 100 micro M progesterone produced large (up to 12-fold) and transient (5 min) increases in [Ca(2+)](i). These effects were abolished in EGTA-containing solutions, and were associated with large increases in the rate at which extracellularly administered Mn(2+) quenched the intracellular Fura signal. Lower concentrations of progesterone (10-100 micro M) produced smaller increases in [Ca(2+)](i) that were concentration dependent, and 17beta-estradiol induced large, rapid and brief increases in [Ca(2+)](i) at 100 nM and smaller oscillations in [Ca(2+)](i) at 10 nM. In cells pretreated with thapsigargin, 100 micro M progesterone produced slower increases in [Ca(2+)](i) that were maintained for several minutes. These results demonstrate rapid non-genomic actions of progesterone and estradiol on resting Ca(2+) influx and [Ca(2+)](i) that may involve specific interactions with a recently discovered steroid-binding protein in the plasma membrane of lens epithelial cells.     

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

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The Effect of Dietary Fibre on Gut Microbiota,Lipid Profile,and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background: A disequilibrium of the gut microbial community has been closely associated with systemic inflammation and metabolic syndromes including type 2 diabetes. While low fibre and high fat diets may lead to dysbiosis of the gut microbiome as a result of the loss of useful microbes, it has been reported that a high fibre diet may prevent the fermentation of protein and may promote eubiosis of gut microbiota. Aim: This review aims to evaluate the effect of dietary fibre (DF) on gut microbiota, lipid profile, and inflammatory markers in patients with type 2 diabetes. Methods: The PRISMA framework was relied on to conduct this systematic review and meta-analysis. Searches were carried out using electronic databases and reference list of articles. Results: Eleven studies were included in the systematic review, while ten studies were included in the meta-analysis. The findings revealed five distinct areas including the effects of DF on (a) gut microbiota (122 participants); (b) lipopolysaccharides (LPS, 79 participants) and lipopolysaccharides binding protein (LBP, 81 participants); (c) lipid profile; (d) inflammatory markers; and (e) body mass index (BMI, 319 participants). The relative abundance of Bifidobacterium increased by 0.73 (95% CI: 0.57, 0.89) in the DF group in contrast to the control (p < 0.05). With respect to LPS, the level was lower in the DF group than the control and the difference was significant (p < 0.05). The standardised mean difference for LPS was −0.45 (95% CI: −0.90, −0.01) although the difference between the two groups in relation to LBP was not significant (p = 0.08) and the mean difference was 0.92 (95% CI: −0.12, 1.95). While there was a decrease of −1.05 (95% CI: −2.07, −0.02) with respect to total cholesterol (356 participants) in the DF group as compared with the control (p < 0.05), both groups were not significantly different (p > 0.05) in the other lipid parameters. The difference between the groups was significant (p < 0.05) in relation to C-reactive protein, and the mean difference was 0.43 (95% CI: 0.02, 0.84). This could be due to the short duration of the included studies and differences in participants’ diets including the amount of dietary fibre supplements. However, the groups were not significantly different (p > 0.05) with respect to the other inflammatory markers. The meta-analysis of the BMI showed that the DF group decreased by −0.57 (95% CI: −1.02, −0.12) as compared with the control and this was significant (p < 0.01). Conclusion: DF significantly (p < 0.05) increased the relative abundance of Bifidobacterium and significantly decreased (p < 0.05) LPS, total cholesterol, and BMI as compared with the control. However, DF did not seem to have an effect that was significant on LBP, triglyceride, HDL cholesterol, LDL cholesterol, IL-6, TNF-α, adiponectin, and leptin. These findings have implications for public health in relation to the use of dietary fibre in nutritional interventions and as strategies for managing type 2 diabetes.     

Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway.

PURPOSE: Overexpression of eIF4E in surgical margins of head and neck cancer patients is an independent risk factor for recurrence. We hypothesize that overexpressed eIF4E is functionally active in tumor margins through activation of the Akt/mammalian target of rapamycin (mTOR) pathway EXPERIMENTAL DESIGN: Western blots and/or immunohistochemistry were performed to determine whether phosphorylation of mTOR and activation of its downstream molecules eIF4E-binding protein-1 (4E-BP1) and p70 S6 kinase and the upstream modulator of mTOR, Akt, were expressed in margins overexpressing eIF4E. RESULTS: There was a significant association between phospho-4E-BP1 and eIF4E expression of a margin or a significant difference in phospho-4E-BP1 expression between the eIF4E-positive and -negative margins (P < 0.01). A significant association between eIF4E and phospho-p70 S6 kinase as well as eIF4E and phospho-mTOR was also noted (P < 0.05). Western blot analysis indicated a highly significant difference in the phosphorylation status of 4E-BP1 between tumors and resection margins. A total of 89% of the 4E-BP1-expressing margins expressed more of the phosphorylated (beta, gamma, and delta) isoforms, whereas 81% of the 4E-BP1-expressing tumors expressed more of the unphosphorylated alpha isoform. A similar difference in Akt activation was noted between eIF4E-positive margins and tumors (P < 0.05). CONCLUSIONS: Overexpression of eIF4E is functionally active in tumor margins through activation of the Akt/mTOR signaling pathway. The greater degree of expression of downstream targets and upstream regulators of mTOR in margins compared with the tumors indicates preferential activation of the Akt/mTOR signaling pathway in margins overexpressing eIF4E. Rapamycin analogs can potentially be used as adjuvant therapy for patients with eIF4E-positive margins.     

Assessment of sickness severity of illness in neonates: review of various neonatal illness scoring systems

Sickness severity scores are widely used for neonates admitted to neonatal intensive care units to predict severity of illness and risk of mortality and long-term outcome. These scores are also used frequently for quality assessment among various neonatal intensive care unit and hospital. Accurate and reliable measures of severity of illness are required for unbiased and reliable comparisons especially for benchmarking or comparative quality improvement care studies. These scores also serve to control for population differences when performing studies such as clinical trials, outcome evaluations, and evaluation of resource utilisation. Although presently there are multiple scores designed for neonates’ sickness assessment but none of the score is ideal. Each score has its own advantages and disadvantages. We did literature search for identifying all neonatal sickness severity score and in this review article, we discuss these scores along with their merits and demerits.