Potential therapeutic effects of curcumin in gastric cancer

Despite recent advancements in understanding of the biology of gastric cancer, treatment of patients with advanced gastric cancer remains a major problem. Among different type of phytochemicals, curcumin, a welltable -known phytochemical, has been shown to be a promising cancer chemopreventive agent. Pharmacokinetics, safety, and efficacy of curcumin have been evaluated in several clinical trials against numerous diseases, and for the treatment of human cancer. In the present review, we have collected in vitro and in vivo investigations and studied the chemosensitizing and anticancer effects of curcumin against the gastric cancer cells. In summary, curcumin has been found to have efficient chemosensitizing effect and also inhibits viability, proliferation, and migration of gastric cancer cells mainly via cell cycle arrest and induction of apoptosis by both mitochondrial-dependent and -independent pathways.     

GVI phospholipase A2 role in the stimulatory effect of sphingosine-1-phosphate on TRPC5 cationic channels

The Transient Receptor Potential Canonical 5 (TRPC5) protein forms calcium-permeable cationic channels that are stimulated by G protein-coupled receptor agonists. The signaling pathways of such agonist effects are poorly understood. Here we investigated the potential for involvement of lysophosphatidylcholine (LPC) and arachidonic acid generated by group 6 (GVI) phospholipase A2 (PLA2) enzymes, focusing on stimulation of TRPC5 by sphingosine-1-phosphate (S1P) which acts via a pertussis toxin-sensitive (Gi/o protein) pathway without Ca²⁺-release. Experiments were on HEK 293 cells containing conditional expression of human TRPC5. Channel activity was recorded using an intracellular calcium indicator or whole-cell patch-clamp and PLA2 activity was detected using ³H-arachidonic acid. S1P stimulated PLA2 and TRPC5 activities. Both effects were suppressed by the GVI PLA2 inhibitor bromoenol lactone. Knock-down of GVI PLA2 by RNA interference suppressed channel activity evoked by S1P whereas activity evoked by the direct channel stimulator LPC was unaffected. Arachidonic acid did not stimulate the channels. Prior exposure of channels to LPC but not arachidonic acid suppressed channel activity evoked by S1P but not gadolinium, a putative direct stimulator of the channels. The data suggest roles of LPC and GVI PLA2 in S1P-evoked TRPC5 activity.     

Competitive interactions in Escherichia coli populations: the role of bacteriocins

Explaining the coexistence of competing species is a major challenge in community ecology. In bacterial systems, competition is often driven by the production of bacteriocins, which are narrow-spectrum proteinaceous toxins that serve to kill closely related species, providing the producer better access to limited resources. Bacteriocin producers have been shown to competitively exclude sensitive, nonproducing strains. However, the dynamics between bacteriocin producers, each lethal to its competitor, are largely unknown. In this study, we used in vitro, in vivo and in silico models to study competitive interactions between bacteriocin producers. Two Escherichia coli strains were generated, each carrying a DNA-degrading bacteriocin (colicins E2 and E7). Using reporter-gene assays, we showed that each DNase bacteriocin is not only lethal to its opponent but, at lower doses, can also induce the expression of its opponent''s toxin. In a well-mixed habitat, the E2 producer outcompeted its adversary; however, in structured environments (on plates or in mice colons), the two producers coexisted in a spatially ‘frozen'' pattern. Coexistence occurred when the producers were initiated with a clumped spatial distribution. This suggests that a ‘clump'' of each producer can block invasion of the other producer. Agent-based simulation of bacteriocin-mediated competition further showed that mutual exclusion in a structured environment is a relatively robust result. These models imply that colicin-mediated colicin induction enables producers to successfully compete and defend their niche against invaders. This suggests that localized interactions between producers of DNA-degrading toxins can lead to stable coexistence of heterogeneously distributed strains within the bacterial community and to the maintenance of diversity.     

Unraveling the iron deficiency responsive proteome in <i>Arabidopsis?</i>shoot by iTRAQ-OFFGEL approach

Iron (Fe) is required by plants for basic redox reactions in photosynthesis and respiration, and for many other key enzymatic reactions in biological processes. Fe homeostatic mechanisms have evolved in plants to enable the uptake and sequestration of Fe in cells. To elucidate the network of proteins that regulate Fe homeostasis and transport, we optimized the iTRAQ-OFFGEL method to identify and quantify the number of proteins that respond to Fe deficiency in the model plant Arabidopsis. In this study, Fe deficiency was created using Fe-deficient growth conditions, excess zinc (Zn), and use of the irt1-1 mutant in which the IRT1 Fe transporter is disrupted. Using the iTRAQ-OFFGEL approach, we identified 1139 proteins, including novel Fe deficiency-responsive proteins, in microsomal fractions isolated from 3 different types of Fe-deficient shoots compared with just 233 proteins identified using conventional iTRAQ-CEX. Further analysis showed that greater numbers of low-abundance proteins could be identified using the iTRAQ-OFFGEL method and that proteins could be identified from numerous cellular compartments. The improved iTRAQ-OFFGEL method used in this study provided an efficient means for identifying greater numbers of proteins from microsomal fractions of Arabidopsis shoots. The proteome identified in this study provides new insight into the regulatory cross talk between Fe-deficient and excess Zn conditions.     

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

Background

The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries.

Methods and Findings

We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30–100%) and 81% (range 26–100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22–99%) and 60% (range 19–100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44–100%) of infants were tested for HIV and 11% (range 3–18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis.

Conclusion

The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed.     

Access to Primary Care and Visits to Emergency Departments in England: A Cross-Sectional,Population-Based Study

Background

The number of visits to hospital emergency departments (EDs) in England has increased by 20% since 2007-08, placing unsustainable pressure on the National Health Service (NHS). Some patients attend EDs because they are unable to access primary care services. This study examined the association between access to primary care and ED visits in England.

Methods

A cross-sectional, population-based analysis of patients registered with 7,856 general practices in England was conducted, for the time period April 2010 to March 2011. The outcome measure was the number of self-referred discharged ED visits by the registered population of a general practice. The predictor variables were measures of patient-reported access to general practice services; these were entered into a negative binomial regression model with variables to control for the characteristics of patient populations, supply of general practitioners and travel times to health services.

Main Result and Conclusion

General practices providing more timely access to primary care had fewer self-referred discharged ED visits per registered patient (for the most accessible quintile of practices, RR = 0.898; P<0.001). Policy makers should consider improving timely access to primary care when developing plans to reduce ED utilisation.     

Rising Obesity-Related Hospital Admissions among Children and Young People in England: National Time Trends Study

Objective

To describe the trends in hospital admissions associated with obesity as a primary diagnosis and comorbidity, and bariatric surgery procedures among children and young people in England.

Design

National time trends study of hospital admissions data between 2000 and 2009.

Participants

Children and young people aged 5 to 19 years who were admitted to hospital with any diagnosis of obesity.

Main outcome measures

Age- and sex-specific admission rates per million children.

Results

Between 2000 and 2009, age- and sex-specific hospital admission rates in 5–19 year olds for total obesity-related diagnoses increased more than four-fold from 93.0 (95% CI 86.0 to 100.0) per million children to 414.0 (95% CI 410.7 to 417.5) per million children, largely due to rising admissions where obesity was mentioned as a co-morbidity. The median age of admission to hospital over the study period was 14.0 years; 5,566 (26.7%) admissions were for obesity and 15,319 (73.3%) mentioned obesity as a comorbidity. Admissions were more common in girls than boys (56.2% v 43.8%). The most common reasons for admission where obesity was a comorbid condition were sleep apnoea, asthma, and complications of pregnancy. The number of bariatric surgery procedures has risen from 1 per year in 2000 to 31 in 2009, with the majority were performed in obese girls (75.6%) aged 13–19 years.

Conclusions

Hospital admission rates for obesity and related comorbid conditions have increased more than four-fold over the past decade amongst children and young people. Although some of the increase is likely to be due to improved case ascertainment, conditions associated with obesity in children and young people are imposing greater challenges for health care providers in English hospitals. Most inpatient care is directed at dealing with associated conditions rather than primary assessment and management of obesity itself.