A cross-sectional investigation of regional patterns of diet and cardio-metabolic risk in India

<p>Abstract</p> <p>Background</p> <p>The role of diet in India's rapidly progressing chronic disease epidemic is unclear; moreover, diet may vary considerably across North-South regions.</p> <p>Methods</p> <p>The India Health Study was a multicenter study of men and women aged 35-69, who provided diet, lifestyle, and medical histories, as well as blood pressure, fasting blood, urine, and anthropometric measurements. In each region (Delhi, n = 824; Mumbai, n = 743; Trivandrum, n = 2,247), we identified two dietary patterns with factor analysis. In multiple logistic regression models adjusted for age, gender, education, income, marital status, religion, physical activity, tobacco, alcohol, and total energy intake, we investigated associations between regional dietary patterns and abdominal adiposity, hypertension, diabetes, and dyslipidemia.</p> <p>Results</p> <p>Across the regions, more than 80% of the participants met the criteria for abdominal adiposity and 10 to 28% of participants were considered diabetic. In Delhi, the "fruit and dairy" dietary pattern was positively associated with abdominal adiposity [highest versus lowest tertile, multivariate-adjusted OR and 95% CI: 2.32 (1.03-5.23); P_trend= 0.008] and hypertension [2.20 (1.47-3.31); P_trend< 0.0001]. In Trivandrum, the "pulses and rice" pattern was inversely related to diabetes [0.70 (0.51-0.95); P_trend= 0.03] and the "snacks and sweets" pattern was positively associated with abdominal adiposity [2.05 (1.34-3.14); P_trend= 0.03]. In Mumbai, the "fruit and vegetable" pattern was inversely associated with hypertension [0.63 (0.40-0.99); P_trend= 0.05] and the "snack and meat" pattern appeared to be positively associated with abdominal adiposity.</p> <p>Conclusions</p> <p>Cardio-metabolic risk factors were highly prevalent in this population. Across all regions, we found little evidence of a Westernized diet; however, dietary patterns characterized by animal products, fried snacks, or sweets appeared to be positively associated with abdominal adiposity. Conversely, more traditional diets in the Southern regions were inversely related to diabetes and hypertension. Continued investigation of diet, as well as other environmental and biological factors, will be needed to better understand the risk profile in this population and potential means of prevention.</p

Relationships between hypoxia markers and the leptin system, estrogen receptors in human primary and metastatic breast cancer: effects of preoperative chemotherapy

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is marked by enhanced expression of hypoxia-inducible factor-α (HIF-1α) and glucose transporter-1 (Glut-1). Hypoxic conditions have also been associated with overexpression of angiogenic factors, such as leptin. The aim of our study was to analyze the relationships between hypoxia markers HIF-1α, Glut-1, leptin, leptin receptor (ObR) and other breast cancer biomarkers in primary and metastatic breast cancer in patients treated or untreated with preoperative chemotherapy.</p> <p>Methods</p> <p>The expression of different biomarkers was examined by immunohistochemistry in 116 primary breast cancers and 65 lymph node metastases. Forty five of these samples were obtained form patients who received preoperative chemotherapy and 71 from untreated patients.</p> <p>Results</p> <p>In primary tumors without preoperative chemotherapy, HIF-1α and Glut-1 were positively correlated (p = 0.02, r = 0.437). HIF-1α in primary and metastatic tumors without preoperative therapy positively correlated with leptin (p < 0.0001, r = 0.532; p = 0.013, r = 0.533, respectively) and ObR (p = 0.002, r = 0.319; p = 0.083, r = 0.387, respectively). Hypoxia markers HIF-1α and Glut-1 were negatively associated with estrogen receptor alpha (ERα) and positively correlated with estrogen receptor beta (ERβ). In this group of tumors, a positive correlation between Glut-1 and proliferation marker Ki-67 (p = 0.017, r = 0.433) was noted. The associations between HIF-1α and Glut-1, HIF-1α and leptin, HIF-1α and ERα as well as Glut-1 and ERβ were lost following preoperative chemotherapy.</p> <p>Conclusions</p> <p>Intratumoral hypoxia in breast cancer is marked by coordinated expression of such markers as HIF-1α, Glut-1, leptin and ObR. The relationships among these proteins can be altered by preoperative chemotherapy.</p

The effect of prior walking on coronary heart disease risk markers in South Asian and European men.

Purpose: Heart disease risk is elevated in South Asians possibly due to impaired postprandial metabolism. Running has been shown to induce greater reductions in postprandial lipaemia in South Asian than European men but the effect of walking in South Asians is unknown. Methods: Fifteen South Asian and 14 White European men aged 19-30 years completed two, 2-d trials in a randomised crossover design. On day 1, participants rested (control) or walked for 60 min at approximately 50% maximum oxygen uptake (exercise). On day 2, participants rested and consumed two high fat meals over a 9h period during which 14 venous blood samples were collected. Results: South Asians exhibited higher postprandial triacylglycerol (geometric mean (95% confidence interval) 2.29(1.82 to 2.89) vs. 1.54(1.21 to 1.96) mmol·L-1·hr-1), glucose (5.49(5.21 to 5.79) vs. 5.05(4.78 to 5.33) mmol·L-1·hr-1), insulin (32.9(25.7 to 42.1) vs. 18.3(14.2 to 23.7) µU·mL-1·hr-1) and interleukin-6 (2.44(1.61 to 3.67) vs. 1.04(0.68 to 1.59) pg·mL-1·hr-1) than Europeans (all ES ≥ 0.72, P≤0.03). Between-group differences in triacylglycerol, glucose and insulin were not significant after controlling for age and percentage body fat. Walking reduced postprandial triacylglycerol (1.79(1.52 to 2.12) vs. 1.97(1.67 to 2.33) mmol·L-1·hr-1) and insulin (21.0(17.0 to 26.0) vs. 28.7(23.2 to 35.4) µU·mL-1·hr-1) (all ES ≥ 0.23. P≤0.01), but group differences were not significant. Conclusions: Healthy South Asians exhibited impaired postprandial metabolism compared with White Europeans, but these differences were diminished after controlling for potential confounders. The small-moderate reduction in postprandial triacylglycerol and insulin after brisk walking was not different between the ethnicities

Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model.

Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2-/- mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen

Transmission blocking activity of a standardized neem (Azadirachta indica) seed extract on the rodent malaria parasite Plasmodium berghei in its vector Anopheles stephensi

<p>Abstract</p> <p>Background</p> <p>The wide use of gametocytocidal artemisinin-based combination therapy (ACT) lead to a reduction of <it>Plasmodium falciparum </it>transmission in several African endemic settings. An increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on <it>Plasmodium </it>stages developing in the vector. Azadirachtin, a limonoid (tetranortriterpenoid) abundant in neem (<it>Azadirachta indica</it>, Meliaceae) seeds, is a promising candidate, inhibiting <it>Plasmodium </it>exflagellation <it>in vitro </it>at low concentrations. This work aimed at assessing the transmission-blocking potential of NeemAzal^®, an azadirachtin-enriched extract of neem seeds, using the rodent malaria <it>in vivo </it>model <it>Plasmodium berghei</it>/<it>Anopheles stephensi</it>.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>females were offered a blood-meal on <it>P. berghei </it>infected, gametocytaemic BALB/c mice, treated intraperitoneally with NeemAzal, one hour before feeding. The transmission-blocking activity of the product was evaluated by assessing oocyst prevalence, oocyst density and capacity to infect healthy mice. To characterize the anti-plasmodial effects of NeemAzal^®on early midgut stages, i.e. zygotes and ookinetes, Giemsa-stained mosquito midgut smears were examined.</p> <p>Results</p> <p>NeemAzal^®completely blocked <it>P. berghei </it>development in the vector, at an azadirachtin dose of 50 mg/kg mouse body weight. The totally 138 examined, treated mosquitoes (three experimental replications) did not reveal any oocyst and none of the healthy mice exposed to their bites developed parasitaemia. The examination of midgut content smears revealed a reduced number of zygotes and post-zygotic forms and the absence of mature ookinetes in treated mosquitoes. Post-zygotic forms showed several morphological alterations, compatible with the hypothesis of an azadirachtin interference with the functionality of the microtubule organizing centres and with the assembly of cytoskeletal microtubules, which are both fundamental processes in <it>Plasmodium </it>gametogenesis and ookinete formation.</p> <p>Conclusions</p> <p>This work demonstrated <it>in vivo </it>transmission blocking activity of an azadirachtin-enriched neem seed extract at an azadirachtin dose compatible with 'druggability' requisites. These results and evidence of anti-plasmodial activity of neem products accumulated over the last years encourage to convey neem compounds into the drug discovery & development pipeline and to evaluate their potential for the design of novel or improved transmission-blocking remedies.</p

Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo

Tumor cells exhibit an altered metabolism characterized by elevated aerobic glycolysis and lactate secretion which is supported by an increase in glucose transport and consumption. We hypothesized that reducing or eliminating the expression of the most prominently expressed glucose transporter(s) would decrease the amount of glucose available to breast cancer cells thereby decreasing their metabolic capacity and proliferative potential

Comparative genome analysis of lignin biosynthesis gene families across the plant kingdom

<p>Abstract</p> <p>Background</p> <p>As a major component of plant cell wall, lignin plays important roles in mechanical support, water transport, and stress responses. As the main cause for the recalcitrance of plant cell wall, lignin modification has been a major task for bioenergy feedstock improvement. The study of the evolution and function of lignin biosynthesis genes thus has two-fold implications. First, the lignin biosynthesis pathway provides an excellent model to study the coordinative evolution of a biochemical pathway in plants. Second, understanding the function and evolution of lignin biosynthesis genes will guide us to develop better strategies for bioenergy feedstock improvement.</p> <p>Results</p> <p>We analyzed lignin biosynthesis genes from fourteen plant species and one symbiotic fungal species. Comprehensive comparative genome analysis was carried out to study the distribution, relatedness, and family expansion of the lignin biosynthesis genes across the plant kingdom. In addition, we also analyzed the comparative synteny map between rice and sorghum to study the evolution of lignin biosynthesis genes within the <it>Poaceae </it>family and the chromosome evolution between the two species. Comprehensive lignin biosynthesis gene expression analysis was performed in rice, poplar and <it>Arabidopsis</it>. The representative data from rice indicates that different fates of gene duplications exist for lignin biosynthesis genes. In addition, we also carried out the biomass composition analysis of nine <it>Arabidopsis </it>mutants with both MBMS analysis and traditional wet chemistry methods. The results were analyzed together with the genomics analysis.</p> <p>Conclusion</p> <p>The research revealed that, among the species analyzed, the complete lignin biosynthesis pathway first appeared in moss; the pathway is absent in green algae. The expansion of lignin biosynthesis gene families correlates with substrate diversity. In addition, we found that the expansion of the gene families mostly occurred after the divergence of monocots and dicots, with the exception of the C4H gene family. Gene expression analysis revealed different fates of gene duplications, largely confirming plants are tolerant to gene dosage effects. The rapid expansion of lignin biosynthesis genes indicated that the translation of transgenic lignin modification strategies from model species to bioenergy feedstock might only be successful between the closely relevant species within the same family.</p