Effect of Roux-en-Y Gastric Bypass Surgery on Bile Acid Metabolism in Normal and Obese Diabetic Rats

In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans.     

Dynamics of the Establishment of Multinucleate Compartments in Fusarium oxysporum

Nuclear dynamics can vary widely between fungal species and between stages of development of fungal colonies. Here we compared nuclear dynamics and mitotic patterns between germlings and mature hyphae in Fusarium oxysporum. Using fluorescently labeled nuclei and live-cell imaging, we show that F. oxysporum is subject to a developmental transition from a uninucleate to a multinucleate state after completion of colony initiation. We observed a special type of hypha that exhibits a higher growth rate, possibly acting as a nutrient scout. The higher growth rate is associated with a higher nuclear count and mitotic waves involving 2 to 6 nuclei in the apical compartment. Further, we found that dormant nuclei of intercalary compartments can reenter the mitotic cycle, resulting in multinucleate compartments with up to 18 nuclei in a single compartment.     

Potential of diallyl sulfide bearing pH-sensitive liposomes in chemoprevention against DMBA-induced skin papilloma

Diallyl sulfide (DAS), an active component of garlic, possesses strong anti-neoplastic properties against various forms of cancer. In the present study, we have evaluated chemo-preventive effects of liposomized DAS (conventional egg PC and pH-sensitive liposomes) against DMBA-induced skin papilloma. Various liposome-based novel formulations of DAS (250 microg/mouse) were applied topically, after one hour of exposure to DMBA (52 microg/mouse/dose), to the animals. The animals were treated thrice weekly for the total period of 12 weeks. The efficacy of the various liposomal formulations of DAS was evaluated on the basis of parameters such as incidence of tumorogenesis and total numbers and sizes of induced tumor nodules. The liposomized DAS formulations also were assessed for their effect on the expression of p53wt, p53mut, and p21/Waf1. The results of the present study showed that liposomized DAS could effectively delay the onset of tumorogenesis and reduce the cumulative numbers and sizes of tumor papillomas in treated mice. Treatment of DMBA-exposed animals with the liposomal formulation of DAS ensued in upregulation of p53wt and p21/Waf1, while levels of p53mut expression reduced down. The promising chemo-preventive nature of liposomal DAS may form the basis for establishing effective means of controlling various forms of cancer, including skin papilloma.     

Reversal of systemic hypertension-associated cardiac remodeling in chronic pressure overload myocardium by ciglitazone

Elevated oxidative stress has been characterized in numerous disorders including systemic hypertension, arterial stiffness, left ventricular hypertrophy (LVH) and heart failure. The peroxisome proliferator activated receptor gamma (PPARgamma) ameliorates oxidative stress and LVH. To test the hypothesis that PPARgamma decreased LVH and cardiac fibrosis in chronic pressure overload, in part, by increasing SOD, eNOS and elastin and decreasing NOX4, MMP and collagen synthesis and degradation, chronic pressure overload analogous to systemic hypertension was created in C57BL/6J mice by occluding the abdominal aorta above the kidneys (aortic stenosis-AS). The sham surgery was used as controls. Ciglitazone (CZ, a PPARgamma agonist, 4 microg/ml) was administered in drinking water. LV function was measured by M-Mode Echocardiography. We found that PPARgamma protein levels were increased by CZ. NOX-4 expression was increased by pressure-overload and such an increase was attenuated by CZ. SOD expression was not affected by CZ. Expression of iNOS was induced by pressure-overload, and such an increase was inhibited by CZ. Protein levels for MMP2, MMP-9, MMP-13 were induced and TIMP levels were decreased by pressure-overload. The CZ mitigated these levels. Collagen synthesis was increased and elastin levels were decreased by pressure-overload and CZ ameliorated these changes. Histochemistry showed that CZ inhibited interstitial and perivascular fibrosis. Echocardiography showed that CZ attenuated the systolic and diastolic LV dysfunction induced by pressure-overload. These observations suggested that CZ inhibited pressure-overlaod-induced cardiac remodeling, and inhibition of an induction of NOX4, iNOS, MMP-2/MMP-13 expression and collagen synthesis/degradation may play a role in pressure-overload induced cardiac remodeling.     

Effects of dietary palm oil on serum lipid peroxidation, antithrombin III, plasma cyclic AMP, and platelet aggregation.

Intravascular thrombus formation in association with lipid depositions in the arterial wall is thought to be involved in the process of atheroma formation. We have previously shown the beneficial effect of palm oil on the serum lipid profile resulting in a lowering of serum triacylglycerol and an elevation of the HDL/LDL ratio. The present study investigates the effect of dietary palm oil on the biochemical parameters associated with clotting and platelet aggregation in young rats (70 g body wt) fed a palm oil diet over a period of 10 weeks. Palm oil-fed rats showed significantly lower levels of fibrinogen and serum lipid peroxide and elevated AtIII levels resulting in a prolongation of clotting time. Reduced platelet aggregation and ATP release associated with a prolongation of bleeding time were also found. These findings, together with our earlier findings on the effect of palm oil on the serum lipid profile, suggest that dietary palm oil may be antithrombotic as well as beneficial in preventing the deposition of lipids on the vessel wall and may, therefore, be protective against the development of atherosclerosis.     

Chitinase Production in Solid-State Fermentation by Enterobacter sp. NRG4 Using Statistical Experimental Design

The optimization of nutrient levels for chitinase production by Enterobacter sp. NRG4 in solid-state fermentation conditions (SSF) was carried out using response surface methodology (RSM) based on central composite design (CCD). The design was employed by selecting wheat bran-to-flake chitin ratio, moisture level, inoculum size, and incubation time as model factors. The results of first-order factorial design experiments showed that all four independent variables have significant effects on chitinase production. The optimum concentrations for chitinase production were wheat bran-to-flake chitin ratio, 1; moisture level, 80%; inoculum size, 2.6 mL; and incubation time, 168 h. Using this statistical optimization method, chitinase production was found to increase from 616 U · g⁻¹ dry weight of solid substrate to 1475 U · g⁻¹ dry weight of solid substrate.     

The viral restriction factor tetherin/BST2 tethers cytokinetic midbody remnants to the cell surface

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BMI1 Is Expressed in Canine Osteosarcoma and Contributes to Cell Growth and Chemotherapy Resistance

BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.     

Carotenoid biosynthesis genes in rice: structural analysis, genome-wide expression profiling and phylogenetic analysis

Carotenoids, important lipid-soluble antioxidants in photosynthetic tissues, are known to be completely absent in rice endosperm. Many studies, involving transgenic manipulations of carotenoid biosynthesis genes, have been performed to get carotenoid-enriched rice grain. Study of genes involved in their biosynthesis can provide further information regarding the abundance/absence of carotenoids in different tissues. We have identified 16 and 34 carotenoid biosynthesis genes in rice and Populus genomes, respectively. A detailed analysis of the domain structure of carotenoid biosynthesis enzymes in rice, Populus and Arabidopsis has shown that highly conserved catalytic domains, along with other domains, are present in these proteins. Phylogenetic analysis of rice genes with Arabidopsis and other characterized carotenoid biosynthesis genes has revealed that homologous genes exist in these plants, and the duplicated gene copies probably adopt new functions. Expression of rice and Populus genes has been analyzed by full-length cDNA- and EST-based expression profiling. In rice, this analysis was complemented by real-time PCR, microarray and signature-based expression profiling, which reveal that carotenoid biosynthesis genes are highly expressed in light-grown tissues, have differential expression pattern during vegetative/reproductive development and are responsive to stress.     

Therapeutic Value of Zinc Supplementation in Acute and Persistent Diarrhea: A Systematic Review

Background

For over a decade, the importance of zinc in the treatment of acute and persistent diarrhea has been recognized. In spite of recently published reviews, there remain several unanswered questions about the role of zinc supplementation in childhood diarrhea in the developing countries. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation.

Methods and Findings

EMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention and treatment of childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. The reviews and published RCTs were qualitatively mapped followed by updated random-effects meta-analyses, subgroup meta-analyses and meta-regression to quantify and characterize the role of zinc supplementation with diarrhea-related outcomes. We found that although there was evidence to support the use of zinc to treat diarrhea in children, there was significant unexplained heterogeneity across the studies for the effect of zinc supplementation in reducing important diarrhea outcomes. Zinc supplementation reduced the mean duration of diarrhea by 19.7% but had no effect on stool frequency or stool output, and increased the risk of vomiting. Our subgroup meta-analyses and meta-regression showed that age, stunting, breast-feeding and baseline zinc levels could not explain the heterogeneity associated with differential reduction in the mean diarrheal duration. However, the baseline zinc levels may not be representative of the existing zinc deficiency state.

Conclusions

Understanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation. To improve the programmatic use of zinc, further evaluations of the zinc salts used, the dose, the frequency and duration of supplementation, and its acceptability are required. The significant heterogeneity of responses to zinc suggests the need to revisit the strategy of universal zinc supplementation in the treatment children with acute diarrhea in developing countries.