Evidence from Co-expression Analysis for the Involvement of Amidase and INS in the Tryptophan-Independent Pathway of IAA Synthesis in Arabidopsis.

The reverse genetic approach has uncovered indole synthase (INS) as the first enzyme in the tryptophan (trp)-independent pathway of IAA synthesis. The importance of INS was reevaluated suggesting it may interact with tryptophan synthase B (TSB) and therefore involved in the trp-dependent pathway. Thus, the main aim of this study was to clarify the route of INS through the analysis of Arabidopsis genome. Analysis of the top 2000 co-expression gene lists in general and specific conditions shows that TSA is strongly positively co-expressed with TSB in general, hormone, and abiotic conditions with mutual ranks of 89, 38, and 180 respectively. Moreover, TSA is positively correlated with TSB (0.291). However, INS was not found in any of these coexpressed gene lists and negatively correlated with TSB (- 0.046) suggesting unambiguously that these two routes are separately and independently operated. So far, the remaining steps in the INS pathway have remained elusive. Among all enzymes reported to have a role in IAA synthesis, amidase was found to strongly positively co-expressed with INS in general and light conditions with mutual ranks of 116 and 141 respectively. Additionally, amidase1 was found to positively correlate with INS (0.297) and negatively coexpressed with TSB concluding that amidase may exclusively involve in the trp-independent pathway.

Implications of enigmatic transglutaminase 2 (TG2) in cardiac diseases and therapeutic developments.

Cardiac diseases are the leading cause of mortality and morbidity worldwide. Mounting evidence suggests that transglutaminases (TGs), tissue TG (TG2) in particular, are involved in numerous molecular responses underlying the pathogenesis of cardiac diseases. The TG family has several intra- and extracellular functions in the human body, including collagen cross-linking, angiogenesis, cell growth, differentiation, migration, adhesion as well as survival. TGs are thiol- and calcium-dependent acyl transferases that catalyze the formation of a covalent bond between the γ-carboxamide group of a glutamine residue and an amine group, thus increasing the stability, rigidity, and stiffness of the myocardial extracellular matrix (ECM). Excessive accumulation of cross-linked collagen leads to increase myocardial stiffness and fibrosis. Beyond TG2 extracellular protein cross-linking action, increasing evidence suggests that this pleiotropic TG isozyme may also promote fibrotic diseases through cell survival and profibrotic pathway activation at the signaling, transcriptional and translational levels. Due to its multiple functions and localizations, TG2 fulfils critical yet incompletely understood roles in myocardial fibrosis and associated heart diseases, such as cardiac hypertrophy, heart failure, and age-related myocardial stiffness under several conditions. This review summarizes current knowledge and existing gaps regarding the ECM-dependent and ECM-independent roles of TG2 and highlights the therapeutic prospects of targeting TG2 to treat cardiac diseases.

Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats.

This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.

Lipid and hematological parameters in hyperleptinemic healthy Arab male youth in Jordan.

To analyze the influence ofhyperleptinemia on fasting lipid and hematological parameters in healthy Arab male youth in Jordan, this cross-sectional study was carried out in April 2009 on a sample of 120 students aged 18-24 years. Subjects were stratified by fasting leptin into two groups (control, <12.7 ng mL(-1) vs. hyperleptenimic, e_< 12.7 ng mL(-1)) and BMI (normal weight, < 25 kgm(-2) vs. overweight/obese, BMI e_< 25 kg m(-2)). Fasting serum leptin, blood glucose, lipid profile and hematological parameters values were determined by standard kit methods. Mean serum leptin concentrations were more than five times as high in hyperleptenemic subjects than in control subjects (p < 0.001). Compared with control group, significant elevations (p < 0.01) were observed in the means total cholesterol, LDL cholesterol and triglyceride levels of hyperleptenemic group whereas no significant differences was detected in HDL-cholesterol. Except the changes of WBC count, MCH and slightly MCHC, there were no differences between both groups in any other term of hematological parameters. In conclusion, changes in lipid variables and some hematological parameters may increase plasma viscosity as a step during atherosclerosis pathogenesis in male youth at risk for dyslipidemia and cardiovascular diseases. Thus, hyperleptinemia could be a useful index in identifying healthy youth male subjects but this hypothesis needs further investigation.

Anti-diabetic activity of Ferula assafoetida extract in normal and alloxan-induced diabetic rats.

The aim of the present study was to evaluate the possible anti-diabetic potential of Asafetida extract against the pancreatic beta-cells damage from alloxan-induced diabetes in rats and some hormones related to diabetes mellitus. Asafetida induced significant reduction in blood glucose and increasing of serum insulin, our data indicate that the level of glucose in the animals that subjected with alloxan was 10.28 +/- 0.85 mmol L(-1) p < 0.05 comparing with control group 3.27 +/- 0.25 p < 0.05, the level of blood glucose in diabetic group when subjected with Asafetida extract decreasing to 6.75 +/- 0.31 p < 0.05. There was significant amount of insulin secretion in diabetic animals when subjected with Asafetida extract 0.48 +/- 0.05 p < 0.05 in comparison with diabetic animal's 0.33 +/- 0.06 p < 0.05. These findings suggested that Asafetida extract treatment exerts therapeutic protective effect in diabetes by preserving pancreatic beta-cells integrity and significant activity extract, which supports traditional usage to prevent diabetic complications.