Metabolic and molecular action of <Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> (fenugreek) and trace metals in experimental diabetic tissues

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.     

Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but independent of NLRP3

Introduction

The protein platform called the NOD-like-receptor -family member (NLRP)-3 inflammasome needs to be activated to process intracellular caspase-1. Active caspase-1 is able to cleave pro-Interleukin (IL)-1β, resulting in bioactive IL-1β. IL-1β is a potent proinflammatory cytokine, and thought to play a key role in the pathogenesis of Lyme arthritis, a common manifestation of Borrelia burgdorferi infection. The precise pathways through which B. burgdorferi recognition leads to inflammasome activation and processing of IL-1β in Lyme arthritis has not been elucidated. In the present study, we investigated the contribution of several pattern recognition receptors and inflammasome components in a novel murine model of Lyme arthritis.

Methods

Lyme arthritis was elicited by live B. burgdorferi, injected intra-articularly in knee joints of mice. To identify the relevant pathway components, the model was applied to wild-type, NLRP3-/-, ASC-/-, caspase-1-/-, NOD1-/-, NOD2-/-, and RICK-/- mice. As a control, TLR2-/-, Myd88-/- and IL-1R-/- mice were used. Peritoneal macrophages and bone marrow-derived macrophages were used for in vitro cytokine production and inflammasome activation studies. Joint inflammation was analyzed in synovial specimens and whole knee joints. Mann-Whitney U tests were used to detect statistical differences.

Results

We demonstrate that ASC/caspase-1-driven IL-1β is crucial for induction of B. burgdorferi-induced murine Lyme arthritis. In addition, we show that B. burgdorferi-induced murine Lyme arthritis is less dependent on NOD1/NOD2/RICK pathways while the TLR2-MyD88 pathway is crucial.

Conclusions

Murine Lyme arthritis is strongly dependent on IL-1 production, and B. burgdorferi induces inflammasome-mediated caspase-1 activation. Next to that, murine Lyme arthritis is ASC- and caspase-1-dependent, but NLRP3, NOD1, NOD2, and RICK independent. Also, caspase-1 activation by B. burgdorferi is dependent on TLR2 and MyD88. Based on present results indicating that IL-1 is one of the major mediators in Lyme arthritis, there is a rationale to propose that neutralizing IL-1 activity may also have beneficial effects in chronic Lyme arthritis.     

Tyrosine phosphorylation of myosin heavy chain during skeletal muscle differentiation: an integrated bioinformatics approach

Background  

Previously it has been shown that insulin-mediated tyrosine phosphorylation of myosin heavy chain is concomitant with enhanced association of C-terminal SRC kinase during skeletal muscle differentiation. We sought to identify putative site(s) for this phosphorylation event.     

Cortisol concentrations in early porcine embryos

A study was conducted to determine the presence of cortisol in body tissue of porcine embryos at days 25 and 35 of gestation. Cortisol concentrations (ng/mg DNA) were low but measurable at day 25 and increased eightfold by day 35 during a time when body weight increased 6.4-fold. At day 35, there was a highly significant positive linear regression of body weight on cortisol concentrations. The source of this embryonic cortisol is not known, but its presence suggests the opportunity for cortisol to influence porcine embryonic development at these early gestational stages.     

Molecular cloning and endometrial expression of porcine amphiregulin

The porcine amphiregulin gene was previously reported to be within the quantitative trait locus (QTL) for uterine capacity on chromosome 8. Because amphiregulin stimulates cell proliferation, the amphiregulin gene might be responsible for this QTL. The objectives of this study were to clone amphiregulin cDNA and compare endometrial expression of its mRNA in pregnant Meishan (M) and White composite (WC) pigs. We obtained two amphiregulin cDNAs, one with 1,221 bp and another with 1,109 bp. The 112 bp difference corresponded to exon 5 of the human amphiregulin gene, which codes for the cytoplasmic domain. Endometrial mRNA expression of amphiregulin was significantly lower in M pigs than in WC pigs during early pregnancy (day 15 - 40 of gestation). Amphiregulin mRNA expression in the endometrium of both M and WC pigs increased (P < 0.01) from days 15 to 20, decreased (P = 0.01) from days 20 to 30, and did not change between days 30 and 40. This may result in reduced amphiregulin protein production leading to the slower development of M conceptuses, contributing to greater uterine capacity and litter size in prolific Chinese M pigs. Porcine genomic sequences isolated from a bacterial artificial chromosome genomic library contained exon 5, suggesting that the deletion of exon 5 in the mRNA may be due to differential splicing. The amphiregulin gene consisted of six exons and five introns spanning 10.3 kb. Mol.