Visfatin is regulated by rosiglitazone in type 2 diabetes mellitus and influenced by NFκB and JNK in human abdominal subcutaneous adipocytes

Visfatin has been proposed as an insulin-mimicking adipocytokine, predominantly secreted from adipose tissue and correlated with obesity. However, recent studies suggest visfatin may act as a proinflammatory cytokine. Our studies sought to determine the significance of this adipocytokine and its potential role in the pathogenesis of T2DM. Firstly, we examined the effects of diabetic status on circulating visfatin levels, and several other adipocytokines, demonstrating that diabetic status increased visfatin*, TNF-α*** and IL-6*** compared with non-diabetic subjects (*p<0.05, **p<0.01, ***p<0.001, respectively). We then assessed the effects of an insulin sensitizer, rosiglitazone (RSG), in treatment naïve T2DM subjects, on circulating visfatin levels. Our findings showed that visfatin was reduced post-RSG treatment [vs. pre-treatment (*p<0.05)] accompanied by a reduction in HOMA-IR**, thus implicating a role for insulin in visfatin regulation. Further studies addressed the intracellular mechanisms by which visfatin may be regulated, and may exert pro-inflammatory effects, in human abdominal subcutaneous (Abd Sc) adipocytes. Following insulin (Ins) and RSG treatment, our in vitro findings highlighted that insulin (100 nM), alone, upregulated visfatin protein expression whereas, in combination with RSG (10 nM), it reduced visfatin*, IKKβ** and p-JNK1/2*. Furthermore, inhibition of JNK protein exacted a significant reduction in visfatin expression (**p<0.01), whilst NF-κB blockade increased visfatin (*p<0.05), thus identifying JNK as the more influential factor in visfatin regulation. Additional in vitro analysis on adipokines regulating visfatin showed that only Abd Sc adipocytes treated with recombinant human (rh)IL-6 increased visfatin protein (*p<0.05), whilst rh visfatin treatment, itself, had no influence on TNF-α, IL-6 or resistin secretion from Sc adipocytes. These data highlight visfatin''s regulation by insulin and RSG, potentially acting through NF-κB and JNK mechanisms, with only rh IL-6 modestly affecting visfatin regulation. Taken together, these findings suggest that visfatin may represent a pro-inflammatory cytokine that is influenced by insulin/insulin sensitivity via the NF-κB and JNK pathways.     

Effect of supplementary feeding of vitamin K1 on difethialone treated Indian gerbil, Tatera indica Hardwicke in laboratory

Two dosages (1 and 2 mg/kg) of vitamin K1 supplementation for 5 and 15 days were given to Indian gerbil T. indica fed on difethialone bait (0.0025%) for one day. The results indicated that the lower dosage could not reverse the anticoagulation process, however the period of mortality was considerably increased from 3-9 days (in control) to 5-14 days (5 days supplementation regime). Subsequently when the vitamin K1 dosage was doubled and given for 15 days, there was 100% reversal of anticoagulation process and all the test gerbils became normal within a month of poisoning with difethialone bait.     

Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

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Comparative Analysis of Disease-Linked Single Nucleotide Polymorphic Markers from Brassica rapa for Their Applicability to Brassica oleracea

Numerous studies using single nucleotide polymorphisms (SNPs) have been conducted in humans, and other animals, and in major crops, including rice, soybean, and Chinese cabbage. However, the number of SNP studies in cabbage is limited. In this present study, we evaluated whether 7,645 SNPs previously identified as molecular markers linked to disease resistance in the Brassica rapa genome could be applied to B. oleracea. In a BLAST analysis using the SNP sequences of B. rapa and B. oleracea genomic sequence data registered in the NCBI database, 256 genes for which SNPs had been identified in B. rapa were found in B. oleracea. These genes were classified into three functional groups: molecular function (64 genes), biological process (96 genes), and cellular component (96 genes). A total of 693 SNP markers, including 145 SNP markers [BRH—developed from the B. rapa genome for high-resolution melt (HRM) analysis], 425 SNP markers (BRP—based on the B. rapa genome that could be applied to B. oleracea), and 123 new SNP markers (BRS—derived from BRP and designed for HRM analysis), were investigated for their ability to amplify sequences from cabbage genomic DNA. In total, 425 of the SNP markers (BRP-based on B. rapa genome), selected from 7,645 SNPs, were successfully applied to B. oleracea. Using PCR, 108 of 145 BRH (74.5%), 415 of 425 BRP (97.6%), and 118 of 123 BRS (95.9%) showed amplification, suggesting that it is possible to apply SNP markers developed based on the B. rapa genome to B. oleracea. These results provide valuable information that can be utilized in cabbage genetics and breeding programs using molecular markers derived from other Brassica species.     

Pharmacovigilance: Effects of herbal components on human drugs interactions involving Cytochrome P450

Cytochrome P450 (CYP P450) enzymes are a superfamily of mono-oxygenases that are found in all kingdoms of life. The CYP P450 enzymes constitute a large superfamily of haem-thiolate proteins involved in the metabolism of a wide variety of both exogenous and endogenous compounds. The CYP activities have been shown to be involved in numerous interactions especially between drugs and herbal constituents. The majority of serious cases of drug interactions are as a result of the interference of the metabolic clearance of one drug by yet another co-administered drug, food or natural product. Gaining mechanistic knowledge towards such interactions has been accepted as an approach to avoid adverse reactions. The inductions and inhibition of CYP enzymes by natural products in the presence of a prescribed drug has led to adverse effects. Herbal medicines such as St. John's wort (Hypericum perforatum), garlic (Allium sativa), piperine (from Piper sp.), ginseng (Ginseng sp.), gingko (Gingko biloba), soya beans (Glycine max), alfalfa (Medicago sativa) and grape fruit juice show clinical interactions when co-administered with medicines. This review documents the involvement of CYP enzymes in the metabolism of known available drugs and herbal products. We also document the interactions between herbal constituents &#38; CYP enzymes showing potential drug-herb interactions. Data on CYP450 enzymes in activation (i.e. induction or inhibition) with natural constituents is also reviewed.