Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease

BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. METHODS: On seventy eight advanced CKD (stages 4 and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or conservative treatment (CT) the following parameters were studied: body mass index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL-cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and 276. Seventy age-and gender-matched healthy subjects served as control subjects. RESULTS: Markedly (P = 0.01) elevated plasma adiponectin levels were observed in CKD patients, especially CT patients, compared to control subjects. The wild type of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and CT patients had significantly higher frequency of the TT genotypes of +276G > T gene (P = 0.04) compared with control subjects. A significant positive correlation was observed between plasma adiponectin and IL6 level, whereas negative correlations were found between adiponectin level, cholesterol, HDL cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6 (P = 0.001) was independently associated with plasma adiponectin levels. The adiponectin gene the 276 GT+TT genotypes were associated with a higher level of adiponectin . CONCLUSIONS: The present study demonstrated that ADPN is related to several metabolic and inflammatory CV risk factors in a manner consistent with the hypothesis that this protein might have a protective role against these factors. We observed an association between the +276G>T SNP in the adiponectin gene and CKD in children. Genetic variation of +276 gene seemed to have a positive impact on circulating adiponectin levels in CKD patients

Sulphated tubers extract from the giant taro Alocasia macrorrhiza inhibits the carcinogenesis initiation and modulates macrophage functions

Alocasia macrorrhizos (L.) G. Don, Araceae, is a traditionally edible plant known as giant taro. This work aimed to prepare sulphatedpolysaccharide extract of A. macrorrhizos tubers (SAM) and to investigate its tumor anti-initiation and anti-promotion activities. Methods:Enzymatic, colorimetric, fluorometric, and cell-based assays were used throughout the study. Tumor anti-initiation activity was investigatedby estimation of SAM effect on cytochrome P450 1A1 (Cyp1A1) glutathione-S-transferases (GST), glutathione (GSH), epoxide hydrolase(mEH), and quinone reductase (QR), while Tumor anti-promotion activity was investigated by macrophage proliferation, nitric oxide (NO),and LPS binding to macrophages. SAM inhibited the carcinogen metabolizing enzyme Cyp1A1 and it induced, to variable extent, thedetoxification enzymes (GST, mEH and QR), especially mEH. Additionally, SAM showed anti-inflammatory property by inhibiting NO andit induced the affinity of macrophage to bind pathogens and neoplastic cells. Additionally, SAM was cytotoxic to colon HCT-116 cells.The findings suggested SAM as a promising inhibitor of the carcinogenesis initiation phase.Keywords: Alocasia macrorrhiza; sulphated; Tumor anti-initiation; Cyp1A1; Epoxide hydrolase; glutathione-S-transferases; quinonereductase; FITC-LPS; macrophag

Sulphated tubers extract from the giant taro Alocasia macrorrhiza inhibits the carcinogenesis initiation and modulates macrophage functions

Alocasia macrorrhizos (L.) G. Don, Araceae, is a traditionally edible plant known as giant taro. This work aimed to prepare sulphatedpolysaccharide extract of A. macrorrhizos tubers (SAM) and to investigate its tumor anti-initiation and anti-promotion activities. Methods:Enzymatic, colorimetric, fluorometric, and cell-based assays were used throughout the study. Tumor anti-initiation activity was investigatedby estimation of SAM effect on cytochrome P450 1A1 (Cyp1A1) glutathione-S-transferases (GST), glutathione (GSH), epoxide hydrolase(mEH), and quinone reductase (QR), while Tumor anti-promotion activity was investigated by macrophage proliferation, nitric oxide (NO),and LPS binding to macrophages. SAM inhibited the carcinogen metabolizing enzyme Cyp1A1 and it induced, to variable extent, thedetoxification enzymes (GST, mEH and QR), especially mEH. Additionally, SAM showed anti-inflammatory property by inhibiting NO andit induced the affinity of macrophage to bind pathogens and neoplastic cells. Additionally, SAM was cytotoxic to colon HCT-116 cells.The findings suggested SAM as a promising inhibitor of the carcinogenesis initiation phase.Keywords: Alocasia macrorrhiza; sulphated; Tumor anti-initiation; Cyp1A1; Epoxide hydrolase; glutathione-S-transferases; quinonereductase; FITC-LPS; macrophag

Polysaccharide extracts of the brown alga <i>Sargassum</i><i>asperifolium</i> possess <i>in vitro</i> cancer chemopreventive properties

<div><p>The cancer chemopreventive activity of the polysaccharide extracts (<b>E1</b>–<b>E4</b>) of <i>Sargassum asperifolium</i>, a brown alga in Red Sea shores in Egypt, was investigated. Tumour anti-initiation activity (the modulation of carcinogen metabolism) indicated that <b>E3</b> and <b>E4</b> were potent anti-initiators by inhibiting the carcinogen activator cytochrome P450-1A, and enhancing carcinogen detoxification enzymes glutathione-<i>S</i>-transferase. Only <b>E4</b> significantly enhanced quinone reductase activity. All polysaccharide extracts possessed anti-promotion property by their anti-inflammatory activity. <b>E3</b> and <b>E4</b> dramatically induced the growth of spleen macrophages. <b>E2</b>, <b>E3</b> and <b>E4</b> significantly inhibited nitric oxide generation from lipopolysaccharide (LPS)-stimulated spleen macrophages, while <b>E1</b>, <b>E3</b> and <b>E4</b> led to significant inhibition of LPS-induced tumour necrosis factor-α. The extracts <b>E1</b>, <b>E2</b> and <b>E4</b> showed cytotoxicity against HepG2 cells, where <b>E2</b> and <b>E4</b> induced cell death due to apoptosis. In conclusion, <b>E3</b> and <b>E4</b> are promising cancer chemopreventive extracts, since they had tumour anti-initiating activity via their protective modulation of carcinogen metabolism.</p></div

Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease

Abstract Background The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. Methods On seventy eight advanced CKD (stages 4 and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or conservative treatment (CT) the following parameters were studied: body mass index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL-cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and 276. Seventy age-and gender-matched healthy subjects served as control subjects. Results Markedly (P = 0.01) elevated plasma adiponectin levels were observed in CKD patients, especially CT patients, compared to control subjects. The wild type of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and CT patients had significantly higher frequency of the TT genotypes of +276G > T gene (P = 0.04) compared with control subjects. A significant positive correlation was observed between plasma adiponectin and IL6 level, whereas negative correlations were found between adiponectin level, cholesterol, HDL cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6 (P = 0.001) was independently associated with plasma adiponectin levels. The adiponectin gene the 276 GT+TT genotypes were associated with a higher level of adiponectin . Conclusions The present study demonstrated that ADPN is related to several metabolic and inflammatory CV risk factors in a manner consistent with the hypothesis that this protein might have a protective role against these factors. We observed an association between the +276G>T SNP in the adiponectin gene and CKD in children. Genetic variation of +276 gene seemed to have a positive impact on circulating adiponectin levels in CKD patients.</p

Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus

B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we hypothesized that an altered phenotype of B cell subsets is associated with T1D in children. Children with T1D (n=29) and control children with normal blood glucose levels (n=14) were recruited. The percentages of different circulating IL10-producing Breg subsets, including B10, immature transitional, and plasmablasts were determined using flow cytometry analysis. Furthermore, the association between different IL10-producing B cells and patient parameters was investigated. The percentage of circulating IL10+CD24hiCD27+ (B10) and IL10+CD24hiCD38hi (immature transitional) subsets of Breg cells was significantly lower in T1D patients than in healthy controls. Moreover, these cells were also negatively correlated with fasting blood glucose and HbA1c levels. Breg cells did not correlate with autoantibody levels in the serum. These findings suggest that certain Breg subsets are numerically deficient in children with T1D. This alteration in frequency is associated with deficient islet function and glycemia. These findings suggest that Breg cells may be involved in the loss of auto-tolerance and consequent destruction of pancreatic cells and could, therefore, be a potential target for immunotherapy

Efficacy and durability of bovine virus diarrhea (BVD) virus killed vaccine adjuvanted with monolaurin.

The bovine virus diarrhea virus (BVDV) causes reproductive, enteric, and respiratory diseases. Vaccination is essential in increasing herd resistance to BVDV spread. The selection of an adjuvant is an important factor in the success of the vaccination process. Monolaurin or glycerol monolaurate is a safe compound with an immunomodulatory effect. This study aimed to evaluate the efficacy of monolaurin as a novel adjuvant. This was examined through the preparation of an inactivated BVDV (NADL strain) vaccine adjuvanted with different concentrations of monolaurin and compared with the registered available locally prepared polyvalent vaccine (Pneumo-4) containing BVD (NADL strain), BoHV-1 (Abou Hammad strain), BPI3 (strain 45), and BRSV (strain 375L), and adjuvanted with aluminum hydroxide gel. The inactivated BVDV vaccine was prepared using three concentrations, 0.5%, 1%, and 2%, from monolaurin as adjuvants. A potency test was performed on five groups of animals. The first group, which did not receive vaccination, served as a control group while three other groups were vaccinated using the prepared vaccines. The fifth group received the Pneumo-4 vaccine. Vaccination response was monitored by measuring viral neutralizing antibodies using enzyme-linked immunosorbent assay (ELISA). It was found that the BVD inactivated vaccine with 1% and 2% monolaurin elicited higher neutralizing antibodies that have longer-lasting effects (nine months) with no reaction at the injection site in comparison to the commercial vaccine adjuvanted by aluminum hydroxide gel