One of the key pathophysiologies of H5N1 infection is excessive proinflammatory cytokine response (cytokine storm) characterized by increases in IFN-β, TNF-α, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced cytokine release can occur via an infection-independent mechanism, however, detail of the cellular signaling involved is poorly understood. To elucidate this mechanism, the effect of inactivated (β-propiolactone-treated) H5N1 on the cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial cells was investigated. We found that the inactivated-H5N1 increased mRNA for IL-6 and CXCL8 but not TNF-α, CCL5 or CXCL10. This effect of the inactivated-H5N1 was inhibited by sialic acid receptor inhibitor (α-2,3 sialidase), adenosine diphosphatase (apyrase), P2Y receptor (P2YR) inhibitor (suramin), P2Y6R antagonist (MRS2578), phospholipase C inhibitor (U73122), protein kinase C inhibitors (BIM and Gö6976) and cell-permeant Ca2+ chelator (BAPTA-AM). Inhibitors of MAPK signaling, including of ERK1/2 (PD98059), p38 MAPK (SB203580) and JNK (SP600125) significantly suppressed the inactivated-H5N1-induced mRNA expression of CXCL8. On the other hand, the inactivated-H5N1-induced mRNA expression of IL-6 was inhibited by SB203580, but not PD98059 or SP600125, whereas SN-50, an inhibitor of NF-κB, inhibited the effect of virus on mRNA expression of both of IL-6 and CXCL8. Taken together, our data suggest that, without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and α-2,3 sialic acid receptors at the cell membrane of host cells, and involves activation of P2Y6 purinergic receptors.
Melamine has been used to increase the amount of measurable nitrogen which is a component of protein. The renal toxicity of melamine has been reported in infants and animals that consumed a mixture of melamine in their food products. This study aimed to investigate the effects of melamine on rat renal function using clearance and histological techniques. Animals were divided into 3 groups: vehicle control, 400 mg/kg melamine and mixture of 400 mg/kg melamine and 400 mg/kg cyanuric acid (p.o., daily for three days). The results showed that blood urea nitrogen level significantly increased in the rats treated with the mixture of melamine and cyanuric acid. The urine flow rate, glomerular filtration rate, renal plasma flow and urinary sodium and potassium excretion rate significantly decreased when compared to vehicle control. These results suggested both glomeruli and renal tubules of rats treated with mixture of melamine and cyanuric acid were damaged. Histological study also confirmed these findings and showed significant glomerular atrophy and dilated renal tubules. Numerous clear brownish-yellow crystals were also found in the distal tubule, collecting tubule and papillary duct. However, rats solely treated with melamine showed no significant difference in renal function or structures.
Metabolic syndrome is an important health problem associated with both subclinical atherosclerosis and an increased risk of cardiovascular disease and it leads to an elevated total mortality. Aortic pulse wave velocity (aPWV) is widely used for noninvasive assessment of arterial stiffness. Ankle-brachial index (ABI) predicts peripheral arterial disease (PAD) of the lower extremities. In addition, malondialdehyde (MDA) is thought to be involved in the development of arterial stiffness. The present study aimed to: (1) compare aPWV, ABI, and MDA between participants with MetS and those without MetS and (2) investigate the correlation of aPWV and ABI with the components of MetS and MDA. A total of 48 Thai elderly subjects were divided into 2 groups (MetS and non-MetS) according to the parameters set by the International Diabetes Federation (IDF). aPWV and ABI were measured using the VaSera VS-1500 system (Fukuda Denshi Co., Tokyo, Japan). MDA was determined by spectrophotometry. aPWV and MDA were significantly higher in the MetS group compared to the participants in the non-MetS group (9.33 ± 2.72 vs. 7.95 ± 1.37 m/s, p = 0.03, and 0.74 ± 0.71 vs. 0.45 ± 0.20 μmol, p = 0.02, respectively). However, ABI did not differ between the groups. Analysis of the risk factors of aPWV in each group revealed that there were no statistical associations between the components of MetS and MDA and aPWV in both the MetS and the non-MetS groups. A high aPWV is more prevalent among patients with MetS than among those without MetS. Monitoring of aPWV might help to explore potential detection of vascular damage in the elderly.
Constipation is a symptom that is widely found in the world’s population. Various dietary supplementations are used to relieve and prevent constipation. Seaweed is widely used for its health benefits. In this study, we aimed to investigate the effects of Sargassum plagiophyllum extract (SPE) on functions of the gastrointestinal tract and gut microbiota. The results show that SPE pretreatment increased the frequency of gut contraction, leading to reduce gut transit time. SPE pretreatment also significantly increased the secretion of Cl− and reduced Na+ absorption, increasing fecal water content in constipated mice (p < 0.05). In addition, the Bifidobacteria population in cecal contents was significantly higher in constipated mice pretreated with 500 mg/kg SPE for 14 days than in untreated constipated mice (p < 0.05). Our findings suggest that SPE can prevent constipation in loperamide-induced mice. This study may be useful for the development of human food supplements from S. plagiophyllum, which prevent constipation.
Objective: To investigate the effect of Gracilaria fisheri oligosaccharides (GFO) on inflammation and colonic epithelial barrier dysfunction in colitis mice. Methods: The animals were treated by oral gavage with distilled water, 1 000 mg/kg inulin, 100, 500, or 1 000 mg/kg GFO for 14 d, or treated with 50 mg/kg mesalamine for 5 d after colitis induction (on day 10). Histopathology, inflammatory cytokines, colonic permeability, and tight junction proteins were investigated by hematoxylin and eosin staining, immunohistochemical staining, Ussing chamber technique, and Western blotting assays, respectively. Results: GFO ameliorated histological damage in colitis mice when compared to untreated colitis mice. Treatments with 100, 500, and 1 000 mg/kg GFO reduced TNF-α expression, while IL-1β was significantly reduced in colitis mice treated with 500 and 1 000 mg/kg. Compared to untreated colitis mice, GFO increased transepithelial electrical resistance, reduced fluorescein isothiocyanate-dextran paracellular flux, and modulated tight junction proteins (occludin and claudin 2) in colitis mice. Conclusions: GFO has anti-inflammatory activity and could modulate colonic epithelial barrier dysfunction in acetic acid-induced colitis mice. Furthermore, GFO could modulate the expression of tight junction proteins that play important roles in colonic barrier function.
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