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interleukin-31 promotes helper t cell type-2 inflmmation in children with allergic rhinitis

Posted by Wenlong L, Renzhong L, Yanqiu C, et al. on 2015-01-13 17:05:00

Background:

Interleukin-31 (IL-31) is a recently described cytokine that is involved in helper T cell type-2 (Th2)-mediated diseases. However, its regulatory effect in the pathogenesis of children allergic rhinitis (AR) needs to be further characterized. This study sought to evaluate the expression and role of IL-31 in children with AR.

Methods:

Sixty children with AR and 20 normal controls were included. IL-31 and Th2 cytokines production in tissue, serum, and nasal lavage was examined by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay, respectively. Peripheral blood mononuclear cells (PBMCs) were purified for in vitro regulation experiment of IL-31. Nasal epithelial cells (NECs) were cultured and stimulated by recombinant IL-31.

Results:

The IL-31 mRNA and protein levels in both serum and nasal lavage were significantly enhanced in AR compared with normal controls, especially in children with asthma. The nasal IL-31 was associated with enhanced local Th2 cytokines and mucin 5AC (MUC5AC) expression. In vitro study showed that IL-31 promotes Th2 cytokines expression and MUC5AC upregulation and thus amplified Th2 inflammation.

Conclusion:

Our results demonstrate that IL-31 expression in AR aggravated and amplified Th2 inflammation as well as mucin production, and provide a possible explanation for IL-31’s regulatory role in the pathogenesis of AR.


Abstract

 

Intermittent hypoxic training (IHT) is a discrete cost-effective method for improving athletic performance and high altitude acclimatization. Unfortunately, IHT protocols widely vary in terms of hypoxia severity, duration, and number of cycles affecting physiological outcomes. In the present study, we evaluated the efficacy of a moderate normobaric IHT protocol (12% FiO2 for 4 h, 4 days) on acclimatization to high altitude (3250 m). Global plasma proteomics studies revealed that IHT elicited acute-phase response proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and alpha-1-acid glycoprotein 2 (AGP 2) as well as altered levels of several apolipoproteins. On subsequent exposure to high altitude, the IH trained volunteers exhibited significant higher arterial oxygen saturation with concomitant lower incidences of acute mountain sickness (AMS) as compared to controls. Interestingly, IH trained subjects exhibited lower levels of positive acute-phase proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and fibrinogen (FGA, FGB, and FGG) both after days 4 and 7 of high altitude ascent. High altitude exposure also decreased the levels of HDL, LDL, and associated proteins as well as key enzymes for assembly and maturation of lipoprotein particles like lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). In contrast, IHT curtailed hypoxia-induced alterations of HDL, LDL, Apo-AI, Apo-B, LCAT, CETP, and PLTP. Further validation of results also corroborated attenuation of hypoxia-induced inflammation and dyslipidemia by IHT. These results provide molecular evidences supporting the use of moderate IHT as a potential non-pharmacological strategy for high altitude acclimatization.

Abstract

 

Azole fungicides are one class of the most extensively applied current-use pesticides. Tebuconazole is a common azole fungicide that has been frequently detected in aquatic ecosystems, thus raising concerns about its ecological safety. However, adverse effects of tebuconazole remain largely unknown, especially with regard to endocrine function in aquatic organisms. In the present study, sexually immature zebrafish were exposed to different concentrations of tebuconazole (0.05, 0.20 and 0.50?mg/L) for 60 days in order to test for transgenerational toxicity on the thyroid endocrine system. Thyroid hormone homeostasis, neuronal, and cardiovascular development were investigated in the F1 generation, which were reared in tebuconazole-free water. In the F0 generation, exposure to 0.20 and 0.50?mg/L tebuconazole reduced both thyroxine (T4) and 3,5,3’-triiodothyronine (T3) levels in females, while the T3 levels were unchanged in males. Decreased heart rate was found in F1 larvae, as well as diminished T4 levels in F1 eggs/larvae. We also observed significantly increased expression of ugt1ab mRNA in two generations of zebrafish. Moreover, expression of mRNA associated with neuronal development (e.g. α1-tubulin, mbp, gap43) and cardiovascular development (e.g. cacna1ab, tnncal) were significantly downregulated in F1 larvae at 5 and 10 dpf. In addition, tebuconazole was detected in F1 eggs following parental exposure, indicating maternal transfer. This study demonstrated that tebuconazole can be transferred to offspring from exposed parents, causing thyroid endocrine disruption and developmental toxicity.


Abstract

 

Necroptosis is suggested to have an important role in the pathogenesis of rhabdomyolysis induced acute kidney injury (AKI). In this study, the renoprotective effect of diacerein on glycerol-induced AKI was investigated. Twenty four male albino rats were included in this study and divided into four groups: (group I) saline control group, (group II) glycerol-treated group, (groups III&IV) diacerein + glycerol -treated groups (25 and 50 mg/kg/day) respectively. Renal malondialdehyde (MDA) level in addition to catalase and heme oxygenase (HO) activities were estimated. Comet assay and histopathological changes were evaluated. The levels of pro-apoptotic Bcl-2-associated X (Bax) protein, tumor necrosis factor alpha (TNF-α) and receptor-interacting serine/threonine-protein kinases 3 (RIPK3) were measured by ELISA. RIPK3 and mixed lineage kinase domain-like pseudokinase (MLKL) mRNA expression were assessed by real time PCR. Glycerol treatment caused significant renal histological abnormalities and functional impairment (increased urea and creatinine). Increased levels of renal MDA with concomitant decrease in renal catalase activity and significant DNA damage in comet assay were observed. High expression of RIPK3 and MLKL in the glycerol-treated group with marked elevation of Bax, TNF-α and RIPK3 levels and HO-1 activity were also documented. Diacerein treatment dependently attenuated glycerol induced structural and functional changes in kidney and significantly elicit reduction of renal tissue oxidative damage whereas it decreased renal expression of RIPK3 and MLKL, and decreased Bax, TNF-α and RIPK3 levels and HO-1 activity.

 

Conclusion

These results demonstrated that diacerein might have potential application in the amelioration of AKI via its anti-oxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic effects.

Relationship Between Angiopoietin-Like Protein 8 and Fasting Serum Triglyceride Level

Posted by H Yamada, I Kusaka, R Saikawa, et al. on 2019-04-15 14:19:00

Abstract


Background

 

The aim of the study was to evaluate the correlation between angiopoietin-like protein 8 (ANGPTL8) and metabolic parameters in non-diabetic healthy humans.


Methods

 

We enrolled 30 healthy Japanese adults (25 men and five women). After 9 h of fasting, we collected blood samples and analyzed the ANGPTL8, lipoprotein lipase (LPL), plasma lipid and glucose metabolic parameters. In addition, we performed 75-g oral glucose tolerance test (OGTT) and measured adipokines (tumor necrosis factor-α, leptin and adiponectin).


Results

 

Median serum ANGPTL8 level was 224 (167 - 437) pg/mL, and serum ANGPTL8 level positively correlated with serum triglyceride level (r = 0.42, P = 0.021) and negatively correlated with LPL level (r = -0.44, P = 0.015). ANGPTL8 level showed no correlation with body mass index (BMI), waist-hip ratio, and homeostasis model assessment of insulin resistance (HOMA-IR) or with adipose tissue-derived adiponectin and leptin levels. Further, ANGPTL8 showed no association with glucose and insulin levels after 75-g OGTT.


Conclusion

 

Serum ANGPTL8 level negatively correlated with LPL levels in healthy Japanese adults. Regulation of ANGPTL8 could be a promising therapeutic target for hypertriglyceridemia.

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