The present study was conducted to test the hypothesis that low concentrations of coated ZnO, as a substitute for a high concentration of ZnO (2250 mg Zn/kg), could improve intestinal immunity function and regulate microbiota composition, thus alleviating the incidence of diarrhoea in weaned piglets. A total of eighty-four cross-bred piglets, weaned at an age of 28 (SEM 1) d, were allocated randomly, on the basis of average initial body weight (7·72 (SEM 0·65) kg), to seven treatment groups as follows: a 250 mg Zn (ZnO)/kg group (low Zn; LZ) and a 2250 mg Zn (ZnO)/kg group (high Zn; HZ) that were offered diets containing ZnO at 250 and 2250 mg Zn/kg, respectively; and five experimental groups in which coated ZnO was added at 250, 380, 570, 760 and 1140 mg Zn/kg basal diet, respectively. The trial lasted 2 weeks. The results indicated that, compared with LZ treatment, supplementation with coated ZnO at 380 or 570 mg Zn/kg reduced (P,0·05) diarrhoea index, increased (P,0·05) duodenal villus height and the ratio of villus height:crypt depth, up-regulated (P,0·05) the gene expression of insulin-like growth factor 1, zonula occludens protein-1, occludin, IL-10 and transforming growth factor b1, and elevated (P,0·05) secretory IgA concentration in the jejunal mucosa. Microbiota richness and the Shannon diversity index were also decreased (P,0·05). Furthermore, piglets in the group fed coated ZnO at 380 or 570 mg Zn/kg did not differ from those in the HZ-fed group in relation to the aforementioned parameters. Collectively, a low concentration of coated ZnO (380 or 570 mg Zn/kg) can alleviate the incidence of diarrhoea by promoting intestinal development, protecting the intestinal mucosal barrier from damage, stimulating the mucosal immune system and regulating the microbiota composition.

Progression of diabetes was studied in male Goto-Kakizaki (GK) spontaneously diabetic rats between 4 and 20 weeks of age, and compared with Wistar-Kyoto (WKY) controls. Five animals from each strain were killed at 4, 8, 12, 16, and 20 weeks of age. Body weight, plasma glucose, and plasma insulin were measured. WKY rats showed a significantly larger weight gain than GK animals from 8 weeks of age onward. Plasma glucose was relatively stable in WKY. By contrast, plasma glucose was higher in GK than WKY even at 4 weeks and continued to increase up to 12 weeks and then maintained a hyperglycemic plateau throughout the remainder of the experiment. Plasma insulin was relatively stable in WKY from 8 weeks onward but was sharply elevated in GK between 4 and 8 weeks. After 8 weeks, insulin declined in GK with GK concentrations lower than WKY at 20 weeks, suggesting beta-cell failure. Gene expression in liver was explored using Affymetrix 230-2 gene arrays. Data mining identified 395 probe sets out of more than 31,000 that were differentially regulated. Excluding unidentifiable probe sets and considering duplicate probe sets, there were 311 genes that were expressed differently in the liver of the two strains. A functional analysis of these genes indicated that disruption of lipid metabolism in the liver is a major consequence of the chronic hyperglycemia in the GK strain. In addition, the results suggest that chronic inflammation contributes significantly to the development of diabetes in the GK rats.

Although hypertension is a worldwide health issue, an incomplete understanding of its etiology has hindered our ability to treat this complex disease. Here we identify arhgap42 (also known as GRAF3) as a Rho-specific GAP expressed specifically in smooth muscle cells in mice and humans. We show that GRAF3-deficient mice exhibit significant hypertension and increased pressor responses to angiotensin II and endothelin-1; these effects are prevented by treatment with the Rho-kinase inhibitor, Y-27632. RhoA activity and myosin light chain phosphorylation are elevated in GRAF3-depleted smooth muscle cells in vitro and in vivo, and isolated vessel segments from GRAF3-deficient mice show increased contractility. Taken together our data indicate that GRAF3-mediated inhibition of RhoA activity in vascular smooth muscle cells is necessary for maintaining normal blood pressure homeostasis. Moreover, these findings provide a potential mechanism for a hypertensive locus recently identified within arhgap42 and provide a foundation for the future development of innovative hypertension therapies.

The current COVID-19 pandemic is probably the worst the world has ever faced since the start of the new millennium. While the respiratory system is the most prominent target of SARS-CoV-2 (the contagion of COVID-19), extra-pulmonary involvement are emerging as important contributors of its morbidity and lethality. This article summarizes the impact of SARS-CoV and SARS-CoV-2 on the endocrine system to facilitate our understanding of the nature of coronavirus-associated endocrinopathy. Although new data are rapidly accumulating on this novel infection, many of the endocrine manifestations of COVID-19 remain incompletely elucidated. We hereby summarize various endocrine dysfunctions including coronavirus-induced new onset diabetes mellitus, hypocortisolism, thyroid hormone and reproductive system aberrations so that clinicians armed with such insights can potentially benefit COVID-19 patients at the bedside.

Type 2 diabetes (T2DM) is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK) rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.

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This study aims to investigate the effects of epigallocatechin gallate (EGCG) on the growth performance and serum metabolic characteristics of heat-stressed broilers. A total of 192 14-day-old Arbor Acres broilers were divided into 4 groups with 6 replicates per group (8 chickens/cage). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300, and 600 mg/kg diet (Groups HS0, HS300, and HS600, respectively). The production performance and serum metabolic characteristics were analyzed at d 21, 28, and 35, respectively. At d 35 of age, heat stress reduced (P < 0.05) the body weight (BW), feed intake (FI) and the contents of serum total protein (TP) and glucose (GLU); inhibited (P < 0.05) alkaline phosphatase (ALP) activity; But increased (P < 0.05) the contents of uric acid (UA), cholesterol (CHOL), triglyceride (TG), and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST). Heat-stressed chickens fed EGCG exhibited a linear increase (P < 0.05) in BW, FI, the levels of serum TP, GLU, and ALP activity; and linear decrease (P < 0.05) in the contents of serum UA, CHOL, and TG, as well as the activities of LDH, CK, and AST. Heat stress also reduced (P < 0.05) the activities of serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) on d 35 and increased (P < 0.05) the GSH-Px and SOD activity on d 21 and malondialdehyde (MDA) contents. There was a linear increase (P < 0.05) in activities of GSH-Px, SOD and CAT at 35 d of age, and linear decreased (P < 0.05) in MDA contents. In conclusion, EGCG can improve the growth performance of broilers by enhancing antioxidant property and alleviating oxidant damage caused by heat stress.

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