Objective To clarify the effects of exercise- and food intake restriction-induced weight reduction on expression of ghrelin in plasma and stomach of obese rats,and to explore the role of ghrelin during weight loss. Methods 100 weaned Sprague-Dawley(SD) rats were randomly divided into control group(fed with standard chow,n= 20) and model group (two-bottle-feeding method,fed with standard chow and high-fat diet simultaneously, n=80). After 20 weeks feeding, Lee' s index of control was used as the reference of diet-induced obesity identification, and then diet-induced obese rats were randomly divided into four groups:obese control group,swimming group,food intake restriction group and swimming+food intake restriction group, eight rats in each group. Rats in swimming group underwent long-term(40 min,6 days/week for 5 weeks)swimming exercise. Calorie in food intake restriction group was restricted 1/3 of normal kcal for 3 weeks,and subsequently restricted 1/3 for 2 weeks. Swimming+food restriction group had the same intervention as swimming and food restriction group. 8 normal diet rats were also chosen as controls. After five weeks of treatments,peripheral fat mass of testis and kidney,ghrelin proteins in plasma and stomach,and ghrelin mRNA in stomach were measured. Results Gastric ghrelin protein and mRNA were significantly lower in obese control group than those in normal control group (P<0.05). However, plasma ghrelin did not decrease markedly in obese control rats(P>0.05). Compared with obese control group,weight and fat mass in all weight loss groups declined notablely(P<0.05);in swimming and swimming+food restriction groups,the expression of ghrelin protein or mRNA in plasma or stomach increased remarkably( P<0.05); in food restriction group, the level of ghrelin mRNA raised significantly (P<0.05), while ghrelin protein in plasma and stomach had not change. Conclusion The level of ghrelin increased in exercise induced weight loss,while showed no significant change in food intake restriction group, suggested that ghrelin might be involved in the process of weight loss induced by exercise.

Objective To investigate the protective mechanism of hypoxia-inducible factor-1α (HIF-1α) in vascular endothelial cells under hypoxia.Methods 1.After a hemorrhagic shock model was established in mice,the vascular endothelial cells were sorted in a shock group (n =3) and a sham operation group (n =3) for RNA-sequencing to analyze the main differential molecules.2.The expression of HIF-1α and glucose transporter-1 (GLUT1) was measured in human umbilical vein endothelial cells (HUVECs) and the mitochondrial membrane potentials were detected in a control group (normal culture,n =3) and a hypoxia group (hypoxia culture for 6 h,n =3).3.The HUVECs cells were transfected with HIF-1α siRNA for 48 h to interfere with HIF-1 α expression,and the control group(n =3) was transfected with control siRNA.The expression of HIF-1α was detected to determine the interference effect.The mRNA and protein expression of GLUT1 was detected in the interference and the control groups after 6 h of hypoxia culture.The mitochondrial membrane potential was detected by fluorescent probe method.Results 1.The transcriptome sequencing in the vascular endothelial cells in the shock and sham operation groups indicated 25 genes with significant differences.The HIF-1 α expression was significantly increased in the shock group (111.70 ± 15.97) than in the sham operation group (53.49 ± 3.26) (P =0.023).2.The expression of HIF-1 α and GLUT1 in the HUVECs cells was significantly increased in the hypoxia group compared with the control group (P ＜ 0.05).The mitochondrial membrane potential was significantly lower in the hypoxia group (0.781 ± 0.023) than in the control group (1.177 ± 0.062) (P ＜ 0.05),indicating aggravated injury.3.There was no significant difference in the mitochondrial membrane potential between the interference group (1.011 ± 0.076) and the control group (1.151 ± 0.031) (P ＞ 0.05).However,after hypoxia culture for 6 h,there was a significant difference in the mitochondrial membrane potential between the interference group (0.514 ± 0.018) and the control group (0.769 ± 0.044) (P ＜ 0.05),also indicating aggravated damage.Conclusions The expression of HIF-1 α may be significantly increased in hemorrhagic shock.In HUVECs under hypoxia,HIF-1 α may up-regulate the expression of GLUT1,promote glucose transport,improve mitochondrial damage and protect vascular endothelial cells.Thus,targeting HIF-1 α may contribute to the treatment of hemorrhagic shock.

Objective To investigate the effects of CD226 knockout ( KO) on obese mice fed with high fat diet and to analyze the composition of immune cells in CD226KO obese mice for further elucidating the immunological mechanism of CD226 involved in high fat diet-induced obesity. Methods Both wild-type ( WT) and CD226KO mice were randomly divided into two groups, high-fat and normal diet groups, and fed for 14 weeks to establish the type 2 diabetes model. Immune cells in mouse spleen and peripheral blood were analyzed by flow cytometry. In in vitro experiments, NK92-MI cells were infected with pshRNA-CD226 lenti-virus to silence CD226 expression, and then qPCR was performed to detect the expression of Foxp3, TNF-αand IFN-γ at mRNA level. Results In the high-fat diet groups, CD226KO mice had lower blood glucose, serum insulin and HOMA-IR than WT mice, but higher HOMA-IS and HOMA-β. CD226KO could reduce compensatory hyperplasia of islet tissue, and significantly down-regulate the proportion of spleen NK cells in mice. The proportion of CD3-CD49b+CD25+Foxp3+regulatory NK cells (NKreg) increased significantly in CD226KO mice. CD226KO could significantly increase Foxp3 expression in NK92-MI cells and decrease the expression of TNF-α and IFN-γ. Conclusions CD226KO can alleviate insulin resistance, increase the number of islet β-cell and improve islet β-cell function in obese mice. The mechanism might be related to the up-regulation of Foxp3+ NKreg ratio.

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

Objective:To analyze the incidence of liver function injury in patients infected with 2019-nCoV omicron variant and its influencing factors.Methods:The clinical data and laboratory findings of 897 COVID-19 patients infected with omicron variant in Zhejiang province from February 23 to July 14, 2022 were retrospectively analyzed. Patients were divide into liver function injury group ( n=243) and non-liver function injury group ( n=654) based on liver function indicators. The clinical characteristics and laboratory tests were compared between the two groups, and influencing factors of liver function injury were analyzed. SPSS 26.0 statistical software was used for data analysis. Results:The incidence of liver injury in this series was 27.09% (243/897). The median age of patients in liver injury group was older, the body mass index (BMI) was higher( Z=-6.237 and -2.166, both P<0.05), the proportions of patients with hypertension and diabetes, and with severe clinical classification were higher ( χ2=17.087, 27.509 and 12.945, all P<0.01) ; the proportion of vaccinated patients was lower ( χ2=17.766, P<0.01) than those in non-liver injury group. The levels of platelet, hemoglobin, albumin and potassium in liver injury group were lower than those in non-liver injury group ( Z=-4.631, -2.368, -10.593 and -2.141, all P<0.05), while serum ALT, AST, γ-GT, urea nitrogen, glucose and hs-CRP levels were higher than those in the non-liver injury group ( Z=-7.451, -8.663, -4.410, -3.824, -3.278 and -3.884, all P<0.01). Multivariate Logistic regression analysis showed that age ( OR=2.580, 95% CI 1.429-4.657, P=0.002), history of diabetes ( OR=3.650, 95% CI 1.698-7.849, P=0.001), and decreased hemoglobin ( OR=1.993, 95% CI 1.066-3.726, P=0.031) and increased hs-CRP ( OR=1.797, 95% CI 1.283-2.517, P=0.001) were risk factors associated with liver function injury, while vaccination ( OR=0.499, 95% CI 0.312-0.798, P=0.004) was the protective factor for liver function. Conclusion:Liver function injury is frequently observed in COVID-19 patients infected with omicron variant, which is linked to age, underlying disease, and elevated inflammatory markers; while vaccination can lower the risk of liver injury in infected patients.

Patients with traumatic brain injury (TBI) may develop neurological complications such as Alzheimer′s disease, stroke and epilepsy, which severely affect their quality of life. Currently, neurological complications after TBI are poorly understood and there are no comprehensive treatments or definitive interventions for them. Complex pathophysiological changes in the brain, systemic immunological responses, and gastrointestinal dysfunction after TBI all severely affect the biodiversity of the intestinal microbiota and related metabolites, which leads to intestinal dysbiosis and metabolic disorders and exert continued effects on the nervous system. Intestinal microbial probiotic flora that colonize in living organisms are a category of active microorganisms beneficial to the host and supplementation of intestinal probiotics can have a modulatory effect on the nervous system directly or indirectly. The targeted therapeutic effects of intestinal microbial probiotic flora on neurological complications after TBI and the intrinsic mechanism of the effects have not been comprehensively summarized currently. For this purpose, the authors reviewed the research progress on the effects of regulating intestinal microbial probiotic flora on post-TBI neurological complications so as to provide a reference for the clinical prevention and treatment of post-TBI neurological complications.

OBJECTIVE: To investigate the effect of miR-186 inhibition on the expression of hypoxia-inducible factor-1α (HIF-α) and mitochondrial function in hypoxic vascular endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) cultured in routine or hypoxic conditions for 6 h were examined for the expression of miR-186. A miR-186 inhibitor was transfected in the HUVECs, and the cells were subsequently cultured in hypoxic condition for 6 h to observe the changes in the mitochondrial structure under an electron microscope. The changes in the mRNA and protein expressions of HIF-1α in response to miR-186 interference were tested using real-time fluorescent quantitative PCR and Western blotting. RESULTS: The expression of miR-18 was mildly increased in HUVECs after hypoxic exposure for 6 h (=0.0188). Interference of miR-186 expression obviously promoted the mRNA and protein expressions of HIF-1α in HUVECs. In hypoxic conditions, miR-186 interference significantly reduced mitochondrial damage in HUVECs as observed under electron microscope (=0.0297). CONCLUSIONS Inhibition of miR-186 protects vascular endothelial cells against hypoxic injuries by promoting HIF-α expression to lessen mitochondrial damage, suggesting the possibility of targeted miR-186 interference for treatment of hemorrhagic shock.
Cell Hypoxia ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; MicroRNAs ; Mitochondria ; Umbilical Veins