Gut microbiota may underlie the predisposition of healthy individuals to COVID-19

The COVID-19 pandemic is spreading globally with high disparity in the susceptibility of the disease severity. Identification of the key underlying factors for this disparity is highly warranted. Here we describe constructing a proteomic risk score based on 20 blood proteomic biomarkers which predict the progression to severe COVID-19. We demonstrate that in our own cohort of 990 individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discovered that a core set of gut microbiota could accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model, and that these gut microbiota features are highly correlated with proinflammatory cytokines in another set of 366 individuals. Fecal metabolomic analysis suggested potential amino acid-related pathways linking gut microbiota to inflammation. This study suggests that gut microbiota may underlie the predisposition of normal individuals to severe COVID-19.

Involvement Endoplasmic Reticulum Stress on Process of Nonalcoholic Fatty Liver Disease Induced by MCD / 中山大学学报(医学科学版)

[Objective] To investigate the effect of the ER stress on the process of nonalcoholic fatty liver disease which is induced by methionine-choline deficient diet.[Methods] C57/BL mice were randomly divided into 8 groups (n =10),group 1-4was given normal diet,5-8 group was given MCD diet.Then took one group from both normal diet and MCD diet in the 2nd,4th,6th,8th week,recorded each group's body weight and liver weight.The liver fibrosis and inflammation in mice were analyzed by histopathological staining and NAS.The expressions of endoplasmic reticulum stress markers such as p-PERK,p-eIF2α,CHOP were detected by Western Blot and real time fluorescent quantitative PCR (q-PCR).[Results] ①The ALT and AST in serum,TG and TC in liver tissue were both higher in MCD group,the same as NAS;②The expressions of PERK,eIF2α,CHOP were significantly higher than the nommal diet group,while the GADD34 expression was lower.What's more,as time went by,the difference was more obvious;3.There was a significant correlation between the ERS index and NAS score in MCD group.[Conclusion]The liver damage and inflammatory response was lifted gradually in the mice fed with MCD diet.The ER stress may take an important role in this process.

Anticancer activities of an anthocyanin-rich extract from black rice against breast cancer cells in vitro and in vivo.

Anthocyanins widely present in human diet and have a variety of health effects. This study investigates the anticancer effects of an anthocyanin-rich extract from black rice (AEBR) on breast cancer cells in vitro and in vivo. AEBR reduced the viability of breast cancer cell lines MCF-7 (ER(+), HER2/neu(-)), MDA-MB-231 (ER(-), HER2/neu(-)), and MDA-MB-453 (ER(-), HER2/neu(+)) and induced apoptosis in MDA-MB-453 cells via the intrinsic pathway in vitro by activating caspase cascade, cleaving poly (ADP-ribose) polymerase (PARP), depolarizing mitochondrial membrane potential, and releasing cytochrome C. Oral administration of AEBR (100 mg/kg/day) to BALB/c nude mice bearing MDA-MB-453 cell xenografts significantly suppressed tumor growth and angiogenesis by suppressing the expression of angiogenesis factors MMP-9, MMP-2, and uPA in tumor tissue. Altogether, this study suggests the anticancer effects of AEBR against human breast cancer cells in vitro and in vivo by inducing apoptosis and suppressing angiogenesis.

JNK mediates TNF-α or H_2O_2-induced insulin resistance in 3T3-L1 adipocytes / 中国病理生理杂志

AIM: To study the role of c-Jun NH_2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-α (TNF-α) or H_2O_2 in 3T3-L1 adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125, then exposed to 1 nmol/L of TNF-α or micromolar H_2O_2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS: Compared to control adipocytes, 12 h incubation with TNF-α or H_2O_2 led to 50%-55% reduction (P<0.01) of the insulin-dependent glucose uptake. JNK1 siRNA transfection significantly inhibited JNK1 expression and blocked the TNF-α or H_2O_2-induced impairments of cellular glucose uptake. Pretreatment with SP600125 (20 μmol/L) resulted in significant increases in insulin-stimulated glucose uptakes in both TNF-α (66%) and H_2O_2 (62%) treated adipocytes (P<0.01). CONCLUSION: JNK plays a key role in TNF-α or H_2O_2 induced insulin resistance in 3T3-L1 adipocytes, and inhibition of JNK over-activation may be a new therapeutic target for insulin resistance.

Association of diet and C-reactive protein with atherosclerosis in type 2 diabetes mellitus patients / 中华临床营养杂志

Objective To compare the characteristics of food and nutrition intake in type 2 diabetes mellitus (T2DM) patients with or without carotid atherosclerosis and analyze the relationship between diets/C-reactive protein (CRP) and carotid intima-media thickness (C-IMT). Methods Sixty patients with T2DM were enrolled and divided into two groups based on C-IMT: group A (C-IMT ＜ 1 mm, n=30) and group B (C-IMT≥1 mm, n=30). All subjects were investigated with questionnaires including 3-day food recall They all took somatometric measurement. Blood and urine samples were collected in all subjects to examine the levels of high sensitive-CRP,C-peptide, blood glucose, glycosylated hemoglobin, blood lipid, renal function, urine microalbumin, and other indicators. Results The intakes of vegetables, fruits, and aquatic products were significantly higher in group A than in group B ( P ＜ 0. 05 ). The intake of vitamin C in group A was significantly higher than that in group B ( P ＜0. 05 ). The levels of CRP in group B was significant higher than that in group A (P = 0. 000). Positive correlation was found between CRP level and C-IMT in T2DM patients ( r = 0. 36, P = 0. 004). Furthermore, CRP was negatively correlated with the intakes of vegetables and fruits ( r = - 0. 334, P = 0. 01 ), aquatic products ( r = -0. 315, P = 0. 016), and vitamin C ( r = - 0. 2786, P = 0. 038 ), respectively. The intake of fruits was negatively correlated with C-IMT (r, = -0. 33, P = 0. 01 ). Conclusions T2DM patients without carotid atherosclerosis intake more vegetables, fruits, aquatic products and vitamin C than those with atherosclerosis. Vegetables, fruits,sea foods and vitamin C may be the protective factors against atherosclerosis in T2DM patients. CRP is associated with the development of atherosclerosis in T2DM patients.

Effects of medium chain triglyceride on insulin resistance in type 2 diabetes mellitus / 中华临床营养杂志

etary oil with MCT can improve insulin resistance.

Iodine nutritional status in adolescents after a decade of salt iodization in three cities of Guangdong / 中华内分泌代谢杂志

A cross-sectional survey of 3589 adolescents was conducted in three cities from different typical geographical zones of Guangdong province. The median urinary iodine concentrations (MUI) of adolescents in Nanxiong, Guangzhou and Maoming were 286.6,204.1 and 166.0μ/L, respectively. The MUI of all these adolescents Was 231.7μg/L, which was slightly higher than the current World Health Organization recommendation.

Area of atherosclerotic plaque in mice with apolipoprotein E genetic defect and serum level of anti-oxidized low density lipoprotein antibody / 中国组织工程研究

BACKGROUND: The oxidation of low density lipoprotein (LDL) is a key influencing factor in the occurrence and development process of atherosclerosis. How is the merit of the method for the detection of the level of anti-serum oxidized LDL (ox-LDL) antibody on the evaluation of atherosclerotic plaque?OBJECTIVE: To study the method for the detection of serum anti-ox-LDL antibody in mice with apolipoprotein E (Apo-E) genetic defect to analyze the merits of serous level of anti-ox-LDL antibody on the evaluation of the area of atherosclerotic plaque in mice with Apo-E genetic defect.DESIGN: Single factor analysis of variance (a case-controlled study)SETTING: Laboratory of nutrition and metabolism diseases in a university.PARTICIPANTS: Mice with Apo-E genetic defect were grouped into positive group (series: C57B L/6J, n = 15), while normal mice were grouped into control group (series: C57BL/6J, n = 15).INTERVENTIONS: Mice of two groups were fed in separate cage on laminar flow shelf for free drinking and eating. The venous blood was drawn from the orbit of mice after 16 weeks for the separation of mice serum. The level of anti-ox-LDL antibody was detected by enzyme-linked immunosorbent assay (ELISA) in the separated serum from either mice with Apo-E genetic defect or normal mice. The area of atherosclerotic plaque was measured by image analysis after oil red O staining.MAIN OUTCOME MEASURES: ox-LDL level and atherosclerotic plaque area in mice with Apo-E genetic defect or normal mice.RESULTS: Anti-ox-LDL antibody level of mice with Apo-E genetic defect was[ (0. 079 ±0. 028)% ], which was significantly higher than [(0. 012± 0.001 )% ] of normal mice ( F= 10. 666, P ＜ 0.01 ). The area of atherosclerotic plaque of mice with Apo-E genetic defect was (26. 25 ± 9.20) %, which was also significantly higher than 0% of normal mice, and moreover, there was a significant correlation between these two factors ( r =0. 638, P ＜ 0.01).CONCLUSION: Serum level of anti-ox-LDL antibody in mice with Apo-E genetic defect is closely correlated with the area of atherosclerotic plaque,which is an important indicator for the generation of atherosclerosis in mice with Apo-E genetic defect.

EFFECTS OF HIGH-FAT DIET ON LIPID METABOLISM IN SR-AⅠ/Ⅱ GENE KNOCK-OUT MICE / 营养学报

Objective To observe the alteration of scavenger receptor class A types Ⅰand Ⅱ (SR-AⅠ/Ⅱ) gene knock-out on lipid metabolism in mice fed with high-fat diet, and explore the underlying mechanism. Method The SR-AⅠ/Ⅱgene knock-out and wild-type male mice were fed with normal and high-fat diet for 12 w. Thereafter, the level of lipid metabolism (such as the levels of lipids in blood and liver) was detected with enzyme method or oil red O staining, and the expression of scavenger receptor class B typeⅠ(SR-BⅠ) and CD36 in liver was analyzed by RT-PCR. Results Under high-fat diet condition, as compared with wild-type mice, the levels of TG, TC, LDL and HDL in SR-AⅠ/Ⅱgene knock-out mice were decreased at 3, 6, 12 w (P0.05). Conclusion The alteration of lipid metabolism induced by high-fat diet in SR-AⅠ/Ⅱgene knock-out mice might be relative with the up-regulated SR-BⅠmRNA expression and the counter transport of peripheral lipids to liver.

Inhibiting severe acute respiratory syndrome-associated coronavirus by small interfering RNA / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the effectiveness of small interfering RNA (siRNA) on inhibiting severe acute respiratory syndrome (SARS)-associated coronavirus replication, and to lay bases for the future clinical application of siRNA for the treatment of viral infectious diseases.</p><p><b>METHODS</b>Vero-E6 cells was transfected with siRNA before SARS virus infection, and the effectiveness of siRNA interference was evaluated by observing the cytopathic effect (CPE) on Vero-E6 cells.</p><p><b>RESULTS</b>Five pairs of siRNA showed ability to reduce CPE dose dependently, and two of them had the best effect.</p><p><b>CONCLUSION</b>siRNA may be effective in inhibiting SARS-associated coronavirus replication.</p>

Structure-activity relationship of anthocyanin phytochemicals in inhibiting oxidized-stress injury of vascular endothelial cells / 第三军医大学学报

Objective To investigate the structure-activity relationship for 21 anthocyanins in inhibiting oxidized injury of endothelial cells,and explore the structural characteristics of anthocyanins closely related to their effects. Methods Endothelial cells were treated by ox-LDL at different concentrations of 50,100,150 or 200 ?g/ml,and MTT assay was used to determine IC50. After pre-incubated for 2 h with different concentrations ( 50,100 or 200 ?mol/L) of anthocyanins and then treated with 100 ?g/ml ox-LDL for another 24 h in endothelial cells,MTT assay was used to detect the cellular viability. After pre-treated for 2 h with different anthocyanins with 100 ?mol/L and treated with ox-LDL for another 24 h,MDA and NO level in the culture media were both measured according to the methods of assay kits. Structure-activity relationship was analyzed according to the respective cellular viability,MDA and NO level. Results Cellular viability was significantly inhibited by ox-LDL in a dose-dependent manner,and the IC50 was 100 ?g/ml. A significant correlation was observed among the effect of anthocyanins on cell viability,MDA production and NO release. The inhibitory effects of anthocyanins in ox-LDL-injured endothelial cells were positively related to the total number of hydroxyl groups and hydroxyl substitutions in B ring. 3′,4′-ortho-dihydroxyl substitution on B-ring and a 3-hydroxyl group on C-ring significantly enhanced the inhibitory effect of anthocyanins,yet methoxylation or glycosylation significantly decreased the effect. 6-hydroxylation substitution might attenuate the inhibitory effect of anthocyanins,while substitution at C5 or C5′ showed no significant influence on the effect of anthocyanins. Anthocyanin with monosaccharose substitution was much stronger than that with disaccharose substitution,while there was no significant difference between anthocyanins with glucoside and that with galacotoside substitution. Delphinidin and delphinidin-3-glucoside were respectively the most effectual anthocyanidin or anthocyanin. Conclusion 3′,4′-ortho-dihydroxyl substitution on B-ring and a 3-hydroxyl group on C-ring are the main structural requirements for anthocyanins in suppressing ox-LDL-induced injury in endothelial cells.

Dual roles of oxidized LDL in modulating expression of inflammatory molecules in HUVECs / 中国病理生理杂志

AIM: To determine the role of LOX-1/PPAR pathway in regulating expression of adhesion molecules elicited by oxidizing low density lipoprotein(Ox-LDL) through Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) in human umbilical vein endothelial cells(HUVECs).METHODS: HUVECs were incubated with Ox-LDL,poly(I),carrageenan or 15-deoxy-△12,14-prostaglanding J2(15d-PGJ2).PPAR mRNA and protein were examined by real time RT-PCR and Western blotting.ICAM-1 and E-selectin were detected by RT-PCR and Western blotting respectively.RESULTS: Ox-LDL increased PPAR expression in HUVECs,which was inhibited by pretreatment of HUVECs with LOX-1 blockers.Preincubation of HUVECs with 15d-PGJ2 attenuated the expression of intercellular adhesion molecule-1(ICAM-1) and E-selectin in response to Ox-LDL.Upregulation of ICAM-1 and E-selectin mediated by Ox-LDL were suppressed more significantly by the combination of 15d-PGJ2 and polyinosonic acid as compared to either 15d-PGJ2 or polyinosonic acid alone.CONCLUSION: The results indicate that Ox-LDL exerts a biphasic effects on inflammatory response.It evokes harmful effects by inflammatory injury on one side and protective effects by triggering the LOX-1/ PPAR signaling pathway on the other hand.

Lectin-like oxidized low density lipoprotein receptor-1 mediates expression of MCP-1 induced by ox-LDL in cultured human vascular endothelial cells / 中国病理生理杂志

AIM: To investigate the effects of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) on the expression of MCP-1 in the cultured human unbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs was incubated with ox-LDL, or preincubated with carrageenan and polyinosinic acid. LOX-1 and MCP-1 mRNA and protein were determined by RT-PCR and Western blot. RESULTS: Incubation of HUVECs with ox-LDL (from 0-100 mg/L) for 24 h markedly increased the expression of LOX-1 and MCP-1 (mRNA and protien) in a concentration-dependent fashion. Preincubation of HUVECs with carrageenan and polyinosinic acid, the chemical inhibitors of LOX-1, for 2 h, ox-LDL-mediated upregulation of LOX-1 and MCP-1 was suppressed (P

Effects of oxidized low density lipoprotein and lysophosphatidylcholine on cholesterol efflux from mouse peritoneal macrophage foam cells / 中国病理生理杂志

AIM: To explore the effects of oxidized low density lipoprotein (OxLDL) and one of its component— lysophosphatidylcholine (LPC) on cholesterol efflux from mouse macrophage foam cells. METHODS: (1) Cholesterol efflux induced by apoAI from mouse peritoneal macrophage foam cells loaded with OxLDL or acylated LDL(AcLDL) was measured. (2) Cholesterol efflux induced by LPC and apoAI from macrophage foam cells separated from normal or apoE gene deficient (E 0) mouse loaded with AcLDL were measured. RESULTS: (1) When the macrophage foam cells were incubated with apoAI, cholesterol efflux from AcLDL-induced macrophage foam cells increased significantly compared to that of OxLDL-induced macrophage foam cells. (2) LPC promoted cholesterol efflux from macrophage foam cells in relation to both dosage and time. When LPC was incubated with E 0 mouse macrophage foam cells, the released cholesterol mass was significantly lower than that of normal mouse macrophage foam cells. It was also found that cholesterol efflux induced by apoAI normally occurred in E 0 mouse macrophage foam cells. CONCLUSIONS: (1) OxLDL accumulated cholesterol in macrophages and impair cholesterol efflux. (2) LPC induced cholesterol efflux from macrophage foam cells, which may occur via apoE pathway.

Effect of high fat diet on UCP2 mRNA expression in white adipose tissue of SR-A Ⅰ/Ⅱ gene knock-out mice / 中国病理生理杂志

AIM: To observe the relationship between UCP2 mRNA expression in white adipose tissue and diet-induced obesity in SR-A I/II gene knock-out(SR-AⅠ/Ⅱ-/-) mice.METHODS: Fluorescent quantitative RT-PCR was used to detect UCP2 mRNA expression in mice epididymal white adipose tissue.The cellular morphological changes were analyzed by using image analysis.Serum TG,TC and LDL-C concentrations were measured by enzymatic determination.RESULTS: After fed with high fat diet for 12 weeks,average body weight of SR-A I/II-/-mice was much higher than that of wild type(SR-A I/II+/+) control mice(P

Effects of anthocyanin on cholesterol efflux from mouse peritoneal macrophage foam cells / 中国病理生理杂志

AIM: To explore the effect of anthocyanin on cholesterol efflux and elucidate its possible molecular mechanism. METHODS: Mouse Peritoneal macrophages were loaded with 50 mg/L AcLDL to induce macrophage-derived foam cells. Cholesterol efflux from macrophage-derived foam cells induced by anthocyanin was determined by enzymatic methods. PPAR-? mRNA and protein expression in macrophage-derived foam cells was assayed by quantitative PCR and western blotting. RESULTS: Anthocyanins had the capacity of promoting cholesterol efflux from mouse peritoneal macrophage-derived foam cells and increased PPAR-? mRNA and protein expression. CONCLUSION: Anthocyain-induced cholesterol efflux may be related to its enhancing PPAR-? mRNA and protein expression.

Effect of MCT on CYP7A1 gene expression and cholesterol metabolism in mice / 中国病理生理杂志

AIM: To explore the effect and the corresponding mechanism of medium chain triglyceride (MCT) on CYP7A1 gene expression in mice. METHODS: C57BL/6J mice (15/group) were respectively received mash as AIN-93G formula (basic control BC), or 1% cholesterol supplemented AIN-93G formula (Chol), or 1% cholesterol and 14% long chain triglyceride (LCT) rich in myristic acid supplemented AIN-93G formula (Chol+LCT), or 1%cholesterol and 14% MCT (caprylic acid/capric acid: 3/1) supplemented AIN-93G formula (Chol+MCT) for 6 weeks. The change of serum total cholesterol (TC), the content of cholesterol in liver, the bile acid pool of mice and the expression of cholesterol 7-hydroxylase (CYP7A 1) gene were investigated. RESULTS: Compared to mice fed Chol diet, the mice fed Chol+MCT diet had the lower serum TC (P

Correlation of adiponectin gene SNP+45 T/G polymorphism with coronary heart disease / 中国病理生理杂志

AIM: To investigate the relationship between adiponectin gene SNP+45 polymorphism and coronary heart disease(CHD) in south China Han population.METHODS: The nondiabetic CHD patients diagnosed by the coronary angiography were selected as CHD subjects(153 cases),and 73 healthy adults served as normal control subjects.The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was performed to identify the distribution pattern of adiponectin gene SNP+45 in all subjects.The levels of plasma adiponectin were measured by ELISA.RESULTS: The frequency of T/G + G/G genotype and G allele in CHD patients were significantly higher than those in control subjects(P

Recent advances in lectin-like oxidized low-density lipoprotein receptor-1 and atherosclerosis / 中国病理生理杂志

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a type-Ⅱ membrane protein belonging to the C-type lectin family molecules, which acts as a cell surface endocytosis receptor for atherogenic oxidized LDL (Ox-LDL). LOX-1 supports the binding internalization and proteolytic degradation of oxidized LDL, but not of significant amounts of acetylated LDL. LOX-1 is initially synthesized as a 40 kD precursor protein with N-linked high mannose-type carbohydrate, which is further glycosylated and processed into a 48-kD mature form. In vivo, endothelial cells that cover early therosclerotic lesions, intimal macrophages and smooth muscle cells in advanced atherosclerotic plaques express LOX-1. LOX-1 is cleaved at membrane proximal extracellular domain and released from the cell surface. Measurement of soluble LOX-1 in vivo may provide novel diagnostic strategy for the evaluation and prediction of atherosclerosis and vascular diseases.

Effect of dietary black rice outer layer fraction on inducible nitric oxide synthase expression in apoE-deficient mice / 中国病理生理杂志

AIM: To explore the effect of dietary black rice outlayer fraction (BRF) on inducible nitric oxide synthase (iNOS) expression, and elucidate the possible mechanism of BRF anti-atherogenesis in apoE-deficient mice. METHODS: After 16 weeks intervention by 5% BRF, aortic iNOS activity in different groups was determined by RIA. iNOS mRNA expression in aorta were analyzed by RT-PCR. RESULTS: Mice in BRF group showed weaker expression of iNOS mRNA and lower iNOS activity than those in positive and WRF group (P0.05). CONCLUSION: The supplementation of BRF has dramatically reduced aortic sinus atherosclerotic plaque areas compared to WRF in apoE-deficient mice and its action of anti-atherogenesis may be attributed to its inhibition of iNOS activity and iNOS mRNA expression.