BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unkn...BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.展开更多
BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria ...BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.展开更多
BACKGROUND Hypoparathyroidism,which can be sporadic or a component of an inherited syndrome,is the most common cause of hypocalcemia.If hypocalcemia is accompanied by other electrolyte disturbances,such as hypokalemia...BACKGROUND Hypoparathyroidism,which can be sporadic or a component of an inherited syndrome,is the most common cause of hypocalcemia.If hypocalcemia is accompanied by other electrolyte disturbances,such as hypokalemia and hypomagnesemia,then the cause,such as renal tubular disease,should be carefully identified.CASE SUMMARY An 18-year-old female visited our clinic because of short stature and facial deformities,including typical phenotypes,such as low ear position,depression of the nasal bridge,small hands and feet,and loss of dentition.The lab results suggested normal parathyroid hormone but hypocalcemia.In addition,multiple electrolyte disturbances were found,including hypokalemia,hypocalcemia and hypomagnesemia.The physical signs showed a short fourth metatarsal bone of both feet.The X-ray images showed cortical thickening of long bones and narrowing of the medulla of the lumen.Cranial computed tomography indicated calcification in the bilateral basal ganglia.Finally,the genetic investigation showed a de novo heterogenous mutation of“FAM111A”(c.G1706A:p.R569H).Through a review of previously reported cases,the mutation was found to be the most common mutation site in Kenny-Caffey syndrome type 2(KCS2)cases reported thus far(16/23,69.6%).The mutation was slightly more prevalent in females than in males(11/16,68.8%).Except for hypocalcemia,other clinical manifestations are heterogeneous.CONCLUSION As a rare autosomal dominant genetic disease of hypoparathyroidism,the clinical manifestations of KCS2 are atypical and diverse.This girl presented with short stature,facial deformities and skeletal deformities.The laboratory results revealed hypocalcemia as the main electrolyte disturbance.Even though her family members showed normal phenotypes,gene detection was performed to find the mutation of the FAM111A gene and confirmed the diagnosis of KCS2.展开更多
Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the invol...Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the involvement of the APOE gene in the onset of T2DM and its vascular complications. Clinical and biochemical parameters were assessed in each participant. APOE genotypes were identified by PCR-RFLP. Arterial stiffness was studied using a pOpmetre<sup>®</sup> which evaluates the pulse wave velocity (ft-PWV). Endothelial dysfunction was studied using an EndoPAT2000<sup>®</sup> which measures endothelium-dependent vasodilation (RHI). In control subjects, the ε3 allele was associated with an increase in fasting blood glucose (r = 2.36, p = 0.018), and a decrease in LDL cholesterol levels (r = −2.17, p = 0.03), and ε4 was associated with an increase in total cholesterol (r = 2.59, p = 0.01), LDL cholesterol (r = 2.84, p = 0.004), and No-HDL cholesterol (r = 2.74, p = 0.006). In type 2 diabetes subjects, the ε2 was associated with a decrease in diastolic blood pressure (r = −2.25, p = 0.02). The ε3 was associated with a decrease in ft-PWV (r = −2.26, p = 0.024) while the ε4 was associated with an increase in ft-PWV (r = 2.52, p = 0.012). Carrying the ε2ε3 genotype would have in 99% a limited risk of developing T2DM, and in event of T2DM, only 1 to 2% would have a significant risk of developing atherosclerosis, which would be severe in 17%. Of the ε2ε4 genotype, 93% had a limited or even possible risk of developing T2DM, the remaining 7% had a very high risk of developing T2DM. Diabetics carrying ε2ε4 had in 7% very high risk of developing atherosclerosis. The latter had a 20% very high risk of being very severe. Subjects carrying the ε3ε4 genotype had a 67% possible or even probable risk of developing T2DM and in the event of diabetes, there was in 34% very high risk of developing atherosclerosis which will not have even the time to evolve towards severity. For subjects carrying the ε3ε3, the risk of developing T2DM and athérosclerosis was higher than that of the ε2ε3, and ε2ε4 genotypes but lower than that ε3ε4 genotype. The physio-pathological role of the APOE gene and the impacts of its polymorphisms are important in the onset and progression of type 2 diabetes mellitus.展开更多
Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell l...Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.展开更多
Objective:To investigate the frequency of exoU and exoY genes in patients with Pseudomonas aeruginosa infection.Methods:In this study,100 clinical isolates of Pseudomonas aeruginosa were collected from patients hospit...Objective:To investigate the frequency of exoU and exoY genes in patients with Pseudomonas aeruginosa infection.Methods:In this study,100 clinical isolates of Pseudomonas aeruginosa were collected from patients hospitalized in educational-therapeutic hospitals and were identified using standard microbiological tests.Then,the antibiotic resistance pattern of the isolates was determined by the disk agar diffusion method.The bacterial DNAs were extracted by the alkaline lysis method.Finally,the presence of exoU and exoY genes was evaluated by the PCR test.Results:In this study,47%,72%,29%,39%,40%,and 44%of the isolates were non-susceptible to piperacillin,aztreonam,ceftazidime,imipenem,tobramycin,and ciprofloxacin,respectively.In addition,95%and 93%of the clinical isolates carried the exoU and exoY genes.Blood and fecal isolates had both virulence genes,while only one wound isolate had neither genes.Meanwhile,all urinary isolates contained the exoY gene and only one isolate lacked the exoU gene.Also,88 isolates simultaneously had both exoU and exoY genes.Conclusions:High prevalence of exoU and exoY genes in this region indicates a significant role of typeⅢsecretion system in pathogenesis of Pseudomonas aeruginosa.The typeⅢsecretion system may be a suitable target to reduce the pathogenicity of this bacterium.展开更多
This study investigated the expression profiles of Writ genes in adult porcine Iongissimus dorsi (LD) from different porcine genotypes and their associations with meat quality. The results showed that Wnt5a gene exp...This study investigated the expression profiles of Writ genes in adult porcine Iongissimus dorsi (LD) from different porcine genotypes and their associations with meat quality. The results showed that Wnt5a gene expression level was the highest in Jinhua (JHP) pigs, followed by Zhongbai (ZBP), DurocxZhongbai (DZB), and Duroc×Yorkshire×Landrace (DYL) pigs, with significant differences between ZBP, DZB, and DYL (P〈0.05). This genotypic order was reversed for Wnt7a, Wnt10b, and Wnt11 expression, with JHP and DYL having the lowest and highest expressive levels, respectively. Wnt5a expression was negatively correlated with pH,5 min and ApH (P〈0.01), some glycolytic markers (P〈0.05), and positively correlated with meat color (a*), shear force (SF) value (P〈0.05), myosion heavy chain (MyHC) I mRNA proportion (P〈0.01), turnover ratio of creatine phosphate (CP), and creatine kinase (CK) activity (P〈0.05). Opposite correlations were observed for Writ2, Wnt7a, Wnt10b, and Wnt11. These results revealed that Wnt5a, Wnt7a, Wnt10b, and Wnt11 gene expressions in adult porcine muscle contributed to differences between porcine genotypes and affected pork quality. Wnt5a gene expression could be beneficial for the formation of high quality pork by regulating muscle fiber types and postmortem energy metabolism.展开更多
AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycem...AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.展开更多
Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asia...Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.展开更多
In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesi...In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis展开更多
Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydro...Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydrofolate reductase gene(MTHFR)polymorphisms might influence the occurrence of coronary heart disease(CHD)in T2DM patients.The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD inT2DM patients.Methods A total of 197 subjects with T2DM were studied,of which 95 patients with CHD.The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method,and compared between patients with CHD and those without CHD.Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD(P=0.011).However,there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD.Furthermore,the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine(Hey)levels(≤15μmol/L)(P=0.006),while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hey levels(>15 μmol/L)(P=0.491).Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hey levels.展开更多
Previous studies on mammals showed that peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)played a prominent role in regulating muscle fiber type transition and composition.However,the role of P...Previous studies on mammals showed that peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)played a prominent role in regulating muscle fiber type transition and composition.However,the role of PGC-1αin chicken muscle has seldom been explored.To investigate the effect of PGC-1αon chicken skeletal muscles in this study,the PGC-1αgene was overexpressed or silenced in chicken primary myoblasts by using lentivirus,and then the effects of the PGC-1αgene overexpression and knockdown on the mRNA expression profile of genes related to myofiber type specificity were examined during fiber formation.The results showed that overexpression of PGC-1αfrom proliferation to differentiation was accompanied by the up-regulated expression of Pax7,MyoD,and CnAα,which was significantly(P<0.01)increased after one day of transfection(1 I).The enhancement of MyoG,MEF2 c,and MyHC SM expression lagged,which was improved significantly(P<0.01)after four days of transfection(1 I3 D).Overexpression of PGC-1αdecreased(P<0.01)the MyHC FWM expression after four days of transfection(1 I3 D),and it had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM during myofiber formation.The effective silence(P<0.01)of PGC-1αby lentivirus mediating short hairpin RNA(shRNA)was detected after four days of transfection(1 I3 D)in cultures,and the lack of its function in chicken primary myoblasts significantly(P<0.01)down-regulated the expression of Pax7,MyoD,CnAα,MyoG,MEF2 c,and MyHC SM,significantly(P<0.01)up-regulated the expression of MyHC FWM,and had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM.These results indicated that the role of PGC-1αin regulating the fiber type specificity of chicken skeletal muscles might be similar to that in mammals,which interplayed with key genes related to myocyte differentiation and calcineurin signaling pathway.展开更多
Group A streptococcus (GAS) causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to inv...Group A streptococcus (GAS) causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to invasive infections and post streptococcal sequelae, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis[1]. GAS harbors a host of virulence factors that contribute to its complex pathogenicity and differences in the disease severity and frequency. M protein, one of the major virulence factors, is encoded by the emm gene induces a type of specific host immune response and confers antiphagocytic properties.展开更多
Background : Cynomolgus disease models that are similar to the preclinical stage of human type 2 diabetes mellitus(T2 DM) were established by feeding middle-aged cynomolgus monkeys different high energy diets to study...Background : Cynomolgus disease models that are similar to the preclinical stage of human type 2 diabetes mellitus(T2 DM) were established by feeding middle-aged cynomolgus monkeys different high energy diets to study the differential expression of diabetes-related genes. Methods : A total of 36 male monkeys were randomly divided into four groups and fed human diets with high sugar, high fat, double high sugar and fat, and a normal diet. The preclinical diabetes phase was determined by monitoring the metabolic characteristic indices and the results of oral glucose tolerance tests( OGTT). The mRNA expression of 45 diabetes-related genes in peripheral blood leukocytes was analyzed using real-time PCR. Results : A total of 22, 25, and 21 genes were significantly up-regulated( P < 0.05) and 5, 7, and 5 genes were significantly down-regulated( P < 0.05) in the above three induced groups, respectively, compared with the control group. Of the 45 tested genes, the expression profiles of 21 genes were consistent. Most of the expression levels in the double high sugar-and-fat individuals were slightly lower than those in the high glucose and high fat groups, although the expression patterns of the three groups were essentially similar. Conclusion : The different high energy diets all induced diabetes and shared some phenotypic properties with human T2 DM. Most of the expression patterns of the related genes were identical. The gene expression profiles could be used as references for the study of early diagnostic indicators and T2 DM pathogenesis.展开更多
In this study, we investigated whether a single nucleotide polymorphism (rs42524 G 〉 C) in the type I alpha 2 collagen gene was associated with sporadic ruptured intracranial aneurysm or its clinical characteristic...In this study, we investigated whether a single nucleotide polymorphism (rs42524 G 〉 C) in the type I alpha 2 collagen gene was associated with sporadic ruptured intracranial aneurysm or its clinical characteristics in patients from Northeast China. Genotyping of the rs42524 G 〉 C polymorphism was carried out using a polymerase chain reaction-restriction fragment length polymorphism assay. The data showed that the frequency of the rs42524 GC + CC genotype was significantly higher than the GG genotype among intracranial aneurysm patients whose Hunt and Hess grading scale was 〉 3. In addition, the rs42524 G 〉 C genotype was found to have a statistically significant association with intracranial aneurysm risk. These findings indicate that the type I alpha 2 collagen gene gene may be involved in a predisposition to intracranial aneurysm in the Northeast Chinese population. Crucially, the rs42524 C allele may be an important risk factor for increased severity of the condition in patients with ruptured intracranial aneurysms.展开更多
Background The association of E670G polymorphism in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and serum lipid profiles is inconsistent in dif- ferent ethnic groups.Bai Ku Yao is a special subgroup...Background The association of E670G polymorphism in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and serum lipid profiles is inconsistent in dif- ferent ethnic groups.Bai Ku Yao is a special subgroup of the Yao minority in China.The present study was undertaken association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Methods A total of 649 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples.Genotyping of the PCSK9 E670G polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing. Results The levels of serum total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C) and apolipoprotein(Apo) AI were lower in Bai Ku Yao than in Han(P【0.01 for all).The frequency of A and G alleles was 98.00%and 2.00%in Bai Ku Yao,and 95.20%and 4.80%in Han(P【0.01);respectively. The frequency of AA,AG and GG genotypes was 95.99%,4.01%and 0%in Bai Ku Yao,and 91.02%, 8.36%and 0.62%in Han(P【0.01);respectively.There were also significant differences in the genotypic and allelic frequencies between n and the ratio of ApoAI to ApoB in Han Chinese but not in Bai Ku Yao were different between the AA and AG/GG genotypes(P【0.05 for all).The G allele carriers had higher serum HDL-C and higher ApoAI to ApoB ratio than the G allele noncarriers.When serum lipid parameters in Han were analyzed according to sex,the G allele carriers had higher serum HDL and ApoAI levels in males (P【0.05),and lower ApoB level and higher ApoAI to ApoB ratio in females(P【0.05 for all).Multiple linear regression analysis showed that serum HDL-C levels were correlated with genotypes in both ethnic groups(P【0.05 each).Serum lipid parameters were also correlated with sex,age,body massindex,alcohol consumption,cigarette smoking,and blood pressure in both ethnic groups(P【0.05-0.001).Conclusions These results suggest that the PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population,both gender show different relations to different serum lipid parameters.The G allele carriers might have higher serum lipid profiles than the G allele noncarriers. ormal LDL-C(≤3.20 mmol/L) and high LDL-C subgroups (】 3.20 mmol/L,P【0.01;respectively) in Bai Ku Yao, and between normal ApoB(≤1.14 g/L) and high ApoB subgroups(】 1.14 g/L,P 【 0.01;respectively) in Han.展开更多
[ Objective] The research aimed to discuss the relationship between the polymorphism of PPARy.2 gene and the susceptibility of type 2 diabetes mellitus (T2DM) in Guangxi Bama mini-pigs. [ Method] 24 Guangxi Bama min...[ Objective] The research aimed to discuss the relationship between the polymorphism of PPARy.2 gene and the susceptibility of type 2 diabetes mellitus (T2DM) in Guangxi Bama mini-pigs. [ Method] 24 Guangxi Bama mini-pigs were fed with high-fat and high-sucrose diet, and partial sequences of exon 2 of PPARy-2 gene were amplified by using PCR method. In addition, the contents of fasting blood glucose and insulin (INS) in Guangxi Bama mini-pigs were determined, and the glucose tolerance test (GTT) was also carried out. [ Result] There was one SNP site (19813A/G) Jn partial sequence of exon 2 of the cloned PPAFly-2 gene, and AA (7 pigs) and AG (17 pigs) genotype were detected. The contents of fasting insulin and 60-min blood glucose in GTT in AG-genotype Guangxi Bama mini-pigs were significantly higher than those of AA genotype ( P 〈0.05), while the incidence of T2DM in AG-genotype Guangxi Bama mini-pigs (71.4%) was obviously higher than that of AA gen- otype (5.9%). [ Conclusion] The polymorphism of 19813A/G in exon 2 of PPARy-2 gene was related with the susceptibility of T2DM in Guangxi Bama mini-pigs.展开更多
We observed the polymorphism distribution and coaction of uncoupling protein 3(UCP3)-55C/T,adiponectin(APN)+45T/G and tumor necrosis factor(TNF)-α-308G/A on the onset and development of T2DM in a Northern Chin...We observed the polymorphism distribution and coaction of uncoupling protein 3(UCP3)-55C/T,adiponectin(APN)+45T/G and tumor necrosis factor(TNF)-α-308G/A on the onset and development of T2DM in a Northern Chinese Han population of 213[100 type 2 diabete(T2DM) patients and 113 health control subjects] by polymerase chain reaction-restriction fragment length polymorphisum(PCR-RFLP) method.Results demonstrate the polymorphism of UCP3-55C/T,APN+45T/G,and TNF-α-308G/A related to T2DM onset and developement.And the individuals carrying UCP3-55T,APN+45G and TNF-α-308A allele had higher T2DM risk.Those results are the first report to evaluate the association of the coaction of UCP3,APN,TNF-α genes polymorphism on T2DM risk and the susceptibility of T2DM in the Northern Chinese Han population.展开更多
Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. Method One hundred and thirty-six Chinese Han p...Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI. Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.展开更多
基金Supported by National Natural Science Foundation of China,No.82100594.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.
基金the Key R&D Project of the Ministry of Science and Technology,No.2016YFC0901200 and 2016YFC0901205.
文摘BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.
基金Supported by National Natural Science Foundation of China,No.82070817.
文摘BACKGROUND Hypoparathyroidism,which can be sporadic or a component of an inherited syndrome,is the most common cause of hypocalcemia.If hypocalcemia is accompanied by other electrolyte disturbances,such as hypokalemia and hypomagnesemia,then the cause,such as renal tubular disease,should be carefully identified.CASE SUMMARY An 18-year-old female visited our clinic because of short stature and facial deformities,including typical phenotypes,such as low ear position,depression of the nasal bridge,small hands and feet,and loss of dentition.The lab results suggested normal parathyroid hormone but hypocalcemia.In addition,multiple electrolyte disturbances were found,including hypokalemia,hypocalcemia and hypomagnesemia.The physical signs showed a short fourth metatarsal bone of both feet.The X-ray images showed cortical thickening of long bones and narrowing of the medulla of the lumen.Cranial computed tomography indicated calcification in the bilateral basal ganglia.Finally,the genetic investigation showed a de novo heterogenous mutation of“FAM111A”(c.G1706A:p.R569H).Through a review of previously reported cases,the mutation was found to be the most common mutation site in Kenny-Caffey syndrome type 2(KCS2)cases reported thus far(16/23,69.6%).The mutation was slightly more prevalent in females than in males(11/16,68.8%).Except for hypocalcemia,other clinical manifestations are heterogeneous.CONCLUSION As a rare autosomal dominant genetic disease of hypoparathyroidism,the clinical manifestations of KCS2 are atypical and diverse.This girl presented with short stature,facial deformities and skeletal deformities.The laboratory results revealed hypocalcemia as the main electrolyte disturbance.Even though her family members showed normal phenotypes,gene detection was performed to find the mutation of the FAM111A gene and confirmed the diagnosis of KCS2.
文摘Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the involvement of the APOE gene in the onset of T2DM and its vascular complications. Clinical and biochemical parameters were assessed in each participant. APOE genotypes were identified by PCR-RFLP. Arterial stiffness was studied using a pOpmetre<sup>®</sup> which evaluates the pulse wave velocity (ft-PWV). Endothelial dysfunction was studied using an EndoPAT2000<sup>®</sup> which measures endothelium-dependent vasodilation (RHI). In control subjects, the ε3 allele was associated with an increase in fasting blood glucose (r = 2.36, p = 0.018), and a decrease in LDL cholesterol levels (r = −2.17, p = 0.03), and ε4 was associated with an increase in total cholesterol (r = 2.59, p = 0.01), LDL cholesterol (r = 2.84, p = 0.004), and No-HDL cholesterol (r = 2.74, p = 0.006). In type 2 diabetes subjects, the ε2 was associated with a decrease in diastolic blood pressure (r = −2.25, p = 0.02). The ε3 was associated with a decrease in ft-PWV (r = −2.26, p = 0.024) while the ε4 was associated with an increase in ft-PWV (r = 2.52, p = 0.012). Carrying the ε2ε3 genotype would have in 99% a limited risk of developing T2DM, and in event of T2DM, only 1 to 2% would have a significant risk of developing atherosclerosis, which would be severe in 17%. Of the ε2ε4 genotype, 93% had a limited or even possible risk of developing T2DM, the remaining 7% had a very high risk of developing T2DM. Diabetics carrying ε2ε4 had in 7% very high risk of developing atherosclerosis. The latter had a 20% very high risk of being very severe. Subjects carrying the ε3ε4 genotype had a 67% possible or even probable risk of developing T2DM and in the event of diabetes, there was in 34% very high risk of developing atherosclerosis which will not have even the time to evolve towards severity. For subjects carrying the ε3ε3, the risk of developing T2DM and athérosclerosis was higher than that of the ε2ε3, and ε2ε4 genotypes but lower than that ε3ε4 genotype. The physio-pathological role of the APOE gene and the impacts of its polymorphisms are important in the onset and progression of type 2 diabetes mellitus.
文摘Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.
文摘Objective:To investigate the frequency of exoU and exoY genes in patients with Pseudomonas aeruginosa infection.Methods:In this study,100 clinical isolates of Pseudomonas aeruginosa were collected from patients hospitalized in educational-therapeutic hospitals and were identified using standard microbiological tests.Then,the antibiotic resistance pattern of the isolates was determined by the disk agar diffusion method.The bacterial DNAs were extracted by the alkaline lysis method.Finally,the presence of exoU and exoY genes was evaluated by the PCR test.Results:In this study,47%,72%,29%,39%,40%,and 44%of the isolates were non-susceptible to piperacillin,aztreonam,ceftazidime,imipenem,tobramycin,and ciprofloxacin,respectively.In addition,95%and 93%of the clinical isolates carried the exoU and exoY genes.Blood and fecal isolates had both virulence genes,while only one wound isolate had neither genes.Meanwhile,all urinary isolates contained the exoY gene and only one isolate lacked the exoU gene.Also,88 isolates simultaneously had both exoU and exoY genes.Conclusions:High prevalence of exoU and exoY genes in this region indicates a significant role of typeⅢsecretion system in pathogenesis of Pseudomonas aeruginosa.The typeⅢsecretion system may be a suitable target to reduce the pathogenicity of this bacterium.
基金supported by the National Natural Science Foundation of China(31172220)the Modern Agro-industry Technology Research System of China(CARS-36)the Science and Technology Projects in Zhejiang Province of China(LY17C170005,2016C02054-4)
文摘This study investigated the expression profiles of Writ genes in adult porcine Iongissimus dorsi (LD) from different porcine genotypes and their associations with meat quality. The results showed that Wnt5a gene expression level was the highest in Jinhua (JHP) pigs, followed by Zhongbai (ZBP), DurocxZhongbai (DZB), and Duroc×Yorkshire×Landrace (DYL) pigs, with significant differences between ZBP, DZB, and DYL (P〈0.05). This genotypic order was reversed for Wnt7a, Wnt10b, and Wnt11 expression, with JHP and DYL having the lowest and highest expressive levels, respectively. Wnt5a expression was negatively correlated with pH,5 min and ApH (P〈0.01), some glycolytic markers (P〈0.05), and positively correlated with meat color (a*), shear force (SF) value (P〈0.05), myosion heavy chain (MyHC) I mRNA proportion (P〈0.01), turnover ratio of creatine phosphate (CP), and creatine kinase (CK) activity (P〈0.05). Opposite correlations were observed for Writ2, Wnt7a, Wnt10b, and Wnt11. These results revealed that Wnt5a, Wnt7a, Wnt10b, and Wnt11 gene expressions in adult porcine muscle contributed to differences between porcine genotypes and affected pork quality. Wnt5a gene expression could be beneficial for the formation of high quality pork by regulating muscle fiber types and postmortem energy metabolism.
基金Supported by The Research Council(TRC),Muscat,Oman,No.RC/MED/BIOC/10/01
文摘AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.
基金This work was supported by the grants from the Special Project of Ministry of Health (No.201302009)and the National Natural Science Foundation of China (No. 81700300).
文摘Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.
文摘In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis
基金the National Key Development Plan for Precision Medicine Research(project number:2017YFC0910004,running period:2018/03-2020/12)Jinan Science Project(project number:201602171,running period:2016/01-2018/12).
文摘Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydrofolate reductase gene(MTHFR)polymorphisms might influence the occurrence of coronary heart disease(CHD)in T2DM patients.The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD inT2DM patients.Methods A total of 197 subjects with T2DM were studied,of which 95 patients with CHD.The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method,and compared between patients with CHD and those without CHD.Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD(P=0.011).However,there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD.Furthermore,the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine(Hey)levels(≤15μmol/L)(P=0.006),while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hey levels(>15 μmol/L)(P=0.491).Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hey levels.
基金supported by the National Natural Science Foundation of China(31301967)the Natural Science Foundation of Jiangsu Province,China(BK20161322)+4 种基金the projects of Key Laboratory for Poultry Genetics and Breeding of Jiangsu Province(JQLAB-ZZ-201703)the Major Breeding Programs in Jiangsu Province,China(PZCZ201728)the earmarked fund for China Agriculture Research System(CARS-41)the Independent Scientific Foundation of Public Welfare Scientific Institutes in Jiangsu Province,China(BM2018026)the Open Projects of Key Laboratory of Chicken Genetics and Breeding,Ministry of Agriculture and Rural Affairs of China(CGB-201704)。
文摘Previous studies on mammals showed that peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)played a prominent role in regulating muscle fiber type transition and composition.However,the role of PGC-1αin chicken muscle has seldom been explored.To investigate the effect of PGC-1αon chicken skeletal muscles in this study,the PGC-1αgene was overexpressed or silenced in chicken primary myoblasts by using lentivirus,and then the effects of the PGC-1αgene overexpression and knockdown on the mRNA expression profile of genes related to myofiber type specificity were examined during fiber formation.The results showed that overexpression of PGC-1αfrom proliferation to differentiation was accompanied by the up-regulated expression of Pax7,MyoD,and CnAα,which was significantly(P<0.01)increased after one day of transfection(1 I).The enhancement of MyoG,MEF2 c,and MyHC SM expression lagged,which was improved significantly(P<0.01)after four days of transfection(1 I3 D).Overexpression of PGC-1αdecreased(P<0.01)the MyHC FWM expression after four days of transfection(1 I3 D),and it had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM during myofiber formation.The effective silence(P<0.01)of PGC-1αby lentivirus mediating short hairpin RNA(shRNA)was detected after four days of transfection(1 I3 D)in cultures,and the lack of its function in chicken primary myoblasts significantly(P<0.01)down-regulated the expression of Pax7,MyoD,CnAα,MyoG,MEF2 c,and MyHC SM,significantly(P<0.01)up-regulated the expression of MyHC FWM,and had no significant impact(P>0.05)on the expression of CnB1,NFATc3,and MyHC FRM.These results indicated that the role of PGC-1αin regulating the fiber type specificity of chicken skeletal muscles might be similar to that in mammals,which interplayed with key genes related to myocyte differentiation and calcineurin signaling pathway.
文摘Group A streptococcus (GAS) causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to invasive infections and post streptococcal sequelae, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis[1]. GAS harbors a host of virulence factors that contribute to its complex pathogenicity and differences in the disease severity and frequency. M protein, one of the major virulence factors, is encoded by the emm gene induces a type of specific host immune response and confers antiphagocytic properties.
基金Science and Technology Planning Project of Guangdong Province,Grant/Award Number:2016A030303037 and 2017A070702014Natural Science Foundation of Guangdong Province,(2018A030313307)+1 种基金National Natural Science Foundation of China,Grant/Award Number:81102358GDAS Special Project of Science and Technology Development,Grant/Award Number:2017GDASCX-0107
文摘Background : Cynomolgus disease models that are similar to the preclinical stage of human type 2 diabetes mellitus(T2 DM) were established by feeding middle-aged cynomolgus monkeys different high energy diets to study the differential expression of diabetes-related genes. Methods : A total of 36 male monkeys were randomly divided into four groups and fed human diets with high sugar, high fat, double high sugar and fat, and a normal diet. The preclinical diabetes phase was determined by monitoring the metabolic characteristic indices and the results of oral glucose tolerance tests( OGTT). The mRNA expression of 45 diabetes-related genes in peripheral blood leukocytes was analyzed using real-time PCR. Results : A total of 22, 25, and 21 genes were significantly up-regulated( P < 0.05) and 5, 7, and 5 genes were significantly down-regulated( P < 0.05) in the above three induced groups, respectively, compared with the control group. Of the 45 tested genes, the expression profiles of 21 genes were consistent. Most of the expression levels in the double high sugar-and-fat individuals were slightly lower than those in the high glucose and high fat groups, although the expression patterns of the three groups were essentially similar. Conclusion : The different high energy diets all induced diabetes and shared some phenotypic properties with human T2 DM. Most of the expression patterns of the related genes were identical. The gene expression profiles could be used as references for the study of early diagnostic indicators and T2 DM pathogenesis.
文摘In this study, we investigated whether a single nucleotide polymorphism (rs42524 G 〉 C) in the type I alpha 2 collagen gene was associated with sporadic ruptured intracranial aneurysm or its clinical characteristics in patients from Northeast China. Genotyping of the rs42524 G 〉 C polymorphism was carried out using a polymerase chain reaction-restriction fragment length polymorphism assay. The data showed that the frequency of the rs42524 GC + CC genotype was significantly higher than the GG genotype among intracranial aneurysm patients whose Hunt and Hess grading scale was 〉 3. In addition, the rs42524 G 〉 C genotype was found to have a statistically significant association with intracranial aneurysm risk. These findings indicate that the type I alpha 2 collagen gene gene may be involved in a predisposition to intracranial aneurysm in the Northeast Chinese population. Crucially, the rs42524 C allele may be an important risk factor for increased severity of the condition in patients with ruptured intracranial aneurysms.
文摘Background The association of E670G polymorphism in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and serum lipid profiles is inconsistent in dif- ferent ethnic groups.Bai Ku Yao is a special subgroup of the Yao minority in China.The present study was undertaken association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Methods A total of 649 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples.Genotyping of the PCSK9 E670G polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing. Results The levels of serum total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C) and apolipoprotein(Apo) AI were lower in Bai Ku Yao than in Han(P【0.01 for all).The frequency of A and G alleles was 98.00%and 2.00%in Bai Ku Yao,and 95.20%and 4.80%in Han(P【0.01);respectively. The frequency of AA,AG and GG genotypes was 95.99%,4.01%and 0%in Bai Ku Yao,and 91.02%, 8.36%and 0.62%in Han(P【0.01);respectively.There were also significant differences in the genotypic and allelic frequencies between n and the ratio of ApoAI to ApoB in Han Chinese but not in Bai Ku Yao were different between the AA and AG/GG genotypes(P【0.05 for all).The G allele carriers had higher serum HDL-C and higher ApoAI to ApoB ratio than the G allele noncarriers.When serum lipid parameters in Han were analyzed according to sex,the G allele carriers had higher serum HDL and ApoAI levels in males (P【0.05),and lower ApoB level and higher ApoAI to ApoB ratio in females(P【0.05 for all).Multiple linear regression analysis showed that serum HDL-C levels were correlated with genotypes in both ethnic groups(P【0.05 each).Serum lipid parameters were also correlated with sex,age,body massindex,alcohol consumption,cigarette smoking,and blood pressure in both ethnic groups(P【0.05-0.001).Conclusions These results suggest that the PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population,both gender show different relations to different serum lipid parameters.The G allele carriers might have higher serum lipid profiles than the G allele noncarriers. ormal LDL-C(≤3.20 mmol/L) and high LDL-C subgroups (】 3.20 mmol/L,P【0.01;respectively) in Bai Ku Yao, and between normal ApoB(≤1.14 g/L) and high ApoB subgroups(】 1.14 g/L,P 【 0.01;respectively) in Han.
基金funded by the Project of Guangxi Science and Technology Basic Condition Platform Construction (11-31-09)
文摘[ Objective] The research aimed to discuss the relationship between the polymorphism of PPARy.2 gene and the susceptibility of type 2 diabetes mellitus (T2DM) in Guangxi Bama mini-pigs. [ Method] 24 Guangxi Bama mini-pigs were fed with high-fat and high-sucrose diet, and partial sequences of exon 2 of PPARy-2 gene were amplified by using PCR method. In addition, the contents of fasting blood glucose and insulin (INS) in Guangxi Bama mini-pigs were determined, and the glucose tolerance test (GTT) was also carried out. [ Result] There was one SNP site (19813A/G) Jn partial sequence of exon 2 of the cloned PPAFly-2 gene, and AA (7 pigs) and AG (17 pigs) genotype were detected. The contents of fasting insulin and 60-min blood glucose in GTT in AG-genotype Guangxi Bama mini-pigs were significantly higher than those of AA genotype ( P 〈0.05), while the incidence of T2DM in AG-genotype Guangxi Bama mini-pigs (71.4%) was obviously higher than that of AA gen- otype (5.9%). [ Conclusion] The polymorphism of 19813A/G in exon 2 of PPARy-2 gene was related with the susceptibility of T2DM in Guangxi Bama mini-pigs.
基金Supported by the Scientific Research Foundation of Jilin Province,China(Nos.2007-0722,2008-2123,20100942)the Grants from the Developing and Reforming Community of Jilin Provinces,China(Nos.2006-1550,20080925,2010-1928)
文摘We observed the polymorphism distribution and coaction of uncoupling protein 3(UCP3)-55C/T,adiponectin(APN)+45T/G and tumor necrosis factor(TNF)-α-308G/A on the onset and development of T2DM in a Northern Chinese Han population of 213[100 type 2 diabete(T2DM) patients and 113 health control subjects] by polymerase chain reaction-restriction fragment length polymorphisum(PCR-RFLP) method.Results demonstrate the polymorphism of UCP3-55C/T,APN+45T/G,and TNF-α-308G/A related to T2DM onset and developement.And the individuals carrying UCP3-55T,APN+45G and TNF-α-308A allele had higher T2DM risk.Those results are the first report to evaluate the association of the coaction of UCP3,APN,TNF-α genes polymorphism on T2DM risk and the susceptibility of T2DM in the Northern Chinese Han population.
文摘Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI. Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.