Objective To study an identified leucine-rich repeats(LRRs)protein,LRR containing 19(LRRC19),and to determine the distribution,localization,and biological function of LRRC19 mRNA expression in spleen cells.Methods Bioinformatics analysis was used to predetermine the structure of LRRC19 gene and protein.The distribution and localization of LRRC19 mRNA expression were detected by hybridization in situ with LRRC19 mRNA specific probes and reverse transcriptase polymerase chain reaction(RT-PCR).Additionally,the activity of secreted alkaline phosphatase(SEAP)was detected for analyzing the nuclear factor-kappa B(NF-?B)activation in HEK293T cells transfected with the expression vector of LRRC19 in vitro.Results LRRC19 was found to be a transmembrane protein,with 4 LRR motifs,a single transmembrane domain and two phosphorylation sites of casein kinase 2(CK2)at cytoplasmic domain,as analyzed through bioinformatics soft wares.Previous study revealed that LRRC19 without cytoplasmic Toll/IL-1 receptor(TIR)domain could activate NF-?B to enhance the expression of proinflammatory cytokines.LRRC 19 could also be demonstrated by ectopic expression in RAW264.7 cells after transfection with murine LRRC19 expression plasmid pcDNA3.1-V5-LRRC19 indicating that it was a transmembrane protein.In persent study,the results of hybridization in situ and RT-PCR showed that LRRC19 mRNA was expressed in the germinal center and splenic cord of mouse spleen.Additionally,LRRC19 was predominantly expressed in CD5+ lymphocyte,known as B1 cell.In vitro study also indicated that several pathogens might significantly enhance the NF-?B activity of the cells transfected with LRRC19.Conclusion LRRC19 might be a transmembrane receptor,and it may be able to recognize the conserved sequence of pathogens,participate in the induction of cell signaling,activate the NF-?B signal pathway,promote transcription of target genes,and modulate the innate immune response.

To evaluate the effects of Yisui Shengxue Granules on expressions of alpha-hemoglobin stabilizing protein (AHSP) and erythroid transcription factor GATA-1 mRNAs in bone marrow of patients with beta-thalassemia, and to explore its possible molecular mechanism.

To explore the effects of Shengmai injection and Xuesaitong injection, compound Chinese herbal medicines for replenishing qi and activating blood, on ventricular fibrillation threshold, heart structure and connexin 43 (Cx43) expression in rats with myocardial infarction (MI).

Objective To investigate the effect of 9-cis retinoid acid(c-RA),a retinoid X receptor(RXR)agonist,on hydrogen peroxide(H2O2)induced apoptosis in cultured rat neonatal cardiomyoeytes,and to explore the mechanism.Method Cultured cardiomyocpes were randomly divided into three groups:normal group treated with vehicle(N group),H2O2 group treated with 100 μmol/L H2O2(H group),and c-RA group pretreated with 100nmol/L c-RA(H+R group).Cell viability was detected by MTT.Morphological changes of apoptotic cardiomyocytes were observed by Hoechst 33258 staining under fluorescence microscope.The apoptotic rate was determined by flow cytometry.Mitochondrial membrane potential(△(ψ)m)was measured by JC-1 dye.Cellular reactive oxygen species(ROS)production was detected by CM-H2DCFDA fluorescent probe.All measurement data wIe expressed as(x±s),and statistically analyzed using one-way ANOVA analysis and Dunnett test.Differences were considered significant when P was＜0.05.Results Treatment with c-RA significantly enhanced cell viability,reduced apoptosis ratio,stabled mitoehondrial membrane potential and reduced level of cellular reactive oxygen species.Conclusions RXR agonist c-RA inhibits H2O2-induced myocyte apoptosis in cultured rat neonatal cardiomyocytes,which may be related to alleviate oxidative stress injury.

Objective To observe the effects of Fuzheng Huayu Capsule on the expressions of the main roles, Rock1 and Rock2, in RhoA/Rock signal transduction pathway in rats with myocardial infarction (MI);To explore the possible mechanism of Fuzheng Huayu Capsule to improve ventricular remodeling in myocardial fibrosis. Methods The MI model was induced by ligation of the left coronary artery. Rats with MI were randomly divided into the model group, Fuzheng Huayu group and Fasudil hydrochloride group. A sham-operation group threading without ligation was setting as a control group, with eight rats in each group. The rats were treated with corresponding medicine for 4 weeks from the second day after modeling. The expression of Rock1, Rock2 and its mRNA were detected by immunohistochemical and real-time PCR method. Results The protein expression of Rock1 and Rock2 in model group were significantly higher than those in the sham-operation group (P<0.05). The protein expression of Rock1 and Rock2 in the Fuzheng Huayu group and Fasudil hydrochloride group were lower than those in the model group. The mRNA expression of Rock2 was significantly higher in the model group than that in the sham-operation group (P<0.05). The mRNA expression of Rock1 in the Fasudil hydrochloride group was lower than that in the model group (P<0.05). The mRNA expression of Rock2 in the Fuzheng Huayu group and Fasudil hydrochloride group was lower than that in the model group (P<0.05). Conclusion Fuzheng Huayu Capsule can decrease the expression of Rock1, Rock2 and Rock2 in the marginal zone of myocardial infarction in rats with MI. The anti ventricular remodeling mechanism of Fuzheng Huayu Capsule maybe related with this.

OBJECTIVE: To investigate the efficacy and safety of Yisui Shengxue Granule (YSSXG), a compound traditional Chinese herbal medicine, in treating beta-thalassemia. METHODS: A randomized single-blinded trial was designed. Sixty patients with beta-thalassemia were divided into two groups: 30 patients in YSSXG-treated group and 30 in placebo parallel-control group. The patients in the two groups were assigned to receive either YSSXG or placebo for three months. The patients' symptoms and their blood indexes such as hemoglobin (Hb), red blood cell (RBC), reticulocytes (Ret) and fetal hemoglobin (HBF) were examined before and after the treatment. Meanwhile, the liver and spleen were examined with B-mode ultrasound. RESULTS: In the YSSXG-treated group, the blood indexes (Hb, RBC, Ret and HBF) and the symptoms of the patients were improved after three-month treatment, with statistical significance compared to those before treatment (P<0.01); hepatauxe and splenomegaly were also relieved (P<0.05) and no adverse reactions were monitored. In the placebo parallel-control group, no significant improvement of the blood indexes and symptoms, as well as the hepatauxe and splenomegaly had been found (P>0.05). CONCLUSION: YSSXG demonstrates obvious clinical efficacy and no adverse reactions in treating beta-thalassemia.

OBJECTIVETo study the effect of Panax notoginseng saponins (PNS) on (synaptophysin, syp) and tau gene expression in the brain tissue in senescence accelerated mouse prone 8 (SAMP 8).

METHODSAMP8 were randomly divided into 4 groups: PNS 23.38, 93.50 mg x kg(-1) group, huperzin A 0.038 6 mg x kg(-1) x d(-1) group and blank control group; the drug groups were treated with the designed drugs respectively per day by intragastric administration for 4 consecutive weeks, and double distilled water was given to blank control group. After treatment, the mRNA content of tau and syp were assayed by reverse transcription (RT) and real-time polymerase chain reaction (real-time PCR).

RESULTCompared with blank control group, the syp mRNA contents were increased in PNS groups (P < 0.05 or P < 0.01), and the tau mRNA content were not significant difference in all groups.

CONCLUSIONThis study suggests that PNS can up-regulate syp gene expression at transcriptional level in the brain of SAMP 8.

Aging ; drug effects ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Gene Expression ; drug effects ; genetics ; Mice ; Panax notoginseng ; chemistry ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; genetics ; metabolism ; Saponins ; pharmacology ; tau Proteins ; genetics ; metabolism

BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.