Objective To explore the myocardial damage and the changes of MB isoenzyme of creatine kinase(CK-MB) and cardial troponin I(cTnI) of rat with endotoxemia at early stage.Methods Sixty SD rats were randomly divided into lipopolysaccharide(LPS) group(LPS group,n=48) and control group(n=12).Rats in LPS group were injected intraperitoneally with LPS(5 mg/kg) and then divided into 6 subgroups according sacrificed time after injection(0.5,1.0,2.0,3.0,12.0,24.0 h).CK-MB/ cTnI in blood was determined with chemiluminescent technique and myocardial pathological damage was observed under the light and transmission electron microscope.Control group was subjected to normal sodium and divided randomly into the same subgroups too.Results The rat diminished their action after beening injected endotoxin 15 minutes,and their reaction were slow.One hour later,they were short of action and reaction.Three hours later,they almost did not move at all,and the glossiness of their pelage were faint.Twenty-four hours later,their foodintake was diminished,their shout were weakened,and their response to stimulus were very thin,the glossiness of pelage were insufficient.Compared with control group,CK-MB increased significantly at 1.0,2.0,3.0,12.0,24.0 h(Pa

Nasal polyps is a common disease in clinical, with nasal mucosal inflammatory hyperplasia. However, the molecular mechanism of it is largely unknown. Tumor suppressor genes, proliferation and apoptosis related genes and cytokines play an important role in the formation and pathological development of nasal polyps. The expression level of tumor suppressor related proteins and receptors is not constant, high level of these expression can stimulate nasal mucosal proliferation, while low or lacking expression may facilitate nasal polyps cells apoptosis. Both proliferation and apoptosis make a big difference in nasal polyps formation and development. This article concludes the relationships between new progressions in nasal polyps pathogenesis and tumor suppressor genes and proliferation apoptosis genes, which not only helps practitioners deeply and comprehensively understand nasall polyps pathogenesis but promotes explorations to effective therapeutics.
Apoptosis ; Apoptosis Regulatory Proteins ; genetics ; Cytokines ; Disease Progression ; Genes, Tumor Suppressor ; Humans ; Nasal Mucosa ; Nasal Polyps ; genetics

To study the mechanisms of total flavonoid from Glycyrrhizae Radix et Rhizoma (TFGR) and its ingredient isoliquiritigenin (ISL) on their regulation of M2 phenotype polarization of macrophages. IL-4 (60 μg x L(-1)) induced RAW264.7 cells for 6 h to establish the M2 macrophage model. TFGR and ISL restrained breast cancer cells migration with the aid of M2 macrophages in vitro. TFGR and ISL inhibited gene and protein expression of Arg-1, up-regulated gene of HO-1 and protein expression of iNOS, enhanced the expression of microRNA 155 and its target gene SHIP1, meanwhile down-regulated.the phosphorylation of STAT3 and STAT6. So TFGR and ISL were the bioactive fraction and ingredient in Glycyrrhizae Radix et Rhizoma to reverse M2 phenotype macrophages polarization. TFGR and ISL inhibited the promotion of M2 macrophages to breast cancer cells migration in vitro, STAT signal pathways and miR155 were partly involved.
Animals ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Polarity ; drug effects ; Chalcones ; pharmacology ; Flavonoids ; pharmacology ; Glycyrrhiza ; chemistry ; Interleukin-4 ; genetics ; metabolism ; Macrophages ; cytology ; drug effects ; metabolism ; Mice ; RAW 264.7 Cells ; Rhizome ; chemistry

To study the regulation of androgen receptor (AR) expression in human prostate cancer LNCaP cells by triptolide (TP) and the possible mechanism, by using qRT-PCR and Western blot, the AR mRNA and protein levels in TP treated LNCaP cells were detected, and the AR protein level in TP and NF-κB inhibitor treated LNCaP cells was also detected; a series of pGL3-AR promoter reporter gene vectors were built using restriction-free cloning method, and the vectors were employed to investigate the effects of TP on the transcriptional activity of AR promoter in LNCaP cells; the upstream proteins which may play regulatory roles were detected using western blot assay. After treated LNCaP cells with TP for 48 h, AR mRNA and protein expressions decreased with increasing TP concentration. The expression of AR target gene PART1 and prostate specific antigen (PSA) was also downregulated by TP treatment; a series of pGL3-AR promoter reporter vectors were constructed and validated by sequencing and luciferase activity; the results of dual luciferase reporter assay showed that TP downregulated AR at the transcriptional level; PI3K/AKT/NF-κB pathway which is associated with AR promoter activity was drowregulated by TP. In conclusion, our results demonstrated that the transcriptional activity of AR in LNCAP cells was downregulated by TP, and PI3K/AKT/NF-κB pathway may be involved in the regulation mechanism.

ABSTRACT:Objective To observe the influence of saikosaponin-d (SSd)on the proliferation and the function of autophagy of human hepatocellular carcinoma (HCC)cell line SMMC-7721 to explore the possible mechanisms. Methods SMMC-7721 was cultured invitro and then treated with SSd of various concentrations (5.0,7.5,10.0, 12.5,15.0 and 17.5 mg/L)for 24,48 and 72 h.We used MTT to detect cell proliferation,selected the optimal concentration and time,and detected the expressions of BECN1 at mRNA and protein levels by PCR and Western blot.Results The inhibition rate of the proliferation of SMMC-7721 cell line increased with the increase of the concentration of SSd,and the highest inhibition rate (60%)appeared when the concentration reached 12.5 mg/L. The expression of BECN1 in the group with SSd was obviously higher than that in the control group (P<0.05). 3-MA decreased not only the expressions of BECN1 at mRNA and protein levels but also the expression of BECN1 when used in conjunction with SSd.Conclusion The inhibiting function of SSd on SMMC-7721 presents a dependency between drug concentration and function time,basically in line with the drug dose-effect relationship. SSd induces the occurrence of autophagic cell death through up-regulating the expression of BECN1 ,thus inhibiting the proliferation of SMMC-7 7 2 1 .

To study the regulation of androgen receptor (AR) expression in human prostate cancer LNCaP cells by triptolide (TP) and the possible mechanism, by using qRT-PCR and Western blot, the AR mRNA and protein levels in TP treated LNCaP cells were detected, and the AR protein level in TP and NF-κB inhibitor treated LNCaP cells was also detected; a series of pGL3-AR promoter reporter gene vectors were built using restriction-free cloning method, and the vectors were employed to investigate the effects of TP on the transcriptional activity of AR promoter in LNCaP cells; the upstream proteins which may play regulatory roles were detected using western blot assay. After treated LNCaP cells with TP for 48 h, AR mRNA and protein expressions decreased with increasing TP concentration. The expression of AR target gene PART1 and prostate specific antigen (PSA) was also downregulated by TP treatment; a series of pGL3-AR promoter reporter vectors were constructed and validated by sequencing and luciferase activity; the results of dual luciferase reporter assay showed that TP downregulated AR at the transcriptional level; PI3K/AKT/NF-κB pathway which is associated with AR promoter activity was drowregulated by TP. In conclusion, our results demonstrated that the transcriptional activity of AR in LNCAP cells was downregulated by TP, and PI3K/AKT/NF-κB pathway may be involved in the regulation mechanism.
Cell Line, Tumor ; Diterpenes ; pharmacology ; Down-Regulation ; Epoxy Compounds ; pharmacology ; Genetic Vectors ; Humans ; Male ; NF-kappa B ; antagonists & inhibitors ; Phenanthrenes ; pharmacology ; Phosphatidylinositol 3-Kinases ; metabolism ; Promoter Regions, Genetic ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; RNA, Messenger ; Receptors, Androgen ; metabolism ; Signal Transduction ; Transcriptional Activation

Objective To evaluate the role of p38 MAPK signal transduction pathway in dexmedetomidine against neurotoxicity induced by bupivacaine.Methods Seventy-two adult male SD rats,successfully implanted with intrathecal catheter without complications,were randomly divided into 6 groups: control group (group C);p38MAPK inhibitor group(group SB);dexmedetomidine group (group D);bupivacaine group (group B);dexmedetomidine and bupivacaine group (group DB);p38MAPK inhibitor and bupivacaine group (group SBB).DMSO 20 μl were injected intrathecally in group C;p38MAPK inhibitor 30 μg and 5% bupivacaine were respectively injected intrathecally in group SB and B;group DB and SBB were respectivel pretreated with dexmedetomidine 75 μg/kg intraperitoneally and p38MAPK inhibitor 30 μg intrathecal injection 20 min before intrathecally injected 5% bupivacaine.Dexmedetomidine 75 μg/kg was injected intraperitoneally in group D.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before intrathecal catheter was implanted (T0),before intrathecal administration (T1) and at 4,8 and 12 h and on 1,2,3,4,5 and 6 days after intrathecal administration (T2-T10).At 24 h after intrathecal administration,6 rats were randomly chosen from each group and sacrificed.The lumbar segment (L4-5) of the spinal cord was removed for detecting neuronal apoptosis (by TUNEL) and phosporylated p38MAPK(p-p38MAPK) expression (by Western blot).Results Compared with T0,MWT was significantly increased and TWL was prolonged at T2-T9 in group B,MWT at T2-T7 was significantly increased and TWL at T2-T6 was prolonged in group DB,MWT was significantly increased and TWL was prolonged at T2-T5 in group SBB (P<0.05).Compared with group C,no significant difference was found in MWT,TWL,the apoptotic index and expression of p-p38MAPK in groups D and SB.MWT was significantly increased and TWL was prolonged at T2-T9 in group B,the apoptotic index and expression of p-p38MAPK were significantly increased in group B (P<0.05).Compared with group B,MWT and TWL at T2-T9,the apoptotic index and expression of p-p38MAPK were significantly decreased in groups DB and SBB (P<0.05).Conclusion Dexmedetomidine can inhibit spinal neurotoxicity induced by bupivacaine in rats via inhibiting apoptosis in spinal cord,and inhibition of p38 MAPK signal transduction pathway may be involved in the underlying mechanism.

Objective To investigate the medication safety and relevant influence factors among the elderly with chronic diseases,to improve the safety of the elderly medication,and provide the theory basis for the rational use of drugs.Methods Questionnaire survey was conducted on 452 elderly outpatients with chronic diseases using self-designed questionnaire.Results 21.7％ (98/452) of the elderly took seven or more drugs.The incidence of adverse drug reactions was 38.4％ (174/452).The prevalence in the top three were cardiovascular disease [61.3％ (277/452)],diabetes [53.5％ (242/452)],and lung disease [42.0％ (190/452)].Old people had unsafe medication behaviors including missing medication,stopping medication on their own,increased or reduced dosages of medicine and taking overdue medication,and so on.Logistic regression analysis showed that the main influence factors of medication safety were age,previous occupation,educational level,monthly household income per capita,medication time,the source of drugs and whether received medication safety health education (P＜0.05).Conclusions Relative lack of safety knowledge,wrong cognition and behaviors exist in the elderly.It is worthy of paying attention to adverse drug reactions and hidden dangers of the elderly.

Objective:To know about the prevalence of depression,anxiety,and suicidal behaviors among newly diagnosed HIV-positive men who have sex with men.Methods:A cross-sectional study with a consecutive sample was conducted in the HIV/AIDS Voluntary Counseling and Testing Clinic of the Center for Disease Control and Prevention.A standard set of questionnaires,namely,the Patient Health Questionnaire Depression Scale (PHQ9),Generalized Anxiety Disorder Scale (GAD-7),and a self-designed suicidal behavior questionnaire were used to assess the subjects'emotional problems.Results:Among 321 newly diagnosed HIV-positive men who had sex with men,the positive rate of depression and anxiety were 41.1％ (132/321) and 31.5％ (101/321),respectively.The rate suicidal ideation after HIV diagnosis was 27.7％ (89/321).Individuals who were living with others,had HIV related clinical symptoms,higher HIV/AIDS related stress,and lower social support were more likely to have positive depressive symptoms.Individuals who were unmarried,had lower HIV/AIDS related stress,and lower social support were more likely to have positive anxiety.The prevalence of suicidal ideation after HIV diagnosis was higher among individuals who were unwilling to join in HIV/AIDS support groups,had HIV related clinical symptoms,higher HIV/AIDS related stress,lower social support,and both positive depression and anxiety symptoms.Conclusion:The prevalence of emotional problems is high among newly diagnosed HIV-positive men who have sex with men.It is warranted to promote mental health service for this vulnerable group.

Objective To evaluate the safety and efficacy of adefovir dipivoxil made in China for treating hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients.Methods This was a multicenter,double-blinded,randomized controlled trial.Two hundred and thirty-eight patients with HBeAg-positive chronic hepatitis B were assigned to receive either adefovir dipivoxil(10 mg/d,120 patients)or placebo(118 patients)for 12 weeks in 5 medical centers in China.Then,both groups of patients entered 36 weeks open-labeled adefovir dipivoxil treatment phase(10 mg/d),The rates of serum HBV DNA clearances,alanine aminotransferase levels(ALT)normalization,HBeAg loss and anti-HBe seroconversion were evaluated respectively during and post the 48-week treatment.Results After 12 weeks of treatment,the rates of serum HBV DNA clearance(real-time fluorescent quanti- tative polymerase chain reaction,the detection limit was 1?10~4 copy per milliliter),ALT normaliza- tion,HBeAg loss and anti-HBe seroconversion of adefovir dipivoxil group were all significantly higher than those of placebo group(50.0% vs 5.1%,35.0% vs 8.5%,12.5% vs 2.5% and 5.8% vs 0, respectively,x~2=59.89,24.52,P0.05).The safety profile of adefovir dipivoxil was similar to that of placebo. Conclusions The safety profile and efficacy of domestic adefovir dipivoxil for treating HBeAg-positive chronic hepatitis B patients are similar to its counterparts that have been licensed aboard.