2.Protective effects of resveratrol on lipopolysaccharide-induced inflammatory toxicity in primary cortical astrocyte cultures.
Ben LIU ; Qing CHEN ; Jiang GUO ; Hao ZHOU ; Bin WANG ; Jin LI ; Shou-yi YU
Journal of Southern Medical University 2011;31(12):2052-2056
OBJECTIVETo study the anti-inflammatory effect of resveratrol in primary cortical astrocyte cultures stimulated by lipopolysaccharide (LPS) and explore the underlying mechanism of this protective effect.
METHODSThe astrocytes were cultured in the presence of resveratrol at different concentrations for 12 h followed by stimulation with lipopolysaccharide (LPS) for another 24 h. Lactate dehydrogenas (LDH) leakage volumes were detected, the cytotoxicity of resveratrol was examined using cell counting kit-8 (CCK-8), the release of NO was measured by Griess reaction, and the expression levels of TNF-α and iNOS were measured using ELISA and Western blotting respectively.
RESULTSThe purity of the astrocytes cultured in vitro was (95.49∓1.86)%. LPS treatment increased LDH leakage and reduced the survival rate of the astrocytes, resulting also in significantly increased NO and TNF-α release and iNOS protein expressions. Within the concentration range of 5-50 µmol/L, resveratrol effectively improved the survival rate of the astrocytes and decreased LDH leakage with a dose-response relationship. Only 25 and 50 µmol/L resveratrol produced obvious inhibitory effect on NO and TNF-α release and iNOS expression, while 5 µmol/L resveratrol had no such effects.
CONCLUSIONHigh concentration of resveratrol can inhibit the release of inflammatory mediators and improve the inflammation injury induced by LPS in astrocytes, the mechanism of which may involve the inhibition of iNOS/NO expression pathway.
Animals ; Animals, Newborn ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Astrocytes ; cytology ; Cerebral Cortex ; cytology ; Inflammation ; chemically induced ; Lipopolysaccharides ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism
3.Correlation of VEGF and Ki67 expression with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma.
Shu-mei JIANG ; Ren-ben WANG ; Jin-ming YU ; Kun-li ZHU ; Dian-bin MU ; Zhong-fa XU
Chinese Journal of Oncology 2008;30(8):602-605
OBJECTIVETo investigate the correlation of expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki67) with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma.
METHODSSamples of pretreatment biopsies and the resected specimens after neoadjuvant therapy in 32 patients with rectal adenocarcinoma were collected, and the expression of Ki67 and VEGF were detected by immunohistochemistry using specific antibodies. The correlation of Ki67 and VEGF expression with clinicopathological factors were analyzed.
RESULTSThe level of VEGF expression was significantly correlated with lymph node metastasis (P = 0.033), depth of tumor invasion (P = 0.007) and TNM stage (P = 0.016), but not with histological type, tumor size, age and gender of the patients (P > 0.05). However, VEGF expression was found to be negatively and significantly correlated with the sensitivity to neoadjuvant chemoradiation (P = 0.016), and a transient increase of VEGF expression was detected in the resected specimens after neoadjuvant therapy (P = 0.035). Ki67 labeling index (Ki67-LI) was found to be significantly correlated with lymph node metastasis (P = 0.028), but not with tumor size, age and gender of the patients (P > 0.05). It was also found that tumors with lower Ki67-LI expression were more sensitive to neoadjuvant therapy than that with higher expression of Ki67-LI (P = 0.032). In contrast with VEGF, the Ki67 expression level decreased after neoadjuvant therapy, but no statistical significance was found between pretreatment and posttreatment specimens (P > 0.05).
CONCLUSIONThe preliminary results of this study demonstrate that the expression of VEGF and Ki67 in pretreatment biopsy of rectal adenocarcinoma may be used as a biomarker to predict tumor response to neoadjuvant chemoradiation.
Adenocarcinoma ; metabolism ; pathology ; surgery ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Female ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Radiotherapy, Conformal ; Rectal Neoplasms ; metabolism ; pathology ; surgery ; therapy ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult
4.Digital pulse wave analyzing method in evaluating arterial compliance based on population study in Chinese 415 adults.
Li ZHANG ; Zhi-kun ZHANG ; Ben-yu JIANG ; Xiu-qing CHEN ; Jie MI
Chinese Journal of Preventive Medicine 2006;40(2):113-115
OBJECTIVETo explore the reliability and validity of digital pulse wave analyzing method in evaluating arterial compliance in population-based study.
METHODSAll 415 adults (132 men and 283 women) aged 20 to 86 years old were selected from urban (220 persons) and rural (195 persons) areas, respectively by a stratified randomly sampling method. Arterial compliance, evaluated by stiffness index (SI), was measured by using digital pulse wave analyzing method from the Pulse trace machine (Micro medical, London), and the SI value was determined accordingly.
RESULTSIn the study on both repeatability and stability, there was a perfect correlation between the frequent measurements for one individual either on one occasion or on two 40-days-apart occasions. The SI values were not significantly different between the urban and the rural, men and women. Multiple stepwise regressions showed that systolic blood pressure and age were positively correlated with SI value, respectively (both P values were less than 0.001). The correlation kept unchanged after taking account of gender, BMI and heart rate. The mean SI values for people aged 20 to 29, 30 to 39, 40 to 49, 50 to 59 and > or = 60 were 7.35, 8.84, 10.41, 10.95 and 12.01 m/s (P < 0.01), respectively.
CONCLUSIONSBoth systolic blood pressure and age should be contributed as the main influencing factors of arterial compliance. Digital pulse wave analyzing method is a preferable measurement in evaluating arterial compliance in population-based study due to its better repeatability and stability.
Adult ; Aged ; Aged, 80 and over ; Arteries ; physiopathology ; Arteriosclerosis ; epidemiology ; physiopathology ; China ; epidemiology ; Compliance ; Female ; Humans ; Male ; Middle Aged ; Pulse ; methods ; Rural Population ; Sampling Studies ; Urban Population
5. Study on rat small intestinal absorption characteristics of gallic acid based on single-pass perfusion model
Zhen-Zhen CHENG ; Ben-Hong ZHOU ; Shan JIANG ; Dan JIN ; Zhen-Zhen CHENG ; Ben-Hong ZHOU ; Kuang-Yu LI
Chinese Pharmacological Bulletin 2021;37(5):669-673
Aim To investigate the absorption characteristics of gallic acid in the intestine, and to provide a theoretical basis for improving the bioavailability of tannins. Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC to determine the concentration of gallic acid. The absorption rate constant Ka and effective apparent permeability coefficient Peff of gallic acid in each intestinal segment were calculated. The effects of different intestinal segments, drug concentrations, pH value, P-glycoprotein (P-gp), and multidrug resistance protein2 (MRP2) on intestinal absorption were assessed. Results The absorption rate constant (Ka) of gallic acid decreased following the sequence of jejunum > duodenum > ileum ≈ colon. With the increase of drug concentration, there was no significant difference in the absorption of gallic acid. The acidic environment (pH 5. 5) was conducive to the absorption of gallic acid. After the addition of P-gp and MRP2 inhibitors, the absorption of gallic acid was significantly different from that without P-gp and MRP2 inhibitors (P < 0. 05). Conclusions Gallic acid can be well absorbed in the intestine of rats, and is best absorbed in jejunum. The absorption mechanism is determined to be passive diffusion. The gallic acid absorption process is affected by the efflux of P-gp and MRP2, which may be the P-gp and MRP2 substrates.
6.Gentiopicroside ameliorates LKB1/AMPK-dependent alcoholic hepatosteatosis via P2x7R-NLRP3 inflammasome
Xia LI ; Yu ZHANG ; Kai-Li XIA ; Min JIANG ; Ben-Wen CUI ; Yan-Ling WU ; Ji-Xing NAN ; Li-Hua LIAN
Chinese Journal of Pharmacology and Toxicology 2018;32(4):265-266
OBJECTIVE Regulating P2x7R- NLRP3 inflammasome activation might be a potentialtherapeutic strategy to treat alcoholic hepatosteatosis. We investigated whether this process would be modulated by gentiopicroside (GPS), which is attributed to the bitterness of gentian root extract. METHODSAn in vivo model was established by intragastrically treating mice with ethanol, and an in vitro modelwas created by treating HepG2 cells with ethanol or treating RAW 264.7 macrophages and murinebone marrow- derived macrophages (BMDMs) with lipopolysaccharides (LPS) plus adenosine triphos-phate (ATP). RESULTS In alcoholic hepatosteatotic mice model, GPS decreased serum aminotrans-ferase and triglyceride accumulation. GPS regulated sterol regulatory element-binding protein-1 (Srebp1),peroxisome proliferators- actived receptors α (PPARα) and acetyl CoA carboxylase (ACC) expressionvia elevating liver kinase B1 (LKB1)/AMP-activated Kinase (AMPK). Suppression of nucleotide-bindingoligomerization domain-like receptor protein 3 (NLRP3), caspase-1 and expression by GPS resulted inthe inhibition of interleukin-1β (IL-1β) production. In ethanol-exposed HepG2 cells, GPS reduced lipo-genesis and promoted lipid oxidation via P2x7R- NLRP3 inflammasome activation. P2x7R silencingenhanced AMPK activity, and reduced Srebp1 expression in ethanol-treated hepatocytes. GPS down-regulated P2x7R-mediated inflammatory response to extracellular ATP in LPS-primed RAW 264.7 macro-phages and BMDMs. Additionally, P2x7R deficiency attenuated IL- 1β cleavage in RAW 264.7 macro-phages, and GPS further suppressed IL-1β cleavage. CONCLUSION Activation of LKB1/AMPK signalingby GPS might be mediated by P2x7R-NLRP3 inflammasome, suggesting a therapeutic utility of P2x7Rblockade in alcoholic hepatosteatosis treatment.
7.Pleurotus citrinopileatus alleviates alcohol-induced fatty liver via upregulating AMPK signaling
Ben-Wen CUI ; Yu ZHANG ; Xia LI ; Kai-Li XIA ; Min JIANG ; Yan-Ling WU ; Ji-Xing NAN ; Li-Hua LIAN
Chinese Journal of Pharmacology and Toxicology 2018;32(4):276-276
OBJECTIVE The current study was designed to investigate the anti-steatosis effect of Pleurotus citrinopileatus extract (PC) and the underlying mechanism in vivo and in vitro. METHODS Acute and chronic alcoholic hepatosteatosis murine models and ethanol-treated HepG2 cells were applied. RESULTS In vitro,the anti-steatosis effect of PC was further confirmed via Nile red staining in HepG2 cells treated with ethanol.Both of acute and chronic alcohol-induced mice hepatosteatosis model,PC decreased serum aminotransferase and triglyceride accumulation. Upregulated sterol-regulatory element binding protein1(Srebp1),purinergic ligand-gated ion channel 7receptor(P2X7R)and downregulated sirtuin1 (SIRT1), adenosine 5′-monophosphate (AMP)-activated protein kinase α (AMPKα) caused by acute and chronic alcohol intake were modulated by PC.In ethanol-exposed HepG2 cells,PC reduced lipid accumulation in a concentration-dependent manner and exhibited superior ability in controlling lipid accumulation compared with metformin. CONCLUSION PC could abolish hepatic lipid accumulation through regulating SIRT1-AMPKα signaling in acute and chronic alcohol-induced hepatic steatosis.
8.Dihydroquercetin ameliorates alcoholic liver steatosis through P2x7R-NLRP3 inflammasome pathway
Yu ZHANG ; Xia LI ; Kai-Li XIA ; Min JIANG ; Ben-Wen CUI ; Yan-Ling WU ; Ji-Xing NAN ; Li-Hua LIAN
Chinese Journal of Pharmacology and Toxicology 2018;32(4):338-339
OBJECTIVE Dihydroquercetin(TAX)is the most abundant dihydroflavone found in on-ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas-trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha-nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1)and Acetyl CoA Carboxylase (ACC) expression via elevating Liver Kinase B1 (LKB1)/ AMP-activated Kinase (AMPK) phosphorylation. Also, TAX upregulated SIRT1 expression, which suppressed by ethanal intake. Suppression of Purinergic 2X7 receptor (P2x7R), nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)and Cysteine protease-1(caspase-1)cleavage by TAX resulted in the inhibi-tion of Interleukin-1β(IL-1β) production and release. Additionally, TAX reduced lipogenesis and pro-moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides (LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells. P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca-pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.
9.Correlation between serum neuron specific enolase level and psychological status of patients with cerebral concussion
Peng-Zhou ZHAO ; Jiang-Bing LUO ; Jing-Lun WU ; Ying-Xiong OU ; Ben-Sheng YANG ; Rui-Tian YU ; Sheng FANG
Chinese Journal of Neuromedicine 2013;12(8):849-851
Objective To study the correlation between the changes of serum neuron specific enolase (NSE) level and psychological statuses in patients with cerebral concussion.Methods Forty patients with cerebral concussion,admitted to our hospital from January 2012 to December 2012,were chosen in our study as experimental group,and other 40 healthy controls performed physical examination in our Physical Examination Center at the same period were chosen.The serum NSE level in the two groups was determined by enzyme-linked immunosorbent assay (ELISA); Symptom Checklist 90 (SCL-90) scale was performed in 40 patients at different times after injury,and these data were compared with those from the national norm; the correlation between the changes of serum NSE level and SCL-90 scores was analyzed.Results The serum NSE level in the experimental group 1 d after the injury was obviously higher than that in the control group (P<0.05); 3 and 7 d after the injury,the serum NSE level in the experimental group was close to normal level,which showed no significant differece as compared with that in the control group (P>0.05).The SCL-90 scores in the experiemtal group 1,3 and 7 d after injury was signficantly higher than that of the national norm (P<0.05).Positive corelation was noted between serum NSE level and SCL-90 scores 1 and 3 d after injury (r=0.498,P=0.001; r=0.418,P=0.007);however,negative corelation was noted btween the two 7 d after injury (r=0.213,P=0.186).Conclusion Different corelation can be noted between serum NSE level and SCL-90 scores at different time points;combined application of serum NSE level and SCL-90 scores can promote the diagnosis and treatment of patients with brain concussion.
10.A prospective cohort study on human immunodeficiency virus and syphilis seroconversion among injecting drug users.
Lu YIN ; Guang-ming QIN ; Yu-hua RUAN ; Li ZHANG ; Qin-ning HAO ; Xian-huang CHEN ; Zheng-qing JIANG ; Ben-li SONG ; Shi-zhu LIU ; Xiao-yun CAO ; Chun HAO ; Kang-lin CHEN ; Yi-ming SHAO
Chinese Journal of Epidemiology 2006;27(4):293-297
OBJECTIVETo study the rate of human immunodeficiency virus (HIV) seroconversion, HIV transmission and related risk factors among injecting drug users (IDUs) in an area of Sichuan province.
METHODSIn November 2002, a community-based baseline survey was conducted to recruit 333 HIV-seronegative IDUs for a prospective cohort study in Xichang county of Sichuan province, China. Follow-up visits were carried out every 6 months to study the situation of drug use, sexual behaviors of the IDUs and blood specimens were collected to test for antibodies against HIV and syphilis.
RESULTSDuring a 24-month follow-up period, cohort retention rate and HIV incidence were 75.7% and 2.53 per 100 person-years [95% confidence interval (CI): 1.10-3.97)], respectively. Multivariate Poisson regression model showed that risk factors which were significantly associated with HIV seroconversion would include: ethnicity (RR = 12.42; 95% CI: 2.72-56.74, P = 0.0012) and needle or syringe sharing in the past 3 months (RR = 4.06; 95% CI: 1.29-12.81, P = 0.0168). Syphilis seroconversion in this cohort was 4.71 per 100 person-years (95% CI: 2.59-6.82). In multivariate Poisson regression being female (RR = 4.42; 95% CI: 1.78-10.99, P = 0.0014) appeared to be the only factor which was significantly associated with syphilis seroconversion.
CONCLUSIONOur study results showed that there was a rapid transmission of HIV and syphilis among IDUs in Sichuan province, suggesting that effective intervention should be urgently taken.
Cohort Studies ; HIV Seropositivity ; immunology ; transmission ; Humans ; Prospective Studies ; Risk Factors ; Sexual Behavior ; Substance Abuse, Intravenous ; Syphilis ; immunology ; transmission