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This study explored the protective effect of atractylenolide Ⅰ(AO-Ⅰ) against acetaminophen(APAP)-induced acute liver injury(ALI) in mice and its underlying mechanism. C57 BL/6 J mice were randomly divided into a control group, an APAP group(500 mg·kg~(-1)), a low-dose combination group(500 mg·kg~(-1) APAP + 60 mg·kg~(-1) AO-Ⅰ), and a high-dose combination group(500 mg·kg~(-1) APAP + 120 mg·kg~(-1) AO-Ⅰ). ALI was induced by intraperitoneal injection of APAP(500 mg·kg~(-1)). AO-Ⅰ by intragastric administration was performed 2 hours before APAP treatment, and the control group received the same dose of solvent by intragastric administration or intraperitoneal injection. The protective effect of AO-Ⅰ against APAP-induced ALI was evaluated by detecting alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in the plasma and H&E staining in liver tissues of mice. The malondialdehyde(MDA) and glutathione(GSH) content and catalase(CAT) activity in mouse liver tissues were detected to evaluate the effect of AO-Ⅰ on APAP-induced oxidative stress in the liver. The proteins in the liver p38 mitogen-activated protein kinase(p38 MAPK), c-jun N-terminal kinase(JNK), and nuclear factor kappa-B p65(NF-κB p65) signaling pathways were measured by Western blot, and the liver inflammatory cytokines interleukin-1β(IL-1β) and interleukin-6(IL-6) were detected by real-time PCR. Compared with the APAP group, the combination groups showed reduced APAP-induced ALT level and liver MDA content, potentiated liver CAT activity, and elevated GSH content. Mechanistically, AO-Ⅰ treatment significantly inhibited APAP-up-regulated MAPK phosphorylation and NF-κB p65, and significantly reduced the transcriptional activities of IL-1β and IL-6, downstream targets of NF-κB p65. AO-Ⅰ can improve APAP-induced ALI and the underlying mechanism is related to the inhibition of the MAPK/NF-κB p65 signaling pathway in APAP-challenged mice.
Subject(s)
Animals , Mice , Acetaminophen/adverse effects , Chemical and Drug Induced Liver Injury/drug therapy , Lactones , NF-kappa B/metabolism , Sesquiterpenes , Signal TransductionABSTRACT
Long non-coding RNAs (lncRNAs) cancer susceptibility candidate 2 (CASC2) has been characterized as atumor suppressor in glioma. Although CASC2 may predict the prognosis of glioma patients, the role andmechanism of CASC2 in human glioblastoma remain to be fully illuminated. Expression of CASC2 and miR18a was detected using RT-qPCR. Cell growth was evaluated by MTT assay, colony formation assay, and flowcytometry; metastasis and epithelial-mesenchymal transition (EMT) were determined with transwell assay andWestern blot, respectively. The target binding between CASC2 and miR-18a was predicted on Starbasesoftware, and confirmed by luciferase reporter assay and RNA immunoprecipitation. Xenograft experimentmeasured tumor growth. As a result, CASC2 was downregulated and miR-18a was upregulated in glioblastomatumor tissues and cells (T98 and A172). Overexpression of CASC2 promoted apoptosis rate and E-cadherinexpression, but suppressed cell viability, colony-forming ability, migration, invasion, and expression ofN-cadherin and Vimentin in T98 and A172 cells, accompanied with tumor growth inhibition in vivo; whereas,silencing of CASC2 exerted the opposite effect on cell growth, metastasis and EMT of T98 and A172 cellsin vitro. However, reintroduction of miR-18a could reverse CASC2 upregulation-mediated suppression onabove cell behaviors in vitro. More importantly, miR-18a was a downstream target for CASC2, and wasnegatively regulated by CASC2. Collectively, this study demonstrated that CASC2 served as tumor suppressorin glioblastoma by inhibiting cell growth, metastasis and EMT both in vitro and in vivo partially via CASC2-miR-18a axis.
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Objective This study was operated to investigate the association between urinary albumin-to-creatinine ratio (UACR) and physical situations as hypertension and prehypertension among women.Methods Blood pressure,height,weight and waist circumference were measured and factors such as cigarette smoking,alcohol intake,family history of hypertension,were investigated.Blood glucose and lipid,serum uric acid,urinary albumin and urinary creatinine were tested on 1796 women aged ≥30 years living in the Jinchang district of Suzhou.Associations between UACR and hypertension as well as prehypertension were analyzed,by using ordinal multinomial logistic regression models.Results The mean levels of UACR were 15.54 (7.67,32.53),9.01 ( 5.45,18.06),7.13 (4.60,12.50 ) mg/g and the rates of higher UACR were 27.57％,13.42％,9.61％ in hypertensive,pre-hypertensive and normotensive subjects,respectively,with significant differences noticed among the three groups (P＜0.05).The average systolic blood pressure/diastolic blood pressure appeared to be 125.3/80.9,128.8/82.7,130.8/84.0 and 135.1/85.9 mm Hg for participants with UACR in the first,second,third and fourth quartile,respectively.The risks of prehypertension or hypertension increased with increasing UACR levels.Dose-response relationship was seen between UACR and risks of prehypertension or hypertension.Multivariable adjusted odds ratios (95％CI) of prehypertension or hypertension in the upper quartiles of UACR were 1.32 ( 1.02,1.70),1.72 ( 1.32,2.24),and 2.37 (1.80,3.11 ),respectively,when compared with the lowest quartile.Conclusion Elevated UACR was associated with both hypertension and prehypertension among women.
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Objective To investigate the association betweenserum nitric oxide and microalbuminuria.Methods Based on a community survey in Jinchang district Suzhou city,a 1 ∶ 2 matched case-control study was performed.A total of 208 cases with microalbuminuria were recruited.The controls were selected from the same community,with the same level of income.After matched with age,gender,waist circumference and fast plasma glucose,a total of 416 controls were selected.Values of serum nitric oxide were tested for all eligible participants.The association between serum nitric oxide level and microalbuminuria were analyzed by using the multivariate conditional logistic regression models.Results The mean level of serum nitric oxide was slightly lower for individuals with microalbuminuria (median,interquartile range:27.75,14.48-42.15 μmol/L) than those without (28.25,17.40-43.45 μ mol/L ).However,the difference was not statistically significant (P=0.316).Results from the multivariable conditional logistic regression model showed that serum nitric oxide level was not associated with microalbuminuria,after adjustment for all the confounders.Compared with the highest level of serum nitric oxide,the odds ratios of microalbuminuria for individuals in the 1 st,2nd and 3rd quartiles were not significantly different,after adjustment for confounders.In pairs with hypertension,the odds of microalbuminuria were 85％ higher for individuals with the lowest level of serum nitric oxide than those with the highest level (OR=1.85,95％ CI:0.96-3.57).Additionally,in pairs without hypertension,the odds of microalbuminuria was just 40％ higher for individuals with the lowest level of serum nitric oxide than those with the highest level (OR=1.40,95％CI:0.58-3.40).Conclusion There was no significant correlation between serum nitric oxide and microalbuminuria in the general population in our study.
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<p><b>OBJECTIVE</b>To investigate the inhibitory activities of caffeoyl glucopyranoses purified from Balanophora japonica Makino on HIV entry and their mechanism.</p><p><b>METHODS</b>HIV-1 Env pseudovirus was used to evaluate the anti-HIV-1 activity of those compounds. ELISA and molecular docking were used to study the mechanism of the actions of the active compounds.</p><p><b>RESULTS</b>We used the HIV-1 Env pseudovirus to test the anti-HIV-1 activity of the six phenolic compounds (final concentration 25 microg/ml), and found that only 1,2,6-Tri-O-caffeoyl-beta-D-glucopyranose (TCGP) and 1,3-Di-O-caffeoyl-4-O-galloyl-beta-D- glucopyranose (DCGGP) could effectively inhibit the entry of HIV-1 Env pseudovirus into the target cells in a dose-dependent manner, with IC(50) values of 5.5-/+0.2 and 5.3-/+0.1 microg/ml, respectively. These two compounds could also blocked the gp41 six-helix bundle formation. Molecular docking analysis suggested that they might bind to the hydrophobic cavity of the gp41 N-trimeric coiled-coil.</p><p><b>CONCLUSION</b>TCGP and DCGGP are potent HIV-1 entry inhibitors targeting gp41 and can serve as lead compounds for developing novel anti-HIV-1 microbicides for prevention of sexual HIV-1 transmission.</p>
Subject(s)
Humans , Anti-HIV Agents , Pharmacology , Balanophoraceae , Chemistry , Cell Line , Gallic Acid , Pharmacology , Glucose , Pharmacology , HIV-1 , Hydrolyzable Tannins , Pharmacology , Plant Extracts , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To develop an objective bioassay for quantitative detection of HIV-induced cell-cell fusion for screening HIV entry inhibitors.</p><p><b>METHODS</b>HL2/3 cells expressing HIV envelope proteins gp120/gp41, Tat, and other HIV proteins were co-cultured with HeLa-CD4-LTR-beta-gal cells expressing CD4 receptor and HIV LTR triggered reporter gene beta-galactosidase. The enzyme activities of beta-galactosidase were detected by a chromogenic substrate, chlorophenol red-beta-galactopyranoside (CPRG). Specific HIV entry inhibitors were used to validate the established detecting method.</p><p><b>RESULTS</b>No syncytium was formed by mixing HL2/3 and HeLa-CD4-LTR-beta-gal cells. However, the membrane could be fused and the Tat expressed by HL2/3 cells could bind to HIV LTR on HeLa-CD4-LTR-beta-gal cells and trigger the expression of beta-galactosidase. CPRG allowed quantitative and sensitive detection of the activity of beta-galactosidase. Further studies showed that HIV entry inhibitors could inhibit the activity of beta-galactosidase in a dose-dependent manner.</p><p><b>CONCLUSION</b>We have developed a simple, cheap, objective and quantitative non-infectious cell-cell fusion bioassay that can be used to screen for anti-HIV agents targeting the virus entry from natural and synthetic compound libraries.</p>