OBJECTIVETo investigate anticancer effects of 5-fluorouracil (5-FU) combined with CL, extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma cell line (JEC).

METHODSJEC cells cultured in vitro in the logarithmic growth phase were seeded in the culture plate and divided into the control group (RPMI 1640), the positive group (10(-4) mol/L 5-FU), the CL groups (at the dose of 0.01, 0.1, 1, 10, and 100 microg/mL), and the CL (0.01, 0.1, 1, 10, and 100 microg/mL) combined with 5-FU groups. Effects of 5-FU combined with CL on JEC cell growth were drawn and measured by MTT and growth curves. Effects of CL combined with 5-FU on the JEC cell differentiation was analyzed by detecting the reduction capability of nitrobenzene thiocyanate (NBT) and lactate dehydrogenase (LDH) contents in the cultured medium. Effects of CL combined with 5-FU on the JEC cell apoptosis and cell proliferation cycle were detected by acridine orange (AO)/ethidium bromide (EB) fluorescent staining and flow cytometry (FCM).

RESULTSThe proliferation inhibitory effect of CL combined with 5-FU on JEC cells was enhanced when compared with that of CL or 5-FU alone (P<0.05). The percentages of NBT positive JEC cells and apoptotic JEC cells increased in the 5-FU combined with CL groups when compared with 5-FU group or the CL group alone (P<0.05). The LDH concentration of the JEC cell culture supernate decreased in 5-FU combined with CL groups (P<0.05). Furthermore, the percentage of G0-G1 phase JEC cells treated by 5-FU combined with CL was higher than that of 5-FU or CL alone (P<0.05).

CONCLUSIONCL could enhance anticancer effects of 5-FU. Its mechanisms might be correlated with reinforcing the cytotoxicity of 5-FU, inducing cell differentiation and apoptosis, and inhibiting cell proliferation and division.

Adenocarcinoma ; pathology ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Endometrial Neoplasms ; pathology ; Female ; Fluorouracil ; pharmacology ; Herb-Drug Interactions ; Humans ; Plant Extracts ; pharmacology ; Rosa ; chemistry

The distribution of the ACTH_(1-39)-immunoreactive neurons in the hypotha- lamus of 4 human adults was examined with ABC immunocytochemical method. The results showed that in addition to ACTH_(1-39)-immunoreactive neurons found in the infundibular nucleus of the hypothalamus which were identical with the previous reports, negafivt ACTH_(1-39)immunoreactive neurons were also found in paraventricular and supraoptic nuclei. These cell bodies were round or elliptic in shape. More negative ACTH_(1-39)immunoreactive fibers were seen in the periventricular layer, paraventricular nucleus and dorsal area of supraoptic nucleus.

Aim To investigate the potential mechanism of osthole promoting autophagy in cervical cancer HeLa cells. Methods HeLa cells were treated with various concentrations of Osthole(0,10,20,40,80,160,240,320 mg·L-1). MTT was used to detect cell vitality. Transmission electron microscopy(TEM)was used to observe the morphology of HeLa cells after osthole intervention. Mondane sulfonyl cadaverine(MDC)staining was used to dectect the level of autophagy. Western blot was employed to analyze the expression levels of mitochondrial protein MFN1 and DPR1. JC-1 flourescence probe was applied to detect mitochondrial membrane potential. Flow cytometry was used to deteminet the release of reactive oxygen species(ROS). A transplanted tumor model of cervical cancer was established in vivo in nude mice. Western blot was used to detect the protein expression levels of PINK1,Parkin and LC3Ⅱ/. Results Osthole could inhibit the proliferation of HeLa cells significantly. Transmission electron microscopy showed that typical autophagosomes were formed in HeLa cells after osthole intervention. The fluorescence intensity of MDC was enhanced. The expression of mitochondrial fusion protein MFN1 was down-regulated after HeLa cells pretreated with osthole,and mitochondrial fission protein DRP1 was up-regulated. Mitochondrial membrane potential decreased. ROS production of HeLa cells was increased by flow cytometry,which could be reversed by autophagy inhibitor 3-MA. Tumor weight in nude mice was inhibited by osthole obviously,which might restrain cervical cancer. Western blot result indicated that the key factors of mitochondrial autophagy PINK1,Parkin and LC3Ⅱ/ratio were up-regulated in HeLa cells. Conclusions Osthole could induce autophagy in HeLa cells and its mechanism may be related to ROS production and PINK1/Parkin pathway.

OBJECTIVETo investigate anticancer effects and potential mechanisms of CL, extract of Rosa roxburghii.

METHODIn vitro anticancer effect was observed in Ehrlich's ascites carcinoma (EAC) mice model. Cell toxicity of CL on human endometrial adenocarcinoma cell line JEC (JEC) cells was measured by MTT reduction test and growth curves drawing by trypan blue dye exclusion method. Lactate dehydrogenase (LDH) concentration of cultured medium was detected by auto-biochemistry-meter. Cell differentiation was showed by detection of NBT reduction ability. Apoptosis was showed by AO/EB fluorescent staining and flow cytometer detection. Cell proliferation cycle was detected by flow cytometer.

RESULTComparing with the negative group, life span of EAC mice treated with CL was prolonged (P <0.05), and thymus index and spleen index of them were raised (P <0.05). The inhibitory effect of CL on JEC cells was in concentration-and time-dependent manner. IC50 of CL on JEC cells was 0.05 microg mL(-1) in 96 hours. Growth curves showed right-shift with CL concentration increasing. The number of NBT positive JEC cells increased and the LDH concentration of cultured medium declined with CL increasing. Apoptosis of JEC cells with CL treated was induced in concentration-dependent manner, apoptotic percentage of CL 10 microg mL(-1) on JEC cells was 25.59% in 24 hours. CL arrested JEC cells in G2-M phase (P <0.05).

CONCLUSIONCL has certainly anticancer effects in vivo and in vitro. Anticancer effect of CL in vivo was in relation to enhancing immune function of EAC mice; anticancer mechanisms of CL on JEC cells may be its direct cytotoxic effect, inducing cell apoptosis and inhibiting cell segmentation.

Adenocarcinoma ; metabolism ; pathology ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Ehrlich Tumor ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Mice ; Plants, Medicinal ; chemistry ; Random Allocation ; Rosa ; chemistry

Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.

Objective To assess the value of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) value at 3.0T diffusion tensor imaging (DTI) in glioma grading before operation. Methods DTI was performed on 104 patients with histologically proved glioma. ADC, FA and DWI maps were produced, and ADC, FA value of solid tumors were measured and compared with the WHO classification of gliomas. Results Fifty-eight gliomas were WHO Ⅱ, 25 were WHO Ⅲ and 21 were WHO Ⅳ. The ADC value of WHO Ⅳ (0.81±0.20)×10~(-3)mm~2/s was lower than that of WHO Ⅲ [(1.05±0.30)×10~(-3)mm~2/s] and WHO Ⅱ[(1.26±0.32)×10~(-3)mm~2/s (P=0.008, P＜0.001)]. The ADC value of WHO Ⅲ was lower than that of WHO Ⅱ (P=0.003). The FA value of WHO Ⅳ (0.18±0.06) was higher than that of WHO Ⅱ (0.15±0.06) (P=0.046). No significance of FA was found between WHO Ⅲ (0.15±0.10) and Ⅱ, nor WHO Ⅳ and Ⅲ. Conclusion ADC and FA value can distinguish different grade gliomas. It is useful in deciding the surgical strategy and predicting the patient's prognosis.

OBJECTIVETo investigate anticancer effect and potential mechanism of tanshinone II(A) (Tan II(A)) on human nasopharyngeal carcinoma cell line CNE cells.

METHODAntiproliferative effect of Tan II(A) on CNE cells was evaluated by morphological examination, cell growth curves, colonial assay and MTT assay. Apoptosis detection was carried out using Hoechest 33258 and PI double-dyeing method. Intracellular Ca2+ concentration and mitochondria membrane potential were detected by fluorospectrophotometer. Bad and MT-1A transcript analysis in CNE cells was analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTTan II(A) could inhibit CNE cells proliferation in dose- and time-dependent manner. 50% inhibiting concentration of Tan II(A) on CNE cells in 24, 48, 72 h was 45.7, 24.8, 3.3 mg x L(-2), respectively. Typical apoptotic morphology such as chromatin aggregation was observed in CNE cells with Tan II(A) treated for 24 h, and the apoptotic inducing effect was in a dose-dependent manner. After treated with Tan II(A), intracellular Ca2+ concentration of CNE cells was increased, mitochondria membrane potential of the cells was decreased, relative mRNA level of Bad and MT-1A was up-regulated.

CONCLUSIONTan II(A) had anticancer effect on CNE cells through apoptosis via calcineurin-dependent pathway and MT-1A downregulation.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Metallothionein ; genetics ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Signal Transduction ; drug effects ; bcl-Associated Death Protein ; genetics

Background and Objectives: Acute myocardial infarction (AMI) often occurs suddenly and leads to fatal consequences. Ferroptosis is closely related to the progression of AMI.However, the specific mechanism of ferroptosis in AMI remains unclear. Methods: We constructed a cell model of AMI using AC16 cells under oxygen and glucose deprivation (OGD) conditions and a mice model of AMI using the left anterior descending (LAD) ligation. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide was employed to determine cell viability. The levels of lactate dehydrogenase, creatine kinase, reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and iron were measured using corresponding kits. Dual luciferase reporter gene assay, RNAbinding protein immunoprecipitation, and RNA pull-down were performed to validate the correlations among AC005332.7, miR-331-3p, and cyclin D2 (CCND2). Hematoxylin and eosin staining was employed to evaluate myocardial damage. Results: AC005332.7 and CCND2 were lowly expressed, while miR-331-3p was highly expressed in vivo and in vitro models of AMI. AC005332.7 sufficiency reduced ROS, MDA, iron, and ACSL4 while boosting the GSH and GPX4, indicating that AC005332.7 sufficiency impeded ferroptosis to improve cardiomyocyte injury in AMI. Mechanistically, AC005332.7 interacted with miR-331-3p, and miR-331-3p targeted CCND2. Additionally, miR-331-3p overexpression or CCND2 depletion abolished the suppressive impact of AC005332.7 on ferroptosis in OGD-induced AC16 cells. Moreover, AC005332.7 overexpression suppressed ferroptosis in mice models of AMI. Conclusions AC005332.7 suppressed ferroptosis in OGD-induced AC16 cells and LAD ligation-operated mice through modulating miR-331-3p/CCND2 axis, thereby mitigating the cardiomyocyte injury in AMI, which proposed novel targets for AMI treatment.

Objective To investigate the iufluence of coke oven emissions on workers" blood pressure and electrocardiographic findings,and to provide a basis for the prevention and treatment of cardiovascular diseases.Methods The concentration of coke oven emissions at the bottom,side,and top of coke ovens was determined in a coking plant.A total of 406 coke oven workers were enrolled as exposure group and 201 office staff members were enrolled as control group.Blood pressure and electrocardiographic findings were compared between the two groups,and the multivariate logistic regression analysis was performed to analyze the influencing factors for hypertension and abnormal electrocardiographic findiugs.Results The concentration of coke oven emissions was the highest at the top of coke ovens,followed by the side and bottom of coke ovens,and there was a significant difference between the exposure group and the control group (P＜0.01).The exposure group had significantly higher detection rates of hypertension,abnormal electrocardiographic findings,and abnormal chest X-ray findings than the control group (P＜0.05).The logistic regression analysis showed that high concentration of coke oven emission and age were risk factors for hypertension and abnormal electrocardiographic findings (P＜0.05).The workers exposed to high-concentration coke oven emissions were more likely to experience hypertension and abnormal electrocardiographic findings than those exposed to low-concentration coke oven emissions (OR=1.7 and 1.9).Conclusion Besides lung injury,coke oven emissions also have adverse effects on the cardiovascular system.Therefore,more effective measures are needed to protect the health of coke oven workers.

Objective To investigate the iufluence of coke oven emissions on workers" blood pressure and electrocardiographic findings,and to provide a basis for the prevention and treatment of cardiovascular diseases.Methods The concentration of coke oven emissions at the bottom,side,and top of coke ovens was determined in a coking plant.A total of 406 coke oven workers were enrolled as exposure group and 201 office staff members were enrolled as control group.Blood pressure and electrocardiographic findings were compared between the two groups,and the multivariate logistic regression analysis was performed to analyze the influencing factors for hypertension and abnormal electrocardiographic findiugs.Results The concentration of coke oven emissions was the highest at the top of coke ovens,followed by the side and bottom of coke ovens,and there was a significant difference between the exposure group and the control group (P＜0.01).The exposure group had significantly higher detection rates of hypertension,abnormal electrocardiographic findings,and abnormal chest X-ray findings than the control group (P＜0.05).The logistic regression analysis showed that high concentration of coke oven emission and age were risk factors for hypertension and abnormal electrocardiographic findings (P＜0.05).The workers exposed to high-concentration coke oven emissions were more likely to experience hypertension and abnormal electrocardiographic findings than those exposed to low-concentration coke oven emissions (OR=1.7 and 1.9).Conclusion Besides lung injury,coke oven emissions also have adverse effects on the cardiovascular system.Therefore,more effective measures are needed to protect the health of coke oven workers.