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@#[摘 要] 目的：探讨银杏内酯B（GKB）是否通过阻抑PI3K/Akt/mTOR信号通路抑制胃癌HGC-27细胞的增殖、凋亡、迁移及侵袭。方法：将HGC-27细胞分为对照、GKB低剂量（100 mg/L）、GKB高剂量（200 mg/L）、GKB高剂量（200 mg/L）+740Y-P（PI3K激活剂）、Ly294002（PI3K抑制剂）组。采用MTT、Edu、FCM、Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，qPCR和WB法分别检测各组细胞中PI3K mRNA、Akt mRNA、mTOR mRNA和Ki-67、caspase-3、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白的表达。构建胃癌HGC-27细胞裸鼠移植瘤模型，观察GKB对移植瘤生长的影响，WB法检测移植瘤组织中Ki-67、caspase-3、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白的表达。结果：体外实验结果表明，与对照组相比，GKB低剂量组、GKB高剂量组、Ly294002组HGC-27细胞的增殖活力及细胞增殖率、迁移和侵袭细胞数，PI3K、Akt、mTOR mRNA表达，以及Ki-67、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白表达均显著降低（均P<0.05）；细胞凋亡率、caspase-3蛋白表达均显著升高（均P<0.05）；740Y-P可部分逆转GKB对HGC-27细胞的抑制作用（均P<0.05）。荷瘤裸鼠实验结果显示，GKB可显著抑制HGC-27细胞裸鼠移植瘤的生长（P<0.05），且可下调PI3K/Akt/mTOR通路相关蛋白的表达。结论：GKB可通过阻抑PI3K/Akt/mTOR信号通路而抑制胃癌HGC-27细胞增殖、迁移与侵袭并促进其凋亡。
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Objective@#To analyze the situation of AIDS knowledge and discrimination among freshmen in Chengdu city, and to explore possible effects of AIDS knowledge on discrimination.@*Methods@#A cluster random sampling was employed to investigate 1 053 college students from 11 universities in Chengdu about their HIV/AIDS knowledge and discrimination. The scores of AIDS knowledge and discrimination of students with different characteristics were analyzed, and the influence path of AIDS knowledge on AIDS discrimination were further analyzed based on different peer relationships.@*Results@#The total scores of AIDS knowledge was negatively correlated to AIDS discrimination( r s =-0.13, P <0.01). After adjusting for confounding factors, the total score of AIDS knowledge was associated with the total score of AIDS discrimination( β =-0.12, P <0.01). AIDS knowledge played a role in AIDS discrimination in intimate, general and unfamiliar peer relationships, with standardized path coefficients of -0.20, -0.24 and -0.18 respectively( P <0.01).@*Conclusion@#AIDS knowledge are correlated with discrimination among freshmen under different peer relationships. More anti-AIDS discrimination courses should be added to AIDS education to reduce the students’ fear and stigma of HIV/AIDS patients and related risk groups.
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Background@#Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients.@*Methods@#A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression.@*Results@#Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P < 0.001), and number of metastatic lesions (r = 0.296, P < 0.001). Compared with the non-metastatic and LVD groups, the HVD group showed the highest PSA (104.98 ng/mL, median) and fibrinogen levels (3.39 g/L, median), as well as the largest proportion of Gleason score >7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001).@*Conclusions@#Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.
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BACKGROUND@#Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients.@*METHODS@#A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression.@*RESULTS@#Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P 7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001).@*CONCLUSIONS@#Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.
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Berberine, a constituent of some traditional Chinese medicinal plants, has been reported to have cytotoxicity effects on different human cancer cell lines. There is no available information about the effects and mechanism of action of berberine on human colon cancer cell line HCT-8. In this paper, the cytotoxicity of berberine on HCT-8 cancer cells was investigated by MTT assay, fluorescence microscopy and flow cytometry analysis. Our data revealed that berberine could significantly inhibit the growth of HCT-8 cells in a dose- and time-dependent manner. Morphology of apoptotic cells was studied with acridine orange/ethidium bromide staining. The concentrations of lactate dehydrogenase and both acid and alkaline phosphatases were significantly increased in cell supernatants after berberine treatment, suggesting cell death. Furthermore, flow cytometry analysis showed that berberine could arrest HCT-8 cells at S phase in a time-dependent manner. To further investigate the apoptotic molecular mechanism, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were used. The up-regulated mRNA and/or protein expressions of Fas, FasL, TNF-a, caspase-3 and down-regulation of pro-caspase-3 suggest that the death receptor pathway may be involved in the apoptotic pathway induced by berberine. Decrease of Bcl-2 and increase of Bax in mRNA and/or protein expressions showed that the Bcl-2 family proteins were involved in berberine-induced apoptosis. We also found that berberine-induced apoptosis was associated with an up-regulated expressions of p53 and prohibitin (PHB), and decreased vimentin expression. These results suggest that berberine can suppress cell growth and reduce cell survival by arresting the cell-cycle and by inducing apoptosis of HCT-8 cells.
Subject(s)
Humans , Berberine/pharmacology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Apoptosis , Berberine/metabolism , Cell Cycle , Cell Line, Tumor , Flow Cytometry , L-Lactate Dehydrogenase/metabolism , Medicine, Chinese Traditional , Microscopy, Fluorescence , RNA, Messenger/metabolism , Repressor Proteins/pharmacology , S Phase , Time Factors , Tetrazolium Salts/pharmacology , Thiazoles/pharmacology , /metabolism , Vimentin/metabolism , /metabolismABSTRACT
Autophagy is a major protein degradation pathway that is essential for stress-induced and constitutive protein turnover. Accumulated evidence has demonstrated that amyloid-β (Aβ) protein can be generated in autophagic vacuoles, promoting its extracellular deposition in neuritic plaques as the pathological hallmark of Alzheimer’s disease (AD). The molecular machinery for Aβ generation, including APP, APP-C99 and β-/γ-secretases, are all enriched in autophagic vacuoles. The induction of autophagy can be vividly observed in the brain at early stages of sporadic AD and in an AD transgenic mouse model. Accumulated evidence has also demonstrated a neuroprotective role of autophagy in mediating the degradation of aggregated proteins that are causative of various neurodegenerative diseases. Autophagy is thus widely regarded as an intracellular hub for the removal of the detrimental Aβ peptides and Tau aggregates. Nonetheless, compelling data also reveal an unfavorable function of autophagy in facilitating the production of intracellular Aβ. The two faces of autophagy on the homeostasis of Aβ place it in a very unique and intriguing position in ADpathogenesis. This article briefly summarizes seminal discoveries that are shedding new light on the critical and unique roles of autophagy in AD and potential therapeutic approaches against autophagy-elicited AD.
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To investigate the absorption kinetics characteristics of icariin for various intestinal segments.Methods: To establish the situ intestinal perfusion model and to study the absorption of icariin for various intestinal segments.Results: Icariin was metabolized quickly in the four intestinal segments.The permeability coefficient(P*eff) were(4.27?0.28),(5.25?0.17),(1.99?0.09),(0.80?0.03) at duodenum,jejunum,ileum,colon,respectively.Icariside can be detected in the four intestine segments in rats by HPLC.Conclusion: Icariin is metabolized into icariside,and then icariside can be absorbed.
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Objective To determine levels of serum Leptin,insulin like growth factor-1(IGF-1),interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-?) in newborn infants with hypoxic-ischemic encephalopathy(HIE).Methods The asphyxiated and normal term neonates were included.The HIE group contained 45 cases and control group 20 cases.Serum Leptin,IGF-1,IL-6 and TNF-? levels were measured by a sensitive enzyme-linked immunosorbent assay.Results In asphyxiated term neonates,serum Leptin,IGF-1,IL-6 and TNF-? levels were significantly higher or lower than those in control group(all P
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Objective To explore the relationship of pathological types of lung cancer with sex, age, site, and clinical diagnosis. Methods The data of 1 310 patients with lung cancer diagnosed with fibrobronchoscopy, was retrospectively analyzed. Results ①The preliminary clinical diagnosed lung cancers which were comfirmed by fibrobronchoscopic biopsy later were mainly small cell lung cancer. ②The percentage of squamous carcinoma was significantly greater in male (78.0%) than in female (49.7%), but the percentage of adenocarcinoma was significantly higher in female (38.1%) than in male (13.1%)(P<0.0001). ③Among the patients with lung cancer, 53.7% was from 40 to 59 years old and 40.2% over 60. The average age of male patients (56.9 years old) was significantly greater than that of female (51.1 years old) (P<0.0001). ④ The average age of patients with squamous carcinoma and adenocarcinoma was greater in male than in female, but that with small cell carcinoma and squamous carcinoma was greater in female than in male. ⑤The percentage of male with lung cancer in the left lung (37.3%) was greater than that of female (26.0%), but the female had lung cancer in the right lung (59.7%) while male had (49.3%). The left and right upper lobe was more (45.4%) in male, but the right upper and lower lobe was more(43.3%) in female. Conclusion ①The fibrobronchoscopic examination is very important in the diagnosis of lung cancer. ②The pathological types and sites of lung cancer is different in different sex and age, which provide the exact bases for medical and surgical treatment for lung cancer.
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Objective To explore the relationship of pathological types of lung cancer with sex, age, site, and clinical diagnosis. Methods The data of 1 310 patients with lung cancer diagnosed with fibrobronchoscopy, was retrospectively analyzed. Results ①The preliminary clinical diagnosed lung cancers which were comfirmed by fibrobronchoscopic biopsy later were mainly small cell lung cancer. ②The percentage of squamous carcinoma was significantly greater in male (78.0%) than in female (49.7%), but the percentage of adenocarcinoma was significantly higher in female (38.1%) than in male (13.1%)(P<0.0001). ③Among the patients with lung cancer, 53.7% was from 40 to 59 years old and 40.2% over 60. The average age of male patients (56.9 years old) was significantly greater than that of female (51.1 years old) (P<0.0001). ④ The average age of patients with squamous carcinoma and adenocarcinoma was greater in male than in female, but that with small cell carcinoma and squamous carcinoma was greater in female than in male. ⑤The percentage of male with lung cancer in the left lung (37.3%) was greater than that of female (26.0%), but the female had lung cancer in the right lung (59.7%) while male had (49.3%). The left and right upper lobe was more (45.4%) in male, but the right upper and lower lobe was more(43.3%) in female. Conclusion ①The fibrobronchoscopic examination is very important in the diagnosis of lung cancer. ②The pathological types and sites of lung cancer is different in different sex and age, which provide the exact bases for medical and surgical treatment for lung cancer.