AIM:To compare postoperative complications and prognosis of esophageal squamous cell carcinoma patients treated with different routes of reconstruction. METHODS:After obtaining approval from the Medical Ethics Committ...AIM:To compare postoperative complications and prognosis of esophageal squamous cell carcinoma patients treated with different routes of reconstruction. METHODS:After obtaining approval from the Medical Ethics Committee of the Sun Yat-Sen University Cancer Center, we retrospectively reviewed data from 306 consecutive patients with histologically diagnosed esophageal squamous cell carcinoma who were treated between 2001 and 2011. All patients underwent radical McKeown-type esophagectomy with at least two-field lymphadenectomy. Regular follow-up was performed in our outpatient department. Postoperative complica-tions and long-term survival were analyzed by treatment modality, baseline patient characteristics, and operative procedure. Data from patients treated via the retrosternal and posterior mediastinal routes were compared. RESULTS:The posterior mediastinal and retrosternal reconstruction routes were employed in 120 and 186 patients, respectively. Pulmonary complications were the most common complications experienced during the postoperative period (46.1% of all patients; 141/306). Compared to the retrosternal route, the posterior mediastinal reconstruction route was associated with a lower incidence of anastomotic stricture (15.8% vs 27.4%, P = 0.018) and less surgical bleeding (242.8 ± 114.2 mL vs 308.2 ± 168.4 mL, P < 0.001). The median survival time was 26.8 mo (range:1.6-116.1 mo). Upon uni/multivariate analysis, a lower preoperative albumin level (P = 0.009) and a more advanced pathological stage (pT; P = 0.006; pN; P < 0.001) were identified as independent factors predicting poor prognosis. The reconstruction route did not influence prognosis (P = 0.477). CONCLUSION:The posterior mediastinal route of reconstruction reduces incidence of postoperative complications but does not affect survival. This route is recommended for resectable esophageal squamous cell carcinoma.展开更多
WT5”BZ] To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. [WT5”BX]Methods.[WT5”BZ] Thymocytes from Kunming mice exposed to whole body irradiation(WBI) with ...WT5”BZ] To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. [WT5”BX]Methods.[WT5”BZ] Thymocytes from Kunming mice exposed to whole body irradiation(WBI) with different doses of X rays were analyzed for the changes in signal molecules of the phospholipase C phosphatidylinositol biphosphate(PLC IP2) and G protein adenylate cyclase(AC) pathways. [WT5”BX]Results.[WT5”BZ]It was found that[Ca 2+ ] i increased in response to doses within 0 2 Gy which was most marked after 0 075 Gy and the increase was accentuated in the presence of Con A. The changes in CD3 and calcineurin(CN) expression of the thymocytes followed the same pattern as the alterations in [Ca 2+ ] i after LDR. The expression of α,β1 and β2 isoforms of protein kinase C(PKC) was all up regulated after 0 075 Gy with the increase in PKC β1 expression being most marked. The cAMP/cGMP ratio and PKA activity of the thymocytes was lowered after low dose radiation and increased after doses above 0 5 Gy in a dose dependent manner, thus giving rise to J shaped dose response curves. The Ca antagonist TMB 8 and cAMP stimulant cholera toxin suppressed the augmented thymocyte proliferation induced by LDR. [WT5”BX]Conclusion.[WT5”BZ]Data presented in the present paper suggest that activation of the PLC PIP2 signal pathway and suppression of the AC cAMP signal pathway are involved in the stimulation of the thymocytes following WBI with low dose X rays.展开更多
A novel marine active polypeptide （PCF）, isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether ...A novel marine active polypeptide （PCF）, isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether UVB-induced HaCaT cell apoptosis occurs via the mitochondrial pathways Apaf-1/caspase-9 and Smac/XIAP/caspase-3. We then investigated the molecular mechanisms controlling the anti-apoptotic effect of PCE Pre-treatment with PCF and caspase-9 inhibitor significantly inhibited UVB-induced apoptosis in HaCaT cells based on a DNA fragmentation assay and Hoechst 33258 staining The expression of Apaf-1 and the cleavage of procaspase-9 were dose-dependently reduced by 1.42-5.96 mmol/L PCF pretreatment in UVB-irradiated HaCaT cells. This was followed by inhibition of cleavage of procaspase-3, whose activation induced cell apoptosis. Meanwhile, PCF significantly and dose-dependently enhanced the activation of ATPase. Furthermore, we demonstrated that PCF strongly inhibited the release of Smac from the mitochondria to cytosol by reducing the degradation of XIAP dose-dependently. We conclude that the protective effect of PCF against UVB irradiation in HaCaT cells may be attributed to the inhibition of the Apaf-1/caspase-9 and Smac/XIAP/caspase-3 apoptotic signaling pathways.展开更多
Here, we provide data suggesting that the absence of silencing of the ectopic reprogramming factors used to reprogram somatic cells to induced pluripotent stem cells （iPSCs） may predispose iPSCs to genomic instabili...Here, we provide data suggesting that the absence of silencing of the ectopic reprogramming factors used to reprogram somatic cells to induced pluripotent stem cells （iPSCs） may predispose iPSCs to genomic instability. We encourage stem cell scientists to undertake an extensive characterization and standardization of much larger cohorts of iPSC lines in order to set up rigorous criteria to define safe and stable bonafide iPSCs.展开更多
Objective To investigate the effect and underlying mechanism of Qingguang’an Granules(青光安颗粒剂,QGAG)on mitochondrial autophagy(mitophagy)of retinal ganglion cells(RGCs)in rats with chronic ocular hypertension(COH...Objective To investigate the effect and underlying mechanism of Qingguang’an Granules(青光安颗粒剂,QGAG)on mitochondrial autophagy(mitophagy)of retinal ganglion cells(RGCs)in rats with chronic ocular hypertension(COH).Methods Sixty Sprague Dawley(SD)rats,half males and half females,were randomly assigned to three groups:the control,model,and QGAG(2.5 g/kg)groups,with 20 rats in each group.Rats’model of COH was established by cauterizing episcleral veins in the model group and QGAG group.Three weeks after successful modeling,rats in the QGAG group were intra-gastrically administered with QGAG,while rats in the control group and the model group received an equal dose of normal saline.After three months of intragastric administration,intraocular pressure(IOP)of all rats was measured.The mitophagy was monitored by the immunofluorescence method,the mitochondrial membrane potential was measured using the JC-1 method,and the morphological changes of mitophagy in RGCs were observed by transmission electron microscopy.Meanwhile,rat RGCs were labeled using the fluorescent gold method,and RGCs density in each group was calculated.Moreover,RGCs apoptosis was observed by TdT-mediated dUTP Nick-End Labeling(TUNEL)assay.Finally,the expression levels of Parkin,optineurin,microtubule-associated protein 1 light chain 3-Ⅱ/microtubule-associated protein 1 light chain 3-Ⅰ(LC3-Ⅱ/LC3-Ⅰ),recombinant lysosomal associated membrane protein 1(LAMP1),and B-cell lymphoma-2(Bcl-2)in RGCs were determined by Western blot assay.The corresponding mRNAs were detected through quantitative real-time polymerase chain reaction(qRT-PCR).Results The QGAG reduced IOP in COH rats,and inhibited mitophagy and apoptosis of RGCs(P<0.05).Besides,the QGAG significantly increased the expression levels of Parkin and Bcl-2(P<0.05),and inhibited the expression levels of optineurin,LAMP1,and LC3-Ⅱ/LC3-Ⅰ(P<0.05)in RGCs of COH rats.Conclusion The QGAG can inhibit mitophagy in RGCs of COH rats and show a protective effect against optic nerve damage caused by glaucoma,which may be mediated through the mitophagy ubiquitination via the Parkin/PINK1-related pathway.展开更多
Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vi...Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vital role in the pathogenesis of Alzheimer’s disease,and has been found to be implicated in tumor growth and metastasis.Therefore,to understand the relationship between APP and 5-fluorouracil(5-FU)resistance in liver cancer,Cell Counting Kit-8,apoptosis and cell cycle assays,western blotting,and reverse transcription-quantitative polymerase chain reaction(q PCR)analysis were performed.The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated,as compared with that in Bel7402 cells.Through successful construction of APP-silenced(si APP)and overexpressed(OE)Bel7402 cell lines,data revealed that the Bel7402-APP751-OE cell line was insensitive,while the Bel7402-si APP cell line was sensitive to 5-FU in comparison to the matched control group.Furthermore,APP overexpression decreased,while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells.Mechanistically,APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes(B-cell lymphoma-2(Bcl-2)and B-cell lymphoma-extra large(Bcl-xl)).Taken together,these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU,providing a new perspective for drug resistance.展开更多
基金Supported by Science and Technology Project of Guangdong Province, China, No. 2010B031600220 and 2008B030303008
文摘AIM:To compare postoperative complications and prognosis of esophageal squamous cell carcinoma patients treated with different routes of reconstruction. METHODS:After obtaining approval from the Medical Ethics Committee of the Sun Yat-Sen University Cancer Center, we retrospectively reviewed data from 306 consecutive patients with histologically diagnosed esophageal squamous cell carcinoma who were treated between 2001 and 2011. All patients underwent radical McKeown-type esophagectomy with at least two-field lymphadenectomy. Regular follow-up was performed in our outpatient department. Postoperative complica-tions and long-term survival were analyzed by treatment modality, baseline patient characteristics, and operative procedure. Data from patients treated via the retrosternal and posterior mediastinal routes were compared. RESULTS:The posterior mediastinal and retrosternal reconstruction routes were employed in 120 and 186 patients, respectively. Pulmonary complications were the most common complications experienced during the postoperative period (46.1% of all patients; 141/306). Compared to the retrosternal route, the posterior mediastinal reconstruction route was associated with a lower incidence of anastomotic stricture (15.8% vs 27.4%, P = 0.018) and less surgical bleeding (242.8 ± 114.2 mL vs 308.2 ± 168.4 mL, P < 0.001). The median survival time was 26.8 mo (range:1.6-116.1 mo). Upon uni/multivariate analysis, a lower preoperative albumin level (P = 0.009) and a more advanced pathological stage (pT; P = 0.006; pN; P < 0.001) were identified as independent factors predicting poor prognosis. The reconstruction route did not influence prognosis (P = 0.477). CONCLUSION:The posterior mediastinal route of reconstruction reduces incidence of postoperative complications but does not affect survival. This route is recommended for resectable esophageal squamous cell carcinoma.
基金This work was supported by a grant from NSFC (No.39570188)
文摘WT5”BZ] To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. [WT5”BX]Methods.[WT5”BZ] Thymocytes from Kunming mice exposed to whole body irradiation(WBI) with different doses of X rays were analyzed for the changes in signal molecules of the phospholipase C phosphatidylinositol biphosphate(PLC IP2) and G protein adenylate cyclase(AC) pathways. [WT5”BX]Results.[WT5”BZ]It was found that[Ca 2+ ] i increased in response to doses within 0 2 Gy which was most marked after 0 075 Gy and the increase was accentuated in the presence of Con A. The changes in CD3 and calcineurin(CN) expression of the thymocytes followed the same pattern as the alterations in [Ca 2+ ] i after LDR. The expression of α,β1 and β2 isoforms of protein kinase C(PKC) was all up regulated after 0 075 Gy with the increase in PKC β1 expression being most marked. The cAMP/cGMP ratio and PKA activity of the thymocytes was lowered after low dose radiation and increased after doses above 0 5 Gy in a dose dependent manner, thus giving rise to J shaped dose response curves. The Ca antagonist TMB 8 and cAMP stimulant cholera toxin suppressed the augmented thymocyte proliferation induced by LDR. [WT5”BX]Conclusion.[WT5”BZ]Data presented in the present paper suggest that activation of the PLC PIP2 signal pathway and suppression of the AC cAMP signal pathway are involved in the stimulation of the thymocytes following WBI with low dose X rays.
基金Supported by the National Natural Science Foundation of China (No 30471458)the Natural Science Foundation of Shandong Province,China (No Z2007c09)
文摘A novel marine active polypeptide （PCF）, isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether UVB-induced HaCaT cell apoptosis occurs via the mitochondrial pathways Apaf-1/caspase-9 and Smac/XIAP/caspase-3. We then investigated the molecular mechanisms controlling the anti-apoptotic effect of PCE Pre-treatment with PCF and caspase-9 inhibitor significantly inhibited UVB-induced apoptosis in HaCaT cells based on a DNA fragmentation assay and Hoechst 33258 staining The expression of Apaf-1 and the cleavage of procaspase-9 were dose-dependently reduced by 1.42-5.96 mmol/L PCF pretreatment in UVB-irradiated HaCaT cells. This was followed by inhibition of cleavage of procaspase-3, whose activation induced cell apoptosis. Meanwhile, PCF significantly and dose-dependently enhanced the activation of ATPase. Furthermore, we demonstrated that PCF strongly inhibited the release of Smac from the mitochondria to cytosol by reducing the degradation of XIAP dose-dependently. We conclude that the protective effect of PCF against UVB irradiation in HaCaT cells may be attributed to the inhibition of the Apaf-1/caspase-9 and Smac/XIAP/caspase-3 apoptotic signaling pathways.
文摘Here, we provide data suggesting that the absence of silencing of the ectopic reprogramming factors used to reprogram somatic cells to induced pluripotent stem cells （iPSCs） may predispose iPSCs to genomic instability. We encourage stem cell scientists to undertake an extensive characterization and standardization of much larger cohorts of iPSC lines in order to set up rigorous criteria to define safe and stable bonafide iPSCs.
基金Regional Fund Project of National Natural Science Foundation of China(81860870)China Postdoctoral Science Foundation(2018M640754)+3 种基金Hunan Natural Science Foundation Project(2020JJ5436)Program of Chinese Medicine Innovative-Backbone Talents of China(Xiang CM[2019]67)Hunan Province“225”Program for Cultivation of High-level Health Talents(Xiang CM[2019]196)Open Fund Project of Hunan Provincial Engineering Technology Research Center for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases and Visual Function Protection with Chinese Medicine(2018YZD02).
文摘Objective To investigate the effect and underlying mechanism of Qingguang’an Granules(青光安颗粒剂,QGAG)on mitochondrial autophagy(mitophagy)of retinal ganglion cells(RGCs)in rats with chronic ocular hypertension(COH).Methods Sixty Sprague Dawley(SD)rats,half males and half females,were randomly assigned to three groups:the control,model,and QGAG(2.5 g/kg)groups,with 20 rats in each group.Rats’model of COH was established by cauterizing episcleral veins in the model group and QGAG group.Three weeks after successful modeling,rats in the QGAG group were intra-gastrically administered with QGAG,while rats in the control group and the model group received an equal dose of normal saline.After three months of intragastric administration,intraocular pressure(IOP)of all rats was measured.The mitophagy was monitored by the immunofluorescence method,the mitochondrial membrane potential was measured using the JC-1 method,and the morphological changes of mitophagy in RGCs were observed by transmission electron microscopy.Meanwhile,rat RGCs were labeled using the fluorescent gold method,and RGCs density in each group was calculated.Moreover,RGCs apoptosis was observed by TdT-mediated dUTP Nick-End Labeling(TUNEL)assay.Finally,the expression levels of Parkin,optineurin,microtubule-associated protein 1 light chain 3-Ⅱ/microtubule-associated protein 1 light chain 3-Ⅰ(LC3-Ⅱ/LC3-Ⅰ),recombinant lysosomal associated membrane protein 1(LAMP1),and B-cell lymphoma-2(Bcl-2)in RGCs were determined by Western blot assay.The corresponding mRNAs were detected through quantitative real-time polymerase chain reaction(qRT-PCR).Results The QGAG reduced IOP in COH rats,and inhibited mitophagy and apoptosis of RGCs(P<0.05).Besides,the QGAG significantly increased the expression levels of Parkin and Bcl-2(P<0.05),and inhibited the expression levels of optineurin,LAMP1,and LC3-Ⅱ/LC3-Ⅰ(P<0.05)in RGCs of COH rats.Conclusion The QGAG can inhibit mitophagy in RGCs of COH rats and show a protective effect against optic nerve damage caused by glaucoma,which may be mediated through the mitophagy ubiquitination via the Parkin/PINK1-related pathway.
基金Project supported by the International Science&Technology Cooperation Program of China(No.2016G02).
文摘Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vital role in the pathogenesis of Alzheimer’s disease,and has been found to be implicated in tumor growth and metastasis.Therefore,to understand the relationship between APP and 5-fluorouracil(5-FU)resistance in liver cancer,Cell Counting Kit-8,apoptosis and cell cycle assays,western blotting,and reverse transcription-quantitative polymerase chain reaction(q PCR)analysis were performed.The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated,as compared with that in Bel7402 cells.Through successful construction of APP-silenced(si APP)and overexpressed(OE)Bel7402 cell lines,data revealed that the Bel7402-APP751-OE cell line was insensitive,while the Bel7402-si APP cell line was sensitive to 5-FU in comparison to the matched control group.Furthermore,APP overexpression decreased,while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells.Mechanistically,APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes(B-cell lymphoma-2(Bcl-2)and B-cell lymphoma-extra large(Bcl-xl)).Taken together,these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU,providing a new perspective for drug resistance.
