Objective:To explore the changes in the expression of autophagy-related protein BECN1 and tumor-associated macrophage marker CD68 in colorectal cancer and investigate their association with clinicopathological feature...Objective:To explore the changes in the expression of autophagy-related protein BECN1 and tumor-associated macrophage marker CD68 in colorectal cancer and investigate their association with clinicopathological features and prognosis in colorectal cancer patients.Methods:Sixty colorectal cancer patients were selected as study subjects.Immunohistochemistry was used to detect the expression of BECN1 and CD68 in both colorectal cancer tissues and adjacent non-cancerous tissues.Based on immunohistochemistry results,patients were divided into a BECN1 high-expression group(33 cases)and low-expression group(27 cases)and a CD68 high-expression group(33 cases)and low-expression group(27 cases).Survival rates and survival times of the two groups were compared using the Kaplan-Meier survival curve and Log-Rank test.The correlation between BECN1 and CD68 expression in colorectal cancer tissues was analyzed.RT-qPCR was employed to examine changes in macrophage-associated markers after BECN1 interference.Results:Expression levels of BECN1 and CD68 in colorectal cancer tissues were significantly higher than those in adjacent tissues and were positively correlated with the TNM stage.Survival analysis showed that patients in the BECN1 and CD68 high-expression groups had shorter overall survival compared to those in the low-expression group(P<0.05).BECN1 and CD68 levels in colorectal cancer patients were positively correlated(P<0.001).BECN1 interference markedly reduced the expression of macrophage markers and decreased M2 polarization.Conclusion:Abnormal expression of BECN1 and CD68 in colorectal cancer patients is associated with TNM stage and poor prognosis,suggesting that BECN1 and CD68 can serve as important indicators for postoperative prognostic evaluation.展开更多
Background:Salvianolate is a compound mainly composed of salvia magnesium acetate,which is extracted from the Chinese herb Salvia miltiorrhiza.In recent years,salvianolate injection has been widely used in the treatme...Background:Salvianolate is a compound mainly composed of salvia magnesium acetate,which is extracted from the Chinese herb Salvia miltiorrhiza.In recent years,salvianolate injection has been widely used in the treatment of cardiovascular diseases,but the mechanism of how it can alleviate cardiotoxicity remains unclear.Methods:The cardiac injury model was constructed by treatment with doxorubicin(Dox)or azithromycin(Azi)in zebrafish larvae.Heart phenotype,heart rate,and cardiomyocyte apoptosis were observed in the study.RNA-sequencing(RNA-seq)analysis was used to explore the underlying mechanism of salvianolate treatment.Moreover,cardiomyocyte autophagy was assessed by in situ imaging.In addition,the miR-30a/becn1 axis regulation by salvianolate was further investigated.Results:Salvianolate treatment reduced the proportion of pericardial edema,recovered heart rate,and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae.Mechanistically,salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes.The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration;overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes,while becn1 knockdown blocked the effects of salvianolate.In addition,miR-30a,negatively regulated by salvianolate,partially inhibited the cardiac amelioration of salvianolate by targeting becn1 directly.Conclusion:This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.展开更多
文摘目的:检测BECN1、膜型微管相关蛋白1轻链3(LC3B)和雷帕霉素靶蛋白(m TOR)在宫颈鳞状上皮病变中的表达,并探讨其临床意义。方法:免疫组化法及荧光原位杂交技术检测宫颈鳞状上皮病变和正常宫颈组织中自噬相关基因BECN1、LC3B和m TOR的蛋白及m RNA表达情况。结果:宫颈鳞状细胞癌(SCC)组和高级别鳞状上皮内病变(HSIL)组中BECN1和LC3B的蛋白及m RNA表达均明显低于正常宫颈组,m TOR的蛋白及m RNA表达明显高于正常宫颈组,差异均有统计学意义(P<0.01)。低级别鳞状上皮内病变(LSIL)组中,BECN1及LC3B的蛋白表达明显低于正常宫颈组,LC3B m RNA表达明显低于正常宫颈组,m TOR m RNA表达高于正常宫颈组,差异均有统计学意义(P<0.01)。SCC组中,BECN1蛋白表达与临床分期及淋巴结转移有关,LC3B蛋白表达与肿瘤细胞分化程度相关,m TOR蛋白表达则与淋巴结转移相关。SCC组中,LC3B表达与BECN1呈正相关,与m TOR呈负相关。结论:自噬相关基因与宫颈鳞状上皮病变的严重程度有关,推测BECN1、LC3B和m TOR异常表达可能导致病变恶化。
基金National Natural Science Foundation of China Youth Fund Project(82203543)Shandong Provincial Natural Science Foundation Youth Fund Project(ZR2022QH267)+2 种基金Shandong Provincial Innovation Development Joint Fund Project(ZR2023LZL008)Binzhou Medical University Research Start-up Fund Project(50012304458)Shandong Province Medical and Health Science and Technology Project(202309030619)。
文摘Objective:To explore the changes in the expression of autophagy-related protein BECN1 and tumor-associated macrophage marker CD68 in colorectal cancer and investigate their association with clinicopathological features and prognosis in colorectal cancer patients.Methods:Sixty colorectal cancer patients were selected as study subjects.Immunohistochemistry was used to detect the expression of BECN1 and CD68 in both colorectal cancer tissues and adjacent non-cancerous tissues.Based on immunohistochemistry results,patients were divided into a BECN1 high-expression group(33 cases)and low-expression group(27 cases)and a CD68 high-expression group(33 cases)and low-expression group(27 cases).Survival rates and survival times of the two groups were compared using the Kaplan-Meier survival curve and Log-Rank test.The correlation between BECN1 and CD68 expression in colorectal cancer tissues was analyzed.RT-qPCR was employed to examine changes in macrophage-associated markers after BECN1 interference.Results:Expression levels of BECN1 and CD68 in colorectal cancer tissues were significantly higher than those in adjacent tissues and were positively correlated with the TNM stage.Survival analysis showed that patients in the BECN1 and CD68 high-expression groups had shorter overall survival compared to those in the low-expression group(P<0.05).BECN1 and CD68 levels in colorectal cancer patients were positively correlated(P<0.001).BECN1 interference markedly reduced the expression of macrophage markers and decreased M2 polarization.Conclusion:Abnormal expression of BECN1 and CD68 in colorectal cancer patients is associated with TNM stage and poor prognosis,suggesting that BECN1 and CD68 can serve as important indicators for postoperative prognostic evaluation.
基金supported by grants from the National Key R&D Program of China(No.2021YFC2500500)the Program of Shanghai Academic Research Leader(No.22XD1423300)+2 种基金the National Natural Science Foundation of China(No.82370357)the National Natural Science Foundation of China(No.81900217)the National Key Research and Development Program of China(No.2023YFC3606500).
文摘Background:Salvianolate is a compound mainly composed of salvia magnesium acetate,which is extracted from the Chinese herb Salvia miltiorrhiza.In recent years,salvianolate injection has been widely used in the treatment of cardiovascular diseases,but the mechanism of how it can alleviate cardiotoxicity remains unclear.Methods:The cardiac injury model was constructed by treatment with doxorubicin(Dox)or azithromycin(Azi)in zebrafish larvae.Heart phenotype,heart rate,and cardiomyocyte apoptosis were observed in the study.RNA-sequencing(RNA-seq)analysis was used to explore the underlying mechanism of salvianolate treatment.Moreover,cardiomyocyte autophagy was assessed by in situ imaging.In addition,the miR-30a/becn1 axis regulation by salvianolate was further investigated.Results:Salvianolate treatment reduced the proportion of pericardial edema,recovered heart rate,and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae.Mechanistically,salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes.The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration;overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes,while becn1 knockdown blocked the effects of salvianolate.In addition,miR-30a,negatively regulated by salvianolate,partially inhibited the cardiac amelioration of salvianolate by targeting becn1 directly.Conclusion:This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
