The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most commo...The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most common malignant tumors worldwide and one of the leading causes of death caused by cancer in China. Hepatocarcinogenesis is a very complex biological process associated with many environmental risk factors and factors in heredity, including abnormal activation of cellular and molecular signaling pathways such as Wnt/β-catenin, hedgehog, MAPK, AKT, and ERK signaling pathways, and the balance between the activation and inactivation of the proto-oncogenes and anti-oncogenes, and the differentiation of liver cancer stem cells. Molecule-targeted therapy, a new approach for the treatment of liver cancer, blocks the growth of cancer cells by interfering with the molecules required for carcinogenesis and tumor growth, making it both specific and selective. However, there is no one drug completely designed for liver cancer, and further development in the research of liver cancer targeted drugs is now almost stagnant. The purpose of this review is to discuss recent advances in our understanding of the molecular mechanisms underlying the development of HCC and in the development of novel strategies for cancer therapeutics.展开更多
Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury.High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to...Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury.High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma.In this study,we established an oligodendrocyte(OLN-93 cell line)model of ferroptosis induced by RSL-3,an inhibitor of glutathione peroxidase 4(GPX4).RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde.RSL-3 also inhibited the main antiferroptosis pathway,i.e.,SLC7A11/glutathione/glutathione peroxidase 4(xCT/GSH/GPX4),and downregulated acyl-coenzyme A synthetase long chain family member 4.Furthermore,we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis.Liproxstatin-1 was more potent than edaravone or deferoxamine.Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation,but also restored the expression of GSH,GPX4 and ferroptosis suppressor protein 1.These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes,and that liproxstatin-1 is a potent inhibitor of ferroptosis.Therefore,liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.展开更多
Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocyt...Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocytes. Loss of nephrin during the development leads to the congenital nephrotic syndrome in children. Reduction of nephrin expression is often observed in adult kidney diseases including diabetic nephropathy and HIV-associated nephropathy. The critical role of nephrin has been confirmed by different animal models with nepbrin knockout and knockdown. Recent studies demonstrate that knockdown of nephrin expression in adult mice aggravates the progression of＇ unilateral nephrectomy and Adriamycin-induced kidney disease In addition to its critical role in maintaining normal glomerular filtration unit in the kidney, nephrin is also expressed in other organs. However, the exact role of nephrin in kidney and extra-renal organs has not been well characterized. Future studies are required to determine whether nephrin could be developed as a drug target to treat patients with kidney disease.展开更多
AIM To explore the induction effects and mechanism of Solanum lyratum Thumb(ST) on human hepatocellularcarcinoma SMMC-7721 cells through the mitochondrial pathway.METHODS The experiments were conducted on three groups...AIM To explore the induction effects and mechanism of Solanum lyratum Thumb(ST) on human hepatocellularcarcinoma SMMC-7721 cells through the mitochondrial pathway.METHODS The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine m RNA expression of Fas, Fas L, caspase-8, caspase-3, p53 and Bcl-2 genes.RESULTS Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased(P<0.05). Besides, the m RNA expression of Fas L and Bcl-2 significantly decreased(P<0.05) while the m RNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group.CONCLUSION ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated Fas L and Bcl-2 in the mitochondrial pathway.展开更多
文摘The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most common malignant tumors worldwide and one of the leading causes of death caused by cancer in China. Hepatocarcinogenesis is a very complex biological process associated with many environmental risk factors and factors in heredity, including abnormal activation of cellular and molecular signaling pathways such as Wnt/β-catenin, hedgehog, MAPK, AKT, and ERK signaling pathways, and the balance between the activation and inactivation of the proto-oncogenes and anti-oncogenes, and the differentiation of liver cancer stem cells. Molecule-targeted therapy, a new approach for the treatment of liver cancer, blocks the growth of cancer cells by interfering with the molecules required for carcinogenesis and tumor growth, making it both specific and selective. However, there is no one drug completely designed for liver cancer, and further development in the research of liver cancer targeted drugs is now almost stagnant. The purpose of this review is to discuss recent advances in our understanding of the molecular mechanisms underlying the development of HCC and in the development of novel strategies for cancer therapeutics.
基金supported by the National Natural Science Foundation of China,Nos.81672171(to XY),81972074(to XY),81930070(to SQF),81620108018(to SQF),and 81772342(to GZN)the National Key R&D Program of China,No.2019YFA0112100(to SQF)the Natural Science Foundation of Tianjin of China,No.19JCZDJC34900(to XY)。
文摘Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury.High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma.In this study,we established an oligodendrocyte(OLN-93 cell line)model of ferroptosis induced by RSL-3,an inhibitor of glutathione peroxidase 4(GPX4).RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde.RSL-3 also inhibited the main antiferroptosis pathway,i.e.,SLC7A11/glutathione/glutathione peroxidase 4(xCT/GSH/GPX4),and downregulated acyl-coenzyme A synthetase long chain family member 4.Furthermore,we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis.Liproxstatin-1 was more potent than edaravone or deferoxamine.Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation,but also restored the expression of GSH,GPX4 and ferroptosis suppressor protein 1.These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes,and that liproxstatin-1 is a potent inhibitor of ferroptosis.Therefore,liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.
文摘Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocytes. Loss of nephrin during the development leads to the congenital nephrotic syndrome in children. Reduction of nephrin expression is often observed in adult kidney diseases including diabetic nephropathy and HIV-associated nephropathy. The critical role of nephrin has been confirmed by different animal models with nepbrin knockout and knockdown. Recent studies demonstrate that knockdown of nephrin expression in adult mice aggravates the progression of＇ unilateral nephrectomy and Adriamycin-induced kidney disease In addition to its critical role in maintaining normal glomerular filtration unit in the kidney, nephrin is also expressed in other organs. However, the exact role of nephrin in kidney and extra-renal organs has not been well characterized. Future studies are required to determine whether nephrin could be developed as a drug target to treat patients with kidney disease.
基金the Guangxi Key Disciplines(Pathogen Biology)[2013]16,Key Laboratory Cultivation Base of Universities in Guangxi(Guangxi Education Research[2014]6)the Science and Technology Research Projects of Universities in Guangxi in 2014,No.YB2014307+1 种基金the Guangxi Natural Science Fund Project,No.2013GXNSFAA019249,No.2014GXNSFBA118148the Scientific Research Project of The Department of Education of Guangxi Zhuang Autonomous Region,No.200810LX327
文摘AIM To explore the induction effects and mechanism of Solanum lyratum Thumb(ST) on human hepatocellularcarcinoma SMMC-7721 cells through the mitochondrial pathway.METHODS The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine m RNA expression of Fas, Fas L, caspase-8, caspase-3, p53 and Bcl-2 genes.RESULTS Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased(P<0.05). Besides, the m RNA expression of Fas L and Bcl-2 significantly decreased(P<0.05) while the m RNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group.CONCLUSION ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated Fas L and Bcl-2 in the mitochondrial pathway.
