Laparoscopic hepatectomy is now a widely accepted surgical technique in hepatobiliary surgery and is comparably safe and efficient to open hepatectomy[1,2].In liver transplantation,studies have underscored the safety ...Laparoscopic hepatectomy is now a widely accepted surgical technique in hepatobiliary surgery and is comparably safe and efficient to open hepatectomy[1,2].In liver transplantation,studies have underscored the safety of laparoscopic or robot-assisted procedures in donor hepatectomy[3-5].Donors undergoing laparoscopic or robot-assisted hepatectomy experience reduced postoperative complications and shorter recovery periods[6-8].Recently,surgeons in Seoul National University Hospital reported several consecutive living donor liver transplantation(LDLT)with pure laparoscope,hybrid laparoscopic with robotic-assistance,and total robot-assistance[9-11].Following closely,surgeons in King Faisal Specialist Hospital at Saudi Arabia reported 3 fully robotic donor hepatectomy and robotic recipient liver graft implantation[12].However,to the best of our knowledge,the laparoscopic implantation for a full-size liver graft has not been reported.展开更多
AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equ...AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2 w group,n = 6) or 4 wk(Control 4 w group,n = 6) or the MCD diet for 2 wk(MCD 2 w group,n = 6) or 4 wk(MCD 4 w group,n = 6). Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16 s r RNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired. Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium) coprostanoligenes group(P < 0.001 and P < 0.05,respectively) and a significant increase in Ruminococcaceae UCG 014 abundance(P < 0.05) after 2 wk. At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P < 0.05,and P < 0.01,respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.展开更多
BACKGROUND Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide.In clinical trials,Lactobacillus rhamnosus GG ATCC 53013(LGG)has been used to treat diarrhea.However,recent randomized con...BACKGROUND Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide.In clinical trials,Lactobacillus rhamnosus GG ATCC 53013(LGG)has been used to treat diarrhea.However,recent randomized controlled trials(RCTs)found no evidence of a beneficial effect of LGG treatment.AIM To evaluate the efficacy of LGG in treating acute diarrhea in children.METHODS The EMBASE,MEDLINE,PubMed,Web of Science databases,and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for metaanalyses and RCTs.The Cochrane Review Manager was used to analyze the relevant data.RESULTS Nineteen RCTs met the inclusion criteria and showed that compared with the control group,LGG administration notably reduced the diarrhea duration[mean difference(MD)-24.02 h,95%confidence interval(CI)(-36.58,-11.45)].More effective results were detected at a high dose≥1010 CFU per day[MD-22.56 h,95%CI(-36.41,-8.72)]vs a lower dose.A similar reduction was found in Asian and European patients[MD-24.42 h,95%CI(-47.01,-1.82);MD-32.02 h,95%CI(-49.26,-14.79),respectively].A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment[MD-15.83 h,95%CI(-20.68,-10.98)].High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea[MD-31.05 h,95%CI(-50.31,-11.80)]and the stool number per day[MD-1.08,95%CI(-1.87,-0.28)].CONCLUSION High-dose LGG therapy reduces the duration of diarrhea and the stool number per day.Intervention at the early stage is recommended.Future trials are expected to verify the effectiveness of LGG treatment.展开更多
BACKGROUND Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease(ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective mi...BACKGROUND Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease(ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus(P. pentosaceus) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism.AIM To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice.METHODS A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pairfed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus. One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples(liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography–mass spectrometry was used to measure short-chain fatty acid(SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing.RESULTS The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus, and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium, and Clostridium. In contrast, P. pentosaceus administration increased the microbial diversity, restored the relative abundance of Lactobacillus, Pediococcus, Prevotella, Clostridium and Akkermansia and increased propionic acid and butyric acid production by modifying SCFA-producing bacteria. Furthermore, the levels of the tight junction protein ZO-1, mucin proteins(mucin [MUC]-1, MUC-2 and MUC-4) and the antimicrobial peptide Reg3β were increased after probiotic supplementation.CONCLUSION Based on these results, the new strain of P. pentosaceus alleviated ethanol-induced liver injury by reversing gut microbiota dysbiosis, regulating intestinal SCFA metabolism, improving intestinal barrier function, and reducing circulating levels of endotoxin and proinflammatory cytokines and chemokines. Thus, this strain is a potential probiotic treatment for ALD.展开更多
As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse an...As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.展开更多
Dysregulation of dickkopf-related protein 1(DKK1)expression has been reported in a variety of human cancers.We previously reported that DKK1 was upregulated in hepatocellular carcinoma(HCC).However,the role of DKK1 in...Dysregulation of dickkopf-related protein 1(DKK1)expression has been reported in a variety of human cancers.We previously reported that DKK1 was upregulated in hepatocellular carcinoma(HCC).However,the role of DKK1 in HCC remains unclear.This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC.The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(qRT-PCR).DKK1 was silenced or overexpressed in HCC cell lines,and in vitro and in vivo studies were performed.Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues(8/22,36.4%)but upregulated in HCC tissues(48/53,90.6%,cohort 1).Significant upregulation of DKK1 was observed in 57.6%(19/33,cohort 2)of HCC tissues by qRT-PCR,and the expression of DKK1 was associated with tumor size(P=0.024)and tumor number(P=0.019).Genetic depletion of DKK1 impaired the proliferation,colony-forming ability,invasion,and tumor formation of HCC cells(HepG2 and HUH-7).Conversely,forced expression of DKK1 increased the proliferation,colony-forming ability,and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo.Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/β-catenin signaling pathway.These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/β-catenin signaling pathway.展开更多
Retraction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-019-0082-5,published online 06 December 2019 The authors have retracted this article.After publication,concerns were raised regardi...Retraction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-019-0082-5,published online 06 December 2019 The authors have retracted this article.After publication,concerns were raised regarding suspected overlap in the cell images in Figs.2 and 3.Specifically.展开更多
Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor...Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms,this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA,and to explore underlying mechanisms.Methods:We screened out miR-203a,the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.In vitro and in vivo functional experiments were performed to assess its regulatory function.The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study.Results:MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis.The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells.We demonstrated the function of miR-203a in inhibiting HCC cell proliferation,migration,clonogenic capacity,and tumor development in vivo.Furthermore,the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers.In concordance with our study,the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a.We also found that BMI1,a gene maintains the self-renewal capacity of stem cells,showed a significant negative correlation with miR-203a in HCC specimen(p<0.001).Similarly,opposite BMI1 changes after overexpression/knockdown of miR203a were also confirmed in vitro.Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding.Conclusions:HBsAg may promote the development of HCC and tumor stemness by inhibiting miR-203a,resulting in poor prognosis.miR-203a may serve as a crucial treatment target in HBsAg-positive HCC.More explicit mechanistic studies and animal experiments need to be conducted as a next step.展开更多
The original version of this article unfortunately contained a mistake.For Fig.la in p.409,the citation of a reference,as well as the permission to reprint this picture,was missing.The correct version and the correspo...The original version of this article unfortunately contained a mistake.For Fig.la in p.409,the citation of a reference,as well as the permission to reprint this picture,was missing.The correct version and the corresponding reference are given below:(a)Chest computed tomography(CT)image of Patient 1 on admission presents multiple ground-glass opacities distributed in the periphery of inferior lobe of both lungs.Reprinted from Zhang et al.(2020),with kind permission from Springer Nature.展开更多
基金supported by the grant from the Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program(SYS-5010–202305).
文摘Laparoscopic hepatectomy is now a widely accepted surgical technique in hepatobiliary surgery and is comparably safe and efficient to open hepatectomy[1,2].In liver transplantation,studies have underscored the safety of laparoscopic or robot-assisted procedures in donor hepatectomy[3-5].Donors undergoing laparoscopic or robot-assisted hepatectomy experience reduced postoperative complications and shorter recovery periods[6-8].Recently,surgeons in Seoul National University Hospital reported several consecutive living donor liver transplantation(LDLT)with pure laparoscope,hybrid laparoscopic with robotic-assistance,and total robot-assistance[9-11].Following closely,surgeons in King Faisal Specialist Hospital at Saudi Arabia reported 3 fully robotic donor hepatectomy and robotic recipient liver graft implantation[12].However,to the best of our knowledge,the laparoscopic implantation for a full-size liver graft has not been reported.
基金the National Natural Science Foundation of China,No.81330011,No.81790631,and No.81790633the Science Fund for Creative Research Groups of the National Natural Science Foundation of China,No.81721091the National Basic Research Program of China(973 program),No.2013CB531401
文摘AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2 w group,n = 6) or 4 wk(Control 4 w group,n = 6) or the MCD diet for 2 wk(MCD 2 w group,n = 6) or 4 wk(MCD 4 w group,n = 6). Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16 s r RNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired. Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium) coprostanoligenes group(P < 0.001 and P < 0.05,respectively) and a significant increase in Ruminococcaceae UCG 014 abundance(P < 0.05) after 2 wk. At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P < 0.05,and P < 0.01,respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.
基金Supported by the National Natural Science Foundation of China,No.81330011
文摘BACKGROUND Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide.In clinical trials,Lactobacillus rhamnosus GG ATCC 53013(LGG)has been used to treat diarrhea.However,recent randomized controlled trials(RCTs)found no evidence of a beneficial effect of LGG treatment.AIM To evaluate the efficacy of LGG in treating acute diarrhea in children.METHODS The EMBASE,MEDLINE,PubMed,Web of Science databases,and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for metaanalyses and RCTs.The Cochrane Review Manager was used to analyze the relevant data.RESULTS Nineteen RCTs met the inclusion criteria and showed that compared with the control group,LGG administration notably reduced the diarrhea duration[mean difference(MD)-24.02 h,95%confidence interval(CI)(-36.58,-11.45)].More effective results were detected at a high dose≥1010 CFU per day[MD-22.56 h,95%CI(-36.41,-8.72)]vs a lower dose.A similar reduction was found in Asian and European patients[MD-24.42 h,95%CI(-47.01,-1.82);MD-32.02 h,95%CI(-49.26,-14.79),respectively].A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment[MD-15.83 h,95%CI(-20.68,-10.98)].High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea[MD-31.05 h,95%CI(-50.31,-11.80)]and the stool number per day[MD-1.08,95%CI(-1.87,-0.28)].CONCLUSION High-dose LGG therapy reduces the duration of diarrhea and the stool number per day.Intervention at the early stage is recommended.Future trials are expected to verify the effectiveness of LGG treatment.
基金Supported by National Natural Science Foundation of China,No. 81330011,No. 81790631,No. 81570512,and No. 81790633Science Fund for Creative Research Groups of the National Natural Science Foundation of China,No. 81121002National Key Research and Development Program of China,No. 2018YFC2000500。
文摘BACKGROUND Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease(ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus(P. pentosaceus) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism.AIM To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice.METHODS A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pairfed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus. One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples(liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography–mass spectrometry was used to measure short-chain fatty acid(SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing.RESULTS The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus, and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium, and Clostridium. In contrast, P. pentosaceus administration increased the microbial diversity, restored the relative abundance of Lactobacillus, Pediococcus, Prevotella, Clostridium and Akkermansia and increased propionic acid and butyric acid production by modifying SCFA-producing bacteria. Furthermore, the levels of the tight junction protein ZO-1, mucin proteins(mucin [MUC]-1, MUC-2 and MUC-4) and the antimicrobial peptide Reg3β were increased after probiotic supplementation.CONCLUSION Based on these results, the new strain of P. pentosaceus alleviated ethanol-induced liver injury by reversing gut microbiota dysbiosis, regulating intestinal SCFA metabolism, improving intestinal barrier function, and reducing circulating levels of endotoxin and proinflammatory cytokines and chemokines. Thus, this strain is a potential probiotic treatment for ALD.
基金Supported by The Special Research Foundation of the National Nature Science Foundation of China,No.81302143the Natural Science Foundation of Guangdong Province,China,No.S2013040015045
文摘As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.
基金This work was supported by The Special Research Foundation of the National Nature Science Foundation of China(81972262,81972255,81772597,81702904)the Guangdong Natural Science Foundation(2018A030313645,2017A030311002,2015A030313101)+6 种基金the Guangdong Science and Technology Foundation(2016A020215199,2017A020215196)the Science and Technology Program of Guangzhou,China(201607010111)the Pearl River S&T Nova Program of Guangzhou,China(201610010022)the Fundamental Research Funds for the Central Universities(17ykpy44,18ykpy22)Grant[2013]163 from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of the Guangzhou Bureau of Science and Information TechnologyGrant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutesgrants from the Guangdong Science and Technology Department(2015B050501004,2017B030314026).
文摘Dysregulation of dickkopf-related protein 1(DKK1)expression has been reported in a variety of human cancers.We previously reported that DKK1 was upregulated in hepatocellular carcinoma(HCC).However,the role of DKK1 in HCC remains unclear.This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC.The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(qRT-PCR).DKK1 was silenced or overexpressed in HCC cell lines,and in vitro and in vivo studies were performed.Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues(8/22,36.4%)but upregulated in HCC tissues(48/53,90.6%,cohort 1).Significant upregulation of DKK1 was observed in 57.6%(19/33,cohort 2)of HCC tissues by qRT-PCR,and the expression of DKK1 was associated with tumor size(P=0.024)and tumor number(P=0.019).Genetic depletion of DKK1 impaired the proliferation,colony-forming ability,invasion,and tumor formation of HCC cells(HepG2 and HUH-7).Conversely,forced expression of DKK1 increased the proliferation,colony-forming ability,and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo.Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/β-catenin signaling pathway.These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/β-catenin signaling pathway.
文摘Retraction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-019-0082-5,published online 06 December 2019 The authors have retracted this article.After publication,concerns were raised regarding suspected overlap in the cell images in Figs.2 and 3.Specifically.
基金supported by The Special Research Foundation of the National Nature Science Foundation of China (81972262,81972255,81801719,81772597)The Guangdong Basic and Applied Basic Research Foundation (2020A1515010117,2018A030313645,2016A030313840)+4 种基金the Fundamental Research Funds for the Central Universities (18ykpy22)Grant [2013]163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information TechnologyGrant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education InstitutesGrant from Guangdong Science and Technology Department (2015B050501004,2017B030314026)Grant from Sun Yat-sen University Clinical Research 5010 Program (2018008).
文摘Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms,this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA,and to explore underlying mechanisms.Methods:We screened out miR-203a,the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.In vitro and in vivo functional experiments were performed to assess its regulatory function.The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study.Results:MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis.The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells.We demonstrated the function of miR-203a in inhibiting HCC cell proliferation,migration,clonogenic capacity,and tumor development in vivo.Furthermore,the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers.In concordance with our study,the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a.We also found that BMI1,a gene maintains the self-renewal capacity of stem cells,showed a significant negative correlation with miR-203a in HCC specimen(p<0.001).Similarly,opposite BMI1 changes after overexpression/knockdown of miR203a were also confirmed in vitro.Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding.Conclusions:HBsAg may promote the development of HCC and tumor stemness by inhibiting miR-203a,resulting in poor prognosis.miR-203a may serve as a crucial treatment target in HBsAg-positive HCC.More explicit mechanistic studies and animal experiments need to be conducted as a next step.
文摘The original version of this article unfortunately contained a mistake.For Fig.la in p.409,the citation of a reference,as well as the permission to reprint this picture,was missing.The correct version and the corresponding reference are given below:(a)Chest computed tomography(CT)image of Patient 1 on admission presents multiple ground-glass opacities distributed in the periphery of inferior lobe of both lungs.Reprinted from Zhang et al.(2020),with kind permission from Springer Nature.
