BACKGROUND Finding active lead anti-hepatocellular carcinoma compounds from traditional Chinese medicine has important research value.AIM To assess the detailed mechanism of oxocrebanine,a compound separated from the ...BACKGROUND Finding active lead anti-hepatocellular carcinoma compounds from traditional Chinese medicine has important research value.AIM To assess the detailed mechanism of oxocrebanine,a compound separated from the traditional Chinese medicinal plant Stephania hainanensis H.S.Lo et Y.Tsoong,and to evaluate its inhibition of the proliferation of human hepatocellular carcinoma cells via apoptosis and autophagy.METHODS MTT,BrdU labeling,and colony formation assays were used to assess the inhibitory effect of oxocrebanine on the growth and proliferation of human hepatocellular carcinoma Hep3B2.1-7 cells.Flow cytometry was used to detect the effect of oxocrebanine on the apoptosis of Hep3B2.1-7 cells.Western blotting was used to assess the expression of apoptosis-related proteins in Hep3B2.1-7 cells.The aforementioned methods were also used to evaluate the effects of oxocrebanine on cell proliferation,autophagy markers,and autophagy-related protein expression levels after adding autophagy inhibitor 3-mA.Furthermore,to verify the anti-hepatocellular carcinoma effect of oxocrebanine in vivo,a nude mouse model was used to investigate the inhibitory effect of oxocrebanine treatment and its mechanism.Apoptosis was detected using a TUNEL assay and the expression of microtubule-associated protein 1 LC3 in tumor specimens was assessed using immunohistochemistry.RESULTS Oxocrebanine effectively inhibited the growth of Hep3B2.1-7 cells,whilst upregulating the protein expression of cleaved caspase-3,downregulating poly(ADP-ribose)polymerase 1 protein expression,increasing the levels of Bax and Bcl-2 antagonist/killer 1 protein expression,and decreasing the levels of Bcl-2 and myeloid cell leukemia 1 protein expression,which could promote apoptosis in Hep3B2.1-7 cells.Oxocrebanine promoted the transformation of LC3-I to LC3-II in Hep3B2.1-7 cells,suggesting the occurrence of autophagy,whilst the autophagy inhibitor 3-MA could reverse this process.Oxocrebanine was also shown to reduce the phosphorylation levels of the eukaryotic translation initiation factor 4EBP1 and ribosomal protein S6 kinase B1(P70S6K),two downstream effector molecules in the PI3K/Akt/mTOR pathway,inducing autophagy in Hep3B2.1-7 cells.Moreover,the tumor-bearing nude mouse experiment indicated that oxocrebanine effectively inhibited the growth of Hep3B2.1-7 cells in vivo.The results of the TUNEL assay and immunohistochemistry also revealed that oxocrebanine induced apoptosis in vivo and increased the expression level of LC3,an autophagy marker.CONCLUSION Oxocrebanine can inhibit the proliferation of human hepatocellular carcinoma cells by promoting apoptosis and inducing autophagy in vitro and in vivo.展开更多
面向高能同步辐射光源(High Energy Photon Source,HEPS)的高性能像素阵列探测器(HEPS-BPIX4)的数据获取系统(Data Acquisition,DAQ)需满足高实时性要求。通过在线压缩图像数据,可有效降低后续传输与存储的压力。针对传统压缩算法在压...面向高能同步辐射光源(High Energy Photon Source,HEPS)的高性能像素阵列探测器(HEPS-BPIX4)的数据获取系统(Data Acquisition,DAQ)需满足高实时性要求。通过在线压缩图像数据,可有效降低后续传输与存储的压力。针对传统压缩算法在压缩率和实时性方面的不足,本文提出了一种基于深度学习目标检测的图像数据在线压缩方法。采用端到端的YOLO(You Only Look Once)目标检测算法,对深度学习模型进行高效训练,并验证了其在HEPS-BPIX4 DAQ数据流中实现在线数据压缩的可行性。实验结果表明,该方法的图像数据在线压缩平均压缩比达到5.88。同时,设计了高效的部署方案,并对性能进行了测试,单线程下的压缩处理速率可达GB∙s^(−1)量级。此外,进一步提出了适用于HEPS-BPIX4 DAQ框架的多线程部署方案,以满足更高的压缩性能需求,为缓解HEPS-BPIX4 DAQ系统高带宽图像数据处理压力提供了新思路。展开更多
目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质...目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质谱进行分离、鉴定。常规培养SK-Hep-1细胞,用0、50、100、150、200、250μg/mL的T-19及RGD-T-19分别处理细胞,分为0μg/mL(对照)组、50μg/mL组、100μg/mL组、150μg/mL组、200μg/mL组、250μg/mL组。CCK-8法、克隆形成实验、划痕愈合实验和Tanswell小室实验、WB法和q PCR法分别检测SK-Hep-1细胞的增殖、迁移、侵袭能力,以及环氧合酶-2(COX-2)、基质金属蛋白酶-2(MMP-2)、MMP-9、组织基质金属蛋白酶抑制剂-1(TIMP-1)、TIMP-2蛋白和MMP-1、MMP-2 mRNA的表达。结果:经质谱鉴定,用Fmoc固相法合成的T-19及RGD-T-19纯度高。T-19和RGD-T-19均能显著抑制SK-Hep-1细胞的增殖、迁移、侵袭能力,抑制COX-2蛋白、MMP-2和MMP-9蛋白及mRNA的表达、促进TIMP-1、TIMP-2蛋白的表达(P <0.05, P <0.01, P <0.001),RGD-T-19的抑制或促进效应均明显强于T-19(均P <0.05)。结论:利用Fmoc固相法合成了纯度高、活性好的T-19及RGD-T-19,两种肽均能抑制SK-Hep-1细胞增殖、侵袭和迁移能力,RGD-T-19作用明显强于T-19。展开更多
Hepatitis B virus(HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnavir...Hepatitis B virus(HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma(HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNAinto the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis.展开更多
AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).M...AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.展开更多
DD4hep serves as a generic detector description toolkit recommended for offline software development in next-generation high-energy physics(HEP)experiments.Conversely,Filmbox(FBX)stands out as a widely used 3D modelin...DD4hep serves as a generic detector description toolkit recommended for offline software development in next-generation high-energy physics(HEP)experiments.Conversely,Filmbox(FBX)stands out as a widely used 3D modeling file format within the 3D software industry.In this paper,we introduce a novel method that can automatically convert complex HEP detector geometries from DD4hep description into 3D models in the FBX format.The feasibility of this method was dem-onstrated by its application to the DD4hep description of the Compact Linear Collider detector and several sub-detectors of the super Tau-Charm facility and circular electron-positron collider experiments.The automatic DD4hep–FBX detector conversion interface provides convenience for further development of applications,such as detector design,simulation,visualization,data monitoring,and outreach,in HEP experiments.展开更多
AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the i...AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.展开更多
基金Supported by National Natural Science Foundation of China,No.82060778the Hainan Provincial Natural Science Foundation of China,No.820RC776+1 种基金the Hainan Province Health Science and Technology Innovation Joint Project,No.WSJK2024MS162the Heilongjiang Province Scientific Research Project of Traditional Chinese Medicine,No.ZHY2024-098.
文摘BACKGROUND Finding active lead anti-hepatocellular carcinoma compounds from traditional Chinese medicine has important research value.AIM To assess the detailed mechanism of oxocrebanine,a compound separated from the traditional Chinese medicinal plant Stephania hainanensis H.S.Lo et Y.Tsoong,and to evaluate its inhibition of the proliferation of human hepatocellular carcinoma cells via apoptosis and autophagy.METHODS MTT,BrdU labeling,and colony formation assays were used to assess the inhibitory effect of oxocrebanine on the growth and proliferation of human hepatocellular carcinoma Hep3B2.1-7 cells.Flow cytometry was used to detect the effect of oxocrebanine on the apoptosis of Hep3B2.1-7 cells.Western blotting was used to assess the expression of apoptosis-related proteins in Hep3B2.1-7 cells.The aforementioned methods were also used to evaluate the effects of oxocrebanine on cell proliferation,autophagy markers,and autophagy-related protein expression levels after adding autophagy inhibitor 3-mA.Furthermore,to verify the anti-hepatocellular carcinoma effect of oxocrebanine in vivo,a nude mouse model was used to investigate the inhibitory effect of oxocrebanine treatment and its mechanism.Apoptosis was detected using a TUNEL assay and the expression of microtubule-associated protein 1 LC3 in tumor specimens was assessed using immunohistochemistry.RESULTS Oxocrebanine effectively inhibited the growth of Hep3B2.1-7 cells,whilst upregulating the protein expression of cleaved caspase-3,downregulating poly(ADP-ribose)polymerase 1 protein expression,increasing the levels of Bax and Bcl-2 antagonist/killer 1 protein expression,and decreasing the levels of Bcl-2 and myeloid cell leukemia 1 protein expression,which could promote apoptosis in Hep3B2.1-7 cells.Oxocrebanine promoted the transformation of LC3-I to LC3-II in Hep3B2.1-7 cells,suggesting the occurrence of autophagy,whilst the autophagy inhibitor 3-MA could reverse this process.Oxocrebanine was also shown to reduce the phosphorylation levels of the eukaryotic translation initiation factor 4EBP1 and ribosomal protein S6 kinase B1(P70S6K),two downstream effector molecules in the PI3K/Akt/mTOR pathway,inducing autophagy in Hep3B2.1-7 cells.Moreover,the tumor-bearing nude mouse experiment indicated that oxocrebanine effectively inhibited the growth of Hep3B2.1-7 cells in vivo.The results of the TUNEL assay and immunohistochemistry also revealed that oxocrebanine induced apoptosis in vivo and increased the expression level of LC3,an autophagy marker.CONCLUSION Oxocrebanine can inhibit the proliferation of human hepatocellular carcinoma cells by promoting apoptosis and inducing autophagy in vitro and in vivo.
文摘目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质谱进行分离、鉴定。常规培养SK-Hep-1细胞,用0、50、100、150、200、250μg/mL的T-19及RGD-T-19分别处理细胞,分为0μg/mL(对照)组、50μg/mL组、100μg/mL组、150μg/mL组、200μg/mL组、250μg/mL组。CCK-8法、克隆形成实验、划痕愈合实验和Tanswell小室实验、WB法和q PCR法分别检测SK-Hep-1细胞的增殖、迁移、侵袭能力,以及环氧合酶-2(COX-2)、基质金属蛋白酶-2(MMP-2)、MMP-9、组织基质金属蛋白酶抑制剂-1(TIMP-1)、TIMP-2蛋白和MMP-1、MMP-2 mRNA的表达。结果:经质谱鉴定,用Fmoc固相法合成的T-19及RGD-T-19纯度高。T-19和RGD-T-19均能显著抑制SK-Hep-1细胞的增殖、迁移、侵袭能力,抑制COX-2蛋白、MMP-2和MMP-9蛋白及mRNA的表达、促进TIMP-1、TIMP-2蛋白的表达(P <0.05, P <0.01, P <0.001),RGD-T-19的抑制或促进效应均明显强于T-19(均P <0.05)。结论:利用Fmoc固相法合成了纯度高、活性好的T-19及RGD-T-19,两种肽均能抑制SK-Hep-1细胞增殖、侵袭和迁移能力,RGD-T-19作用明显强于T-19。
基金Supported by Cassa di Risparmio di Firenze(CRF)and FiorGen Foundation
文摘Hepatitis B virus(HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma(HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNAinto the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis.
文摘AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.
基金supported by the National Natural Science Foundation of China(Nos.12175321,11975021,11675275,and U1932101)National Key Research and Development Program of China(Nos.2023YFA1606000 and 2020YFA0406400)+2 种基金State Key Laboratory of Nuclear Physics and Technology,Peking University(Nos.NPT2020KFY04 and NPT2020KFY05)Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA10010900)National College Students Science and Technology Innovation Project,and Undergraduate Base Scientific Research Project of Sun Yat-sen University。
文摘DD4hep serves as a generic detector description toolkit recommended for offline software development in next-generation high-energy physics(HEP)experiments.Conversely,Filmbox(FBX)stands out as a widely used 3D modeling file format within the 3D software industry.In this paper,we introduce a novel method that can automatically convert complex HEP detector geometries from DD4hep description into 3D models in the FBX format.The feasibility of this method was dem-onstrated by its application to the DD4hep description of the Compact Linear Collider detector and several sub-detectors of the super Tau-Charm facility and circular electron-positron collider experiments.The automatic DD4hep–FBX detector conversion interface provides convenience for further development of applications,such as detector design,simulation,visualization,data monitoring,and outreach,in HEP experiments.
文摘AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.
