Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterfero...BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.展开更多
AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepato...AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-Ⅰ receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation. RESULTS: IGF-Ⅱ stimulated cells proliferated to 2.7 (269% ± 76%) (mean ± SD) (Huh-6) and 2.1 (211% ± 85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ± 11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30% ± 5% (Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6) and 46% ± 1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION: IGF- Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-Ⅰ receptor and PI3 kinase which were good candidates for target of molecular therapy.展开更多
Objective:To investigate the levels of zinc-α-2-glycoprotein(ZAG) among Omani AIDS patients receiving combined antiretroviral therapy(cART).Methods:A total of 80 Omani AIDS patients(45 males and 33 females),average a...Objective:To investigate the levels of zinc-α-2-glycoprotein(ZAG) among Omani AIDS patients receiving combined antiretroviral therapy(cART).Methods:A total of 80 Omani AIDS patients(45 males and 33 females),average age of 36 vears.who were receiving cART at the Saltan Qaboos University Hospital(SQUH).Muscat,Oman,were tested for the levels of ZAG.In addition,SO healthy blood donors(46 males and 34 females),average age of 26 years,attending the SOUH Blood Bank,were tested in parallel as a control group.Measurement of the ZAG levels was performed using a competitive enzyme—linked immunosorbent assay and in accordance with the manufacturer's instructions.Results:The ZAG levels were found to he significantly higher among AIDS patients compared to the healthy individuals(P=0.033).A total of 56(70%) of the AIDS patients were found to have higher levels of ZAG and 16(20%) AIDS patients were found to have high ZAG levels,which are significantly(P>0.031) associated with weight loss.Conclusions:ZAG levels are high among Omani AIDS patients on cART and this necessitales the measurement of ZAG on routine basis,as it is associated with weight loss.展开更多
AIM: TO examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human embryo hepatic cell line L02 was transfected wit...AIM: TO examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and selected by G418. Expression of HCV-core was detected by reverse transcription polymerase chain reaction and Western blotting. The OAS promoter sequence was amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and luciferase activity was assayed. I^ESULTS: L02/core cell line stably expressing HCV- core protein was established. The pGL3-OAS-Luci construct exhibited significant transcriptional activity in the L02/core cells but not in the L02 cells. CONCLUSION: HCV-core protein activates the OAS gene promoter specifically and effectively. Utilization of OAS gene promoter would be an ideal strategy for developing HCV-specific gene therapy.展开更多
AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in v...AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.展开更多
Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cance...Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cancer lead to the development of new targeted therapies for the treatment of advanced and metastatic gastric cancer. The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents.展开更多
14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein caninteract with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Lit...14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein caninteract with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Little isknown about the consequences of these interactions, and thus are the subjects of ongoing studies. 14-3-3 controls cellcycle, cell growth, differentiation, survival, apoptosis, migration and spreading. Recent studies have revealed newmechanisms and new functions of 14-3-3, giving us more insights on this fascinating and complex family of proteins.Of all the seven isoforms, 14-3-3σ seems to be directly involved in human cancer. 14-3-3σ itself is subject to regulationby p53 upon DNA damage and by epigenetic deregulation. Gene silencing of 14-3-3σ by CpG methylation has beenfound in many human cancer types. This suggests that therapy-targeting 14-3-3σ may be beneficial for future cancertreatment.展开更多
AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. ...AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.展开更多
AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retro...AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.展开更多
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
基金the National Natural Science Foundation of China,No.31500650。
文摘BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.
基金Supported by the Japan Society for the Promotion of Science (JSPS) (16590577) and the Kawano Masanori Memorial Foundation for Promotion of Pediatrics (15-6)
文摘AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-Ⅰ receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation. RESULTS: IGF-Ⅱ stimulated cells proliferated to 2.7 (269% ± 76%) (mean ± SD) (Huh-6) and 2.1 (211% ± 85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ± 11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30% ± 5% (Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6) and 46% ± 1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION: IGF- Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-Ⅰ receptor and PI3 kinase which were good candidates for target of molecular therapy.
基金Supported by the Research Council of the Sultanate of Oman(RC/MED/MICR/11/01)the College of Medicine and Health Sciences,Sultan Qaboos University(Internal-Grant/2013).Oman
文摘Objective:To investigate the levels of zinc-α-2-glycoprotein(ZAG) among Omani AIDS patients receiving combined antiretroviral therapy(cART).Methods:A total of 80 Omani AIDS patients(45 males and 33 females),average age of 36 vears.who were receiving cART at the Saltan Qaboos University Hospital(SQUH).Muscat,Oman,were tested for the levels of ZAG.In addition,SO healthy blood donors(46 males and 34 females),average age of 26 years,attending the SOUH Blood Bank,were tested in parallel as a control group.Measurement of the ZAG levels was performed using a competitive enzyme—linked immunosorbent assay and in accordance with the manufacturer's instructions.Results:The ZAG levels were found to he significantly higher among AIDS patients compared to the healthy individuals(P=0.033).A total of 56(70%) of the AIDS patients were found to have higher levels of ZAG and 16(20%) AIDS patients were found to have high ZAG levels,which are significantly(P>0.031) associated with weight loss.Conclusions:ZAG levels are high among Omani AIDS patients on cART and this necessitales the measurement of ZAG on routine basis,as it is associated with weight loss.
基金Supported by National Natural Science Foundation of China,No.30671846
文摘AIM: TO examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and selected by G418. Expression of HCV-core was detected by reverse transcription polymerase chain reaction and Western blotting. The OAS promoter sequence was amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and luciferase activity was assayed. I^ESULTS: L02/core cell line stably expressing HCV- core protein was established. The pGL3-OAS-Luci construct exhibited significant transcriptional activity in the L02/core cells but not in the L02 cells. CONCLUSION: HCV-core protein activates the OAS gene promoter specifically and effectively. Utilization of OAS gene promoter would be an ideal strategy for developing HCV-specific gene therapy.
基金Supported by National Natural Science Foundation of China,No.81472844
文摘AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.
文摘Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cancer lead to the development of new targeted therapies for the treatment of advanced and metastatic gastric cancer. The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents.
文摘14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein caninteract with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Little isknown about the consequences of these interactions, and thus are the subjects of ongoing studies. 14-3-3 controls cellcycle, cell growth, differentiation, survival, apoptosis, migration and spreading. Recent studies have revealed newmechanisms and new functions of 14-3-3, giving us more insights on this fascinating and complex family of proteins.Of all the seven isoforms, 14-3-3σ seems to be directly involved in human cancer. 14-3-3σ itself is subject to regulationby p53 upon DNA damage and by epigenetic deregulation. Gene silencing of 14-3-3σ by CpG methylation has beenfound in many human cancer types. This suggests that therapy-targeting 14-3-3σ may be beneficial for future cancertreatment.
基金Supported by National Natural Science Foundation of China, No. 30771905National Basic Research Program of China (973 Program), No. 2007CB512800+1 种基金Mega-projects of Science Research, No. 008ZX10002-008Beijing Municipal Science & Technology Commission, No. D08050700650803
文摘AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.
文摘AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.