BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,...BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.展开更多
Introduction:Fluorine-18 fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)is a powerful tool for monitoring the response of diffuse large B-cell lymphoma(DLBCL)to therapy,but the crit...Introduction:Fluorine-18 fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)is a powerful tool for monitoring the response of diffuse large B-cell lymphoma(DLBCL)to therapy,but the criteria to interpret PET/CT results remain under debate.We investigated the value of post-treatment PET/CT in predicting the prognosis of DLBCL patients when interpreted according to qualitative visual trichotomous assessment(QVTA)criteria compared with the Deauvil e criteria.Methods:In this retrospective study,final PET/CT scans of DLBCL patients treated with rituximab-based regimens between October 2005 and November 2010 were interpreted using the Deauvil e and QVTA criteria.Survival curves were estimated using Kaplan-Meier analysis and compared using the log-rank test.Results:A total of 253 patients were enrol ed.The interpretation according to the Deauvil e criteria revealed that 181patients had negative PET/CT scan results and 72 had positive results.The 3 year overal survival(OS)rate was significantly higher in patients with negative scan results than in those with positive results(91.6%vs.57.5%,P<0.001).The72 patients with positive scan results according to the Deauville criteria were divided into two groups by the interpretation according to the QVTA criteria:29 had indeterminate results,and 43 had positive results.The 3 year OS rate was significantly higher in patients with indeterminate scan results than in those with positive results(91.2%vs.33.5%,P<0.001)but was similar between patients with negative and indeterminate scan results(91.6%vs.91.2%,P=0.921).Conclusions:Compared with the Deauvil e criteria,using the QVTA criteria for interpreting post-treatment PET/CT scans of DLBCL patients is likely to reduce the number of false positive results.The QVTA criteria are feasible for therapeutic outcome evaluation and can be used to guide risk-adapted therapy.展开更多
Arbscular mycorrhiza(AM),a symbiosis between plants and members of fungi Glomeromycota,improves the resistance,nutrition and material metabolism of plant.Arbuscules generated by symbiotic development,is the main site ...Arbscular mycorrhiza(AM),a symbiosis between plants and members of fungi Glomeromycota,improves the resistance,nutrition and material metabolism of plant.Arbuscules generated by symbiotic development,is the main site of nutrient exchange and genetic material recombination,resulting in physiological changes and gene expression regulation.AM regulates pathogenesis-related protein(PRs) genes and antioxidant enzyme genes against biotic and abiotic stresses.Nutrient exchange induced by AM is directly involved in uptake,transformation and utilization of nutrient elements in plants.Importantly,transporter genes play an important role in phosphate,nitrogen and carbon acquisition.In AM interactions,phosphate transporter(PT) genes,from both arbuscular mycorrhizal fungi and plant root,are induced and there product promote phosphate acquisition;increasing expression of ammonium transporter(AMT) genes and arginine biosynthesis/degradation enzyme genes is in charge of nitrogen acquisition;and promotion mechanism of carbon acquisition is involved in up-regulation of sugar transporter genes.In addition,secondary metabolites,functioned as signal moleculars and defense compounds,are increased with development of AM symbiont by up-regulating related synthetic genes based on different promotion mechanism.Taken together,molecular regulation of plant and arbuscular mycorrhizal fungi,induced by infection process,stimulate plant nutrient acquisition and resist to biotic/abiotic stress.展开更多
Interim 18F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma(DLBCL). This retrospective stud...Interim 18F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma(DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis(PET/CT0), after 2 and 4 cycles of chemotherapy(PET/CT2 and PET/CT4, respectively), and at the end of treatment(F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate(75.8% vs. 38.2%) and 3-year overall survival rate(93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy(15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.展开更多
基金Supported by National Natural Science Foundation of China,No.81930110The National Funded Postdoctoral Researcher Program of China,No.GZC20232406+2 种基金Henan Province Traditional Chinese Medicine Science Research Project,No.2023ZY3040Henan Province Medical Science and Technology Research Plan Joint Construction Project,No.LHGJ20230233National Key Research and Development Program of China,No.2022YFC2303103.
文摘BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.
文摘Introduction:Fluorine-18 fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)is a powerful tool for monitoring the response of diffuse large B-cell lymphoma(DLBCL)to therapy,but the criteria to interpret PET/CT results remain under debate.We investigated the value of post-treatment PET/CT in predicting the prognosis of DLBCL patients when interpreted according to qualitative visual trichotomous assessment(QVTA)criteria compared with the Deauvil e criteria.Methods:In this retrospective study,final PET/CT scans of DLBCL patients treated with rituximab-based regimens between October 2005 and November 2010 were interpreted using the Deauvil e and QVTA criteria.Survival curves were estimated using Kaplan-Meier analysis and compared using the log-rank test.Results:A total of 253 patients were enrol ed.The interpretation according to the Deauvil e criteria revealed that 181patients had negative PET/CT scan results and 72 had positive results.The 3 year overal survival(OS)rate was significantly higher in patients with negative scan results than in those with positive results(91.6%vs.57.5%,P<0.001).The72 patients with positive scan results according to the Deauville criteria were divided into two groups by the interpretation according to the QVTA criteria:29 had indeterminate results,and 43 had positive results.The 3 year OS rate was significantly higher in patients with indeterminate scan results than in those with positive results(91.2%vs.33.5%,P<0.001)but was similar between patients with negative and indeterminate scan results(91.6%vs.91.2%,P=0.921).Conclusions:Compared with the Deauvil e criteria,using the QVTA criteria for interpreting post-treatment PET/CT scans of DLBCL patients is likely to reduce the number of false positive results.The QVTA criteria are feasible for therapeutic outcome evaluation and can be used to guide risk-adapted therapy.
基金financed by the Doctoral Foundation of Ministry of Education of China(20110101110094)
文摘Arbscular mycorrhiza(AM),a symbiosis between plants and members of fungi Glomeromycota,improves the resistance,nutrition and material metabolism of plant.Arbuscules generated by symbiotic development,is the main site of nutrient exchange and genetic material recombination,resulting in physiological changes and gene expression regulation.AM regulates pathogenesis-related protein(PRs) genes and antioxidant enzyme genes against biotic and abiotic stresses.Nutrient exchange induced by AM is directly involved in uptake,transformation and utilization of nutrient elements in plants.Importantly,transporter genes play an important role in phosphate,nitrogen and carbon acquisition.In AM interactions,phosphate transporter(PT) genes,from both arbuscular mycorrhizal fungi and plant root,are induced and there product promote phosphate acquisition;increasing expression of ammonium transporter(AMT) genes and arginine biosynthesis/degradation enzyme genes is in charge of nitrogen acquisition;and promotion mechanism of carbon acquisition is involved in up-regulation of sugar transporter genes.In addition,secondary metabolites,functioned as signal moleculars and defense compounds,are increased with development of AM symbiont by up-regulating related synthetic genes based on different promotion mechanism.Taken together,molecular regulation of plant and arbuscular mycorrhizal fungi,induced by infection process,stimulate plant nutrient acquisition and resist to biotic/abiotic stress.
文摘Interim 18F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma(DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis(PET/CT0), after 2 and 4 cycles of chemotherapy(PET/CT2 and PET/CT4, respectively), and at the end of treatment(F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate(75.8% vs. 38.2%) and 3-year overall survival rate(93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy(15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.
