BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attract...BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.展开更多
Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV6307...Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.展开更多
Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies re...Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies reporting an association between H.pylori-infection in the oral cavity and H.pylori-positive stomach bacterium.This work was designed to determine whether H.pylori is the etiologic agent in periodontal disease,recurrent aphthous stomatitis(RAS),squamous cell carcinoma,burning and halitosis.Record selection focused on the highest quality studies and meta-analyses.We selected 48 articles reporting on the association between saliva and plaque and H.pylori-infection.In order to assess periodontal disease data,we included 12 clinical trials and 1 meta-analysis.We evaluated 13 published articles that addressed the potential association with RAS,and 6 with squamous cell carcinoma.Fourteen publications focused on our questions on burning and halitosis.There is a close relation between H.pylori infection in the oral cavity and the stomach.The mouth is the first extra-gastric reservoir.Regarding the role of H.pylori in the etiology of squamous cell carcinoma,no evidence is still available.展开更多
Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As anima...Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.展开更多
Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus(HCMV) infection.Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloning o...Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus(HCMV) infection.Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloning of mRNA from a HCMV infected individual.Antigen binding specificity,CDR sequence of VH and VL and neutralizing activity on HCMV AD169 stain were analyzed in vitro.The light and heavy chain Fd fragment genes of Fab antibodies were further cloned into a recombinant baculovirus expression vector pAC-κ-Fc to express intact IgG.Secreted products were purified with affinity chromatography using protein G.Results SDS-PAGE and Western blot confirmed the expression of the intact IgG.Immuno-blotting and -precipitation were used to identify HCMV proteins.One Fab monoclonal antibody recognized a conformational HCMV protein.Conclusion IgG antibodies can neutralize the HCMV AD169 strain efficiently at a titer of 2.5 μg/mL and may prove valuable for passive immunoprophylaxis against HCMV infection in humans.展开更多
Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients...Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome CGH arrays. A number of highly frequent genomic aberrations were discovered, which may act as "drivers" of tumor progression. Meanwhile, the genomic profiles of four "normal" breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.展开更多
Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection an...Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis.展开更多
Dear Editor,Bladder cancer is the most common type of genitourinary cancer in China,with an estimated 80,500 new cases and 32,900 related deaths in 2015 alone(Chen et al.,2016).Unlike many other cancers,there has been...Dear Editor,Bladder cancer is the most common type of genitourinary cancer in China,with an estimated 80,500 new cases and 32,900 related deaths in 2015 alone(Chen et al.,2016).Unlike many other cancers,there has been no significant improvement in survival rates for bladder cancer over the last three decades.Specific treatment regimens for bladder cancer and their efficacy vary depending not only on clinical stages,but also on associated risk factors and other personal clinical characteristics.Patients with non-muscle invasive bladder cancer(NMIBC)have a high 5-year recurrence rate of 60%-70%(Berdik,2017)and those with muscle invasive bladder cancer(MIBC)has a relatively poor prognosis with approximately 65%risk of death within 5-year follow-up(Kamat et al.,2016).Therefore,there is an urgent need to develop models for bladder cancer to screen for rational treatment strategies by personalized medicine to improve the clinical assessment and treatment of bladder cancer.展开更多
Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on H...Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.展开更多
因为他们的能力， B 房间通常被认为是有免疫力的反应的积极管理者生产抗体，包括自身抗体。因为 B 房间用作介绍抗原的房间并且在有免疫力的回答施加另外的调节功能，抗体的生产便于最佳的 CD4 <sup>+</sup>T...因为他们的能力， B 房间通常被认为是有免疫力的反应的积极管理者生产抗体，包括自身抗体。因为 B 房间用作介绍抗原的房间并且在有免疫力的回答施加另外的调节功能，抗体的生产便于最佳的 CD4 <sup>+</sup>T 房间激活。然而，某些 B 房间能否定地也由生产规章的 cytokines 并且直接经由 cell-to-cell 接触与病原的 T 房间交往调整有免疫力的反应。B 房间的这些类型被定义为规章的 B (Breg ) 房间。Breg 房间的规章的函数在发炎的鼠标模型被表明了，癌症，移植，并且特别地在 autoimmunity。在这评论，我们集中于在人的自体免疫的疾病导致发展的理解和 Breg 房间的功能和 B 房间的含意的最近的进展。展开更多
Cancer cell lines have been used widely in cancer biology, and as biological or functional cell systems in many biomedical research fields. These cells are usually defective for many normal activities or functions due...Cancer cell lines have been used widely in cancer biology, and as biological or functional cell systems in many biomedical research fields. These cells are usually defective for many normal activities or functions due to significant genetic and epigenetic changes. Normal primary cell yields and viability from any original tissue specimens are usually relatively low or highly variable. These normal cells cease after a few passages or population doublings due to very limited proliferative capacity. Animal models(ferret, mouse, etc.) are often used to study virus-host interaction. However, viruses usually need to be adapted to the animals by several passages due to tropism restrictions including viral receptors and intracellular restrictions. Here we summarize applications of conditionally reprogrammed cells(CRCs), long-term cultures of normal airway epithelial cells from human nose to lung generated by conditional cell reprogramming(CR) technology, as an ex vivo model in studies of emerging viruses. CR allows to robustly propagate cells from non-invasive or minimally invasive specimens, for example, nasal or endobronchial brushing. This process is rapid(2 days) and conditional. The CRCs maintain their differentiation potential and lineage functions, and have been used for studies of adenovirus, rhinovirus, respiratory syncytial virus, influenza viruses, parvovirus, and SARS-CoV. The CRCs can be easily used for airliquid interface(ALI) polarized 3 D cultures, and these coupled CRC/ALI cultures mimic physiological conditions and are suitable for studies of viral entry including receptor binding and internalization, innate immune responses, viral replications, and drug discovery as an ex vivo model for emerging viruses.展开更多
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+5 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005and Open Project of Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education,No.DHYX21-07,No.DHYX22-05,and No.DHYX21-01.
文摘BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.
基金supported by grants from the National Institutes of Health(SBIR R44 AI125060,NIAMS P50 AR072000,and NIAMS P30 AR069655)。
文摘Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.
文摘Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies reporting an association between H.pylori-infection in the oral cavity and H.pylori-positive stomach bacterium.This work was designed to determine whether H.pylori is the etiologic agent in periodontal disease,recurrent aphthous stomatitis(RAS),squamous cell carcinoma,burning and halitosis.Record selection focused on the highest quality studies and meta-analyses.We selected 48 articles reporting on the association between saliva and plaque and H.pylori-infection.In order to assess periodontal disease data,we included 12 clinical trials and 1 meta-analysis.We evaluated 13 published articles that addressed the potential association with RAS,and 6 with squamous cell carcinoma.Fourteen publications focused on our questions on burning and halitosis.There is a close relation between H.pylori infection in the oral cavity and the stomach.The mouth is the first extra-gastric reservoir.Regarding the role of H.pylori in the etiology of squamous cell carcinoma,no evidence is still available.
文摘Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.
文摘Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus(HCMV) infection.Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloning of mRNA from a HCMV infected individual.Antigen binding specificity,CDR sequence of VH and VL and neutralizing activity on HCMV AD169 stain were analyzed in vitro.The light and heavy chain Fd fragment genes of Fab antibodies were further cloned into a recombinant baculovirus expression vector pAC-κ-Fc to express intact IgG.Secreted products were purified with affinity chromatography using protein G.Results SDS-PAGE and Western blot confirmed the expression of the intact IgG.Immuno-blotting and -precipitation were used to identify HCMV proteins.One Fab monoclonal antibody recognized a conformational HCMV protein.Conclusion IgG antibodies can neutralize the HCMV AD169 strain efficiently at a titer of 2.5 μg/mL and may prove valuable for passive immunoprophylaxis against HCMV infection in humans.
基金supported by the Danish Cancer Soci-ety through the budget of the Institute of Cancer Biol-ogy and by grants from the Danish Medical Research Council, the Natural and Medical Sciences Committee of the Danish Cancer Society, Novo Nordisk, the John and Birthe Meyer Foundation, the Solar Fonden, the Stensbygaard Fonden, the Kai Langeog Gundhild Kai Lange Fond, the will of Edith Stern, and the "Race Against Breast Cancer" ProjectThe support of the Marketing Department at the Danish Cancer Society is greatly appreciatedsupported by a project grant from the Hi-Tech Research and Development Program of China (2006AA02A301)
文摘Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome CGH arrays. A number of highly frequent genomic aberrations were discovered, which may act as "drivers" of tumor progression. Meanwhile, the genomic profiles of four "normal" breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.
文摘Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis.
基金The work was supported by grants from National Natural Science Foundation of China(Grant Nos.31270830 and 21572038)Shanghai Association for Science and Technology(Grant No.17401930400)and Development Fund for Shanghai Talents.
文摘Dear Editor,Bladder cancer is the most common type of genitourinary cancer in China,with an estimated 80,500 new cases and 32,900 related deaths in 2015 alone(Chen et al.,2016).Unlike many other cancers,there has been no significant improvement in survival rates for bladder cancer over the last three decades.Specific treatment regimens for bladder cancer and their efficacy vary depending not only on clinical stages,but also on associated risk factors and other personal clinical characteristics.Patients with non-muscle invasive bladder cancer(NMIBC)have a high 5-year recurrence rate of 60%-70%(Berdik,2017)and those with muscle invasive bladder cancer(MIBC)has a relatively poor prognosis with approximately 65%risk of death within 5-year follow-up(Kamat et al.,2016).Therefore,there is an urgent need to develop models for bladder cancer to screen for rational treatment strategies by personalized medicine to improve the clinical assessment and treatment of bladder cancer.
基金the National Natural Science Foundation of China(project no.81971936)Hubei Province's Outstanding Medical Academic Leader Program,Foundation for Innovative Research Groups of the Natural Science Foundation of Hubei(project no.2020CFA015)the Funda-mental Research Funds for the Central Universities(project no.2042022kf1215 and 2042021gf0013)and Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital,Wuhan University.
文摘Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.
文摘因为他们的能力， B 房间通常被认为是有免疫力的反应的积极管理者生产抗体，包括自身抗体。因为 B 房间用作介绍抗原的房间并且在有免疫力的回答施加另外的调节功能，抗体的生产便于最佳的 CD4 <sup>+</sup>T 房间激活。然而，某些 B 房间能否定地也由生产规章的 cytokines 并且直接经由 cell-to-cell 接触与病原的 T 房间交往调整有免疫力的反应。B 房间的这些类型被定义为规章的 B (Breg ) 房间。Breg 房间的规章的函数在发炎的鼠标模型被表明了，癌症，移植，并且特别地在 autoimmunity。在这评论，我们集中于在人的自体免疫的疾病导致发展的理解和 Breg 房间的功能和 B 房间的含意的最近的进展。
基金This work was supported by grants from the National Natural Science Foundation of China （Grant Nos. 31470881, 81072453）, the Specialized Research Fund for the Doctoral Program of Higher Education （Grant No. 20133227110008）, the Health Department Foundation of Jiangsu Province （Grant No. Z201312）, the Graduate Student Research and the Innovation Program of Jiangsu Province （Grant No. KYLX_1074）, the Jiangsu Province ＇333＇ Project （Grant No. BRA2015197 ）, the Priority Academic Program Development of Jiangsu Higher Education Institutions, the National Basic Research Program of China （2014CB541904）, and the Hong Kong Croucher Foundation.
文摘最近的研究在嗅觉的薄板 propria 作为居民干细胞的一种新类型识别了嗅觉的 ecto 间充质的干细胞(OE-MSCs ) 。然而，它仍然保持不清楚是否 OE-MSCs 拥有任何 immunoregulatory 功能。在这研究，我们发现老鼠 OE-MSCs 比骨头表示了更高转变的生长因素贝它和 interleukin-10 层次导出髓的 MSC。在文化， OE-MSCs 经由直接压制受动器 T 房间增长并且增加规章的 T (Treg ) 房间扩大施加了他们的抑制免疫力的能力。在有导致骨胶原的关节炎的老鼠， OE-MSCs 的采纳转移显著地压制了关节炎发作和疾病严厉，它被增加的 Treg 房间伴随并且在 vivo 减少了 Th1/Th17 房间回答。一起拿，我们的调查结果在调整 T 房间回答识别了 OE-MSCs 的新奇功能，显示那 OE-MSCs 可以为风湿性关节炎和另外的自体免疫的疾病的处理代表新房间治疗。
基金part support by a GUMC COVID-19 grant (to XL)the support from Center for Cell Reprogramming,GUMC。
文摘Cancer cell lines have been used widely in cancer biology, and as biological or functional cell systems in many biomedical research fields. These cells are usually defective for many normal activities or functions due to significant genetic and epigenetic changes. Normal primary cell yields and viability from any original tissue specimens are usually relatively low or highly variable. These normal cells cease after a few passages or population doublings due to very limited proliferative capacity. Animal models(ferret, mouse, etc.) are often used to study virus-host interaction. However, viruses usually need to be adapted to the animals by several passages due to tropism restrictions including viral receptors and intracellular restrictions. Here we summarize applications of conditionally reprogrammed cells(CRCs), long-term cultures of normal airway epithelial cells from human nose to lung generated by conditional cell reprogramming(CR) technology, as an ex vivo model in studies of emerging viruses. CR allows to robustly propagate cells from non-invasive or minimally invasive specimens, for example, nasal or endobronchial brushing. This process is rapid(2 days) and conditional. The CRCs maintain their differentiation potential and lineage functions, and have been used for studies of adenovirus, rhinovirus, respiratory syncytial virus, influenza viruses, parvovirus, and SARS-CoV. The CRCs can be easily used for airliquid interface(ALI) polarized 3 D cultures, and these coupled CRC/ALI cultures mimic physiological conditions and are suitable for studies of viral entry including receptor binding and internalization, innate immune responses, viral replications, and drug discovery as an ex vivo model for emerging viruses.
