Pygeum africanum （Tadenan） is a popular phytotherapeutic agent used in the treatment of symptomatic benign prostatic hyperplasia. The active compounds of the drug have not been identified, and determining the plasma...Pygeum africanum （Tadenan） is a popular phytotherapeutic agent used in the treatment of symptomatic benign prostatic hyperplasia. The active compounds of the drug have not been identified, and determining the plasma concentration of the drug is, therefore, not possible. Because there are conflicting results on the efficacy of this drug, we aimed to investigate its effect on prostate cell growth in vitro using human serum collected before and after Pygeum africanum intake. We used primary and organotypic cultures of human prostatic stromal myofibroblast cell line WPMY and prostatic epithelial cell line PNT2. We also used fresh benign prostatic tissue. The serum of a treated man induced decreases in the proliferation of primary cells, organotypic cells and WPMY cells but not PNT2 cells. We also analysed the effect of treated serum on the gene expression profile of WPMY cells. The transcriptome analysis revealed an upregulation of genes involved in multiple tumour suppression pathways and a downregulation of genes involved in inflammation and oxidative-stress pathways. The oral intake of Pygeum africanum resulted in serum levels of active substances that were sufficient to inhibit the proliferation of cultured myofibroblasts prostatic cells. This inhibition was associated with changes in the transcriptome. Asian Journal of Andrology（2012） 14, 499-504; doi：lO.1038/aja.2011.132; published online 26 December 2011展开更多
Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor progno...Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor prognosis.Several mutated genes and epigenetic changes have been detected in CCA,with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets.Accessing tumoral components and genetic material is therefore crucial for the diagnosis,management and selection of targeted therapies;but sampling tumor tissue,when possible,is often risky and difficult to be repeated at different time points.Liquid biopsy(LB)represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples.Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated,allowing a real-time monitoring of the tumor genetic profile or the response to therapy.In this review,we analysis the current evidence on the possible roles of LB(circulating DNA,circulating RNA,exosomes,cytokines)in the diagnosis and management of patients affected by CCA.展开更多
Low anterior resection can be a challenging operation, especially in obese male patients and in particular after radiotherapy. Transanal total mesorectal excision(Ta TME) might offer technical advantages over laparosc...Low anterior resection can be a challenging operation, especially in obese male patients and in particular after radiotherapy. Transanal total mesorectal excision(Ta TME) might offer technical advantages over laparoscopic or open approaches particularly for tumors in the distal third of the rectum. The aim of this article is to review the current experience with Ta TME. The limits and future developments are also explored. Although the experience with Ta TME is still limited, it might be a promising alternative to laparoscopic TME, especially for difficult cases where laparoscopy is too demanding. The preliminary data on complications and short-term oncological outcomes are good, but also emphasize the importance of careful patient selection. Finally, there is a need for large-scale trials focusing on long-term outcomes and oncological safety before widespread adoption can be recommended.展开更多
Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by t...Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct.The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified counterparts.In contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune response.CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio n.In the latter,they hold immense potential as mediators of immune tolerance for recipients of allotransplants.However,current research into CAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic use.This review examines the rationale behind the development of CAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of CAR-Tregs in transplantation models to date.展开更多
Background and aims The intrahepatic processes associated with chronic hepatitis B(CHB),especially in the context of hepatitis delta virus(HDV)and HIV co-infection,require a better understanding.Spatial transcriptomic...Background and aims The intrahepatic processes associated with chronic hepatitis B(CHB),especially in the context of hepatitis delta virus(HDV)and HIV co-infection,require a better understanding.Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes,guiding new personalised treatments.Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape,cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus(HBV)and HDV or HIV co-infection.Method The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded(FFPE)biopsies from three treatment-naive patients with chronic HBV and HDV or HIV co-infection.The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest(ROIs).Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas.A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions.Results Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses.Shared features including‘cytotoxicity’and‘B cell receptor signalling’were consistent across patients,suggesting common elements alongside individual traits.HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment,whereas HIV/HBV co-infection featured genes related to interferon response regulation.Varied cellular characteristics and immune cell populations,with an abundance ofγδT cells in the HDV/HBV sample,were observed within analysed regions.Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression.Conclusion This proof-of-principle study shows the value of this platform in investigating the complex immune landscape,highlighting relevant host pathways to disease pathogenesis.展开更多
Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential....Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential.There is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation.We convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and gastroenterologists.The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers.We divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD outcomes.For each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD.There is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.展开更多
文摘Pygeum africanum （Tadenan） is a popular phytotherapeutic agent used in the treatment of symptomatic benign prostatic hyperplasia. The active compounds of the drug have not been identified, and determining the plasma concentration of the drug is, therefore, not possible. Because there are conflicting results on the efficacy of this drug, we aimed to investigate its effect on prostate cell growth in vitro using human serum collected before and after Pygeum africanum intake. We used primary and organotypic cultures of human prostatic stromal myofibroblast cell line WPMY and prostatic epithelial cell line PNT2. We also used fresh benign prostatic tissue. The serum of a treated man induced decreases in the proliferation of primary cells, organotypic cells and WPMY cells but not PNT2 cells. We also analysed the effect of treated serum on the gene expression profile of WPMY cells. The transcriptome analysis revealed an upregulation of genes involved in multiple tumour suppression pathways and a downregulation of genes involved in inflammation and oxidative-stress pathways. The oral intake of Pygeum africanum resulted in serum levels of active substances that were sufficient to inhibit the proliferation of cultured myofibroblasts prostatic cells. This inhibition was associated with changes in the transcriptome. Asian Journal of Andrology（2012） 14, 499-504; doi：lO.1038/aja.2011.132; published online 26 December 2011
文摘Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor prognosis.Several mutated genes and epigenetic changes have been detected in CCA,with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets.Accessing tumoral components and genetic material is therefore crucial for the diagnosis,management and selection of targeted therapies;but sampling tumor tissue,when possible,is often risky and difficult to be repeated at different time points.Liquid biopsy(LB)represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples.Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated,allowing a real-time monitoring of the tumor genetic profile or the response to therapy.In this review,we analysis the current evidence on the possible roles of LB(circulating DNA,circulating RNA,exosomes,cytokines)in the diagnosis and management of patients affected by CCA.
文摘Low anterior resection can be a challenging operation, especially in obese male patients and in particular after radiotherapy. Transanal total mesorectal excision(Ta TME) might offer technical advantages over laparoscopic or open approaches particularly for tumors in the distal third of the rectum. The aim of this article is to review the current experience with Ta TME. The limits and future developments are also explored. Although the experience with Ta TME is still limited, it might be a promising alternative to laparoscopic TME, especially for difficult cases where laparoscopy is too demanding. The preliminary data on complications and short-term oncological outcomes are good, but also emphasize the importance of careful patient selection. Finally, there is a need for large-scale trials focusing on long-term outcomes and oncological safety before widespread adoption can be recommended.
基金supported by the European Union’s Horizon 2020 Research and Innovation Program(RESHAPE,825392)to Joanna Hester and Fadi Issasupported by the Restore Research Trust。
文摘Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct.The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified counterparts.In contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune response.CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio n.In the latter,they hold immense potential as mediators of immune tolerance for recipients of allotransplants.However,current research into CAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic use.This review examines the rationale behind the development of CAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of CAR-Tregs in transplantation models to date.
基金supported by the US Department of Health and Human Services,National Institute of Health/National Institute of Allergy and Infectious Diseases/award(R01AI55182)to DPan Academy of Medical Sciences Starter Grant(SGL021/1030)+3 种基金Seedcorn funding Rosetrees/Stoneygate Trust(A2903)and Mid-Career Research Award from The Medical Research Foundation(MRF-044-0004-F-GILL-C0823)to USGMedical Sciences Division(0011187)Pump-Priming grant awarded to FI and JAMcKResearch in the McKeating laboratory is funded by a Wellcome Investigator Award 200838/Z/16/Z,Wellcome Discovery Award 225198/Z/22/ZChinese Academy of Medical Sciences Innovation Fund for Medical Science,China(grant number:2018-I2M-2-002).
文摘Background and aims The intrahepatic processes associated with chronic hepatitis B(CHB),especially in the context of hepatitis delta virus(HDV)and HIV co-infection,require a better understanding.Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes,guiding new personalised treatments.Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape,cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus(HBV)and HDV or HIV co-infection.Method The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded(FFPE)biopsies from three treatment-naive patients with chronic HBV and HDV or HIV co-infection.The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest(ROIs).Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas.A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions.Results Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses.Shared features including‘cytotoxicity’and‘B cell receptor signalling’were consistent across patients,suggesting common elements alongside individual traits.HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment,whereas HIV/HBV co-infection featured genes related to interferon response regulation.Varied cellular characteristics and immune cell populations,with an abundance ofγδT cells in the HDV/HBV sample,were observed within analysed regions.Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression.Conclusion This proof-of-principle study shows the value of this platform in investigating the complex immune landscape,highlighting relevant host pathways to disease pathogenesis.
文摘Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential.There is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation.We convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and gastroenterologists.The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers.We divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD outcomes.For each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD.There is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.
