Telomeres are nucleoprotein structures located at the end of each chromosome,which function in terminal protection and genomic stability.Telomeric damage is closely related to replicative senescence in vitro and physi...Telomeres are nucleoprotein structures located at the end of each chromosome,which function in terminal protection and genomic stability.Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo.As relatively long-lived mammals based on body size,bats display unique telomeric patterns,including the upregulation of genes involved in alternative lengthening of telomeres(ALT),DNA repair,and DNA replication.At present,however,the relevant molecular mechanisms remain unclear.In this study,we performed cross-species comparison and identified EPAS1,a well-defined oxygen response gene,as a key telomeric protector in bat fibroblasts.Bat fibroblasts showed high expression of EPAS1,which enhanced the transcription of shelterin components TRF1 and TRF2,as well as DNA repair factor RAD50,conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion.Based on a human single-cell transcriptome atlas,we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation.Using in vitro-cultured human pulmonary endothelial cells,we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans.In addition,the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence.In conclusion,we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging,drawing insights from the longevity of bats.展开更多
BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatme...BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.展开更多
BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study eval...BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS:Male Sprague Dawley rats were randomly divided into 3 treatment groups(n=6,each):sham-operated,vehicle(normal saline)^+TBI,and PACAP^+TBI.Normal saline or PACAP(1 ug/5uL) was administered intracerebroventricularly 20 minutes before TBI.Right parietal cortical contusion was produced via a weight-dropping method.Brains were extracted 24 hours after trauma.Histological changes in brains were examined by HE staining.The numbers of CD4^+ and CD8^+ T cells in blood and the spleen were detected via flow cytometry.RESULTS:In injured brain regions,edema,hemorrhage,inflammatory cell infiltration,and swollen and degenerated neurons were observed under a light microscope,and the neurons were disorderly arrayed in the hippocampi.Compared to the sham group,average CD4^+ CD8" lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI^+vehicle,and CD4^+ CD8^+ were increased.In rats administered PACAP prior to TBI,damage was attenuated as evidenced by significantly increased CD4^+,and decreased CD8^+,T lymphocytes in blood and the spleen.CONCLUSION:Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.展开更多
基金supported by the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(202201AS070044)National Key Research&Developmental Program of China(2021YFA0805701)+1 种基金Chinese Academy of Sciences(CAS)“Light of West China”Program(xbzg-zdsys-202113)Kunming Science and Technology Bureau(2022SCP007)。
文摘Telomeres are nucleoprotein structures located at the end of each chromosome,which function in terminal protection and genomic stability.Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo.As relatively long-lived mammals based on body size,bats display unique telomeric patterns,including the upregulation of genes involved in alternative lengthening of telomeres(ALT),DNA repair,and DNA replication.At present,however,the relevant molecular mechanisms remain unclear.In this study,we performed cross-species comparison and identified EPAS1,a well-defined oxygen response gene,as a key telomeric protector in bat fibroblasts.Bat fibroblasts showed high expression of EPAS1,which enhanced the transcription of shelterin components TRF1 and TRF2,as well as DNA repair factor RAD50,conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion.Based on a human single-cell transcriptome atlas,we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation.Using in vitro-cultured human pulmonary endothelial cells,we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans.In addition,the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence.In conclusion,we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging,drawing insights from the longevity of bats.
基金Shanghai Pudong New Area Health Commission’s Excellent Young Medical Talent Training Plan,No.PWRq2020-68Shanghai Pudong New Area Health Commission Discipline Leader Training Project,No.PWRd2020-16Shanghai Pudong New Area Science and Technology Development Fund,No.PKJ2020-Y36.
文摘BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.
文摘BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS:Male Sprague Dawley rats were randomly divided into 3 treatment groups(n=6,each):sham-operated,vehicle(normal saline)^+TBI,and PACAP^+TBI.Normal saline or PACAP(1 ug/5uL) was administered intracerebroventricularly 20 minutes before TBI.Right parietal cortical contusion was produced via a weight-dropping method.Brains were extracted 24 hours after trauma.Histological changes in brains were examined by HE staining.The numbers of CD4^+ and CD8^+ T cells in blood and the spleen were detected via flow cytometry.RESULTS:In injured brain regions,edema,hemorrhage,inflammatory cell infiltration,and swollen and degenerated neurons were observed under a light microscope,and the neurons were disorderly arrayed in the hippocampi.Compared to the sham group,average CD4^+ CD8" lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI^+vehicle,and CD4^+ CD8^+ were increased.In rats administered PACAP prior to TBI,damage was attenuated as evidenced by significantly increased CD4^+,and decreased CD8^+,T lymphocytes in blood and the spleen.CONCLUSION:Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.
