Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have s...Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have switched from a cancercentric model to a TME-centric one,considering the increasing significance of TME in cancer biology.Nonetheless,the clinical efficacy of therapeutic strategies targeting TME,especially the specific cells or pathways of TME,remains unsatisfactory.Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods.Herein,we present an updated image of TME with emphasis on hypoxic niche,immune microenvironment,metabolism microenvironment,acidic niche,innervated niche,and mechanical microenvironment.We then summarize conventional drugs including aspirin,celecoxib,β-adrenergic antagonist,metformin,and statin in new antitumor application.These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice.We also provide our outlook on directions and potential applications of TME theory.This review depicts a comprehensive and vivid landscape of TME from biology to treatment.展开更多
A major feature of neurodegeneration is disruption of central nervous system homeostasis,during which microglia play diverse roles.In the central nervous system,microglia serve as the first line of immune defense and ...A major feature of neurodegeneration is disruption of central nervous system homeostasis,during which microglia play diverse roles.In the central nervous system,microglia serve as the first line of immune defense and function in synapse pruning,injury repair,homeostasis maintenance,and regulation of brain development through scavenging and phagocytosis.Under pathological conditions or various stimulations,microglia proliferate,aggregate,and undergo a variety of changes in cell morphology,immunophenotype,and function.This review presents the features of microglia,especially their diversity and ability to change dynamically,and reinterprets their role as sensors for multiple stimulations and as effectors for brain aging and neurodegeneration.This review also summarizes some therapeutic approaches for neurodegenerative diseases that target microglia.展开更多
The culturable bacterial population and phospholipid fatty acid （PLFA） profile of casing soil were investigated at different mushroom （Agaricus bisporus） cropping stages. The change in soil bacterial PLFAs was alw...The culturable bacterial population and phospholipid fatty acid （PLFA） profile of casing soil were investigated at different mushroom （Agaricus bisporus） cropping stages. The change in soil bacterial PLFAs was always accompanied by a change in the soil eulturable bacterial population in the first flush. Comparatively higher culturable bacterial population and bacterial PLFAs were found in the casing soil at the primordia formation stage of the first flush. There was a significant increase in the ratio of fungal to bacterial PLFAs during mushroom growth. Multivariate analysis of PLFA data demonstrated that the mushroom cropping stage could considerably affect the microbial community structure of the casing soil. The bacterial population increased significantly from casing soil application to the primordia formation stage of the first flush. Casing soil application resulted in an increase in the ratio of gram-negative bacterial PLFAs to gram-positive bacterial PLFAs, suggesting that some gram-negative bacteria might play an important role in mushroom sporophore initiation.展开更多
Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment...Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.展开更多
Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognos...Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognosis.1 Although,N4-Acetylcytidine(ac4C)represents one of the extensive chemical modifications in mRNAs that plays a pivotal role in modulating mRNA stability and the mRNA translation process(Fig.1b).展开更多
Background Although the use of hepatitis B immunoglobulin （HBIG） may lead to a significant reduction in recurrent hepatitis B virus （HBV） infection and improve the survival of patients who have undergone liver tra...Background Although the use of hepatitis B immunoglobulin （HBIG） may lead to a significant reduction in recurrent hepatitis B virus （HBV） infection and improve the survival of patients who have undergone liver transplantation （LT） for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients. Methods Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing （ABI 3037）. Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred. Results Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 （45.5%0） subjects, whereas TG in 31（40.3%） and GG in 11（14.3%）. In the 559G carrier group （n=42, 54.5%）, the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group （n=35, 45.5%）, the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups （P〈0.05）. Conclusions A single nucleotide polymorphism （T/G） at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detectina FCGR3A aenotypes can be a clinical reference, of the HBIG administ展开更多
Background： The effect of ovarian hyperstimulation syndrome （OH SS） on pregnancy outcomes of in vitro fertilization （IVF） patients is still ambiguous. Tbis study aimed to analyze pregnancy outcomes of IVF with or...Background： The effect of ovarian hyperstimulation syndrome （OH SS） on pregnancy outcomes of in vitro fertilization （IVF） patients is still ambiguous. Tbis study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients. Methods： A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm deliver）,, preterm birth before 34 weeks＇ gestation, cesarean delivery, low birth weight （LBW）, and small-for-gestational age （SGA） between the two groups. Odds ratios （ORs） and 95% confidence intervals （Cls） of measure of clinical pregnancy were also analyzed. Results： The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients （91.8% vs. 43.5%, P 〈 0.001）. After controlling for drug protocol and causes of infertility, the adjusted ORs of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 （95% CI, 1.86-11.61 ） and 5.83 （95% CI, 3.45-9.86）, respectively. There were no significant differences in rates of muhiple pregnancy （4.0% vs. 3.7%） and miscarriage （16.1% vs. 17.5%） between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth （82.1% vs. 78.8%）, preterm delivery （20.9% vs. 17.5%）, preterm birth before 34 weeks＇ gestation （8.6% vs. 7.9%）, cesarean delivery （84.9% vs. 66.3%）, LBW （30.2% vs. 23.5%）, and SGA （21.9% vs. 17.6%） between the two groups. Conclusion： OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.展开更多
基金supported by funding from the Project Nn10 of Harbin Medical University Cancer Hospital(Grant Number Nn102017-02)National Natural Science Foundation of China(Grant Number 81602323,81872149)+3 种基金Outstanding Youth Project of Heilongjiang Provincial Natural Science Foundation(Grant Number YQ2019H027)Distinguished Young Scholars of Harbin Medical University Cancer Hospital(Grant Number JCQN2018-03)Yong Elite Training Foundation Grant of Harbin Medical University Cancer Hospital(Grant Number JY2016-02)Haiyan Fund Project of Harbin Medical University Cancer Hospital(Grant Number JJQN 2018-10).
文摘Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have switched from a cancercentric model to a TME-centric one,considering the increasing significance of TME in cancer biology.Nonetheless,the clinical efficacy of therapeutic strategies targeting TME,especially the specific cells or pathways of TME,remains unsatisfactory.Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods.Herein,we present an updated image of TME with emphasis on hypoxic niche,immune microenvironment,metabolism microenvironment,acidic niche,innervated niche,and mechanical microenvironment.We then summarize conventional drugs including aspirin,celecoxib,β-adrenergic antagonist,metformin,and statin in new antitumor application.These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice.We also provide our outlook on directions and potential applications of TME theory.This review depicts a comprehensive and vivid landscape of TME from biology to treatment.
基金the National Natural Science Foundation of China,Nos.81401279(to ZYY),81873740(to ZYY)China International Medical Exchange Fund,No.2019-anesthesia-14(to ZYY)+3 种基金the Natural Science Foundation of Shanghai of China,No.18ZR1443100(to ZYY)Wuxin Project of International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine of China,No.2018-38(to ZYY)Shanghai Jiao Tong University School of Medicine,Innovation Center of Translational Medicine Collaboration of China,No.TM201729(to ZYY)the 12th Undergraduate Training Programs for Innovation of Shanghai Jiao Tong University School of Medicine of China,No.1218201(to YX,MZJ and WLJ)。
文摘A major feature of neurodegeneration is disruption of central nervous system homeostasis,during which microglia play diverse roles.In the central nervous system,microglia serve as the first line of immune defense and function in synapse pruning,injury repair,homeostasis maintenance,and regulation of brain development through scavenging and phagocytosis.Under pathological conditions or various stimulations,microglia proliferate,aggregate,and undergo a variety of changes in cell morphology,immunophenotype,and function.This review presents the features of microglia,especially their diversity and ability to change dynamically,and reinterprets their role as sensors for multiple stimulations and as effectors for brain aging and neurodegeneration.This review also summarizes some therapeutic approaches for neurodegenerative diseases that target microglia.
基金Project supported by the National Natural Science Foundation of China (No.30671207)the Key Program of Science and Technology Plan of Zhejiang Province, China (No.2003C32042)the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education, China
文摘The culturable bacterial population and phospholipid fatty acid （PLFA） profile of casing soil were investigated at different mushroom （Agaricus bisporus） cropping stages. The change in soil bacterial PLFAs was always accompanied by a change in the soil eulturable bacterial population in the first flush. Comparatively higher culturable bacterial population and bacterial PLFAs were found in the casing soil at the primordia formation stage of the first flush. There was a significant increase in the ratio of fungal to bacterial PLFAs during mushroom growth. Multivariate analysis of PLFA data demonstrated that the mushroom cropping stage could considerably affect the microbial community structure of the casing soil. The bacterial population increased significantly from casing soil application to the primordia formation stage of the first flush. Casing soil application resulted in an increase in the ratio of gram-negative bacterial PLFAs to gram-positive bacterial PLFAs, suggesting that some gram-negative bacteria might play an important role in mushroom sporophore initiation.
基金This study was supported by research grants from the National Natural Science Foundation of China to H.H.(82060442)the Foundation of the Education Department of Guizhou Province(no.[2022]214)+1 种基金the Undergraduate Teaching Engineering Construction Project of Guizhou College of Traditional Chinese Medicine to Y.X.(no.GZY-JG(2018)6)This work was funded in part by the China Scholarship Council(No.202008520053 to Y.X.).
文摘Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.
基金the National Natural Science Foundation of China(Grant no.81960273)Gansu Natural Science Foundation(No.18JR3RA343)+4 种基金Gansu Fund project for Distinguished Young Scholars(No.18JR3RA262)the Key Projects of Department of Science and Technology in Gansu Province,China(No.1602FKDA001)the Science and Technology Innovation and Development Special Funding of Gansu province,China(G.F.R[2018]No.32)the Science and Technology Bureau 2018 Fund of the Chengguan District(2018KJGG0037)National Key Research and Development Program of China(No.2017FYA0205302).
文摘Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognosis.1 Although,N4-Acetylcytidine(ac4C)represents one of the extensive chemical modifications in mRNAs that plays a pivotal role in modulating mRNA stability and the mRNA translation process(Fig.1b).
基金the State Key Basic Research and Development Program of China(973,No.2003CB515500)the Natural Science Foundation of Zhejiang Province (No. 2004C33108).
文摘Background Although the use of hepatitis B immunoglobulin （HBIG） may lead to a significant reduction in recurrent hepatitis B virus （HBV） infection and improve the survival of patients who have undergone liver transplantation （LT） for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients. Methods Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing （ABI 3037）. Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred. Results Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 （45.5%0） subjects, whereas TG in 31（40.3%） and GG in 11（14.3%）. In the 559G carrier group （n=42, 54.5%）, the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group （n=35, 45.5%）, the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups （P〈0.05）. Conclusions A single nucleotide polymorphism （T/G） at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detectina FCGR3A aenotypes can be a clinical reference, of the HBIG administ
文摘Background： The effect of ovarian hyperstimulation syndrome （OH SS） on pregnancy outcomes of in vitro fertilization （IVF） patients is still ambiguous. Tbis study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients. Methods： A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm deliver）,, preterm birth before 34 weeks＇ gestation, cesarean delivery, low birth weight （LBW）, and small-for-gestational age （SGA） between the two groups. Odds ratios （ORs） and 95% confidence intervals （Cls） of measure of clinical pregnancy were also analyzed. Results： The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients （91.8% vs. 43.5%, P 〈 0.001）. After controlling for drug protocol and causes of infertility, the adjusted ORs of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 （95% CI, 1.86-11.61 ） and 5.83 （95% CI, 3.45-9.86）, respectively. There were no significant differences in rates of muhiple pregnancy （4.0% vs. 3.7%） and miscarriage （16.1% vs. 17.5%） between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth （82.1% vs. 78.8%）, preterm delivery （20.9% vs. 17.5%）, preterm birth before 34 weeks＇ gestation （8.6% vs. 7.9%）, cesarean delivery （84.9% vs. 66.3%）, LBW （30.2% vs. 23.5%）, and SGA （21.9% vs. 17.6%） between the two groups. Conclusion： OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.
