Obesity is a major risk factor for diabetes,cardiovascular disease,and certain cancers.It arises from a chronic positive energy balance.This is usually due to unrestricted access to food in the context of genetic and ...Obesity is a major risk factor for diabetes,cardiovascular disease,and certain cancers.It arises from a chronic positive energy balance.This is usually due to unrestricted access to food in the context of genetic and epigenetic vulnerabilities.And an increasingly sedentary lifestyle.Over the past few decades,our understanding of the fluid and nervous systems that mediate energy balance control has greatly improved.However,our ability to formulate effective strategies to slow the current obesity epidemic has been hampered,mainly because we have limited knowledge of the resistance mechanisms of metabolic hormones such as leptin.Resistance to leptin is a sign of obesity,leptin is a key hormone for neuroendocrine control of energy balance.In the past few years,we have made tremendous progress in our in-depth research on the cellular pathways that disrupt the action of leptin.In this review,we discuss the molecular mechanisms of leptin resistance and how to use them as targets for obesity drug therapy.展开更多
Two brown spot disease resistant varieties of tobacco, named NC89 V1 and NC89 V2, were obtained by first inducing from disease sensitive NC89 with the two hypovirulent viruses ToMV N14 and CMV SV52, then tissue ...Two brown spot disease resistant varieties of tobacco, named NC89 V1 and NC89 V2, were obtained by first inducing from disease sensitive NC89 with the two hypovirulent viruses ToMV N14 and CMV SV52, then tissue culturing the plants and finally seed breeding. The disease resistance for both varieties was verified to be stable in three generations. The transcription activities of five plant defense response genes, pr 1a, chi, chs, pal, and lox, in NC89, NC89 V1, and NC89 V2 were studied through RNA blot hybridization. Genome DNA structural differences among the three tobacco lines were identified using randomly amplified polymorphic DNA(RAPD).展开更多
With the flourishing development of precision medicine,theranostics,generally recognized as the integration of diagnosis and treatment,has emerged as a prominent trend in clinical research.However,theranostics primari...With the flourishing development of precision medicine,theranostics,generally recognized as the integration of diagnosis and treatment,has emerged as a prominent trend in clinical research.However,theranostics primarily emphasizes the end result of integration,without providing sufficient details on how precise diagnosis and synergetic individualized treatment could be achieved and what clinical challenges could be effectively addressed in clinical practice.Molecular probe technology provides a robust method to bridge the gap between theory and practice.Through meticulous design of the chemical structure,imaging labels or drugs were conjugated to tumor-targeting peptides,antibodies,or inducers to form molecular probes,which allow a seamless switch between targeted intervention and targeted imaging with consistency in time,space,and biodistribution.Thus,this review proposes a concept called“molecular eye”,which refers to a comprehensive system for precise diagnosis and treatment of major clinical diseases based on molecular probe technology.This medical system emphasizes the chemical basis of probe development and optimization,which can provide precise actionable information for clinical decision making,allow molecular-targeted therapy,expand the indications of old therapy,and accelerate the regulatory approval of molecular drugs.“Molecular eye”resembles the piercing eye of the Monkey King,which can detect previously“invisible”diseases and facilitate disease diagnosis,treatment,real-time evaluation,and pathology research,guiding drug development.The emergence of the“molecular eyes”will provide opportunities and challenges in the fields of clinical practice and medical research and propel the progression of contemporary medicine toward precision medicine.展开更多
Terpenoids are the largest and most diverse class of plant-specialized metabolites, which function in diverse physiological processes during plant development. In the biosynthesis of plant terpenoids, short-chain pren...Terpenoids are the largest and most diverse class of plant-specialized metabolites, which function in diverse physiological processes during plant development. In the biosynthesis of plant terpenoids, short-chain prenyltransferases （SC-PTs）, together with terpene synthases （TPSs）, play critical roles in determining terpenoid diversity. SC-PTs biosynthesize prenyl pyrophosphates with different chain lengths, and these compounds are the direct precursors of terpenoids. Arabidopsis thaliana possesses a subgroup of SC-PTs whose functions are not clearly known. In this study, we focus on 10 geranylgeranyl pyro- phosphate synthase-like [GGPPSL] proteins, which are commonly thought to produce GGPP [C20]. We found that a subset of members of the Arabidopsis GGPPSL gene family have undergone neo- functionalization： GGPPSL6, 7, 9, and 10 mainly have geranylfarnesyl pyrophosphate synthase activity （C25; renamed AtGFPPS1, 2, 3, and 4）, and GGPPSL8 produces even longer chain prenyl pyrophosphate （〉C30; renamed polyprenyl pyrophosphate synthase 2, AtPPPS2）. By solving the crystal structures of AtGFPPS2, AtPPPS2, and AtGGPPS11, we reveal the product chain-length determination mechanism of SC-PTs and interpret it as a ＂three floors＂ model. Using this model, we identified a novel GFPPS clade distributed in Brassicaceae plants and found that the GFPPS gene typically occurs in tandem with a gene encoding a TPS, forming a GFPPS-TPS gene cluster.展开更多
Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast ...Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre- existing T-cell function to modulate antitumor immunity. in this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/ PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural informationwill benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.展开更多
Antibiotic resistance and the growing burden of bacteria-induced cancers highlight the urgent need for innovative therapeutic approaches.Drug repurposing,leveraging pre-approved antibiotics for novel applications,is a...Antibiotic resistance and the growing burden of bacteria-induced cancers highlight the urgent need for innovative therapeutic approaches.Drug repurposing,leveraging pre-approved antibiotics for novel applications,is a promising strategy to address this challenge.Antibiotics designed to combat bacterial infections can inhibit microbial activity and target cellular mechanisms associated with oncogenesis.Chronic bacterial infections,such as those caused by Salmonella typhi,Helicobacter pylori,and Escherichia coli,contribute significantly to gallbladder,gastric,kidney,and bladder cancers.These infections induce inflammation,DNA damage,and the disruption of cellular pathways,promoting the development of cancer.Antibiotics such as doxycycline,rifampicin,and azithromycin demonstrate anticancer properties by inhibiting angiogenesis,inducing apoptosis,and regulating key pathways including the interleukin(IL)-6 signaling pathway and autophagy-related pathways.This dual action enhances chemotherapeutic efficacy and addresses bacteria-induced oncogenesis,offering a cost-effective and time-efficient alternative to traditional drug discovery.Herein,we review the intricate mechanisms by which bacteria-induced cancer arises and explore the groundbreaking potential of repurposing antibiotics as dual-action therapies in oncology.By elucidating the pivotal role of biofilms in persistent infections and highlighting untapped therapeutic opportunities in antibiotic repurposing,this review underscores a transformative approach to cancer treatment.This article explores the potential of repurposing antibiotic drugs for cancer treatment and highlights the prospects of drug repurposing strategies.展开更多
基金This work was supported by the Postgraduate Innovation Funding project of Hebei University(Grant No:hbu2020ss083).
文摘Obesity is a major risk factor for diabetes,cardiovascular disease,and certain cancers.It arises from a chronic positive energy balance.This is usually due to unrestricted access to food in the context of genetic and epigenetic vulnerabilities.And an increasingly sedentary lifestyle.Over the past few decades,our understanding of the fluid and nervous systems that mediate energy balance control has greatly improved.However,our ability to formulate effective strategies to slow the current obesity epidemic has been hampered,mainly because we have limited knowledge of the resistance mechanisms of metabolic hormones such as leptin.Resistance to leptin is a sign of obesity,leptin is a key hormone for neuroendocrine control of energy balance.In the past few years,we have made tremendous progress in our in-depth research on the cellular pathways that disrupt the action of leptin.In this review,we discuss the molecular mechanisms of leptin resistance and how to use them as targets for obesity drug therapy.
文摘Two brown spot disease resistant varieties of tobacco, named NC89 V1 and NC89 V2, were obtained by first inducing from disease sensitive NC89 with the two hypovirulent viruses ToMV N14 and CMV SV52, then tissue culturing the plants and finally seed breeding. The disease resistance for both varieties was verified to be stable in three generations. The transcription activities of five plant defense response genes, pr 1a, chi, chs, pal, and lox, in NC89, NC89 V1, and NC89 V2 were studied through RNA blot hybridization. Genome DNA structural differences among the three tobacco lines were identified using randomly amplified polymorphic DNA(RAPD).
基金supported by the National Natural Science Foundation of China(12275135)Jiangsu Province University Natural Science Research Project(21KJB350015)Nanjing Medical University High Level Talent Introduction Research Initiation Fund(NMUR20210003).
文摘With the flourishing development of precision medicine,theranostics,generally recognized as the integration of diagnosis and treatment,has emerged as a prominent trend in clinical research.However,theranostics primarily emphasizes the end result of integration,without providing sufficient details on how precise diagnosis and synergetic individualized treatment could be achieved and what clinical challenges could be effectively addressed in clinical practice.Molecular probe technology provides a robust method to bridge the gap between theory and practice.Through meticulous design of the chemical structure,imaging labels or drugs were conjugated to tumor-targeting peptides,antibodies,or inducers to form molecular probes,which allow a seamless switch between targeted intervention and targeted imaging with consistency in time,space,and biodistribution.Thus,this review proposes a concept called“molecular eye”,which refers to a comprehensive system for precise diagnosis and treatment of major clinical diseases based on molecular probe technology.This medical system emphasizes the chemical basis of probe development and optimization,which can provide precise actionable information for clinical decision making,allow molecular-targeted therapy,expand the indications of old therapy,and accelerate the regulatory approval of molecular drugs.“Molecular eye”resembles the piercing eye of the Monkey King,which can detect previously“invisible”diseases and facilitate disease diagnosis,treatment,real-time evaluation,and pathology research,guiding drug development.The emergence of the“molecular eyes”will provide opportunities and challenges in the fields of clinical practice and medical research and propel the progression of contemporary medicine toward precision medicine.
文摘Terpenoids are the largest and most diverse class of plant-specialized metabolites, which function in diverse physiological processes during plant development. In the biosynthesis of plant terpenoids, short-chain prenyltransferases （SC-PTs）, together with terpene synthases （TPSs）, play critical roles in determining terpenoid diversity. SC-PTs biosynthesize prenyl pyrophosphates with different chain lengths, and these compounds are the direct precursors of terpenoids. Arabidopsis thaliana possesses a subgroup of SC-PTs whose functions are not clearly known. In this study, we focus on 10 geranylgeranyl pyro- phosphate synthase-like [GGPPSL] proteins, which are commonly thought to produce GGPP [C20]. We found that a subset of members of the Arabidopsis GGPPSL gene family have undergone neo- functionalization： GGPPSL6, 7, 9, and 10 mainly have geranylfarnesyl pyrophosphate synthase activity （C25; renamed AtGFPPS1, 2, 3, and 4）, and GGPPSL8 produces even longer chain prenyl pyrophosphate （〉C30; renamed polyprenyl pyrophosphate synthase 2, AtPPPS2）. By solving the crystal structures of AtGFPPS2, AtPPPS2, and AtGGPPS11, we reveal the product chain-length determination mechanism of SC-PTs and interpret it as a ＂three floors＂ model. Using this model, we identified a novel GFPPS clade distributed in Brassicaceae plants and found that the GFPPS gene typically occurs in tandem with a gene encoding a TPS, forming a GFPPS-TPS gene cluster.
基金This work was supported by the National Basic Research Program （973 Program） （Nos. 2013CB531502 and 2014CB542503）, the National Natural Science Foundation of China （Grant Nos. 31390432 and 31500722）, Grand S＆T project of China Health and Family Planning Commission （2013ZX10004608-002 and 2016ZX10004201-009）, the Strategic Priority Research Program of the Chinese Academy of Sciences （CAS XDB08020100）. GFG is supported partly as a leading principal investigator of the NSFC Innovative Research Group （81321063）.
文摘Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre- existing T-cell function to modulate antitumor immunity. in this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/ PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural informationwill benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
文摘Antibiotic resistance and the growing burden of bacteria-induced cancers highlight the urgent need for innovative therapeutic approaches.Drug repurposing,leveraging pre-approved antibiotics for novel applications,is a promising strategy to address this challenge.Antibiotics designed to combat bacterial infections can inhibit microbial activity and target cellular mechanisms associated with oncogenesis.Chronic bacterial infections,such as those caused by Salmonella typhi,Helicobacter pylori,and Escherichia coli,contribute significantly to gallbladder,gastric,kidney,and bladder cancers.These infections induce inflammation,DNA damage,and the disruption of cellular pathways,promoting the development of cancer.Antibiotics such as doxycycline,rifampicin,and azithromycin demonstrate anticancer properties by inhibiting angiogenesis,inducing apoptosis,and regulating key pathways including the interleukin(IL)-6 signaling pathway and autophagy-related pathways.This dual action enhances chemotherapeutic efficacy and addresses bacteria-induced oncogenesis,offering a cost-effective and time-efficient alternative to traditional drug discovery.Herein,we review the intricate mechanisms by which bacteria-induced cancer arises and explore the groundbreaking potential of repurposing antibiotics as dual-action therapies in oncology.By elucidating the pivotal role of biofilms in persistent infections and highlighting untapped therapeutic opportunities in antibiotic repurposing,this review underscores a transformative approach to cancer treatment.This article explores the potential of repurposing antibiotic drugs for cancer treatment and highlights the prospects of drug repurposing strategies.
