Dear Editor,Predicting a patient's response to cancer therapies and identifying additional molecular targets is crucial for advancing cancer treatment.BRAFvoe-specific inhibitors have demonstrated promising initia...Dear Editor,Predicting a patient's response to cancer therapies and identifying additional molecular targets is crucial for advancing cancer treatment.BRAFvoe-specific inhibitors have demonstrated promising initial clinical results in solid tumors;however,side effects and drug resistance are common,and for most patients,response to BRAFvoot inhibitor therapy is transient.展开更多
Background: Stroke causes substantial death and disability worldwide, challenging healthcare systems and impacting patients' lives. Research on stroke biomarkers can aid in the development of targeted therapies, w...Background: Stroke causes substantial death and disability worldwide, challenging healthcare systems and impacting patients' lives. Research on stroke biomarkers can aid in the development of targeted therapies, while Zhenbao Pills (ZBP) from traditional Chinese medicine may enhance recovery from neurological disorders. Further investigations into the mechanisms of ZBP are crucial for better stroke management.Methods: This research accessed databases to pinpoint the core components and identify the targets of ZBP and stroke. "Drug-component-target" networks were established, followed by enrichment analysis of identified targets. We also used Mendelian randomization (MR) to assess causal relationships between feature genes and stroke incidence, for which colocalization was employed for validation. Furthermore, molecular docking and Gene Expression Omnibus (GEO) datasets were used for preliminary confirmation.Results: This study identified 14 core components and 105 stroke-related targets for ZBP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets are involved mainly in oxidative stress processes, lipid metabolism, and the PI3K-Akt signaling pathway. Correlation with stroke risk was determined through MR analysis, which revealed that the VEGFA and ARG1 genes were negatively correlated with stroke risk and GATM was positively correlated. Additionally, the stable interactions of molecular docking and differential expression of key genes support their potential therapeutic relevance.Conclusion: Stroke may be mitigated through essential constituents of ZBP (e.g., luteolin, quercetin, and isorhamnetin) that target pivotal genes (e.g., VEGFA, ARG1, and GATM), including characteristic genes, and the modulation of oxidative stress and inflammation-related pathways. These discoveries hold important implications for clinical practice and future research endeavors.展开更多
Prostate cancer is one of the most prevalent cancers in men,and there is no cure when it advances to a late stage.Antiandrogens are routinely used in clinics for prostate cancer treatment,and darolutamide(Daro)is the ...Prostate cancer is one of the most prevalent cancers in men,and there is no cure when it advances to a late stage.Antiandrogens are routinely used in clinics for prostate cancer treatment,and darolutamide(Daro)is the latest FDA-approved antiandrogen drug.^(1)Despite its efficacy,potential drug resistance poses significant challenges in the clinical setting.This study seeks to uncover the molecular mechanisms behind darolutamide resistance and identify potential therapeutic targets to overcome this resistance.展开更多
Osteosarcoma(OS)is a highly aggressive bone tumor that predominantly affects teenagers and young adults,characterized by rapid growth and a high propensity for metastasis.1 Despite significant advancements in surgical...Osteosarcoma(OS)is a highly aggressive bone tumor that predominantly affects teenagers and young adults,characterized by rapid growth and a high propensity for metastasis.1 Despite significant advancements in surgical techniques and chemotherapy,the survival rate for OS patients has plateaued over the past decades.2 Understanding the molecular mechanisms underlying OS progression and identifying new therapeutic targets remain critical for improving patient outcomes.Long non-coding RNAs(lncRNAs)are a class of functional RNA molecules that are typically over 200 nucleotides in length and cannot code for proteins.3 Initially considered as“junk DNA”,recent studies have revealed the crucial roles lncRNAs play in a wide range of biological processes,including cellular differentiation,apoptosis,inflammation,and cancer.展开更多
文摘Dear Editor,Predicting a patient's response to cancer therapies and identifying additional molecular targets is crucial for advancing cancer treatment.BRAFvoe-specific inhibitors have demonstrated promising initial clinical results in solid tumors;however,side effects and drug resistance are common,and for most patients,response to BRAFvoot inhibitor therapy is transient.
基金funded by the 2021 Inner Mongolia Higher Education Scientific Research Project(NJZY21063)the 2023 Project of the Natural Science Foundation of the Inner Mongolia Autonomous Region(2023LHMS08081).
文摘Background: Stroke causes substantial death and disability worldwide, challenging healthcare systems and impacting patients' lives. Research on stroke biomarkers can aid in the development of targeted therapies, while Zhenbao Pills (ZBP) from traditional Chinese medicine may enhance recovery from neurological disorders. Further investigations into the mechanisms of ZBP are crucial for better stroke management.Methods: This research accessed databases to pinpoint the core components and identify the targets of ZBP and stroke. "Drug-component-target" networks were established, followed by enrichment analysis of identified targets. We also used Mendelian randomization (MR) to assess causal relationships between feature genes and stroke incidence, for which colocalization was employed for validation. Furthermore, molecular docking and Gene Expression Omnibus (GEO) datasets were used for preliminary confirmation.Results: This study identified 14 core components and 105 stroke-related targets for ZBP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets are involved mainly in oxidative stress processes, lipid metabolism, and the PI3K-Akt signaling pathway. Correlation with stroke risk was determined through MR analysis, which revealed that the VEGFA and ARG1 genes were negatively correlated with stroke risk and GATM was positively correlated. Additionally, the stable interactions of molecular docking and differential expression of key genes support their potential therapeutic relevance.Conclusion: Stroke may be mitigated through essential constituents of ZBP (e.g., luteolin, quercetin, and isorhamnetin) that target pivotal genes (e.g., VEGFA, ARG1, and GATM), including characteristic genes, and the modulation of oxidative stress and inflammation-related pathways. These discoveries hold important implications for clinical practice and future research endeavors.
基金supported by the US National Institutes of Health(No.R33AI133697 to Q.F.,R01CA211861 to B.H.).
文摘Prostate cancer is one of the most prevalent cancers in men,and there is no cure when it advances to a late stage.Antiandrogens are routinely used in clinics for prostate cancer treatment,and darolutamide(Daro)is the latest FDA-approved antiandrogen drug.^(1)Despite its efficacy,potential drug resistance poses significant challenges in the clinical setting.This study seeks to uncover the molecular mechanisms behind darolutamide resistance and identify potential therapeutic targets to overcome this resistance.
基金supported by grants from the National Natural Science Foundation of China(No.81601902)the China Postdoctoral Science Foundation(No.2015M572817)+1 种基金the Natural Science Foundation of Hubei Province,China(No.2015CFB240)the Research Fund of Shanghai Municipal Health Commission for Clinical Research in Medical Science(China)(No.202040084).
文摘Osteosarcoma(OS)is a highly aggressive bone tumor that predominantly affects teenagers and young adults,characterized by rapid growth and a high propensity for metastasis.1 Despite significant advancements in surgical techniques and chemotherapy,the survival rate for OS patients has plateaued over the past decades.2 Understanding the molecular mechanisms underlying OS progression and identifying new therapeutic targets remain critical for improving patient outcomes.Long non-coding RNAs(lncRNAs)are a class of functional RNA molecules that are typically over 200 nucleotides in length and cannot code for proteins.3 Initially considered as“junk DNA”,recent studies have revealed the crucial roles lncRNAs play in a wide range of biological processes,including cellular differentiation,apoptosis,inflammation,and cancer.
