Signal Transduction and Targeted Therapy最新文献_第10页

Decoding the genetic program of micronucleus formation: linking chromosomal instability to human disease 解码微核形成的遗传程序：将染色体不稳定性与人类疾病联系起来

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-14 DOI: 10.1038/s41392-024-01869-2

Jörg Fahrer

引用次数: 0

Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents 非保守表位主导了 COVID-19 康复者体内原有的 T 细胞免疫反向作用

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-12 DOI: 10.1038/s41392-024-01876-3

Xin Wang, Jie Zhang, Maoshun Liu, Yuanyuan Guo, Peipei Guo, Xiaonan Yang, Bingli Shang, Min Li, Jinmin Tian, Ting Zhang, Xi Wang, Ronghua Jin, Jikun Zhou, George F. Gao, Jun Liu

{"title":"Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents","authors":"Xin Wang, Jie Zhang, Maoshun Liu, Yuanyuan Guo, Peipei Guo, Xiaonan Yang, Bingli Shang, Min Li, Jinmin Tian, Ting Zhang, Xi Wang, Ronghua Jin, Jikun Zhou, George F. Gao, Jun Liu","doi":"10.1038/s41392-024-01876-3","DOIUrl":"https://doi.org/10.1038/s41392-024-01876-3","url":null,"abstract":"The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+ T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+ T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+ T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer. 用于结直肠癌靶向联合治疗的可编程基因细胞膜伪装纳米粒子。

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-12 DOI: 10.1038/s41392-024-01859-4

Yun Yang, Qingya Liu, Meng Wang, Lang Li, Yan Yu, Meng Pan, Danrong Hu, Bingyang Chu, Ying Qu, Zhiyong Qian

{"title":"Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer.","authors":"Yun Yang, Qingya Liu, Meng Wang, Lang Li, Yan Yu, Meng Pan, Danrong Hu, Bingyang Chu, Ying Qu, Zhiyong Qian","doi":"10.1038/s41392-024-01859-4","DOIUrl":"10.1038/s41392-024-01859-4","url":null,"abstract":"Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens, including prolonged circulation in the bloodstream, specific cell recognition and targeting capabilities, and potential for immunotherapy. Herein, we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM NPs. Comprising microporous Prussian blue nanoparticles (MPB NPs) serving as both a photothermal sensitizer and carrier for 3-bromopyruvate (3BP), these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory protein α (SIRPα) with enhanced affinity to CD47. As a result, MPB-3BP@CM NPs inherit the characteristics of the original cell membrane, exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer (CRC) cells. Notably, blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by macrophages. Additionally, 3BP, an inhibitor of hexokinase II (HK2), suppresses glycolysis, leading to a reduction in adenosine triphosphate (ATP) levels and lactate production. Besides, it promotes the polarization of tumor-associated macrophages (TAMs) towards an anti-tumor M1 phenotype. Furthermore, integration with MPB NPs-mediated photothermal therapy (PTT) enhances the therapeutic efficacy against tumors. These advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for CRC. Concurrently, it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond the code: the role of histone methylation in cancer resistance and therapy 超越代码：组蛋白甲基化在癌症抗药性和治疗中的作用

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-12 DOI: 10.1038/s41392-024-01878-1

Daniel Noerenberg, Frederik Damm

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Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein. 法尼基转移酶抑制剂洛纳法尼通过阻断融合糖蛋白的构象变化抑制呼吸道合胞病毒感染。

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-10 DOI: 10.1038/s41392-024-01858-5

Qi Yang, Bao Xue, Fengjiang Liu, Yongzhi Lu, Jielin Tang, Mengrong Yan, Qiong Wu, Ruyi Chen, Anqi Zhou, Lijie Liu, Junjun Liu, Changbin Qu, Qingxin Wu, Muqing Fu, Jiayi Zhong, Jianwei Dong, Sijie Chen, Fan Wang, Yuan Zhou, Jie Zheng, Wei Peng, Jinsai Shang, Xinwen Chen

{"title":"Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein.","authors":"Qi Yang, Bao Xue, Fengjiang Liu, Yongzhi Lu, Jielin Tang, Mengrong Yan, Qiong Wu, Ruyi Chen, Anqi Zhou, Lijie Liu, Junjun Liu, Changbin Qu, Qingxin Wu, Muqing Fu, Jiayi Zhong, Jianwei Dong, Sijie Chen, Fan Wang, Yuan Zhou, Jie Zheng, Wei Peng, Jinsai Shang, Xinwen Chen","doi":"10.1038/s41392-024-01858-5","DOIUrl":"10.1038/s41392-024-01858-5","url":null,"abstract":"Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathology of pain and its implications for therapeutic interventions 疼痛病理学及其对治疗干预的影响

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-08 DOI: 10.1038/s41392-024-01845-w

Bo Cao, Qixuan Xu, Yajiao Shi, Ruiyang Zhao, Hanghang Li, Jie Zheng, Fengyu Liu, You Wan, Bo Wei

{"title":"Pathology of pain and its implications for therapeutic interventions","authors":"Bo Cao, Qixuan Xu, Yajiao Shi, Ruiyang Zhao, Hanghang Li, Jie Zheng, Fengyu Liu, You Wan, Bo Wei","doi":"10.1038/s41392-024-01845-w","DOIUrl":"https://doi.org/10.1038/s41392-024-01845-w","url":null,"abstract":"Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141292672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Anti-lymphangiogenesis for boosting drug accumulation in tumors. 更正：抗淋巴管生成，促进药物在肿瘤中的蓄积。

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-08 DOI: 10.1038/s41392-024-01883-4

Chunling Wang, Junchao Xu, Xiaoyu Cheng, Ge Sun, Fenfen Li, Guangjun Nie, Yinlong Zhang

引用次数: 0

Linking IL-10 signaling with lipid metabolic programs in macrophages: dysregulated ceramide homeostasis drives colitis 将 IL-10 信号与巨噬细胞中的脂质代谢程序联系起来：神经酰胺平衡失调是结肠炎的诱因

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-08 DOI: 10.1038/s41392-024-01864-7

Imke Atreya, Markus F. Neurath

引用次数: 0

First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial. 针对转移性胰腺癌的一线 Penpulimab（一种抗 PD1 抗体）和 anlotinib（一种血管生成抑制剂）联合纳布-紫杉醇/吉西他滨（PAAG）：一项前瞻性、多中心、生物分子探索性 II 期试验。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-07 DOI: 10.1038/s41392-024-01857-6

Huizi Sha, Fan Tong, Jiayao Ni, Yi Sun, Yahui Zhu, Liang Qi, Xiaoqin Li, Wei Li, Yan Yang, Qing Gu, Xing Zhang, Xiaoxuan Wang, Chan Zhu, Dongsheng Chen, Baorui Liu, Juan Du

{"title":"First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.","authors":"Huizi Sha, Fan Tong, Jiayao Ni, Yi Sun, Yahui Zhu, Liang Qi, Xiaoqin Li, Wei Li, Yan Yang, Qing Gu, Xing Zhang, Xiaoxuan Wang, Chan Zhu, Dongsheng Chen, Baorui Liu, Juan Du","doi":"10.1038/s41392-024-01857-6","DOIUrl":"10.1038/s41392-024-01857-6","url":null,"abstract":"Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes 早期胰岛素治疗对新诊断的 2 型糖尿病患者心血管事件发生率的实际效果

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-06-06 DOI: 10.1038/s41392-024-01854-9

Sihui Luo, Xueying Zheng, Wei Bao, Sheng Nie, Yu Ding, Tong Yue, Yilun Zhou, Ying Hu, Hua Li, Qiongqiong Yang, Qijun Wan, Bicheng Liu, Hong Xu, Guisen Li, Gang Xu, Chunbo Chen, Huafeng Liu, Yongjun Shi, Yan Zha, Yaozhong Kong, Guobin Su, Ying Tang, Mengchun Gong, Linong Ji, Fan Fan Hou, Jianping Weng

{"title":"Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes","authors":"Sihui Luo, Xueying Zheng, Wei Bao, Sheng Nie, Yu Ding, Tong Yue, Yilun Zhou, Ying Hu, Hua Li, Qiongqiong Yang, Qijun Wan, Bicheng Liu, Hong Xu, Guisen Li, Gang Xu, Chunbo Chen, Huafeng Liu, Yongjun Shi, Yan Zha, Yaozhong Kong, Guobin Su, Ying Tang, Mengchun Gong, Linong Ji, Fan Fan Hou, Jianping Weng","doi":"10.1038/s41392-024-01854-9","DOIUrl":"https://doi.org/10.1038/s41392-024-01854-9","url":null,"abstract":"Early insulin therapy is capable to achieve glycemic control and restore β-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0