Jie Wang, Fan Jiang, Peng Cheng, Zhaoyang Ye, Linsheng Li, Ling Yang, Li Zhuang, Wenping Gong
{"title":"Construction of novel multi-epitope-based diagnostic biomarker HP16118P and its application in the differential diagnosis of Mycobacterium tuberculosis latent infection.","authors":"Jie Wang, Fan Jiang, Peng Cheng, Zhaoyang Ye, Linsheng Li, Ling Yang, Li Zhuang, Wenping Gong","doi":"10.1186/s43556-024-00177-z","DOIUrl":"10.1186/s43556-024-00177-z","url":null,"abstract":"<p><p>Tuberculosis (TB) is an infectious disease that significantly threatens human health. However, the differential diagnosis of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) remains a challenge for clinicians in early detection and preventive intervention. In this study, we developed a novel biomarker named HP16118P, utilizing 16 helper T lymphocyte (HTL) epitopes, 11 cytotoxic T lymphocyte (CTL) epitopes, and 8 B cell epitopes identified from 15 antigens associated with LTBI-RD using the IEDB database. We analyzed the physicochemical properties, spatial structure, and immunological characteristics of HP16118P using various tools, which indicated that it is a hydrophilic and relatively stable alkaline protein. Furthermore, HP16118P exhibited good antigenicity and immunogenicity, while being non-toxic and non-allergenic, with the potential to induce immune responses. We observed that HP16118P can stimulate the production of high levels of IFN-γ<sup>+</sup> T lymphocytes in individuals with ATB, LTBI, and health controls. IL-5 induced by HP16118P demonstrated potential in distinguishing LTBI individuals and ATB patients (p=0.0372, AUC=0.8214, 95% CI [0.5843 to 1.000]) with a sensitivity of 100% and specificity of 71.43%. Furthermore, we incorporated the GM-CSF, IL-23, IL-5, and MCP-3 induced by HP16118P into 15 machine learning algorithms to construct a model. It was found that the Quadratic discriminant analysis model exhibited the best diagnostic performance for discriminating between LTBI and ATB, with a sensitivity of 1.00, specificity of 0.86, and accuracy of 0.93. In summary, HP16118P has demonstrated strong antigenicity and immunogenicity, with the induction of GM-CSF, IL-23, IL-5, and MCP-3, suggesting their potential for the differential diagnosis of LTBI and ATB.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"15"},"PeriodicalIF":6.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11056354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexis Woodward, Benjamin Southard, Sampurna Chakraborty, Aaron O Bailey, Gabriela N F Faria, Patrick McKernan, Wajeeha Razaq, Roger G Harrison
{"title":"Correction: annexin A5-DM1 protein-drug conjugate for the treatment of triple-negative breast cancer.","authors":"Alexis Woodward, Benjamin Southard, Sampurna Chakraborty, Aaron O Bailey, Gabriela N F Faria, Patrick McKernan, Wajeeha Razaq, Roger G Harrison","doi":"10.1186/s43556-024-00180-4","DOIUrl":"10.1186/s43556-024-00180-4","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"16"},"PeriodicalIF":4.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Wu, Yuan Fang, Yunru Gu, Haoyang Shen, Yangyue Xu, Tingting Xu, Run Shi, Duo Xu, Jingxin Zhang, Kai Leng, Yongqian Shu, Pei Ma
{"title":"Fat mass and obesity-associated protein (FTO) mediated m<sup>6</sup>A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay.","authors":"Xi Wu, Yuan Fang, Yunru Gu, Haoyang Shen, Yangyue Xu, Tingting Xu, Run Shi, Duo Xu, Jingxin Zhang, Kai Leng, Yongqian Shu, Pei Ma","doi":"10.1186/s43556-024-00172-4","DOIUrl":"10.1186/s43556-024-00172-4","url":null,"abstract":"<p><p>Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m<sup>6</sup>A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m<sup>6</sup>A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m<sup>6</sup>A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"11"},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lincheng Zhang, Peng Liu, Li Zhuang, Sunbin Ling, Qifan Zhan, Wei Zhou, Renyi Su, Lu Yin, Qingyang Que, Jiachen Hong, Jiaqi Bao, Chuxiao Shao, Jinzhen Cai, Shusen Zheng, Xiao Xu
{"title":"mTOR inhibitor reduces nontumour-related death in liver transplantation for hepatocellular carcinoma.","authors":"Lincheng Zhang, Peng Liu, Li Zhuang, Sunbin Ling, Qifan Zhan, Wei Zhou, Renyi Su, Lu Yin, Qingyang Que, Jiachen Hong, Jiaqi Bao, Chuxiao Shao, Jinzhen Cai, Shusen Zheng, Xiao Xu","doi":"10.1186/s43556-024-00170-6","DOIUrl":"10.1186/s43556-024-00170-6","url":null,"abstract":"<p><p>Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18-1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08-0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"9"},"PeriodicalIF":4.0,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural and functional insights of NINJ1 in plasma membrane rupture during cell death.","authors":"Chehao Lee, Yuqing Liang, Yang Li","doi":"10.1186/s43556-023-00169-5","DOIUrl":"10.1186/s43556-023-00169-5","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"8"},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexis Woodward, Benjamin Southard, Sampurna Chakraborty, Aaron O Bailey, Gabriela N F Faria, Patrick McKernan, Wajeeha Razaq, Roger G Harrison
{"title":"Annexin A5-DM1 protein-drug conjugate for the treatment of triple-negative breast cancer.","authors":"Alexis Woodward, Benjamin Southard, Sampurna Chakraborty, Aaron O Bailey, Gabriela N F Faria, Patrick McKernan, Wajeeha Razaq, Roger G Harrison","doi":"10.1186/s43556-023-00167-7","DOIUrl":"10.1186/s43556-023-00167-7","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"7"},"PeriodicalIF":4.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine.","authors":"Shanqiang Qu, Rongyang Xu, Guozhong Yi, Zhiyong Li, Huayang Zhang, Songtao Qi, Guanglong Huang","doi":"10.1186/s43556-023-00165-9","DOIUrl":"10.1186/s43556-023-00165-9","url":null,"abstract":"<p><p>Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor heterogeneity, along with considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as in vitro cell cultures and in vivo animal models, demonstrate significant limitations that fall short of satisfying the research requisites. Patient-derived tumor organoids, which recapitulate the structures, specific functions, molecular characteristics, genomics alterations and expression profiles of primary tumors. They have been efficaciously implemented in illness portrayal, mechanism exploration, high-throughput drug screening and assessment, discovery of innovative therapeutic targets and potential compounds, and customized treatment regimen for cancer patients. In contrast to conventional models, tumor organoids offer an intuitive, dependable, and efficient in vitro research model by conserving the phenotypic, genetic diversity, and mutational attributes of the originating tumor. Nevertheless, the organoid technology also confronts the bottlenecks and challenges, such as how to comprehensively reflect intra-tumor heterogeneity, tumor microenvironment, tumor angiogenesis, reduce research costs, and establish standardized construction processes while retaining reliability. This review extensively examines the use of tumor organoid techniques in fundamental research and precision medicine. It emphasizes the importance of patient-derived tumor organoid biobanks for drug development, screening, safety evaluation, and personalized medicine. Additionally, it evaluates the application of organoid technology as an experimental tumor model to better understand the molecular mechanisms of tumor. The intent of this review is to explicate the significance of tumor organoids in cancer research and to present new avenues for the future of tumor research.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"6"},"PeriodicalIF":6.3,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10859360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unlocking γδ T cell power: pathways that boost cancer defense.","authors":"Yuhao Yao, Zhi Zong, Long Zhang","doi":"10.1186/s43556-023-00168-6","DOIUrl":"10.1186/s43556-023-00168-6","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"5"},"PeriodicalIF":6.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10838885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chromosomal instability (CIN) triggers immune evasion and metastatic potential in cancer through rewired STING signalling.","authors":"Mrinal K Ghosh, Srija Roy","doi":"10.1186/s43556-023-00166-8","DOIUrl":"10.1186/s43556-023-00166-8","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"4"},"PeriodicalIF":6.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}