{"title":"Comprehensive plasma metabolomics profiling develops diagnostic biomarkers of obstructive hypertrophic cardiomyopathy.","authors":"Hao Cui, Yifan Wang, Xiumeng Hua, Jing Han, Han Mo, Shun Liu, Hongmei Wang, Siyuan Huang, Yiqi Zhao, Xiao Chen, Qian Zhao, Hao Jia, Yuan Chang, Jiangping Song","doi":"10.1186/s40364-025-00768-0","DOIUrl":"10.1186/s40364-025-00768-0","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is the common cause of sudden cardiac death in young people and is characterized by cardiac hypertrophy. Non-HCM caused left ventricular hypertrophy (LVH) is more common in the population, especially in people with hypertension, obesity, and diabetes. In order to identify high-risk populations, a screening technique that can rapidly differentiate between HCM and LVH patients should be developed. Plasma metabolomics may help develop useful biomarkers for the disease diagnosis. We performed a comprehensive plasma metabolomic analysis on a total of 720 individuals, included 441 HCM patients, 160 LVH patients, and 119 normal controls (NC) (derivation cohort = 368, validation cohort = 352). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to construct discriminant models based on metabolomics, and the result showed significant changes in plasma metabolic profiling among the HCM, LVH, and NC. The prospective diagnostic biomarkers for HCM patients have been examined using variable importance in projection, fold change, and FDR. Acylcarnitines efficiently distinguished HCM and LVH patients, with a C14:0-carnitine AUC of 0.937 shown by the reiver operator characteristic (ROC) curve analysis. The biomarkers for the diagnosis of HCM patients was verified in another independent validation cohort. This study is the largest plasma metabolomics analysis of Chinese Han patients with HCM, finding biomarkers that can be used to distinguish between HCM from LVH patients. These results highlight the great potential value of plasma metabolic profiling analysis on HCM diagnoses.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"55"},"PeriodicalIF":9.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Varun Dewaker, Vivek Kumar Morya, Yoo Hee Kim, Sung Taek Park, Hyeong Su Kim, Young Ho Koh
{"title":"Revolutionizing oncology: the role of Artificial Intelligence (AI) as an antibody design, and optimization tools.","authors":"Varun Dewaker, Vivek Kumar Morya, Yoo Hee Kim, Sung Taek Park, Hyeong Su Kim, Young Ho Koh","doi":"10.1186/s40364-025-00764-4","DOIUrl":"https://doi.org/10.1186/s40364-025-00764-4","url":null,"abstract":"<p><p>Antibodies play a crucial role in defending the human body against diseases, including life-threatening conditions like cancer. They mediate immune responses against foreign antigens and, in some cases, self-antigens. Over time, antibody-based technologies have evolved from monoclonal antibodies (mAbs) to chimeric antigen receptor T cells (CAR-T cells), significantly impacting biotechnology, diagnostics, and therapeutics. Although these advancements have enhanced therapeutic interventions, the integration of artificial intelligence (AI) is revolutionizing antibody design and optimization. This review explores recent AI advancements, including large language models (LLMs), diffusion models, and generative AI-based applications, which have transformed antibody discovery by accelerating de novo generation, enhancing immune response precision, and optimizing therapeutic efficacy. Through advanced data analysis, AI enables the prediction and design of antibody sequences, 3D structures, complementarity-determining regions (CDRs), paratopes, epitopes, and antigen-antibody interactions. These AI-powered innovations address longstanding challenges in antibody development, significantly improving speed, specificity, and accuracy in therapeutic design. By integrating computational advancements with biomedical applications, AI is driving next-generation cancer therapies, transforming precision medicine, and enhancing patient outcomes.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"52"},"PeriodicalIF":9.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rujie Zheng, Wenjuan Song, Che Wang, Xiaoyu Du, Chunlei Liu, Xiaotong Sun, Chengzhi Lu
{"title":"Deubiquitinase OTUD7B stabilizes HNF4α to alleviate pressure overload-induced cardiac hypertrophy by regulating fatty acid oxidation and inhibiting ferroptosis.","authors":"Rujie Zheng, Wenjuan Song, Che Wang, Xiaoyu Du, Chunlei Liu, Xiaotong Sun, Chengzhi Lu","doi":"10.1186/s40364-025-00766-2","DOIUrl":"10.1186/s40364-025-00766-2","url":null,"abstract":"<p><strong>Background: </strong>Cardiac hypertrophy, a leading cause of heart failure, threatens global public health. Deubiquitinating enzymes (DUBs) are critical in cardiac pathophysiology by regulating protein stability, function, and degradation. Here, we investigated the role and regulating mechanism of ovarian tumor domain-containing 7B (OTUD7B) in cardiac hypertrophy by modulating fatty acid metabolism.</p><p><strong>Methods: </strong>Mice subjected to transverse aortic constriction (TAC) and cardiomyocytes treated with phenylephrine (PE) were used to explore the role of OTUD7B in myocardial hypertrophy. The potential molecular mechanisms underlying OTUD7B's regulation of cardiac hypertrophy were explored through transcriptome analysis and further validated in cardiomyocytes.</p><p><strong>Results: </strong>Reduced OTUD7B expression was observed in hypertrophic hearts following TAC surgery. Cardiac-specific OTUD7B deficiency exacerbated, while OTUD7B overexpression mitigated, pressure overload-induced hypertrophy and cardiac dysfunction both in vivo and in vitro. OTUD7B knockdown resulted in ferroptosis, as evidenced by decreased mitochondrial cristae, increased Fe<sup>2+</sup> ion content, lipid peroxide accumulation, while OTUD7B overexpression inhibited ferroptosis. Mechanistically, transcriptomic analysis identified OTUD7B plays a role in the regulation of fatty acid metabolism and pathological cardiac hypertrophy. OTUD7B was found to directly bind to HNF4α, a transcription factor regulating fatty acid oxidation-related genes. Further, OTUD7B exerted deubiquitination activity to stabilize the HNF4α protein by removing K48-linked ubiquitin chains, thereby preventing its degradation via the proteasomal pathway and linking the HNF4α degradation and ferroptosis. Finally, ferroptosis inhibitors, ferrostatin-1, alleviated OTUD7B inhibition-induced ferroptosis, fatty acid metabolism suppression, and myocardial hypertrophy.</p><p><strong>Conclusions: </strong>We confirmed that OTUD7B is involved in the regulation of ferroptosis in pressure overload-induced cardiac hypertrophy and highlighted that OTUD7B alleviates cardiac hypertrophy by regulating ferroptosis and fatty acid oxidation through deubiquitination and stabilization of HNF4α.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"53"},"PeriodicalIF":9.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gamma delta T cells and their immunotherapeutic potential in cancer.","authors":"Stephen G Cieslak, Reza Shahbazi","doi":"10.1186/s40364-025-00762-6","DOIUrl":"10.1186/s40364-025-00762-6","url":null,"abstract":"<p><p>Gamma-delta (γδ) T cells are a unique subset of T lymphocytes that play diverse roles in immune responses, bridging innate and adaptive immunity. With growing interest in their potential for cancer immunotherapy, a comprehensive and inclusive exploration of γδ T cell families, their development, activation mechanisms, functions, therapeutic implications, and current treatments is essential. This review aims to provide an inclusive and thorough discussion of these topics. Through our discussion, we seek to uncover insights that may harbinger innovative immunotherapeutic strategies. Beginning with an overview of γδ T cell families including Vδ1, Vδ2, and Vδ3, this review highlights their distinct functional properties and contributions to anti-tumor immunity. Despite γδ T cells exhibiting both anti-tumor and pro-tumor activities, our review elucidates strategies to harness the anti-tumor potential of γδ T cells for therapeutic benefit. Moreover, our paper discusses the structural intricacies of the γδ T cell receptor and its significance in tumor recognition. Additionally, this review examines conventional and emerging γδ T cell therapies, encompassing both non-engineered and engineered approaches, with a focus on their efficacy and safety profiles in clinical trials. From multifunctional capabilities to diverse tissue distribution, γδ T cells play a pivotal role in immune regulation and surveillance. By analyzing current research findings, this paper offers insights into the dynamic landscape of γδ T cell-based immunotherapies, underscoring their promise as a potent armamentarium against cancer. Furthermore, by dissecting the complex biology of γδ T cells, we learn valuable information about the anti-cancer contributions of γδ T cells, as well as potential targets for immunotherapeutic interventions.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"51"},"PeriodicalIF":9.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anqi Lin, Yanxi Ding, Zhengrui Li, Aimin Jiang, Zaoqu Liu, Hank Z H Wong, Quan Cheng, Jian Zhang, Peng Luo
{"title":"Glucagon-like peptide 1 receptor agonists and cancer risk: advancing precision medicine through mechanistic understanding and clinical evidence.","authors":"Anqi Lin, Yanxi Ding, Zhengrui Li, Aimin Jiang, Zaoqu Liu, Hank Z H Wong, Quan Cheng, Jian Zhang, Peng Luo","doi":"10.1186/s40364-025-00765-3","DOIUrl":"10.1186/s40364-025-00765-3","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a primary first-line treatment for type 2 diabetes. This has raised concerns about their impact on cancer risk, spurring extensive research. This review systematically examines the varied effects of GLP-1RAs on the risk of different types of tumors, including overall cancer risk and specific cancers such as thyroid, pancreatic, reproductive system, liver, and colorectal cancers. The potential biological mechanisms underlying their influence on cancer risk are complex, involving metabolic regulation, direct antitumor effects, immune modulation, and epigenetic changes. A systematic comparison with other antidiabetic agents reveals notable differences in their influence on cancer risk across drug classes. Additionally, critical factors that shape the relationship between GLP-1RAs and cancer risk are thoroughly analyzed, including patient demographics, comorbidities, treatment regimens, and lifestyle factors, offering essential insights for developing individualized treatment protocols. Despite significant research progress, critical gaps remain. Future research should prioritize elucidating the molecular mechanisms behind the antitumor effects, refining individualized treatment strategies, investigating early tumor prevention applications, assessing potential benefits for non-diabetic populations, advancing the development of novel therapies, establishing robust safety monitoring frameworks, and building precision medicine decision-making platforms. These efforts aim to establish novel roles for GLP-1RAs in cancer prevention. and treatment, thereby advancing the progress of precision medicine.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"50"},"PeriodicalIF":9.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nan Zhang, Qiao Liu, Daihan Wang, Xiaoyun Wang, Zhaoping Pan, Bo Han, Gu He
{"title":"Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy.","authors":"Nan Zhang, Qiao Liu, Daihan Wang, Xiaoyun Wang, Zhaoping Pan, Bo Han, Gu He","doi":"10.1186/s40364-025-00759-1","DOIUrl":"10.1186/s40364-025-00759-1","url":null,"abstract":"<p><p>Galectins play pivotal roles in cellular recognition and signaling processes by interacting with glycoconjugates. Extensive research has highlighted the significance of Galectins in the context of cancer, aiding in the identification of biomarkers for early detection, personalized therapy, and predicting treatment responses. This review offers a comprehensive overview of the structural characteristics, ligand-binding properties, and interacting proteins of Galectins. We delve into their biological functions and examine their roles across various cancer types. Galectins, characterized by a conserved carbohydrate recognition domain (CRD), are divided into prototype, tandem-repeat, and chimera types based on their structural configurations. Prototype Galectins contain a single CRD, tandem-repeat Galectins contain two distinct CRDs linked by a peptide, and the chimera-type Galectin-3 features a unique structural arrangement. The capacity of Galectins to engage in multivalent interactions allows them to regulate a variety of signaling pathways, thereby affecting cell fate and function. In cancer, Galectins contribute to tumor cell transformation, angiogenesis, immune evasion, and metastasis, making them critical targets for therapeutic intervention. This review discusses the multifaceted roles of Galectins in cancer progression and explores current advancements in the development of Galectin-targeted therapies. We also address the challenges and future directions for integrating Galectin research into clinical practice to enhance cancer treatment outcomes. In brief, understanding the complex functions of Galectins in cancer biology opens new avenues for therapeutic strategies. Continued research on Galectin interactions and their pathological roles is essential for developing effective carbohydrate-based treatments and improving clinical interventions for cancer patients.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"49"},"PeriodicalIF":9.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyung Taek Hong, Sungyeun Bae, Yoon Sunwoo, Juyeon Lee, Hyun Jin Park, Bo Kyung Kim, Jung Yoon Choi, Joo-Youn Cho, Kyung-Sang Yu, Jaeseong Oh, Hyoung Jin Kang
{"title":"Pharmacokinetics of post-transplant cyclophosphamide and its associations with clinical outcomes in pediatric haploidentical hematopoietic stem cell transplantation.","authors":"Kyung Taek Hong, Sungyeun Bae, Yoon Sunwoo, Juyeon Lee, Hyun Jin Park, Bo Kyung Kim, Jung Yoon Choi, Joo-Youn Cho, Kyung-Sang Yu, Jaeseong Oh, Hyoung Jin Kang","doi":"10.1186/s40364-025-00749-3","DOIUrl":"10.1186/s40364-025-00749-3","url":null,"abstract":"<p><strong>Background: </strong>Post-transplantation cyclophosphamide (PTCy) has paved the way for the increased use of alternative donors, including haploidentical familial donors, with acceptable engraftment and graft-versus-host disease (GVHD) rates. However, pharmacokinetic studies of PTCy in the pediatric population following myeloablative conditioning regimens are scarce.</p><p><strong>Methods: </strong>We conducted a prospective and comprehensive pharmacokinetic analysis of pre- and post-transplantation cyclophosphamide levels in pediatric patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) using a myeloablative busulfan-based conditioning regimen. A total of 14 samples were collected from each patient. Plasma concentrations of cyclophosphamide and carboxycyclophosphamide were analyzed, and clinical outcomes were recorded. The simulated pharmacokinetic profiles of cyclophosphamide and its metabolites were compared among different age groups using real-world data.</p><p><strong>Results: </strong>A total of 15 pediatric patients (median age at HSCT 9.6 years, range 1.6-16.8) were enrolled. Thirteen patients had malignant disease. All patients achieved successful neutrophil engraftment, and the cumulative incidences of grade 2-4 acute GVHD and moderate-to-severe chronic GVHD were 13.3% and 14.7%, respectively. The patterns of cyclophosphamide pharmacokinetic parameters were similar between the pre- and post-HSCT doses. The metabolic ratio increased with subsequent doses of PTCy. Patients with severe veno-occlusive disease showed a higher cumulative area under the curve (AUC) of carboxycyclophosphamide (62.6 vs. 40.2 mg x h/L, P = 0.025), while patients with > grade 3 hemorrhagic cystitis had a higher cumulative AUC of cyclophosphamide (1256.2 vs. 778.2 mg x h/L, P = 0.009). In contrast, there were no notable differences in the pharmacokinetic parameters of cyclophosphamide and carboxycyclophosphamide between the groups with and without acute and chronic GVHD. The AUC of cyclophosphamide and its metabolite were similar in children weighing ≥ 30 kg and the virtual adult population.</p><p><strong>Conclusions: </strong>Our study provides insights into the pharmacokinetic profile of cyclophosphamide and its metabolite, carboxycyclophosphamide, in pediatric patients undergoing haploidentical HSCT with PTCy. The intricate interplay between pharmacokinetic parameters and post-HSCT complications suggests the need for tailored adjustments in PTCy dosage, particularly in pediatric patients subjected to myeloablative conditioning regimens.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"48"},"PeriodicalIF":9.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Global, regional and national burden of rheumatoid arthritis from 1990 to 2021, with projections of incidence to 2050: a systematic and comprehensive analysis of the Global Burden of Disease study 2021.","authors":"Yingnan Ma, Haiyan Chen, Wenhua Lv, Siyu Wei, Yuping Zou, Ruilin Li, Jiacheng Wang, Wei She, Linna Yuan, Junxian Tao, Xuying Guo, Shuo Bi, Hongsheng Tian, Ye Ma, Hongmei Sun, Chen Sun, Jing Xu, Yu Dong, Jingxuan Kang, Hongchao Lv, Mingming Zhang, Yongshuai Jiang","doi":"10.1186/s40364-025-00760-8","DOIUrl":"10.1186/s40364-025-00760-8","url":null,"abstract":"<p><strong>Background: </strong>To provide insights into rheumatoid arthritis (RA) epidemiological trends, including prevalence, incidence, disability-adjusted life years (DALYs), corresponding average annual percentage change (AAPC), gender disparities, regional variations, age-specific rates, socio-economic correlations, risk factors, and future projections.</p><p><strong>Methods: </strong>Data were extracted from the Global Burden of Disease Study (GBD) 2021. AAPC was calculated by joinpoint regression and two-sample Mendelian randomization (MR) analysis was performed to verify the causal relationship between the smoking factor and RA. The future incidence trend was predicted by the Bayesian age-period-cohort (BAPC) model.</p><p><strong>Results: </strong>Global age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) increased significantly while age-standardized DALYs rate (ASDR) decreased from 1990 to 2021. Regional variations were pronounced, with Andean Latin America reporting the highest burden. Females consistently exhibited higher age-standardized rate (ASR) across all metrics. Age-specific prevalence, incidence, and DALYs rates peaked at different age groups, highlighting complex demographic dynamics. Socio-demographic index (SDI) analysis demonstrated a positive correlation between RA burden and socio-economic development. The two-sample MR analysis confirmed a causal effect between smoking and RA. From 2022 to 2050, the ASIR will increase moderately.</p><p><strong>Conclusions: </strong>The study underscores the escalating burden of RA globally, emphasizing the need for healthcare providers to be aware of the effects of aging populations and other societal factors on the risk of developing RA, and to develop targeted interventions, including smoking cessation programs, age- and gender-appropriate healthcare, and early diagnosis strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"47"},"PeriodicalIF":9.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic changes of bone microarchitecture and volumetric mineral density assessed by HR-pQCT in patients with cervical cancer after concurrent chemoradiotherapy: a prospective study.","authors":"Weishi Cheng, Yijun Wu, Jing Shen, Hui Guan, Li Zhang, Hongnan Zhen, Yinjie Tao, Weibo Xia, Zhikai Liu, Fuquan Zhang","doi":"10.1186/s40364-025-00754-6","DOIUrl":"10.1186/s40364-025-00754-6","url":null,"abstract":"<p><p>Bone changes in patients undergoing pelvic radiotherapy remain unclear. This study initially utilized high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess the dynamic changes in bone microarchitecture and volumetric bone mineral density (BMD) in patients with cervical cancer before and after concurrent chemoradiotherapy. This prospective, observational study included patients with squamous carcinoma of the cervix scheduled for concurrent chemoradiotherapy. Patients underwent HR-pQCT, dual-energy X-ray absorptiometry (DXA) and laboratory tests before chemoradiotherapy, and at three and six months post-chemoradiotherapy. DXA, serving as the clinical standard for measuring BMD, was employed alongside HR-pQCT to provide complementary insights into bone micro-changes. The primary endpoint comprised changes in total (Tt.vBMD), trabecular (Tb.vBMD) and cortical (Ct.vBMD) volumetric BMD at the distal radius and tibia between pre-chemoradiotherapy and 6 months post-chemoradiotherapy. A total of 21 patients were enrolled, and one patient chose to withdraw (median age: 54.5 years). Tt.vBMD significantly decreased three months (distal radius: -1.65%, P = 0.008; distal tibia: -2.4%, P < 0.001) and six months (distal radius: -3.03%, P = 0.003; distal tibia: -2.69%, P = 0.002) post-chemoradiotherapy compared to baseline. Similarly, Tb.vBMD and Ct.vBMD demonstrated a significant downward trend post-chemoradiotherapy, with mean percent changes at three months of -0.73% and - 1.59% for the distal radius, and - 1.95% and - 1.50% for the distal tibia, respectively. The trends in BMD changes measured by DXA align with those observed using HR-pQCT. Regarding the laboratory tests, estradiol levels significantly decreased post-chemoradiotherapy, while follicle stimulating hormone and luteinizing hormone levels significantly increased. The results found that concurrent chemoradiotherapy was associated with the changes in bone volume, microstructure and BMD, especially in BMD three months post-chemoradiotherapy. Most of the bone micro-changes had not reverted by six months. This study explored the feasibility of early fracture risk identification post-chemoradiotherapy, aiding physicians in taking timely measures to improve prognosis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"46"},"PeriodicalIF":9.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alberto Ocana, Atanasio Pandiella, Cristian Privat, Iván Bravo, Miguel Luengo-Oroz, Eitan Amir, Balazs Gyorffy
{"title":"Integrating artificial intelligence in drug discovery and early drug development: a transformative approach.","authors":"Alberto Ocana, Atanasio Pandiella, Cristian Privat, Iván Bravo, Miguel Luengo-Oroz, Eitan Amir, Balazs Gyorffy","doi":"10.1186/s40364-025-00758-2","DOIUrl":"10.1186/s40364-025-00758-2","url":null,"abstract":"<p><p>Artificial intelligence (AI) can transform drug discovery and early drug development by addressing inefficiencies in traditional methods, which often face high costs, long timelines, and low success rates. In this review we provide an overview of how to integrate AI to the current drug discovery and development process, as it can enhance activities like target identification, drug discovery, and early clinical development. Through multiomics data analysis and network-based approaches, AI can help to identify novel oncogenic vulnerabilities and key therapeutic targets. AI models, such as AlphaFold, predict protein structures with high accuracy, aiding druggability assessments and structure-based drug design. AI also facilitates virtual screening and de novo drug design, creating optimized molecular structures for specific biological properties. In early clinical development, AI supports patient recruitment by analyzing electronic health records and improves trial design through predictive modeling, protocol optimization, and adaptive strategies. Innovations like synthetic control arms and digital twins can reduce logistical and ethical challenges by simulating outcomes using real-world or virtual patient data. Despite these advancements, limitations remain. AI models may be biased if trained on unrepresentative datasets, and reliance on historical or synthetic data can lead to overfitting or lack generalizability. Ethical and regulatory issues, such as data privacy, also challenge the implementation of AI. In conclusion, in this review we provide a comprehensive overview about how to integrate AI into current processes. These efforts, although they will demand collaboration between professionals, and robust data quality, have a transformative potential to accelerate drug development.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"45"},"PeriodicalIF":9.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}