Molecular Diagnosis & Therapy最新文献

{"title":"Prademagene Zamikeracel: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40291-025-00804-7","DOIUrl":"10.1007/s40291-025-00804-7","url":null,"abstract":"<p><p>Prademagene zamikeracel (ZEVASKYN™) is an autologous cell sheet-based gene therapy developed by Abeona Therapeutics Inc. for the treatment of wounds in patients with recessive dystrophic epidermolysis bullosa. Prademagene zamikeracel contains the patient's own genetically modified cells with functional copies of the COL7A1 gene, as patients lacking functional copies of this gene may develop chronic open wounds caused by the separation of dermal layers. This article summarizes the milestones in the development of prademagene zamikeracel leading to this first approval for treatment of wounds in adult and paediatric patients with recessive dystrophic epidermolysis bullosa.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"701-704"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Revakinagene Taroretcel: First Approval.","authors":"Sheridan M Hoy","doi":"10.1007/s40291-025-00802-9","DOIUrl":"10.1007/s40291-025-00802-9","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"705"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty Acid Desaturase: The Yin or Yang of Disease Pathology.","authors":"Veeksha V Shetty, Shilpa S Shetty","doi":"10.1007/s40291-025-00796-4","DOIUrl":"10.1007/s40291-025-00796-4","url":null,"abstract":"<p><p>Fatty acid desaturases are key enzymes in lipid metabolism, crucial for converting saturated fatty acids into monounsaturated fatty acids. This review examines the roles of stearoyl-CoA desaturase, fatty acid desaturase 1, fatty acid desaturase 2 and fatty acid desaturase 3 in health and disease, highlighting their impact on cellular functions such as membrane fluidity, signalling and energy homeostasis. Dysregulation of desaturase activity can have significant implications for human health, contributing to the development of various pathological conditions, including cardiovascular disease, metabolic disorders and cancer. Fatty acid desaturase 1 and fatty acid desaturase 2 overexpression in cancer correlates with tumour growth and chemoresistance, marking them as potential therapeutic targets. The development of inhibitors targeting stearoyl-CoA desaturase and fatty acid desaturase 1 offers promising therapeutic avenues for metabolic diseases and cancer. This review underscores the critical roles of desaturases in various diseases. It emphasises the need for ongoing research to develop effective diagnostic, prognostic and therapeutic strategies, ultimately improving patient outcomes in altered fatty acid metabolism conditions.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"637-654"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Metagenomic Next-Generation Sequencing Workflow with a Novel Host Depletion Method for Enhanced Pathogen Detection.","authors":"Yen-Chia Chen, Po-Hsiang Liao, Yen-Wen Chen, David Hung-Tsang Yen, Chorng-Kuang How, Chia-Ming Chang","doi":"10.1007/s40291-025-00797-3","DOIUrl":"10.1007/s40291-025-00797-3","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a critical condition requiring timely and accurate pathogen identification. Traditional blood cultures are slow and often yield low sensitivity. Metagenomic next-generation sequencing (mNGS) offers broad and rapid pathogen detection but is hindered by excessive human DNA background in blood samples. This study evaluated a novel Zwitterionic Interface Ultra-Self-assemble Coating (ZISC)-based filtration device designed to deplete host cells and enhance microbial DNA recovery for improved mNGS diagnostics.</p><p><strong>Methods: </strong>We assessed the novel filter's performance in depleting white blood cells (WBCs) while preserving microbial integrity using spiked blood samples. Comparisons were made with other host depletion techniques, including differential lysis and CpG-methylated DNA removal. Analytical sensitivity was tested using spiked microbial communities at varying genome equivalents (GEs). Clinical validation involved eight blood culture-positive sepsis patient samples, processed with and without filtration, for both genomic DNA (gDNA) and cell-free DNA (cfDNA)-based mNGS. All libraries were sequenced on a NovaSeq600 with at least 10 million reads per sample.</p><p><strong>Results: </strong>The novel filter achieved > 99% WBC removal across various blood volumes and allowed unimpeded passage of bacteria and viruses. Compared to other depletion methods, the novel filtration was more efficient, less labor-intensive, and preserved microbial reads. mNGS with filtered gDNA detected all expected pathogens in 100% (8/8) of clinical samples, with an average microbial read count of 9351 reads per million (RPM), over tenfold higher than unfiltered samples (925 RPM). In contrast, cfDNA-based mNGS showed inconsistent sensitivity and was not significantly enhanced by filtration (1251-1488 RPM). Finally, the novel filtration did not alter the microbial composition, making it suitable for accurate pathogen profiling.</p><p><strong>Conclusion: </strong>The workflow with the novel host depletion method significantly enhanced the analytical sensitivity of gDNA-based mNGS by reducing the host DNA background and enriching microbial content. This approach improved diagnostic yield in sepsis and may be a valuable tool for further clinical infectious disease diagnostics.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"689-699"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Potential of ctDNA in Precision Medicine for Breast Cancer.","authors":"Juscelino Carvalho de Azevedo Junior, Fernanda Jardim da Silva, Anna Carolina Lima Rodrigues, Stefanie Braga Maia de Sousa, Jéssica Manoelli Costa da Silva, Iago Barroso Ramos, Bárbara do Nascimento Borges, Vanessa Morais Freitas, Danielle Queiroz Calcagno","doi":"10.1007/s40291-025-00800-x","DOIUrl":"10.1007/s40291-025-00800-x","url":null,"abstract":"<p><p>Circulating tumor DNA has emerged as a minimally invasive and dynamic tool for providing real-time genetic insights into solid tumors, including breast cancer. Circulating tumor DNA is released into the bloodstream through apoptosis, necrosis, or active secretion, and it reflects tumor heterogeneity, which continues to be a major challenge in breast cancer treatment. Advances in high-sensitivity technologies, such as next-generation sequencing and digital polymerase chain reaction, have enabled the detection of key genetic alterations, offering applications in early diagnosis, monitoring minimal residual disease, identifying drug resistance mechanisms, and predicting relapse. Some circulating tumor DNA-based tests have already received regulatory approval for clinical use in patients with breast cancer, and additional studies are underway to expand their applicability. However, low concentrations of circulating tumor DNA and the necessity for standardization across different platforms remain a challenge for the expanded application. In this review, we present an overview of the genetic variants detected in circulating tumor DNA from patients with breast cancer, emphasizing their potential utility in guiding personalized therapeutic strategies and predicting treatment responses across the diverse molecular subtypes of the disease.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"603-615"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Chemogenetics for the Treatment of Spasticity.","authors":"Kelly Poth, Roy Raheb Khelo, Anthony Donsante, Nicholas M Boulis","doi":"10.1007/s40291-025-00798-2","DOIUrl":"10.1007/s40291-025-00798-2","url":null,"abstract":"<p><p>The management of spasticity poses a significant challenge for both physicians and patients. This condition, often characterized by increased muscle tone, clonus, and muscle spasms, can be painful, disrupt daily activities, and increases the risk of injuries. First-line treatment for spasticity includes oral medications, such as baclofen, but these drugs can have significant side effects due to inhibitory effects on neural circuits, such as drowsiness and dizziness. Surgical approaches can be applied to patients for whom oral medications fail. However, these treatments can have life-threatening side effects or are irreversible. An emerging technology, chemogenetics, has the potential to provide targeted relief of spasticity, combining a non-destructive surgical approach with the convenience of an oral medication. This Current Opinion describes the current treatment approaches for spasticity, the pathophysiology of this condition, the current state of chemogenetics, and how this technology may be applied to patients with poorly controlled spasticity. Although the use of this approach is at an early developmental stage, we believe that it shows great promise.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"563-569"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Profile of 35 Patients with Glycogen Storage Disease Type 1b: A Comparative Analysis Before and During SGLT2 Inhibitor Therapy.","authors":"Maja Djordjevic Milosevic, Anita Skakic, Bozica Kecman, Sara Stankovic, Ivona Kovacevic, Sonja Pavlovic, Maja Stojiljkovic","doi":"10.1007/s40291-025-00795-5","DOIUrl":"10.1007/s40291-025-00795-5","url":null,"abstract":"<p><strong>Background: </strong>Glycogen storage disease type 1b (GSD 1b) is an ultra-rare disease worldwide, whereas in Serbia it has an unexpectedly high prevalence. GSD 1b is the result of variants in the SLC37A4 gene and reduced function of the enzyme glucose 6 phosphate translocase (G6PT). In addition to the classic symptoms of GSD 1a, patients with GSD 1b have neutropenia and impaired neutrophil function.</p><p><strong>Methods: </strong>The genotype and clinical profile were analyzed in 35 patients, 26 of whom were children. In all patients, pathogenic variants in the SLC37A4 gene were confirmed using Sanger or next-generation sequencing (NGS). Eight different variants were found. The following clinical data were analyzed: age at diagnosis, first symptoms of GSD 1b, severity of intestinal symptoms, lowest neutrophil count, mean hemoglobin value, height, body mass index (BMI), and quality of life. Patients were classified into four groups based on the severity of their intestinal symptoms.</p><p><strong>Results: </strong>In our study 30 patients received empagliflozin therapy. Our data are comprised of information from a total of 62 treatment years and include self-reported quality-of-life surveys before and during empagliflozin therapy. The average age at which empagliflozin was introduced in pediatric patients was 8.5 years, with the youngest two patients, both female, starting SGLT2 inhibitor therapy at the age of two.</p><p><strong>Conclusions: </strong>Our findings suggest that empagliflozin therapy significantly improves neutropenia recovery by reducing the frequency of recurrent infections and inflammatory bowel disease (IBD)-like symptoms. This improvement was demonstrated by a marked reduction in skin and mucosal infections, particularly oral ulcers, as well as an increase in hemoglobin levels and overall stature.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"655-673"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary Overview and Future Perspectives: ESR1 Mutations, Liquid Biopsy, and Artificial Intelligence for a New Era of Personalized Medicine in ER+ Breast Cancer.","authors":"Serafina Martella, Giacomo Cusumano, Thilini Hemali Senevirathne, Dimitrios Stylianakis, Enrico Palmas, Nerina Denaro, Chiara Tommasi, Mario Scartozzi, Lorenzo Gerratana, Cinzia Solinas","doi":"10.1007/s40291-025-00811-8","DOIUrl":"https://doi.org/10.1007/s40291-025-00811-8","url":null,"abstract":"<p><p>ESR1 gene mutations represent one of the main mechanisms of acquired resistance to endocrine therapy (ET) in estrogen receptor-positive (ER+) breast cancer. The introduction of liquid biopsy as a minimally invasive technique for analyzing circulating tumor DNA (ctDNA) has opened new avenues for real-time mutation monitoring and personalized treatment strategies. This review explores the clinical relevance of ESR1 mutations in endocrine resistance, the potential of liquid biopsy for early detection and monitoring, and the integration of advanced sequencing technologies and artificial intelligence to improve diagnostic accuracy. Preclinical and clinical studies on key mutations (D538G, Y537S) were analyzed, emerging technologies [(next-generation sequencing (NGS), digital droplet PCR (ddPCR), Cancer Personalized Profiling by deep Sequencing (CAPP-Seq), Targeted Digital Sequencing (TARDIS)] were compared, and survival data from seven major studies were summarized to assess the impact of ESR1 mutations on progression-free survival (PFS) and overall survival (OS). The results show that these mutations, particularly those affecting the ligand-binding domain, are associated with reduced efficacy of aromatase inhibitors and increased tumor aggressiveness. Liquid biopsy proves useful for early detection of resistance mutations and dynamic disease monitoring, but its clinical implementation is limited by low ctDNA levels, technological variability, and the lack of standardized clinical cut-offs. Integration with tissue biopsy, radiomics, and artificial intelligence (AI)-based platforms enhances its clinical utility and prognostic value. In conclusion, liquid biopsy, when combined with advanced technologies and predictive tools, represents an innovative resource for the personalized management of ER+ breast cancer, with the potential to guide timely therapeutic interventions and improve long-term survival.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Aging: From Molecular Mechanisms to Targeted Therapies.","authors":"Jenyfer María Fuentes-Mendoza, Marcio José Concepción-Zavaleta, Juan Muñoz-Moreno, Luis Concepción-Urteaga, José Paz Ibarra, Regina Garza-Boullosa, Viviana Cardoso-Pérez","doi":"10.1007/s40291-025-00812-7","DOIUrl":"https://doi.org/10.1007/s40291-025-00812-7","url":null,"abstract":"<p><p>Cardiovascular aging is a complex biological process involving progressive cellular and molecular changes that impair heart and vascular function. This review evaluates both fundamental mechanisms and therapeutic strategies, focusing on how recent advances in pharmacology, gene therapy, and regenerative medicine can be translated into clinical practice to mitigate age-related cardiovascular decline. We conducted a comprehensive analysis of peer-reviewed studies from 2000 to 2023, examining molecular pathways of cardiovascular aging and their modulation through pharmacological, genetic, and lifestyle interventions. The review prioritized clinical trials, translational research, and meta-analyses to assess therapeutic efficacy and safety. Current evidence highlights the effectiveness of senolytic drugs such as dasatinib and quercetin in reducing age-related cardiovascular dysfunction, while rapamycin and metformin show promise in improving cardiac longevity through metabolic regulation. Gene therapies, including clustered regularly interspaced short palindromic repeats (CRISPR)-based interventions, demonstrate potential in preclinical models for cardiac regeneration. Stem cell therapies and nanotechnology-based drug delivery systems are emerging as innovative approaches to enhance tissue repair. In addition, lifestyle modifications such as Mediterranean diet adherence and exercise significantly improve vascular health in aging populations. However, challenges remain in drug delivery, patient-specific responses, and long-term safety of novel therapies. The integration of targeted pharmacological treatments, advanced regenerative techniques, and personalized lifestyle interventions represents a transformative approach to managing cardiovascular aging. Future research should focus on optimizing therapeutic combinations, refining delivery methods, and validating biomarkers for clinical monitoring. A multidisciplinary strategy combining these advances will be essential to improve cardiovascular outcomes in aging populations.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Potential of Cross-Specimen microRNA Panels as Biomarkers for Colorectal Cancer: A Systematic Review and Meta-analysis.","authors":"Atta Ullah Khan, Maria Ali, Muhammad Aamir Wahab","doi":"10.1007/s40291-025-00805-6","DOIUrl":"https://doi.org/10.1007/s40291-025-00805-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Colorectal cancer remains a major global health challenge, necessitating the development of accurate non-invasive diagnostic tools. Circulating and excretory microRNAs (miRNAs) are promising biomarkers owing to their stability and regulatory roles in tumorigenic pathways. While single miRNA assays often lack sufficient diagnostic accuracy, panels combining multiple miRNAs have shown enhanced performance. This systematic review and meta-analysis evaluated the diagnostic accuracy of multi-miRNA panels and explored their mechanistic relevance to colorectal cancer pathogenesis.</p><p><strong>Methods: </strong>A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted through March 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO (CRD420251060655). Eligible studies assessed the diagnostic accuracy of multi-miRNA panels for colorectal cancer using extractable data on sensitivity, specificity, and area under the curve. Data were extracted independently by two reviewers. A bivariate random-effects model was used to calculate pooled diagnostic estimates. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, and heterogeneity was evaluated using I² statistics. Subgroup analyses were conducted by sample type (e.g., plasma, serum, stool) and panel size. Target genes of recurrent miRNAs were mapped to canonical colorectal cancer-related pathways.</p><p><strong>Results: </strong>Twenty-nine studies comprising 5497 participants (3070 colorectal cancer cases and 2427 controls) and 35 multi-miRNA panels were included. Pooled sensitivity was 0.85 (95% confidence interval 0.80-0.88), specificity was 0.84 (95% confidence interval 0.80-0.88), and the area under the curve was 0.90, despite substantial heterogeneity (I² > 77%). Panels derived from plasma samples showed the highest balanced performance (sensitivity 0.88; specificity 0.87), while three-miRNA panels exhibited the best diagnostic trade-offs. Mechanistic analysis of 42 recurrent miRNAs revealed consistent involvement in key colorectal cancer pathways, including PI3K/AKT, Wnt/β-catenin, epithelial-mesenchymal transition, angiogenesis, and immune regulation.</p><p><strong>Conclusions: </strong>Multi-miRNA panels derived from diverse biospecimen sources demonstrate high diagnostic accuracy for colorectal cancer and are mechanistically linked to fundamental oncogenic pathways. Future efforts should focus on panel standardization, biospecimen-specific validation, and integration into clinical workflows to advance precision oncology.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}