MedComm最新文献

Circular RNAs (circRNAs) are characterized by their covalently closed structure, remarkable stability, and precise spatiotemporal regulation, evolving from once-overlooked transcriptional byproducts to pivotal molecular regulators. In addition to their well-established function as microRNA sponges, circRNAs serve as protein scaffolds, transcriptional modulators, and even templates for functional peptide synthesis. This review synthesizes recent breakthroughs across the entire circRNA life cycle, encompassing biogenesis, degradation, nucleocytoplasmic transport, and extracellular vesicle-mediated secretion, while systematically analyzing their multifaceted involvement in tumorigenesis, immune evasion, metastatic dissemination, programmed cell death, and tumor–microbiome crosstalk. We highlight their exceptional potential as liquid biopsy biomarkers and critically assess translational applications in circRNA-based vaccines, targeted delivery platforms, and engineered cell therapies like CAR-T. Emerging artificial intelligence approaches that accelerate circRNA discovery, functional characterization, and therapeutic design are also discussed. Addressing current challenges in standardization and delivery methodologies, we propose future directions for incorporating circRNAs and their encoded proteins into precision oncology and next-generation immunotherapies. Together, these advances position circRNAs as a transformative paradigm with the potential to revolutionize cancer diagnostics, targeted therapeutics, and RNA vaccine development.

mRNA medicine is an emerging therapeutic approach that utilizes messenger RNA to synthesize functional proteins directly within target cells. This technology offers notable advantages including rapid development cycles, diverse therapeutic applications, and adaptable platform design for various diseases. However, mRNA therapeutic development faces substantial challenges, particularly in determining optimal mRNA sequences and developing effective delivery systems that ensure stability and achieve precise delivery. Current development processes often involve extensive experimental screening, highlighting the need for more efficient computational approaches. This review first introduces fundamental concepts in the mRNA vaccine field and systematically analyzes the roles and limitations of computational tools in advancing mRNA vaccine development across three key areas: sequence optimization, modification strategies, and delivery system optimization. Finally, we present the current application status of mRNA vaccines and discuss future prospects, highlighting emerging computational opportunities that may shape next-generation mRNA vaccine development. This review spans the entire mRNA vaccine development pipeline, providing a foundational resource for researchers and facilitating technological advancement in this rapidly evolving field.

Significant residual cardiovascular risk persists in patients diagnosed with coronary artery disease despite intensive lipid-lowering therapy. Although insulin resistance (IR) is an established epidemiological risk factor, the biological mechanisms by which it promotes plaque destabilization remain poorly understood. This single-center retrospective study, involving 1271 patients, investigated the relationships between four validated IR indices—triglyceride-glucose (TyG), TyG–body mass index (TyG–BMI), metabolic score for insulin resistance (METS-IR), and atherogenic index of plasma (AIP)—and high-risk coronary plaque characteristics quantified by coronary computed-tomography angiography. Patients with coronary atherosclerosis demonstrated significantly higher IR indices than plaque-free controls, with all indices exhibiting strong correlations with a high-risk plaque burden. During follow-up, 41 patients experienced major adverse cardiovascular events (MACEs), and higher TyG index, AIP, and METS–IR independently predicted MACE after multivariable adjustment, whereas TyG–BMI exhibited a similar but non-significant trend. A composite model integrating high-risk plaque burden, pericoronary fat attenuation index, and the four IR indices achieved superior prognostic accuracy, substantially outperforming individual biomarkers. These findings provide novel mechanistic insights into how metabolic dysfunction promotes coronary plaque vulnerability and identify a promising integrated approach for residual risk stratification in patients with coronary artery disease. In this study, IR indices (TyG, TyG-BMI, AIP, and METS-IR) correlated high-risk coronary plaque features in 1271 patients. During 48-month follow-up, all indices independently predicted MACEs. Combined with coronary imaging markers, the composite model achieved AUC 0.82, revealing metabolic dysfunction drives plaque destabilization in coronary disease.

Gastric mucosal integrity is essential for maintaining systemic homeostasis, serving as the primary defense against external insults. Ethanol ingestion is a major clinical cause of gastric mucosal injury, yet effective prevention or treatment remains limited. This study investigates the protective role of nitrate against ethanol-induced gastric ulcers and its underlying mechanisms. In vivo, nitrate significantly ameliorated ethanol-induced gastric bleeding, edema, inflammation, and mucus layer thinning in rats, while strengthening the vascular endothelial barrier. Transcriptomic analyses and trefoil factor 2 (Tff2)-knockdown rats experiment identified Tff2 as the key gene responsible for mediating nitrate's protective effects against ethanol. In vitro, TFF2 was found to be a crucial target for nitrates, which enhance the migratory reparative capacities of human gastric epithelial cells. Further assays revealed that RBPJ regulates the TFF2 promoter, and NICD–RBPJ complex formation is critical for TFF2 transcriptional repression. We demonstrate for the first time that TFF2 is a central effector in nitrate-mediated gastric mucosal defense and repair and implicate the Notch signaling pathway in TFF2 regulation. These findings suggest nitrate exerts a protective effect on the gastric mucosa through multiple ways. TFF2 modulation as a potential preventive strategy for ethanol-induced gastric ulcers.

Bone metastasis (BoMet) is a common complication in various cancers. Approximately 20–30% of patients with cancer develop BoMet, which is most frequently associated with solid tumors, such as breast, prostate, and lung cancers. BoMet can lead to skeletal-related events such as fractures, bone pain, and hypercalcemia, negatively affecting the patient's quality of life and markedly shortening overall survival. The development of BoMet is a complex, multistep process driven by dynamic interactions between tumor cells and the bone microenvironment. The bone microenvironment provides a supportive niche for disseminated tumor cells, where intricate signaling networks and stromal interactions regulate the initiation, dormancy, reactivation, and progression of BoMet. Although current bone-targeted therapies can reduce the incidence of these complications, the clinical outcomes for patients with BoMet remain poor. Therefore, elucidating the molecular mechanisms governing these interactions is essential for identifying new therapeutic strategies. This review systematically explores the molecular drivers of BoMet progression, dynamic interactions within the metastatic niche, available preclinical models, established treatment modalities, and emerging therapeutic approaches. As fundamental research continues to advance toward clinical translation, the outlook for patients with BoMet is expected to improve significantly.

RNA-targeted therapy is reshaping molecular medicine by shifting the traditional “protein-centric” view toward an “RNA-regulatory network” paradigm. Beyond carrying genetic information, RNA plays essential roles in posttranscriptional regulation, signaling pathways, and epigenetic modulation. Advances in high-throughput sequencing, structural biology, and delivery technologies have accelerated the development of diverse RNA therapeutics, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNA (miRNA) modulators, messenger RNA (mRNA) therapeutics, aptamers, short hairpin RNA, and CRISPR/Cas-guided single-guide RNAs. However, a concise comparison of these major RNA modalities and the translational barriers that limit their broader clinical application is still lacking. This review outlines the mechanisms and representative applications of these RNA-based strategies in gene silencing, editing, protein replacement, immune activation, and targeted drug delivery. Special emphasis is placed on ASOs and siRNAs for neurological, metabolic, and infectious diseases, as well as mRNA therapeutics that are transforming vaccine development. Common challenges-such as in vivo stability, delivery efficiency, and immune activation-are also discussed. Finally, we highlight how chemical modification, nanotechnology, and artificial intelligence-assisted design are enhancing the specificity, stability, and safety of RNA therapeutics, providing a framework for advancing next-generation precision RNA medicine.

Mechanical ventilation (MV) serves as a critical intervention to maintain adequate gas exchange. Unfortunately, MV often leads to the development of ventilator-induced lung injury (VILI). VILI pathogenesis involves alveolar-capillary barrier disruption, dysregulated inflammation, and mechanotransduction-driven cellular dysfunction, but the interplay of these mechanisms remains incompletely understood. Here, we review the types of mechanical stress in VILI, key signaling pathways implicated in MV-induced lung injury, with particular emphasis on the impact of altered mechanical forces in VILI. Furthermore, we discuss the cell-specific mechanisms in VILI. We also delineate the intricate molecular mechanisms that orchestrate intercellular communication in VILI. In addition, we discuss the limitations of current clinical strategies, and the identification of novel drug targets with transformative potential for treatment of VILI. Moreover, we summarize the current and emerging therapeutic strategies and discuss the existing knowledge gaps and future directions for VILI prevention. By integrating mechanical mechanistic insights with translational perspectives, this review identifies novel biomarkers and potential therapeutics to mitigate VILI. Our synthesis not only advances the understanding of VILI pathophysiology but also provides a framework for precision medicine approaches in critical care, ultimately optimizing MV outcomes.

Pulmonary hypertension (PH) is a fatal condition that affects individuals with systemic sclerosis (SSc), a multiorgan fibrotic disease with limited treatment options. A central feature of PH is vascular remodeling, defined by the narrowing of the arteriole lumen due to cell proliferation and extracellular matrix deposition. Herein, we identify a central mechanism that can regulate multiple transcripts important for vascular remodeling. The highlight of our study is the demonstration that reduced pulmonary artery smooth muscle (PASMC) Nudt21, which codes for the RNA binding protein Cleavage and Polyadenylation Specificity Factor Subunit 5 (CPSF5) The, known to regulate alternative polyadenylation, results in heightened right ventricle systolic pressures in mice exposed to hypoxia–sugen. We also report that increased PASMC proliferation is present in mice with reduced PASMC Nudt21 under normoxic conditions, recapitulating features of hypoxia–sugen exposure. Our studies reveal that reduced CPSF5 leads to 3′ untranslated region shortening of PTGER3 and CBFB, the latter contributing to increased levels of proliferative transcription factor RUNX1. We also identify miR-3163 as novel negative regulator of NUDT21 expression in PH. These observations are validated in remodeled vessels from patients with SSc associated with PH and in and point to common mechanisms of RNA processing deficits that contribute to vascular remodeling in PH.

Although BRAF is frequently mutated across multiple cancer types, its clinical utility as a prognostic biomarker has remained inconsistent in clinical practice, likely due to additional events modulating BRAF signaling pathways. This inconsistency has driven our investigation into the broader landscape of BRAF signaling and the development of a robust molecular signature to assess BRAF-driven oncogenic activity. To achieve this, we introduced BRAF25, a transcriptional signature designed to effectively capture BRAF oncogenic activity. Our findings reveal that 25.6% of TCGA colorectal cancer (CRC) tumors exhibit BRAF pathway activation, even in 19.4% of BRAF wild-type (WT) cases, suggesting alternative mechanisms driving pathway activation. The BRAF-active subtype, termed BAG-3 (BRAF Activity Group-3), demonstrated reduced responsiveness to chemotherapy and anti-BRAF therapy. Notably, BRAF25 subtyping addresses the limitations of using BRAF mutation alone to predict patient survival. We experimentally screened and validated DUSP6 as a sensitizing target for anti-BRAF therapy, enhancing BRAF inhibitor efficacy in CRC. Furthermore, pan-cancer analyses implicate the BRAF25 signature in poor prognosis across diverse BRAF-driven malignancies. In conclusion, stratifying patients by transcriptional BRAF oncogenic activity, instead of relying solely on BRAF mutation status, provides a more precise approach to guide clinical decision-making and improve therapeutic outcomes.

Traditional Chinese medicine (TCM), consisting of a complete TCM diagnosis and treatment system, is a valuable treasure in the long river of Chinese clinical history. However, the subjective diagnosis, ambiguous mechanisms, and complex formulas make it slightly lag behind the development of modern medicine. With the emergence of novel technologies such as artificial intelligence (AI) and nanotechnology, TCM modernization has regained its promise of hope. In this review, we provide an overview of applications of AI and nanotechnology to assist TCM modernization. Firstly, we summarize the auxiliary TCM diagnosis approaches based on machine learning and deep learning, which facilitate “four diagnostic methods” (inspection, auscultation–olfaction, inquiry, and pulse palpation) with standard and quantifiable data collection, and objective syndrome differentiation and diagnostic decisions. Secondly, a comprehensive overview of the nanotechnology used to enhance the therapeutic effects of TCM is provided, including optimizing TCM formulas and enhancing active targeting. Finally, we summarize the current challenges, clinical translation, and future perspectives of AI, TCM diagnosis, and nanotechnology. Our review and insights aim to provide valuable guidance for the continued advancement of TCM modernization.