Molecular Biomedicine分子生物医学
Molecular Biomedicine(英文缩写 MOL BIOMED),ISSN 2662-8651,eISSN 2662-8651,中文译名:分子生物医学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-10-01 至 2026-09-30，按本站收录文献的发表日期统计。
期刊介绍
Molecular Biomedicine 最新收录文献
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1. Characterization of SPP1 + macrophages and their correlation with resistance to neoadjuvant chemotherapy in colorectal cancer liver metastasis.
PMID:日期:2026-10-05Neoadjuvant chemotherapy (NAC) for colorectal cancer liver metastasis (CRLM) remains a major clinical challenge, with outcomes varying widely among patients, yet the mechanisms that drive therapeutic resistance remain incompletely understood. In this study, we integrated single‑cell RNA‑sequencing and spatial transcriptomics of patient tumor specimens to dissect the interplay between the hepatic tumor microenvironment and chemotherapy resistance. We identified a specific macrophage subpopulation marked by elevated expression of Secreted Phosphoprotein 1 (SPP1) that is significantly enriched in insufficient responders to NAC. Mechanistically, these SPP1 + macrophages exhibit a pro‑tumoral transcriptomic profile and directly suppress CD8 + T cell cytotoxic function through the SPP1‑CD44 signaling axis, as demonstrated by in vitro co‑culture assays, a large‑scale tissue microarray, and multiple syngeneic mouse models. Spatially, they are scattered throughout the tumour and form dense barriers that sequester CD8 + T cells and drive their exhaustion. Strikingly, this spatial configuration inversely correlates with cytotoxic activity and adaptive immune signatures and thereby reinforces a local immunosuppressive niche that sustains chemoresistance. These data provide the missing link: effective chemotherapy requires an immune‑active hepatic microenvironment, and SPP1 + macrophage infiltration actively disrupts this state, which in turn promotes clinical resistance. In a preclinical CRLM model, SPP1 blockade synergised with anti‑PD‑1, inducing significant tumour regression and restoring T‑cell function. Collectively, our findings position SPP1 + macrophages as central drivers of NAC resistance in CRLM and highlight the spatial immune barrier they create as a promising therapeutic target for overcoming chemoresistance and improving immunotherapy responses.
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2. {"_":"Targeting the CD4 effector memory T cells re-expressing CD45RA suppressor galectin-7: a multi-omics-guided therapeutic strategy for idiopathic pulmonary fibrosis.","sup":["+"]}
PMID:日期:2026-10-05Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options. Although single-cell and spatial transcriptomics have revealed cellular heterogeneity within the IPF lung microenvironment, the immune drivers with causal relevance remain poorly defined. Here, through large-scale Mendelian randomization integrating multi-omics data, we identified a consistent negative causal association between the proportion of CD4⁺ effector memory T cells re-expressing CD45RA (TEMRA) and IPF risk. Multi-platform validation-including single-cell RNA sequencing, flow cytometry, and multiplex immunofluorescence-confirmed a significant reduction in CD4⁺ TEMRA frequency in both peripheral blood and lung tissues of IPF patients, establishing this subset as a clinically relevant biomarker. Spatial transcriptomics further revealed a negative correlation between TEMRA differentiation signatures and local fibrotic burden. Mechanistically, integrated single-cell analyses pinpointed metaplastic KRT5⁺ basal cells as a key epithelial population with the capacity to disrupt immune homeostasis. These aberrant epithelial cells upregulate Galectin-7 (LGALS7), which we demonstrate competes with IL-7 for receptor binding, suppresses STAT5 phosphorylation, and limits CD4⁺ TEMRA differentiation, thereby uncovering a previously unrecognized epithelial-immune crosstalk axis in IPF. Guided by these findings, virtual screening of 20,000 compounds identified neoeriocitrin as a Galectin-7 inhibitor that restores STAT5 phosphorylation in vitro and attenuates pulmonary fibrosis in vivo. This study positions Galectin-7 as a druggable target and establishes a novel framework linking epithelial dysfunction to immune dysregulation in IPF.
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3. Oncolytic virus encoding decorin and the CD40 ligand boosts T-cell response and achieves a durable antitumor response during breast cancer treatment.
PMID:日期:2026-10-05Triple-negative breast cancer (TNBC) remains an aggressive disease with limited treatment options. Oncolytic adenoviruses represent a promising platform, but their efficacy as single agents is often insufficient. This study examined whether an oncolytic adenovirus co-delivering decorin (DCN) and CD40 ligand (CD40L), designated rAd.DCN.CD40L, could enhance antitumor activity and immune activation against TNBC. Recombinant adenoviruses expressing DCN (rAd.DCN), CD40L (rAd.CD40L), or both proteins were constructed and evaluated in breast cancer cells using cell viability, apoptosis, migration, invasion, and damage-associated molecular pattern (DAMP) release assays. Compared with rAd.DCN or rAd.CD40L alone, rAd.DCN.CD40L triggered greater apoptosis and tumor cell death and elicited more pronounced DAMP release. Co-culture experiments also revealed enhanced dendritic cell function following rAd.DCN.CD40L treatment. For in vivo evaluation, syngeneic 4T1 and EMT-6 subcutaneous tumor models and a 4T1 lung metastasis model were employed. rAd.DCN.CD40L substantially delayed tumor growth and improved survival in tumor-bearing mice. Flow cytometric and histological analyses further confirmed enhanced local and systemic T-cell responses, elevated CD8⁺ T-cell activity, and modulated inflammatory macrophage phenotypes. Mechanistically, western blot analysis showed that rAd.DCN.CD40L may contribute to extracellular matrix remodeling and the down-regulation of the expression of epithelial-mesenchymal transition (EMT)-associated genes. Notably, CD8⁺ T-cell depletion markedly attenuated the therapeutic efficacy of rAd.DCN.CD40L, demonstrating that CD8⁺ T cells are critical functional effectors of tumor control. Collectively, these findings indicate that a DCN- and CD40L-armed oncolytic adenovirus represents a promising combinatorial strategy for TNBC immunotherapy, and warrants further preclinical and clinical investigation.
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5. Bile acid signaling in health and disease.
PMID:日期:2026-10-02Bile acids (BAs), cholesterol-derived amphipathic metabolites which are traditionally regarded as digestive surfactants, are now recognized as pleiotropic signaling molecules that act through ligand-, receptor-, and tissue-specific mechanisms to maintain systemic homeostasis. They exert biological functions via nuclear receptors (FXR, PXR, VDR, CAR) and membrane receptors (TGR5, S1PR2, MRGPRX4). These receptors activate transcriptional and membrane-initiated programs, including FXR-SHP/FGF19 feedback, TGR5-cAMP-PKA signaling, S1PR2-ERK/AKT/RhoA pathways, MRGPRX4-dependent Ca⁺ signaling, PXR/CAR/VDR-driven detoxification responses, and non-receptor-mediated membrane and mitochondrial stress pathways. This review discusses how the diversity of BA structures, hepatic synthesis, conjugation, transportation, enterohepatic circulation, and microbiota-mediated transformation generates receptor- and tissue-specific signals. Furthermore, we summarize the physiological functions of BA signaling in lipid, glucose, and energy metabolism, intestinal epithelial integrity, mucosal immunity, neuroendocrine regulation, musculoskeletal adaptation, and renal water-salt balance. Additionally, we discuss the effects of disrupted BA signaling on cholestatic and metabolic liver diseases, alcohol-associated liver disease, hepatocellular carcinoma, inflammatory bowel disease, BA diarrhea, colorectal cancer, obesity, type 2 diabetes, atherosclerosis, and biliary tract diseases. Finally, the therapeutic strategies that modulate BA signaling, including the use of FXR and TGR5 agonists, FGF19 analogues, transporter inhibitors, enzyme-targeting methods, microbiota-based treatments, and hydrophilic BA therapies, are evaluated. By categorizing BA biology according to the production of ligands, receptor activation, tissue responses, and disease mechanisms, this review highlights BA signaling as an integrated regulatory network and a tractable therapeutic axis in health and disease.
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6. {"_":"Precision base-editing of the cryptic 3' acceptor site to correct the RNA splicing defect of β-thalassemia.","sup":["654"]}
PMID:日期:2026-09-30β-Thalassemia is one of the most common inherited disorders worldwide and is caused by mutations affecting β-globin production. β mutation (IVS2-654, C > T) is one of the most frequently occurring β-thalassemia alleles in Han Chinese population, which activates a cryptic 3' splice site and leads to aberrant RNA splicing. Previous studies demonstrated that direct base editing of the IVS2-654 mutation is challenging because suitable single-guide RNAs (sgRNAs) cannot effectively target this site. Here we investigated an alternative therapeutic strategy by targeting the mutation-activated cryptic 3' splice acceptor site, rather than the disease-causing mutation itself. We first introduced base substitutions into the cryptic splice acceptor site in a β-thalassemia mouse model using CRISPR-Cas9-mediated homology-directed repair, which restored normal RNA splicing and validated the therapeutic rationale of this approach. We then generated base-edited β mice by microinjecting Td-CBEmax mRNA together with sgRNAs targeting the cryptic splice acceptor site into one-cell embryos. Base editing was successfully achieved in 78% of live-born β mice, of which 86% produced correctly spliced β-globin transcripts. Restoration of normal RNA splicing was accompanied by marked improvement of hematological parameters and tissue pathology in most base-edited founder mice and their offspring compared with non-edited β mice. Together, these findings demonstrate that mutation-activated cryptic splice sites are therapeutically actionable targets for precision base editing and provide proof of concept for a precise and effective strategy to correct aberrant RNA splicing in β-thalassemia.
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7. SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.
7. SGLT2抑制剂：机制、生理学与药理学及临床应用PMID:日期:2026-09-30Sodium-glucose cotransporter 2 (SGLT2) is a low-affinity, high-capacity transporter expressed predominantly in the renal proximal tubule, where it mediates the sodium-coupled reabsorption of most filtered glucose. SGLT2 inhibitors have evolved from glucose-lowering agents into disease-modifying therapies across the cardio-renal-metabolic continuum. Blockade of proximal tubular transport induces glycosuria, osmotic diuresis, restoration of tubuloglomerular feedback, resetting of renal haemodynamics, and altered fluid compartmentalisation. These early renal and circulatory effects interact with systemic metabolic adaptations, including pseudo-starvation signalling, erythropoiesis, altered uric acid handling, and changes in substrate availability. At the cellular level, SGLT2 inhibition has been linked to improved ionic homeostasis and mitochondrial quality control, reduced oxidative stress, modulation of inflammation, and attenuation of maladaptive tissue remodelling. Endothelial injury may connect these cellular effects with microvascular dysfunction and fibrosis. Endothelial dysfunction and endothelial-to-mesenchymal transition (EndMT) offer a mechanistic framework for understanding the relationship between microvascular injury and fibrosis. However, EndMT is best viewed as one component of a broader endothelial-stromal stress response rather than as a single proven mediator of clinical benefit. These pharmacodynamic and cellular effects help explain the consistent clinical efficacy of SGLT2 inhibitors across type 2 diabetes, chronic kidney disease, and heart failure (HF), while also informing emerging applications in acute HF, after myocardial infarction, and in patients with arrhythmia or metabolic dysfunction-associated steatohepatitis. This Review integrates mechanistic, pharmacological, and clinical evidence to identify unresolved translational gaps and future directions, including mechanism-informed biomarkers, imaging, spatial multi-omics, phenotype-guided patient stratification, dual sodium-glucose cotransporter 1/2 inhibition, and rational combination therapy.
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8. Aryl hydrocarbon receptor is involved in DNA damage repair after liver injury with diethylnitrosamine in mice.
8. 芳香烃受体参与二乙基亚硝胺诱导的小鼠肝损伤后的DNA损伤修复PMID:日期:2026-09-29Aryl hydrocarbon receptor (AhR) is a transcription factor traditionally involved in toxicological and carcinogenic cellular processes linked to xenobiotics. In recent decades, a new physiological role has emerged, in which AhR has been shown to be a key regulator of different processes such as the cell cycle, cell proliferation, apoptosis, pluripotency, and stemness. Recent studies have suggested a possible role for AhR in the DNA damage response (DDR) and repair mechanisms. To assess this point, in this work we used diethylnitrosamine (DEN) to induce liver injury and DNA damage in wild type (WT) and AhR knockout (KO) mice. We analysed the protein expression levels of several DDR (H2AX, 53BP1, and BRCA1) and cell proliferation (Ki67, AFP, and PCNA) markers. Therefore, we demonstrate that following DNA damage, the absence of AhR results in a shift towards apoptosis and compensatory proliferation mechanisms, accompanied by reduced repair fidelity of DNA damage compared with than in WT mice, compromising genomic stability. We also mapped the interactome profile of AhR, identifying new partners involved in both repair and proliferation processes. In conclusion, our results highlight the relevant role of AhR in cell proliferation and DNA repair processes, which can be key in different pathologies, such as cancer.
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9. MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.
PMID:日期:2026-09-29Major facilitator superfamily domain-containing protein 2A (MFSD2A) is a sodium-dependent lysolipid transporter that delivers lysophosphatidylcholine-bound fatty acids, particularly docosahexaenoic acid, across specialized cellular interfaces. This Review synthesizes structural, biochemical, physiological, genetic, and disease evidence through an evidence-weighted transport-to-barrier-to-disease framework. We first examine substrate recognition, sodium coupling, conformational transport, and the membrane lipid consequences of lysophosphatidylcholine uptake. We then detail the best-established physiological setting, central nervous system endothelium, where MFSD2A supports brain docosahexaenoic acid accretion, blood-brain barrier maturation, and suppression of caveolae-mediated transcytosis. Evidence from the retina, placenta, lung, kidney, epidermis, and immune cells is compared to define tissue-specific deployment rather than a universal downstream pathway. Rare biallelic variants and experimental loss-of-function models provide the strongest disease evidence, linking impaired lysolipid transport to deficient brain lipid supply, microcephaly, and neurodevelopmental abnormalities. Acquired vascular injury studies associate MFSD2A dysregulation with barrier leakage, whereas proposed roles in cancer, immunotherapy response, and patient stratification remain context-dependent and largely associative. We also assess translational concepts, including barrier stabilization, central nervous system drug delivery, biomarker development, and structure-guided modulation, emphasizing unresolved requirements for selectivity, reversibility, safety, and prospective validation. By distinguishing transporter-intrinsic mechanisms from secondary lipid remodeling and disease correlations, this Review clarifies which functions are established, which are tissue restricted, and which remain hypotheses. This framework identifies experimental priorities for linking MFSD2A activity to clinically informative phenotypes without extrapolating beyond current evidence.
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10. mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.
10. mRNA脂质纳米颗粒疫苗：现状、挑战与未来前景PMID:日期:2026-09-28mRNA vaccines have become a clinically validated vaccine platform, as demonstrated by the success of COVID-19 vaccines such as Comirnaty and Spikevax, owing to their rapid design, manufacturing scalability, and capacity to induce in situ antigen expression. A key factor underlying this success is the lipid nanoparticle (LNP) delivery system, which protects mRNA from degradation and promotes efficient cellular uptake and cytoplasmic delivery, thereby enabling the full potential of mRNA technology. The continued advancement of mRNA-LNP vaccines requires integrated optimization of mRNA design, LNP composition, and delivery strategies to achieve improved stability, efficient intracellular delivery, and balanced immune responses. Despite remarkable progress, challenges related to formulation stability, long-term storage stability, safety and reactogenicity concerns, and durability of immune protection continue to hinder the broader application of mRNA-LNP vaccine platforms. This review provides an integrated overview of recent advances in mRNA-LNP vaccines, covering mRNA molecular engineering, LNP composition and delivery mechanisms, immune responses, clinical progress, and current developmental challenges. Furthermore, emerging strategies, including thermostable formulations, next-generation LNPs with improved targeting capability, emerging RNA platforms, and artificial intelligence-assisted optimization of RNA sequences and lipid materials, are discussed. By summarizing current achievements and future opportunities, this review highlights key principles guiding the rational design of safer, more stable, and more precise mRNA-LNP vaccine platforms and provides insights into accelerating their clinical translation.