MOLECULAR MEDICINE分子医学
MOLECULAR MEDICINE(英文缩写 MOL MED),ISSN 1076-1551,eISSN 1528-3658,中文译名:分子医学 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：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.382 | Q1 |
| 2022 | 5.700 | Q1 |
| 2023 | 6.000 | Q1 |
| 2024 | 6.400 | Q1 |
| 2025 | 8.300 | Q1 |
MOLECULAR MEDICINE 最新收录文献
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1. BRIP1, a G-quadruplex DNA helicase, protects against AID-induced genomic instability by limiting R-loop accumulation.
1. BRIP1是一种G-四链体DNA解旋酶，通过限制R环积累来防止AID诱导的基因组不稳定性PMID:日期:2026-09-30BRIP1 (BRCA1-interacting protein 1) or FANCJ is a 5'-3' DNA helicase that plays critical roles in the maintenance of genome stability through its involvement in DNA repair, replication stress responses, and the resolution of DNA secondary structures or non-B DNAs. Defects in the BRIP1 helicase gene are associated with an increased risk of various cancers. It has been shown that BRIP1-deficient mice are predisposed to B-cell lymphoma. Because activation-induced cytidine deaminase (AID)-dependent genomic instability resulting from its mistargeting to non-immunoglobulin genes is a major hallmark of B-cell lymphoma, and non-B DNA structures, including G-quadruplexes (G4) and RNA-DNA hybrids (R-loops), are implicated in AID-induced genomic instability, we asked whether BRIP1 helicase limits these secondary structures to suppress AID-mediated oncogenesis. We knocked down (KD) BRIP1 in the CH12F3-2A mouse B-cell, a model cell line for studying AID-induced physiological and non-physiological events and their underlying mechanisms. We also used biophysical assays and in silico tools to study non-B DNAs at human AID off-target sites. Here, we report that BRIP1 KD increased the frequency of AID-induced events, including IgM-to-IgA antibody switching, somatic hypermutation (SHM), DNA double-strand breaks (DSBs), and IgH/c-Myc chromosomal translocations. However, BRIP1 KD does not affect either the end-joining of AID-induced DNA breaks or the synapsis of switch regions. Importantly, BRIP1 KD resulted in the accumulation of R-loops at both AID targets and off-targets. Furthermore, in silico analysis revealed G4s as the most prevalent form of non-B DNA conformation at AID off-target sites in human. We propose that BRIP1 suppresses AID-induced genomic instability by resolving non-B DNA, thereby potentially limiting the accumulation of genomic lesions that contribute to B-cell lymphoma. These findings revealed that BRIP1 prevents the excessive accumulation of non-B DNAs at AID target sites and suppresses AID-mediated genomic instability. These data also provide a possible explanation for why BRIP1-deficient mice are predisposed to B-cell lymphoma.
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2. The protein kinase IKK epsilon shapes the melanoma tumor microenvironment by modulating angiogenesis and the T-cell immunity.
PMID:日期:2026-09-30Inhibitor of nuclear factor kappa-B kinase epsilon (IKKε) contributes to tumorigenesis and metastasis in various cancers. In melanoma, it is overexpressed and constitutively active. Inhibition of IKKε by either knockdown or pharmaceutical compounds reduce tumor progression by suppressing key molecular pathways within melanoma tumor cells. However, within the tumor microenvironment (TME), the role of this protein remains to be fully elucidated. Multiplex immunohistochemistry was performed on human primary melanomas to assess IKKε expression in tumor and immune cell compartments. In the mouse model, B16BL6 melanoma cells were injected subcutaneously into the flanks of wildtype and IKKε-deficient mice, and tumor growth was monitored over time. Flow-cytometric analyses characterized intratumoral immune cell populations in both genotypes, followed by in vivo CD8⁺ T-cell depletion to determine their contribution to tumor control. To elucidate molecular mechanisms underlying the differential tumor growth, we conducted targeted and untargeted proteomic analyses, which indicated regulation of angiogenic pathways which were further examined by assessing specific protein changes in tumor tissue and performing in vitro angiogenesis assays. The reduced tumor growth observed in IKKε knock-out (KO) mice was concomitant with elevated levels of cytotoxic CD8⁺ and γδ-T-cells, and a diminished presence of neutrophils. Furthermore, our data revealed that isolated CD8⁺ T-cells from IKKε KO mice exhibited a higher activity in comparison to their wildtype counterparts. In addition, the depletion of CD8⁺ cells reversed the antitumor efficacy of IKKε depletion. Proteomic analysis of tumor lysates revealed a reduction of several chemokines in IKKε KO mice compared to wildtype controls, that might contribute to the reduced tumor growth and suggested that an inhibition of angiogenesis may support the antitumor activity in IKKε KO mice. This hypothesis could be confirmed by further protein analyses and angiogenesis assays. Our data imply that IKKε expression in melanoma is not only important in the tumor cells but also in the tumor microenvironment by regulation of the immune response and angiogenesis. Consequently, inhibition of IKKε may offer a novel therapeutic approach for melanoma, complementing existing therapies that target pathways within tumor cells and antitumor immune responses in the tumor microenvironment.
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3. Urinary collagen type I degradation products as common fibrosis biomarkers in chronic diseases.
3. 尿液I型胶原降解产物作为慢性疾病中常见的纤维化生物标志物PMID:日期:2026-09-23Fibrosis, characterised by excessive accumulation of collagen type I (COL1), is a common feature of chronic diseases, including liver diseases (LDs), chronic kidney disease (CKD) and heart failure (HF). COL1 degradation products can be detected in urine by proteomics/ peptidomics analyses and may serve as non-invasive biomarkers of fibrosis. We aimed to identify a common molecular signature of fibrosis across these diseases that may ultimately guide interventions to slow disease progression and prevent organ damage. Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n = 127), CKD (n = 263) or HF (n = 187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n = 110), CKD (n = 93), HF (n = 32) and controls (n = 643). We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p < 0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p < 0.0001), 0.951 (95% CI 0.931-0.971, p < 0.0001) and 0.950 (95% CI 0.903-0.997, p < 0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p = 0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p = 0.045). A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.
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4. Proteogenomic Analysis of HDAC4 and HDAC5 in Uveal Melanoma.
PMID:日期:2026-09-22Uveal melanoma (UM) is a rare but aggressive cancer arising from cells of the uveal tract that is highly resistant to therapy once it has metastasized. In drug screening experiments, we identified a high sensitivity of primary UM cell lines to the pan-histone deacetylase (HDAC) inhibitor panobinostat and addressed the question whether two class IIa HDACs, HDAC4 and HDAC5, could serve as potential therapeutic targets in UM. Selective pharmacological inhibition of HDAC4/5, as well as stable knockdown of HDAC4 or HDAC5, did not strongly affect cell viability, differentiation, apoptosis or necrosis, and did not sensitize cells to other HDAC or MEK inhibitors. Proteogenomics analysis revealed 73% concordance and only 7% discordance in the expression of transcripts and proteins. Concordance reached 92% for significant transcripts. Despite the lack of severe global gene and protein expression changes in HDAC4- or HDAC5-knockdown UM cell lines, the expression of individual cancer-related genes and signaling pathways was differently regulated following HDAC4 or HDAC5 knockdown. This was particularly evident in the NF-κB pathway, which showed decreased NF-κB p65 phosphorylation in UM cell lines with monosomy in chromosome 3 (M3) genotype and mutations in BRCA1-associated protein 1 (BAP1). In summary, our results suggest that HDAC4/5 inhibitors alone are insufficient for monotherapy in UM cells, but the identification of HDAC4/5-regulated genes involved in cancer progression provides a rationale for exploring combination strategies that include HDAC4/5 inhibition.
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6. HEATR1 deficiency enhanced gastric cancer cell PANoptosis to boost anti-tumor immunity.
PMID:日期:2026-09-04Despite the promise of immune checkpoint inhibitors (ICIs) for gastric cancer (GC) treatment, limited cytotoxic T cell infiltration remains a major barrier to therapeutic efficacy. This study investigates whether targeting HEAT repeat containing 1 (HEATR1) can induce immunogenic PANoptosis to enhance anti-tumor immunity. Bioinformatics analysis of TCGA-STAD cohort, syngeneic mouse models, and patient-derived organoids (PDOs) were employed to assess HEATR1 function. Mechanistic studies examined STAT1/IRF1 signaling, PANoptosis markers, and dendritic cell (DC) activation. Therapeutic efficacy was evaluated in combination with anti-PD1 immunotherapy. HEATR1 expression inversely correlated with CD8 T cell infiltration in GC tissues and was associated with advanced tumor stage and lymph node metastasis. HEATR1 knockdown suppressed tumor growth in immunocompetent but not T cell-deficient mice, demonstrating immune-dependency. Mechanistically, HEATR1 deficiency stabilized STAT1 by inhibiting proteasome-mediated degradation, thereby sensitizing GC cells to IFN-γ-induced PANoptosis through STAT1/IRF1 signaling activation. This inflammatory cell death released damage-associated molecular patterns, which promoted DC maturation and cross-priming of CD8 T cells. The resulting IFN-γ secretion established a positive feedback loop amplifying tumor cell PANoptosis. PDO models confirmed that HEATR1-silenced organoids exhibited enhanced PANoptosis and DC-mediated CD8 T cell expansion. HEATR1 knockdown synergized with anti-PD1 therapy to significantly inhibit tumor progression. HEATR1 deficiency enhances GC cell sensitivity to IFN-γ-mediated PANoptosis via STAT1/IRF1 pathway activation, creating an immunogenic tumor microenvironment that potentiates ICI efficacy. These findings identify HEATR1 as a promising therapeutic target for improving GC immunotherapy outcomes.
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7. Research advances on CD47 in digestive system cancers: from molecular mechanisms to clinical translation.
PMID:日期:2026-09-03CD47 is a major innate immune checkpoint molecule that interacts with signal regulatory protein α (SIRPα) to deliver a "don't eat me" signal and restrain macrophage-mediated phagocytosis. Accumulating evidence indicates that dysregulated CD47 expression is associated with immune escape, treatment resistance, and adverse clinicopathological features in several digestive system cancers, although the strength of these associations varies across tumor types. This narrative review provides an integrative overview of CD47 structure, ligand interactions, signaling and immune-regulatory functions, and summarizes reported expression patterns and available evidence regarding regulatory mechanisms and relevant mechanistic contexts in esophageal, gastric, colorectal, hepatocellular, pancreatic, and biliary tract cancers. We further review therapeutic strategies targeting the CD47-SIRPα axis, including anti-CD47 antibodies, SIRPα fusion proteins, bispecific antibodies, and emerging cell-based and nanotechnology-based platforms, with particular attention to recent clinical developments. Finally, we critically discuss translational challenges, including hematologic toxicity and antigen sink, assay standardization and biomarker selection, resistance mechanisms, optimization of combination regimens, and the need for prospective validation of hypothesis-generating biomarker signals. By integrating recent 2025-2026 clinical developments with mechanistic and engineering advances, including lessons from unsuccessful or discontinued clinical programs, this review provides a balanced perspective on the opportunities and remaining barriers to the clinical translation of CD47-directed therapy in digestive system cancers.
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8. WHAMM deficiency alters splenic B-cell populations, BCR signaling, and actin remodeling.
PMID:日期:2026-08-28Members of the Wiskott-Aldrich syndrome protein (WASP) family orchestrate cytoskeletal reorganization that modulates B-cell receptor (BCR) signaling and B-cell fate decisions. WHAMM, a WASP-family nucleation-promoting factor member that associates with actin, membranes and microtubules, has not been functionally characterized in B cells. To investigate the role of WHAMM in B-cell development and function, we analyzed a conditional mouse model in which Whamm was deleted in the B-cell lineage. WHAMM-deficient mice exhibited altered splenic B-cell composition, characterized by an accumulation of splenic transitional B cells and a reduction of follicular B cells. Meanwhile, WHAMM deficiency altered the spatial organization and kinetics of proximal BCR signaling, and modified the dynamics of BCR-induced actin remodeling. However, WHAMM-deficient B cells showed largely preserved BCR internalization, antigen presentation, PI3K-AKT-mTOR signaling, ROS production, and mitochondrial membrane potential. Together, this work indicates that WHAMM helps shape splenic B-cell populations and regulates proximal BCR signaling and actin dynamics, while several downstream functional responses remain largely preserved in this study.
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9. NETs drive CD4⁺ T cell dysfunction in sepsis via mitochondrial ROS and impaired calcium signalling.
9. NETs通过线粒体ROS和钙信号受损驱动脓毒症中CD4⁺ T细胞功能障碍PMID:日期:2026-08-19Sepsis is a life-threatening condition with high mortality, in which sepsis-induced immunosuppression-characterized by CD4 T cell dysfunction and apoptosis-worsens clinical outcomes. The mechanistic link between neutrophil extracellular traps (NETs) and CD4 T cell fate in sepsis remains poorly elucidated. We integrated plasma analysis from 50 sepsis patients and 31 healthy controls, a murine cecal ligation and puncture (CLP) sepsis model, and in vitro assays with Jurkat cells and primary CD4 T cells. We investigated the effects of NETs on CD4 T cell calcium signaling and mitochondrial function, and verified the therapeutic efficacy of DNase I combined with the mitochondrial-targeted antioxidant mitoTEMPO. Circulating NETs were significantly elevated in sepsis patients, positively correlated with disease severity (SOFA score) and negatively correlated with peripheral CD4 T cell counts. NETs disrupted intracellular calcium homeostasis by inhibiting store-operated calcium entry, suppressing calcineurin activity and NFAT nuclear translocation, thus impairing T cell activation and IL-2 production. Additionally, NETs induced mitochondrial dysfunction via excessive mitochondrial reactive oxygen species (mtROS) production and reduced mitochondrial calcium uptake, leading to loss of mitochondrial membrane potential, structural damage, and subsequent CD4 T cell apoptosis. In CLP mice, monotherapy with either DNase I or mitoTEMPO partially attenuated CD4 T cell injury, while the combination significantly improved 7-day survival compared with monotherapy or vehicle, reduced plasma organ injury markers, and alleviated splenic lymphocyte apoptosis. The NETs-mtROS axis represents an important pathway driving CD4 T cell death in sepsis. Dual targeting of NETs and mitochondrial oxidative stress holds promising therapeutic potential for ameliorating sepsis-induced immunosuppression.
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10. Label-free optical biomarker for prostate cancer diagnosis.
PMID:日期:2026-08-17Reprogramming of cellular metabolism in cancer leads to changes in the activity of metabolic coenzymes NAD(P)H and FAD which can be used as markers of tumorigenesis and metastasis. NAD(P)H and FAD form coupled redox pair and regulator of mitochondrial energy metabolism. Since NAD(P)H and FAD are endogenous and auto fluorescent, the coupled redox pair can hence be exploited as a reporter for metabolic activity in tumor microenvironment. We have developed a 2P-FLIRR assay (2-photon Fluorescence Lifetime based Redox Ratio), a sensitive metabolic optical biomarker for tumor diagnosis in prostate cancer (PCa) patients' tissue sections. We have imaged and used our novel 2P-FLIRR metric which is the ratio of the enzyme-bound fractions of NAD(P)H and FAD to evaluate PCa patients' surgically resected tissue sections. These were PCa adenocarcinomas with different Gleason grades. In comparison with conventional H&E histopathology, our 2P-FLIRR assay showed the potential to distinguish tumor-enriched regions from normal prostate tissue in unstained frozen patient tissue sections. Lower FLIRR values were observed to correspond to tumor versus higher FLIRR values to normal prostate. This pilot feasibility study demonstrates that 2P-FLIRR detects metabolic contrast between prostate cancer and normal prostate tissue in frozen human patient tissue sections. Our study identifies for the first time quantitative 2P-FLIRR as a potential sensitive diagnostic optical biomarker for PCa.