J Transl Med [JOURNAL]
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200 papers
BRD4-mediated histone H4K12 lactylation drives ovarian cancer progression by activating the Ube2v1-DDX3X ubiquitination axis.
Jiang Y, Lyu T, Zhou T … +2 more , Zhu C, Feng W
J Transl Med · 2026 Jun · PMID 42374413 · Full text
BACKGROUND: Aberrant histone lactylation is emerging as a pivotal player in tumorigenesis. However, its role in epithelial ovarian cancer (EOC) has not been fully elucidated to date. METHODS: Histone lactylation levels w...
BACKGROUND: Aberrant histone lactylation is emerging as a pivotal player in tumorigenesis. However, its role in epithelial ovarian cancer (EOC) has not been fully elucidated to date. METHODS: Histone lactylation levels were detected using western blotting and immunohistochemistry in EOC and their prognostic value was evaluated. By integrating CUT&Tag and RNA-seq data, we pinpointed Ubiquitin-conjugating E2 enzyme variant 1(Ube2v1) as the crucial gene regulated by Histone H4K12 lactylation (H4K12la). The role of H4K12la on enhancing Ube2v1 expression was confirmed through RT-PCR, western blotting, ChIP, and dual-luciferase reporter assays. Target proteins interacting with and regulated by Ube2v1 were identified using IP-MS and validated by Co-IP. A histone modification compound library was used to screen potential modulators of H4K12la. MALDI-TOF/TOF MS was used to detect in vitro enzymatic products to investigate the potential lactylation activity of BRD4. RESULTS: H4K12la was significantly elevated in EOC tissues and associated with poor patient survival. We identified Ube2v1 as a key target gene activated by H4K12la. Ube2v1 promoted EOC cell proliferation and inhibited apoptosis by forming a complex with Ubc13 to catalyze the K63-linked ubiquitination and subsequent autophagic degradation of DDX3X. Through a targeted compound screen, we discovered that BET inhibitors, especially inhibitors that target BRD4 via the PROTAC approach, could significantly downregulate the level of H4K12la. Crucially, our findings suggest that BRD4 might play a direct role in modulating H4K12 lactylation. The expression levels of BRD4, H4K12la, and Ube2v1 were positively correlated in clinical EOC samples and ovarian cancer cell lines. CONCLUSION: Our study uncovers a previously unrecognized function of BRD4 in regulating histone lactylation and delineates the oncogenic BRD4/H4K12la/Ube2v1/DDX3X axis in EOC. These findings not only provide a profound mechanistic insight into EOC progression but also firmly establish the therapeutic rationale for targeting BRD4, via PROTAC inhibitors, in the treatment of EOC.
Navigating AI and machine learning in cancer research: an end-to-end translational framework.
Saha S, Ali MS, Tengli AK … +4 more , Prasad SR, Mallikarjunaswamy P, Pillappan R, Javarappa KK
J Transl Med · 2026 Jun · PMID 42365374 · Full text
Cancer is a complex and heterogeneous disease that is characterized by multi-level biological variability. Advances in high-throughput technologies have led to large-scale, high-dimensional data sets in cancer research,...
Cancer is a complex and heterogeneous disease that is characterized by multi-level biological variability. Advances in high-throughput technologies have led to large-scale, high-dimensional data sets in cancer research, creating a pressing need for powerful computational techniques for successful data analysis. Current techniques may be inadequate for this purpose, thus underscoring the potential of artificial intelligence (AI) and machine learning (ML) for successful data analysis. This review provides a comprehensive pipeline for artificial intelligence/machine learning in cancer research, including preclinical research, clinical decision support, and real-world implementation. It emphasizes several important technologies, data integration, and implementation challenges. The review critically examines multi-omics fusion architectures, regularization-based machine learning, batch-effect harmonization, explainable AI, and federated learning, while addressing translational barriers including algorithmic bias, covariate drift, and regulatory asynchrony across Indian, US, and EU frameworks. Anchored by Decision Curve Analysis as a clinical utility benchmark, this narrative framework establishes that meaningful progress in precision oncology, early detection, and patient outcomes demands not only predictive accuracy but also externally validated, population-representative, and governance-compliant AI systems capable of sustained real-world oncology impact.
Removal of aging microenvironment of bone defects can effectively promote bone defect repair.
Huang J, Long H, Malik MA … +2 more , Wu S, Cao X
J Transl Med · 2026 Jun · PMID 42365373 · Full text
BACKGROUND: Bone defects remain a significant challenge in orthopedics, and despite the widespread use of mesenchymal stem cells (MSCs) in regenerative medicine, their therapeutic performance in vivo often falls short of...
BACKGROUND: Bone defects remain a significant challenge in orthopedics, and despite the widespread use of mesenchymal stem cells (MSCs) in regenerative medicine, their therapeutic performance in vivo often falls short of expectations. Emerging evidence suggests that the local microenvironment particularly age-related or injury-induced cellular senescence may compromise MSC function. In this study, we investigated how a senescent vascular niche arising after bone injury influences MSC proliferation, differentiation, and its possible mechanisms involved in regeneration and clearing of the aging microenvironment. METHODS: A femoral trochlear defect was created in 3-month-old SD rats (n = 6/group) to characterize temporal senescence changes using SA-β-Gal staining, p16/CD31 immunofluorescence, and expression of Cdkn1a/Cdkn2a. Primary endothelial cells (ECs) were isolated and senescence-induced with 400 µM H₂O₂ for 45 min. MSCs were co-cultured with senescent ECs (SnECs) in 3D collagen I hydrogels (2 mg/mL, ~ 5 kPa). Quercetin, selected from DrugAge screening (20 µM), was incorporated into a 4 wt% thermosensitive hydrogel (TSH-Q) to enable 7-day sustained release. Bone regeneration was assessed by µCT, histology, and immunofluorescence at 1 and 4 weeks post-injury. RESULTS: Bone defects triggered a biphasic senescence response: early senescence occurred predominantly in peri-defect osteocytes at 1 week, while robust senescence was later observed in neovascular endothelial cells by week 4. SnECs significantly impaired MSC biological functions, reducing migration, chondrogenic differentiation (Safranin O intensity), and mineralization (Alizarin Red) (all p < 0.01). Local delivery of quercetin via TSH-Q cleared approximately 81% of p16⁺ endothelial cells in vivo and enhanced bone repair, increasing BV/TV compared with unloaded TSH (p < 0.001). In the early stage of bone defects, aging cells mainly represent bone cells in the tissues surrounding the bone defect. At later staged, with no changes in the microenvironment, the aging of vascular endothelial cells in the new tissues and blood vessels was most significant. We successfully induced endothelial cell senescence and further explored the functional impact of SnECs on MSCs and found that aging ECs led to a decline in MSCs effects in aging, including reduced proliferation, chondrogenic differentiation, osteogenic differentiation, tissue repair, and mineralization. The therapeutic effects of MSCs and the repair of bone defects were effectively promoted by constructing a quercetin thermosensitive hydrogel sustained-release system to improve the aging microenvironment of bone defects. CONCLUSIONS: Bone injury generates a senescent vascular niche that markedly disrupts MSC-mediated regeneration. Targeted rejuvenation of this niche using sustained-release quercetin effectively restores MSC function and significantly accelerates bone reconstruction. These findings highlight the aging microenvironment as a key therapeutic target for improving MSC-based treatments for bone defects.
Chlorogenic acid attenuates skin senescence and UVR-induced photoaging via the modulation of mitochondrial function.
Li R, Hu C, Zhou P … +8 more , Si G, Cui J, He Y, Han Y, Zhang J, Li W, Wang L, Jiang J
J Transl Med · 2026 Jun · PMID 42365366 · Full text
BACKGROUND: Mitochondrial function plays a critical role in skin aging. Chlorogenic acid (CGA), a botanical compound, has demonstrated regulatory effects on mitochondrial function and senescence inhibition. However, whet...
BACKGROUND: Mitochondrial function plays a critical role in skin aging. Chlorogenic acid (CGA), a botanical compound, has demonstrated regulatory effects on mitochondrial function and senescence inhibition. However, whether the anti-aging effects of CGA are attributable to its regulation of mitochondrial function remains unclear. There is a need to investigate the anti-aging effect and mechanism of CGA by modulating mitochondrial function, particularly its mode of action on mitochondrial function. METHODS: Normal human dermal fibroblasts and human epidermal keratinocytes were used to detect the regulation of collagen I production, mitochondrial functions, and anti-aging properties of CGA and confirmed by mitochondrial transplantation. The photo-aging mouse model was established by ultraviolet (UV) radiation, followed by the treatment of CGA-gel (1 mmol/kg/d) for 14 days. The skin tissues were collected and tested. RESULTS: CGA promotes collagen I (Col1) production by activating the TGF-β/Smad signaling pathway, while concurrently inhibiting cellular senescence. CGA administration significantly reduced the expression of p21, senescence-associated secretory phenotype (SASP) production, and SA-β-Gal activity in skin cells. Additionally, CGA treatment notably enhanced mitochondrial function, improving disrupted mitochondrial cristae in senescent cells and boosting the oxidative phosphorylation (OXPHOS) process. ATP levels increased by approximately 40-80% following CGA treatment. Mitochondrial transplantation further confirmed CGA's anti-aging effects are linked to mitochondrial function. CGA significantly mitigated UV-induced reduction in Col1, suppressed p21 expression and SASP production, and improved mitochondrial morphology and structure in vivo. CONCLUSION: CGA promotes Col1 production and attenuates skin cellular senescence, with these effects being directly associated with mitochondrial regulation. Thus, CGA holds promise as a potent agent for preventing cellular senescence.
Translational human gut microbiome research: What are the missing pieces of the puzzle?
Fassarella M, Smidt H
J Transl Med · 2026 Jun · PMID 42365269 · Full text
BACKGROUND: Human gut microbiome research has expanded remarkably over the past two decades, revealing the fundamental role of gut microbes in human health and disease. Despite these advances, translation into evidence-b...
BACKGROUND: Human gut microbiome research has expanded remarkably over the past two decades, revealing the fundamental role of gut microbes in human health and disease. Despite these advances, translation into evidence-based clinical practice and public health implementation remains exceptionally limited. This integrative translational perspective review evaluates human gut microbiome research across four critical aspects: translational successes, barriers to effective translation, applicability of frameworks from other medical disciplines, and strategies to enhance translational progress. MAIN TEXT: Human gut microbiome research was evaluated through the lens of translational medical research principles, as summarised below. (1) Translational successes in human gut microbiome research are explored by analysing the developmental pathways of major microbiome-based or microbiome-targeted approaches, including faecal microbiota transplantation, probiotics, postbiotics, prebiotics, and dietary interventions, despite overall limited clinical and public health translation. (2) Established translational medical research frameworks served as a foundation to identify missing elements in current human gut microbiome research, including progression through T0-T4 phases, bidirectional knowledge flow, prioritization of unmet patient and societal health needs, patient-centric approaches, stakeholder engagement, and interdisciplinary collaboration. Integration of these principles is discussed in light of the specific characteristics, challenges, and limitations of human gut microbiome research. (3) Translational barriers in human gut microbiome research were analysed beyond limited integration of translational medical principles. These arise from the inherent complexity and high-dimensional nature of the gut microbiome, temporal and inter-individual variability, confounding factors, inconsistent methodological standardization and validation, and fragmentation across research efforts. Collectively, these barriers hinder causal inference, resulting in a low-quality evidence base and limiting effective translation. (4) A framework to advance translational human gut microbiome research is proposed based on the previous findings, including strategic priorities such as education and training in translational research principles for gut microbiome researchers. CONCLUSIONS: Human gut microbiome research remains largely confined to early translational phases, with progression toward effective translation limited by intrinsic and methodological barriers that hinder causal inference and high-level evidence generation. Integration of core translational medical research principles offers a pathway to bridge these gaps, with education and training of gut microbiome researchers emerging as a key priority for advancing translational progress.
Histone lactylation boosted SET8 potentiates carcinogenesis and angiogenesis of pancreatic ductal adenocarcinoma by cooperating with MTA1/NuRD complex.
Liu X, Tuergong A, Wang M … +5 more , Shi W, Tian X, Ting X, Cui L, Si W
J Transl Med · 2026 Jun · PMID 42363279 · Full text
BACKGROUND: The pathophysiological role of lysine methyltransferase SET domain-containing protein 8 (SET8) in pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. Emerging evidence suggests that histone lac...
BACKGROUND: The pathophysiological role of lysine methyltransferase SET domain-containing protein 8 (SET8) in pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. Emerging evidence suggests that histone lactylation, a novel post-translational modification, may influence tumor progression. However, the interplay between SET8 and lactate metabolism in PDAC pathogenesis has not been elucidated. METHODS: Immunohistochemical staining and bioinformatics analysis of clinical databases were performed to evaluate SET8 expression and its prognostic relevance in PDAC. Affinity purification coupled with mass spectrometry (MS), co-immunoprecipitation (Co-IP), and glutathione S-transferase (GST) pull-down assays were conducted to identify interactions between SET8 and the MTA1/NuRD complex. Functional roles of the SET8/MTA1/NuRD complex were assessed using chromatin immunoprecipitation (ChIP)-seq, RT-qPCR, western blot, wound healing, transwell invasion, endothelial tube formation, in vivo Chicken Yolk Sac Membrane (YSM) assays, and Masson staining. RESULTS: SET8 expression was significantly upregulated in PDAC and correlated with poor prognosis. SET8 physically interacted with the MTA1/NuRD complex via direct binding to MTA1, as confirmed by Co-IP and GST pull-down assays. The SET8/MTA1/NuRD complex repressed tumor suppressor genes, including SOCS2, through chromatin remodeling. Depletion of SET8 or MTA1 reduced tumorigenesis, angiogenesis, and metastasis. Overexpression of SET8 promoted oncogenic phenotypes in an MTA1-dependent manner. Mechanistically, lactate dehydrogenase A (LDHA)-mediated histone lactylation drove SET8 expression, linking metabolic reprogramming to epigenetic dysregulation. CONCLUSIONS: This study identifies SET8 as a proto-oncogene in PDAC, whose expression is regulated by histone lactylation. The SET8/MTA1/NuRD complex facilitates tumor progression by epigenetically silencing SOCS2, highlighting a crosstalk between histone methylation and deacetylation. Targeting the lactylation-SET8/MTA1/NuRD axis may offer a novel therapeutic strategy for PDAC, particularly by restoring SOCS2-mediated tumor suppression. These findings deepen our understanding of metabolic-epigenetic interplay in cancer and provide actionable insights for clinical intervention.
A multidisciplinary critical appraisal and future research agenda for neuromodulation in spinal pain: beyond acute analgesia and correlative mechanisms.
Huang D, Lin M, Dong J
J Transl Med · 2026 Jun · PMID 42363268 · Full text
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Optimizing the mucosal frontier: longevity and epithelial barriers in prime-boost mRNA vaccine strategies.
Tang X, Jiang F, Ni S
J Transl Med · 2026 Jun · PMID 42363256 · Full text
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Beyond resistance: optimizing CAR-T sequencing following bispecific antibody failure in DLBCL.
Zhang W, Fang Y, Gao S … +1 more , Yao Y
J Transl Med · 2026 Jun · PMID 42363202 · Full text
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DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.
Wang H, Wu Z, Yang R … +10 more , Xu S, Yao S, Wu Z, Xiao L, Que Y, He P, Ma Q, Xu T, Wei W, Hu Y
J Transl Med · 2026 Jun · PMID 42363192 · Full text
BACKGROUND: Histone lactylation, a novel posttranslational modification driven by glycolytic lactate, has emerged as a key regulator of tumorigenesis. However, its role in osteosarcoma (OS) progression and the underlying...
BACKGROUND: Histone lactylation, a novel posttranslational modification driven by glycolytic lactate, has emerged as a key regulator of tumorigenesis. However, its role in osteosarcoma (OS) progression and the underlying metabolic‒epigenetic crosstalk remain poorly understood. METHODS: Using immunohistochemistry, molecular biology, and functional assays in vitro and in vivo, we investigated lactylation levels, DHX9 regulation, Lactylation and glycolytic activity in osteosarcoma models. Techniques included CUT&Tag, LC-MS/MS, site-directed mutagenesis, and xenograft studies. RESULTS: Here, we show global lactylation levels were significantly elevated in OS tissues compared with paracancerous controls. Glycolysis inhibition suppressed H3K9la and impeded OS malignancy. CUT&Tag identified H3K9la enrichment at the DHX9 promoter. DHX9 knockdown inhibited proliferation, migration, and invasion (in vitro) and tumor growth (in vivo), whereas DHX9 overexpression had the opposite effects. LC‒MS/MS revealed K1024 as a functional lactylation site on DHX9-K1024R mutation (lactylation-deficient) disrupted a feedforward loop: (1) reduced PKM2/LDHA expression → impaired glycolysis → decreased H3K9la; and (2) suppressed malignant phenotypes. Conversely, DHX9-K1024T (lactylation mimetic) partially rescued glycolytic enzyme expression and H3K9la levels. CONCLUSION: We elucidated a self-amplifying H3K9la-DHX9-K1024la-glycolysis circuit that drives OS progression. DHX9 lactylation at K1024 serves as a critical metabolic‒epigenetic interface, suggesting that K1024 lactylation may represent a potential therapeutic target, warranting further investigation.
Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.
Wang R, Yan F, Duan F … +7 more , Xia W, Wang W, Wang Z, Sun F, Yu C, Zhang H, Yang L
J Transl Med · 2026 Jun · PMID 42363186 · Full text
BACKGROUND: Ubiquitin-Specific Protease 14 (USP14) is a proteasome-associated deubiquitinase historically viewed as a pro-tumorigenic driver of the ubiquitin-proteasome system (UPS) by stabilizing oncoproteins. Recent ev...
BACKGROUND: Ubiquitin-Specific Protease 14 (USP14) is a proteasome-associated deubiquitinase historically viewed as a pro-tumorigenic driver of the ubiquitin-proteasome system (UPS) by stabilizing oncoproteins. Recent evidence expands this view, positioning USP14 as a central regulator that integrates tumor cell-intrinsic malignancy, tumor microenvironment (TME) remodeling, and resistance to multiple therapies. Importantly, USP14 exerts functions beyond canonical deubiquitination, including non-catalytic and scaffolding activities, and is subject to complex allosteric regulation. MAIN BODY: This review synthesizes emerging regulatory crosstalks that broaden the functional landscape of USP14 in cancer. We first outline the dynamic allosteric regulatory network of USP14 and its activation modes, emphasizing post-translational modifications (PTMs)-notably phosphorylation and lactylation-that modulate USP14 activity and connectivity beyond traditional links to cell cycle control and metabolism. We then consolidate the signaling frameworks through which USP14 contributes to resistance across therapeutic modalities, including targeted therapies, chemotherapy, radiotherapy, and immunotherapy, highlighting both shared and treatment-specific mechanisms. In parallel, we discuss context-dependent tumor-suppressive roles of USP14 and detail its non-catalytic scaffolding functions that reshape signaling outputs independent of enzymatic activity. Collectively, these classical and non-classical mechanisms depict USP14 as a systems-level coordinator of oncogenic signaling, adaptive stress responses, and microenvironmental interactions. CONCLUSIONS: By integrating catalytic and non-catalytic functions with PTM-driven allosteric regulation, we propose a unified regulatory model in which USP14 operates as a master node connecting malignancy, TME dynamics, and therapeutic resistance. This framework provides strategic guidance for developing next-generation allosteric inhibitors and combination strategies aimed at overcoming clinical drug resistance and exploiting context-specific vulnerabilities in USP14-regulated networks.
Claudin18.2 and the PD-1/PD-L1 axis in gastric cancer: mechanistic insights and implications for combination immunotherapy.
Lu Y, Ma J, Wang Y … +6 more , Li Y, Gu C, Fei J, Yang J, Li J, Dai P
J Transl Med · 2026 Jun · PMID 42363179 · Full text
INTRODUCTION: Claudin18.2 is a highly specific therapeutic target selectively expressed in gastric cancer cells. Emerging evidence suggests that Claudin18.2 positivity may be associated with an immunosuppressive tumor mi...
INTRODUCTION: Claudin18.2 is a highly specific therapeutic target selectively expressed in gastric cancer cells. Emerging evidence suggests that Claudin18.2 positivity may be associated with an immunosuppressive tumor microenvironment and suboptimal responses to PD-1/PD-L1 blockade. However, the underlying mechanisms and therapeutic implications remain incompletely understood. METHODS: This article is a narrative review with a structured search. Relevant studies published up to 30 September 2025 were identified through searches of PubMed, Embase, Web of Science, Cochrane Library, and Scopus. Predefined inclusion and exclusion criteria were applied to select studies that addressed the relationship among Claudin18.2 expression, tumor immune microenvironment characteristics, immune checkpoint regulation, and immunotherapy outcomes in gastric cancer. RESULTS: Claudin18.2-positive gastric cancer presents a distinct immunosuppressive microenvironment, characterized by reduced NK cell infiltration, altered macrophage and neutrophil composition, dysregulated cytokine signaling, and increased infiltration of CD8 + and CD4 + T cells with evidence of functional impairment or exhaustion within the tumor core. Mechanistically, Claudin18.2 modulates immune checkpoint pathways by upregulating PD-1 through the PKC/ERK-MAPK pathway. Claudin18.2-targeted therapy may also indirectly regulate PD-L1 expression through immune activation and the JAK/STAT signaling pathway. Importantly, immune activation induced by Claudin18.2-targeted antibodies, CAR-T cells, bispecific antibodies, and ADCs (Antibody-Drug Conjugates) may partially reverse immune suppression and enhance sensitivity to PD-1/PD-L1 inhibition, although direct evidence remains limited. CONCLUSION: This review suggests that Claudin18.2 may serve as a key regulator of immune dysfunction rather than immune exclusion in gastric cancer, providing a potential biological rationale for combinatorial strategies integrating Claudin18.2-targeted therapies with immune checkpoint inhibition. Given the heterogeneity of available studies and the indirect nature of some evidence, these insights should be interpreted as exploratory; they may nonetheless help guide patient stratification and inform the rational design of future combination immunotherapy trials in Claudin18.2-positive gastric cancer.
Disrupting the epithelial-effector axis in type 2 inflammation: the strategic superiority of dual TSLP/IL-13 blockade in achieving immunological reset.
Han Y, Guo B, Fang Y … +1 more , Yao Y
J Transl Med · 2026 Jun · PMID 42363175 · Full text
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Overcoming Paradigm Inertia: Publishing Incentives and Peer Review Bias as the True Rate-Limiting Steps in Reducing Animal Research.
Du Y, Fang Y, Ni S
J Transl Med · 2026 Jun · PMID 42363167 · Full text
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Q-Bone system: an intelligent quantitative system for alveolar bone loss to assist the diagnosis of periodontitis - model development and validation.
Li W, Liu J, Ji GP … +3 more , Yao Z, Fan DP, Lin J
J Transl Med · 2026 Jun · PMID 42351208 · Full text
OBJECTIVES: To develop and validate the Q-Bone system, an intelligent quantitative system for anatomically driven assessment of alveolar bone loss and assistance in the diagnosis of periodontitis across multiple clinical...
OBJECTIVES: To develop and validate the Q-Bone system, an intelligent quantitative system for anatomically driven assessment of alveolar bone loss and assistance in the diagnosis of periodontitis across multiple clinical centers and imaging devices. METHODS: This study included 1,273 periodontitis cases from four clinical centers using diverse imaging devices. A multitask deep learning model, Deep Gradient Network (DGNet), was employed for tooth segmentation and anatomical keypoint localization, and was integrated with an anatomically driven, curvature-based quantification algorithm for alveolar bone resorption ratio (ABRR) measurement. Performance was evaluated using internal and multicenter external datasets, including patient-level agreement analysis for Stage, Grade, and Extent. RESULTS: The Q-Bone system demonstrated strong performance: tooth segmentation achieved an S-measure of 0.929, and keypoint localization reached a PRCK@0.5 of 0.994 in internal validation. Tooth-level ABRR showed high agreement with specialist measurements, with an ICC of 0.973 and minimal bias (- 0.238%). In the multicenter clinical validation cohort (n = 174), agreement between Q-Bone and the specialist reference standard was high at the patient level, with Cohen's κ values of 0.9351 for Stage, 0.9367 for Grade, and 0.9770 for Extent. For the ordinal outcomes of Stage and Grade, linear weighted κ values were 0.9508 and 0.9515, respectively. CONCLUSIONS: The Q-Bone system enables automated tooth segmentation, anatomical keypoint localization, tooth-level quantification of alveolar bone loss, and patient-level assessment across Stage, Grade, and Extent. It showed high agreement with specialist reference standards across multicenter and cross-device settings, supporting its applicability as a standardized imaging-based assistance tool for periodontal evaluation.
Dynamic gut microbiota shift in chronic liver disease progression: machine learning models and the E/Er ratio as a predictive biomarker.
Mengting D, Zhaoyang J, Jingjing D … +7 more , Jianbo W, Tongtong Y, Linling Z, Jiaying Q, Jialu L, Ping C, Mingzhi X
J Transl Med · 2026 Jun · PMID 42351186 · Full text
BACKGROUND: Chronic liver disease (CLD) and its progression to compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF) represent a global health crisis with high mortality. The...
BACKGROUND: Chronic liver disease (CLD) and its progression to compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF) represent a global health crisis with high mortality. The "gut-liver axis" plays a pivotal role in this progression, yet a systematic characterization of the dynamic microbial evolution across the entire disease spectrum remains elusive. We aimed to systematically characterize the gut microbiota's dynamic evolution across the spectrum of chronic liver disease and to develop machine-learning models for predicting its critical transitions. METHODS: In this retrospective cohort study, 947 patients with liver disease (CLD, n = 464; CC, n = 159; DC, n = 260; ACLF, n = 64) were enrolled. The relative abundances of 10 dominant gut microbiota-including Enterococcus, Lactobacillus, Clostridium leptum, Clostridium butyricum, Eubacterium rectale, Faecalibacterium prausnitzii, Bacteroides, Enterobacterium, Bifidobacterium, and Atopobium cluster-were quantified via qPCR. Random Forest (RF) models were constructed to predict transitions between disease stages. The discriminatory efficacy of the Enterococcus/Eubacterium rectale Ratio (E/Er Ratio) was further evaluated using Receiver Operating Characteristic (ROC) analysis. RESULTS: Four distinct dynamic evolutionary patterns were identified. The pro-inflammatory/anti-inflammatory ratio increased 5.4-fold from CLD to ACLF. Random Forest models accurately predicted all disease transitions. The model for the DC-to-ACLF transition performed best (Area Under the Curve, AUC = 0.961), with clinical parameters (PT, TBil) being the strongest predictors. While the addition of microbial features yielded a modest incremental gain in AUC for the late-stage transition, indices such as the Specific-Butyrate-to-Total ratio were identified as key features, providing critical biological insights into the systemic failure of the gut-liver axis. The E/Er Ratio further served as a robust, non-invasive marker for identifying critical disease turning points. CONCLUSION: Liver disease progression is characterized by a systematic shift in the gut microbiota from an anti-inflammatory, butyrate-rich state to a pro-inflammatory, pathogen-dominant environment. The integrated RF models and the E/Er Ratio provide a powerful, non-invasive framework for the early prediction and risk stratification of chronic liver disease progression, offering potential targets for gut-centered therapeutic interventions.
Magnesium and gender in long COVID.
Chambers PW
J Transl Med · 2026 Jun · PMID 42351174 · Full text
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The integrated clinico-scientific system for gastrointestinal diseases combining Chinese and Western medicine.
Liang Z, Zha H, Wang F … +2 more , Lin W, Zhang W
J Transl Med · 2026 Jun · PMID 42351173 · Full text
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Role of viral and host factors in determining the outcome of HBV-associated acute liver failure.
Farci P, Battista D, Engle RE … +10 more , Chu E, Chen Z, Jeffrey B, Rule J, Nguyen H, Raini S, Takeda S, Follman D, Alter HJ, Lee WM
J Transl Med · 2026 Jun · PMID 42351169 · Full text
BACKGROUND: Acute hepatitis B virus (HBV) infection encompasses a broad clinical spectrum, from self-limited hepatitis to acute liver injury (ALI), acute liver failure (ALF), subacute liver failure, and ALF on chronic HB...
BACKGROUND: Acute hepatitis B virus (HBV) infection encompasses a broad clinical spectrum, from self-limited hepatitis to acute liver injury (ALI), acute liver failure (ALF), subacute liver failure, and ALF on chronic HBV reactivation. This study investigates how host and viral factors interact to shape the clinical spectrum of HBV-associated ALF. METHODS: We analyzed 231 serial serum samples from 49 well-characterized patients including 36 with HBV-associated ALF and 13 with acute hepatitis B. Among ALF patients, 7 had ALI, 7 acute and 11 subacute liver failure, and 11 ALF on chronic HBV. Viral factors, including HBV replication, genotype, sequence diversity and viral evolution by next-generation sequencing (NGS) were assessed alongside host immune responses and cytokine profiles by proteomics. RESULTS: Demographics were similar across groups. Mortality was highest in subacute liver failure and ALF on chronic HBV (82%) and intermediate in acute liver failure (43%). The three forms of ALF differed by clinical, virologic, and immunologic features. Acute liver failure was characterized by markedly elevated alanine aminotransferase and high IgM anti-HBc titers, whereas ALF on CHB showed higher serum HBV DNA, HBV RNA and HBcrAg levels. HBV genotype A predominated (63%), followed by D (15%), C (9%), and others (2-6%). NGS of the basal core promoter and precore/core regions revealed highly homogeneous viral populations in acute and subacute liver failure throughout follow-up, while ALF on CHB showed marked viral heterogeneity. Genetic diversity was genotype-dependent, unrelated to disease severity, and significantly lower in genotype A than D. Acute liver failure was associated with broad type 1 cytokine response (i.e. IP-10, MIP-1α, MIP-1β, TNF-α, and IFN-γ), restricted type 2 cytokine response (i.e. IL-4 and sCD137), along with proinflammatory (i.e. MCP-1, Il-6, and IL-8) and homeostatic (i.e. IL-7) cytokines, whereas subacute liver failure and ALF on chronic HBV exhibited low and restricted, but distinct cytokine profiles. Elevated GM-CSF and PDGF-BB at admission predicted transplant-free survival. CONCLUSIONS: Distinct clinical, serologic, virologic, and cytokine profiles correlate with disease severity, highlighting differing pathogenic mechanisms across HBV-associated ALF forms. Early biomarkers, including GM-CSF and PDGF-BB, may help predict recovery and guide individualized management to improve survival.
Integrative transcriptomic analysis identifies meningeal-hippocampal immune communication in Alzheimer's disease.
Yan C, Chen Z, Yan Y … +4 more , Wang M, Chen W, Zhou F, Liu Q
J Transl Med · 2026 Jun · PMID 42351167 · Full text
BACKGROUND: Alzheimer's disease (AD) exhibits spatial heterogeneity, yet the mechanisms by which immune-active meninges communicate with vulnerable brain regions during disease progression remain unclear. This study aime...
BACKGROUND: Alzheimer's disease (AD) exhibits spatial heterogeneity, yet the mechanisms by which immune-active meninges communicate with vulnerable brain regions during disease progression remain unclear. This study aimed to investigate meninges-hippocampus crosstalk and map the communication patterns during AD pathology development. METHODS: We employed 5xFAD transgenic and PS19 tau-pathology mouse models and integrated bulk RNA sequencing, proteomics, and spatial transcriptomics across time-course analyses to distinguish AD pathology from normal aging processes. Transcription factor activity inference was coupled with ligand-receptor dynamics analysis to examine regulatory modules in homeostatic and disease-associated microglia. RESULTS: We identified structure-specific disease genes, including a robust 19-gene hippocampal signature that was reproducible across an independent 5xFAD dataset and PS19 tau-pathology dataset. Spatial analysis defined a disease progression axis that transferred to the independent spatial dataset, where meningeal spots were enriched in advanced disease progression layers and disease modules showed consistent gradients. Ligand-receptor and microglial-state LRaxis analyses further supported candidate communication axes associated with pathology gradients and state-specific regulatory modules in both homeostatic and disease-associated microglia. CONCLUSIONS: Our spatial framework supports the meninges as a candidate modulatory interface associated with hippocampal pathology in AD mouse models. These mouse-derived, computationally inferred ligand-receptor and regulatory modules should be considered hypothesis-generating candidates that require validation in human AD tissues and functional perturbation studies before translational relevance can be inferred.
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