tbuckley/cabot-search huggingface dataset:
Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application
Authors: Jiayi Jin, Lijun Yue, Maoru Du, Feng Geng, Xue Gao, Yuming Zhou, Qianqian Lu, Xiaohong Pan
Journal: MedComm (2025)

ABSTRACT Molecular hydrogen (H 2 ), recognized as the smallest gas molecule, is capable of permeating cellular membranes and diffusing throughout the body. Due to its high bioavailability, H 2 is considered a therapeutic gas for the treatment of various diseases. The therapeutic efficacy of hydrogen is contingent upon factors such as the administration method, duration of contact with diseased tissue, and concentration at targeted sites. H 2 can be administered exogenously and is also produced endogenously within the intestinal tract. A comprehensive understanding of its delivery mechanisms and modes of action is crucial for advancing hydrogen medicine. This review highlights H₂’s mechanisms of action, summarizes its administration methods, and explores advancements in treating intestinal diseases (e.g., inflammatory bowel disease, intestinal ischemia–reperfusion, colorectal cancer). Additionally, its applications in managing other diseases are discussed. Finally, the challenges associated with its clinical application and potential solutions are explored. We propose that current delivery challenges faced by H 2 can be effectively addressed through the use of nanoplatforms; furthermore, interactions between hydrogen and gut microbiota may provide insights into its mechanisms for treating intestinal diseases. Future research should explore the synergistic effects of H 2 in conjunction with conventional therapies and develop personalized treatment plans to achieve precision medicine.
Comment on “A Proposal for a New Pathogenesis-guided Classification for Inherited Epidermal Differentiation Disorders”
Authors: Mark Eisner, Thomas Sharkey, John Common, Neil Rajan
Journal: British Journal of Dermatology (2025)

A response to a gene based nomenclature for the epidermal differentiation disorders. This letter outlines potential pitfalls around inequity but also opportunities this approach may offer.
Characterisation of the clinical and photobiological features of solar urticaria: a United Kingdom multicentre cross-sectional study
Authors: Navandeep K Thumber, Hana Elsbahi, Conn McGrath, Evangelos A A Christou, Susan Walker, Harsha Naik, Keyna Bintcliffe, Sally H Ibbotson, Sophie Weatherhead, Adam Fityan, Victoria Goulden, Lesley E Rhodes, Kirsty J Rutter, Annette Wagner, Clive Grattan, Hiva Fassihi, John Ferguson, Robert Sarkany, Christos Tziotzios, Michael Simpson, John McGrath, Sheila M McSweeney
Journal: British Journal of Dermatology (2025)

Solar urticaria (SU) is a rare photodermatosis characterised by abnormal immune responses to specific wavelengths of solar radiation with release of histamine and other mediators from cutaneous mast cells. Clinically, it manifests within minutes of sun exposure, causing erythemal flares and wheals that persist for up to 24 hours, as well as occasional angioedema. To date, few studies have characterised the SU phenotype in large disease cohorts. As part of a wider genetic investigation of SU, this descriptive cross-sectional study was undertaken to characterise the clinical and photobiological features of SU patients in the UK.
Deep immunophenotyping and clustering identifies biomarkers predictive of lymphoma in primary Sjögren disease
Authors: Cindy Marques, Paul Régnier, Anna Maciejewski‐Duval, Clara Richard de Vesvrotte, Thomas Vazquez, Camille Montardi, Bénédicte Manoury, Karim Dorgham, Cloé Comarmond, Arsène Mekinian, Michelle Rosenzwajg, Alexandre Le Joncour, Matheus Vieira, Georgina Maalouf, Gaëlle Leroux, Fanny Domont, Anne‐Claire Desbois, Adrien Mirouse, David Klatzmann, JE Gottenberg, Patrice Cacoub, David Saadoun
Journal: Arthritis & Rheumatology (2025)

Objective Patients with primary Sjögren Disease (pSD) are prone to develop non‐Hodgkin's lymphoma (NHL‐pSD) but relevant biomarkers are lacking. We aimed to determine new biomarkers predictive of NHL in patients with pSD. Methods 206 pSD patients fulfilling ACR/EULAR 2016 criteria were included and divided into three groups: pSD, lymphoproliferative pSD (Arl‐pSD), and NHL‐pSD. Deep flow cytometry immunophenotyping of B and T cell compartments as well as serum IFNα quantification were coupled to clinical, biological and histopathological data analysis. Results We identified CD11c + FcRL5 + tissue‐like memory B cells and IFNγ + TNFα + conventional T cells as significantly associated with NHL in pSD. These clusters showed progressive enrichment in Arl‐pSD and NHL‐pSD as compared to pSD. The combination of these two populations abundances discriminates NHL‐pSD patients with a sensitivity of 78.9% and a specificity of 76.8%, thus overcoming alone the performance of the sum of conventional clinical and biological markers such as cryoglobulinemia vasculitis, parotid enlargement, adapted clinESSDAI, RF antibodies, low C4 and elevated serum IFNα (68.4% and 78.0% respectively). CD11c + FcRL5 + tissue‐like memory B cells were associated with occurrence of mucosa‐associated lymphoid tissue marginal‐zone lymphoma (MALT NHL), while IFNγ + TNFα + conventional T cells were more indicative of non‐MALT B‐cell NHLs. Conclusion We unveil novel biomarkers of NHL in pSD based on an integrative analysis coupling deep immunophenotyping and clinical, biological and histopathological data. Furthermore, these markers allow distinguishing B‐cell NHL subtypes in pSD.
Corrigendum to “Association of metabolic signatures of air pollution with MASLD: Observational and Mendelian randomization study” [J Hepatol (2025) 10.1016/j.jhep.2024.09.033]
Authors: Shanshan Ran, Jingyi Zhang, Fei Tian, Zhengmin Min Qian, Shengtao Wei, Yuhua Wang, Ge Chen, Junguo Zhang, Lauren D Arnold, Stephen Edward McMillin, Hualiang Lin
Journal: Journal of Hepatology (2025)
3‐year Results of Tapering TNFi to Withdrawal Compared to Stable TNFi Among Patients with Rheumatoid Arthritis in Sustained Remission: A Multicenter Randomized Trial
Authors: Kaja E. Kjørholt, Nina Paulshus Sundlisæter, Anna‐Birgitte Aga, Joseph Sexton, Inge C. Olsen, Åse S. Lexberg, Tor M. Madland, Hallvard Fremstad, Christian A. Høili, Gunnstein Bakland, Cristina Spada, Hilde Haukeland, Inger M. Hansen, Ellen Moholt, Karen Holten, Till Uhlig, Tore K. Kvien, Daniel H. Solomon, Désirée van der Heijde, Espen A. Haavardsholm, Siri Lillegraven
Journal: Arthritis & Rheumatology (2025)

Objectives Tapering of tumor necrosis factor inhibitor (TNFi) treatment in rheumatoid arthritis (RA) remission is debated. We assessed the effect of tapering TNFi to withdrawal versus continued stable TNFi on flare‐free survival and joint damage progression over three years. Methods ARCTIC REWIND was a multicenter, open‐label, non‐inferiority trial including patients with RA in remission for ≥12 months on stable TNFi therapy. Patients were randomized 1:1 to taper TNFi to withdrawal or continue stable treatment. The primary endpoints of the current study were flare‐free survival and radiographic progression over three years. Flare‐free survival was analyzed by Kaplan‐Meier methods, flare rates by Cox regression, and radiographic progression by logistic mixed effects models. Results Of 99 randomized patients, 92 received the allocated therapy, 80 completed 3‐year follow‐up. Mean baseline DAS based on 44 joint count was 0.8, csDMARD co‐medication was used by 90%. After 3 years, 25% (95%CI: 13‐38%) remained flare‐free in the tapering TNFi group compared to 85% (70‐93%) in the stable group, corresponding hazard ratio for flare 9.4 (3.9‐22.8), p&lt;0 . 0001. In the tapering group 6/41 (15%) experienced radiographic progression, compared with 3/38 (8%) in the stable group, risk difference 6.7% (‐7.1%‐20.5%, p=0.3). Adverse events occurred in 81% of the patients in the tapering group, and 89% of the patients in the stable group. Conclusion In contrast to those receiving stable TNFi treatment, a minority of RA patients in remission tapering TNFi to withdrawal remained flare‐free over three years. There was no statistically significant difference in radiographic progression between the groups.
Pangenome analysis reveals structural variation associated with seed size and weight traits in peanut
Authors: Kunkun Zhao, Hongzhang Xue, Guowei Li, Annapurna Chitikineni, Yi Fan, Zenghui Cao, Xiaorui Dong, Huimin Lu, Kai Zhao, Lin Zhang, Ding Qiu, Rui Ren, Fangping Gong, Zhongfeng Li, Xingli Ma, Shubo Wan, Rajeev K Varshney, Chaochun Wei, Dongmei Yin
Journal: Nature Genetics (2025)
Intravascular vs. surface cooling in out-of-hospital cardiac arrest patients receiving hypothermia after hospital arrival: a post hoc analysis of the TTM2 trial
Authors: Akil Awad, Martin Jonsson, Johan Holgersson, Janus Christian Jakobsen, Jacob Hollenberg, Matthew Thomas, Pedro D Wendel Garcia, Mattias Ringh, Anders M Grejs, Thomas R Keeble, Jan Bělohlávek, Alain Cariou, Filippo Annoni, Gisela Lilja, Fabio Silvio Taccone, Christian Rylander, Niklas Nielsen, Josef Dankiewicz, Per Nordberg
Journal: Intensive Care Medicine (2025)
Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation: Erratum
Authors: Yun-Xin Lu, Qi-Nian Wu, Dong-Liang Chen, Le-Zong Chen, Zi-Xian Wang, Chao Ren, Hai-Yu Mo, Ya Chen, Hui Sheng, Ying-Nan Wang, Yun Wang, Jia-Huan Lu, De-Shen Wang, Zhao-Lei Zeng, Feng Wang, Feng-Hua Wang, Yu-Hong Li, Huai-Qiang Ju, Rui-Hua Xu
Journal: Theranostics (2025)

[This corrects the article DOI: 10.7150/thno.21745.].
Pilot first-in-human CCR2 PET/CT to detect abdominal aortic aneurysm wall instability
Authors: Santiago Elizondo-Benedetto, Deborah Sultan, Ryan Wahidi, Mahdjoub Hamdi, Mohamed S Zaghloul, Shahab Hafezi, Batool Arif, Laura K McDonald, Kitty Harrison, Dakkota Thies, Gyu Seong Heo, Hannah Luehmann, Lisa Detering, J Westley Ohman, Zachary J Wanken, Luis A Sanchez, Joseph E Ippolito, Jie Zheng, Robert J Gropler, Richard Laforest, Yongjian Liu, Mohamed A Zayed
Journal: Theranostics (2025)

Objective: In a pilot first-in-human study, we aimed to evaluate the feasibility of Positron Emission Tomography/Computed Tomography (PET/CT) imaging of C-C chemokine receptor type 2 (CCR2) to aid in the diagnosis of abdominal aortic aneurysm (AAA) instability. Rationale: Risk stratification of AAAs is an unmet clinical need. Patients often remain asymptomatic until they acutely rupture. Current imaging techniques focus on AAA diameter and growth rate, neglecting key cellular and molecular processes. Methods: A pilot, prospective, single-center, case-control study evaluated patients with and without AAAs. The study subjects received intravenous administration of a CCR2-specific radiotracer, followed by PET/CT assessment. Surgical AAA specimens were collected to evaluate CCR2 content and extracellular matrix integrity. PET/CT signals were evaluated in the AAA wall in the para-renal, mid-infrarenal, and aneurysm sac, and analyzed relative to patient demographics, AAA anatomical segmentation, and wall rupture potential index (RPI). Results: The AAA group was elderly (70.7 ± 7.3), with an aneurysm diameter of 4.86 ± 0.75 cm, and a higher prevalence of hyperlipidemia and statin use. Regardless of the anatomical segment analyzed, AAA surgical patients demonstrated a higher CCR2 radiotracer signal in the aortic tissue than others. However, no correlation was observed between the radiotracer signal and the AAA diameter. Patients with a higher radiotracer signal, particularly in the AAA posterior wall of the maximum-diameter region, were significantly correlated with RPI (P = 0.03). Histomorphic analysis demonstrated significantly elevated CCR2 levels, along with increased macrophage infiltration, matrix metalloproteinase activity, and severe elastin degradation. Conclusions: This first-in-human study demonstrated that CCR2 PET/CT molecular imaging is feasible and can identify increased wall instability in individuals with AAAs, especially in those at higher risk of disease progression.
Targeting neutrophil extracellular traps in cancer progression and metastasis
Authors: Ji Zhang, Changhong Miao, Hao Zhang
Journal: Theranostics (2025)

Neutrophils serve as pivotal effectors and regulators of the intricate immune system. Their contributions are indispensable, encompassing the obliteration of pathogens and a significant role in both cancer initiation and progression. Conversely, malignancies profoundly affect neutrophil activity, maturation, and lifespans. Cancer cells manipulate their biology to enhance or suppress the key functions of neutrophils. This manipulation is one of the most remarkable defensive mechanisms used by neutrophils, including the formation of neutrophil extracellular traps (NETs). NETs are filamentous structures comprising DNA, histones, and proteins derived from cytotoxic granules. In this review, we discuss the bidirectional interplay in which cancer elicits NET formation, and NETs concurrently facilitate cancer progression. Here, we discuss how vascular dysfunction and thrombosis induced by neutrophils and NETs contribute to an elevated risk of mortality from cardiovascular complications in patients with cancer. Ultimately, we propose a series of therapeutic strategies that hold promise for effectively targeting NETs in clinical settings.
AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma
Authors: Mingjuan Lei, Yiu To Yeung, Wenna Nie, Ran Yang, Jian Li, Hanyong Chen, Ran Zhao, Kangdong Liu, Zigang Dong
Journal: Theranostics (2025)

Rationale: As the most common form of lung cancer, non-small cell lung cancer (NSCLC) is still a challenging disease. Even though molecular-targeted drugs have greatly benefited NSCLC patients, the limited number of effective targets and the emergence of drug resistance necessitate further research to identify new candidates and improve clinical outcomes. Phosphatidylinositol-3,4,5-triphosphate-dependent RAC exchange factor-2 (PREX2) is highly expressed in multiple cancer types and poses high mutation frequency in lung cancer. However, the study of PREX2 in lung cancer, especially NSCLC, is few and unclear, thus, the role of PREX2 and the regulatory mechanism of PREX2 in NSCLC is worthy of further investigation. Methods: To determine the tumor-promoting effects of PREX2 in NSCLC, we established PREX2 knockdown NSCLC cells, then assessed cell growth in vitro and in cell-derived xenograft (CDX) mouse model. Furtherly, we used the urethane-induced lung carcinogenesis mouse model to confirm the significance of PREX2 in vivo. Additionally, we identified AHCYL1 as a novel PREX2-interacting protein through pull-down assay and liquid chromatography with tandem mass spectrometry (LC-MS/MS) and investigated the mechanisms of PREX2 GEF activity regulated by AHCYL1 using various molecular biology assays, including western blotting, in vitro GEF assay and active RAC1 pull-down assay. Results: Our study suggests that PREX2 and AHCYL1 both promote NSCLC cell growth and proves that AHCYL1 enhances the GEF activity of PREX2 by alleviating the mutual inhibition between PREX2 and PTEN. Consequently, AHCYL1 intensifies the tumor-promoting effects of PREX2 in NSCLC. Conclusion: Overall, our results indicate that PREX2 and AHCYL1 promote lung cancer development and reveal a novel regulatory mechanism of PREX2 GEF activity by AHCYL1, which will contribute to the understanding of NSCLC pathogenesis and offer new targets and strategies for the diagnosis and treatment of NSCLC.
Spatially segregated APOE<sup>+</sup> macrophages restrict immunotherapy efficacy in clear cell renal cell carcinoma
Authors: Qintao Ge, Jialin Meng, Zhongyuan Wang, Aihetaimujiang Anwaier, Jiahe Lu, Xi Tian, Yue Wang, Jianfeng Yang, Hailiang Zhang, Dingwei Ye, Wenhao Xu
Journal: Theranostics (2025)

Background: Immunotherapy has revolutionized cancer treatment and holds great potential for them, including metastatic clear cell renal cell carcinoma (ccRCC). However, immune resistance remains a major obstacle, limiting its efficacy and durability. Understanding the mechanisms of immune tolerance in the tumor microenvironment (TME) is pivotal for overcoming these challenges and enhancing therapeutic outcomes. Methods: Over 2000 samples, including a real-world cohort of 230 advanced ccRCC patients treated with immune checkpoint blockade (ICB) were analyzed. Single-cell RNA sequencing data from 13 tumor regions were categorized into ICB-exposed, ICB-resistant, and ICB-responsive groups. Multiple robust algorithms and multiplex immunofluorescence were used to explore TME composition and macrophage heterogeneity. Spatial communication dynamics were further investigated. In vitro experiments were performed to evaluate the impact of SPP1 on 786-O and 769-P cells. Co-culture experiments with THP-1-derived macrophages, followed by Western blot, flow cytometry, and functional assays, were performed to investigate SPP1-mediated macrophage polarization and its impact on tumor progression. Results: The results revealed an elevated presence of Apolipoprotein E (APOE)+ macrophages in ICB-resistant ccRCC. Notably, higher APOE+ macrophage proportion indicated shorter prognosis and worse response to ICB (P < 0.001). Elevated expression of CCAAT Enhancer Binding Protein Delta (CEBPD) was markedly linked to several immunosuppressive pathways, hindering T cell recruitment, promoting exhaustion, ultimately diminishing poorer prognosis and worse ICB efficacy. Meanwhile, upregulated Secreted Phosphoprotein 1 (SPP1) significantly enhances the proliferation, clonal formation, and migration of ccRCC cells. Tumor-derived SPP1. Additionally, SPP1 signaling from malignant cells appeared to recruit APOE+ macrophages to tumor margins, and promotes macrophage polarization into APOE+ M2-like macrophages. In the vicinity of the tumor, these APOE+ macrophages shape immunosuppressive TME by releasing abundant TGF-β signals, limiting anti-tumor effector T cells activity in ICB-resistant tumors, and contributing to tumor progression. Conclusion: This study reveals the critical role of APOE+ macrophages in promoting immune suppression and resistance to ICB therapy in ccRCC. By promoting T cell exhaustion and immunosuppressive signaling, particularly via localized TGF-β, these spatially segregated macrophages undermine treatment efficacy. Targeting APOE+ macrophages, especially in conjunction with ICB, presents a promising strategy to overcome immune resistance and enhance outcomes for ccRCC patients.
Apolipoprotein E promotes primary resistance to AR-targeted therapy via inducing TRIM25-mediated AR ubiquitination and sensitizes immunotherapy in prostate cancer
Authors: Chaofan Liu, Xi Wang, Qinyu Li, Xintao Gao, Kai Zeng, Beining Li, Jianping Miao, Bolong Zheng, Jihong Liu, Zhihua Wang, Xianglin Yuan, Bo Liu
Journal: Theranostics (2025)

Rationale: Prostate cancer (PCa) growth is facilitated by the androgen receptor (AR) and its downstream signaling pathways, making AR-targeted therapy crucial for treating advanced stages. Despite this, the response to AR-targeted therapies is inconsistent, with a significant proportion of patients even exhibiting unresponsiveness to therapy from the outset, known as primary resistance. Therefore, a refined categorization framework is imperative for the timely detection of resistant phenotypes and the exploration of novel therapeutic avenues. Methods: Tissue microarrays and clinical cohorts were employed to delineate the impact of APOE on the prognostic outcomes and therapeutic resistance in PCa patients. Employing flow cytometry, immunoprecipitation, and mass spectrometry, we dissected the molecular underpinnings of APOE's role in conferring resistance to AR-targeted interventions. Single-cell RNA sequencing elucidated the intricate transcriptomic profiles of PCa with elevated APOE expression. Additionally, the therapeutic potential of anti-PD-L1 agents in treating PCa with APOE induction was rigorously assessed. Results: In this study, we elucidated the pivotal role of APOE in mediating primary resistance to AR-targeted therapy in PCa through the suppression of AR signaling pathways. Mechanistically, APOE was found to enhance the ubiquitination and subsequent degradation of AR by mediating the interaction between the E3-ligase TRIM25 and AR, concurrently dampening the transcriptional activity of AR. Additionally, elevated APOE expression was correlated with an augmented response to anti-PD-L1 treatment, hinting at the therapeutic advantage of immunotherapy in APOE-high PCa contexts. Conclusions: APOE expression could serve as a prognostic biomarker, pivotal for forecasting responses to both AR-targeted therapy and immunotherapy, thereby offering an innovative strategy for the personalized selection of treatment modalities in PCa.
Investigating post-infection anxiety- and depression-like behaviors in a SARS-CoV-2 mouse model
Authors: Qian Ge, Shan Zhou, Jose Porras, Panfeng Fu, Ting Wang, Jianyang Du, Kun Li
Journal: Theranostics (2025)

Rationale: The COVID-19 pandemic, driven by SARS-CoV-2, has resulted in a wide range of neuropsychiatric symptoms associated with post-acute sequelae (PASC). However, the mechanisms by which SARS-CoV-2 impacts the brain and leads to persistent behavioral changes remain poorly understood. We hypothesize that SARS-CoV-2 exposure induces neuroinflammation and microglial activation, leading to anxiety- and depression-like behaviors in mice. Methods: We established a SARS-CoV-2 mouse model using the virulent SARS2-N501YMA30 strain to investigate its impact on the central nervous system (CNS). We assessed neuroinvasion via immunostaining of dsRNA and markers for neuronal, astrocyte, and microglia in brain slices. Behavioral changes were evaluated at 2 weeks, 2 months, and 4 months post-infection. Molecular and cellular analyses included bulk RNA-seq, Golgi-Cox staining, field excitatory postsynaptic potential (fEPSP) recordings, immunofluorescence, and quantitative real-time PCR (qRT-PCR) to assess gene expression, neuronal morphology, and microglial activation in the brain. Results: We demonstrated that intranasal inoculation of SARS2-N501YMA30 results in viral dissemination to multiple brain regions, including the amygdala and the prefrontal cortex (PFC). Behavioral assays indicated a marked elevation in anxiety- and depression-like behaviors post-infection. A comparative analysis of RNA expression profiles disclosed alterations in the post-infected brains. Additionally, we observed dendritic spine remodeling on neurons within the amygdala after infection. Infection with SARS2-N501YMA30 was associated with microglial activation and a subsequent increase in microglia-dependent neuronal activity in the amygdala. Transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. Conclusion: Our findings provide evidence that SARS-CoV-2 neuroinvasion plays a critical role in the development of lasting behavioral sequelae observed in PASC. These data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.