tbuckley/cabot-search huggingface dataset:
The gut microbiota predicts and time-restricted feeding delays experimental colitis
Authors: Hannah K. Ruple, Eva Haasis, Anna Bettenburg, Carina Maier, Carolin Fritz, Laura Schüle, Sarah Löcker, Yvonne Soltow, Lynn Schintgen, Nina S. Schmidt, Celine Schneider, Axel Lorentz, W. Florian Fricke
Journal: Gut Microbes (2025)

The etiology of inflammatory bowel disease (IBD) remains unclear, treatment options unsatisfactory and disease development difficult to predict for individual patients. Dysbiosis of the gastrointestinal microbiota and disruption of the biological clock have been implicated and studied as diagnostic and therapeutic targets. Here, we examine the relationship of IBD to biological clock and gut microbiota by using the IL-10 deficient (IL-10-/-) mouse model for microbiota-dependent spontaneous colitis in combination with altered (4 h/4 h) light/dark cycles to disrupt and time-restricted feeding (TRF) to restore circadian rhythmicity. We show that while altered light/dark cycles disrupted the intestinal clock in wild type (WT) mice, IL-10-/- mice were characterized by altered microbiota composition, impaired intestinal clock, and microbiota rhythmicity irrespective of external clock disruption, which had no consistent colitis-promoting effect on IL-10-/- mice. TRF delayed colitis onset reduced the expression of inflammatory markers and increased the expression of clock genes in the intestine, and increased gut microbiota rhythmicity in IL-10-/- mice. Compositional changes and reduced rhythmicity of the fecal microbiota preceded colitis and could predict colitis symptoms for individual IL-10-/- mice across different experiments. Our findings provide perspectives for new diagnostic and TRF-based, therapeutic applications in IBD that should be further explored.
Circular RNA circBNC2 inhibits tumorigenesis by modulating ferroptosis and acts as a nanotherapeutic target in prostate cancer
Authors: Xiang Pan, Kailai Chen, Wei Gao, Meiqi Xu, Fanlong Meng, Mengyuan Wu, Zi Qi Wang, Yun Qi Li, Wanhai Xu, Manjie Zhang, Yakun Luo
Journal: Molecular Cancer (2025)
Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal
Authors: Xie Song, Zijie Xia, Dayne Martinez, Bing Xu, Zachary Spritzer, Yanjie Zhang, Erin Nugent, Yugong Ho, Barbara Terzic, Zhaolan Zhou
Journal: Cell Reports Medicine (2025)

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental syndrome caused by mutations in the X-linked CDKL5 gene. The early onset of CDD suggests that CDKL5 is essential during development, but post-developmental re-expression rescues multiple CDD-related phenotypes in hemizygous male mice. Since most patients are heterozygous females, studies in clinically relevant female models are essential. Here, we systematically compare phenotype reversal across age and sex using two independent mouse models of CDD. We find that early re-activation of endogenous Cdkl5 in heterozygous females reverses most phenotypes, except working memory. Later re-expression improves several traits but has limited effects on cognitive function. Seizure prevention is more effective with early intervention in heterozygous females but becomes limited after seizure onset. These findings demonstrate the robust potential of CDKL5 re-expression to reverse CDD-related phenotypes in both sexes while underscoring the critical impact of age and disease stage in designing clinical trials.
A multivariable prediction model for invasive pulmonary aspergillosis in immunocompromised patients with acute respiratory failure (IPA-GRRR-OH score)
Authors: Alice Friol, Guillaume Dumas, Frédéric Pène, Alexandre Demoule, Achille Kouatchet, Laurent Argaud, Naike Bigé, Anne-Sophie Moreau, François Barbier, Djamel Mokart, Virginie Lemiale, Elie Azoulay
Journal: Intensive Care Medicine (2025)
Vvax001, a Therapeutic Vaccine for Patients with HPV16-positive High-grade Cervical Intraepithelial Neoplasia: a Phase II Trial
Authors: Anneke L. Eerkens, Martha D. Esajas, Koen Brummel, Annegé Vledder, Nienke van Rooij, Annechien Plat, Stefany B. Avalos Haro, Sterre T. Paijens, Lorian Slagter-Menkema, Ed Schuuring, Naomi Werner, Jos G.W. Kosterink, Bart-Jan Kroesen, Jan C. Wilschut, Toos Daemen, Joost Bart, Hans W. Nijman, Marco de Bruyn, Refika Yigit
Journal: Clinical Cancer Research (2025)

Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3). Patients with newly diagnosed HPV16-positive CIN3 were eligible for participation. Patients received 3 immunizations of Vvax001 (5x107 infectious particles) at a three-week interval. Up to 19 weeks after the last immunization patients were monitored for regression of CIN3 by colposcopy. A colposcopy-guided biopsy was taken at the last visit and a standard of care loop excision was performed only in case of remaining CIN2/3. Histopathologic response rates, HPV16 clearance, treatment-related adverse events (trAEs), and vaccine-induced immune responses were assessed. A total of 18 patients were enrolled and fully immunized. Colposcopic examination revealed a reduction in CIN3 lesion sizes in 17/18 patients (94%) already evident from 3 weeks onwards after the last immunization. A histopathological complete response (regression to CIN1 or no dysplasia) was observed in 9/18 patients (50%), and HPV16 clearance in 10/16 patients (63%). Vvax001 did not induce clearance of other HPV types. To date, no recurrences have been observed, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious AEs were observed. Treatment with Vvax001 is safe, feasible, and shows preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions.
Iron Drives Eosinophil Differentiation in Allergic Airway Inflammation Through Mitochondrial Metabolic Adaptation
Authors: Fei Li, Haoyu Tang, Yuejue Wang, Qian Wu, Lingling Dong, Jamil Z Kitoko, Jiaqi Huang, Haixia Chen, Ruixin Jia, Zhengyuan Liu, Chao Zhang, Xufei Du, Wen Li, Zhihua Chen, Huahao Shen, Songmin Ying
Journal: Advanced Healthcare Materials (2025)

Abstract Eosinophils play a crucial role as effector cells in asthma pathogenesis, with their differentiation being tightly regulated by metabolic mechanisms. While the involvement of iron in various cellular processes is well known, its specific role in eosinophil differentiation has largely remained unexplored. This study demonstrates that iron levels are increased during the differentiation process from eosinophil progenitors to mature and activated eosinophils in the context of allergic airway inflammation. Through experiments involving iron chelators, supplements, and iron‐deficient or iron‐enriched diets, the indispensable role of iron in eosinophil lineage commitment both in vitro and in vivo is demonstrated. Remarkably, iron chelation effectively suppresses eosinophil differentiation and alleviates airway inflammation in a house dust mite(HDM)‐induced mouse model of allergic asthma. Mechanistically, iron promotes the expression of transcription factors that enforce eosinophil differentiation, and maintains mitochondrial metabolic activities, leading to specific metabolic shifts within the tricarboxylic acid (TCA) cycle, with succinate promoting eosinophil differentiation. Overall, this study highlights the function of iron and underlying metabolic mechanisms in eosinophil differentiation, providing potential therapeutic strategies for asthma control.
The micro(nano)plastics perspective: exploring cancer development and therapy
Authors: Xiangying Deng, Yajun Gui, Lin Zhao
Journal: Molecular Cancer (2025)

Microplastics, as an emerging environmental pollutant, have received widespread attention for their potential impact on ecosystems and human health. Microplastics are defined as plastic particles less than 5 millimeters in diameter and can be categorized as primary and secondary microplastics. Primary microplastics usually originate directly from industrial production, while secondary microplastics are formed by the degradation of larger plastic items. Microplastics are capable of triggering cytotoxicity and chronic inflammation, and may promote cancer through mechanisms such as pro-inflammatory responses, oxidative stress and endocrine disruption. In addition, improved microplastics bring new perspectives to cancer therapy, and studies of microplastics as drug carriers are underway, showing potential for high targeting and bioavailability. Although current studies suggest an association between microplastics and certain cancers (e.g., lung, liver, and breast cancers), the long-term effects and specific mechanisms still need to be studied. This review aimed at exploring the carcinogenicity of microplastics and their promising applications in cancer therapy provides important directions for future research and emphasizes the need for multidisciplinary collaboration to address this global health challenge.
TPMS‐Gyroid Scaffold‐Mediated Up‐Regulation of ITGB1 for Enhanced Cell Adhesion and Immune‐Modulatory Osteogenesis
Authors: Jing Wang, Zenan Huang, Zhenzhong Han, Jing Luan, Zihan Li, Xutong Guo, Dongxu Yang, Yazhou Cui, Jinxiang Han, Duo Xu
Journal: Advanced Healthcare Materials (2025)

Abstract The porous structure is crucial in bone tissue engineering for promoting osseointegration. Among various structures, triply periodic minimal surfaces (TPMS) ‐Gyroid has been extensively studied due to its superior mechanical and biological properties. However, previous studies have given limited attention to the impact of unit cell size on the biological performance of scaffolds. In this research, four TPMS‐Gyroid titanium scaffolds with different unit cell sizes (TG15, TG20, TG25, and TG30) are fabricated using Selective Laser Melting (SLM) to explore their effects on osseointegration. Mechanical tests revealed that TG15 and TG20 exhibited superior compressive strength. In vitro experiments demonstrated that TG20 facilitated better cell adhesion through robust integrin protein expression initially, which subsequently enhanced cell proliferation and osteogenic differentiation. Furthermore, macrophages on TG20 showed higher Integrin β1 (ITGB1) expression, promoting their polarization to the M2 phenotype, which suppressed inflammation, fostered bone integration, and angiogenesis. In vivo studies confirmed TG20's effectiveness in promoting bone ingrowth by reducing inflammation. This study highlights TG20's structural advantages, making it a promising bone scaffold with exceptional osteogenic and angiogenic properties through osteoimmune microenvironment modulation. Therefore, TG20 holds significant potential for applications in bone tissue engineering.
Genetic Insights into Sarcomatoid Hepatocellular Carcinoma: Critical Role of ARID2 in Pathogenesis and Immune Feature
Authors: Naoshi Nishida
Journal: Clinical and Molecular Hepatology (2025)

sarcomatoid hepatocellular carcinoma (sHCC), conventional HCC (cHCC), tumor immune microenvironment (TME), molecular targeted agents (MTAs), immune checkpoint inhibitors (ICIs), epithelial-mesenchymal transition (EMT), recurrence-free survival (RFS), switch/sucrose nonfermenting (SWI/SNF), overall survival (OS)
Association between exposure to particulate matter and heart rate variability in vulnerable and susceptible individuals
Authors: Yong Whi Jeong, Hayon Michelle Choi, Youhyun Park, Yongjin Lee, Ji Ye Jung, Dae Ryong Kang
Journal: npj Digital Medicine (2025)

Particulate matter (PM) exposure can reduce heart rate variability (HRV), a cardiovascular health marker. This study examines PM1.0 (aerodynamic diameters <1 μm), PM2.5 (≥1 μm and <2.5 μm), and PM10 (≥2.5 μm and <10 μm) effects on HRV in patients with environmental diseases as chronic disease groups and vulnerable populations as control groups. PM levels were measured indoors and outdoors for five days in 97 participants, with 24-h HRV monitoring via wearable devices. PM exposure was assessed by categorizing daily cumulative PM concentrations into higher and lower exposure days, while daily average PM concentrations were used for analysis. Results showed significant negative associations between exposure to single and mixtures of different PM metrics and HRV across all groups, particularly in chronic airway disease and higher air pollution exposed groups. These findings highlight that even lower PM levels may reduce HRV, suggesting a need for stricter standards to protect sensitive individuals.
ROS-differentiated release of Apelin-13 from hydrogel comprehensively treats myocardial ischemia-reperfusion injury
Authors: Penghao Zhen, Qiaochu Jiang, Fuchao Yu, Xuan Xu, Qin Wei, Xiaoyang Liu, Xianbao Sun, Gaolin Liang, Jiayi Tong
Journal: Journal of Controlled Release (2025)
Biomimetic exosome harnessing exosomal lipidomics and functional proteins for PEDF-pDNA delivery in high altitude pulmonary edema intervention
Authors: Huiyang Li, Jinming Liu, Hong Wang, Chengyi Xu, Guangwei Shi, Jianling Zhao, Lu Zhang, Mengjun Zeng, Liqun Jiang
Journal: Journal of Controlled Release (2025)
Harnessing the Potential of Human Breast Milk to Boost Intestinal Permeability for Nanoparticles and Macromolecules
Authors: Si Naftaly, Topaz Pery, Rawan Mhajne, Areen Ashkar, Maya Davidovich-Pinhas, Assaf Zinger
Journal: Journal of Controlled Release (2025)

The intricate interplay between human breast milk, nanoparticles, and macromolecules holds promise for innovative nutritional delivery strategies. Compared to bovine milk and infant formula, this study explores human breast milk's role in modulating intestinal permeability and its impact on nanoparticle and macromolecule transport. Comparative analysis with bovine milk and infant formula reveals significant elevations in permeability with human breast milk, accompanied by a decrease in transepithelial electrical resistance, suggesting enhanced paracellular transport. Mechanistically, human breast milk reduces Zonula occludens-1 levels, suggesting a regulatory role in intestinal barrier function. Through in vitro and ex vivo evaluations, we aim to understand better the mechanisms behind enhanced permeability and how human breast milk affects nanoparticle physicochemical properties, potentially modulating their behavior. Specifically, human breast milk improves the intestinal permeability of liposomes in a porcine intestinal model, with associated changes in the composition of milk proteins corona related to liposome charge. These findings underscore the unexploited potential of human breast milk in facilitating transport across the intestinal barrier, offering novel avenues for human nutritional delivery and therapeutic interventions.
The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant
Authors: Emilie Le Rhun, Andrea Bink, Joerg Felsberg, Dorothee Gramatzki, Sebastian Brandner, Jamal K Benhamida, Antje Wick, Joerg C Tonn, Malte Mohme, Ghazaleh Tabatabai, David Capper, Matija Snuderl, Evangelia Razis, Michael W Ronellenfitsch, Nicolas Neidert, Ho-Keung Ng, Ute Pohl, Tejus Bale, Stefanie Quach, David Rieger, Ulrich Schüller, Julia Onken, Katharina Drüschler, Claude-Alain Maurage, Luca Regli, Estelle Healy, Maya Graham, Tibor Hortobagyi, Simon Paine, Leslie Bridges, Tereza Lausova, Valentina Medici, Philipp Sievers, David Schrimpf, Wolfgang Wick, Felix Sahm, Guido Reifenberger, Andreas von Deimling, Michael Weller
Journal: Neuro-Oncology (2025)

Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 WHO classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors. We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, CNS WHO grade 4 and profiled the imaging, histological and molecular landscape of their tumors. Compared with glioblastoma, H3 G34-mutant diffuse hemispheric gliomas exhibited less avid contrast enhancement, necrosis and edema on MRI. Comprehensive analyses of mutational and DNA copy number profiles revealed recurrent mutations in TP53 and ATRX, homozygous deletions of CDKN2A/B, and amplifications of PDGFRA, EGFR, CCND2, and MYCN. MGMT promoter methylation was detected in 79 tumors (75%); 11 tumors (13%) showed DNA copy number profiles suggestive of circumscribed deletions on 10q26.3 involving the MGMT locus. Median survival was 21.5 months. Female sex, gross total resection, and MGMT promoter methylation were positive prognostic factors on univariate analysis. Among radiological, pathological and molecular features, absence of pial invasion, and presence of microvascular proliferation and CDK6 amplification were positive prognostic factors on univariate analyses. This study refines the clinical and molecular landscape of H3 G34-mutant diffuse hemispheric gliomas. Dedicated trials for this novel tumor type are urgently needed.
Prenatal exposure to chemotherapy increases the mutation burden in human neonatal hematopoietic stem cells
Authors: Ilana Struys, Carolina Velázquez, Joske Ubels, Charlotte L. LeJeune, Markus J. van Roosmalen, Axel K.M. Rosendahl Huber, Anais J.C.N. van Leeuwen, Wouter Bossuyt, Bernard Thienpont, Thierry Voet, Kristel Van Calsteren, Liesbeth Lenaerts, Ruben van Boxtel, Frédéric Amant
Journal: Cancer Discovery (2025)

Abstract Chemotherapy is included in the standard of care for cancer treatment during pregnancy. However, whether prenatal exposure to maternal chemotherapy treatment has a mutagenic impact on the fetal genome, remains unexplored. Therefore, we investigated mutation accumulation in hematopoietic stem and progenitor cells (HSPCs) from neonates born to pregnant cancer patients treated with chemotherapy, as well as healthy pregnant women and untreated pregnant cancer patients. The mutational burden in HSPCs from neonates born to untreated pregnant cancer patients and to healthy controls was similar, but increased after prenatal exposure to varying types of chemotherapy regimens. Mutational signature analyses attributed the excess mutations to clock-like processes, which are active during normal cellular aging, or to direct mutagenesis by platinum-based drugs in neonates prenatally exposed to platinum-containing regimens. Our findings in the neonatal hematopoietic compartment are consistent with mutational signatures previously identified in cells of cancer survivors directly exposed to these chemotherapeutic drugs.
Impact of SARS-CoV-2 spike antibody positivity on infection and hospitalisation rates in immunosuppressed populations during the omicron period: the MELODY study
Authors: Lisa Mumford, Rachel Hogg, Adam Taylor, Peter Lanyon, Mary Bythell, Sean McPhail, Joseph Chilcot, Gillian Powter, Graham S Cooke, Helen Ward, Helen Thomas, Stephen P McAdoo, Liz Lightstone, Sean H Lim, Gavin J Pettigrew, Fiona A Pearce, Michelle Willicombe
Journal: The Lancet (2025)
Metabolic profiling of meningioma reveals novel subgroup-specific biologic insights and outcome dependencies
Authors: Alexander P Landry, Justin Z Wang, Leeor S Yefet, Jeff Liu, Vikas Patil, Wen-Jiang Zhang, Julio Sosa, Yosef Ellenbogen, Chloe Gui, Andrew Ajisebutu, Kenneth Aldape, Andrew Gao, Thomas Kislinger, Eric X Chen, Farshad Nassiri, Gelareh Zadeh
Journal: Neuro-Oncology (2025)

Abstract Background Our group and others have recently identified four molecular groups of meningioma, with unique underlying biology and outcomes. The relevance of group-specific metabolite profiles (particularly among hypermetabolic tumours), has not been explored. Methods We performed untargeted metabolic profiling of meningiomas representing each molecular group and WHO grade. Prognostic biochemicals were identified using Cox regression and their biological importance was explored using RNA and protein-based pathway analyses. Validation was performed using targeted high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Results Global metabolic profiling identified 560 unique biochemicals. We identified a 21-metabolite outcome signatures which is strongly predictive of outcome after adjusting for WHO grade, extent of resection, and receipt of adjuvant radiotherapy (HR 326.49, 95%CI 16.72-6375.48, p &amp;lt; 0.0001). The abundance of N6-trimethyllysine was associated with earlier time to recurrence on our whole cohort (log-rank p = 0.009) and within hypermetabolic and WHO grade 2 tumours specifically; this was validated using targeted HPLC-MS/MS on two cohorts. Consensus RNA and protein expression analysis demonstrated as association between N6-trimethyllysine abundance and activation of oxidative phosphorylation pathways, which portended worse outcomes in the hypermetabolic subgroup but, interestingly, better outcomes in the proliferative subgroup. By contrast, upregulated pyruvate and lactate transporters were associated with worse outcomes in proliferative meningiomas specifically. Conclusions This is the first study to demonstrate a subgroup-specific prognostic role of N6-trimethyllysine in hypermetabolic meningiomas, offering increasingly granular outcome predictions using a widely accessible technique (HPLC-MS/MS). We also suggest fundamental differences in preferred energy utilization between and a potential need for subgroup-specific therapies.
Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS)
Authors: Jonathan I Silverberg, Lawrence F Eichenfield, Andrew Blauvelt, Alan D Irvine, Emma Guttman-Yassky, Richard G Langley, Richard B Warren, Lars E French, Jakob Felding, Anne Weiss, Claus B Pedersen, Morten L Jensen, Anna Carlsson, Morten O A Sommer, Kim Kjøller, Eric L Simpson
Journal: British Journal of Dermatology (2025)

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD. Objectives To evaluate the optimal dose, efficacy and safety of orismilast twice-daily (BID) in patients with moderate-to-severe AD. Methods This 16-week, multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (NCT05469464) included patients from 48 centers in Europe and the United States. Adults with moderate-to-severe AD were given (1:1:1:1) BID orismilast 20, 30, or 40 mg, or placebo. The primary endpoint was percentage change in Eczema Area and Severity Index (EASI); secondary: achievement of a score of Clear (0) or Almost Clear (1) with ≥2-point improvement by Investigator Global Assessment (IGA 0/1); achievement of peak pruritus numerical rating scale (PPNRS) reduction of ≥4 points; and achievement of a reduction in EASI of 75%, 90%, and 100% (EASI75, EASI90, EASI100, respectively) from baseline; all week 16. Results Overall, 233 patients were randomly assigned to orismilast 20 mg (n=58), 30 mg (n=61), 40 mg (n=59), or placebo (n=55). At week 16, Reductions in EASI (%-point) from baseline to week 16 were seen across orismilast groups and placebo (p&amp;gt;0.05 for orismilast versus placebo). Significantly more patients achieved IGA 0/1 with a ≥2-point improvement with orismilast 20 mg and 40 mg versus placebo (p&amp;lt;0.05). Significantly greater proportions of patients achieving a ≥4-point reduction in PPNRS were demonstrated with orismilast at week 2. The safety profile was consistent with that of the PDE4 class, with no major safety concerns reported. Conclusions These data support the clinical relevance of selective PDE4B/D inhibition with orismilast, potentially offering a convenient, novel, oral therapy for the treatment of AD.