tbuckley/cabot-search huggingface dataset:
Creatine-mediated ferroptosis inhibition is involved in the intestinal radioprotection of daytime-restricted feeding
Authors: Yingjuan He, Gaomei Zhao, Xue Ouyang, Shaobo Wang, Yin Chen, Chenwenya Li, Yongwu He, Jining Gao, Songling Han, Jinghong Zhao, Junping Wang, Cheng Wang
Journal: Gut Microbes (2025)

Ionizing radiation-induced intestinal injury (IRIII) is a catastrophic disease lack of sufficient medical countermeasures currently. Regulation of the gut microbiota through dietary adjustments is a potential strategy to mitigate IRIII. Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention with pleiotropic health benefits. Whether this dietary pattern influences the pathogenesis of IRIII remains vague. We evaluated the impact of TRF on intestinal radiosensitivity in this study and discovered that only daytime TRF (DTRF), not nighttime TRF, could ameliorate intestinal damage in mice that received a high dose of IR. Faecal metagenomic and metabolomic studies revealed that the intestinal creatine level was increased by approximate 9 times by DTRF, to which the Bifidobacterium pseudolongum enrichment contribute. Further investigations showed that creatine could activate the energy sensor AMP-activated protein kinase in irradiated enterocytes and induce phosphorylation of acetyl-CoA carboxylase, resulting in reduced production of polyunsaturated fatty acids and reduced ferroptosis after IR. The administration of creatine mitigated IRIII and reduced bacteremia and proinflammatory responses. Blockade of creatine import compromised the ferroptosis inhibition and mitigation of DTRF on IRIII. Our study demonstrates a radioprotective dietary mode that can reshape the gut microbiota and increase intestinal creatine, which can suppress IR-induced ferroptosis, thereby providing effective countermeasures for IRIII prevention.
Beta 2 adrenergic receptor gene methylation activates innate lymphoid cells to drive hypertension in lymphocyte deficient hosts
Authors: Wei Chen, Sara Perrotta, Liang Xiao, Lorenzo Carnevale, Marwa A Abd-ElDayem, Elizabeth M Hennen, Luis Miguel Rivera-Medina, David M Patrick, Mingfang Ao, Fabio Pallante, Azzurra Zonfrilli, Shilin Zhao, Agnese Migliaccio, Lan Lan, Stefania Fardella, Giuseppe Sciumè, Francesco Mastroiacovo, Giuseppe Lembo, Daniela Carnevale, David G Harrison
Journal: Cardiovascular Research (2025)

Abstract Aims T cells contribute to hypertension; however, hypertension occurs in settings of T cell deficiency. Methods and results We studied two colonies of T/B cell-deficient RAG-1−/− mice with disparate responses to angiotensin II, being one protected from blood pressure increase and the other one responsive. This difference depends on the capability of hypertensive RAG-1−/− mice to expand natural killer and innate lymphoid cells (NK/ILCs) that produce pro-hypertensive cytokines. This process is regulated by the DNA methylation status of the β2 adrenergic receptor (β2-AdR). Angiotensin II caused blood pressure elevation in T and NK/ILCs-deficient mice only when either T or NK/ILCs cells were adoptively reconstituted. Additional studies showed NK cell expansion in humans that underwent B cell depletion, and this was augmented in those with hypertension. Conclusions These findings illustrate that the modulation of NK/ILCs activation by adrenergic signalling governs an escape mechanism in lymphocyte-deficient host, enabling the development of hypertension.
<i>Helicobacter pylori</i> γ-glutamyltransferase is linked to proteomic adaptions important for colonization
Authors: Sonja Fuchs, Michaela K. Fiedler, Nicole Heiduk, Andreas Wanisch, Cora Mibus, Dharmesh Singh, Aleksandra W. Debowski, Barry J. Marshall, Michael Vieth, Christine Josenhans, Sebastian Suerbaum, Stephan A. Sieber, Markus Gerhard, Raquel Mejías-Luque
Journal: Gut Microbes (2025)

Helicobacter pylori γ-glutamyltransferase (gGT) is a virulence factor that promotes bacterial colonization and immune tolerance. Although some studies addressed potential functional mechanisms, the supportive role of gGT for in vivo colonization remains unclear. Additionally, it is unknown how different gGT expression levels may lead to compensatory mechanisms ensuring infection and persistence. Hence, it is crucial to unravel the in vivo function of gGT. We assessed acid survival under conditions mimicking the human gastric fluid and elevated the pH in the murine stomach prior to H. pylori infection to link gGT-mediated acid resistance to colonization. By comparing proteomes of gGT-proficient and -deficient isolates before and after infecting mice, we investigated proteomic adaptations of gGT-deficient bacteria during infection. Our data indicate that gGT is crucial to sustain urease activity in acidic environments, thereby supporting survival and successful colonization. Absence of gGT triggers expression of proteins involved in the nitrogen and iron metabolism and boosts the expression of adhesins and flagellar proteins during infection, resulting in increased motility and adhesion capacity. In summary, gGT-dependent mechanisms confer a growth advantage to the bacterium in the gastric environment, which renders gGT a valuable target for the development of new treatments against H. pylori infection.
<i>Fusobacterium nucleatum</i> exacerbates colitis via STAT3 activation induced by Acetyl-CoA accumulation
Authors: Zixuan Xiang, Xiangyun Li, Xiaoli Wang, Beiying Deng, Haodong He, Miao Xu, Xiaohan Wu, Cheng Tan, Yafei Liu, Baoping Yu, Jixiang Zhang, Weiguo Dong
Journal: Gut Microbes (2025)

Fusobacterium nucleatum (F. nucleatum) has emerged as a potential contributor to ulcerative colitis (UC) pathogenesis, although the specific mechanisms remain incompletely understood. This study demonstrates that F. nucleatum promotes colitis by disrupting intestinal barrier integrity, inducing apoptosis in epithelial cells, and modulating inflammatory pathways. Furthermore, we demonstrate that F. nucleatum promotes STAT3 acetylation at K685, followed by phosphorylation at Y705, thereby enhancing its transcriptional activity and exacerbating colitis severity. Additionally, F. nucleatum-mediated upregulation of acetyl-CoA levels is responsible for STAT3 acetylation, linking metabolic processes to UC pathophysiology. Pharmacological inhibition of acetyl-CoA production effectively mitigates F. nucleatum-induced colitis in experimental models, suggesting potential therapeutic strategies targeting these pathways. These findings unveil a novel regulatory pathway in F. nucleatum-associated UC progression and offer new insights for future UC prevention and treatment.
Global burden of skin and subcutaneous diseases: an update from the Global Burden of Disease Study 2021
Authors: Pengcheng Huai, Peiye Xing, Yilin Yang, Yaoyao Kong, Furen Zhang
Journal: British Journal of Dermatology (2025)

The global burden of dermatitis and scabies remains high among skin diseases. Basal cell carcinoma has been the fastest growing skin disease since 1990. Children, adolescents and the elderly had higher disability-adjusted life years from skin disease than other age groups.
A ROS-responsive nanoprodrug-engineered phage biotherapy for precision treatment of multidrug-resistant Gram-negative bacterial pneumonia
Authors: Lanlan Dong, Baohua Zhao, Yifei Lu, Lanlan Li, Can Huang, Xuan Zhou, Tingting You, Wei Qian, Jianxiang Zhang, Gaoxing Luo
Journal: Journal of Controlled Release (2025)
High Global Prevalence of Steatotic Liver Disease and Associated Subtypes: a Meta-analysis
Authors: Glenn Jun Kit Ho, Faith Xin Ning Tan, N Apoorva Sasikumar, Ethan Kai Jun Tham, Donghyun Ko, Do Han Kim, Pojsakorn Danpanichkul, Zhenning Yu, Cheng Xianda, Zi Xuan Zhang, Karn Wijarnpreecha, Thanawin Pramotedham, Mazen Noureddin, Daniel Q Huang, Yoshio Sumida, Atsushi Nakajima, Ming-Hua Zheng, Hirokazu Takahashi, Cheng Han Ng, Mark Muthiah
Journal: Clinical Gastroenterology and Hepatology (2025)
Potent therapeutic efficacy of intranasally deliverable paclitaxel modified with pH-sensitive and PEGylated polymeric micelle against glioblastoma
Authors: Young-Beom Kim, Soo-Hwan Lee, Dayananda Kasala, Yuebin Zhao, Ao Jiao, JinWoo Hong, Jin Su Kim, A Rum Yoon, Chae-Ok Yun
Journal: Journal of Controlled Release (2025)
Multimodal glioma immunotherapy combining TLR9-targeted STAT3 antisense oligodeoxynucleotides with PD1 immune checkpoint blockade
Authors: Chia-Yang Hung, Elaine Y Kang, Karol Jacek, Chunsong Yu, Xiaowei Zhang, Yicheng Zhu, Maryam Aftabizadeh, Robyn A Wong, Benham Badie, Piotr Swiderski, Bożena Kaminska, Darya Alizadeh, Amy B Heimberger, Christine Brown, Marcin Kortylewski
Journal: Neuro-Oncology (2025)

Abstract Background Therapeutic resistance in glioblastoma (GBM) is multifactorial and results from genetic heterogeneity, the immunoprivileged localization and the potently tolerogenic microenvironment. Signal transducer and activator of transcription 3 (STAT3) plays a key role in both glioma cell survival and immune evasion reinforcing GBM resistance. Methods Here, we describe a new cell-selective and double-stranded STAT3 antisense oligonucleotide (CpG-STAT3dsASO) for targeting human/mouse glioma cells and GAMs but not T-cells. The oligonucleotide safety and efficacy against orthotopic GBM was assessed in immunocompetent or immunodeficient mice. Results CpG-STAT3dsASO injected intracranially/intratumorally was well-tolerated and reduced progression of human U251 GBM xenotransplants and mouse GL261 or neural cell-derived QPP8 gliomas. Unlike the single-stranded oligonucleotide, local CpG-STAT3dsASO administration did not trigger type-I IFN-dependent neurotoxicities in immunocompetent mice within the therapeutic dose range. CpG-STAT3dsASO activated intratumoral GAMs, such as dendritic cells, macrophages and microglia, thereby expanding CD4+ Th1 cells while reducing TREG numbers. CpG-STAT3dsASO monotherapy did not have curative effects as it led to recruitment of only limited numbers of mostly exhausted effector CD8+ T-cells. However, when combined with systemic PD1 inhibition, CpG-STAT3dsASO/anti-PD1 treatments caused regression of GL261 as well as immunotherapy-resistant QPP8 gliomas and resulted in long-term survival of the majority of mice. The combination treatment boosted CD8+ effector T-cell activity, while promoting their intratumoral interaction with activated CD4+ Th1 cells and activated macrophages as indicated by spatial transcriptomics. Conclusions Our results suggest rationale for the GBM immunotherapy using CpG-STAT3dsASO to disrupt GAMs-dependent immune evasion, thereby restoring sensitivity to PD1-blockade and facilitating T-cell-mediated antitumor immune responses.
Exploring the toxicological network in diabetic microvascular disease
Authors: Siyuan Song, Liji Huang, Xiqiao Zhou, Jiangyi Yu
Journal: International Journal of Surgery (2025)

Purpose: This study investigates how endocrine-disrupting chemicals contribute to diabetic microvascular disease. Methods: This study assessed endocrine-disrupting chemical toxicity using PubChem, ProTox 3.0, and ChEMBL. Relevant EDC targets were identified via SwissTargetPrediction and Similarity Ensemble Approach. Gene targets for diabetic microvascular diseases (diabetic kidney disease, retinopathy, and sensory polyneuropathy) were retrieved from CTD, GeneCards, and OMIM. Candidate targets were identified by intersecting EDC and disease-related targets. A protein-protein interaction network was built using STRING to identify hub genes. Functional enrichment analysis was conducted via Metascape. Molecular docking of EDC compounds with hub targets was performed using Discovery Studio and CDOCKER. Hub targets were validated through immunohistochemical staining, single-cell distribution, subcellular localization assays, and gene expression analysis in external HPA and GEO datasets. Results: A total of 843, 474, and 623 potential toxic targets were identified for diabetic kidney disease, diabetic retinopathy, and diabetic sensory polyneuropathy, respectively. KEGG pathway analysis linked EDC toxicity in diabetic kidney disease to key pathways such as cancer, chemokine signaling, apoptosis, calcium signaling, and drug metabolism (cytochrome P450), with hub targets including EGFR, ALB, MYC, ESR1, and HSP90AA1. Diabetic retinopathy was associated with MAPK, ERBB, NOD-like receptor signaling, and renal cell carcinoma pathways, with ALB, EGFR, MYC, BCL2, and CD4 identified as hub targets. For diabetic sensory polyneuropathy, EDCs may influence chemokine, apoptosis, ERBB, VEGF, and JAK-STAT signaling pathways, with ALB, EGFR, MYC, ESR1, and BCL2 as key targets. Molecular docking confirmed strong binding activity between EDC components and hub targets. Conclusion: This study offers a theoretical basis for identifying toxic targets and mechanisms by which endocrine-disrupting chemicals contribute to diabetic microvascular diseases.
Reverse‑sequence endoscopic nipple‑sparing mastectomy with direct‑to‑implant breast reconstruction and air inflation adjustment technique in patients with large or severely ptotic breast: a single-center prospective cohort study
Authors: Hui Dai, Xiaoman Cao, Hao Wu, Faqing Liang, Yanyan Xie, Kawun Chung, Qing Zhang, Tianyuan Li, Zhenggui Du
Journal: International Journal of Surgery (2025)

Background: The applicability of reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) with direct-to-implant breast reconstruction (DIBR) is worth exploring in patients with large or severely ptotic breasts (LSPB) who were not recommended or even considered contraindicated in open NSM, conventional endoscopic NSM, and robotic NSM. The study aimed to compare the safety and aesthetic outcomes between patients with LSPB and non-LSPB (NLSPB) undergoing R-E-NSM with DIBR. Materials and methods: The single-center prospective cohort study enrolled 562 patients undergoing R-E-NSM and DIBR. Surgical safety, aesthetic outcomes, and oncologic safety were compared between patients with LSPB and NLSPB. Results: After propensity score matching, 88 LSPB patients and 256 NLSPB patients were included (median [IQR] follow-up time: 21.0 [13.8, 32.4] vs. 23.0 [10.6, 32.2] months, P = 0.889). The mastectomy weight was significantly higher in the LSPB group (576.6 ± 144.8 g vs. 330.1 ± 105.7 g, P &lt; 0.001). There were no significant differences in any complications (27.3% vs. 22.7%, P = 0.381), major complications (6.8% vs. 3.1%, P = 0.230), minor complications (20.5% vs. 21.1%, P = 0.889) and implant-related complications (21.6% vs. 24.6%, P = 0.566) between the LSPB and the NLSPB groups. In the LSPB group, the Ueda scores in patients with air inflation adjustment technique (AIAT) were better than those without AIAT, though no significant difference (P = 0.110). Compared to the NLSPB group without AIAT, the LSPB group with AIAT had similar Ueda scores (P = 0.870) and a significantly higher increase in BREAST-Q scores of breast satisfaction (P = 0.004). Oncologic outcomes had no significant difference between the two groups (all P&gt;0.05). Conclusion: R-E-NSM with DIBR and AIAT provides comparable surgical safety and aesthetic outcomes for patients with LSPB and NLSPB, offering a new option for LSPB patients.
Age- and diet-instructed metabolic rewiring of the tumor–immune microenvironment
Authors: Ana Belén Plata-Gómez, Ping-Chih Ho
Journal: The Journal of Experimental Medicine (2025)

The tumor–immune microenvironment (TIME) plays a critical role in tumor development and metastasis, as it influences the evolution of tumor cells and fosters an immunosuppressive state by intervening the metabolic reprogramming of infiltrating immune cells. Aging and diet significantly impact the metabolic reprogramming of the TIME, contributing to cancer progression and immune evasion. With aging, immune cell function declines, leading to a proinflammatory state and metabolic alterations such as increased oxidative stress and mitochondrial dysfunction, which compromise antitumor immunity. Similarly, dietary factors, particularly high-fat and high-sugar diets, promote metabolic shifts, creating a permissive TIME by fostering tumor-supportive immune cell phenotypes while impairing the tumoricidal activity of immune cells. In contrast, dietary restrictions have been shown to restore immune function by modulating metabolism and enhancing antitumor immune responses. Here, we discuss the intricate interplay between aging, diet, and metabolic reprogramming in shaping the TIME, with a particular focus on T cells, and highlight therapeutic strategies targeting these pathways to empower antitumor immunity.
BCOR loss promotes both retinoblastoma growth and susceptibility to IGF1R inhibition
Authors: Su-Chan Lee, Satoshi Nakata, Lujain Alaali, Kaixuan Wang, Pei-Chi Tsai, Khoa Pham, Brent A Orr, Quynh T Tran, Laura Asnaghi, Eric Raabe, Charles G Eberhart
Journal: Neuro-Oncology (2025)

Abstract Background BCL-6 corepressor (BCOR) loss of function alterations are common in clinically aggressive retinoblastoma. The study aim was to determine if BCOR loss promotes the growth and dissemination of retinoblastoma cells, and identify the pathways it regulates in these retinal tumors of childhood. Methods Gain and loss of function strategies were used to modulate BCOR levels in a panel of retinoblastoma cell lines, and the effects on proliferation, clonogenicity, apoptosis and migration were assessed in vitro and in murine xenograft models. Results BCOR knockdown or knockout in retinoblastoma lines with high protein levels increased tumor growth, invasion, clonogenicity and chemoresistance in vitro, while increased expression in low BCOR lines slowed growth. Growth of retinoblastoma xenografts was similarly sensitive to BCOR gain or loss. BCOR reduction resulted in upregulation of IGF1 and activation of IGF1 receptor (IGF1R) signaling, and the effects of IGF1R inhibition were dependent on BCOR level. In vitro, reduction of retinoblastoma growth and induction of apoptosis by the IGF1R inhibitors linsitinib and AEW541 was also significantly stronger in cells with low BCOR as compared to controls. Both linsitinib and AEW541 suppressed colony formation in a dose-dependent manner in BCOR knockout or knockdown cells. Finally, high BCOR levels rendered retinoblastoma xenografts insensitive to linsitinib. Conclusions Loss of BCOR function is associated with more aggressive retinoblastoma cell line growth and chemoresistance, at least in part due to increased IGF1R signaling. Inhibiting IGF1R pharmacologically had a marked anti-tumor effect in aggressive retinoblastoma lacking BCOR, suggesting it as a new therapeutic target, although this still needs to be confirmed in clinical samples with BCOR mutations.
Preventing and correcting polycystic ovary syndrome by targeting anti-Müllerian hormone signaling in minipuberty and adulthood in mice
Authors: Ludovica Cotellessa, Veronica Sobrino, Mauro S B Silva, Maxime Delit, Hélène Maitre, Emilie Caron, Gaëtan Ternier, Natalia da Silva Lima, Tori Lhomme, Frank Giton, Andrea Sorrentino, Laura Carraresi, Giovanna Di Nardo, Ruben Nogueiras, Manuel Tena-Sempere, Vincent Prevot, Paolo Giacobini
Journal: Cell Metabolism (2025)

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, causes significant reproductive and metabolic comorbidities, with no current cure. Gestational androgen and anti-Müllerian hormone (AMH) excess are linked to PCOS, and prenatal aberrant exposure to these hormones induces PCOS-like traits in animal models. However, whether the AMH effects on PCOS programming could extend to early postnatal life remains unknown. Clinical observations showed higher AMH levels during minipuberty in infants of mothers with PCOS, but whether this contributes to PCOS development is uncertain. Here, we show that exposure to high AMH levels during minipuberty in mice causes PCOS-like reproductive and metabolic defects in both sexes. A neutralizing antibody targeting AMH receptor 2 (AMHR2) prevented these defects when administered during minipuberty and alleviated symptoms when given in adulthood. These findings highlight the causal role of elevated AMH in PCOS and suggest AMHR2-targeting therapy as a potential preventive or curative approach.
Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC
Authors: Lorenza Rimassa, Stephen L Chan, Bruno Sangro, George Lau, Masatoshi Kudo, Maria Reig, Valeriy Breder, Min-Hee Ryu, Yuriy Ostapenko, Wattana Sukeepaisarnjaroen, Maria Varela, David Tougeron, Oxana V Crysler, Mohamed Bouattour, Tu Van Dao, Vincent C Tam, Adilson Faccio, Junji Furuse, Long-Bin Jeng, Yoon Koo Kang, Robin K Kelley, Michael J Paskow, Di Ran, Ioannis Xynos, John F Kurland, Alejandra Negro, Ghassan K Abou-Alfa
Journal: Journal of Hepatology (2025)
Bioadhesive drug-loaded microparticles prolong drug retention in the middle ear and ameliorate cisplatin-induced hearing loss
Authors: Zhi-Bin Zhou, Xue Bai, Zhi-Yong Zhou, Zi-Yue Lin, Bing Liao, Fei Gong, Mei-Qun Wang, Xu-Bo Chen, Yue-Hui Liu, Hong-Ping Chen, Kai Xu
Journal: Journal of Controlled Release (2025)
Efficacy and safety of izokibep in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study
Authors: Peter C. Taylor, Philip J. Mease, Kurt de Vlam, Shephard Mpofu, Dieter Wetzel, Anne M. Stevens, Brian Wiens, Lisa Osterling Koskinen, Sven Ohlman, Joachim Feldwisch, Fredrik Y. Frejd, Nikolai C. Brun, Jan Brandt-Juergens, Edit Drescher, Eva Dokoupilova, Anna Rowińska-Osuch, Nadia Abdel-Kader Martin, Frank Behrens
Journal: Annals of the Rheumatic Diseases (2025)
Endocrine Therapy Omission in Estrogen Receptor–Low (1%-10%) Early-Stage Breast Cancer
Authors: Grace M. Choong, Tanya L. Hoskin, Judy C. Boughey, James N. Ingle, Matthew P. Goetz
Journal: Journal of Clinical Oncology (2025)

PURPOSE Adjuvant endocrine therapy (ET) improves overall survival (OS) in estrogen receptor (ER)–positive early-stage breast cancer (BC). However, the benefit of ET for those with ER-low BC (ER 1%-10%) is unclear. METHODS Using the National Cancer Database, we studied patients with high-risk stage I to III, ER-low BC (defined as immunohistochemistry 1%-10%) who received (neo)adjuvant chemotherapy and did or did not initiate ET. OS was analyzed with ET initiation as a time-dependent covariate using Cox proportional hazards regression. RESULTS Of 10,362 patients with stage I to III ER-low BC, 7,018 received chemotherapy and met inclusion criteria. ET omission was 42% at 12 months and more common in patients with tumors that were progesterone receptor–negative, human epidermal growth factor receptor 2–negative, higher-grade (grade 2/3) and higher Ki-67 (≥20%; all P &lt; .001) and those who received neoadjuvant chemotherapy (NAC; P &lt; .001). With a median follow-up of 3 years, 586 deaths were observed. In a multivariable analysis, ET omission was associated with a higher risk of death (hazard ratio [HR], 1.23 [95% CI, 1.04 to 1.46]; P = .02), with a greater impact in those with higher ER levels: ER 1%-5% (HR, 1.15 [95% CI, 0.91 to 1.45]; P = .24) versus ER 6%-10% (HR, 1.42 [95% CI, 1.00 to 2.02]; P = .048). Among patients treated with NAC (n = 4,377, 62%), ET omission was associated with worse OS in those with residual disease (RD; HR, 1.26 [95% CI, 1.00 to 1.57]; P = .046) but not in those who achieved a pathologic complete response (HR, 1.06 [95% CI, 0.62 to 1.80]; P = .84). CONCLUSION In ER-low, early-stage BC, ET omission is associated with significantly worse OS, especially in patients with RD after NAC and those with higher (6%-10%) ER levels. Until prospective data are available, patients with ER-low BC should be counseled regarding the potential benefit of ET.