tbuckley/cabot-search huggingface dataset:
Asthma Alleviation by Ginsenoside Rb1 via Promotion of Treg Proliferation and Inflammatory T Cell Inhibition
Authors: Susanna Choi, Seung‐Ah Yoo, Kon‐Young Ji, Dong Ho Jung, Saseong Lee, Kang‐Gu Lee, Ki‐Myo Kim, Joo Young Lee, Myung‐A Jung, Bo‐Jeong Pyun, Jung Hur, Joon Young Choi, Chin Kook Rhee, Wan‐Uk Kim, Taesoo Kim
Journal: Allergy (2025)

ABSTRACT Background Regulatory T cells (Tregs) are living drugs with feasibility, tolerability, and therapeutic benefits. Although Tregs are linked to asthma prognosis through inflammation regulation, no therapeutic agents specifically designed to manage asthma by upregulating Tregs have been developed to date. Methods We screened a library of 250 natural products using a cytometric bead array. Among the selected candidates, gRb1 was identified for further investigation. The effects of gRb1 on Treg and Th17 populations were evaluated in mouse asthma models and human PBMCs from both healthy donors and asthma patients using flow cytometry and cytokine analysis. Results In inflammatory conditions, ginsenoside Rb1 (gRb1, a major ginseng component) increased IL‐10‐ and TGF‐β‐expressing Treg populations and decreased the Th17 population; activated phospho‐STAT5 and NFAT1 in Tregs; inhibited NFAT1 activation in conventional T cells (Tconvs); increased Treg proliferation and Tconv–Treg differentiation, inhibiting Tconv proliferation; and reduced inflammatory cytokine secretion by Tconvs. In asthma model mice, suppression of asthma symptoms by gRb1 was associated with elevated Treg and lower Th17, Th1, and Th2 counts. gRb1 treatment of stimulated PBMCs from patients with asthma and healthy donors increased IL‐10‐ and TGF‐β‐expressing Treg populations and decreased IL‐17A‐, IL‐22‐, IFN‐γ‐, and TNF‐α‐expressing T‐cell populations. Conclusions gRb1 alleviate asthma by shifting the Treg–inflammatory T cell balance. These findings suggest a strategy for enhancing Treg activity through treatment with gRb1. This may provide a novel therapeutic approach for asthma and related disorders.
Early‐Life Quarantine Increases the Development of Infant Atopic Dermatitis: A Birth Cohort Study in China
Authors: Yi Hu, Jiuru Zhao, Qianwen Shen, Dongjian Yang, Wei Li, Ze Chen, Meng Ni, Baihe Li, Zhenying Lin, Chunyu Cheng, Dongting Yao, Qianqian Zhang, Xiaorui Liu, Hong Li, Xiaoyi Huang, Zheng Tang, Zhiwei Liu
Journal: Allergy (2025)
Patient‐Reported Outcomes in the Phase III OASIS‐HAE Study of Donidalorsen for Hereditary Angioedema
Authors: Marc A. Riedl, Aaron Yarlas, Laura Bordone, Sabrina Treadwell, Sophie Wang, Kenneth B. Newman, Danny M. Cohn
Journal: Allergy (2025)

ABSTRACT Background Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, frequently severe swelling that negatively impacts patients' quality of life (QoL). In the phase III OASIS‐HAE study (NCT05139810), donidalorsen reduced HAE attack rate, increased disease control, and improved QoL. Here, we report further analysis of donidalorsen's impact on QoL and other patient‐reported outcomes (PROs). Methods This double‐blind, placebo‐controlled study randomized patients with HAE to donidalorsen 80 mg or placebo once every 4 (Q4W) or 8 weeks (Q8W) over 24 weeks. PROs included Angioedema (AE)‐QoL Questionnaire, Angioedema Control Test (AECT), Patient Global Impression of Severity (PGIS), and Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions (WPAI+CIQ). Results Ninety patients received donidalorsen Q4W ( n = 45), donidalorsen Q8W ( n = 23), or placebo ( n = 22). A larger percentage of the donidalorsen Q4W group (88%) achieved clinically meaningful improvement (≥ 6‐point reduction) in AE‐QoL total score vs. placebo (45%). Both donidalorsen groups reported larger least‐squares mean (LSM) changes from baseline to week 24 vs. placebo in AE‐QoL functioning (difference: Q4W, −24.5; Q8W, −16.1), fears/shame (Q4W, −23.9; Q8W, −20.1), and nutrition (Q4W, −15.7; Q8W, −10.7) domains. Donidalorsen improved AECT scores vs. placebo (difference: Q4W, 6.0; Q8W, 4.1). A greater proportion of the donidalorsen Q4W group reported decreased disease severity vs. the placebo group (PGIS; 82% vs. 44%). Donidalorsen Q4W showed benefits vs. placebo in the presenteeism, overall work/school impairment, and activity impairment domains of the WPAI+CIQ. Conclusions Donidalorsen significantly improved QoL and other PROs vs. placebo in patients with HAE.
Developments of radioligands with an albumin-binding moiety of 4-(P-Iodophenyl) butyric acid
Authors: Lingxin Meng, Jianyang Fang, Xiaoru Lin, Rongqiang Zhuang, Lumei Huang, Yesen Li, Xianzhong Zhang, Zhide Guo
Journal: Journal of Controlled Release (2025)
Role of gut microbiome in suppression of cancers
Authors: Yao Xu, Zhaoyu Gao, Jiaying Liu, Qianqian Yang, Shunjiang Xu
Journal: Gut Microbes (2025)

The pathogenesis of cancer is closely related to the disruption of homeostasis in the human body. The gut microbiome plays crucial roles in maintaining the homeostasis of its host throughout lifespan. In recent years, a large number of studies have shown that dysbiosis of the gut microbiome is involved in the entire process of cancer initiation, development, and prognosis by influencing the host immune system and metabolism. Some specific intestinal bacteria promote the occurrence and development of cancers under certain conditions. Conversely, some other specific intestinal bacteria suppress the oncogenesis and progression of cancers, including inhibiting the occurrence of cancers, delaying the progression of cancers and boosting the therapeutic effect on cancers. The promoting effects of the gut microbiome on cancers have been comprehensively discussed in the previous review. This article will review the latest advances in the roles and mechanisms of gut microbiome in cancer suppression, providing a new perspective for developing strategies of cancer prevention and treatment.
Minimization or withdrawal of oral pharmacotherapy in chronic heart failure patients with improved myocardial function: A systematic review
Authors: Yuxiang Luo, Wenbin Xiao, Yusuf Z. Sener, Wouter C. Meijers, Robert M.A. van der Boon, Elfatih A. Hasabo, Osama Soliman, Rudolf A. de Boer, Kadir Caliskan
Journal: European Journal of Heart Failure (2025)

Abstract Aims The necessity of lifelong treatment and polypharmacy in chronic heart failure (HF) patients with improved myocardial function remains debated. This systematic review aims to synthesize current literature regarding this issue. Methods and results A systematic literature search was performed in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from the inception to 18 October 2024. Seven studies ( n = 552) reporting minimization or withdrawal of pharmacotherapy in chronic HF patients with improved ejection fraction or stable New York Heart Association status were included. Findings were heterogeneous due to variations in study design and protocols. Loop diuretic withdrawal was favoured by one non‐randomized study ( n = 26) and one randomized controlled trial (RCT) ( n = 188). Minimization of angiotensin receptor–neprilysin inhibitors ( n = 77) or withdrawal of mineralocorticoid receptor antagonists (MRA) ( n = 70) was not favourable. Carvedilol monotherapy was favoured by one small‐sample RCT ( n = 60). One RCT ( n = 51) reported a high overall relapse rate (65%) following multiple drug withdrawal in recovered patients with dilated cardiomyopathy. Another RCT ( n = 80) found a low occurrence of cardiac dimensional deterioration (7.5%) following multiple drug withdrawal in post‐cardiac resynchronization therapy patients with normalized ejection fraction. However, 28% required drug re‐initiation due to cardiac comorbidities. Conclusion The existing evidence on minimizing or withdrawing oral pharmacotherapy in chronic HF patients with improved myocardial function remains very limited and heterogeneous, supporting only loop diuretic withdrawal and possibly carvedilol monotherapy, but not the minimization or withdrawal of renin–angiotensin system inhibitors, MRA, or the combination of HF medications. Large RCTs are needed to determine the appropriate treatment strategy.
One for multiple: Physics-informed synthetic data boosts generalizable deep learning for fast MRI reconstruction
Authors: Zi Wang, Xiaotong Yu, Chengyan Wang, Weibo Chen, Jiazheng Wang, Ying-Hua Chu, Hongwei Sun, Rushuai Li, Peiyong Li, Fan Yang, Haiwei Han, Taishan Kang, Jianzhong Lin, Chen Yang, Shufu Chang, Zhang Shi, Sha Hua, Yan Li, Juan Hu, Liuhong Zhu, Jianjun Zhou, Meijing Lin, Jiefeng Guo, Congbo Cai, Zhong Chen, Di Guo, Guang Yang, Xiaobo Qu
Journal: Medical Image Analysis (2025)
MicroRNA-loaded Antioxidant Nanoplatforms for Prevention and Treatment of Experimental Acute and Chronic Uveitis
Authors: Siting Sheng, Huiling Zhao, Lirui Liu, Dan Chen, Xingdi Wu, Chujun Liu, Xinyu Ma, Jing-Wei Xu, Jian Ji, Haijie Han, Wen Xu
Journal: Biomaterials (2025)
Reversible downregulation of HLA class I in adenoid cystic carcinoma
Authors: Annie Li, Bianca L Gonda, Elizabeth M Codd, Adam von Paternos, Dawn R Mitchell, Markus D Herrmann, Prinjali Kalyan, Samantha E Flynn, Thuc Q Dzu, Chengzhuo Gao, Edwin Zhang, Julia J Mendel, Julia C Thierauf, Peter M Sadow, Thomas Denize, Diane Yang, Florian J Fintelmann, Jo Anne Fordham, Ross D Merkin, Atul K Bhan, Yu-Chung Huang, Jeffrey Raizer, William C Faquin, Daniel L Faden, Xin Gao, Jong Chul Park, Lori J Wirth, Stefan T Kaluziak, A John Iafrate
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Adenoid cystic carcinoma (ACC) is a rare, but lethal cancer with low response rates to systemic therapies, such as cytotoxic chemotherapy and immune-checkpoint inhibitors (ICIs). Despite extensive clinical trials, no effective treatments for patients with recurrent or metastatic ACC are available, and ACC mortality rates remain poor. Methods We employed automated multiplex immunofluorescence (mIF), single-cell RNA sequencing (scRNA-seq) Gene Expression analysis, RNA in-situ hybridization, and spatial transcriptomics analysis to characterize the immune landscape of ACC tumors, ACC metastasis, and normal tissues from regions where ACCs arise. Based on results from these studies, we treated freshly resected ACCs with interferon-γ or a stimulator of the interferon genes (STING) agonist in vitro. Additionally, we included one patient with ACC in a phase 1 clinical study of a novel STING agonist (dazostinag) plus pembrolizumab. Results The mIF analysis revealed that ACC tumors are immunologically “cold”, with few tumor-infiltrating T-lymphocytes and low programmed death-ligand 1 (PD-L1) expression. The most striking finding was a very low beta-2-microglobulin (B2M) expression in nearly all ACCs, with only focal expression found in some ACC metastases. mIF and RNA sequencing analyses of normal salivary gland and breast tissues revealed a p63+, NFIB+, basal duct cell population, with similarly low B2M/human leukocyte antigen (HLA) class I expression. Spatial transcriptomics analysis of the focally B2M-positive ACC metastases uncovered the genetic pathway driving upregulation of B2M, an interferon-γ program mediating the reintroduction of HLA-I/B2M; the significantly upregulated genes included IRF1, GBP1, and TAP1 . On short-term treatment of primary ACC tissues in vitro with interferon-γ or a STING agonist, we observed strongly upregulated HLA class I/B2M expression. Moreover, treatment of a patient with recurrent, metastatic breast ACC with a STING agonist and pembrolizumab led to a partial response with a 70% tumor reduction. Conclusions Low B2M/HLA class I expression may explain why ACCs are immunologically cold and the lack of response to ICIs. Our findings suggest that the normal cell of ACC origin exists in a B2M/HLA-class I low state, and that pharmacologic manipulation with immune activators, such as STING agonists, can restore HLA/B2M in ACCs, as supported by the promising response observed in a patient with metastatic ACC. These findings indicate a potential path to urgently needed immunotherapies.
MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence
Authors: Margaux Tual, Angélique Bellemare-Pelletier, Susan Moore, Delphine Guipouy, Negar Farzam-Kia, Leila Jafarzadeh, Jordan Quenneville, Benoit Barrette, Marc K Saba-El-Leil, Jean-Sebastien Delisle, Etienne Gagnon
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Chimeric antigen receptor T cell (CAR-T)-based immunotherapies have reshaped the therapeutic landscape of cancer treatment, in particular for patients afflicted with leukemia. However, defects in CAR behaviors and clinical complications have hindered their widespread application across diverse cancer types. Chief among these defects is high tonic signaling, absent in native activating immune receptors, which accelerates T cell exhaustion and undermines treatment efficacy. We hypothesized that these limitations arise because current CAR architectures fail to replicate the modular design of native activating immune receptors, which integrate distinct receptor and signaling modules. This modular assembly is crucial for maintaining proper receptor regulation and function. Methods Therefore, we set forth to develop a modular chimeric antigen receptor leveraging the same assembly principles found in native activating immune receptors to reestablish the intrinsic safeguards in receptor expression and signaling. Results The resulting Modular Actuation Receptor Complex (MARC) displayed surface expression levels akin to its native immune receptor counterpart, the NK cell receptor KIR2DS3, while eliminating tonic signaling. In a clinically relevant mouse leukemia model, MARC-T cells exhibited remarkable long-term persistence and a less exhausted phenotype compared with conventional CAR-T cells. Conclusions With its modular architecture, the MARC offers unparalleled opportunities for optimization and broad applicability across different cell types, paving the way for transformative advancements in cell-based therapies. This innovation holds immense promise as a next-generation therapeutic tool in clinical settings.
Discovery and validation of frameshift-derived neopeptides in Lynch syndrome: paving the way for novel cancer prevention strategies
Authors: Cristina Bayó, Giancarlo Castellano, Fátima Marín, Joaquín Castillo-Iturra, Teresa Ocaña, Hardeep Kumari, Maria Pellisé, Leticia Moreira, Liseth Rivero, Maria Daca-Alvarez, Oswaldo Ortiz, Sabela Carballal, Rebeca Moreira, Julia Canet-Hermida, Marta Pineda, Capella Gabriel, Georgina Flórez-Grau, Manel Juan, Daniel Benitez-Ribas, Francesc Balaguer
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Lynch syndrome (LS), caused by germline pathogenic variants in the mismatch repair genes, leads to high rates of frameshift-derived neopeptide (FSDN) expression due to microsatellite instability (MSI). While colorectal cancer (CRC) prevention is effective, most LS-related tumors lack such strategies. Cancer vaccines targeting FSDNs offer a promising approach for immune interception in LS. This study aimed to identify and validate LS-related FSDNs to develop vaccines for cancer prevention. Methods We identified LS-related coding MS mutations and predicted FSDN with high coverage on common Human Leukocyte Antigen (HLA)-I and II alleles. We validated FSDN-associated mutations in colorectal adenomas (CrAD), endometrial cancers (EC), and CRC samples from patients with LS, non-LS tumors, and cell lines. Immunogenicity was assessed through interferon (IFN)-γ enzyme-linked immunospot and flow cytometry analysis of tissue-infiltrating lymphocytes (TILs) from LS carriers. Results We prioritized 53 HLA-I and 45 HLA-II FSDNs in MSI tumors using in silico predictions. Validation revealed 86.7% of FSDN-associated mutations present in LS-CRC samples, with a median of 7.67 (6.5–9) mutations in CrADs and 6.02 (2–10) in CRCs. Sequencing of CrAD and EC samples showed 95% and 77.5% of predicted FSDN-associated mutations, respectively. MSI cancer cell lines transcribed 69.8% of FSDNs. Immunogenicity assays showed that 71% of potential FSDNs elicited IFN-γ responses, with a median of 7.37 (1–10.75) HLA-I and 6 (2–5.75) HLA-II FSDNs per patient. After prioritizing 24 FSDN, in a cohort of 19 LS-derived samples (4 CrAD and 15 normal mucosa), 52% (10/19) demonstrated T-cell reactivity to an HLA-I neoantigen pool. CD8+CD137+ activation markers increased significantly (p=0.037) over time and peptide-specific cells were detected by pentamer staining. Conclusions Our predicted FSDN set has optimal coverage among LS carriers and can induce IFN-γ inflammatory responses in LS-derived TILs, offering an opportunity for vaccine development.
Therapeutic Potential of Centhaquine Citrate, a Selective Alpha-2B Adrenoceptor Agonist, in the Management of Circulatory Shock
Authors: Matthieu Legrand, Amaresh Ranjan, Shruthi Rammohan, Daniel De Backer, Marlies Ostermann, Anil Gulati, Jean-Louis Vincent, Ashish K Khanna
Journal: Drugs (2025)
Unravelling the causality between inflammatory bowel disease and polycystic ovary syndrome mediated by gut microbiota and blood metabolism: insights from two prospective cohort studies
Authors: Zhaoman Wan, Xueyu Hao, Feiling Huang, Hanqiao Dai, Yubo Fan, Tianyao Chu, Hongyan Chen, Min Cui, Hong Yang, Xinlei Zhang, Rong Chen, Peng Zhang
Journal: Gut (2025)
A Common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice
Authors: Cristina Bodas, Irene Felipe, Brice Chanez, Miguel Lafarga, Evangelina Lopez de Maturana, Jaime Martinez de Villarreal, Natalia Del Pozo, Marina Malumbres, Pierfrancesco Vargiu, Ana Cayuela, Isabel Peset, Katelyn Connelly, Jason Hoskins, Raúl Méndez, Laufey Amundadottir, Núria Malats, Sagrario Ortega, Francisco X Real
Journal: Gut (2025)

Background Genome-wide association studies have identified an exon 6 CTRB2 deletion variant proposed to increase pancreatic cancer risk. Objective To acquire evidence on its causal role, we developed and analysed a new mouse strain carrying an equivalent variant in Ctrb1 , the mouse CTRB2 orthologue. Design We used CRISPR/Cas9 to introduce a 707 bp deletion encompassing Ctrb1 exon 6 ( Ctrb1 Δexon6 ). This mutation closely mimics the human variant. Mice carrying the mutant allele were profiled at 3 months to assess their phenotype. Results Ctrb1 Δexon6 mutant mice express a truncated CTRB1 that accumulates in the endoplasmic reticulum (ER). The pancreas of homozygous mutant mice displays reduced chymotrypsin activity, total protein synthesis and amylase secretion. The histological aspect of the pancreas is inconspicuous but ultrastructural analysis shows evidence of dramatic ER stress and cytoplasmic and nuclear inclusions. Transcriptomic studies of the mutant pancreas reveal downregulation of the acinar programme and increased activity of ER stress-related and inflammatory pathways. Agr2 is one of the most upregulated genes in mutant pancreata. Heterozygous mice have an intermediate phenotype. Ctrb1 Δexon6 mutant mice exhibit impaired recovery from acute caerulein-induced pancreatitis. Administration of tauroursodeoxycholic acid or sulindac partially alleviates the phenotype. A transcriptomic signature derived from the mutant pancreata is significantly enriched in normal human pancreas of CTRB2 exon 6 deletion variant carriers from the GTEx cohort. Conclusions This mouse strain provides evidence that the exon 6 deletion causes ER stress and inflammation and is an excellent model to understand its contribution to pancreatic cancer and identify preventive strategies.
Prognostic Significance of Volumetric Parameters on Pretreatment FDG PET/CT in Patients With Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab Therapy
Authors: Jeong Won Lee, Sang Mi Lee, Beodeul Kang, Jung Sun Kim, Chansik An, Hong Jae Chon, Su Jin Jang
Journal: Clinical Nuclear Medicine (2025)

Background: This study aimed to assess prognostic significance of FDG PET/CT parameters in predicting progression-free survival (PFS) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab therapy. Patients and Methods: We retrospectively enrolled 78 patients with HCC who underwent FDG PET/CT before atezolizumab plus bevacizumab therapy and identified intrahepatic target tumor lesions on pretreatment imaging studies. From PET/CT images, we measured SUVmax, tumor-to-normal liver uptake ratio, metabolic tumor volume, and total lesion glycolysis (TLG) for intrahepatic tumor lesions, as well as SUVmax for extrahepatic metastatic lesions (extrahepatic SUVmax). Results: In comparisons of PET/CT parameters, patients with progressive disease demonstrated significantly higher TLG values than those achieving complete or partial response ( P &lt; 0.05). In the multivariate survival analysis, TLG independently predicted both PFS ( P = 0.019) and OS ( P = 0.003). Metabolic tumor volume was significantly associated with OS alone ( P = 0.010), and extrahepatic SUVmax was significantly associated with only PFS ( P = 0.045). Patients with high TLG values experienced poorer PFS and OS than those with low TLG values ( P &lt; 0.05). Conclusions: TLG in intrahepatic HCC lesions was significantly associated with treatment response and served as an independent prognostic factor for PFS and OS. TLG could be a potential imaging biomarker for predicting clinical outcomes in patients with HCC receiving atezolizumab plus bevacizumab therapy.
Analysis of the prespecified FIDELITY pooled patient dataset examined the efficacy and safety of finerenone in patients with an acute change in estimated glomerular filtration rate.
Authors: Sankar D Navaneethan, Stefan D Anker, Gerasimos Filippatos, Bertram Pitt, Peter Rossing, Luis M Ruilope, Phyllis August, Meike Brinker, Andrea Lage, Luke Roberts, Charlie Scott, Pantelis Sarafidis
Journal: Kidney International (2025)
Targeted delivery of IL-21 neutralizing nanotherapeutics to lymph nodes and kidney allografts attenuates B cell alloimmunity.
Authors: Hengcheng Zhang, Gianmarco Sabiu, Sungwook Jung, Manuel A Podestà, Jing Zhao, Maya Gempler, Minako Yamamura, Jinxu Miao, George C Tsokos, Ahmad Karadagi, Tatsuo Kawai, Reza Abdi, Peter T Sage
Journal: Kidney International (2025)