tbuckley/cabot-search huggingface dataset:
Tumor Vascular Occlusion by Calcium-based Thermosensitizer Provokes Continuous Cavitation Effect and Thermal Energy Transition Efficiency of Radiofrequency Ablation Therapy
Authors: Guichun Zeng, Xiayi Liang, Yuan Ling, Xiaoqi Zhu, Qin Wang, Zelun Li, Junjie Liu, Xiaobo Wang, Guanhua Qiu, Kangning Yan, Duo Wang, Jie Chen
Journal: Biomaterials (2024)
Engineering M2 Macrophage-Derived Exosomes Modulate Activated T Cell Cuproptosis to Promote Immune Tolerance in Rheumatoid Arthritis
Authors: Guoquan Wu, Tianyu Su, Peng Zhou, Rongze Tang, Xu Zhu, Jin Wang, Minghao Chao, Liying Fan, Hanrong Yan, Peng Ye, Dehong Yu, Fenglei Gao, Hongliang Chen
Journal: Biomaterials (2024)
How active cholesterol coordinates cell cholesterol homeostasis: Test of a hypothesis
Authors: Yvonne Lange, Theodore L Steck
Journal: Progress in Lipid Research (2024)

How do cells coordinate the diverse elements that regulate their cholesterol homeostasis? Our model postulates that membrane cholesterol forms simple complexes with bilayer phospholipids. The phospholipids in the plasma membrane are of high affinity; consequently, they are fully complexed with the sterol. This sets the resting level of plasma membrane cholesterol. Cholesterol in excess of the stoichiometric equivalence point of these complexes has high chemical activity; we refer to it as active cholesterol. It equilibrates with the low affinity phospholipids in the intracellular membranes where it serves as a negative feedback signal to a manifold of regulatory proteins that rein in ongoing cholesterol accretion. We tested the model with a review of the literature regarding fourteen homeostatic proteins in enterocytes. It provided strong albeit indirect support for the following hypothesis. Active cholesterol inhibits cholesterol uptake and biosynthesis by suppressing both the expression and the activity of the gene products activated by SREBP-2; namely, HMGCR, LDLR and NPC1L1. It also reduces free cell cholesterol by serving as the substrate for its esterification by ACAT and for the synthesis of side-chain oxysterols, 27-hydroxycholesterol in particular. The oxysterols drive cholesterol depletion by promoting the destruction of HMGCR and stimulating sterol esterification as well as the activation of LXR. The latter fosters the expression of multiple homeostatic proteins, including four transporters for which active cholesterol is the likely substrate. By nulling active cholesterol, the manifold maintains the cellular sterol at its physiologic set point.
Peripheral tumor necrosis factor production is a predictor for remission under adalimumab in Crohn’s disease
Authors: Bosse Jessen, Marcell T. Tordai, I. Freise, J.J. Staudacher, L.M. Haag, L. Kredel, M. Schumann, C. Weidinger, E. Sonnenberg, Britta Siegmund
Journal: Clinical Gastroenterology and Hepatology (2024)
CaCO3-encircled hollow CuS nanovehicles to suppress cervical cancer through enhanced calcium overload-triggered mitochondria damage
Authors: Pengfei Wang, Xichen Sun, Liuyan Tang, Ningning Li, Qing Wang, Bicheng Gan, Yuezhou Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Cervical cancer stands is a formidable malignancy that poses a significant threat to women's health. Calcium overload, a minimally invasive tumor treatment, aims to accumulate an excessive concentration of Ca
Biomimetic nanoparticles co-deliver hirudin and lumbrukinase to ameliorate thrombus and inflammation for atherosclerosis therapy
Authors: Mengying Cheng, Tianxiang Yue, Hong Wang, Lai Jiang, Qiaoling Huang, Fanzhu Li
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most likely leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the dynamic pathological development of AS, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn2+. HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects, including alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.
Transcriptional regulatory program controlled by MYB in T-cell acute lymphoblastic leukemia
Authors: Xiaoman Shao, Rui Yokomori, Jolynn Zu Lin Ong, Haoqing Shen, Dennis Kappei, Leilei Chen, Allen Eng Juh Yeoh, Shi Hao Tan, Takaomi Sanda
Journal: Leukemia (2024)
Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study
Authors: Chien-Chih Chou, Ssu-Yu Pan, Yi-Jing Sheen, Jun-Fu Lin, Ching-Heng Lin, Hui-Ju Lin, I-Jong Wang, Chien-Hsiang Weng
Journal: Ophthalmology (2024)
Repeated shifts in sociality are associated with fine-tuning of highly conserved and lineage-specific enhancers in a socially flexible bee
Authors: Beryl M Jones, Andrew E Webb, Scott M Geib, Sheina Sim, Rena M Schweizer, Michael G Branstetter, Jay D Evans, Sarah D Kocher
Journal: Molecular Biology and Evolution (2024)

Comparative genomic studies of social insects suggest that changes in gene regulation are associated with evolutionary transitions in social behavior, but the activity of predicted regulatory regions has not been tested empirically. We used STARR-seq, a high-throughput enhancer discovery tool, to identify and measure the activity of enhancers in the socially variable sweat bee, Lasioglossum albipes. We identified over 36,000 enhancers in the L. albipes genome from three social and three solitary populations. Many enhancers were identified in only a subset of L. albipes populations, revealing rapid divergence in regulatory regions within this species. Population-specific enhancers were often proximal to the same genes across populations, suggesting compensatory gains and losses of regulatory regions may preserve gene activity. We also identified 1182 enhancers with significant differences in activity between social and solitary populations, some of which are conserved regulatory regions across species of bees. These results indicate that social trait variation in L. albipes is associated with the fine-tuning of ancient enhancers as well as lineage-specific regulatory changes. Combining enhancer activity with population genetic data revealed variants associated with differences in enhancer activity and identified a subset of differential enhancers with signatures of selection associated with social behavior. Together, these results provide the first empirical map of enhancers in a socially flexible bee and highlight links between cis-regulatory variation and the evolution of social behavior.
A phase 3 randomized trial of sulopenem vs. ertapenem in patients with complicated intraabdominal infections
Authors: Michael W. Dunne, Steven I. Aronin, Anita F. Das, Karthik Akinapelli, Jeanne D. Breen, Michael T. Zelasky, Sailaja Puttagunta
Journal: Clinical Microbiology and Infection (2024)
Recent advances in reactive oxygen species (ROS)-responsive drug delivery systems for photodynamic therapy of cancer
Authors: Danrong Hu, Yicong Li, Ran Li, Meng Wang, Kai Zhou, Chengqi He, Quan Wei, Zhiyong Qian
Journal: Acta Pharmaceutica Sinica B (2024)

Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) have garnered significant attention in cancer research because of their potential for precise spatiotemporal drug release tailored to high ROS levels within tumors. Despite the challenges posed by ROS distribution heterogeneity and endogenous supply constraints, this review highlights the strategic alliance of ROS-responsive DDSs with photodynamic therapy (PDT), enabling selective drug delivery and leveraging PDT-induced ROS for enhanced therapeutic efficacy. This review delves into the biological importance of ROS in cancer progression and treatment. We elucidate in detail the operational mechanisms of ROS-responsive linkers, including thioether, thioketal, selenide, diselencide, telluride and aryl boronic acids/esters, as well as the latest developments in ROS-responsive nanomedicines that integrate with PDT strategies. These insights are intended to inspire the design of innovative ROS-responsive nanocarriers for enhanced cancer PDT.
The R.O.A.D. to precision medicine
Authors: Dimitris Bertsimas, Angelos Georgios Koulouras, Georgios Antonios Margonis
Journal: npj Digital Medicine (2024)

Abstract We propose a novel framework that addresses the deficiencies of Randomized clinical trial data subgroup analysis while it transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision medicine. Our approach counters the effects of unobserved confounding in observational data through a two-step process that adjusts predicted outcomes under treatment. These adjusted predictions train decision trees, optimizing treatment assignments for patient subgroups based on their characteristics, enabling intuitive treatment recommendations. Implementing this framework on gastrointestinal stromal tumors (GIST) data, including genetic sub-cohorts, showed that our tree recommendations outperformed current guidelines in an external cohort. Furthermore, we extended the application of this framework to RCT data from patients with extremity sarcomas. Despite initial trial indications of universal treatment necessity, our framework identified a subset of patients who may not require treatment. Once again, we successfully validated our recommendations in an external cohort.
Symbiotic probiotic communities with multiple targets successfully combat obesity in high-fat-diet-fed mice
Authors: Dingming Guo, Yun Deng, Qianqian Yang, Min Li, Xiangfeng Wang, Xuchun Wan, Junqing He, Ying Xu, Wenxin Huang, Guohua Lin, Ya Xu, Yi Sun, Ruilin Zhang, Wei-Hua Chen, Zhi Liu
Journal: Gut Microbes (2024)

Probiotics hold great potential for treating metabolic diseases such as obesity. Given the complex and multifactorial nature of these diseases, research on probiotic combination with multiple targets has become popular. Here, we choose four obesity-related targets to perform high-throughput screening, including pancreatic lipase activity, bile salt hydrolase activity, glucagon-like peptide-1 secretion and adipocyte differentiation. Then, we obtained 649 multi-strain combinations with the requirement that each must cover all these targets in principle. After in vitro co-culture and in vivo co-colonization experiments, only four (<0.7%) combinations were selected as symbiotic probiotic communities (SPCs). Next, genome-scale metabolic model analysis revealed that these SPCs showed lower metabolic resource overlap and higher metabolic interaction potential involving amino acid metabolism (Ammonium, L−Lysine, etc.) and energy metabolism (Phosphate, etc.). Further animal experiments demonstrated that all SPCs exhibited a good safety profile and excellent effects in improving obesity and associated glucose metabolism disruptions and depression-like behaviors in high-fat-diet-fed mice. This anti-obesity improvement was achieved through reduced cholesterol level, fat accumulation and inhibited adipocyte differentiation. Taken together, our study provides a new perspective for designing multi-strain combinations, which may facilitate greater therapeutic effect on obesity and other complex diseases in the future.
Immunometabolism: signaling pathways, homeostasis, and therapeutic targets
Authors: Rongrong Xu, Xiaobo He, Jia Xu, Ganjun Yu, Yanfeng Wu
Journal: MedComm (2024)

Abstract Immunometabolism plays a central role in sustaining immune system functionality and preserving physiological homeostasis within the organism. During the differentiation and activation, immune cells undergo metabolic reprogramming mediated by complex signaling pathways. Immune cells maintain homeostasis and are influenced by metabolic microenvironmental cues. A series of immunometabolic enzymes modulate immune cell function by metabolizing nutrients and accumulating metabolic products. These enzymes reverse immune cells’ differentiation, disrupt intracellular signaling pathways, and regulate immune responses, thereby influencing disease progression. The huge population of immune metabolic enzymes, the ubiquity, and the complexity of metabolic regulation have kept the immune metabolic mechanisms related to many diseases from being discovered, and what has been revealed so far is only the tip of the iceberg. This review comprehensively summarized the immune metabolic enzymes’ role in multiple immune cells such as T cells, macrophages, natural killer cells, and dendritic cells. By classifying and dissecting the immunometabolism mechanisms and the implications in diseases, summarizing and analyzing advancements in research and clinical applications of the inhibitors targeting these enzymes, this review is intended to provide a new perspective concerning immune metabolic enzymes for understanding the immune system, and offer novel insight into future therapeutic interventions.
An inflammatory cytokine signature predicts IgA nephropathy severity and progression
Authors: Lei Chen, Xizhao Chen, Guangyan Cai, Hongli Jiang, Xiangmei Chen, Min Zhang
Journal: MedComm (2024)

Abstract IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, resulting in end‐stage renal disease and increased mortality rates. Prognostic biomarkers reflecting molecular mechanisms for effective IgAN management are urgently needed. Analysis of kidney single‐cell transcriptomic sequencing data demonstrated that IgAN expressed high‐expression levels of inflammatory cytokines TNFSF10, TNFSF12, CCL2, CXCL1, and CXCL12 than healthy controls (HCs). We also measured the urine proteins in 120 IgAN (57 stable and 63 progressive) and 32 HCs using the proximity extension assay (PEA), and the multivariable and least absolute shrinkage and selection operator (LASSO) logistic regression analysis both revealed that CXCL12, MCP1 were the prognostic significant variables to predict IgAN progression severity. These two proteins exhibited negative correlation with the estimated glomerular filtration rate (eGFR) and patients with higher expression levels of these two proteins had a higher probability to have poorer renal outcome. We further developed a risk index model utilizing CXCL12, MCP1, and baseline clinical indicators, which achieved an impressive area under the curve (AUC) of 0.896 for prediction of IgAN progression severity. Our study highlights the significance of the inflammatory protein biomarkers for noninvasive prediction of IgAN severity and progression, offering valuable insights for clinical management.
Single‐cell transcriptomics reveals IRF7 regulation of the tumor microenvironment in isocitrate dehydrogenase wild‐type glioma
Authors: Jinwei Li, Shengrong Long, Zhang Yang, Wei Wei, Shuangqi Yu, Quan Liu, Xuhui Hui, Xiang Li, Yinyan Wang
Journal: MedComm (2024)

Abstract Mutations in isocitrate dehydrogenase (IDH) are important markers of glioma prognosis. However, few studies have examined the gene expression regulatory network (GRN) in IDH‐mutant and wild‐type gliomas. In this study, single‐cell RNA sequencing and spatial transcriptome sequencing were used to analyze the GRN of cell subsets in patients with IDH‐mutant and wild‐type gliomas. Through gene transcriptional regulation analysis, we identified the M4 module, whose transcription factor activity is highly expressed in IDH wild‐type gliomas compared to IDH‐mutants. Enrichment analysis revealed that these genes were predominantly expressed in microglia and macrophages, with significant enrichment in interferon‐related signaling pathways. Interferon regulatory factor 7 (IRF7), a transcription factor within this pathway, showed the highest percentage of enrichment and was primarily localized in the core region of wild‐type IDH tumors. A machine‐learning prognostic model identified novel subgroups within the wild‐type IDH population. Additionally, IRF7 was shown to promote the proliferation and migration of T98G and U251 cells in vitro, and its knockdown affected glioma cell proliferation in vivo. This study systematically established the regulatory mechanism of IDH transcriptional activity in gliomas at the single‐cell level and drew a corresponding cell map. The study presents a transcriptional regulatory activity map for IDH wild‐type gliomas, involving single‐cell RNA sequencing and spatial transcriptomics to identify gene regulatory networks, machine learning models for IDH subtyping, and experimental validation, highlighting the role of IRF7 in glioma progression.
Prognostic impact of age on outcomes of hepatic decompensation in patients with compensated cirrhosis (CHESS2102): an international, multicenter cohort study
Authors: Shanghao Liu, Jia Li, Yujun Wong, Hyung Joon Yim, Masashi Hirooka, Hirayuki Enomoto, Qing Xie, Erhei Dai, Amr Shaaban Hanafy, Zhujun Cao, Lili Zhao, Kok Ban Teh, Tae Hyung Kim, Young Kul Jung, Yohei Koizumi, Yoichi Hiasa, Takashi Nishimura, Hiroko Iijima, Qingyi Tian, Xinru Guo, Yansheng Jia, Jinfang Sun, Chuan Liu, Xiaolong Qi
Journal: MedComm (2024)

Abstract Baveno VII criteria (B7C) and Baveno VI criteria (B6C) have been widely used to estimate the risk of hepatic decompensation. However, the impact of age on these criteria warrants further investigation. The international, multicenter cohort study included 1138 patients with compensated cirrhosis (median follow‐up of 40.6 months), aiming to evaluate the value of age in predicting hepatic decompensation. We identified age as an independent predictor of hepatic decompensation, with 60 years determined as the optimal cut‐off value. The occurrence of decompensation was 18.7% and 6.7% in the older (age ≥60 years) and younger (age &lt;60 years) groups, respectively ( p &lt; 0.001). We subsequently integrated age into the existing Baveno criteria. In patients not meeting Baveno criteria (defined as not meeting B6C or B7C), the older group exhibited a significantly elevated risk of decompensation compared to the younger group ( p &lt; 0.05). However, no significant difference was observed between the older and younger groups in patients meeting Baveno criteria ( p &gt; 0.05). In conclusion, our study demonstrated that integrating age into the Baveno criteria could enhance the assessment of hepatic decompensation. Age should be considered before discharging patients with compensated cirrhosis from the surveillance of hepatic decompensation.
Resolving the CD4-testing crisis to help end AIDS-related deaths
Authors: Omar Syarif, Rita Oladele, Tinne Gils, Radha Rajasingham, Jonathan Falconer, Pamela Achii, Edna Tembo, Donald Denis Tobaiwa, Kenneth Mwehonge, Charlotte Schutz, Nelesh P Govender, Graeme Meintjes, David B Meya, Angela Loyse
Journal: The Lancet Global Health (2024)
Myeloid subsets impede the efficacy of anti-PD1 therapy in patients with advanced gastric cancer (WJOG10417GTR study)
Authors: Hirokazu Shoji, Chie Kudo-Saito, Kengo Nagashima, Hiroshi Imazeki, Kai Tsugaru, Naoki Takahashi, Takeshi Kawakami, Yusuke Amanuma, Takeru Wakatsuki, Naohiro Okano, Yukiya Narita, Yoshiyuki Yamamoto, Rika Kizawa, Kei Muro, Kazunori Aoki, Narikazu Boku
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Gastric cancer (GC) is one of the most common and deadly malignant diseases worldwide. Despite revolutionary advances, the therapeutic efficacy of anti-PD1/PDL1 monoclonal antibodies in advanced GC is still low due to the emergence of innate and acquired resistance to treatment. Myeloid cells represent the majority of human immune cells. Therefore, their increase, decrease, and abnormality could have a significant impact on the patient’s immune system and the progression of cancer, and reprogramming, inhibiting, and eliminating the tumor-supportive types may improve the immunological situation and efficacy of immunotherapy. However, the significance of myeloid cells in anti-PD1/PDL1 therapy remains unclear in GC. In the WJOG10417GTR study on GC, we sought to identify myeloid determinants that could predict anti-PD1 therapeutic efficacy and also serve as potential therapeutic targets. Methods We collected tumor tissues and peripheral blood from 96 patients with advanced GC before and 1 month after anti-PD1 nivolumab monotherapy, and the isolated whole leucocytes were analyzed by flow cytometry for various immune cell populations, including many myeloid subsets. Then, the relationship between the cellular levels and progression-free survival (PFS) or overall survival (OS) was statistically analyzed. Results We found that high levels of several myeloid subsets expressing molecules that have been targeted in drug discovery but not yet approved for clinical use were significantly associated with shorter PFS/OS as compared with low levels: PDL1 + and CTLA4 + myeloid subsets within tumors at baseline, PDL1 + , B7H3 + and CD115 + myeloid subsets in peripheral blood at baseline, and LAG3 + , CD155 + and CD115 + myeloid subsets in peripheral blood at post-treatment. Conclusions This study revealed that these myeloid subsets are significant risk factors in nivolumab therapy for advanced GC. Targeting them may be useful as diagnostic biomarkers to predict potential anti-PD1 therapeutic efficacy, and also as therapeutic targets for accelerating the development of new drugs to improve clinical outcomes in immunotherapy for GC.