Control of Intestinal Inflammation, Colitis-Associated Tumorigenesis, and Macrophage Polarization by Fibrinogen-Like Protein 2

Fibrinogen-like protein 2 (Fgl2) is critical for immune regulation in the inflammatory state. Elevated Fgl2 levels are observed in patients with inflammatory bowel disease (IBD), but little is known about its functional significance. In this study, we sought to investigate the role of Fgl2 in the development of intestinal inflammation and colitis-associated colorectal cancer (CAC). Here, we report that Fgl2 deficiency increased susceptibility to dextran sodium sulfate-induced colitis and CAC in a mouse model. During colitis development, the expression of the membrane-bound and secreted forms of Fgl2 (mFgl2 and sFgl2, respectively) in the colon were increased and predominantly expressed by colonic macrophages. In addition, using bone marrow chimeric mice, we determined that Fgl2 function in colitis is strictly related to its expression in the hematopoietic cells. Loss of Fgl2 induced the polarization of M1, but suppressed that of M2 both in vivo and in vitro, independent of intestinal inflammation. Thus, Fgl2 suppresses intestinal inflammation and CAC development through its role in macrophage polarization and may serve as a therapeutic target in inflammatory diseases, including IBD

Intracellular activation of complement C3 leads to PD-L1 antibody treatment resistance by modulating tumor-associated macrophages

Complement aids in the construction of an immunosuppressive tumor microenvironment. Tumor cell–derived C3 has been previously reported, but whether and how it acts on antitumor immunity remains to be elucidated. Here, we describe a mechanism for tumor cell–derived C3 in suppressing antitumor immunity. Tumor cell–derived C3 was activated intracellularly, which results in generation of C3a. C3a modulated tumor-associated macrophages via C3a-C3aR-PI3Kγ signaling, thereby repressing antitumor immunity. Deletion of C3 in tumor cells that had high C3 expression enhanced efficacy of anti–PD-L1 treatment. Collectively, our results suggest tumor cell–derived C3 may be a useful target for cancer immunotherapy and that targeting C3 in tumor cells may enhance antitumor immunity

Treatment of Rheumatoid Arthritis Using Combination of Methotrexate and Tripterygium Glycosides Tablets—A Quantitative Plasma Pharmacochemical and Pseudotargeted Metabolomic Approach

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic destructive synovitis and is associated with progressive disability, systemic difficulties, premature death, and socioeconomic costs. Early intervention with disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX) and its combination regimen would provide obvious benefits to patients, healthcare systems and society. MTX and tripterygium glycosides tablets (TGTS) are most frequently prescribed medicines for RA, and the combination of them occurs frequently in anti-RA prescriptions. While the underlying combination mechanisms and the affected variation of drug blood level remain unclear. According to the American College of Rheumatology criteria for improvement, clinical evaluation following three treatment groups (i.e., MTX and TGTS mono- and combined groups) were carried out at baseline and at the end of 12 weeks in a randomized controlled clinical trial. To monitor the affected variation of drug blood level and perturbation of metabolites caused by MTX plus TGTS combined to treat active RA, the collected plasma samples were analyzed using RRLC-QqQ-MS and UHPLC-QE Orbitrap HRMS instruments. As a result, 39 metabolites including 7 MTX-related metabolites, 13 TGTS-related migratory ingredients and 19 characteristic endogenous metabolites, were quantitatively determined in plasma samples of RA patients after oral administration. The potential mechanism of MTX and TGTS combination were preliminarily elucidated on the aspect of clinical biochemical test indicators integrated with quantitative plasma pharmacochemistry and the pseudotargeted metabolomics

Retraction note: endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme

Accepted manuscrip

ChatRadio-Valuer: A Chat Large Language Model for Generalizable Radiology Report Generation Based on Multi-institution and Multi-system Data

Radiology report generation, as a key step in medical image analysis, is critical to the quantitative analysis of clinically informed decision-making levels. However, complex and diverse radiology reports with cross-source heterogeneity pose a huge generalizability challenge to the current methods under massive data volume, mainly because the style and normativity of radiology reports are obviously distinctive among institutions, body regions inspected and radiologists. Recently, the advent of large language models (LLM) offers great potential for recognizing signs of health conditions. To resolve the above problem, we collaborate with the Second Xiangya Hospital in China and propose ChatRadio-Valuer based on the LLM, a tailored model for automatic radiology report generation that learns generalizable representations and provides a basis pattern for model adaptation in sophisticated analysts' cases. Specifically, ChatRadio-Valuer is trained based on the radiology reports from a single institution by means of supervised fine-tuning, and then adapted to disease diagnosis tasks for human multi-system evaluation (i.e., chest, abdomen, muscle-skeleton, head, and maxillofacial $\&$ neck) from six different institutions in clinical-level events. The clinical dataset utilized in this study encompasses a remarkable total of \textbf{332,673} observations. From the comprehensive results on engineering indicators, clinical efficacy and deployment cost metrics, it can be shown that ChatRadio-Valuer consistently outperforms state-of-the-art models, especially ChatGPT (GPT-3.5-Turbo) and GPT-4 et al., in terms of the diseases diagnosis from radiology reports. ChatRadio-Valuer provides an effective avenue to boost model generalization performance and alleviate the annotation workload of experts to enable the promotion of clinical AI applications in radiology reports

Control of Intestinal Inflammation, Colitis-Associated Tumorigenesis, and Macrophage Polarization by Fibrinogen-Like Protein 2

Fibrinogen-like protein 2 (Fgl2) is critical for immune regulation in the inflammatory state. Elevated Fgl2 levels are observed in patients with inflammatory bowel disease (IBD), but little is known about its functional significance. In this study, we sought to investigate the role of Fgl2 in the development of intestinal inflammation and colitis-associated colorectal cancer (CAC). Here, we report that Fgl2 deficiency increased susceptibility to dextran sodium sulfate-induced colitis and CAC in a mouse model. During colitis development, the expression of the membrane-bound and secreted forms of Fgl2 (mFgl2 and sFgl2, respectively) in the colon were increased and predominantly expressed by colonic macrophages. In addition, using bone marrow chimeric mice, we determined that Fgl2 function in colitis is strictly related to its expression in the hematopoietic cells. Loss of Fgl2 induced the polarization of M1, but suppressed that of M2 both in vivo and in vitro, independent of intestinal inflammation. Thus, Fgl2 suppresses intestinal inflammation and CAC development through its role in macrophage polarization and may serve as a therapeutic target in inflammatory diseases, including IBD

MOESM1 of Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health

Additional file 1: Table S1. Flavonoids isolated from Citrus species. The table summarized flavones (including polymethoxylated flavones), flavonols, flavanones and flavanonols from Citrus species including C. aurantifolia, C. aurantium, C. canaliculata, C. clementina, C. erythrosa, C. grandis, C. hassaku, C. hystrix, C. junos, C. kinokuni, C. leiocarpa, C. limon, C. limonimedica, C. medica, C. microcarpa, C. paradisi, C. reticulate, C. sinensis, C. suhuiensis, C. tachibana, C. tamurana and C. unshiu

MOESM2 of Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health

Additional file 2: Table S2. Alkaloids, coumarins, limonoids, carotenoids and phenolic acids isolated from Citrus species. The table summarized alkaloids, coumarins, limonoids, carotenoids and phenolic acids from Citrus species including C. aurantifolia, C. aurantium, C. bergamia, C. canaliculata, C. clementina, C. grandis, C. hassaku, C. junos, C. kinokuni, C. leiocarpa, C. limon, C. limonimedica, C. maxima, C. microcarpa, C. myrtifolia, C. paradisi,, C. reticulate,C. sinensis, C. tachibana and C. unshiu