Dapeng Chen

Concurrent dysregulation of COX-2 and soluble epoxide hydrolase (sEH) disrupts arachidonic acid homeostasis to drive macrophage activation in inflammatory bowel disease (IBD). Here, we identify tetrandrine (TET), a bisbenzylisoquinoline alkaloid from Stephania tetrandra S. Moore, as a novel dual inhibitor of COX-2 and sEH. In vivo, TET significantly attenuated DSS-induced UC in mice, reversing weight loss, elevated disease activity index, colonic shortening, and histological lesions. TET restored intestinal integrity via downregulating serum pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α), reducing epithelial cell apoptosis and upregulating tight junction proteins. Peptide-centric local stability assay (PELSA) and cellular thermal shift assay (CETSA) identified COX-2 and sEH as direct targets of TET. Mechanistically, TET directly bound to both enzymes with moderate inhibitory activities (IC~50~ = 13.19 and 11.27 μmol/L, respectively). Notably, TET induced ubiquitin-mediated proteasomal degradation of both COX-2 and sEH, while genetic knockout of sEH significantly abrogated the protective effects of TET. Additionally, TET modulated gut microbiota composition, increasing beneficial bacteria including Lachnospiraceae_NK4A136 and Turicibacter. TET demonstrated no detectable toxicity at therapeutic doses and showed superior efficacy compared to sulfasalazine. Collectively, these findings support the therapeutic potential of S. tetrandra-derived alkaloids for IBD treatment through regulation of arachidonic acid metabolism.

Cells die extensively each day under physiological and pathological conditions, yet dying cells and cell corpses are not merely passive endpoints. Increasing evidence shows that they actively shape their microenvironment during death-program execution, signal release or exposure, corpse processing, and responses of neighboring cells and phagocytes. We here summarize six major roles of dying cells and cell corpses: promoting tissue turnover and remodeling, supporting neighboring-cell survival, mediating intercellular communication, providing metabolic substrates and rewiring phagocyte metabolism, facilitating corpse recognition and clearance, and modulating immune responses. Overall, they provide a broader framework for understanding cell death and identifying therapeutic opportunities.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation, epithelial barrier disruption and immune dysfunction. Alleviating and curing these pathological manifestations is the goal of IBD treatment. Despite substantial advances in targeted immunotherapies and anti-inflammatory strategies, achieving sustained intestinal mucosal healing remains a major clinical challenge. Dynamin-related protein 1 (Drp1) is a GTPase that mediates mitochondrial fission and plays a crucial role in maintaining the dynamic balance of mitochondrial morphology and function. In IBD, Drp1 expression is frequently upregulated and continuously activated, resulting in excessive fission and fragmentation of mitochondria. This mitochondrial dysregulation contributes to ATP depletion and excessive reactive oxygen species (ROS) production, thereby exacerbating disease progression and amplifying inflammatory signaling. This review highlights the distinctive role of Drp1 as an integrative node in IBD. Specifically, we connect mitochondrial dynamics with epithelial barrier failure, immune dysregulation, inflammatory cell death, and intestinal microenvironment remodeling. We further emphasize the potential relevance of Drp1 for biomarker-based patient stratification and mechanism-informed therapeutic targeting, thereby distinguishing this review from more descriptive accounts of mitochondrial dysfunction in intestinal inflammation.

Cam morphology is associated with acetabular cartilage lesions and early-onset osteoarthritis in patients with femoroacetabular impingement syndrome. Here, we propose a novel iterative rabbit model of cam morphology to characterize the pathophysiology of femoroacetabular impingement-related cartilage lesions. We described a repeatable method for establishing a New Zealand white rabbit model of cam morphology by interfering with the epiphyseal tubercle and evaluated the histological outcomes of acetabular cartilage lesions. Cam morphology and subchondral bone were evaluated by micro-CT scanning. The expression of anabolic and catabolic biomarkers of acetabular cartilage was investigated via western blotting and immunohistochemical staining. Chondrocyte apoptosis was detected via TUNEL staining. Kinematics of the hip joint in the sagittal plane were evaluated by a passive optical motion capture system. There were remarkable pathological similarities between this model and human diseases. The cam morphology rabbit model exhibited early cartilage degeneration and subsequent phenotypes of hip osteoarthritis, and this pathological process is not affected by surgical trauma. Hip motion in the cam morphology models resembled that in the healthy controls, and had only a slightly lower joint angle at all phases of the half-bounding gait cycle. This model preserved the natural and predictable movement pattern. This rabbit model of cam morphology replicates the disease phenotype and allows for scientifically sound evaluation of disease mechanisms. It can be employed to study human cam-type femoroacetabular impingement syndrome.

The management of inflammatory bowel disease (IBD), which is characterized by immunodeficiency, has attracted increasing attention, highlighting the necessity for more precise and streamlined diagnostic approaches in clinics. Calprotectin, an immune cell-derived protein with inherent anti-inflammatory and antimicrobial properties, plays a pivotal role in immune regulation and intestinal homeostasis. Its expression levels are intricately linked to IBD activity, enabling differentiation between inflammatory and non-inflammatory states while predicting recurrence risks. As a non-invasive biomarker, fecal calprotectin (FC) and serum calprotectin (SC) analysis offers high reproducibility and clinical utility, facilitating both IBD diagnosis and real-time disease monitoring. Beyond its diagnostic specificity in distinguishing IBD from other gastrointestinal disorders, calprotectin also emerges as a promising therapeutic target, due to its dual role in modulating inflammatory pathways and interacting with the gut microbiota. With collaborative advancements in standardized detection protocols and innovative research methodologies, it is anticipated that calprotectin-based strategies will be integrated into mainstream clinical practice for IBD.

As life expectancy rises and the aging population grows, Alzheimer’s disease (AD) has become a significant global health concern. AD is a complex neurodegenerative disorder with an unclear etiology. Current hypotheses primarily focus on β-amyloid (Aβ) aggregation, tau protein hyperphosphorylation, and neuroinflammation as key pathological processes. Given the limited efficacy of existing therapeutic strategies, there is an urgent need to explore novel treatment options. Marine natural products have garnered significant attention due to their unique chemical structures and diverse bioactivities, demonstrating potential for multi-target interventions in AD. This review systematically summarizes the roles of marine-derived compounds, including polysaccharides, carotenoids, and polyphenols, in modulating Aβ aggregation, mitigating tau protein pathology, and regulating gut–brain axis dysfunction. Furthermore, the challenges of current research are discussed, with an emphasis on improving blood–brain barrier permeability and optimizing drug delivery systems to facilitate clinical translation.

Background: Regulatory T (Treg) cells is required to dampen immune responses against intestinal microbiota, which aid in a healthy body to promise that the resident gut microbiota should not attract the attention of the immune system. Inflammation and inflammatory bowel disease (IBD) can be induced if the immune system fails to ignore the resident gut microbiota and targets them instead. D-mannose, a common monosaccharide in nature, has been shown to ameliorate multiple autoimmune diseases. This study aimed to investigate the therapeutic effect of D-mannose on mice ulcerative colitis (UC) induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and elucidate its underlying mechanisms.Methods: To simulate human IBD, we constructed a mouse model of UC by injecting TNBS into the colon.Results: Our results demonstrated that D-mannose treatment effectively alleviated TNBS-induced UC in mice, as evidenced by the amelioration of UC symptoms. D-mannose treatment significantly reduced inflammation by decreasing the expression of proinflammatory cytokines and inflammation mediators. D-mannose treatment also significantly inhibited oxidative stress, promoted the expression of GSH and SOD, decreased the expression of MDA. Mechanistically, D-mannose upregulated the proportion of both CD4(+) Tregs and CD8(+) Tregs.Conclusion: In summary, our study provides the first evidence of the therapeutic effect of D-mannose on mice with UC, which is likely mediated by upregulating Treg proportions.