Prostate cancer (PCa) remains one of the most common malignancies in men worldwide, yet modifiable environmental contributors remain incompletely defined. Aromatic hydrocarbons (AHs), particularly benzene and polycyclic aromatic hydrocarbons (PAHs), are widespread pollutants in ambient air, occupational settings, tobacco smoke, and high-temperature cooking emissions. In this review, we synthesize evidence from population-based and occupational epidemiology, dietary exposure proxies, animal carcinogenesis models, organoid systems, and cell-based mechanistic studies to assess the biological plausibility of AH-related prostate carcinogenesis. Human studies support modest but recurrent associations between long-term exposure to traffic-related mixtures, benzene-containing emissions, PAH-generating cooking practices, and increased PCa risk, with stronger duration–response signals in occupational settings. Experimental evidence further indicates that benzo[a]pyrene and related PAHs can induce prostatic mutagenesis, oxidative and genotoxic stress, endocrine perturbation, epigenetic remodeling, and immunosuppressive changes in the tumor microenvironment. The most coherent mechanisms involve AhR–AR crosstalk, CYP1A1/1B1-mediated bioactivation, ROS generation, DNA-adduct formation, DNMT1/HDAC6-associated epigenetic regulation, JAK2/STAT3-linked survival signaling, epithelial–mesenchymal transition, and IDO/TDO–kynurenine–AhR-mediated immune suppression. Collectively, current evidence supports a biologically plausible framework in which AH exposure may contribute to PCa initiation and progression and may intersect with pathways implicated in therapy resistance, although causal inference remains constrained by exposure misclassification, mixture complexity, and limited longitudinal biomarker data. Future studies should integrate precise exposure assessment with prostate-specific molecular studies, organoid systems, animal models, and prospective human cohorts.

Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by immune dysregulation and skin barrier impairment. As a core regulatory axis, interleukin-mediated macrophage polarization modulates the inflammatory cascade and barrier repair via NF-κB/STAT6/NLRP3 pathway crosstalk. This narrative review systematically summarizes the bidirectional regulatory mechanism of the interleukin-macrophage polarization axis in AD, clarifies the vicious cycle linking immune imbalance, inflammatory amplification and barrier damage, and updates targeted interventions including biological agents and natural products. We further analyze the translational challenges of this axis and propose future directions for precise stratified therapy. This review innovatively integrates the immune-barrier crosstalk mechanism and translational insights, providing a theoretical basis for pathogenesis-oriented precise treatment of refractory AD.

Diabetic cardiomyopathy (DCM) results in high mortality with surprisingly rare therapeutic approaches. Anacardic acid (AA) shows broad pharmacological properties, but its effect on DCM was unknown. This study aims to investigate the effect and molecular action of AA on DCM. KKAy mice, a model of spontaneous type 2 diabetes, were fed a high-fat diet, and were subsequently administered with AA by gavage at 5 mg/kg for 14 weeks. AA attenuated cardiac dysfunction, pathological injuries, inflammation, fibrosis, oxidative stress, and apoptosis. Mechanistically, AA was enriched in the colon, but not serum and heart, improving colonic histopathological scores, enhancing colonic tight junction protein expression and reducing serum lipopolysaccharide level, suggesting colonic epithelial barrier integrity (CEBI) as a key target of AA. In vitro experiment employed high glucose and palmitic acid-challenged colonic epithelial cells as a cell model of CEBI, showing that AA at 5 µmol/L reversed the impaired expression of tight junction proteins. RNA-sequencing identified Pde2a gene to be significantly inhibited by AA. Lentivirus-induced Pde2a overexpression in colonic epithelial cells abolished the protective effect of AA on CEBI. The present study reports that AA enhances CEBI to attenuate DCM, possibly through inhibiting colonic epithelial expression of Pde2a.

BACKGROUND:Ginseng (Panax ginseng C. A. Mey.) exerts immunomodulatory effects partly mediated by its polysaccharides and interactions with gut microbiota. However, due to the structural complexity of ginseng polysaccharides, knowledge of their oral fate and direct microbiota interactions remains limited. PURPOSE:This study aims to elucidate the oral fate of neutral and acidic polysaccharides in ginseng, analyze core gut microbiota genera and their immunomodulatory effects mechanisms. METHODS:Structural analysis was conducted on neutral and acidic polysaccharides from ginseng. Thereafter, in vitro digestion and fermentation were performed, with metagenomic and metatranscriptomic profiling. The results were validated in conventional and pseudo‑germ-free immunosuppressed mouse models, and the immunomodulatory mechanisms of the core gut microbiota were investigated. RESULTS:The in vivo and in vitro findings indicated that neutral and acidic polysaccharides exhibit different digestive properties and gut microbiota degradation patterns, differ in short-chain fatty acid production tendencies, bind to GPR-41/43 receptors, upregulate MAPK-p38 phosphorylation, and promote proliferation of intestinal immune cells. CONCLUSION:This work systematically elucidated the digestive characteristics of ginseng polysaccharides and laid the groundwork for future studies on the specificity and structure-function relationships of plant-derived polysaccharides.

As a severe microvascular complication of diabetes, diabetic nephropathy (DN) lacks safe and effective preventive interventional strategies. Previous enterostomy-based colonic perfusion studies have shown that colon-targeted DHA delivery has superior hypoglycemic efficacy to intragastric or intrajejunal administration, though its invasiveness limits clinical translation. Notably, the naturally occurring esterified form of DHA and astaxanthin (DHA-acylated astaxanthin ester, DHA-AST) has been reported to exhibit intrinsic colon-targeted delivery properties. Here we report that oral DHA-AST exerts a significant renoprotective effect against DN in a preventive intervention model of KKAy mice, with superior efficacy to an equimolar DHA in combination with AST (DHA + AST). Specifically, relative to the DHA + AST group, DHA-AST gavage achieved selective colonic DHA enrichment, more effectively ameliorated systemic glucose dyshomeostasis, renal dysfunction, and histopathological damage, and suppressed renal inflammation, oxidative stress and fibrosis. These renoprotective effects were observed alongside improvements in systemic glucose homeostasis. Integrated multi-omics analyses revealed that DHA-AST remodeled gut microbiota composition and associated metabolic profiles, increased colonic trehalose production, and promoted the accumulation of trehalose in the kidneys. Oral trehalose supplementation partially phenocopied the renoprotective effects of DHA-AST against DN in KKAy mice. Combined network pharmacology and molecular docking assays identified HSP90AA1 as a putative molecular target of trehalose. Functional validation using TGF-β1-challenged glomerular mesangial cells showed that recombinant HSP90AA1 protein reversed the inhibitory effect of trehalose on profibrotic gene expression, whereas HSP90AA1 knockdown enhanced this effect. These findings demonstrate that DHA-AST ameliorates DN in association with a putative colon-kidney axis involving trehalose and HSP90AA1, providing preclinical evidence for the development of DHA-AST and trehalose as nutritional intervention candidates for DN.

Diabetes mellitus (DM) is a severe chronic disease that results in high morbidity and mortality. DM causes endothelial injury (DEI) as a basis for cardiovascular complications of DM with few effective approaches developed for its intervention. Krill oil (KO) possesses anti-inflammatory and anti-oxidative activities, but its effect on DEI is unknown. Hence, the aims of this study were to investigate the effect and molecular mechanism of KO on DEI. To investigated the preventive effect of KO on DEI, streptozotocin and high-fat diet-induced type 2 diabetic mice were fed with KO for 6 months. RNA sequencing for endothelial cells (ECs) was used to explore the mechanism of KO’s protective function. To clarify the role of nuclear factor erythroid 2-related factor 2 (Nfe2l2 or NRF2) signaling in KO’s protection against DEI, Nfe2l2 gene-silenced ECs or knockout mice were treated with KO. Molecular docking assay and surface plasmon resonance assay were carried out to reveal binding between Kelch like ECH associated protein 1 (KEAP1) and major components of KO. KO significantly alleviated DEI and aortic pathological injury in the wild-type diabetic mice. RNA sequencing revealed that KO dramatically activated NRF2 antioxidant signaling in high glucose-challenged ECs, the effect of which was further confirmed in the diabetic aortas. Nfe2l2 gene deletion or silencing completely abolished KO’s protection against DEI in vivo and in vitro, demonstrating that NRF2 was required for KO’s action. Further, molecular docking assay and surface plasmon resonance assay identified that KO’s functional component astaxanthin (AST), but not docosahexaenoic acid and eicosapentaenoic acid, was able to bind the Kelch domain of KEAP1, promoting nuclear translocation of NRF2 which activated antioxidant gene expression. The comparison of the effects of KO and AST on endothelial NRF2 nuclear translocation suggested that KO might activate NRF2 at least partially through AST-KEAP1 interaction. KO activates NRF2 to prevent diabetic endothelial injury in part through AST-induced inhibition of KEAP1.

Septic cardiomyopathy (SCM) leads to heart failure, with few effective approaches for its intervention. Fucoxanthin (FX) possesses anti-inflammatory capacity, but its effect on SCM remains unknown. Herein, we report that FX protects against cardiac dysfunction in a lipopolysaccharide (LPS)-induced mouse model of sepsis with a dramatic reduction of inflammatory cell infiltration in the heart tissue. The analysis of human and mouse databases revealed M1-polarized macrophages as the most evidently infiltrated immune cells into the heart tissue under septic conditions. This phenomenon was found in the current mouse model, which was significantly inhibited by FX. FX blunted macrophage M1 polarization in vitro that provoked inflammation in cardiomyocytes. Further, bromodomain-containing protein 2 (BRD2) was predicted as a molecular target of FX. Moreover, FX decreased BRD2 protein in both mouse hearts and macrophages in the presence of LPS. BRD2 overexpression abolished FX's macrophage-silencing effect. Notably, FX decreased BRD2 levels and inhibited inflammation in peripheral monocyte-derived macrophages from patients with SCM. The present study offers FX and BRD2 as a novel approach and molecular target for SCM intervention.

ABSTRACT Sepsis‐associated acute kidney injury (SA‐AKI) results in high mortality due to the lack of effective interventions. The current study reports the protective effect of cardamonin (CAD), a member of the chalcone family, against SA‐AKI using a lipopolysaccharide (LPS)‐stimulated mouse model. CAD was administered by gavage to the mice for 1 week prior to the intraperitoneal injection of LPS, showing a dramatic prevention of renal dysfunction and pathological damage, as well as renal inflammation, oxidative stress, and tubular pyroptosis. Surprisingly, CAD was undetectable in the serum but was significantly enriched in the colon. Metabolomic analysis of the colonic content identified that columbianetin acetate (CA) was drastically increased by CAD. Further measurements confirmed the increase of CA levels in both the colonic content and serum. One‐week oral delivery of CA produced a remarkable preventive effect on LPS‐induced AKI in mice. Combination of network pharmacology, molecular docking, and surface plasmon resonance identified high mobility group box 1 (HMGB1) as the primary target of CA. Further investigation found that CA competed with LPS to bind HMGB1, reducing cellular uptake of LPS, stabilizing lysosomes, and mitigating renal tubular cell pyroptosis. The present study may provide CAD and CA as effective nutritional approaches for SA‐AKI intervention.

Krill oil, extracted from Antarctic krill, is rich in nutrients, including high concentrations of n-3 polyunsaturated fatty acids (n-3 PUFAs), phospholipids (PLs), astaxanthin, vitamins, flavonoids, and other bioactive compounds. Our previous research demonstrated that krill oil exerts anti-inflammatory, antioxidant, and metabolic regulatory effects. Given that inflammation and oxidative stress are key molecular mechanisms underlying metabolicassociated steatotic liver disease (MASLD), we investigated the protective effects and potential mechanisms of krill oil (KO) against MASLD. In this study, C57BL/6 J mice were fed either a methionine- and choline-sufficient (MCS) or methionine- and choline-deficient (MCD) diet and were administered krill oil (KO) or olive oil (OO) for four weeks. Compared to control or OO intervention, KO significantly alleviated liver injury, decreased expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX4), improved oxidative stress markers, and lowered levels of the inflammatory cytokines TNF-alpha, IL-1 beta, and IL-6. Additionally, KO treatment ameliorated fibrosis such as reducing Col1a1 and Col3a1 levels and improving liver histopathology. Furthermore, KO effectively decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and p38, which belonged to mitogen-activated protein kinases (MAPK) signal pathway, and reduced the elevated levels of secreted protein acidic and rich in cysteine (SPARC) induced by MCD diet in liver. These findings are consistent with our observations in high fat diet (HFD) and streptozocin (STZ) induced type 2 diabetic mice. In vitro, KO reduced inflammation, oxidative stress, and fibrosis genes expression, as well as suppressing MAPK pathway, in human hepatic stellate cells activated by SPARC overexpression. Inflammation and oxidative stress were upregulated in macrophages which was co-cultured with SPARC overexpressed hepatic stellate cells, while KO reduced the phenotype in macrophages. Therefore, the effects of KO intervention on mitigating liver inflammation, oxidative stress, and fibrosis might associated with reduced SPARC and inhibited MAPK signaling.

White adipose tissue (WAT) dysfunction is a crucial contributor to insulin resistance (IR), which is the key cause for type 2 diabetes mellitus (T2DM). Macrophage infiltration and M1 polarization induce WAT dysfunction. Krill oil (KO) possesses anti-inflammation activity, but its effect on WAT dysfunction under T2DM remained unclear. To this end, T2DM was established in mice followed by a 6-month KO supplementation, showing that KO significantly lowered fasting blood glucose level, mitigated insulin resistance, and improved WAT dysfunction. Notably, KO decreased the number of infiltrated M1-polarized macrophages in the WAT. Moreover, lipolysis and insulin signaling impairment of the WAT were inhibited by KO. In vitro, KO blunted lipopolysaccharide-induced macrophage M1 polarization. Furthermore, in co-culture experiments, these KO-treated macrophages resulted in a less expression of inflammatory factors and resistin, an elevation of adiponection level, as well as an enhanced lipid storage capacity in adipocytes. In summary, the current study found that KO might improve adipocyte dysfunction and insulin resistance by inhibiting macrophage M1 polarization, providing a potential approach for T2DM intervention.

Chronic kidney disease (CKD) is often accompanied by comorbidities such as skeletal disorders and vascular calcification, which significantly elevate the mortality risk among affected patients. In recent years, dysbiosis of the gut microbiota has emerged as a key pathological factor in the progression of CKD, particularly through the accumulation of its metabolic product, trimethylamine-N-oxide (TMAO). TMAO is produced in the liver via the gut microbiota’s metabolism of dietary precursors such as choline, betaine, and L-carnitine. It is primarily excreted via the kidneys, and its levels are markedly elevated in CKD patients due to impaired renal function. Studies have demonstrated that TMAO is not only closely associated with an increased risk of vascular calcification but may also exacerbate skeletal disorders in CKD patients by disrupting bone metabolism. This review aims to elucidate the mechanisms underlying TMAO’s role in CKD, particularly focusing on its critical involvement in the kidney-bone-vascular axis. Based on existing evidence, we propose potential therapeutic strategies for modulating gut microbiota and TMAO levels, including dietary modifications, probiotic interventions, TMA cleavage enzyme inhibitors, FMO3 inhibitors, and pharmacological regulation, to improve skeletal and cardiovascular health in CKD patients.

Introduction and Objective: The optimal glucose targets in gestational diabetes mellitus (GDM) remains unknown. This study aimed to investigate the threshold of hyperglycemia associated with adverse outcomes in GDM using continuous glucose monitoring (CGM). Methods: This prospective cohort study recruited a total of 717 singleton pregnant women with GDM performing CGM during pregnancy. Time above ranges (TARs) were calculated as the percentage of time above the glucose thresholds from 5.6 to 8.1 mmol/L (100 to 145 mg/dl, increase by 5mg/dl each) during the whole CGM period respectively. Multivariate logistic regression analysis and restricted cubic spline (RCS) curve analysis were employed to explore the optimal threshold and range of TAR. Results: Of the 717 GDM women, 172 (24.0%) had LGA infants, and 144 (20.1%) had composite adverse outcomes. Only TARs with a threshold of 6.9 mmol/L (TAR>6.9) or above were significantly associated with the risk of LGA after adjusting confounders. For per absolute 5% increase in TAR>6.9, the risk of LGA was increased by 9.8% (OR 1.098, 95% CI: 1.008, 1.195). RCS curve showed that when TAR>6.9 > 26.0%, the risk of LGA increases with elevating TAR>6.9. Conclusion: A glucose level exceeding 6.9 mmol/L and TAR>6.9 > 26.0% were significantly associated with higher risk of LGA in women with GDM. Strict glycemic control may result in better prognoses. G. Liang: None. S. Yan: None. Y. Wang: None. J. Lu: None. H. Wu: None. J. Zhou: None. Y. Wang: None. the National Key Research and Development Program of China (2021YFC2501600, 2021YFC2501601); National Health Commission Medical Health Science and Technology Development Research Center "Innovative medicine post-marketing clinical research research project” (WKZX2023CX150002); Shanghai Science and Technology Commission Foundation (No. 21Y11904800; No. 23ZR1451500).

Colorectal cancer (CRC) incidence rises with age, driven by factors such as diet. Inulin, a soluble fiber found in plants like Jerusalem artichoke and chicory, may influence CRC risk by modulating gut microbiota and improving metabolic profiles. This systematic review and meta-analysis evaluate the effects of inulin on CRC in animal models and explore its underlying mechanisms. A comprehensive search of nine databases led to the selection of 12 studies from an initial pool of 114 articles, based on predefined inclusion criteria. Standardized meta-analyses were performed for eligible studies. Results indicate that inulin supplementation significantly reduced aberrant crypt foci count in rats (SMD = -3.805, 95% CI, -7.348 to -0.262, p < 0.001), increased cecal weight (SMD = 6.723, 95% CI, 3.395-10.051, p = 0.000), enhanced colonic lactobacillus counts (SMD = 1.307, 95% CI, 0.644-1.970, p = 0.000), decreased coliform bacteria (SMD = -1.659, 95% CI, -2.147 to -1.171, p = 0.000), and elevated colonic short-chain fatty acids (SCFAs) levels, including acetate (SMD = 3.50, 95% CI, 1.111-5.890, p < 0.001), propionate (SMD = 3.081, 95% CI, 1.416-4.746, p < 0.001), and butyrate (SMD = 4.471, 95% CI, 2.464-6.478, p < 0.001). This systematic review demonstrates inulin's chemopreventive effects against CRC in animal models by enhancing beneficial gut bacteria (e.g., lactobacillus) and boosting SCFAs. Findings advocate integrating inulin-rich foods/supplements into prevention strategies for precision prebiotic development via SCFA-mediated epigenetic and antitumor mechanisms.

Background:Immunoglobulin A nephropathy (IgAN), recognized as the leading cause of primary glomerular disease worldwide, continues to present unresolved complexities in its underlying pathogenic mechanisms. Emerging evidence underscores ferroptosis, an iron-mediated regulated cell death pathway driven by the accumulation of lipid peroxides, as a potential contributor to various pathological conditions. Despite growing interest in this field, the exact molecular pathways governing ferroptosis activation in IgAN progression remain incompletely understood and require systematic investigation. The aim of this study was to identify ferroptosis-related feature gene (FFG) for the potential diagnosis of IgAN and to investigate its relationship with renal immune cell infiltration. Methods:Renal tissue microarray datasets (GSE93798, GSE104948, GSE99339) from IgAN patients and normal controls were retrieved from GEO database. The ferroptosis-related genes were obtained from the Ferrb database. Machine learning algorithms (LASSO, SVM-RFE, random forest) were employed to screen FFGs. The findings were validated in an IgAN mouse model using immunohistochemistry and western blotting. Gene set enrichment analysis (GSEA) was conducted to explore the underlying mechanism of FFG in IgAN. Immune cell infiltration characteristics were also analyzed vis CIBERSORT algorithm. Results:A total of 180 ferroptosis-related differentially expressed genes were identified in IgAN. Among them, dual specificity phosphatase 1 (DUSP1) was screened as FFG by three machine learning algorithms. DUSP1 exhibited significant downregulation in renal tissues of both IgAN patients and mice. Enhanced transcriptional abundance demonstrated significant positive associations with ferroptosis-associated biomarkers glutathione peroxidase-4 (GPX4) and cystine/glutamate antiporter (SLC7A11/xCT), while displaying an inverse relationship with acyl-CoA synthetase long-chain isoform 4 (ACSL4) expression. GSEA further identified DUSP1's functional enrichment in critical signaling networks, particularly mitogen-activated protein kinase (MAPK) cascades, ERBB receptor tyrosine kinase pathways, and Janus kinase-signal transducer (JAK-STAT) transduction mechanisms. Immunoinfiltration analysis demonstrated increased infiltration of T follicular helper cells, activated NK cells, and M1 macrophages in the renal tissues of IgAN patients, with DUSP1 expression showing negative correlations with these proinflammatory cell types. Conclusion:Our research successfully identified DUSP1 as a ferroptosis-related biomarker in IgAN patients, and explored its potential mechanism in the pathogenesis of IgAN and its potential relationship with immune cell infiltration. These findings are of great significance for the diagnosis and prospective treatment strategies for IgAN patients.

The issue of loss of efficacy with infliximab (IFX) treatment in Crohn's disease (CD) significantly limits its clinical use. This study aims to investigate the role of therapy combined with partial enteral nutrition (PEN) in maintaining the efficacy of infliximab. Consecutive CD patients undergoing IFX for induction and maintenance therapy were included, with a follow-up period of at least 54 weeks and endoscopy performed around 54 weeks. Subsequent longitudinal monitoring evaluated improvements in the Crohn's Disease Activity Index (CDAI) score at 14 weeks and endoscopic remission at 54 weeks. Among the 176 included patients, 99 (56%) were in the IFX monotherapy group, and 77 (44%) were in the IFX + PEN group. A significantly higher proportion of patients in the IFX + PEN group achieved clinical response (defined as a CDAI decrease ≥70 points) compared to those in the IFX group at 14 weeks (87.01% vs. 74.75%, p = 0.043), as well as a higher proportion achieving endoscopic remission at 54 weeks (84.42% vs. 65.66%, p = 0.005). Meanwhile, combination therapy with PEN emerged as an independent protective predictor of endoscopic remission at 54 weeks in two multivariate-adjusted models, with ORs of 3.34 and 3.33, respectively (both p < 0.05). Subgroup analysis and interaction test results further supported that all CD patients can benefit from combination therapy with PEN. Infliximab treatment combined with partial enteral nutrition is beneficial for both short-term clinical response and long-term endoscopic remission in CD patients.

Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) caused by dysregulation of the complement system. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Owing to its diverse and nonspecific clinical manifestations, early diagnosis of the condition is challenging and typically requires excluding other TMA-related conditions, such as thrombotic thrombocytopenic purpura and hemolytic uremic syndrome caused by Escherichia coli infection. Accurate diagnosis relies on the recognition of typical TMA symptoms, laboratory testing, and the exclusion of other conditions. Treatments typically include plasma exchange, supportive care, and complement-targeted therapy. Eculizumab, a complement component 5 inhibitor, plays a crucial role in aHUS treatment in severe cases as well as when traditional interventions fail. In this case report, we described a female Han Chinese patient who developed aHUS following an upper respiratory tract infection, initially presented with intermittent seizures, and received treatment with eculizumab, plasma exchange, and hemodialysis. The patient ultimately remained dialysis-dependent; however, they achieved complete remission for other systemic complications of aHUS. We emphasized in this case report the importance of timely diagnosis and treatment of aHUS as well as the potential value of eculizumab in improving patient outcomes. Furthermore, successful treatment and follow-up results provide insights into the management of this rare disease, including long-term dialysis requirements and disease monitoring after remission. Thus, clinicians can better understand the clinical manifestations of aHUS and its associated diagnostic challenges, treatment strategies, and long-term management needs.

The simultaneous occurrence of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and light chain proximal tubulopathy (LCPT) presents a unique diagnostic and therapeutic challenge. PGNMID is characterized by monoclonal immunoglobulin deposition in glomeruli, leading to proliferative glomerular pathology, while LCPT involves monoclonal light chain deposition in proximal tubular cells, causing tubulointerstitial damage. Both conditions are classified under monoclonal gammopathy of renal significance (MGRS), but their coexistence in a single patient is exceedingly rare. This case report details the presentation of a patient with nephrotic syndrome and renal insufficiency, where renal biopsy revealed both PGNMID and LCPT. Treatment with bortezomib, cyclophosphamide, and dexamethasone achieved clinical remission and significant renal function recovery. This case emphasizes the critical role of renal biopsy in the diagnosis, particularly in the absence of detectable monoclonal proteins, and demonstrates the efficacy of targeted therapy in managing such complex renal pathologies. These findings contribute to a better understanding of MGRS and may guide future therapeutic strategies for similar cases.

Background: Vine tea, derived from selenium-rich regions of China, has been shown through systematic pharmacological approaches to potentially exhibit significantly superior anti-inflammatory effects in dextran sodium sulfate-induced colitis. However, the mechanism of action is still unclear. Materials and methods: This study analyzed the total flavonoid fraction of Vine tea (VTF) using untargeted metabolomics with UHPLC-OE-MS mass spectrometry. The chemical composition of the VTF samples was characterized through a comprehensive review of literature reports and relevant databases for network pharmacology. We constructed a visualization network linking VTF, compounds, pathways, and ulcerative colitis using GO and KEGG analyses. To evaluate the therapeutic effects of VTF on UC, we established a mouse model of ulcerative colitis induced by 3 % dextran sodium sulfate and assessed the effects of VTF treatment. Additionally, a cellular model was developed, and the Cell Counting Kit-8 assay was used to determine the optimal dosing concentration of VTF in neutrophils. Laser confocal microscopy was employed to analyze the co-localization of P62-LC3 and the expression of Citronelated Histone H3 following VTF intervention. Results: This study identified the five main components of total flavonoids in Vine tea using UHPLC-OE-MS non-targeted metabolomics. We explored the potential mechanisms of VTF intervention in ulcerative colitis using network pharmacology. This analysis identified 112 linker genes. The GO and KEGG enrichment analyses suggested that the inhibitory effect of VTF on intestinal inflammation might be related to the PI3K-AKT-mTOR signaling pathway. In vivo experimental validation revealed that VTF significantly increased colon length and decreased the Disease Activity Index score (P < 0.05). VTF also reduced serum levels of inflammatory factors TNF-alpha and IL-1 beta (P < 0.05), improved colon histopathology, and restored the levels of intestinal tight junction proteins Occludin and Zonula Occludens-1. These findings suggest that VTF can ameliorate ulcerative colitis in the colon of mice. In vitro, VTF upregulated cellular macroautophagy through the PI3K-AKT-mTOR signaling pathway and inhibited the release of Neutrophil Extracellular Traps. However, In vitro experiments revealed no direct relationship between autophagy and Neutrophil Extracellular Traps under VTF intervention. Conclusion: The mechanism by which VTF ameliorate Dextran Sodium Sulfate-induced ulcerative colitis in mice may involve promoting autophagy through downregulation of the PI3K-AKT-mTOR signaling pathway, reducing the release of Neutrophil Extracellular Traps, and restoring the intestinal barrier. However, no direct relationship was observed between the autophagy induced by VTF intervention and the release of Neutrophil Extracellular Traps.

Obesity is associated with skeletal muscle mass loss and physical dysfunction. Krill oil (KO) has been shown to be beneficial in human health. However, the effect of KO on obesity-induced skeletal muscle atrophy is still unclear. In this study, the male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity, and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks. The results showed that KO treatment reduced body weight, fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice. Importantly, KO treatment attenuated skeletal muscle atrophy in HFD-fed mice, as evidenced by preserving skeletal muscle mass, average myofiber cross-sectional area and grip strength. KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle. Additionally, KO treatment inhibited the transcriptional activities of nuclear factor-κB (NF-κB ) p65 and forkhead box O 3a (FoxO3a), and then down-regulated muscle atrophy F-box (MAFbx) and muscle-specific RING finger protein 1 (MuRF1) protein levels in skeletal muscle from HFD-fed mice. KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway. Furthermore, KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1α pathway. Collectively, KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.

Background Lupus nephritis (LN) emerges as a severe complication of systemic lupus erythematosus (SLE), significantly affecting patient survival. Despite improvements in treatment reducing LN’s morbidity and mortality, existing therapies remain suboptimal, emphasizing the necessity for early detection to improve patient outcomes.Methods This study employs bioinformatics and machine learning to identify and validate potential LN biomarkers using immunohistochemistry (IHC). It explores the relationship between these biomarkers and the clinical and pathological characteristics of LN, assessing their prognostic significance. The research provides deeper mechanistic insights by employing Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the study characterizes the immune profiles of LN patients through the CIBERSORT algorithm, focusing on the role of interferon-inducible protein 44 (IFI44) as a key biomarker.Results IFI44 shows elevated expression in LN-affected kidneys, compared to healthy controls. The levels of IFI44 positively correlate with serum creatinine and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and inversely with serum complement C3 and initial estimated glomerular filtration rate (eGFR).Conclusion IFI44 is identified as a promising biomarker for LN, offering potential to refine the assessment of disease progression and predict clinical outcomes. This facilitates the development of more personalized treatment strategies for LN patients.