Inflammation and ferroptosis play a crucial role in cisplatin (CP)-induced acute kidney injury (AKI). Silybin (SYB), a polyphenolic flavonoid, has shown renal protective effects, but its underlying mechanisms remain unclear. CP-induced HK-2 cell and mouse AKI models were used to explore the role of SYB. CCK-8, lactate dehydrogenase release, flow cytometry, and calcein/PI staining, were performed to evaluate cell viability, proliferation, and apoptosis. Oxidative stress and ferroptosis markers were measured, while renal function was assessed by serum creatinine and urea nitrogen. Mitochondrial ultrastructure was examined, and histological staining was conducted to analyze renal pathology and iron deposition. Western blotting detected HDAC6, NF-κB, NLRP3, and ferroptosis-related proteins expression. SYB treatment alleviated CP-induced mitochondrial damage, reduced lactate dehydrogenase release, inflammatory cytokines, oxidative stress, and ferroptosis, and improved proliferation and viability in HK-2 cells. In mice, 100 mg/kg SYB decreased serum creatinine, urea nitrogen, and cytokine levels, while ameliorating renal tissue injury. Mechanistically, SYB downregulated HDAC6 and inhibited NF-κB/NLRP3 activation, thereby suppressing ferroptosis. Notably, overexpression of HDAC6 restored NF-κB/NLRP3 activity and attenuated the protective effects of SYB. In conclusion, SYB mitigates CP-induced AKI by reducing inflammation and ferroptosis by modulating the HDAC6/NF-κB/NLRP3 pathway.

Objective Obesity-related glomerulopathy (ORG) lacks targeted therapies. Rhein, a bioactive anthraquinone from Rhei Radix et Rhizoma, was evaluated for its effects on inflammation, renal function, and gut microbiota in high-fat diet-induced ORG mice. Methods C57BL/6J mice were fed a 60% fat diet for 12 weeks to establish ORG, followed by 300 mg/kg/day rhein free intake for 12 weeks. Serum cytokines (IL-6, TNF-α), renal histopathology, and 16S rRNA microbiome sequencing were analyzed. Results Rhein significantly reduced body weight (P < 0.001), serum triglycerides (P < 0.01), and proteinuria (P < 0.001), while improving glomerular lesions. It also markedly lowered serum levels of IL-6, TNF-α, and creatinine. 16S rRNA sequencing revealed that rhein restored gut microbiota diversity (e.g., Chao1 index increased from 303.58 to 425.78) and reversed the Firmicutes/Bacteroidetes imbalance (76.86%–62.15%). Analysis of similarities (ANOSIM) further confirmed a significant difference in microbial community structure between the Rhein and Model groups (R = 0.926, p = 0.008). Conclusion Rhein mitigates ORG progression is associated with anti-inflammatory, lipid-lowering, and microbiota-modulating mechanisms, offering a novel therapeutic strategy.

Osteoarthritis (OA) is a chronic degenerative joint disease driven by multifactorial causes, including aging, mechanical stress, and inflammation. Mechanical loading through exercise can either exacerbate or alleviate OA symptoms depending on intensity. Substance P (SP), a neuropeptide involved in inflammation and mechanotransduction, has been implicated in cartilage and bone remodeling. This study aimed to investigate how SP deficiency plus exercise intensity interact to influence disease progression in a surgical murine OA model. OA was induced in male wild-type (WT) and SP knockout (Tac1-/-) mice via destabilization of the medial meniscus (DMM). Mice were then exposed to moderate or intense treadmill exercise for up to eight weeks. Cartilage degeneration was assessed histologically using OARSI scoring. Cartilage stiffness was evaluated via atomic force microscopy (AFM), and subchondral and metaphyseal bone morphology was analyzed by high-resolution nanoCT. Serum cytokine levels were measured with multiplex ELISA. DMM surgery induced OA-like cartilage damage in most groups, and moderate exercise failed to prevent degeneration. However, SP-deficient mice subjected to intense exercise showed preserved cartilage matrix stiffness and morphology comparable to Sham controls. In contrast, SP deficiency as well as intense exercise promoted meniscal ossification and subchondral bone sclerosis, with increased bone volume fraction and trabecular thickness. These changes were consistent with prior findings in SP-deficient mice without exercise. Serum analysis revealed elevated levels of proinflammatory cytokines (e.g., CXCL10, VEGF-A, CCL2, CCL4) in SP-deficient mice after Sham surgery, although these did not correspond to the cartilage degradation timeline. SP plays a dual role in OA pathogenesis: its absence may protect cartilage from mechanical stress-induced stiffening but also promotes ectopic meniscal ossification and subchondral bone alterations. Additionally, SP appears to modulate systemic inflammatory responses independently of joint degeneration. These findings position SP as a key regulator of neuroimmune and mechanobiological processes in OA and highlight its potential as a therapeutic target for load-induced joint pathology.

Gut barrier dysfunction contributes to acute decompensation (AD) of cirrhosis progression but, it is not acknowledged in severity or prognostic scores due to a lack of appropriate assessment tools. We investigated serum villin-1 (VIL1), an epithelial brush-border associated actin-binding protein, as a non-invasive marker for gut injury and prognosis in AD cirrhosis. Serum VIL1 was measured in 338 cirrhosis patients (discovery n = 130, validation n = 208, including acute-on-chronic liver failure [ACLF]) from MICROB-PREDICT cohorts and 50 healthy controls (HC). Duodenal biopsies (n = 49 patients, n = 11 HC) were assessed for tissue VIL1 via immunohistochemistry. Serum cytokine profiling linked serum VIL1 levels to systemic inflammation. Compared to HC, both serum and tissue VIL1 levels were lower in stable AD patients. However, serum VIL1 progressively increased with AD severity, peaking in ACLF. Serum VIL1 was associated with 90-day mortality (AUROC: 0.721, p < 0.001; similar to MELD: 0.722, p < 0.001). A cut-off > 12.79 ng/mL enhanced the prognostic accuracy provided by severe disease stage, defined as CLIF-C AD score ≥ 50 or ACLF (low VIL1: 17.5% vs. high VIL1: 53.6% mortality). This threshold was associated with increased systemic inflammation, suggesting enhanced bacterial translocation. VIL1 was an independent predictor of 90-day mortality (HR: 2.52, CI: 1.648-3.848, p < 0.001) in Cox regression. All findings were confirmed in the validation cohort. Serum VIL1 is a non-invasive indicator of gut barrier damage and short-term mortality in AD cirrhosis. Incorporating VIL1 assessment into risk stratification methods improves prognostic accuracy by capturing an essential, yet previously overlooked component of disease progression.

Background The complex interaction between the adaptive immune system and innate immunological components causes rheumatoid arthritis (RA), a systemic autoimmune disorder that involves synovitis and joint deformity. Brain- spleen axis is a reciprocal cross-communicative circuit serves a crucial role in maintaining immunomodulation and homeostasis. RA complicates extra-articular manifestations in spleen and brain. Exposure to ionizing radiation might exacerbate the severity of RA. Recently, beta- sitosterol (BS), which is a promising phytosterols, has shown efficacy against various inflammatory models. Objective Here, we aim at exploring the immunomodulatory effect of BS on the inflammatory responses in arthritic and arthritic-irradiated rats involving articular and extra-articular manifestation implicated in the brain-spleen axis. Materials and Methods Adjuvant- induced arthritic rats were subjected to fractionated doses of γ-radiation (2 Gy/fraction once per week for 4 successive weeks, up to a total dose of 8 Gy) and either treated with BS (40 mg/kg b.wt./day, p.o.) or the standard anti-RA drug, methotrexate (MTX) (0.5 mg/kg; twice weekly, i.p). Results BS ameliorated the arthritic clinical signs, improved histopathological insults, and osteopathological damage as revealed by X- radiography. Moreover, a notable alleviation in key inflammatory culprits was observed in ankle joints. Also, BS modulated apelin-13/APJ and protein kinase C (PKC)/AMP-activated protein kinase (AMPK)/nuclear factor erythroid-2-related factor-2 (Nrf2) signaling pathways in spleen and brain, as well as reduced oxidative stress, augmented antioxidant defenses, and diminished pro-inflammatory cytokines in serum, spleen, and brain that was supported histopathologically. Conclusion BS exhibited an immunomodulatory effect involving the brain-spleen axis in arthritic and arthritic-irradiated rats.

Integrating proteomics, metabolomics, and network pharmacology to investigate the mechanism of Cordyceps sinensis in the treatment of COPD rats.

T1-mapping quantitative assessment of renal function and changes in serum cytokine levels after renal transplantation in children.

Variants in the Glucocorticoid Receptor gene (NR3C1), asthma control and serum cytokine levels.

Loss of PINCH2 leads to myogenic urinary retention in mice.

A tumor microenvironment-based classification of gastric cancer for more effective diagnosis and treatment.

Evaluation of a prebiotic mannan-oligosaccharide on Salmonella Enteritidis cecal colonization and immune response of broiler chickens.

Therapeutic potential of AAV8-mediated IL-17RA extracellular domain gene delivery in an imiquimod-induced mouse model of psoriasis.

Predictive nomogram integrating thymic CT features and serum cytokine profiles for prognosis in non-thymomatous ocular myasthenia gravis: A validated model

Echinococcus granulosus sensu lato, a cestode that inhabits the small intestines of canids, causes cystic echinococcosis (CE), a globally distributed zoonosis, through its larval stage. Vaccination is a cost-effective strategy to control E. granulosus infection in dogs. However, although dogs are the definitive hosts and main sources of CE transmission, no effective oral vaccines are currently available for them. Three E. granulosus proteins, enolase (EgENO), severin (EgSev), and cyclophilin (EgCyc), were selected as novel oral vaccine candidates. These proteins were fused to the CotB spore-coat protein and expressed on the surface of Bacillus subtilis spores. A cocktail vaccine comprising the three recombinant spores was orally administered to beagles. Two weeks after the booster immunization, each dog was challenged with 70,000 protoscoleces. At 21days post-infection, necropsies were performed to assess the intestinal parasite burden and calculate the worm reduction rates. Fecal and serum samples were collected weekly to measure secretory IgA, IgG, and cytokine responses. Histopathological analysis of intestinal tissues was also performed. The cocktail vaccine reduced intestinal E. granulosus colonization by 62.26% (P < 0.05) compared with B. subtilis 168 spore-only controls. Vaccinated dogs developed both mucosal and humoral immune responses against E. granulosus antigens. By day 14 post-boost immunization, serum cytokine profiling revealed that levels of IFN-γ, IL-4, and IL-10 in the vaccinated group were significantly higher than those in the control group (P < 0.05). Histopathological analysis confirmed that the vaccine caused no adverse effects and alleviated the intestinal damage induced by the parasite. This study demonstrates that B. subtilis spores serve as a safe and effective bacterial carrier to deliver E. granulosus antigens, supporting their potential in protecting dogs against E. granulosus infection. The heterogeneity in immune responses among vaccinated dogs should be addressed in future studies to secure consistent herd-level protection.

Short-term impact of bariatric surgery on systemic inflammation in patients with asthma.

Breed-specific variation in canine cytokine profiles in a leishmaniosis-endemic region.

Dysregulation of serum cytokine profile in Saudi Arabian multiple sclerosis patients: A case-control study

Gut microbiota-mediated immunomodulation underlies the anti-tumor effects of a novel ginseng polysaccharide.

The activation of neutrophils by cytokines and cell-free DNA might precede hemoconcentration in dengue. Then, the neutrophil extracellular traps (NETs) and the neutrophils in the peripheral blood mononuclear cell (PBMC) fraction, referred to as low-density granulocytes (LDGs), were explored. The blood samples at 5days of fever from patients with dengue were collected and categorized into dengue without and with warning signs (DWoWS and DWWS). Meanwhile, the patients with hemoconcentration were excluded. The NET-associated parameters, as determined by serum cell-free DNA and the fluorescent staining in the polymorphonuclear (PMN) fraction, in the DWWS group (n = 31) were higher than in DWoWS (n = 40). Meanwhile, complete blood count, serum cytokines (IFN-α, TNF-α, and IL-6), and LDGs were not different. The extracellular traps (ETs), stained by neutrophil elastase (NE) and myeloperoxidase (MPO), in the PBMC fraction of the DWWS group were higher than in DWoWS, while the ETs were non-detectable in healthy volunteers. The recombinant IFN-α and cell-free DNA reduced the density of regular neutrophils isolated from healthy volunteers into LDGs (measured by gradient separation) and also induced NETs (evaluated by NE and MPO co-expression). Meanwhile, CD66b (an adhesion molecule) and apoptosis in these LDGs were more prominent than in regular neutrophils. The NETs and LDGs presented in blood samples of patients with dengue might be due to the activation by IFN-α and cell-free DNA. However, only NETs could differentiate DWWS from DWoWS. Further studies to use NETs and LDGs in clinical practice are interesting.

Early response in cytokine and miR-124a, -125b, -223 expression to anti-CD20 in Multiple Sclerosis and its animal model - a preliminary analysis.