Search Results (1,040)

Background/Objectives: Eosinophilic myocarditis (EM) is a rare, life-threatening inflammatory cardiomyopathy driven by eosinophil cytotoxicity and extracellular trap formation. Interleukin-5 (IL-5) inhibition may disrupt this pathogenic cascade. We reviewed contemporary evidence on IL-5 blockade in EM and contextualized it with an illustrative case. Methods: We searched PubMed through May 2025 for reports of EM treated with mepolizumab or benralizumab. Inclusion criteria were consistent with prior cohorts: acute cardiac symptoms with biomarker elevation plus abnormalities on transthoracic echocardiography and/or cardiac magnetic resonance imaging (CMR), along with documented IL-5-targeted therapy. We extracted clinical, imaging, biopsy, treatment-timing, and outcome data and included one institutional case. Results: Twenty-one episodes were analyzed (median age, 45 years; 10 men). Underlying conditions included eosinophilic granulomatosis with polyangiitis (10 cases; 48%), hypereosinophilic syndrome (5 cases; 24%), drug reaction with eosinophilia and systemic symptoms (DRESS, 3 cases; 14%), and eosinophilic asthma (3 cases; 14%). Treatments involved mepolizumab in 17 cases (81%) and benralizumab in 4 (19%); 4 patients received “early-start” therapy within 14 days of EM diagnosis. Among the 11 episodes with reported left ventricular ejection fraction (LVEF) at baseline and follow-up, the median baseline LVEF was 40% (range, 30–62), with 10 of 11 (91%) <50%. On follow-up, all 11 patients improved: 4 normalized (≥50%) and 7 improved to 40–49%. CMR (n = 18) demonstrated late gadolinium enhancement in 14 cases (78%), edema in 9 (50%), and intracardiac thrombus in 4 (22%). Endomyocardial biopsy confirmed eosinophilic infiltration in 13 of 15 cases (87%). Outcomes included one death (fulminant DRESS), one recovery following veno-arterial extracorporeal membrane oxygenation, and one successful heart transplantation. Illustrative case: A 24-year-old man on a steroid taper received mepolizumab 300 mg on Day 4. His LVEF improved from 47% to 59% by Day 15, accompanied by biomarker decline and successful steroid tapering. Conclusions: Across published cases and our institutional experience, IL-5–targeted therapy appears safe, steroid-sparing, and associated with rapid ventricular recovery, particularly when initiated early. Although limited, these findings support the need for prospective trials to define the optimal agent, dosing, timing, and integration with standard immunosuppression and anticoagulation. Full article

Background/Objectives: Global warming and concomitant extreme weather events have markedly increased the incidence of heat stroke. Heat stroke (HS) poses a substantial threat to cerebral health by triggering neuroinflammation and accelerating neurodegenerative processes. The activation of the Nod-like receptor protein 3 (NLRP3) inflammasome for interleukin-1β (IL-1β) secretion has been implicated as a critical mechanism underlying HS-related fatalities. However, the potential role of specific dietary factors to counteract heat stroke-induced neurotoxicity remains largely underexplored. We previously reported that eicosapentaenoic acid (EPA) and urolithin A (UroA), a gut metabolite of ellagic acid, effectively suppress NLRP3 inflammasome activation against metabolic or pathogenic insults. This study aimed to assess the impact of eicosapentaenoic acid (EPA), urolithin A (UroA), and their combination on mitigating heatstroke-mediated NLRP3 inflammasome activation in microglial cells. Methods: In vitro heatstroke conditions were replicated by subjecting murine BV2 microglial cells to a high temperature (41 °C) under hypoxic conditions. To achieve nutrient loading, BV2 cells were preincubated with either EPA (50 µM) or UroA (10 µM). NLRP3 inflammasome activation was evaluated by proinflammatory gene expression, caspase-1 cleavage in cells, and IL-1β secretion to the medium. The caspase-1 activation was determined using a luciferase-based inflammasome and protease activity reporter (iGLuc) assay. Results: Exposure to high temperatures under hypoxia successfully mimicked HS conditions and promoted NLRP3 inflammasome activation in BV2 cells. Both EPA and UroA substantially attenuated the heat stroke-induced priming of proinflammatory genes. More importantly, EPA and UroA demonstrated a synergistic effect in mitigating HS-induced active caspase-1 production, leading to a dramatic decrease in IL-1β secretion. This synergistic effect between EPA and UroA was further confirmed by the iGLuc reporter assay. Conclusions: Dietary enrichment with EPA and UroA precursors may constitute an efficacious strategy for mitigating heat stroke-mediated neuroinflammation and neurodegenerative diseases. Full article

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated the effects of ZP on ligature-induced experimental periodontitis (EPD) in male Sprague Dawley rats. Animals were assigned to vehicle control, ligature control, ZP-treated (25, 50, and 100 mg/kg), or indomethacin-treated (5 mg/kg) groups (n = 10 per group) and orally administered the respective treatments daily for 10 days after ligature placement. ZP significantly reduced anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissue. ZP suppressed the production of inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, in both gingival tissues and lipopolysaccharide-stimulated RAW 264.7 macrophages, through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In addition, ZP decreased myeloperoxidase activity and reduced matrix metalloproteinase-8 expression, thereby preserving collagen areas. ZP also restored the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) balance, leading to a reduction in osteoclast numbers and their occupancy on the alveolar surface, and it effectively ameliorated horizontal alveolar bone loss. Furthermore, ZP exhibited antioxidant effects by lowering malondialdehyde levels and inducible nitric oxide synthase activity in gingival tissues. Statistical analysis was performed using ANOVA followed by a post hoc test, with significance set at p < 0.05. These findings indicate that ZP mitigates periodontitis through combined antimicrobial, anti-inflammatory, antioxidant, and anti-resorptive actions, supporting its potential as a therapeutic candidate for periodontitis. Full article

Objective: This study aims to explore the feasibility of a non-invasive and simple method for discriminating between health and periodontitis (PRD), facilitating early and objective diagnosis of PRD before detectable periodontal attachment loss and monitoring treatment outcomes. Methods: Salivary samples were collected from 16 PRD-free patients (G1) and 10 patients with PRD (G2). The analysis included salivary matrix metalloproteinase-8 (MMP-8), major anti-inflammatory interleukins (IL-4 and IL-10), pro-inflammatory cytokines (IL-1β, IL-8, and interferon α [IFN-α]), and the cytokine IL-6. Clinical and salivary assessments were performed at baseline (TP0) for both groups and after periodontal treatment for G2 (TP1). Results: PRD indices were significantly higher in G2-TP0, lower in G1, and intermediate in G2-TP1. Except for IL-6, the biomarkers were significantly correlated with nearly all PRD clinical indices. Logistic regression and receiver operating characteristic (ROC) curve analyses showed statistical significance for MMP-8, IL-1β, IL-4, IL-8, and IL-10 when comparing G1 and G2 at TP0. MMP-8 was also significant when comparing G2-TP0 and G2-TP1, while IL-1β and IL-10 showed borderline significance. IL-8 was significant when comparing G1 and G2-TP1. Conclusions: The molecular network demonstrated great potential for early diagnosis and monitoring of therapy response, providing a promising basis for future research. Among the biomarkers, MMP-8, IL-1β, IL-4, IL-8, and IL-10 showed the strongest statistical correlations with the clinical indices. The inflammation-related biomolecules behaved differently among untreated PRD (G2-TP0), treated (G2-TP1), and healthy individuals (G1). Healthy individuals and those with treated PRD may regulate inflammation significantly differently from those with untreated PRD. Full article

Cellular senescence is a major barrier to the therapeutic application of human mesenchymal stem cells (hMSCs), as it compromises their proliferative capacity, differentiation potential, and regenerative efficacy. In this study, we investigated whether FN9-10ELP, a recombinant extracellular matrix (ECM)-mimetic fusion protein composed of fibronectin type III domains 9 and 10 conjugated to elastin-like polypeptides (ELPs), could attenuate etoposide-induced senescence in human turbinate-derived MSCs (hTMSCs). Premature senescence was induced by treatment with 20 µM etoposide, and the protective effects of FN9-10ELP were evaluated in terms of cell viability (using the MTT assay), senescence-associated gene expression (by RT-qPCR analysis), nuclear morphology (after staining with 4’,6-diamidino-2-phenylindole (DAPI)), and SA-β-galactosidase activity. FN9-10ELP treatment significantly improved cell viability and reduced the expression of senescence-associated secretory phenotype (SASP) genes, including interleukin-6 (IL-6), interleukin-8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1). Furthermore, FN9-10ELP alleviated nuclear enlargement and decreased the proportion of SA-β-gal-positive cells, indicating suppression of the senescence phenotype. These findings demonstrate that FN9-10ELP effectively counteracts chemotherapy-induced senescence in hMSCs and highlight its potential as a promising biomaterial for regenerative medicine and anti-aging therapies. Full article

Objectives: In this study, our aim is to summarise the available data on the correlation between sarcopenia and sleep disturbances as a consequence of changes in the myokine concentrations. Methods: Our research was conducted by searching through PubMed, Mendeley and Google Scholar. In our analysis, 63 studies are included from the years 2011 to 2025. Among these studies, there are clinical trials, cross-sectional studies, reviews, systematic reviews and meta-analyses. Discussion: There is vast evidence confirming that sleep disturbances are more common among sarcopenic patients. On the other hand, sarcopenia is frequently observed among people with worse quality of sleep. It is also well documented that sarcopenia leads to changes in the myokine serum concentrations, and similar changes are observed among people suffering from sleep disturbances. Sarcopenic patients have lower levels of irisin, BDNF (brain-derived neurotrophic factor), meteorin and IL-15 (interleukin 15) and higher concentrations of FGF-21 (fibroblast growth factor 21) and interleukins 1β, 6 and 10. Lower levels of irisin, BDNF and meteorin, and higher levels of FGF-21 and interleukins 6 and 10, lead to sleep disturbances, like insomnia, reduction of REM (rapid eye movement) sleep time and lower slow-wave activity during the NREM (non-rapid eye movement) sleep phase. These changes are also observed in obstructive sleep apnea (OSA). More severe OSA is correlated with lower levels of irisin and meteorin and higher levels of FGF-21 and interleukins 6 and 8. Conclusions: Taking into account the similarities in the myokine concentration changes in sarcopenia and in sleep disturbances, it may be concluded that alterations in the myokine levels induced by sarcopenia provoke sleep disturbances. However, it is necessary to further investigate these correlations to understand them better. Full article

Background/Objectives: After the 2022 mpox outbreak also outside Africa, risk groups including people living with HIV (PLWH) were vaccinated with the Modified Vaccinia Ankara–Bavarian Nordic vaccine (MVA-BN). Previous data on PLWH showed that two vaccinations induced specific T cell responses in 64% of the patients and natural monkeypox virus (MPXV) infection in 100%. The initial T cell response assay took place at a median of approximately 100 days post-vaccination and 300 days post-infection. Methods: This study investigates the durability of T cell immunity in PLWH by retesting patients approximately two years after initial assessment. We were able to retest 27 of 33 vaccinated patients and 7 of 10 patients after MPXV infection. T cells were stimulated with the same orthopoxvirus-derived peptide pools as in the initial study, and interferon (IFN)-γ and interleukin (IL)-2 ELISpot assays were performed. Results: The ELISpot assays showed specific T cell responses in 59% and 86% of twice vaccinated and previously infected patients, respectively. Paired analysis revealed no significant differences between previous and current data (short- and long-term follow-up), with IL-2 ELISpot results showing positive correlations at both time points (r = 0.67, p = 0.0001). Long-term IFN-γ responses after MPXV infection were 4.3 times higher (p < 0.01), and IL-2 responses were 2.9 times higher (p = 0.05) than after vaccination. Conclusions: Our data indicates that T cell responses to Orthopoxviruses remain overall stable for 2–3 years in PLWH, with long-term immunity being stronger after natural MPXV infection than after two vaccinations. Full article

Fracture healing failure affects millions globally, yet early molecular mechanisms remain poorly understood. This study aimed to characterize initial fracture response through analyzing peripheral blood hematology, multiplex cytokine profiles, and microRNA (miRNA) expression in fracture hematoma within the first 5 days post-injury. In a prospective cohort of 64 patients with acute clavicle fractures, we assessed hematological parameters, cytokine levels via multiplex immunoassays, and miRNA expression through RNA sequencing, and quantitative PCR (qPCR) validation. Fracture severity and time elapsed post-injury were key drivers of molecular response variability. Severe fractures (type C) were associated with older patient age and impaired hematological parameters, including reduced hemoglobin, erythrocyte counts, and hematocrit. Leukocyte counts declined over time, reflecting evolving systemic inflammation. Severity-dependent cytokines included eotaxin, interferon alpha-2 (IFNα2), interleukin-1 alpha (IL-1α), macrophage inflammatory protein-1 (MIP-1α), whereas interferon gamma-induced protein 10 (IP-10) and MIP-1α distinguished temporal healing phases. MiRNA profiling revealed 55 miRNAs with significant time-dependent expression changes (27 downregulated, 28 upregulated). Five key miRNAs (miR-140-5p, miR-181a-5p, miR-214-3p, miR-23a-3p, miR-98-5p) showed robust temporal patterns and enrichment in cytokine signaling pathways critical for bone repair. This work presents the first detailed molecular portrait of early human fracture healing, highlighting hematological, immune cytokine, and miRNA networks orchestrating repair. These insights provide a foundation for biomarkers development to predict healing outcomes and support precision-targeted interventions in fracture management. Full article

Background: A cytokine storm can lead to organ dysfunction and death in critically ill children. Extracorporeal hemoperfusion aims to reduce hyperinflammation by filtering out mid-range cytokines (e.g., IL-6), but pediatric data remain limited. Methods: We conducted a narrative review with PRISMA-guided screening of PubMed, Scopus, and Google Scholar for pediatric reports of HA330/HA380 from January 2020 to June 2025. Due to heterogeneity in populations, circuits, and outcome timing, the results were synthesized descriptively. Three studies met the inclusion criteria: a prospective series of 12 patients with septic shock using HA330, a single case of a pediatric heart transplant with HA380 during cardiopulmonary bypass, and a retrospective comparative cohort study of Pediatric Intensive Care Unit (PICU) oncology patients on continuous renal replacement therapy (CRRT) comparing HA330 (n = 11) versus CytoSorb (n = 10). Results: Three studies involving 23 pediatric patients were analyzed. The median age was 8 years, and 56.5% of patients were male. Most patients underwent hemoadsorption with HA330 via continuous renal replacement therapy (CRRT) or continuous venovenous hemodiafiltration (CVVHDF). Post-treatment reductions were noted in interleukin-6 (IL-6) (mean −69.6%), C-reactive protein (CRP) (−59.0%), and procalcitonin (PCT) (−70.4%). Severity scores (Pediatric Logistic Organ Dysfunction-2 (PELOD-2), Pediatric Risk of Mortality-3 (PRISM-3), and Pediatric Sequential Organ Failure Assessment (pSOFA) improved significantly (p = 0.002). The mean PICU stay was 15.6 days. The survival rate was 87%, and no hemoadsorption-related adverse events were reported. Conclusions: HA330/380 hemoadsorption is a safe and potentially effective treatment for pediatric cytokine storms, reducing inflammation and improving clinical status. However, larger, standardized studies are needed to confirm these findings and guide clinical use. Full article

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) encompasses a spectrum of liver conditions and involves gut–liver axis crosstalk. We aimed to evaluate whether oral vancomycin modifies liver injury and the cecal microbiota in a methionine–choline-deficient (MCD) diet model of NASH. Male C57BL/6J mice (n = 28) were block-randomized to four groups (n = 7 each) for 10 weeks: standard diet (STD); MCD diet; STD + vancomycin (VANC); and MCD + VANC (2 mg/mouse ≈ 50 mg/kg, every 72 h). After 10 weeks, liver tissues were analyzed for histological changes, cytokine levels [interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor beta 1 (TGF-β1)], and immunohistochemical markers [ubiquitin and cytokeratin 18 (CK18)]. Cecal microbiota composition was evaluated with 16S ribosomal RNA (rRNA) sequencing. The MCD reproduced key NASH features (macrovesicular steatosis, lobular inflammation). Vancomycin shifted steatosis toward a microvesicular pattern and reduced hepatocyte injury: CK18 and ubiquitin immunoreactivity were decreased in MCD + VANC vs. MCD, and hepatic IL-8 and TGF-β1 levels were lower in MCD + VANC vs. STD. Taxonomically, STD mice had Lactobacillus-rich microbiota. The MCD diet alone reduced alpha diversity (α-diversity), modestly lowered Firmicutes and increased Desulfobacterota/Fusobacteriota. Vancomycin alone caused a much larger collapse in richness, depleting Gram-positive commensals and promoting blooms of Escherichia–Shigella, Klebsiella, Parabacteroides, and Akkermansia. In the MCD + VANC group, vancomycin profoundly remodeled the microbiota, eliminating key commensals (e.g., Lactobacillus) and enriching Desulfobacterota, Fusobacteriota, and Campylobacterota. Oral vancomycin in the MCD model of NASH improved liver injury markers and altered steatosis morphology, but concurrently reprogrammed the gut into a low-diversity, pathobiont-enriched ecosystem with near-loss of Lactobacillus. These findings highlight a therapeutic trade-off—hepatic benefit accompanied by microbiome cost—that should guide microbiota-targeted strategies for NAFLD/NASH. Full article

MPs are pervasive pollutants in marine ecosystems, posing risks to aquatic organisms due to their small size and bioaccumulation potential. This study investigated the intestinal toxicity of MP particles extracted from mangrove sediments in zebrafish, comparing the effects before and after microbial degradation. Zebrafish were exposed to either undegraded MPs or microbially degraded MP extracts at concentrations of 0 (control), 2, 10, and 50 mg/L for 21 days in 10 L tanks (stocking density: 10 fish/L), with three replicate tanks per concentration. MPs were dispersed ultrasonically before addition to the water. Intestinal samples were collected on 7, 14, and 21 days for the analysis of immune response (tumor necrosis factor-alpha, TNF-α; interleukin-1 beta, IL-1β; interleukin-6, IL-6; interleukin-8, IL-8) and antioxidant activity (superoxide dismutase, SOD; catalase, CAT). Histopathological analysis revealed intestinal wall thinning, villus damage, and epithelial cell detachment in zebrafish exposed to both undegraded and degraded MP extracts; however, undegraded MPs induced more severe intestinal damage. Results indicated dynamic changes in cytokine expression: TNF-α decreased initially before increasing, while IL-1β and IL-8 first rose then declined. IL-6 peaked on day 7, dropped by day 14, and increased again on day 21. CAT expression decreased, whereas SOD increased only in the pre-degradation group. Microbial degradation reduced intestinal damage severity, with effects intensifying at higher MP exposure levels. These findings demonstrate that MPs can impair zebrafish digestive systems, but microbial degradation mitigates their toxicity. This study underscores the importance of biodegradation as a potential environmental remediation strategy and provides experimental evidence on MPs’ impact on aquatic organisms. Full article

Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers and modulate neurotransmitter levels. Material and Methods: A total of 30 rats were taken and randomly grouped into five groups: group I—control; group II—METH 100 mg/kg/i.p.; group III—METH + cubebin (10 mg/kg/p.o.); group IV—METH + cubebin (20 mg/kg/p.o.); and group V—cubebin per os at 20 mg/kg. After a 14-day oral regimen, behavioral activities were assessed utilizing the Morris water maze (MWM). Biochemical analysis included neurotransmitters, including dopamine (DA), norepinephrine (NE), and gamma-aminobutyric acid (GABA); oxidative stress markers (malondialdehyde (MDA); nitric oxide (NO), catalase (CAT), reduced glutathione (GSH)); inflammatory cytokines [interleukin (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]; neurotrophic factors (BDNF, CREB); and apoptotic markers (caspase-3 and caspase-9). Furthermore, molecular docking and simulation studies were conducted. Results: Treatment with cubebin led to a marked reduction in latency during the MWM task. It significantly modulated the oxidative stress markers (SOD, GSH, CAT, MDA, and NO), inflammatory cytokines (IL-6, IL-1β, TNF-α), neurotrophic factors (CREB, BDNF), apoptotic markers (NFkB, caspase-3, caspase-9), and neurotransmitters (NE, DA, and GABA) in METH-induced memory-impaired rats. The results of molecular dynamics simulation (MDS) provided insight into the mechanisms that associate proteins CREB, BDNF, and caspase-3 in conformational dynamics upon binding to cubebin. Conclusions: In conclusion, cubebin administration improved cognitive function in rats by modulating antioxidant enzyme activity, reducing pro-inflammatory cytokines, and regulating neurotransmitter levels, demonstrating its potential neuroprotective effects against MA-induced neurodegeneration. Full article

Objectives: The current study focused on the kidney protection and antioxidant properties along with the potential anti-ferroptotic activity of Geranium macrorrhizum L. (G. macrorrhizum) oil to ameliorate the acute renal oxidative tissue damage and toxicity of the aminoglycoside antibiotic gentamicin (GM) in an experimental murine model. Methods: The research was carried out with mature Balb/c mice distributed into four groups (n = 6). Application of GM (200 mg kg⁻¹ intraperitoneal injection for 10 days) was performed to induce kidney injury. Only saline was administered to the controls. The remaining groups were administered G. macrorrhizum oil (50 mg kg⁻¹ per dose) either used alone or in combination with GM. To assess the renal antioxidant status, the activities of specific antioxidant enzymes, indicators of lipid and DNA peroxidation and renal functional damage were examined using standard commercial kits, ELISA and EPR spectroscopy. Results: G. macrorrhizum oil analysis revealed 20 organic components belonging to mono- and sesquiterpenoids and long-chain hydrocarbons. The antioxidant and anti-inflammatory effects of G. macrorrhizum oil were demonstrated by reduced malondialdehyde, ROS, 8-hydroxy-2′-deoxyguanosine and cytokine levels (especially interleukin-1β) compared with GM. Furthermore, increased activation of superoxide dismutase, catalase and glutathione (GSH) were observed in the kidney homogenates of the animals which received GM in combination with G. macrorrhizum oil compared with the GM group. Additional changes in the GSH/glutathione peroxidase-4 axis were detected, suggesting the possible anti-ferroptotic potential of the oil. Nephroprotection was also demonstrated by elevated PGC-1α expression (peroxisome proliferator-activated receptor γ coactivator 1-alpha) and reduced KIM-1 levels (kidney injury molecule-1) following application of the oil. Conclusions: The preserved kidney antioxidant and functional properties in the groups treated with oil suggest that Geranium macrorrhizum L. could be utilized clinically to mitigate the toxic effects of GM application. Full article

The spleen is essential for immunity, mediating host defense against pathogens and regulating immunological homeostasis. Western-style diets commonly cause the aggregation of body fat and the emergence of obesity. This state might lead to damage to the spleen’s functions. However, the effects of Western-style diets on gene expression and metabolic regulation in the spleen have not yet been fully explored. In this study, C57BL/6 mice were fed either a high-fat diet (HFD) or standard chow (CHFD) for 10 weeks starting at 8 weeks old. Weekly weights were recorded, and spleens were weighed at 18 weeks. The results showed that HFD mice had significantly higher body weights from 12 weeks (p < 0.05) and a higher splenic index at 18 weeks (p < 0.01). HE staining revealed disrupted spleen structures and infarcted areas in the HFD group. Transcriptome sequencing highlighted immune-related pathways, including inflammatory response and interleukin-6 production. Among the differentially expressed genes (DEGs), PCK1, ALDH9A1, and ALDH7A1 were significantly upregulated in the HFD group, whereas PLA2G2F and PLA2G4F exhibited significant downregulation. APOB emerged as a key hub gene in PPI analysis. Metabolomics analysis identified significantly different metabolites (SDMs), including Rifamycins, 7-Ketodeoxycholic Acid, Folinic Acid, and Lotaustralin, as key biomarkers for an HFD, while 1-Methylnicotinamide and Prostaglandin E1 were significant for CHFD. KEGG enrichment linked glycerophospholipid and arachidonic acid metabolism to both transcriptome and metabolome results. The joint analysis of transcriptome and metabolome data revealed that SLC22A8 was negatively correlated with Biliverdin and 1-methylnicotinamide, and MCPT1 was inversely correlated with 7-Ketodeoxycholic Acid. These findings offer insights into the molecular mechanisms and metabolites that influence spleen immunity and systemic immune homeostasis. Full article

Erythropoietin (EPO), clinically used as a therapeutic agent for patients with renal anemia, has been reported to exert tissue protective effects independently of hematopoiesis. Insulin resistance is a pathophysiological condition that causes hypertension, diabetes mellitus, and dyslipidemia, leading to vascular and renal injury. The present study investigated whether EPO would improve insulin resistance and vascular and renal injury in chronic sucrose treatment-induced insulin resistant model rats. Sucrose (12%) was given in drinking water for 10 weeks to induce insulin resistance, and EPO (75 U/kg, 3 times/week) was administered subcutaneously for the last 4 weeks. Responses to the oral glucose tolerance test and values of the homeostatic model assessment for insulin resistance indicated that EPO improved insulin resistance in sucrose-treated rats. Though there were no differences in the expression of phospho-Akt (Ser473)/total Akt among all groups, EPO increased that of phospho-STAT3 (Tyr705)/total STAT3 in the liver. Macrophage infiltration into the adventitial area of the aorta and renal overexpression of monocyte chemoattractant protein-1 in the sucrose-treated group were suppressed by EPO treatment, suggesting anti-inflammatory effects of EPO. EPO also decreased collagen I expression in the kidney. A proinflammatory M1-type macrophage marker, tumor necrosis factor-α, was decreased, and anti-inflammatory M2-type macrophage markers, arginase-1 and interleukin-10, were increased by EPO treatment. These results suggest that EPO improved insulin resistance and vascular and renal inflammation in the setting of insulin resistance. Full article