Chronic prostatitis-induced excessive inflammation and oxidative stress (OS) damage substantially affect men's quality of life. However, its treatment remains a major clinical challenge. Therefore, the identification of drugs that can decrease chronic prostatitis and oxidative stress targets is urgent and essential. CXCR4 is a classic chemokine receptor that is crucially associated with the occurrence and development of inflammation. This investigation aimed to elucidate how CXCR4 affects prostatitis regression and progression. The effect of CXCR4 on chronic prostatitis was evaluated by HE staining, immunohistochemistry, immunofluorescence, PCR, and TUNEL analyses. Furthermore, CXCR4 influence on metabolism was also evaluated by monitoring body weight, body temperature, food intake, and LC/MS. Additionally, chromatin immunoprecipitation, Western blot, and double luciferase reporter gene assays were carried out to elucidate the mechanism by which CXCR4 modulates Fads2 transcription by PPARγ. Lastly, ROS, DHE, mito-tracker, and ATP were utilized to validate the α-linolenic acid's protective effect against OS in prostate epithelial cells. It was revealed that the inhibition of CXCR4 can effectively alleviate prostatitis in mice. Furthermore, downregulating CXCR4 expression can markedly reduce the inflammatory cell infiltration in mouse prostates, decrease the elevated levels of DNA damage markers,MDA and 4-HNE, and mitigate apoptosis of prostatic epithelial cells. Moreover, treatment of CXCR4 knockdown mice with a PPARγ inhibitor revealed different degrees of changes in the above phenotypes. Mechanistically, the PPARγ protein translocates to the nucleus and serves as a transcription factor to regulate Fads2 expression, thereby altering PUFA metabolism. Additionally, in vitro experiments indicated that α-linolenic acid can effectively alleviate OS damage and RWPE-1 cell apoptosis by protecting mitochondrial function and enhancing the antioxidant capacity of prostatic epithelial cells. In conclusion, reducing the levels of CXCR4 can alleviate inflammation and OS damage in chronic prostatitis.

Perioperative neurocognitive dysfunction (PND) occurs in elderly individuals undergoing anesthesia and surgery. To explore the potential molecular mechanisms, we performed right-sided cervical exploratory surgery under sevoflurane anesthesia in 18-month-old male Sprague-Dawley rats. Anxiety-depression-like behaviors and learning memory abilities were assessed using the Open Field Test (OFT) and Novel Object Recognition (NOR). Additionally, the hippocampus was collected one day after surgery for inflammatory factor detection, TUNEL staining, and metabolomics analysis. Mendelian randomization (MR) analyses were subsequently conducted to validate the causal relationships by using a series of GWAS datasets related to representative differential metabolites as exposures and cognitive impairment as endpoints. The results indicated that rats exposed to anesthesia and surgery exhibited poorer cognitive performance, significant elevations in hippocampal inflammatory factors such as IL-1β and TNF-α, and extensive neuronal apoptosis. LC-MS/MS-based untargeted metabolomics identified 19 up-regulated and 32 down-regulated metabolites in the test group, with 6 differential metabolites involved in metabolic pathways enriched according to the KEGG database. ROC analysis revealed a correlation between α-linolenic acid (ALA) and linoleic acid (LA) and the development of PND. Further MR analysis confirmed that ALA was significantly associated with cognitive performance and the risk of depression, while LA was significantly associated with the risk of memory loss. Taken together, our results identified ALA and LA as potentially powerful biomarkers for PND.

The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.

To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.

A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.

Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.

This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

α-linolenic acid (ALA, 18:3n-3) is a carboxylic acid composed of 18 carbon atoms and three cis double bonds, and is an essential fatty acid indispensable to the human body. This study aims to systematically review related studies on the dietary sources, metabolism, and pharmacological effects of ALA. Information on ALA was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library, and Europe PMC using a combination of keywords including "pharmacology," "metabolism," "sources." The following findings are mainly contained. (a) ALA can only be ingested from food and then converted into eicosapentaenoic acid and docosahexaenoic acid in the body. (b) This conversion process is relatively limited and affected by many factors such as dose, gender, and disease. (c) Pharmacological research shows that ALA has the anti-metabolic syndrome, anticancer, antiinflammatory, anti-oxidant, anti-obesity, neuroprotection, and regulation of the intestinal flora properties. (d) There are the most studies that prove ALA has anti-metabolic syndrome effects, including experimental studies and clinical trials. (e) The therapeutic effect of ALA will be affected by the dosage. In short, ALA is expected to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of ALA.

Sulfasalazine is a recognized therapy for inflammatory bowel disease and is of paramount importance for maintaining intestinal barrier homeostasis. However, its effects on blood-brain barrier (BBB) function and inflammation have not yet been explored. We sought to examine whether sulfasalazine has anti-inflammatory and antiapoptotic effects on the BBB. hCMEC/D3 cells are a well-established BBB in vitro model, were treated with 1 μg/mL Escherichia coli O111:B4 lipopolysaccharide for 12 h. The cell counting kit-8 assay was used to assess cell viability. The cells were also treated with gradient concentrations of sulfasalazine for 12 h. The levels of apoptosis-related proteins and inflammatory factors (IL-1χ and TNF-α IL-6) were measured by western blotting. ZO-1 and F-actin expression was measured by immunofluorescence staining. This study confirmed that 5 mM sulfasalazine improved the maintenance of BBB integrity and relieved lipopolysaccharide-induced inflammatory apoptosis and showed that sulfasalazine might be an effective treatment for BBB disruption.

Flaxseed oil is rich in α-linolenic acid (ALA), which is the metabolic precursor of EPA and DHA. The present study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model. Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5 % maize oil v. 5 % flaxseed oil) and LPS challenge (saline v. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 μg/kg body weight LPS or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 PUFA contents, protein:DNA ratio and pyruvate dehydrogenase complex quantity in muscles (P < 0·05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) 2 and their downstream signalling molecules in muscles and decreased plasma concentrations of TNF-α, IL-6 and IL-8, and mRNA expression of TNF-α, IL-1β and IL-6 (P < 0·05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated protein kinase B (Akt) 1:total Akt1 and phosphorylated Forkhead box O (FOXO) 1:total FOXO1 and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1 and pyruvate dehydrogenase kinase 4 in muscles (P < 0·05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of the TLR4/NOD and Akt/FOXO signalling pathways.