Levels Of Interleukin Research Articles

Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF

During or after chemotherapy, cognitive impairments characterized by forgetfulness, difficulty concentrating, and depressive and anxiety-like symptoms are observed. There is limited research examining the effects of rosuvastatin (RVS), an HMG-CoA reductase inhibitor, in the context of neuroinflammation-related cognitive disruption. Here, we aimed to investigate the neuroprotective potential of RVS against doxorubicin (DOX)-induced cognitive impairments. Experimental groups were planned as control (normal saline, intraperitoneal), DOX (total cumulative dose 10 mg/kg, intraperitoneal), RVS (10 mg/kg, oral, 20 days), and RVS + DOX. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, genetic, histopathological, and immunohistochemical examinations. Results from Morris water maze (MWM), passive avoidance, locomotion activity, and elevated plus maze (EPM) tests showed that DOX administration caused behavioral disorders. Moreover, DOX increased the levels of inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α), while decreasing the levels of interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase, catalase (SOD), endothelial nitric oxide (eNOS), and catalase (CAT). Co-treatment with RSV significantly attenuated DOX-induced behavioral changes and oxidative stress markers. In addition, similar to the immunohistochemical results, we determined that it increased the expression levels of extracellular signal-related kinases 1/2 (ERK1/2), cyclic adenosine monophosphate response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) and restored the histopathological structure of the brain. Therefore, these results indicated that RSV has a neuroprotective effect against DOX-induced cognitive impairment by reducing neurobehavioral impairments, exerting antioxidant and anti-inflammatory effects, and modulating brain growth factors.Graphical RSV ameliorated DOX-induced cognitive impairments by assessing oxidative stress, BDNF, CREB, and ERK1/2 expression. These beneficial effects induced by RSV provided strong protection against both cognitive dysfunction and anxiety-like behavior. RSV may help prevent or alleviate cognitive dysfunction in patients with various types of cancer undergoing chemotherapy and may have potential benefit in neurodegenerative diseases

An experimental study on the effect of polydatin on retinal ganglion cell apoptosis induced by optic nerve injury

Objective: To investigate the effect of polydatin on retinal ganglion cell (RGC) apoptosis induced by optic nerve injury. Methods: It was an experimental research, conducted from October 2022 to December 2023. Retina-optic nerve explants from C57BL/6 mice were cultured in vitro to simulate optic nerve injury, and a computer-generated random number table was used for complete randomization, assigning the explants to the 0-day uncultured group (immediately detected after sampling), the model group (cultured for 1, 3 or 5 days to establish the injury model), and the polydatin group (with polydatin added throughout the intervention on the basis of the model group). The retinal tissues were collected, and the glial fibrillary acidic protein (GFAP), calcium ion binding protein 1 (Iba1), and ganglion cell marker Brn3a were detected by immunofluorescence staining. The effects of polydatin on the activation of astrocytes and microglia and RGC survival were observed. The expressions of GFAP, Vimentin, Iba1, B-lymphocytoma-2-associated X protein (Bax), lyzed C-caspase 3, and B-lymphocytoma-2 were detected by Western blotting. Real-time fluorescence quantitative PCR was used to detect the mRNA transcription levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10. One-way analysis of variance and LSD-t test were used for statistical analysis. Results: Immunofluorescence staining showed that compared with the model group, the polydatin group inhibited the activation of astrocytes and microglia and protected the RGCs. With explant culture for 1, 3, and 5 days, the expressions of GFAP (0.74±0.01, 0.70±0.04, 0.68±0.02), Vimentin (0.67±0.02, 1.91±0.09, 1.25±0.05), Iba1 (0.87±0.10, 2.36±0.13, 1.64±0.11), Bax (2.48±0.10, 0.37±0.02, 1.69±0.11), and C-caspase 3 (0.77±0.03, 2.49±0.09, 1.65±0.08) in the polydatin group were lower than those in the model group [GFAP (1.23±0.01, 1.17±0.01, 1.77±0.04), Vimentin (1.21±0.02, 2.67±0.06, 1.42±0.03), Iba1 (1.13±0.02, 3.51±0.07, 2.16±0.08), Bax (3.53±0.12, 1.27±0.06, 3.24±0.15), and C-caspase 3 (1.54±0.08, 3.38±0.17, 2.18±0.08)]. The expression of B-lymphocytoma-2 in the polydatin group (2.41±0.09, 1.67±0.07, 6.84±0.20) was higher than that in the model group (1.73±0.08, 0.96±0.07, 2.36±0.33). The differences were statistically significant (all P<0.05). In addition, the mRNA transcription levels of TNF-α (0.47±0.13, 12.07±0.56, 18.06±2.58) and IL-6 (0.55±0.12, 7.48±1.02, 41.35±7.08) in the polydatin group were lower than those in the model group [TNF-α (4.67±0.52, 26.62±2.62, 42.43±4.97) and IL-6 (1.21±0.06, 15.66±0.62, 67.46±3.78)]. The level of IL-10 (0.52±0.07, 2.98±0.24, 5.61±1.23) in the polydatin group was higher than that in the model group (0.06±0.03, 0.12±0.03, 2.64±0.74). The differences were statistically significant (all P<0.05). Conclusion: Polydatin can inhibit the activation of glial cells and the expression of inflammatory factors induced by optic nerve injury, thus enhancing the survival of RGCs.

Liujunzi Decoction Regulated Intestinal Flora Homeostasis to Relieve Lung-Gut Axis Inflammation in Asthma Flora Disorder Mice: Possibly Related to GATA3/ILC2.

To explore the effects and mechanism of Chinese medicine Liujunzi Decoction (LJZD) on regulating microbial flora in mice with asthma flora disorder. Thirty BALB/c female mice were divided into control, model, LJZD [3.5 g/(kg•d), by gavage], dexamethasone [DXMS, 0.7 mg/(kg•d), intraperitoneal injection], and Clostridium butyricum [CB, 230 mg/(kg•d), by gavage] groups according to a random number table, 6 mice in each group. The asthma flora disorder mice model was induced with ovalbumin (OVA). Lung and gut lesions were analyzed by hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stainings. The secretory immunoglobulin A (sIgA) protein expression in lung and gut tissues was detected by Western blot. Flow cytometry was used to detect the relative counts of GATA binding protein 3 (GATA3)/type 2 innate lymphoid cells (ILC2) in lung and gut. The levels of inflammatory factors in lung and gut tissues were detected by enzyme-linked immunosorbent assay (ELISA). Chao1 and Shannon index were used to compare microbial abundance and diversity in alveolar lavage fluid and cecal contents. The similarity or difference in the composition of mice microbial communities was analyzed through cluster analysis. The serum short-chain fatty acids (SCFAs) content was detected by ultra performance liquid chromatograph mass spectrometer (LC-MS)/MS. The asthma flora disorder model mice showed obvious asthma-related symptoms, but LJZD treatment effectively alleviated these symptoms. LJZD restored alveolar wall thickening, airway inflammatory cell infiltration, gut tissue structure destruction, and inflammatory cell infiltration in asthma flora disorder mice. LJZD downregulated the sIgA protein expression in mice (P<0.05). Moreover, LJZD decreased the activation of GATA3/ILC2s in lung and gut tissue (P<0.01), and reduced the levels of interleukin (IL)-5, IL-33, IL-25, IL-9 and IL-13 (P<0.01). LJZD treatment returned the abundance of microbial species and the microbial community structure of alveolar lavage fluid and cecal content in asthma flora disorder mice to the normal state. The SCFAs content and body metabolism were also improved. LJZD exerted anti-asthmatic effects by improving the microbial balance of lung-gut axis and affecting systemic metabolism, consequently regulating the GATA3/ILC2s axis to impact the lung inflammatory response.

White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study

BackgroundStudies have reported that white matter hyperintensities (WMHs) are associated with disturbances in immune function, and the relationship between WMHs and cognitive impairments have been documented in various clinical populations. The present study was to examine the relationship between WMHs, immune function, and cognitive impairments in patients with schizophrenia (SCH) remains unknown.MethodsA sample of 127 drug-naïve first episode SCH and 72 healthy controls (HCs) were included in this study. Serum levels of cytokines and oxidative stress indices were measured using enzyme-linked immunosorbent assay and microtiter plate method. WMHs were assessed using T2-weighted magnetic resonance imaging scanning, and cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery.ResultsWe found patients with SCH are more likely to present with WMHs compared with HCs (OR = 2.076, 95%CI 1.007–4.277, p = 0.048). SCH with WMHs displayed more pronounced cognitive deficits in domains including speed of processing, working memory, verbal learning, visual learning, reasoning, and problem-solving compared with patients without WMHs (p < 0.05). Correlation analysis showed that the volume of WMHs was negative correlated with the problem-solving score (r=-0.331, p = 0.042) in patients with SCH. Within the SCH group, patients with WMHs exhibited elevated levels of interleukin-2 (IL-2), reactive oxygen species (ROS), and superoxide dismutase (SOD), along with lower levels of serum interleukin-4 (IL-4) and interferon-γ (IFN-γ) compared with those without WMHs (p < 0.05). The mediation analyses demonstrated that serum levels of IFN-γ in SCH had fully indirect effects on cognitive function, mediated by the WMHs.ConclusionsThis study suggests that WMHs may play a vital mediating role in the relationship between inflammation, oxidative stress, and cognitive impairments in SCH. Future studies exploring the potential clinical utility of WMHs as biomarkers for early detection and intervention of SCH are warranted.

Exploring the role of CD13 and inflammatory factors in radiation enteritis: insights from high-throughput proteomics and Mendelian randomization analysis

BackgroundRadiation enteritis (RE) is an unavoidable complication during radiotherapy for pelvic malignancies, characterized by chronic inflammation, fibrosis, and vascular injury in the intestinal tissue. Currently, there is a lack of research that delves into the relationship between inflammatory factors and key proteins in RE. MethodsThis study employed high-throughput proteomics to analyze intestinal tissues from RE rats and healthy controls, identifying differentially expressed key proteins. The degree of intestinal damage was validated through HE staining. Furthermore, five Mendelian randomization methods were used to analyze the causal relationship between 70 serum circulating inflammatory factors and CD13 levels. Sensitivity analyses, including heterogeneity tests, leave-one-out tests, and horizontal pleiotropy tests, were performed to ensure the robustness and reliability of the results.ResultsCD13 was identified as a key differentially expressed protein, with its expression significantly upregulated in RE rats and positively correlated with disease severity. Bidirectional Mendelian randomization analysis revealed causal relationships between CD13 and four inflammatory factors: increased levels of CCL28 and EN-RAGE may promote the rise in CD13, while increased levels of TAM-binding protein may be associated with decreased CD13 levels. Additionally, higher CD13 levels were found to be associated with increased levels of interleukin-12. Sensitivity analyses indicated good consistency and reliability in terms of heterogeneity and pleiotropy for these exposure variables.ConclusionThis study reveals the potential mechanistic role of CD13 in RE. Moreover, the identified CD13-associated inflammatory factors offer potential targets for the development of new prevention and treatment strategies, with significant clinical implications.

Changes of serum inflammatory markers and immune function in children with bronchial asthma complicated with mycoplasma pneumoniae infection before and after treatment and their clinical significance

Objective: To evaluate the changes of serum inflammatory markers and immune function in children with bronchial asthma complicated with Mycoplasma pneumoniae infection before and after treatment. Methods: This was a retrospective study. Thirty children with bronchial asthma complicated with mycoplasma pneumoniae infection were selected as the experimental group and 30 healthy children as the control group at Baoding First Central Hospital from December 2022 to December 2023. The levels of inflammatory markers interleukin-2(IL-2), interleukin-4(IL-4), Serum Amyloid A(SAA), Procalcitonin(PCT), immune markers immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM) and CD4+ were detected before and after treatment, and the changes were compared with those of the control group. Results: Compared with the control group before treatment, the levels of immune markers, inflammatory markers IL-2, IL-4 and SAA in the experimental group were significantly different (p &lt; 0.05). However, there was no significant difference between the two groups in PCT (p &gt; 0.05) level. In the experimental group, except PCT, the levels of other inflammatory markers and immune markers were significantly improved after treatment, and the difference was statistically significant (P &lt; 0.05). Conclusion: Inflammatory markers and immune function of children with bronchial asthma complicated with Mycoplasma pneumoniae infection were abnormal to a certain extent, and the improvement was obvious after treatment. The result may have certain reference value for diagnosing the disease and determining its treatment effects. doi: https://doi.org/10.12669/pjms.41.5.11067 How to cite this: Shi XJ, Tian HM, Li CX, Wei JK. Changes of serum inflammatory markers and immune function in children with bronchial asthma complicated with mycoplasma pneumoniae infection before and after treatment and their clinical significance. Pak J Med Sci. 2025;41(5):1506-1510. doi: https://doi.org/10.12669/pjms.41.5.11067 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Obacunone acts as a histone deacetylase 1 inhibitor to limit p38MAPK signaling and alleviate osteoarthritis progression

BackgroundOsteoarthritis (OA) is an age-related progressive degenerative disorder characterized by cartilage extracellular matrix degradation and inflammation. In this study, we explored the function and mechanism of action of obacunone (OB) in inhibiting OA progression.MethodsThe degradation of articular cartilage and its severity were examined using Safranin O-fast green and hematoxylin and eosin (HE) staining. Chondrocyte survival was evaluated using a cell counting kit-8 assay. In addition, qRT-PCR, western blot analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay were performed to evaluate the effects of OB on cartilage injury.ResultsOB mitigated cartilage lesions in rats with anterior cruciate ligament transaction-induced OA. The protein expression of collagen II was increased and the protein expression of ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS-5), matrix metalloproteinase (MMP)-13, and RUNX family transcription factor 2 (RUNX2) was reduced in the articular cartilage of OB-treated rats. Moreover, OB exhibited anti-inflammatory activities by reducing the serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and IL-18. In IL-1β-stimulated primary chondrocytes, OB dose-dependently elevated the expression of collagen II, and decreased the expression of ADAMTS-5, MMP-13, RUNX2 and inflammatory cytokines. Histone deacetylase 1 (HDAC1) was identified as a predicted OB target. OB inhibited HDAC1 expression to limit the activation of p38MAPK signaling. The transfection of chondrocytes with HDAC1 or p38MAPK overexpression plasmids reversed the chondroprotective effects of OB.ConclusionOB mitigated OA progression by binding to HDAC1 and inhibiting p38MAPK signaling, indicating that OB may be a promising drug for the treatment of OA.

Robust differentiation of NK cells from MSLN.CAR-IL-15-engineered human iPSCs with enhanced antitumor efficacy against solid tumors.

Human induced pluripotent stem cells (iPSCs) offer a promising source for chimeric antigen receptor (CAR)-engineered natural killer (NK) products. However, complex iPSC-NK (iNK) manufacturing challenges clinical use. Here, we identified LiPSC-GR1.1 as a superior iPSC line for iNK production. By engineering LiPSC-GR1.1 with a mesothelin (MSLN)-targeting CAR and interleukin-15 (IL-15), we achieved robust differentiation of iPSCs into mature activated iNK cells with enhanced tumor killing efficacy, superior tumor homing, and vigorous proliferation. Single-cell transcriptomic analysis revealed that transforming growth factor-β (TGF-β)-producing tumor cells up-regulated major histocompatibility complex molecules and down-regulated MSLN post-CAR-IL-15 iNK treatment. Tumor-infiltrating CAR-IL-15 iNK cells exhibited high levels of CAR, IL-15, and NK-activating receptors, negligible checkpoint exhaustion markers, and extremely low levels of NK suppressive factors CISH, TGFBR2, and BATF, enabling them to sustain activation, metabolic fitness, and effective tumor killing within TGF-β-rich hypoxic tumor microenvironment. Overall, we developed MSLN.CAR-IL-15-engineered GR1.1-iNK therapy with enhanced antitumor efficacy for solid tumor treatment.

Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis

ABSTRACT Background: Post-traumatic stress disorder (PTSD) is a complex condition linked to inflammation. The causality between inflammatory cytokines and PTSD risk remains unclear. Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) data from 41 inflammatory cytokines and PTSD. Additional analyses included differential gene expression, protein–protein interaction, and functional enrichment to explore underlying mechanisms. Results: MR analysis indicated that higher levels of stem cell factor (SCF) and interleukin-4 (IL-4) are associated with a reduced risk of PTSD. Genes POGZ and LRIG2 were identified as mediators, implicated in the TGF-beta signalling pathway. Conclusion: Our findings suggest a protective role of certain cytokines against PTSD and highlight potential molecular mediators. This knowledge could inform future therapeutic strategies for PTSD.

The anti-inflammatory ability of n-3 PUFAs: optimization of compositions and concentrations in mouse hepatocytes

Purpose This study aims to investigate the impact of the compositions and concentrations of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are significant n-3 polyunsaturated fatty acids (n-3 PUFAs), on the anti-inflammatory properties of lipopolysaccharide (LPS)-stimulated mouse hepatocytes. Design/methodology/approach A mouse hepatocyte inflammation model was established using LPS to evaluate the anti-inflammatory effects of a combination therapy with EPA, ALA and DHA. Interleukin-10 (IL-10), lipoxin A4 (LXA4) and tumor necrosis factor-α(TNF-α) were measured to evaluate the anti-inflammatory ability of hepatocytes. The compositions and concentrations of EPA, ALA and DHA were optimized by response surface methodology to obtain the best anti-inflammatory effect. Findings The optimal inflammatory model was established with 10 µg/mL LPS treatment for 24 h. Maximal cell viability was found at EPA concentration of 150 µM, ALA concentration of 400 µM and DHA concentration of 600 µM. The optimal concentrations of n-3 PUFAs for anti-inflammatory activity in mouse hepatocytes were obtained through single-factor experiments and response surface analysis, with EPA 141.41 µM, ALA 405.45 µM and DHA 551.76 µM. Under optimized conditions, the experimental results for TNF-α, IL-10 and LXA4 levels were close to the theoretical prediction, indicating that the mathematical model was extremely accurate and versatile. Originality/value This study systematically explored the specific effects of different ratios and concentrations of ALA, EPA and DHA on the anti-inflammatory ability of mouse hepatocytes, offering an experimental foundation for the advancement of novel anti-inflammatory medicines and nutritional supplements.

Chronic inflammation response as a key factor in polycystic ovary syndrome among patients with bipolar disorder.

Chronic inflammation response as a key factor in polycystic ovary syndrome among patients with bipolar disorder.

Polystyrene microplastics trigger colonic inflammation in rats via the TLR4/NF-κB/COX-2 pathway and modulation of intestinal microbiota.

Polystyrene microplastics trigger colonic inflammation in rats via the TLR4/NF-κB/COX-2 pathway and modulation of intestinal microbiota.

Highland Barley Improves DSS-Induced Ulcerative Colitis in C57BL/6J Mice.

The prevalence of ulcerative colitis (UC) increases with unhealthy eating habits. Both surgery and medication have the potential to treat the condition, but they may also have more negative effects. This study investigated the anti-inflammatory mechanism of 20% and 40% doses of different highland barley (HB) components (whole grain, peeled, and bran) in a 2% dextran sulfate sodium induced UC mouse model. The results showed that supplementation with a 20% dose of peeled HB restored body weight, disease activity index, colon length, serum interleukin-1β and interleukin-10 levels, liver glutathione peroxidase content, and superoxide dismutase activity to normal levels in mice compared to UC mice. Moreover, the damage caused by UC to the mice's colon was significantly reduced, and the relative expression levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were all significantly downregulated. Additionally, it increased the abundance of Bacteroidota and Firmicutes, improving the balance of gut microbiota.

Therapeutic promise of a sulfated (1 → 4) galactan from edible sea grape Caulerpa racemosa: modulation of cytokine expression in lipopolysaccharide-induced CALU-1 cells.

Therapeutic promise of a sulfated (1 → 4) galactan from edible sea grape Caulerpa racemosa: modulation of cytokine expression in lipopolysaccharide-induced CALU-1 cells.

Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation.

Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation.

Diosmin-loaded chitosan nanoparticles mitigate doxorubicin-evoked cardiotoxicity in rats by featuring oxidative imbalance mechanism, NF-κB, and Bcl-2/Bax pathways.

Diosmin-loaded chitosan nanoparticles mitigate doxorubicin-evoked cardiotoxicity in rats by featuring oxidative imbalance mechanism, NF-κB, and Bcl-2/Bax pathways.

Circulating inflammatory cytokines and risk of aortic stenosis: A Mendelian randomization analysis.

Circulating inflammatory cytokines and risk of aortic stenosis: A Mendelian randomization analysis.

Nebulized riclinoctaose mitigates ovalbumin-induced allergic asthma by attenuating mast cell activation.

Nebulized riclinoctaose mitigates ovalbumin-induced allergic asthma by attenuating mast cell activation.

Decreased circulating CD39+ regulatory T cell frequencies following non-traumatic brain death.

Decreased circulating CD39+ regulatory T cell frequencies following non-traumatic brain death.

β-Hydroxybutyrate aggravates LPS-induced inflammatory response in bovine endometrial epithelial cells by activating the oxidative stress/NF-κB signaling pathway.

β-Hydroxybutyrate aggravates LPS-induced inflammatory response in bovine endometrial epithelial cells by activating the oxidative stress/NF-κB signaling pathway.