Serum Levels Of IL-6 Research Articles

Treatment with tofacitinib attenuates muscle loss through myogenin activation in the collagen-induced arthritis

Abstract Background Sarcopenia is a muscle disease characterized by reduction of muscle strength and muscle mass. In RA, 25.9 to 43.3% of the patients present sarcopenia. The loss of muscle mass observed in RA patients occurs either by activation of catabolic pathways or by inhibition of anabolic pathways. Despite having a list of drugs capable of treating RA inflammation, their effect on muscle is unclear. Our objective was to evaluate the tofacitinib effect on the muscle mass of collagen-induced arthritis (CIA) mice. Methods CIA was induced in male DBA/1J mice by subcutaneous injection of Type 2 Collagen plus Freund Adjuvant. Animals were randomized into 3 groups: CIA + tofacitinib; CIA + vehicle; and healthy controls. Treatment was administered twice a day, between days 18 and 45 after induction. Clinical score, edema, and body weight were evaluated during the experimental period. After euthanasia, tibiotarsal joints were collected for assessment of disease histopathological score, and tibialis anterior (TA) and gastrocnemius (GA) muscles were weighed to assess muscle mass. Muscle atrophy was evaluated by measurement of TA myofiber cross-sectional area (CSA). Protein expression was evaluated by western blot using GA homogenates. Serum inflammatory markers were evaluated by ELISA. Statistical analysis included ANOVA followed by Tukey’s or with Kruskal-Wallis. The statistical difference was assumed for p < 0.05. Results Tofacitinib treatment decreased arthritis severity by reducing clinical score, and hind paw edema in comparison with the vehicle group. Tofacitinib showed weight gain, higher TA and GA weights, and increased CSA compared to the vehicle group. On day 45, Tofacitinib presented increased muscle strength compared to the vehicle group, however, no difference was found in muscle fatigue. Pax7 expression was unchanged, while MyoD expression showed an increasing trend, and myogenin expression was significantly increased in Tofacitinib compared to vehicle and control groups. The treatment didn’t modify Murf-1 expression. Tofacitinib mice showed decreased serum levels of TNF and increased IL-6 serum levels. Conclusion Tofacitinib attenuated muscle loss in arthritic mice, increased muscle weight and muscle CSA. Activation of satellite cell regeneration, based on the increased expression of myogenin, is a potential mechanism involved in tofacitinib action against muscle loss.

Effects of Nigella sativa on disease activity, T lymphocytes and inflammatory cytokine profiles in pediatric systemic lupus erythematosus: A randomized controlled trial

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, requiring long-term treatment that can have side effects, particularly in pediatric patients. Nigella sativa (NS) has shown potential for improving SLE symptoms due to its anti-inflammatory and immunomodulatory effects. The aim of this study was to investigate the immunomodulatory effect of N. sativa oil (NSO) on disease activity, T lymphocyte activity and inflammatory cytokine profiles in pediatric SLE patients. A randomized, double-blinded, placebo-controlled clinical trial was conducted at Saiful Anwar Hospital in Malang, Indonesia, from January 2022 to January 2023. Pediatric patients with SLE were randomly assigned to receive either one gram of NSO or a placebo containing starch in capsule form as adjunct therapy alongside their SLE primary treatment. Blood samples were collected before treatment and after eight weeks of daily capsules. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K); flow cytometry was used to identify T helper lymphocytes, and serum cytokine levels were measured using ELISA. The statistical analysis tests were performed to compare the outcomes between groups at baseline or after the treatment, and within-group comparisons before and after the study period, as appropriate. A total of 32 patients were included in the study. A significant decrease in the SLEDAI-2K score was observed at post-treatment in both the NSO and placebo groups (p<0.001 and p=0.025, respectively). The percentage of T helper 17 (Th17) cells was significantly reduced in both the NSO and placebo groups post-treatment compared to pre-treatment (p=0.026 and p=0.034, respectively). Conversely, the post-treatment percentage of regulatory T (Treg) cells increased significantly in both groups. A significant reduction in interleukin (IL)-2 levels was observed in the NSO and placebo groups at post-treatment compared to pre-treatment (p=0.006 and p=0.046, respectively). Additionally, there were increases in IL-4 and IL-6 serum levels in both groups at post-treatment compared to pre-treatment (p<0.05). This study highlights that although disease activity was not significantly different between NSO and placebo groups, NSO could affect the inflammatory cytokine profiles in pediatric SLE patients.

Hemin attenuates bleomycin-induced lung fibrosis in mice by regulating the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model. The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA. Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

F-Box and WD repeat domain containing 7 induces infectious osteomyelitis by regulating MYB stability and ubiquitination.

Osteomyelitis is a bone inflammation initiated by invading pathogens. Macrophages and inflammation play essential roles in osteomyelitis. F-Box and WD repeat domain containing 7 (Fbxw7) is a tumour suppressor and E3 ubiquitin ligase. In the present study, the potential roles of Fbxw7 in osteomyelitis were explored. The mRNA level of Fbxw7 was measured in bone marrow cells from patients with osteomyelitis and Staphylococcus aureus (S. aureus)-infected macrophages. The conditional knockout mice with Fbxw7 deficiency in myeloid cells were generated. The expression of interleukin (IL)-6, IL-23a and nitric oxide synthase 2 (Nos2) was measured in S. aureus-infected Fbxw7-deficient bone marrow-derived macrophages (BMDMs). The body weight loss, bacterial burden, bone loss and formation and serum level of IL-6, IL-23 and TNF-α were measured in S. aureus-infected Fbxw7 conditional KO mice. The interacting partners of Fbxw7 were predicted using STRING and the interaction were tested. Elevated expression of Fbxw7 was observed in bone marrow cells from patients with osteomyelitis and in S. aureus-infected macrophages. The expression of IL-6, IL-23a and Nos2 was remarkably suppressed in S. aureus-infected Fbxw7-deficient BMDMs. Fbxw7 conditional knockout mice had less body weight loss, higher bacterial burden, less bone loss and formation and decreased serum level of cytokines. Fbxw7 interacted with MYB. S. aureus-infected Fbxw7-deficient BMDMs had higher level of MYB and less ubiquitination of MYB. Fbxw7 promotes osteomyelitis symptoms by regulating ubiquitination and stability of MYB.

Correlation of biochemical markers and inflammatory cytokines in autism spectrum disorder (ASD)

IntroductionAutism Spectrum Disorder (ASD) is a disorder that severely affects neurodevelopment, and its underlying causes are not yet entirely understood. Research suggests that there may be a connection between the occurrence of ASD and changes in immune responses. This study aims to know if some biochemical and inflammatory cytokines are promising biomarkers for ASD and whether they are involved in the pathogenesis of ASD.MethodsThe serum levels of CRP, TNF-α, TGF-β, IL-1β, IL-10, 1 L-8, and IL-6 were measured in all of the patients (n = 22) and in the healthy (n = 12) children using ELISA method.ResultsThe serum concentrations of IL-10 and IL-8 were significantly lower in the ASD patients compared to the control group (p < 0.05) and there were not significant differences between CRP, TNF-α, TGF-β, IL-6 and IL-1β levels in two groups. There were positive correlations between CRP and IL-10, also CRP and IL-8, in ASD group. In contrast to the ASD patients, the correlations of IL-8, IL-10, and CRP were not significant in the control group.ConclusionIn conclusion, this study highlights the potential role of certain biochemical markers and inflammatory cytokines in ASD. Specifically, the lower levels of IL-10 and IL-8 in ASD patients, along with the significant correlations between CRP and these cytokines, suggest an altered immune response in individuals with ASD. These findings support the hypothesis that immune dysregulation may be involved in ASD pathogenesis. Further research is needed to explore these biomarkers and their mechanistic links to ASD, which could lead to improved diagnostics or therapeutic strategies.

Traditional Chinese herbal formula, Fuzi-Lizhong pill, produces antidepressant-like effects in chronic restraint stress mice through systemic pharmacology

Ethnopharmacological relevanceFuzi-Lizhong pill (FLP) is a well-validated traditional Chinese medicine (TCM) formula that has long been used in China for gastrointestinal disease and adjunctive therapy for depression. In our previous study, we reported that the principal herb of FLP, Aconitum carmichaelii Debx. (Fuzi), exhibits antidepressant-like effects. However, there have been no reports on whether FLP produces antidepressant-like effects and its potential molecular mechanisms. Aim of the studyWe aim to demonstrate the antidepressant-like effects of FLP in chronic restraint stress (CRS) mice and to explore the associated molecular mechanisms. Materials and methodsThe active components and probable molecular targets of FLP, as well as the targets related to depression, were identified through network pharmacology. A protein-protein interaction (PPI) network was generated using the overlapping targets, followed by the visualization as well as identification of the core targets associated with the antidepressant-like action of FLP. Subsequently, KEGG and GO enrichment analyses were conducted. UHPLC-MS/MS was employed to further detect the active compounds in FLP. Molecular docking was applied to assess the connections between the active components as well as the core targets. The efficacy of FLP in treating depression and its molecular mechanisms were examined using western blotting, ELISA, 16S rRNA sequencing, HE staining, Nissl staining, and Golgi-Cox staining in a CRS-induced mouse model. ResultsNetwork pharmacology and UHPLC-MS/MS analyses indicated that the active compounds of FLP comprised taraxerol, songorine, neokadsuranic acid B, ginkgetin, hispaglabridin B, quercetin, benzoylmesaconine and liquiritin. KEGG pathway analysis implicated that the PI3K/Akt/mTOR as well as MAPK signaling pathways are closely related to the therapeutic effects of FLP on depression. Molecular docking analysis demonstrated that the main components of FLP bind to PI3K, AKT, mTOR, BDNF and MAPK. FLP significantly decreased immobility in mice that were elevated by CRS in the FST and the TST. FLP also significantly increased sucrose preference in mice after CRS in the SPT. FLP upregulated proteins associated with BDNF-TrkB and PI3K/Akt/mTOR signaling and downregulated proteins associated with MAPK signaling. Serum levels of CORT, IL-6, IL-1β, and TNF-α in CRS mice were significantly decreased following treatment with FLP. In addition, FLP ameliorated CRS-induced gut microbiota dysbiosis as demonstrated by 16S rRNA sequencing analysis. FLP ameliorated CRS-induced intestinal inflammation and neuronal damage. Finally, antidepressant-like effects and concomitant increases in dendritic spine density induced by FLP administration were also reduced after rapamycin treatment. ConclusionThese results demonstrate that FLP has antidepressant-like effects in mice exposed to CRS that involve activation of the PI3K/Akt/mTOR signaling pathway, increase in spinogenesis, inhibition of the MAPK signaling pathway, decrease in inflammation, and amelioration of gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of FLP on depression.

Profiling of Toll-like Receptors and Related Signaling Mediators in the Pathogenesis of Morphea

Introduction: Morphea, also known as localized scleroderma, is a rare fibrosing inflammatory disease of unknown pathogenesis. Objectives: Although the genetic basis for morphea is important, the evaluation of Toll-like receptors (TLR) in this disease is quite limited. We aimed to evaluate TLR expression levels and serum IL-6, IL-17A, TGF-b1, FGF, and VEGF levels in patients with morphea, and compare these results with healthy controls. Methods: The expression levels of TLRs in the lesional and non-lesional adjacent skin of patients with morphea, and normal skin of healthy controls were evaluated by RT-PCR whereas serum levels of IL-6, IL-17A, TGF-b1, FGF, and VEGF were evaluated by ELISA. Results: Based on our findings, TLR1 gene expression increased 34.3-fold in the lesional skin of patients with morphea. In addition, IL-6, IL-17A, TGF-β, FGF and VEGF were found to be higher in the blood samples of the patient group than in the healthy group. Conclusion: TLRs are important parts of the pathogenesis of morphea, and a better understanding of it will lead to more directed and effective treatments. We believe that this study will be important for pioneering TLR-targeted therapeutic approaches in the treatment of morphea in the future.

CCN5/WISP2 serum levels in patients with coronary artery disease and type 2 diabetes and its correlation with inflammation and insulin resistance; a machine learning approach

IntroductionStudies have shown various effects of CCN5/WISP2 on metabolic pathways, yet no prior investigation has established a link between its serum levels and CAD and/or T2DM. Therefore, this study seeks to explore the relation between CCN5 and the risk factor of CAD and/or diabetes, in comparison to individuals with good health, marking a pioneering endeavor in this field. MethodsThis case-control study investigates serum levels of CCN5, TNF-α, IL-6, adiponectin, and fasting insulin in a population of 160 individuals recruited into four equal groups (T2DM, CAD, CAD-T2DM, and healthy controls). Statistical tests comprise Chi-square tests, ANOVA, Spearman correlation, and logistic regression. ROC curves were used to represent the diagnostic potential of CCN5. Disease states are predicted by machine learning algorithms: Decision Tree, Gradient Boosted Trees, Random Forest, Naïve Bayes, and KNN. These models' performance was evaluated by various metrics, all of which were ensured to be robust by applying 10-fold cross-validation. Analyses were done in SPSS and GraphPad Prism and RapidMiner software. ResultsThe CAD, T2DM, and CAD-T2DM groups had significantly higher CCN5 concentrations compared to the healthy control group (CAD: 336.87 ± 107.36 ng/mL, T2DM: 367.46 ± 102.15 ng/mL, CAD-T2DM: 404.68 ± 108.15 ng/mL, control: 205.62 ± 63.34 ng/mL; P < 0.001). A positive and significant correlation was observed between CCN5 and cytokines (IL-6 and TNF-α) in all patient groups (P < 0.05). Multinomial logistic regression analysis indicated a significant association between CCN5 and T2DM-CAD, T2DM, and CAD conditions (P < 0.001) even after adjusting for gender, BMI, and age (P < 0.001). Regarding the machine learning models, the Naïve Bayes model showed the best performance for classifying cases of T2DM, achieving an AUC value of 0.938±0.066. For predicting CAD, the Random Forest classifier achieved the highest AUC value of 0.994±0.020. In the case of CAD-T2DM prediction, the Naïve Bayes model demonstrated the highest AUC of 0.981±0.059, along with an Accuracy of 97.50 % ± 7.91 % and an F-measure of 96.67 % ± 10.54 %. ConclusionOur study has revealed, for the first time, a positive connection between CCN5 serum levels and the risk of developing T2DM and CAD. Nonetheless, more research is needed to ascertain whether CCN5 can serve as a predictive marker.

Moringa oleifera Lam. seed lectin (WSMoL) reduces chronic stress-induced anxiety and depression in mice by lessening inflammation and balancing brain chemicals

Phyto-based treatments for anxiety and depression are gaining attention. The efficacy of the water-soluble Moringa oleifera seed lectin (WSMoL) in reducing acute anxiolytic and depressive-like behaviors in mice has been previously demonstrated. In the present study, it was evaluated the effects of WSMoL on reducing anxiety and depressive-like symptoms in a mouse model of unpredictable chronic mild stress (UCMS). The animals were divided into groups and exposed to a four-week UCMS regimen. Following this, the mice received daily intraperitoneal injections of vehicle (non-stressed and UCMS control groups), WSMoL (2 or 4 mg/kg), or fluoxetine (10 mg/kg) for 21 days. Neurobehavioral tests included the open field test and elevated plus maze test to assess anxiety-like behavior, and the tail suspension test and sucrose preference test to evaluate depression-like behavior. Biochemical analyses measured serum corticosterone and cytokines as well brain levels of cytokines and monoamines. All tests indicated that WSMoL significantly (p < 0.05) reversed the anxiety and depression-like behaviors induced by UCMS. The stress protocol increased serum corticosterone levels and WSMoL treatment was not able to normalize corticosterone secretion. WSMoL treatment reduced serum and brain levels of IL-2, IL-6, and TNF-α, indicating reduced neuroinflammation, and increased brain levels of dopamine, serotonin, and noradrenaline. In summary, WSMoL mitigated UCMS-induced anxiety and depression-like behaviors by reducing neuroinflammation and modulating brain monoamine levels.

Peripheral biomarkers of Parkinson’s disease and its correlation with clinical symptoms: a case-control study

BackgroundInflammation significantly impacts Parkinson’s disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive.ObjectiveTo identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD.Methods79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD.ResultsCompared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups.ConclusionElevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD.

Impact of HHIP gene polymorphisms on phenotypes, serum IL-17 and IL-18 in COPD patients of the Chinese Han population

BackgroundGenetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population.MethodsA case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders.ResultsOur study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes.ConclusionThis study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes.Trial registrationwww.chictr.org.cn ID: ChiCTR2300071579 2023-05-18.

Increased serum level of IL-6 predicts poor prognosis in anti-MDA5-positive dermatomyositis with rapidly progressive interstitial lung disease

BackgroudAnti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-positvie DM) is a subtype of dermatomyositis with a poor prognosis, characterized by rapidly progressive interstitial lung disease (RP-ILD). The study aims to investigate the significance of serum cytokines profiles and peripheral lymphocytes in predicting prognoses of anti-MDA5-positvie DM with RP-ILD. Furthermore, it seeks to analyze longitudinal data of lymphocytes during hospitalization to identify distinct trajectories and cluster patients accordingly.MethodsA total of 168 patients with anti-MDA5-positive DM were enrolled in this retrospective study from two cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the predictors of 6-month all-cause mortality and RP-ILD. Group-based trajectory modeling (GBTM) was employed to model the trajectories of longitudinal peripheral lymphocytes.ResultsIn the multivariate Cox regression analysis, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, lymphocytes from 0.5 to 1.0 × 109 /L, older age, and elevated LDH were identified as independent predictors of 6-month all-cause mortality. Furthermore, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, and lymphocytes from 0.5 to 1.0 × 109 /L were found to be independent predictors of RP-ILD. Additionally, three trajectory groups of lymphocytes within the first week after admission were established based on GBTM. These groups included: Group 1, with low-level of lymphocytes that declined; Group 2, with medium-level of lymphocytes that slightly rose; and Group 3, with high-level of lymphocytes that rose. Notably, group 1 showed the highest mortality (90.7%) and all experiencing RP-ILD. Increased expression of IL-6 in lung tissues was observed in two cases with RP-ILD compared to two cases without RP-ILD. We also found the increased infiltration of CD4 + and CD8 + T cells, particularly CD8 + T cells, in lung tissues from patients with RP-ILD.ConclusionsOur study demonstrated that increased level of serum IL-6 (≥ 13.41pg/mL) and severe lymphopenia were promising predictors of 6-month all-cause mortality and the occurrence of RP-ILD in anti-MDA5-positive DM patients. Furthermore, tracking distinct trajectories of lymphocytes during hospitalization can be utilized to cluster patients.

Alginate from Ericaria crinita Possesses Antioxidant Activity and Attenuates Systemic Inflammation via Downregulation of Pro-Inflammatory Cytokines

Alginates are anionic polysaccharides present in the cell walls of brown seaweeds. Various biological activities of alginate and its derivatives have been described. In this study, we assessed the potential of alginate obtained from Ericaria crinita (formerly Cystoseira crinita) to scavenge free radicals and function as a ferric ion reductor. The anti-inflammatory effect on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment was also examined. Ericaria crinita alginate showed antioxidant activities of IC50 = 505 µg/mL (DPPH) and OD700 &gt; 2 (ferric reducing power). A significant decrease in serum levels of IL-1β was observed only in animals treated with the polysaccharide at a dose of 100 mg/kg bw. Both doses of E. crinita alginate (25 and 100 mg/kg bw) significantly reduced the serum concentrations of pro-inflammatory cytokines TNF-α and IL-6, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. Our findings show the potential of E. crinita alginate to act as an antioxidant and anti-inflammatory agent. It is likely that the exhibited antioxidant ability of the polysaccharide contributes to its antiphlogistic effects. More in-depth studies are needed to fully understand the specific mechanisms and the molecular pathways involved in these activities.

The triple combination DBDx alleviates cytokine storm and related lung injury

Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.

Strobilanthes sarcorrhiza root phenolic extract prevent diabetic nephropathy in mice by regulating NF-κB/IL-1β signaling and glycerophospholipid metabolism

Strobilanthes sarcorrhiza, a folk medicine from China, is known to treat kidney deficiency and lumbago. However, its protective effects and mechanisms against diabetic nephropathy (DN) remain unclear. This study aimed to investigate the effects and mechanisms of Strobilanthes sarcorrhiza root phenolic extract (CTS) on streptozotocin (STZ)-induced DN in mice. Firstly, the constituents in CTS were characterized by UPLC-QTOF-MS. Thirty-three constituents were identified, including 12 phenylethanoid glycosides and their derivatives, 14 phenylpropanoid glycosides derivatives, 6 polyphenols derivatives, and 1 other constituent. Then, utilizing the identified constituents of CTS, network pharmacology was used to anticipate potential pathways against DN. Thirty-two out of thirty-three constituents showed anti-DN activity; their mechanism of action was significantly linked to tumor-, glycosylation-, metabolism-related pathways, etc. Furthermore, the effectiveness of CTS against DN and its in vivo mechanism was assessed by combining immunohistochemistry, untargeted metabolomics, biochemical evaluation, and histopathological examination. The findings showed that CTS improved blood glucose and lipid levels in diabetic mice, reduced serum levels of ALT, CREA, UREA, IL-1β, and IL-17, decreased pathological damage and fibrosis in kidney tissue, and lowered the protein expression of VEGF, Laminin, TNF-α, and NF-κB in kidney tissue. Metabolomics results indicated that CTS alleviated DN mainly by regulating glycerophospholipid metabolism. To the best of our knowledge, this study is the first to report that Strobilanthes sarcorrhiza attenuates DN, potentially through the inhibition of the NF-κB pathway, leading to a reduction in the inflammatory response and fibrosis of renal tissue. These findings suggest that Strobilanthes sarcorrhiza could be a promising therapeutic agent for DN.

Serum interleukin-10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase-4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i-related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i-unrelated BP, 17 patients with DPP4i-related BP, and 13 healthy controls were analyzed. Patients with DPP4i-related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)-erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti-BP180 antibody than patients with DPP4i-unrelated BP. The serum interleukin (IL)-6 level was significantly higher in patients with DPP4i-related BP than in healthy controls (P = 0.0037). The serum IL-10 level was significantly higher in patients with DPP4i-related BP than in patients with DPP4i-unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI-blister/erosions score (r = 0.757, P = 0.001), BPDAI-erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI-total score (r = 0.833, P < 0.001) in patients with DPP4i-related BP. In conclusion, patients with DPP4i-related BP had increased serum levels of IL-6 and IL-10 compared with healthy controls and positive correlations between the serum IL-10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL-10 level is a potential objective biomarker of disease severity in patients with DPP4i-related BP.

Protective Effects of Annona Atemoya Extracts on Inflammation, Oxidative Stress, and Renal Function in Cadmium-Induced Nephrotoxicity in Wistar Rats.

Cadmium (Cd), a highly toxic heavy metal from agricultural activities, and its exposure can lead to impaired renal function by increasing reactive oxygen species. The atemoya fruit is known for its high phenolic and antioxidant compounds. This study aimed to evaluate the effects of atemoya extracts on renal function, oxidative stress parameters, and inflammatory biomarkers in a cadmium-induced nephrotoxicity model. Three aqueous extracts were prepared from different parts of the atemoya fruit: seeds, peel, and pulp. Twenty-five male Wistar rats were allocated into four groups: control, seed, peel, and pulp extracts at 2 g/kg for 25 days. All treatment groups administered intraperitoneal injections of cadmium chloride (CdCl2) (2 mg/kg) to induce renal damage. The cadmium-treated groups showed decreased creatinine clearance, SOD, CAT, and GPx activities (p < 0.05) and increased serum levels of TNF-α and IL-6 compared to the control group (p < 0.05). The treatment with seed, peel, and pulp extracts increased creatinine clearance (p < 0.05), increased SOD, CAT, and GPx activities (p < 0.05), and reduced serum levels of TNF-α and IL-6 compared to the Cd group (p < 0.05). This study supports the use of atemoya as a promising candidate for mitigating nephrotoxicity and highlights the importance of its antioxidant and anti-inflammatory properties in renal health.

Effects of 6-week olanzapine treatment on serum IL-2, IL-4, IL-8, IL-10, and TNF-α levels in drug-naive individuals with first-episode schizophrenia

BackgroundSchizophrenia is a complex neuropsychiatric disorder. Growing evidence indicates that the activation of the inflammatory response system with interleukin (IL)-2, IL-4, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of schizophrenia,. However, clinical data on cytokine levels in patients with schizophrenia treated with antipsychotics are inconsistent or inconclusive. In this study, we have examined inflammatory factors’ alterations and their relationship to changes in clinical symptoms before and after olanzapine treatment of drug-naive patients with first-episode schizophrenia.MethodsWe recruited 142 hospitalized patients with first-episode schizophrenia as a study group; blood samples were collected, and the patients were assessed for clinical symptoms at baseline and after 6 weeks of olanzapine treatment. One hundred individuals with no history of mental illness were also recruited as healthy controls. Blood samples were collected, and the serum levels of IL-2, IL-4, IL-8, IL-10, and TNF-α were determined using an enzyme cycling assay. The severity of clinical symptoms was assessed according to the Positive and Negative Syndrome Scale (PANSS).ResultsIndividuals with schizophrenia had lower IL-8 levels and higher IL-10 levels than healthy controls (P < 0.001). Positive correlations were detected between serum IL-2 and IL-10 concentrations and each subscale of the PANSS (all P < 0.05). Moreover, a negative correlation existed between the serum IL-8 concentration and the PANSS negative score (r = − 0.172, P = 0.040). After 6 weeks of treatment, serum IL-8 levels in the patient group were lower than at baseline (P < 0.001), whereas serum IL-10 and TNF-α levels were higher than at baseline (all P < 0.05). Therefore, serum IL-10 can be determined as an independent risk factor for outcome in patients with first-episode schizophrenia (P = 0.02, OR = 2.327). Furthermore, serum IL-2, IL-10, and TNF-α levels were significantly lower, whereas the serum IL-8 level was significantly higher (P < 0.001) in the healthy control group than in the “response” and “no-response” treatment groups respectively.ConclusionsOur results indicate that serum IL-2, IL-8, IL-10, and TNF-α levels may be involved in the pathophysiological mechanisms of schizophrenia and correlate with the effects of olanzapine.

Systemic profile of pro-inflammatory and anti-inflammatory cytokines and its changes in patients with cataract after surgery

Background. Due to its high prevalence and morbidity, cataract is an urgent medical and social problem. In recent years, immune inflammation, in particular the immune regulation of dystrophic processes, has been of great importance in the pathogenesis of eye diseases. Immunological disorders play a crucial role in the development of age-related eye diseases (cataract, corneal dystrophy, glaucoma, age-related macular degeneration). The effect of pro-inflammatory and anti-inflammatory cytokines on the development of age-related cataract remains understudied, as well at their role in predicting the course of the postoperative period after extraction of age-related cataract has not been fully stu­died, which determines the relevance of the study. The objective: to assess the state of cytokine profile in patients with age-related cataract by determining the content of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins in blood serum before and after surgical treatment of cataract. Materials and methods. The level of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory cytokines (IL-4, IL-10) was studied before and after surgical treatment in 28 patients with age-related cataract (56 eyes), 8 men and 20 women aged 42 to 82 years. The average age of the patients was 71.79 ± 1.90 years. Serum content of cytokines was determined by the enzyme-linked immunosorbent assay using test systems Vector-Best-Ukraine. Results. There was no excess of IL-1β and IL-6 reference values in the blood serum of patients with age-related cataract prior to surgical treatment. Analysis of the pro-inflammatory IL-6 in these patients depending on sex revealed a significant increase in its level by 1.3 times in men and a significant decrease by 1.1 times in women compared to its average content (p &lt; 0.06 and p &lt; 0.01, respectively). The level of anti-inflammatory IL-4 and IL-10 in the blood serum of the examined patients was within the reference values. When studying the content of pro-inflammatory and anti-inflammatory interleukins in serum depending on sex and age in patients with age-related cataract aged 75 years and older, there was a statistically significant increase in IL-6 and IL-10. In this age group, the level of IL-6 was 1.4 times higher in men compared to women, and IL-10 was 1.8 times higher in women than in men. In patients with age-related cataract after surgical treatment, serum content of pro-inflammatory IL-1β, IL-6 and anti-inflammatory IL-4, IL-10 was higher than levels before surgery. The highest levels of IL-1β, IL-6 were in patients with postoperative corneal edema. Serum content of IL-6 in patients with postoperative corneal edema was higher compared to that of IL-1β. Levels of IL-4, IL-10 were higher in patients with postoperative corneal edema, IL-10 in these patients prevailed over IL-4. Conclusions. In patients with age-rela­ted cataract, the content of pro-inflammatory and anti-inflammatory cytokines in the blood serum corresponds to reference values and has no signi­ficant differences from the control group. However, determination of the cytokine profile in people with age-related cataract revealed a violation of the systemic immunological status depending on age and gender. According to our results, patients with age-related cataract over 75 years of age had a significant increase in the level of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 in blood serum. In this age group, IL-6 was higher in men and IL-10 was higher in women. We also noted the absence of significant differences in the content of IL-1β, which may indicate a more specific value of IL-6 levels for the development of cataract. In patients with age-related cataract after surgical treatment, serum levels of pro-inflammatory IL-1β, IL-6 and anti-inflammatory IL-4, IL-10 were higher than preoperative ones. The highest levels of IL-1β, IL-6 were in the blood serum of patients with postope­rative corneal edema, and a decrease in the level of IL-4, IL-10 was also noted in cases of corneal edema. Serum content of IL-6 in patients with postoperative corneal edema was higher than that of IL-1β, and IL-10 prevailed over IL-4 levels.

The mechanism of wen jing tang in the treatment of endometriosis: Insights from network pharmacology and experimental validation

BackgroundEndometriosis (EM) is a hormone-dependent condition marked by progressively severe secondary dysmenorrhea, significantly impacting patients' quality of life and overall health. Wen Jing Tang (WJT), a traditional Chinese medicinal formulation derived from the Synopsis of the Golden Chamber, has proven to be an effective therapeutic agent for EM. However, the precise molecular mechanisms underlying its efficacy remain unclear. ObjectiveThis study aims to elucidate the underlying mechanisms of WJT in the treatment of EM by integrating network pharmacology analysis with experimental validation. MethodsThe chemical constituents and target sites of WJT were obtained from the TCMSP database, while EM-related target genes were sourced from OMIM, TTD, GeneCards, and the DrugBank databases. A "herbs-components-targets" network was constructed using Cytoscape 3.9.1. The intersecting target genes of WJT and EM were then uploaded to the STRING database for protein-protein interaction (PPI) analysis. Subsequently, the common target genes were subjected to GO and KEGG enrichment analysis via the DAVID database. Molecular docking were employed to analyze the binding affinities between the top five core components and their respective targets. Additionally, ELISA were used to quantify the serum levels of IL-6, IL-1β, E2, and P in EM model rats. The expression levels of TNF-α, HIF1A, STAT3, and EGFR mRNA and proteins in ectopic endometrial tissue were assessed using q-PCR and Western blotting. ResultsA total of 250 chemical components and 553 targets were identified in WJT, while 3491 EM-related targets were screened from multiple databases. Among these, 187 common targets between WJT and EM were found, with quercetin, kaempferol, and beta-sitosterol emerging as the core chemical components, and AKT1, IL6, TNF, and IL1B identified as the key targets. These core components demonstrated strong binding affinities to the targets. GO and KEGG enrichment analyses revealed that the shared targets were primarily involved in the HIF1 signaling pathway. Furthermore, compared to the control group, the EM model rats exhibited an increased ectopic endometrial area, disordered glandular and stromal cells, and notable inflammatory infiltration. Serum levels of IL-6, IL-1β, E2, and P were significantly elevated (P < 0.01), and the expression of TNF-α, HIF1A, STAT3, and EGFR in the ectopic endometrium was markedly increased (P < 0.01). Following WJT intervention, the ectopic endometrial area in model rats was reduced, the morphology and structure of the endometrial cells showed improvement, and serum levels of IL-6, IL-1β, E2, and P were significantly decreased (P < 0.05). WJT also inhibited the expression of HIF1 pathway-related proteins TNF-α, HIF1A, STAT3, and EGFR (P < 0.05). ConclusionThe mechanism by which WJT prevents and treats EM may involve the reduction of inflammation through the inhibition of the HIF1 signaling pathway.