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The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA. Here, we validated the quality of DNA derived from DBS samples from SSA studies and provided evidence of quantitative recovery of inflammatory cytokines using these DBS samples through comparison with paired frozen plasma. Significant differences in DNA, protein yields, and inflammatory biomarker levels were also observed between PLWH with/without KS. Establishing the fitness of DBS samples for studies of KS pathogenesis extends the number of projects that can be supported by these ACSR special collections and provides evidence that DBS collection for future KS research is a practical option in resource-limited settings.

Background: Major depressive disorder (MDD) and schizophrenia (SCH) are common and severe mental disorders that are mainly diagnosed depending on the subjective identification by psychiatrists. Finding potential objective biomarkers that can distinguish these two diseases is still meaningful. Methods: In the present study, we investigate the differences in plasma inflammatory cytokines and short-chain fatty acids (SCFAs) among patients with MDD (n = 24) and SCH (n = 24), and gender- and age-matched healthy controls (HC, n = 27) and identify potential plasma biomarkers. Results: We found that the concentrations of pro-inflammatory cytokines were increased, whereas the anti-inflammatory cytokines were decreased in both MDD and SCH. Meanwhile, except for an increase in 4-Methylvaleric acid, other SCFAs with statistical differences were reduced in both MDD and SCH. Moreover, potential biomarker panels were developed that can effectively discriminate MDD from HC (AUC = 0.997), SCH from HC (AUC = 0.999), and from each other (MDD from SCH, AUC = 0.983). Conclusions: These data suggest that alterations in plasma cytokines and SCFAs might be one of the potential features for distinguishing MDD and SCH. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100051243, registration date: 2021/09/16. [ABSTRACT FROM AUTHOR]

Objective: Investigating the causal relationship between inflammatory cytokines and Non-alcoholic fatty liver disease(NAFLD) and identifying and quantifying the role of serum ferritin as a potential mediator. Methods: Genetic summary statistics were derived from open genome-wide association study (GWAS) databases. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the relationship between inflammatory cytokines (8,293 individuals) and NAFLD (8,434 cases, 770,180 controls). Furthermore, we used two-step MR to quantitate the proportion of the effect of serum ferritin-mediated inflammatory cytokines on NAFLD. In this study, we primarily utilized inverse-variance-weighted Mendelian randomization (MR-IVW) and reverse MR analysis methods, while other methods were also performed for sensitivity analysis, false discovery rate (FDR) <0.0012 as statistical significance in MR analyses. Results: Our results indicated that high levels of Eotaxin, regulated upon activation normal T cell expressed and presumably secreted(RANTES), Interleukin-2(IL-2), macrophage migration inhibitory factor(MIF), tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) and Stem cell factor(SCF) were associated with increased risks of NAFLD, while high Cutaneous T cell-attracting chemokine(CTACK) and Interleukin-16(IL-16) levels that reduced the risk of NAFLD.The proportion of genetically predicted NAFLD mediated by ferritin was 2.1%(95% CI = 1.39%−5.61%). Conclusion: In conclusion, our study identified a causal relationship between inflammatory cytokines and NAFLD, with a small proportion of the effect mediated by ferritin, but a majority of the effect of inflammatory cytokines on NAFLD remains unclear. Further research is needed on additional risk factors as potential mediators. [ABSTRACT FROM AUTHOR]

AbstractCancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time (p < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning (p = .002), attention (p < .001), language (p < .001), recall (p = .005), and orientation (p < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function (ρ = 0.68, p < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3 (ρ = 0.2, p = .09; for TP3, ρ = 0.16, p = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients. 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed. TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P = 0.79). TL was significantly negatively associated with age (β = −0.007, P < 0.001). In addition, log TNF-α levels were significantly negatively associated with TL (P = 0.009), in both the BD patients (P = 0.02) and HCs (P = 0.05). We found a significant association between TNF-α levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed. • Bipolar disorder patients may not have telomere length shortening • Plasma tumor necrosis factor-α levels may be associated with telomere length shortening • Bipolar disorder subtypes and mood states may not relate to telomere length shortening [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1 A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009–1.095, P = 0.02) and oncostatin-M (OSM) levels ([OR] = 1.041, [95% CI] = 1.001–1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884–0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929–0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922–0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have suggested a potential association between gut microbiota and the development of alcohol-related liver disease (ALD). However, the causal relationship between gut microbiota and ALD, as well as the role of inflammatory cytokines as mediators, remains unclear. This study aims to explore the causal relationship between gut microbiota and ALD using Mendelian randomization (MR) methods, and to analyze the mediating role of inflammatory cytokines. Methods: Gut microbiota, 91 inflammatory cytokines, and ALD were identified from summary data of large-scale genome-wide association studies (GWAS). MR was employed to investigate the causal relationship between gut microbiota, cytokines, and ALD, with the inverse variance-weighted method (IVW) as the primary statistical approach. Additionally, we examined whether inflammatory cytokines act as mediating factors in the pathway from gut microbiota to ALD. Results: The IVW results confirmed two positive and one negative causal effect between genetic liability in the gut microbiota and ALD. Escherichia coli (P= 0.003) was identified as a protective factor for ALD, while Roseburia hominis (P=0.023) and Family Porphyromonadaceae (P=0.038) were identified as risk factors for ALD. Furthermore, there were five positive and two negative causal effects between inflammatory cytokines and ALD, with CUB domain-containing protein 1 (P= 0.035), Macrophage colony-stimulating factor 1 (P=0.047), Cystatin D (P = 0.035), Fractalkine (P=0.000000038), Monocyte chemoattractant protein-1 (P=0.004) positively associated with ALD onset. CD40L receptor (P= 0.044) and Leukemia inhibitory factor (P = 0.024) exhibited protective effects against ALD. Mediation MR analysis indicated that CUB domain-containing protein 1 (mediation proportion=1.6%, P=0.035), Cystatin D (mediation proportion=1.5%, P=0.012), and Monocyte chemoattractant protein-1 (mediation proportion=3.3%, P=0.005) mediated the causal effect of Roseburia hominis on ALD. Conclusion: In conclusion, our study supports a causal relationship among gut microbiota, inflammatory cytokines and ALD, with inflammatory cytokines potentially acting as mediating factors in the pathway from gut microbiota to ALD. [ABSTRACT FROM AUTHOR]

Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression levels of tumor necrosis factor a (TNF-α), interleukins (ILs), matrix metalloproteinases (MMPs), and chitinase (YKL-40) in the knee joint fluid of patients with knee osteoarthritis (KOA), and their correlations with Kellgren-Lawrence (K-L) grade of knee imaging. Methods A total of 100 KOA patients undergoing the knee arthroplasty were enrolled and their knee joint fluid was extracted before the joint surgery. The expression levels of TNF-α, IL-1β, IL-6, IL-8, IL-15, and MMP-3, MMP-9, MMP-13, YKL-40 in the knee joint fluid were detected using cytometric bead array and ELISA, respectively. Patients were grouped according to the K-L scores. The independent influencing factors of KL-4 were determined by comparison between the two groups and binary logistic regression. Spearman method was used to analyze the correlations between the above molecules and K-L grades. Results Among 100 patients with KOA, 25 were males and 75 were females. The mean age was 64. 32 years and the mean course of the disease was 8. 98 years. There were 55 with KL-3 grade and 45 with KL-4 grade. TNF-α, IL-1β, MMP-13, and YKL-40 were highly expressed in KL-3, while IL-6, IL-8, IL-15, MMP-3, and MMP-9 were highly expressed in KL-4. IL-15 and MMP-9 were significantly different between the two groups (P < 0.05) . The result of univariate and multivariate logistic regression showed that IL-15 odds ratio (OR) = 1.575 95% confidence interval (CI): 1.286-1.929; P < 0.001 ] and MMP-9 ( OR = 1.032, 95% CI: 1.008-1.056, P = 0.01 ) were independent risk factors for the KL-4. IL-15 ( r = 0.22 P < 0.05 ) and MMP-9 r = 0.297 P < 0.05 ) were positively correlated with K-L grades. Conclusion The expressions of IL-15 and MMP-9 in the knee joint fluid of KOA patients are higher than that of KL-4 patients. IL-15 and MMP-9 are independent risk factors for the KL-4. There is a positive correlation between IL-15 and MMP-9 levels and the progression of radiographic K-L grades. IL-15 and MMP-9 may provide references for clinical evaluation and progression of this disease. [ABSTRACT FROM AUTHOR]

Pericytes (PCs) contribute to brain capillary/BBB integrity and PC migration is a hallmark for brain capillary leakage following pro-inflammatory insults. Estradiol promotes endothelial barrier integrity by inhibiting tumor necrosis factor-alpha (TNF-α)-induced PC migration. However, the underlying mechanisms remain unclear. Since micro-RNAs (miRs) regulate BBB integrity and increases in miR638 and TNF-α occur in pathological events associated with capillary leakage, we hypothesize that TNF-α mediates its capillary disruptive actions via miR638 and that estradiol blocks these actions. Using quantitative reverse transcription PCR, we first assessed the modulatory effects of TNF-α on miR638. The treatment of PCs with TNF-α significantly induced miR638. Moreover, transfection with miR638 mimic induced PC migration, whereas inhibitory miR638 (anti-miR) abrogated the pro-migratory actions of TNF-α, suggesting that TNF-α stimulates PC migration via miR638. At a molecular level, the pro-migratory effects of miR638 involved the phosphorylation of ERK1/2 but not Akt. Interestingly, estradiol downregulated the constitutive and TNF-α-stimulated expression of miR638 and inhibited the TNF-α-induced migration of PCs. In PCs treated with estrogen receptor (ER) ER-α, ER-β, and GPR30 agonists, a significant downregulation in miR638 expression was solely observed in response to DPN, an ER-β agonist. DPN inhibited the pro-migratory effects of TNF-α but not miR638. Additionally, the ectopic expression of miR638 prevented the inhibitory effects of DPN on TNF-α-induced PC migration, suggesting that interference in miR638 formation plays a key role in mediating the inhibitory actions of estradiol/DPN. In conclusion, these findings provide the first evidence that estradiol inhibits TNF-α-induced PC migration by specifically downregulating miR638 via ER-β and may protect the neurovascular unit during injury/stroke via this mechanism. [ABSTRACT FROM AUTHOR]

AbstractIn order to make more rational use of Flemingia Philippinensis, a systematic separation from the roots of F. philippinensis was performed in the current study. The investigation of chemical constituents resulted in the isolation of a rare prenylated isoflavone-quinone, fleminquinone A (1), together with four known analogues (2–5). Their structures were established by extensive physical and spectroscopic data analysis. Anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide induced mouse mononuclear macrophage leukemia cells RAW 264.7 model. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2. Compound 1 also significantly affected the levels of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Although activation of astrocytes is critical in developing neuropathic pain (NP) following nerve injury, the underlying mechanisms of NP and therapeutic management for NP are still vague. Importantly, the decreases in the levels of astrocytic glutamate transporter‐1 (GLT‐1) in the spinal dorsal horn result in enhanced excitatory transmission and cause persistent pain. P2Y1 purinergic receptor (P2Y1R) has been shown to enhance many inflammatory processes. The up‐regulated expression of astrocytic P2Y1R is crucial to participate in pain transduction under conditions of nerve injury and peripheral inflammation considering that P2Y1R is potentially involved in glutamate release and synaptic transmission. This study indicates that the expression of P2Y1R in the spinal cord was increased accompanied by the activation of A1 phenotype astrocytes in the rat model of spinal nerve ligation (SNL). Astrocyte‐specific knockdown of P2Y1R alleviated SNL‐induced nociceptive responses and mitigated A1 reactive astrocytes, which subsequently increased GLT‐1 expression. Conversely, in naïve rats, P2Y1R over‐expression induced a canonical NP‐like phenotype and spontaneous hypernociceptive responses and increased the concentration of glutamate in the spinal dorsal horn. Besides, our in vitro data showed that the proinflammatory cytokine tumour necrosis factor‐alpha contributes to A1/A2 astrocyte reactivity and Ca2+‐dependent release of glutamate. Conclusively, our results provide novel insights that as a significant regulator of astrocytic A1/A2 polarization and neuroinflammation, P2Y1R may represent a potential target for the treatment of SNL‐induced NP. [ABSTRACT FROM AUTHOR]

Objective: Allergic rhinitis (AR) is a growing public health problem worldwide. Respecting the significance of the modified Lund-Kennedy (MLK) score in rhinitis assessment, we delved into its evaluation value on the sublingual immunotherapy (SLIT) efficacy in AR patients. Methods: Totally 100 AR patients were enrolled, with pre- and post-SLIT MLK score, total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), inflammatory cytokines, and immune function-related parameters compared. The correlations of MLK score with TNSS/TMS/VAS, as well as with IL-4/INF-γ/eosinophil (EOS)/percentage/specific immunoglobulin (sIgE)/sIgG were assessed by Spearman correlation analysis. The value of MLK score on assessing SLIT efficacy in AR patients was analyzed. Results: SLIT treatment reduced MLK/TNSS/TMS/VAS scores, abated IL-4 level/EOS percentage/sIgE, and elevated INF-γ/sIgG levels. MLK score was positively correlated with pre- and post-SLIT TNSS score (rpre−treatment = 0.592, rpost−treatment = 0.756), TMS score (rpre−treatment = 0.385, rpost−treatment = 0.718), VAS score (rpre−treatment = 0.369, rpost−treatment = 0.704), IL-4 (rpre−treatment = 0.553, rpost−treatment = 0.639), EOS percentage (rpre−treatment = 0.511, rpost−treatment = 0.632), and sIgE (rpre−treatment = 0.472, rpost−treatment = 0.524), and negatively with INF-γ (rpre−treatment = −0.418, rpost−treatment = −0.578) and sIgG4 (rpre−treatment = −0.460, rpost−treatment = −0.613). The MLK score had an area under curve of 0.846 (77.01% sensitivity, 76.92% specificity, 4 cut-off value) and 0.944 (91.67% sensitivity, 92.11% specificity, 2 cut-off value) for assessing SLIT treatment as effective and markedly effective for the patients, respectively. Conclusion: The MLK score had good evaluation value on the efficacy of SLIT treatment in AR patients. [ABSTRACT FROM AUTHOR]

This study investigated the effects of Enterococcus hirae (Eh) derived from Ningxiang pigs on growth performance, diarrhea incidence, and immune responses in ETEC-challenged piglets. The results showed that compared to the CON group, ETEC infection significantly reduced the average daily gain (ADG) and average daily feed intake (ADFI), increased rectal temperature, and resulted in a diarrhea rate of up to 24%. Additionally, ETEC infection significantly increased the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of piglets. Compared to the ETEC group, orally Eh significantly increased ADFI in ETEC-infected piglets, reduced the diarrhea rate to 11.53%, reduced the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of ETEC-infected piglets. Furthermore, correlation analysis revealed that the levels of SCFAs (particularly acetate) were significantly negatively correlated with the expression levels of inflammatory cytokines in colonic and splenic tissues, suggesting that acetate may be a key metabolite in the anti-inflammatory effects of Eh. These results indicate that Eh can enhance the protection of piglets against ETEC K88 via intestine-acetate-spleen axis, thereby alleviating diarrhea and improving growth performance in piglets. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is the abnormal coagulation of blood in deep veins, which impairs venous return and includes deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of VTE is increasing, leading to severe complications and sequelae. Despite the widespread application of multi-omics analyses in vascular disease research, identifying the specific links between various metabolic products, cytokines, and VTE, as well as their potential mediating roles, requires further validation due to confounding factors. Methods: Summary statistics for 1,091 metabolites, 309 metabolite ratios (8,299 individuals), and 41 inflammatory cytokines (8,293 individuals) were obtained from the largest genome-wide association studies (GWAS). Summary statistics for VTE (21,021 cases, 391,160 controls), DVT (6,501 cases, 357,111 controls), and PE (10,046 cases, 401,128 controls) were derived from the FinnGen R10 dataset. We initially examined causal relationships using two-sample MR analysis, followed by Two-step Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR) to identify potential mediating mechanisms. Results: We identified causal associations for 78 blood metabolites with VTE, 79 with DVT, and 81 with PE. Among all 41 inflammatory cytokines included, only plateletderived growth factor BB (PDGF-BB) levels showed a causal relationship with increased risks of VTE, DVT, and PE. MVMR analysis revealed that the associations between glycocholate levels and VTE, DVT, and PE were mediated by PDGF-BB, accounting for 14.54% (p=2.84E-04), 17.10% (p=3.64E-05), and 10.44% (p=1.39E02), respectively. Furthermore, the associations between dodecanedioate (C12:1- DC) levels and VTE and DVT were also mediated by PDGF-BB, accounting for 12.79% (p=6.10E-04) and 12.17% (p=2.13E-04), respectively. Conclusion: This study reveals significant associations between specific blood metabolites and the risks of VTE, DVT, and PE, with some associations potentially mediated by PDGF-BB. [ABSTRACT FROM AUTHOR]

Objective: Previous observational studies have indicated associations between various inflammatory cytokines and diabetic nephropathy (DN) caused by type 2 diabetes mellitus (T2DM). However, the causality remains unclear. We aimed to further evaluate the causal association between 91 inflammatory cytokines and DN using bidirectional two-sample Mendelian randomization (MR) analysis. Method: Summary statistics for DN were obtained from a publicly available genome-wide association study (GWAS) analysis. Data pertaining to inflammatory cytokines were derived from a GWAS protein quantitative trait locus (pQTL) study. The primary analytical approach employed the inverse variance weighted (IVW) method, complemented by MR-Egger regression, weighted mode (WM), and weighted median (WME) methods to evaluate the causal association between inflammatory cytokines and DN. Sensitivity analyses were conducted to validate the robustness of the findings. Result: Among individuals of European ancestry, the IVW method results revealed a positive causal association between the gene expression of tumor necrosis factor ligand superfamily member 14 (TNFSF14), and TNF-related activation-induced cytokine (TRANCE) with DN. Conversely, a negative causal association was observed between the gene expression of interleukin-1-alpha (IL-1α), and transforming growth factor-alpha (TGF-α) with DN. Among individuals of East Asian ancestry, the IVW method results indicated a negative causal association between the gene expression of glial cell line-derived neurotrophic factor (GDNF) and DN. Notably, these findings persisted without evidence of horizontal pleiotropy or heterogeneity, ensuring their robustness and reliability. Conclusion: The MR analysis underscores a causal association between inflammatory cytokines and DN, providing an important reference and evidence for the study of DN. [ABSTRACT FROM AUTHOR]

Introduction: Opioids have been shown to induce neuroinflammation and immune cell activation, that might contribute to some of the opioid side effects, such as opioid-induced tolerance and paradoxical hyperalgesia. In this context, TLR4/MD-2 complex has been proposed as an off-target site for opioid action. This study was aimed at investigating the effect of fentanyl on lipopolysaccharide (LPS)-induced TLR4/MD-2 activation in rat primary microglia and human monocyte-derived macrophages (MDM). Materials and Methods: The effect of fentanyl was first explored by measuring the expression and release of different proinflammatory mediators in primary rat microglia and human MDM by real-time PCR and ELISA. Then, the involvement of TLR4/MD-2 signaling was investigated studying NF-κB activation in HEK293 cells stably transfected with human TLR4, MD-2, and CD14 genes (HEK-Blue hTLR4 cells) and in human MDM. Results: Fentanyl increased mRNA levels, as well as the LPS-induced secretion of proinflammatory mediators in primary microglia and MDM. Two inhibitors of TLR4/MD-2 signaling, namely the oxazoline derivative of N-palmitoylethanolamine (PEA-OXA) and CLI-095, blocked the production and release of proinflammatory cytokines by microglia stimulated with LPS and fentanyl, suggesting that TLR4/MD-2 could be the target of the proinflammatory activity of fentanyl. Finally, we showed that fentanyl in combination with LPS activated NF-κB signaling in human MDM and in HEKBlue hTLR4 cells and this effect was blocked by inhibitors of TLR4/MD-2 complex. Discussion: These results provide new insight into the mechanism of the proinflammatory activity of fentanyl, which involves the activation of TLR4/MD-2 signaling. Our findings might facilitate the development of novel inhibitors of TLR4/MD-2 signaling to combine with opioid-based analgesics for effective and safe pain management. [ABSTRACT FROM AUTHOR]

Objective: The mechanisms driving the progression of infantile spasms are not well understood. We aimed to investigate the changes and correlations of the gut microbiota, the hypothalamus-pituitary-adrenal (HPA) axis hormones, and the inflammatory cytokines in children with infantile spasms before and after treatment in order to provide a reference for future pathogenesis research. Methods: Children with infantile spasms who were admitted to our hospital were recruited into the case group. The case group was divided into the pre-treatment group (group A, n = 14), the 2 weeks after treatment group (group B), and the 1 month after treatment group (group C). On the other hand, healthy children with the same sex ratio as the case group were recruited into the control group (group D, n = 14). Three stool and blood samples were collected before treatment, 2 weeks after treatment, and 1 month after treatment. The serum samples were analyzed using cytometric bead array (CBA), enzyme-linked immunosorbent assay (ELISA), and chemiluminescent immunoassay (CLIA) to measure the levels of HPA axis hormones and inflammatory cytokines. The collected stool samples were sequenced using 16S rDNA. Results: The pre-treatment group demonstrated elevated levels of corticotropin-releasing hormone (CRH), interleukin 2 (IL-2), IL-4, IL-6, and IL-17a, which decreased with treatment. The level of CRH was lower in the effective group than that in the ineffective group. Sutterellaceae was lower in the pretreatment group than that in the control group. Lachnospiracea_incertae_sedis was positively associated with CRH concentration (p < 0.05). After treatment, Sutterellaceae was negatively associated with IL-2 and TNF-a (p < 0.05). Conclusion: This study found that imbalance of the gut microbiota may be involved in the pathogenesis of infantile spasms and is related to the response to adrenocorticotropic hormone (ACTH). Lachnospiraceae and Lachnospiracea_ incertae_sedis might be involved in the disease onset. Sutterellaceae might have a link to children's improved health. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints—including oxidative stress markers and transcriptional regulation—in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1–750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM. [ABSTRACT FROM AUTHOR]

Experimental evidence suggests that, in the inflamed gut of inflammatory bowel disease (IBD) patients, interleukin-34 (IL-34) triggers detrimental signaling pathways. Factors/mechanisms regulating IL-34 production in IBD remain poorly characterized. Bromodomain-containing 4 (BRD4), a transcriptional and epigenetic regulator, is over-expressed in IBD, and studies in cancer cells suggest that BRD4 might positively control IL-34 expression. This study aimed to assess whether, in IBD, BRD4 regulates IL-34 expression. In IBD, there was an up-regulation of both IL-34 and BRD4 compared to the controls, and the two proteins co-localized in both lamina propria mononuclear cells (LPMCs) and epithelial cells. Flow cytometry analysis of CD45+ LPMCs confirmed that the percentages of IL-34- and BRD4-co-expressing cells were significantly higher in IBD than in the controls and showed that more than 80% of the IL-34-positive CD45-LPMCs expressed BRD4. IL-34 and BRD4 were mainly expressed by T cells and macrophages. IL-34 expression was reduced in IBD LPMCs transfected with BRD4 antisense oligonucleotide and in the colons of mice with dextran sulfate sodium-induced colitis treated with JQ1, a pharmacological inhibitor of BRD4. These data indicate that BRD4 is a positive regulator of IL-34 in IBD, further supporting the pathogenic role of BRD4 in IBD-associated mucosal inflammation. [ABSTRACT FROM AUTHOR]

Chronic disease inflammation requires safe complementary treatments. The pericarp of Passiflora tripartita var. mollissima (PTM) contains potential anti-inflammatory metabolites. This study aimed to evaluate the bioactive components, antioxidant capacity, and anti-inflammatory effects of PTM extracts at two ripening stages. The bioactive compounds in the hydrophilic and lipophilic extracts of mature and green pericarps were identified by GC-MS and UV–VIS, while the antioxidant capacity was measured by free radical reduction. Anti-inflammatory effects were tested using a rat paw edema model with carrageenan-induced edema, indomethacin, or PTM extracts (100, 250, and 500 mg/kg). The effect of mature hydrophilic extract was further evaluated in an air pouch model, where rats received the placebo, carrageenan, indomethacin, or the extract (500 and 1000 mg/kg). Leukocytes, cytokines, and markers of oxidative stress were evaluated. The results showed the presence of organic compounds, total phenols, and flavonoids. The mature hydrophilic extract exhibited the highest antioxidant activity. At 500 mg/kg, it reduced edema, leukocyte migration, and levels of IL-1β, IL-6, and TNF-α while managing oxidative stress and preventing histological damage. In conclusion, PTM contains bioactive compounds with potential pharmacological properties. The hydrophilic extract of the mature pericarp, at a dose of 500 mg/kg, exhibits an enhanced antioxidant and anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the NF-κB pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of SOX9. These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms. [ABSTRACT FROM AUTHOR]

The inflammatory cytokine response is essential for protective immunity, yet bacterial and viral pathogens often elicit an exaggerated response ("cytokine storm") harmful to the host that can cause multi-organ damage and lethality. Much has been published recently on the cytokine storm within the context of the coronavirus pandemic, yet bacterial sepsis, severe wound infections and toxic shock provide other prominent examples. The problem of the cytokine storm is compounded by the increasing incidence of multidrug-resistant bacterial strains. We created an incisive molecular tool for analyzing the role of the B7/CD28 costimulatory axis in the human inflammatory response. To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, we uniquely targeted the engagement of CD28 with its B7 co-ligands by means of short peptide mimetics of the human CD28 and B7 receptor homodimer interfaces. These peptides are not only effective tools for dissecting mechanism but also serve to attenuate the inflammatory response as a broad host-oriented therapeutic strategy against the cytokine storm. Indeed, such peptides protect mice from lethal Gram-positive bacterial superantigen-induced toxic shock even when dosed in molar amounts well below that of the superantigen and show promise in protecting humans from the severe inflammatory disease necrotizing soft tissue infections ('flesh-eating' bacterial sepsis) following traumatic wound injuries. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) therapy holds promise for treating various clinical conditions. The activation process is crucial in releasing growth factors and cytokines from platelets, enhancing the therapeutic properties of PRP. Standard activation methods involve autologous thrombin or collagen, with variations in efficacy and growth factor release. This study explores the impact of acetylsalicylic acid (ASA), a commonly used antiplatelet drug, on PRP activation. The results indicate that non-activated PRP extracted from the whole blood of ASA-treated patients exhibits increased inflammatory cytokine concentrations, notably TNFa. After activation with autologous thrombin/CaCl2 or collagen IV, the measured fluorescence intensities suggest varying release patterns between treated and non-treated groups. Understanding the influence of ASA on platelet activation holds implications for personalized medicine and optimizing outcomes for individual patients undergoing PRP therapy. This research sheds light on the potential challenges associated with using antiplatelet drugs, emphasizing the need for careful consideration in tailoring PRP-based regenerative therapies. [ABSTRACT FROM AUTHOR]

Neuroinflammation is increasingly recognized as a pivotal factor in the development and progression of neurodegenerative disorders. While correlations between inflammatory cytokines and these diseases are documented, the definitive causal dynamics remain to be elucidated. We explored the causal association between 91 circulating inflammatory cytokines and Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Parkinson's disease (PD) through Mendelian randomization analysis. Leveraging genetic variants from the most comprehensive genome‐wide association studies (GWAS) available for these cytokines, AD, ALS, MS and PD, we sought to uncover the causality. Our study validated a causal influence of genetically determined cytokine levels on the susceptibility to AD, with notable cytokines including C‐X‐C motif chemokine 1 (OR = 0.9993, p = 0.0424), Interleukin‐18 (OR = 0.9994, p = 0.0186), Leukaemia inhibitory factor receptor (OR = 0.9993, p = 0.0122) and Monocyte chemoattractant protein‐1 (OR = 0.9992, p = 0.0026) in risk attenuation. Additionally, a positive causal relationship was identified between two cytokines—C‐C motif chemokine 19 (OR = 1.0005, p = 0.0478) and Fms‐related tyrosine kinase 3 ligand (OR = 1.0005, p = 0.0210)—and AD incidence. Conversely, transforming growth factor‐alpha (OR = 0.8630, p = 0.0298), CD40L receptor (OR = 0.7737, p = 1.1265E‐09) and Interleukin‐12 subunit beta (OR = 0.8987, p = 0.0333) showed inverse associations with ALS, MS and PD, respectively. The consistency observed in various MR analyses, alongside sensitivity analysis, underscored the absence of horizontal pleiotropy, thus supporting our causal findings. This study reveals, for the first time, a genetically anchored causal nexus between levels of circulating inflammatory cytokines and the risk of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage. Methods: We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -800C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88). Results: Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice. Conclusions: Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer's solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke. Methods: Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins. Results: Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived. Conclusions: NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, and recent research suggests that gut microbiota and inflammatory cytokines may play a significant role in its pathogenesis. However, the specific effects of these factors on ITP and their relationships remain unclear. We conducted a two‐step, two‐sample Mendelian randomization study using an inverse variance‐weighted approach to investigate the causal role of the gut microbiota in ITP and the mediating effect of inflammatory cytokines on their association. The results showed that among the 473 gut microbiota species, 11 were positively associated and 12 were negatively associated with the risk of ITP. Among the 91 screened inflammatory cytokines, five (CXCL10, CXCL5, IL‐12RA, TRAIL, and VEGF‐A) were found to have a causal relationship with ITP. Mediation analysis revealed that the gut microbiota UBA1066 promoted the occurrence of ITP through CXCL10 mediation, with a mediation effect of 0.118932 (95% CI: 0.049471–0.188393) accounting for 9.95% of the total effect. Gut microbiota Treponema promoted ITP through VEGF‐A mediation, with a mediation effect of 0.045873 (95% CI: 0.01456–0.07718) accounting for 4.28% of the total effect. Gut microbiota Haloplasma promoted the occurrence of ITP via CXCL5. The mediating effect of CXCL5 was 0.038409 (95% CI = 0.00107718–0.07575082), with a mediating ratio of 16.79%. This study revealed a causal relationship between gut microbiota composition and ITP risk, highlighting three inflammatory cytokines as potential causal mediators of this relationship. These findings provide potential targets and biomarkers for the prevention and treatment of ITP with significant clinical implications. [ABSTRACT FROM AUTHOR]

The applications of herbal medicine have recently acquired growing interest in range of the prophylaxis and treatment of diseases. Olibanum has been used since ancient eras and several reports studied the pharmacological characteristics of boswellic acid, particularly their effect on the inflammatory response, analgesic properties, and anti-arthritic activity mostly in cell lines, but new approaches include animal models to assess these natural derivatives effects taking into consideration of being safer than synthetic preparations. The impact of olibanum oil on several parameters was studied in rats during this study. These included white blood cell (WBC) count, lactate dehydrogenase (LDH), and C reactive protein (CRP), as well as other pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and the cytokine interleukin -10 (IL-10) that is antiinflammatory. Total WBCs in addition to IL-10 levels significantly increased in the oil-treated group in comparison with the control one, while the rats treated with olibanum oil revealed a significant reduced level of LDH, CRP, IL-6 and TNF- α compared with the controls (p < 0.05). These outcomes indicate that olibanum oil treatment are manifested by cytokine changes, it can improve the anti-inflammatory response and down-regulate the pro-inflammatory cytokines. So, the promising impact of olibanum oils as an immunomodulator could be used in alternative therapies. [ABSTRACT FROM AUTHOR]

Purpose: To determine the serum levels of cytokines, interleukins (IL) and tumor necrosis factor (TNF) in multiple sclerosis (MS) patients and compare with those in healthy individuals. Methods: Twenty-two (22) adult patients with MS and 44 healthy controls, matched for age and gender, and visiting the King Abdulaziz University Hospital, Jeddah, Saudi Arabia were divided into groups I and II, respectively. Serum levels of interferon-gamma (IFN-γ), tumor necrosis factor and interleukins were determined for both groups. Cytokine levels were assessed using Luminex® xMAP® technology in 22 Saudi MS patients and 22 matched healthy controls. Results: There were no significant differences in mean age between Group I (30.14 ± 10.51) and Group II (30.22 ± 5.22) participants (p = 0.982). Furthermore, the levels of IFN-γ, IL-6, IL-8, IL-1ß and TNF-a in the serum were significantly higher in Group I patients than in controls (p < 0.0001 for all). Furthermore, a strong positive correlation was found between IFN-γ and IL-8 (r = 0.467, p = 0.028) in MS patients. Conclusion: Patients with MS release significant amounts of inflammatory cytokines, which play a crucial role in understanding the clinical course of MS. These findings enhance the understanding of MS pathophysiology and guide future studies toward developing targeted treatments to mitigate disease progression and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Background/Objectives: The global SARS-CoV-2 outbreak has escalated into a critical public health emergency, with the spike glycoprotein S1 subunit of SARS-CoV-2 (spike-S1) linked to inflammation in lung tissue and immune cells. Luteolin, a flavone with anti-inflammatory properties, shows promise, but research on its effectiveness against long-COVID-related inflammation and spike protein-induced responses remains limited. This study aims to elucidate the underlying mechanisms of inflammation in THP-1 cells induced by the spike-S1. Additionally, it seeks to assess the potential of luteolin in mitigating inflammatory responses induced by the spike-S1 in a THP-1 macrophage model. Methods: The gene expression profiles of spike-S1 in THP-1 cells were analyzed by transcriptome sequencing. The inhibitory effect of luteolin on ER stress and inflammation in spike-S1-induced THP-1 cells was investigated using Western blotting, RT-PCR, and ELISA. Results: The candidate genes (CAMK2A, SIGLEC7, PPARGC1B, SEC22B, USP28, IER2, and TIRAP) were upregulated in the spike-S1-induced THP-1 group compared to the control group. Among these, calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) was identified as the most promising molecule in spike-S1-induced THP-1 cells. Our results indicate that the spike S1 significantly increased the expression of ER-stress markers at both gene and protein levels. Luteolin significantly reduced ER stress by decreasing the expression of ER-stress marker genes and ER-stress marker proteins (p < 0.01). Additionally, luteolin exhibited anti-inflammatory properties upon spike S1-induction in THP-1 cells by significantly suppressing IL-6, IL-8, and IL-1β cytokine secretion in a dose-dependent manner (p < 0.05). Furthermore, our results revealed that luteolin exhibited the downregulation of the MAPK pathway, as evidenced by modulating the phosphorylation of p-ERK1/2, p-JNK and p-p38 proteins (p < 0.05). Conclusions: The results from this study elucidate the mechanisms by which the spike S1 induces inflammation in THP-1 cells and supports the use of naturally occurring bioactive compounds, like luteolin, against inflammation-related SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Low-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms. Methods: The participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p < 0.05. Results: After controlling for age, BMI, smoking and alcohol consumption, in 2015 the serum concentrations of IL-17A and TNFα in 2015 were significantly positively associated with the CES-D scores of women (standardised β (B) =.027, p < 0.01 and B = 0.26, p < 0.01, respectively). The serum concentrations of IL-17A and TNFα of men were significantly positively associated with the CES-D scores of 2019 (B = 0.62, p = 0.02 and B = 0.59, p = 0.02, respectively). Conclusions: In this cross-sectional study, we found a significant positive correlation between the depressive symptoms and serum TNFα and IL-17A levels of women. In addition, our longitudinal findings suggest the possibility that TNFα and IL-17A could elevate the depressive symptoms of men. [ABSTRACT FROM AUTHOR]

Lung cancer is a serious health and life issue, with the fastest-growing incidence and fatality rates worldwide. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to be a significant cause of increased lung cancer risk. The main idea of this research was to disclose the linkage between both IL-6 rs1800795 and IL-1β rs16944 variants and susceptibility to non-small-cell lung cancer (NSCLC) in Egyptians. This case–control design was composed of 127 cases and 138 controls, which were genotyped using the ARMS-PCR technique. To examine the NSCLC susceptibility under various genetic models, the odds ratio (OR) and 95% confidence intervals (CIs) were determined by logistic regression. Rs1800795 of the IL-6 gene was linked to higher odds of NSCLC under the allele model (adjusted, OR 2.28; 95% CI 1.2–4.33; p = 0.011). In the genetic models, IL-6 rs1800795 elevated the odds of NSCLC, while IL-1β rs16944 decreased the odds of NSCLC. Stratification analysis showed that IL-6 rs1800795 greatly increased the NSCLC risk in females and adenocarcinoma subtypes, whereas IL-1β rs16944 largely decreased the NSCLC risk for males, patients aged < 55, and nonsmokers. Regarding clinical data, the IL-6 variant was remarkably correlated with tumor size. This work primarily established that IL-6 and IL-1β variants have a great impact on NSCLC development in the Egyptian population; thus, it may be a supportive guide for earlier NSCLC prevention. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HS) results from burns or trauma, causing aesthetic and functional issues. However, observational studies have linked inflammatory cytokines to HS, but the causal pathways involved are unclear. We aimed to determine how circulating inflammatory cytokines contribute to HS formation. Two-sample Mendelian randomization (MR) was used to identify genetic variants associated with hypertrophic scar in a comprehensive, publicly available genome-wide association study (GWAS) involving 766 patients and 207,482 controls of European descent. Additionally, data on 91 plasma proteins were drawn from a GWAS summary involving 14,824 healthy participants. Causal relationships between exposures and outcomes were investigated primarily using the inverse variance weighted (IVW) method. Furthermore, a suite of sensitivity analyses, including MR‒Egger and weighted median approaches, were concurrently employed to fortify the robustness of the conclusive findings. Finally, reverse MR analysis was conducted to evaluate the plausibility of reverse causation between hypertrophic scar and the cytokines identified in our study. In inflammatory cytokines, there was evidence of inverse associations of osteoprotegerin(OPG) levels(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01), and leukemia inhibitory factor(LIF) levels(OR = 0.51, 95% CI = 0.32 ∼ 0.82, p = 0.01) are a nominally negative association with hypertrophic scar risk, while CUB domain-domain-containing protein 1(CDCP1) level(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01) glial cell line-derived neurotrophic factor(GDNF) levels(OR = 1.42, 95% CI = 1.03 ∼ 1.96, p = 0.01) and programmed cell death 1 ligand 1(PD-L1) levels(OR = 1.47, 95% CI = 1.92 ∼ 2.11, p = 0.04) showed a positive association with hypertrophic scar risk. These associations were similar in the sensitivity analyses. According to our MR findings, OPG and LIF have a protective effect on hypertrophic scar, while CDCP1, GDNF, and PD-L1 have a risk-increasing effect on Hypertrophic scar. Our study adds to the current knowledge on the role of specific inflammatory biomarker pathways in hypertrophic scar. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for hypertrophic scar prevention and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have reported a complex relationship between inflammatory cytokines and kidney stone disease (KSD). The purpose of this paper is to investigate the potential causal impact of inflammatory cytokines on KSD by Mendelian randomization (MR) analysis. Methods: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between inflammatory cytokines and kidney stone disease. Utilizing GWAS summary data of inflammatory cytokines and KSD, we performed the first two-sample MR analysis. Genetic variants in GWASs related to inflammatory cytokines were employed as instrumental variables (IVs). The data on cytokines were derived from 14,824 participants and analyzed by utilizing the Olink Target-96 Inflammation Panel. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Reverse MR analysis, Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. Results: 91 cytokines were enrolled in the MR analysis after strict quality control of IV. The IVW analysis revealed 2 cytokines as risk factors for KSD: Cystatin D (OR 1.06, 95% CI 1.01–1.11), Fibroblast growth factor 5 (OR 1.06, 95% CI 1.00–1.12), suggesting they are positively associated with the occurrence of kidney stones. We also found 3 protective associations between cytokines and KSD: Artemin (OR 0.86, 95% CI 0.78–0.96), T-cell surface glycoprotein CD6 isoform (OR 0.92, 95% CI 0.88–0.98), STAM-binding protein (OR 0.83, 95% CI 0.69–0.99). There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our MR Egger's intercept test, Cochrane Q-test, and MR-PRESSO, which were all > 0.05. Conclusions: Our study explored a variety of inflammatory cytokines related to KSD through MR analysis, which validated several previous findings and provided some new potential biomarkers for KSD. However, the findings require further investigation to validate their exact functions in the pathogenesis and evolution of KSD. [ABSTRACT FROM AUTHOR]

Background: Observational studies have highlighted the pivotal role of inflammatory cytokines in cirrhosis progression. However, the existence of a causal link between inflammatory cytokines and cirrhosis remains uncertain. In this study, we conducted a bidirectional Mendelian randomization (MR) analysis at a summarized level to illuminate the potential causal relationship between the two variables. Methods: This study utilized genetic variance in cirrhosis and inflammatory cytokines from a genome-wide association study (GWAS) of European descent. The MR-PRESSO outlier test, Cochran's Q test, and MR-Egger regression were applied to assess outliers, heterogeneity, and pleiotropy. The inverse variance weighted method and multiple sensitivity analyses were used to evaluate causalities. Furthermore, the validation set was used for simultaneous data validation. Results: The inflammatory cytokine monocyte chemoattractant protein 3 (MCP-3) was supposedly associated with a greater risk of cirrhosis. And cirrhosis was significantly correlated with increased levels of hepatocyte growth factor (HGF). Conclusions: This study suggests that MCP-3 might be associated with the etiology of cirrhosis, while several inflammatory cytokines could potentially play a role in its downstream development. Additionally, the progression of cirrhosis was associated with elevated levels of HGF, suggesting a possible role for liver repair functions. [ABSTRACT FROM AUTHOR]

Allergic disorders, including asthma, rhinitis and atopic dermatitis, are significant global health concerns, primarily driven by dysregulated immune responses. Key cytokines, such as interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13), play a pivotal role in orchestrating allergic inflammation. Conventional treatments, although effective in symptom management, often have side effects and do not adequately address the immune dysregulation. As a result, there is growing interest in exploring natural alternatives with fewer adverse effects. This study investigates the in vitro anti-allergic potential of Croton bonplandianum ethanolic extract (CBEE) by evaluating its effect on IL-5 and IL-13 production in stimulated THP-1 cell cultures. The results demonstrate that CBEE significantly downregulates IL-5 and IL-13 production, indicating its potential as a natural anti-allergic agent. These findings suggest that Croton bonplandianum could provide a novel approach to managing allergic disorders by targeting key mediators of inflammation. [ABSTRACT FROM AUTHOR]

Background: Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH. Methods: Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH. Results: Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1β, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function. Conclusions: Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Previous research has discovered that surfactant protein A (SP-A) is involved in the pathophysiology processes of certain lung illnesses. However, no definitive clinical studies have delved into the function of SP-A in individuals afflicted with community-acquired pneumonia (CAP). A prospective cohort study was used to investigate the relationships between blood SP-A levels and the severity and prognosis among CAP patients. Materials and methods: This study included 260 patients with CAP. Clinical traits and demographic data were examined during hospitalization. The concentrations of serum SP-A and serum interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). In addition, to evaluate the severity of CAP, a variety of scores, including the CURB-65, PSI, SMART-COP, and APACHE II, were employed. Results: The serum levels of SP-A at admission exhibited a gradual decline as the severity scores of CAP increased. Through Spearman correlation analysis, we observed an association between serum SP-A and some clinical indicators among CAP patients. Furthermore, results from a multiple linear regression model suggested changes in PSI scores (-17.868 scores, 95% CI: -32.743, -2.993) affect serum SP-A more than CURB-65 (-0.547 scores, 95% CI: -0.964, -0.131), SMART-COP (-1.097 scores, 95% CI: -1.889, -0.304) and APACHE II (-3.475 scores, 95% CI: -5.874, -1.075) with age, hypertension, diabetes mellitus, cerebral infarction, coronary heart disease, and bronchitis adjusted. In addition, the prognosis in CAP patients was monitored. Throughout their hospital stay, higher serum levels of SP-A decreased the risks of mechanical ventilation (RR: 0.315; 95% CI: 0.106, 0.937), vasoactive agents (RR: 0.165; 95% CI: 0.034, 0.790), intensive care unit (ICU) admissions (RR: 0.218; 95% CI: 0.066, 0.717) and longer hospital stays (RR: 0.397; 95% CI: 0.167, 0.945). Conclusion: In CAP patients, inverse dose-response correlations exist between serum SP-A levels with severity scores as well as prognosis at admission, suggesting that SP-A may take part in the CAP pathophysiological processes. Moreover, lower serum SP-A on admission is associated with an elevated prognostic risk of mechanical ventilation, the use of vasoactive agents, longer hospital stays, ICU admission, and mortality. Therefore, as a biomarker, SP-A may have the potential to predict the severity and poor prognosis of CAP patients. [ABSTRACT FROM AUTHOR]

Background: Alcoholic liver disease (ALD) significantly contributes to global morbidity and mortality. The role of inflammatory cytokines in alcohol-induced liver injury is pivotal yet not fully elucidated.Objectives: To establish a causal link between inflammatory cytokines and ALD using a Mendelian Randomization (MR) framework.Methods: This MR study utilized genome-wide significant variants as instrumental variables (IVs) for assessing the relationship between inflammatory cytokines and ALD risk, focusing on individuals of European descent. The approach was supported by comprehensive sensitivity analyses and augmented by bioinformatics tools including differential gene expression, protein-protein interactions (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and analysis of immune cell infiltration.Results: Our findings reveal that increased levels of stem cell growth factor beta (SCGF-β, beta = 0.141, p = .032) and interleukin-7 (IL-7, beta = 0.311, p = .002) are associated with heightened ALD risk, whereas higher levels of macrophage inflammatory protein-1α (MIP-1α, beta = -0.396, p = .004) and basic fibroblast growth factor (bFGF, beta = -0.628, p = .008) are linked to reduced risk. The sensitivity analyses support these robust causal relationships. Bioinformatics analyses around inflammatory cytokine-associated SNP loci suggest multiple pathways through which cytokines influence ALD.Conclusion: The genetic evidence from this study convincingly demonstrates that certain inflammatory cytokines play directional roles in ALD pathogenesis. These findings provide insights into the complex biological pathways involved and underscore the potential for developing targeted therapies that modulate these inflammatory responses, ultimately improving clinical outcomes for ALD patients. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis. Methods: We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods. Results: GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA. Conclusion: Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between homocysteine (Hcy), 25-hydroxyvitamin D [25-(OH)-D], high mobility group protein B1 (HMGB1) and oxidative stress indexes and inflammatory cytokines in serum and aqueous humor of patients with age-related cataract (ARC). Methods: 135 ARC patients admitted to The Sixth People's Hospital of Chengdu from January 2021 to January 2023 were selected as ARC group and 60 patients with ocular trauma in the same period were selected as control group. The levels of Hcy, 25(OH)-D, HMGB1, oxidative stress indexes [superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-PX)] and inflammatory cytokines [tumor necrosis factor-a (TNF-a), interleukin (IL) -1B, IL-6, IL-8] in serum and aqueous humor were detected. The correlation between serum and aqueous humor Hcy, 25(OH)-D, HMGB1 and oxidative stress and inflammatory cytokine levels in ARC patients were analyzed by Pearson correlation analysis. Results: The levels of Hcy, HMGB1, MDA, TNF-a, IL-1B, IL-6 and IL-8 in serum and aqueous humor in ARC group were higher than those in control group, while the levels of 25-(OH)-D, SOD, CAT and GSH-PX were lower than those in control group(P<0.05). Pearson correlation analysis showed that, Hey and HMGB1 in serum and aqueous humor of ARC patients were negatively correlated with SOD, CAT and GSH-PX, and positively correlated with MDA, TNF-α, IL-1B, IL-6 and IL-8 (P<0.05). 25-(OH)-D was positively correlated with SOD, CAT and GSH-PX, and negatively correlated with MDA, TNF-α, IL-1B, IL-6 and IL-8 (P<0.05). Conclusions: The levels of Hey and HMGB1 in serum and aqueous humor of ARC patients increase, and the level of 25(OH)-D decrease, which is significantly correlate with oxidative stress and inflammatory cytokines. Hcy, HMGB1, 25-(OH)-D may be involve in the development of ARC through oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

Healthy lifestyle reduces the risk of inflammation-related diseases. This study assessed how lifestyle changes affect inflammatory cytokines over 2 months. Involving 179 apparently healthy participants recruited from community, collecting data on lifestyles (smoking, alcohol, BMI, daily activity, sleep, diet) and measured inflammatory cytokines (TNF-α, IL-1β, IL-17A, CRP, IL-8, IL-18, IFN-γ) plus pepsinogens (PG I, PG II) at the baseline and 2-month follow-up. The combined adverse lifestyle score is the sum of scores across six lifestyles, with higher scores indicating more adverse lifestyle factors. Use multiple linear regression and mixed linear models to analyze the relationship between the changes in lifestyle and inflammatory cytokines (follow-up values minus baseline values). For every 1-point increase in combined adverse lifestyle score, IL-17A increased by 0.98 (95% CI 0.23, 1.73) pg/mL, IFN-γ increased by 1.79 (95% CI 0.39, 3.18) pg/mL. Decreased changes in daily activity were associated with higher IL-17A (β = 1.83, 95% CI 0.53, 3.13) and IFN-γ (β = 2.59, 95% CI 0.9, 4.98). Excluding daily activity, changes in combined adverse lifestyle scores were not associated with changes in inflammatory cytokines. Lifestyle improvements at 2-month intervals may reduce TNF-α, IL-17A and IFN-γ, with daily activity making the greatest contribution. [ABSTRACT FROM AUTHOR]

Background: Both inflammatory cytokines and the gut microbiome are susceptibility factors for vascular dementia (VaD). The trends in the overall changes in the dynamics of inflammatory cytokines and in the composition of the gut microbiome are influenced by a variety of factors, making it difficult to fully explain the different effects of both on the different subtypes of VaD. Therefore, this Mendelian randomization (MR) study identified the inflammatory cytokines and gut microbiome members that influence the risk of developing VaD and their causal effects, and investigated whether inflammatory cytokines are gut microbiome mediators affecting VaD. Methods: We obtained pooled genome-wide association study (GWAS) data for 196 gut microbiota and 41 inflammatory cytokines and used GWAS data for six VaD subtypes, namely, VaD (mixed), VaD (multiple infarctions), VaD (other), VaD (subcortical), VaD (sudden onset), and VaD (undefined). We used the inverse-variance weighted (IVW) method as the primary MR analysis method. We conducted sensitivity analyses and reverse MR analyses to examine reverse causal associations, enhancing the reliability and stability of the conclusions. Finally, we used multivariable MR (MVMR) analysis to assess the direct causal effects of inflammatory cytokines and the gut microbiome on the risk of VaD, and performed mediation MR analysis to explore whether inflammatory factors were potential mediators. Results: Our two-sample MR study revealed relationships between the risk of six VaD subtypes and inflammatory cytokines and the gut microbiota: 7 inflammatory cytokines and 14 gut microbiota constituents were positively correlated with increased VaD subtype risk, while 2 inflammatory cytokines and 11 gut microbiota constituents were negatively correlated with decreased VaD subtype risk. After Bonferroni correction, interleukin-18 was correlated with an increased risk of VaD (multiple infarctions); macrophage migration inhibitory factor was correlated with an increased risk of VaD (sudden onset); interleukin-4 was correlated with a decreased risk of VaD (other); Ruminiclostridium 6 and Bacillales were positively and negatively correlated with the risk of VaD (undefined), respectively; Negativicutes and Selenomonadales were correlated with a decreased risk of VaD (mixed); and Melainabacteria was correlated with an increased risk of VaD (multiple infarctions). Sensitivity analyses revealed no multilevel effects or heterogeneity and no inverse causality between VaD and inflammatory cytokines or the gut microbiota. The MVMR results further confirmed that the causal effects of Negativicutes, Selenomonadales, and Melainabacteria on VaD remain significant. Mediation MR analysis showed that inflammatory cytokines were not potential mediators. Conclusion: This study helps us to better understand the pathological mechanisms of VaD and suggests the potential value of targeting increases or decreases in inflammatory cytokines and gut microbiome members for VaD prevention and intervention. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to explore the expression of inflammatory cytokines (ICs) in Fabry disease (FD), the correlation between ICs and FD phenotypes, and the impact of enzyme replacement therapy (ERT) on IC expression. Methods: We recruited 67 FD patients and 44 healthy controls (HCs) and detected concentrations of the following ICs: interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-1β. We also analyzed the impact of ERT on IC expression in FD patients and the relationship between IC expression and sex, genotype, phenotype, disease burden, and biomarkers. Results: Most ICs were significantly higher in FD patients than in HCs. A number of ICs were positively correlated with clinical aspects, including disease burden (Mainz Severity Score Index [MSSI]) and cardiac and renal markers. IL-8 was higher in the high MSSI (P-adj=0.026*) than in the low MSSI. Conclusions: ICs were upregulated in FD patients, indicating the role of the innate immune process in FD etiology. ERT ameliorated FD-related inflammatory activation, at least to some extent. IC expression was positively correlated with disease burden and clinical markers in FD. Our findings indicated that the inflammatory pathway may be a promising therapeutic target for FD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To systematically review the effects of activating blood circulation and removing blood stasis on inflammatory cytokines and efficacy in psoriasis vulgaris and medication rules. METHODS: CNKI, VIP, Wanfang Data, CBM, PubMed, the Cochrane Library and Embase databases were retrieved to collect randomized controlled trials (RCT) of method of activating blood circulation and removing blood stasis in the treatment of psoriasis vulgaris. The retrieval time was from the establishment of the data base to Sept. 2023. Literature screening and data extraction were independently conducted by two researchers. The quality of included studies was evaluated by the modified Jadad scale. Meta-analysis was performed by Stata 17. 0. After the extracted names of traditional Chinese medicine were normalized, the frequency of high-frequency drug use were counted by Microsoft Excel 2019, the drug association rules were analyzed by SPSS modeler 18. 0, and the complex network diagram of traditional Chinese medicine was drawn by Cytoscape 3. 10. 1. RESULTS: A total of 15 studies were included, with a total sample size of 1 541 cases (10 cases dropped, 1 531 cases actually included), including 770 cases in the observation group (6 cases dropped, 764 cases actually included, received formula of activating blood circulation and removing blood stasis as the main effectand or combined with other therapy), 771 cases in the control group (4 cases dropped, 767 cases actually included, received formula do not primarily focus on activating blood circulation and removing blood stasis or utilize Western medical treatments). Meta-analysis showed that the expression level of inflammatory cytokines in the observation group was better than that in the control group, with statistically significant difference (SMD = - 1. 243,95% CI = - 1. 785- -0. 701,P =0. 000). Subgroup analysis of inflammatory cytokines showed that compared with the control group, the expression levels of interleukin (IL) 2, IL-4, IL-10, IL-17, IL-23, tumor necrosis factor α and gamma interferon in observation group were significantly improved, with statistically significant difference ( P < 0. 05), there was no significant difference in IL-18 level between two groups (P=0.708). The total effective rate of observation group was higher than that of control group (RR=1.211,95%CI =1.157-1.268,P =0.000), and PASI score was lower than that of control group (WMD=-2.756,95%CI =-3.359--2.153,P =0. 000), the differences were statistically significant. There was no significant difference in the incidence of adverse drug reactions between two groups (RR = 0. 838,95%CI = 0. 581- 1. 208,P =0. 344). Date mining showed that a total of 15 prescriptions were enrolled, including 57 traditional Chinese medicines. The total frequency of drugs was 181 times, and frequency of 7 traditional Chinese medicines were ≥ 9 times. Results of association rule analysis showed that high-frequency drugs and core drugs used in the treatment of psoriasis vulgaris by activating blood circulation and removing blood stasis included Carthami flos, Angelicae sinensis radix, Juglandis semen, Radix salviae, Spatholobus suberectus dunn, Rehmannia glutinosa, Smilacis Glabrae Rhixoma, and licorice. And the commonly used drug pairs included Juglandis semen-Carthami flos, Juglandis semen- Angelicae sinensis radix, Carthami flos-Angelicae sinensis radix. CONCLUSIONS: The method of activating blood circulation and removing blood stasis can improve the level of inflammatory cytokines in psoriasis vulgaris, regulate the inflammatory response, relieve the symptoms of psoriasis lesions, and improve the clinical efficacy. The high-frequency drugs and core drugs used are Carthami flos, Angelicae sinensis radix, Juglandis semen, Radix salviae, Spatholobus suberectus dunn, Rehmannia glutinosa, Smilacis Glabrae Rhixoma, and licorice. However, high-quality, large sample, multi-center randomized double-blind clinical trials are still needed to verify the above research results in the future [ABSTRACT FROM AUTHOR]

Objective：To investigate the effect of sevoflurane on M1 polarization of alveolar macrophages induced by lipopoly-saccharide (LPS) by regulating p38/MAPK signaling pathway. Methods：RAW264.7 cells were stimulated with 1 μg/ml LPS for 24 h and exposed to different concentrations (1%, 2%, 4%) of sevoflurane. After that, MTT, ELISA, RT-qPCR and Western blot assays were used to detect cell viability, inflammation factors and signaling pathway-related protein levels. Results：LPS stimulation led to de-creased cell viability and M2-type anti-inflammatory cytokine levels, and increased M1-type pro-inflammatory cytokine levels and phosphorylation of p38/MAPK in RAW264.7 cells (P<0.05). After sevoflurane treatment, the cell viability and anti-inflammatory cyto-kine levels were significantly enhanced, and the pro-inflammatory cytokine levels and phosphorylation of p38 were significantly decreased in a concentration-dependent manner (P<0.05) . The p38/MAPK inhibitor SB202190 intensified the inhibitory effect of sevoflu-rane on M1-type polarization of alveolar macrophages. Conclusion：Sevoflurane inhibits LPS-induced M1 polarization of alveolar mac-rophages, possibly by regulation of the p38/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The genetic association between urticaria and mental disorders and whether inflammatory cytokines mediate this process remains unclear. Materials and methods: A Mendelian randomization (MR) approaches to elucidate the causal relationship between urticaria and mental disorders and to validate the mediation of inflammatory cytokines. Genome‐wide association study (GWAS) databases used were obtained from Psychiatric Genomics Cooperation (PGC), GWAS Catalog, and FinnGen Consortium. Our study was conducted using inverse variance weighted (IVW) and Bayesian weighted MR (BWMR) methods for joint analysis. Results: The MR results showed that urticaria increased the risk of attention deficit hyperactivity disorder (ADHD) (odds ratio [OR] =$ = $ 1.088, 95% confidence interval [CI]: 1.026–1.154, p=$ = $ 0.0051); cholinergic urticaria increased the risk of bipolar disorder (BD) (OR =$ = $ 1.012, 95% CI: 1.001–1.022, p=$ = $ 0.0274); dermatographic urticaria increased the risk of ADHD (OR =$ = $ 1.057, 95% CI: 1.005–1.112, p=$ = $ 0.0323); idiopathic urticaria increased the risk of schizophrenia (SCZ) (OR =$ = $ 1.057, 95% CI: 1.005–1.112, p=$ = $ 0.0323); other unspecified urticaria increased the risk of ADHD (OR =$ = $ 1.085, 95% CI: 1.023–1.151, p=$ = $ 0.0063). We found that eight inflammatory cytokines were negatively associated with mental disorders and seven inflammatory cytokines were positively associated with mental disorders. Finally, our results suggested that inflammatory cytokines do not act as mediators between urticaria and mental disorders. Conclusions: Our study reveals a causal relationship between urticaria and the increased risk of mental disorders. We suggest that the treatment of urticaria could incorporate psychiatric interventions and mental health assessment of patients. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the localised effects of intrauterine ozone therapy on endometrial recovery in mares with endometritis. Our investigation assessed changes in gene expression profiles of anti‐inflammatory (IL‐1RA and IL‐10), proinflammatory (IL‐R1B3i and TNFα) and pleiotropic (IL‐6) cytokines, along with detailed histological measurements of epithelial and endometrial thickness and the glandular area ratio. Twenty mares were assigned to a 2 × 2 factorial design based on endometritis diagnosis and treatment (control or 42 μg/mL ozone insufflation), resulting in four groups: NC (negative for endometritis/control), NO (negative/ozone), PC (positive/control) and PO (positive/ozone). Oestrus was induced with 2 mg of oestradiol benzoate on Days −1, 1 and 3, plus 1 mg on Day 5. Day 0 marked the initial uterine treatment, followed by insufflations on Days 1 and 2 with O3 (ozone) or O2 (control). Uterine biopsies were taken before treatment on Day 0 and Day 6 for histological analysis and gene expression assessment. Data were analysed using a statistical model that included endometritis status, treatment type, biopsy times (D0 and D6) and their interactions, analysed with Proc Glimmix. Regardless of treatment or endometritis status, significant biopsy effects (p < 0.01) indicated increased epithelial height and endometrial thickness in Day 6 samples. Analysis of IL‐1 and TNFα revealed a significant interaction (p < 0.05) among endometritis, treatment and biopsy, with higher IL‐1B3i expression on Day 6 in the PC group. The treatment effect (p < 0.04) showed a higher frequency (p < 0.01) of animals with positive modulation in the PC group (66.7%) versus the PO group (0.0%). An interaction effect (p = 0.08) between endometritis and treatment resulted from higher IL‐1RA expression on Day 6 in the PC group compared to the PO group. Biopsy effect was significant for IL‐10 (p < 0.01), indicating higher values in the second sample associated with tissue repair. In the short‐term evaluation, ozone therapy did not influence endometrial morphology and may modulate cytokine expression, specifically the reduction in IL‐1 and TNFα levels. Therefore, this therapy appears to be a safe and potentially effective treatment for modulating the inflammatory response in mares with endometritis. [ABSTRACT FROM AUTHOR]

Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1β, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS. [ABSTRACT FROM AUTHOR]