Concentrations Of Inflammatory Cytokines Research Articles

Small nucleolar RNA host gene 1 silence inhibits the lipopolysaccharide-induced microglial apoptosis and inflammation.

Microglia activation is an early mediator of neuroinflammation and a major contributor to spinal damage and motor dysfunction. This study was designed to investigate the role of small nucleolar RNA host gene 1 (SNHG1) on the apoptosis and inflammatory response of microglial cell BV-2 and its underlying molecular mechanism. The C5 lamina contusion-induced mouse model of spinal cord injury (SCI) was constructed. Mouse microglia BV2 was stimulated by lipopolysaccharide (LPS) to establish the in vitro model of SCI. The quantitative reverse transcription polymerase chain reaction method was used to quantify RNA expression levels. Enzyme-linked immunosorbent assays were used to quantify concentrations of inflammatory cytokines. Protein levels were assessed by western blotting, and apoptosis was assessed by flow cytometry. Dual luciferase reporter gene assay and RNA pull-down assay were conducted to investigate the binding relationships between molecules. Upregulation of SNHG1 and downregulation of miR-195-5p were observed in the spinal cords of SCI mouse model. LPS treatment led to elevation of SNHG1 expression in BV2 cells, as well as accelerated apoptosis and inflammation. Evident mitigation of LPS-induced BV2 cell damage was observed after SNHG1 knockdown. MiR-195-5p was identified as a target of SNHG1. Inhibition of miR-195-5p restored the impact of SNHG1 knockdown on cell damage of LPS-treated BV2 cells. Furthermore, miR-195-5p can target activating transcription factor-6 (ATF6). In summary, SNHG1 knockdown ameliorates LPS-induced microglial apoptosis and inflammatory response via the miR-195-5p/ATF6 axis, providing a novel direction for SCI treatment.

Miniaturized implantable temperature sensors for the long-term monitoring of chronic intestinal inflammation.

Diagnosing and monitoring inflammatory bowel diseases, such as Crohn's disease, involves the use of endoscopic imaging, biopsies and serology. These infrequent tests cannot, however, identify sudden onsets and severe flare-ups to facilitate early intervention. Hence, about 70% of patients with Crohn's disease require surgical intestinal resections in their lifetime. Here we report wireless, miniaturized and implantable temperature sensors for the real-time chronic monitoring of disease progression, which we tested for nearly 4 months in a mouse model of Crohn's-disease-like ileitis. Local measurements of intestinal temperature via intraperitoneally implanted sensors held in place against abdominal muscular tissue via two sutures showed the development of ultradian rhythms at approximately 5 weeks before the visual emergence of inflammatory skip lesions. The ultradian rhythms showed correlations with variations in the concentrations of stress hormones and inflammatory cytokines in blood. Decreasing average temperatures over the span of approximately 23 weeks were accompanied by an increasing percentage of inflammatory species in ileal lesions. These miniaturized temperature sensors may aid the early treatment of inflammatory bowel diseases upon the detection of episodic flare-ups.

The Relationship Between Intra-articular Fracture Energy and a Patient's Inflammatory Response.

Prior studies have demonstrated elevated inflammatory cytokine concentrations in the synovial fluid of articular fracture patients postinjury. Similarly, CT-based fracture energy measurements have been correlated with posttraumatic osteoarthritis risk after pilon fracture. The purpose of this study was to determine the associations between synovial fluid cytokine levels, fracture energy, and overall trauma to the body in articular fracture patients. Acute tibial plateau, tibial plafond, and rotational ankle fracture patients were prospectively enrolled from December 2011 through January 1, 2019. Synovial fluid concentrations of interleukin-1 beta, interleukin-1 receptor antagonist, IL-6, IL-8, IL-10, matrix metallopeptidase-1, MMP-3, and MMP-13 were quantified. Patient CT scans were used to calculate fracture energy. The Injury Severity Score (ISS) was used to relate cytokine levels to whole-body injury severity. Spearman rho correlation coefficients were calculated to assess the relationship between injury severity metrics and synovial fluid cytokine, chemokine, and matrix metallopeptidase concentrations. Eighty-seven patients were enrolled with 42 had a tibial plateau fractures (OTA/AO 41B1-2, 41B2-14, 41B3-3, 41C1-3, 41C2-4, 41C3-16), 24 patients had a tibial plafond fracture (OTA/AO 43B1-2, 43B2-4, 43B3-5, 43C1-2, 43C2-3, 43C3-8), and 21 had a rotational ankle fracture (OTA/AO 44B1-3, 44B2-3, 44B3-6, 44C1-4, 44C2-5). Fracture energy significantly differed between fracture patterns, with ankle fractures involving substantially less fracture energy (median = 2.92 J) than plafond (10.85 J, P < 0.001) and plateau fractures (13.05 J, P < 0.001). After adjustment for multiple comparisons, MMP-3 was significantly correlated with transformed fracture energy (r = 0.41, 95% confidence interval [CI], 0.22-0.58, P < 0.001), while IL-1β was significantly correlated with the Injury Severity Score (Spearman ρ = 0.31, 95% CI, 0.08-0.49, P = 0.004). Synovial fluid MMP-3 concentration was significantly correlated with CT-quantified fracture energy in intra-articular fracture patients. Given that in clinical practice fracture energy tends to correlate with posttraumatic osteoarthritis risk, MMP-3 may warrant further investigation for its role in posttraumatic osteoarthritis development after articular fracture. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ameliorative effects of topical ramelteon on imiquimod-induced psoriasiform inflammation in mice.

Psoriasis is a long-lasting, immune-related inflammatory skin disease that affects 2-3% of the global population. It is distinguished by erythematous, silvery, and scaly patches. Ramelteon is a type of melatonin agonist that is used to treat insomnia. It has enhanced non-classical immunomodulatory and anti-inflammatory activities. The aim of the study is to assess the ameliorative effects of topical ramelteon on imiquimod (IMQ)-aggravated psoriasiform-like dermatosis in mice. The 32 albino mouse males were placed into six groups of eight animals, all of them. With the exception of the control group, all groups gained a once-a-day regimen of topical imiquimod 5% cream at a dose of 62.5mg for eight uninterrupted days, while mice in the control group gained vaseline-based ointment alternately. Immediately after an 8-day induction period in the imiquimod group, mice in the clobetasol and ramelteon treatment groups obtained a twice-daily regimen of topical clobetasol propionate 0.05% ointment and 0.1% ointment, respectively, for a further 8days. This extends the total duration of the experimental study to 16 continuous days. The findings of our study found that ramelteon significantly mitigated the concentrations of inflammatory cytokines in the skin tissue, including interleukin (IL)-6, IL-17A, IL-23, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF), as well as the scores associated with psoriatic lesions, including erythema, scaling, skin thickening, ear thickness, and overall cumulative PASI scores. Additionally, the anti-inflammatory impact of ramelteon was achieved by markedly increasing IL-10 levels in the skin tissue and correcting cutaneous histopathological alterations. Ramelteon ointment (0.1%) was comparable to that of clobetasol (0.05%) ointment in alleviating a mouse model of imiquimod-induced psoriasiform inflammation; this is probably due to its potential anti-inflammatory and immunomodulatory activities. Therefore, ramelteon could be a good additive option for therapeutic management of immune-triggered inflammatory conditions such as psoriasis.

Photodynamic Therapy of LD4-Photosensitizer Attenuates the Acute Pneumonia Induced by Klebsiella pneumoniae.

Klebsiella pneumoniae is a Gram-negative bacterium that induces acute lung injury (ALI) and inflammation in humans, necessitating immediate hospitalization and treatment. At present, the clinical treatment is largely dependent on hormones or antibiotics but is associated with drawbacks posed by the lack of eradication of the bacterium upon treatment and drug resistance. Therefore, there is an urgent need for novel and effective treatments. The current study investigated the treatment of K. pneumonia-induced ALI using a photosensitizer LD4 in conjunction with photodynamic therapy (PDT). The water content in the lungs (corresponding to edema) of a rat model of pneumonia induced by K. pneumoniae was reduced upon treatment with LD4-PDT. The counts of leukocyte, lymphocyte, and polymorphonuclear leukocyte in the blood were determined in the rat model of pneumonia, as were the concentrations of inflammatory cytokines (estimated using an enzyme-linked immunosorbent assay). The LD4-PDT treatment prominently reduced the levels of interleukin (IL)-6, IL-10, tumor necrosis factor-α, superoxide dismutase, and immune cells. Results suggest that LD4-PDT considerably alleviates the inflammation and oxidative stress caused by K. pneumoniae in the rat model of pneumonia. Furthermore, it could effectively improve the survival rate in the rat model of K. pneumonia-induced pneumonia and ameliorate histological changes while protecting the integrity of the pulmonary epithelial cells. These results highlight the potential application of LD4 as a photosensitizer for treating acute pneumonia induced by K. pneumoniae.

Attenuating Renal Interstitial Fibrosis by Shenqi Pill viaReducing Inflammation Response Regulated by NF-κBPathway In Vitro and In Vivo.

One of the most significant clinical features of chronic kidney disease is renal interstitial fibrosis (RIF). This study aimed to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. RIF model was established by conducting unilateral ureteral obstruction (UUO) surgery on rat or stimulating human kidney-2 (HK-2) cell with transforming growth factor β1 (TGFβ1). After modeling, the rats in the SQP low dose group (SQP-L), SQP middle dose group (SQP-M) and SQP high dose group (SQP-H) were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the TGFβ1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing serum. In in vivo assays, serum creatinine (SCr) and blood urea nitrogen (BUN) content were measured, kidney histopathology was evaluated., and α-smooth muscle actin (α-SMA) expression was detected by immunohistochemistry. Interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content, inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were assessed. Meanwhile, cell viability, inflammatory cytokines content, α-SMA expression, IKBα and P65 phosphorylation were detected in vitro experiment. Results. SQP exhibited reno-protective effect by decreasing SCr and BUN content, improving renal interstitial damage, blunting fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after the treatment with SQP-containing serum, viability and α-SMA expression were remarkably decreased in TGFβ1-stimulated HK-2 cell. Furthermore, SQP markedly down-regulated IL-1β, IL-6, and TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro. Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa B (NF-κB) pathway related inflammatory response, which indicates that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.

Paradoxical eosinophilic and cytokine responses to oral corticosteroid treatment in patients with asthma exacerbations

BackgroundThymic stromal lymphopoietin (TSLP) orchestrates eosinophilic inflammation, which may increase in asthma exacerbations. On the contrary, miR-1 inhibits TSLP-mediated eosinophil trafficking in lung endothelium. Whether the balance of TSLP and miR-1 levels determines the response to oral corticosteroids during the treatment of asthma exacerbations remains unknown. ObjectiveTo investigate the involvement of TSLP/miR-1 axis in inflammatory response to OCS treatment for asthma exacerbations. MethodsWe measured the concentrations of TSLP and other inflammatory cytokines and miR-1 expression during acute asthmatic exacerbations treated with standard oral corticosteroids (OCS) in a real-life setting. Twenty eight consecutive patients with acute asthma exacerbations treated with OCS for 1 week at the Emergency Department (ED) were studied prospectively. Steroid responders (SR) were identified by a significant reduction in blood eosinophils, whereas paradoxical responders (PR) showed no markedly decreased or even increased absolute blood eosinophil counts after OCS treatment. Differential white blood cell counts, blood cytokine levels and miR-1 expression within and between groups were compared before and after OCS treatment. The baseline cytokine concentrations in both groups were compared with those of stable asthmatics (SA). ResultsOCS treatment significantly reduced TSLP levels in steroid responders whereas this effect did not occur in paradoxical responders (P = 0.006 and P = 0.742, respectively). In contrast, miR-1 expression was unchanged in steroid responders in response to OCS, whereas it was markedly reduced in the paradoxical responders, despite higher expression at baseline compared with stable asthmatics, which may account for slower resolution of the exacerbation. ConclusionsIn some asthmatic patients with acute exacerbations who do not suppress eosinophils after a course of OCS, there is a paradoxical decrease in plasma miR-1 and increase in TSLP compared with steroid responders, which may result in slower clinical recovery.

Insight into the Antioxidant Activity of Ascorbic Acid-Containing Gelatin Nanoparticles in Simulated Chronic Wound Conditions.

Chronic wounds differ from acute wounds by remaining in the inflammatory phase for a long time. This chronic inflammation confers a high concentration of inflammatory cytokines, proteases, and ROS. Likewise, the pH environment of chronic wounds has been recorded within the range of 7.2-8.9 due to the alkaline by-products of bacterial proliferation. In this work, differences in pH between healthy skin and chronic cutaneous wounds have been used for the design and development of pH-responsive gelatin-based nanoparticles (NPs). Ascorbic acid (AA), as an antioxidant compound that can neutralize reactive oxygen species (ROS), has been the therapeutic model compound included in these NPs. The goal of the present work has been the preparation and characterization (physicochemical and biological properties) of NPs for the effective release of AA under simulated chronic wound conditions. In vitro experiments demonstrated total AA release at pH corresponding to the chronic wounds. The biocompatible character of these gelatin-based NPs based on their hemolytic and cytotoxicity responses has been highlighted under in vitro conditions. The reversible and protective antioxidant properties of the AA-including NPs in erythrocytes and skin cell lines, respectively, have been confirmed to be modulated by the gelatin A gel strength.

N-acetyl cysteine augments adipose tissue-derived stem cell efficacy on inflammatory markers and regulatory T cell system balance in an allergic asthma model

Background Allergic asthma is a destructive inflammatory process in the respiratory system. The anti-inflammatory and antioxidant effects of N-acetylcysteine (NAC) have been reported in patients with obstructive pulmonary disease. On the other hand, several studies have shown the modulatory effects of mesenchymal stem cells on the immune system and inflammatory responses. Accordingly, the purpose of the current study was to evaluate the effect of administration of adipose tissue-derived stem cells (ADSCs) plus NAC on regulatory T cell system balance in an allergic asthma model. Methods Eighty Sprague– Dawley rats were randomly divided into the following groups: Control, Plasmalite, Allergic asthma, Allergic asthma + ADSCs, NAC, Allergic asthma + NAC, Allergic asthma + ADSCs + NAC and Allergic asthma + Prednisolone. at the end of the experiment, arterial blood gas analysis, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), inflammatory cytokine concentration, total IgE and specific OVA-IgE levels, gene expression levels of CD4+-T cell subsets, pulmonary indicators, edema, and lung histopathology were evaluated in all groups. Results Administration of NAC plus ADSCs demonstrated a significant decrease in total WBC and eosinophil counts, which was in line with remarkable decrease in IL-17 and TNF-α concentrations and increases in IL-10 level compared with other treated groups. NAC plus ADSC treatment showed significant increases in Treg gene expression, although Th17 and Th2 expression significantly decreased compared with that in prednisolone- treated rats. Conclusion The results of the present study documented that the administration of ADSCs plus NAC has an inhibitory effect on the inflammation caused by allergic asthma in a rat model. The improvement of inflammatory indexes was significantly higher than that with prednisolone treatment.

Tannic acid alleviates ETEC K88-induced intestinal damage through regulating the p62-keap1-Nrf2 and TLR4-NF-κB-NLRP3 pathway in IPEC-J2 cells.

Tannic acid (TA), a naturally occurring polyphenol, has shown diverse potential in preventing intestinal damage in piglet diarrhea induced by Enterotoxigenic Escherichia coli (ETEC) K88. However, the protective effect of TA on ETEC k88 infection-induced post-weaning diarrhea and its potential mechanism has not been well elucidated. Therefore, an animal trial was carried out to investigate the effects of dietary supplementation with TA on the intestinal diarrhea of weaned piglets challenged with ETEC K88. In addition, porcine intestinal epithelial cells were used as an in vitro model to explore the mechanism through which TA alleviates intestinal oxidative damage and inflammation. The results indicated that TA supplementation (2 and 4 g kg-1) reduced diarrhea rate, enzyme activity (diamine oxidase [DAO] and Malondialdehyde [MAD]) and serum inflammatory cytokines concentration (TNF-α and IL-1β) (P < 0.05) compared to the Infection group (IG), group in vivo. In vitro, TA treatment effectively alleviated ETEC-induced cytotoxicity, increased the expression of ZO-1, occludin and claudin-1 at both mRNA and protein levels. Moreover, TA pre-treatment increased the activity of antioxidant enzymes (such as T-SOD) and decreased serum cytokine levels (TNF-α and IL-1β). Furthermore, TA increased cellular antioxidant capacity by activating the Nrf2 signaling pathway and decreased inflammatory response by down-regulating the expression of TLR4, MyD88, NF-kB and NLRP3. The present study showed that TA reduced the diarrhea rate of weaned piglets by restoring the intestinal mucosal mechanical barrier function, alleviating oxidative stress and inflammation. The underlying mechanism was achieved by modulating the p62-keap1-Nrf2 and TLR4-NF-κB-NLRP3 pathway. © 2024 Society of Chemical Industry.

Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats

Sepsis-induced cardiac injury represents a major clinical challenge, amplifying the urgency for effective therapeutic interventions. This study aimed to delve into the individual and combined prophylactic effects of Vitamin C (Vit C) and Coenzyme Q10 (CoQ10) against inflammatory heart injury in a cecal ligation and puncture (CLP) induced polymicrobial sepsis rat model. Thirty adult female Sprague–Dawley rats were randomly divided into five groups: Control, CLP, Vitamin C, CoQ10, and Vit C + CoQ10, each consisting of six rats. Treatments were administered orally via gavage for 10 days prior to the operation. Eighteen hours post-sepsis induction, the animals were euthanized, and specimens were collected for analysis. The study examined variations in oxidative (TOS, OSI, MDA, MPO) and antioxidative markers (TAS, SOD, CAT, GSH), histopathological changes, inflammatory cytokine concentrations (TNF-α, IL-1β), nitric oxide (NO) dynamics, and cardiac indicators such as CK-MB. Impressively, the combined regimen markedly diminished oxidative stress, and antioxidative parameters reflected notable enhancements. Elevated NO levels, a central player in sepsis-driven inflammatory cascades, were effectively tempered by our intervention. Histological examinations corroborated the biochemical data, revealing diminished cardiac tissue damage in treated subjects. Furthermore, a marked suppression in pro-inflammatory cytokines was discerned, solidifying the therapeutic potential of our intervention. Interestingly, in certain evaluations, CoQ10 exhibited superior benefits over Vit C. Collectively, these findings underscore the potential therapeutic promise of Vit C and CoQ10 combination against septic cardiac injuries in rats.

Bioactive metabolites of OMEGA-6 and OMEGA-3 fatty acids are associated with inflammatory cytokine concentrations in maternal and infant plasma at the time of delivery

Inflammation is necessary for a healthy pregnancy. However, unregulated or excessive inflammation during pregnancy is associated with severe maternal and infant morbidities, such as pre-eclampsia, abnormal infant neurodevelopment, or preterm birth. Inflammation is regulated in part by the bioactive metabolites of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs). N-6 FAs have been shown to promote pro-inflammatory cytokine environments in adults, while n-3 FAs have been shown to contribute to the resolution of inflammation; however, how these metabolites affect maternal and infant inflammation is still uncertain. The objective of this study was to predict the influence of n-6 and n-3 FA metabolites on inflammatory biomarkers in maternal and umbilical cord plasma at the time of delivery. Inflammatory biomarkers (IL-1β, IL-2, IL-6, IL-8, IL-10, and TNFα) for maternal and umbilical cord plasma samples in 39 maternal-infant dyads were analyzed via multi-analyte bead array. Metabolites of n-6 FAs (arachidonic acid and linoleic acid) and n-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) were assayed via liquid chromatography-mass spectrometry. Linear regression models assessed relationships between maternal and infant inflammatory markers and metabolite plasma concentrations. Increased plasma concentrations of maternal n-6 metabolites were predictive of elevated pro-inflammatory cytokine concentrations in mothers; similarly, higher plasma concentrations of umbilical cord n-6 FA metabolites were predictive of elevated pro-inflammatory cytokine concentrations in infants. Higher plasma concentrations of maternal n-6 FA metabolites were also predictive of elevated pro-inflammatory cytokines in infants, suggesting that maternal n-6 FA status has an intergenerational impact on the inflammatory status of the infant. In contrast, maternal and cord plasma concentrations of n-3 FA metabolites had a mixed effect on inflammatory status in mothers and infants, which may be due to the inadequate maternal dietary intake of n-3 FAs in our study population. Our results reveal that maternal FA status may have an intergenerational impact on the inflammatory status of the infant. Additional research is needed to identify how dietary interventions that modify maternal FA intake prior to or during pregnancy may impact maternal and infant inflammatory status and associated long-term health outcomes.

Intra-articular VEGF and MMP-1 are the Primary Drivers of Worse Baseline KOOS Symptoms and Quality of Life Subscores at Time of Knee Chondroplasty

Objectives: Biomarkers are a topic of interest in orthopaedics in the setting of osteoarthritis and patients undergoing knee arthroscopy for any reason. However, in patients undergoing knee arthroscopy for chondral defects, the influence of cytokines on patient pain and function is not fully understood. The purpose of this study is to investigate the concentrations of synovial inflammatory cytokines in patients undergoing arthroscopic chondroplasty for chondral defects in the knee and correlate those cytokine levels with baseline patient reported outcome measures (PRO’s) and defect characteristics. We hypothesized that the synovial cytokine environment will correlate with patient symptoms more so than baseline defect characteristics. Methods: Sixty patients 18-50 years old undergoing arthroscopic chondroplasty for knee cartilage defects were enrolled. Patients were assigned preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee International Knee Documentation Committee (IKDC) Subjective Knee Forms. Preoperative magnetic resonance images were used to calculate AMADEUS (Area Measurement And Depth Underlying Structure) scores.1 All patients received a successful synovial fluid aspiration just prior to initiation the arthroscopic procedure. The number of defects, total defect area, and ICRS grades were recorded based on intraoperative assessment. Patients with concomitant procedures beyond partial meniscectomy were excluded. Multiplex ELISA analyzed aspirations for: PDGF-BB, CCL-5/RANTES, MMP-3, MMP-1, EGF, VEGF, IL-1a, FGF-2, CCL-2, BMP-2, and aggrecan. Univariate correlation testing was used to assess significance between cartilage defect characteristics, PROs, and cytokine concentrations (Figure 1). The Akaike Information Criterion (AIC) was utilized to select the best-fit multivariate regression model using the 4 most significant independent variables for each cytokine (Figure 2). AIC best-fit modeling was repeated for each PRO that had at least two significant cytokine associations on univariate testing (Figure 3). Significance was set at P&lt;0.05. Results: MMP-1 had a positive correlation with number of defects treated (P=0.016) and negative correlation with KOOS quality of life (QOL) subscores (P=0.035; R2 =0.173). VEGF was positively correlated with defects treated (P=0.005) and negatively correlated with KOOS Symptoms scores (P=0.035; R2 =0.225). The treatment of multiple defects was an independent predictor of elevated IL-1a (P=0.002, R2 =0.202). CCL-2 was positively correlated with multiple defects (P=0.012) and negatively with KOOS QOL (P=0.016, R2 =0.173). Female sex was correlated with higher concentrations of MMP-3 (P=0.007, R2 =0.144), FGF (P=0.012, R2 =0.178), and BMP-2 (P=0.008; R2 = 0.169). BMP-2 was negatively correlated with KOOS Symptom (P=0.019). The primary driver of preoperative KOOS Symptoms scores on multivariate analysis was VEGF (P=0.023, R2 =0.120), influencing patient symptoms beyond defect characteristics. Similarly, KOOS QOL was independently correlated with MMP-1 concentration (P= 0.045, R2 =0.079), more so than ICRS grade (Figure 3). Conclusions: Multivariate regression analysis revealed that elevated MMP-1 was the primary driver of worse preoperative KOOS QOL scores, more so than defect characteristics such as the number of lesions treated. Similarly, worse preoperative KOOS Symptoms scores were more strongly correlated with elevated VEGF concentrations rather than defect ICRS grades. Our study demonstrated that synovial fluid cytokines appear to be the primary drivers of patients’ subjective assessments of their pain and function preoperatively.

Research Note: The effect of photoperiod on the NLRP3 inflammasome and gut microbiota in broiler chickens

The present study aimed to investigate the effect of photoperiod on the intestinal inflammation and gut microbiota. A total of 96 broiler chickens were divided into 2 groups and fed separately under 2 different photoperiods (12L:12D group and 23L:1D group) for 21 d. The results showed that the photoperiod of 23L:1D damaged duodenal tissue structure (intestinal villus erosion, mucosal epithelial cell detachment, and inflammatory cell infiltration), significantly increased the concentration of inflammatory cytokines (IL-1β, IL-18, IL-6, and TNF-α) and significantly increased the mRNA expression levels and protein expression levels of NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) and caspase1 (P <0.05) compared with 12L:12D, which indicating that extended photoperiod induced intestinal injury and activated NLRP3 inflammasome. 16S rRNA sequencing analysis revealed that Bacteroides was significantly decreased, Ruminococcus_torques_group, norank_f_Desulfovibrionaceae, GCA-900066575, Defluviitaleaceae_UCG-011, Lachnospiraceae_FCS020_group, norank_f_UCG-010 and norank_f_norank_o_Clostridia_vadinBB60_group and were significantly increased in the 23L:1D group, compared with the 12L:12D group (P < 0.05). The correlation analysis between differential microbial communities and intestinal inflammation showed that the relative abundance of Bacteroides was negatively correlated with the mRNA expression level of NLRP3 (P < 0.05) and the relative abundance of Ruminococcus_torques_group was positively correlated with the mRNA expression level of NLRP3 (P < 0.05). linear discriminant analysis (LDA) effect size (LEfSe) results (LDA > 4) showed that the relative abundance of Bacteroides was dramatically higher (P < 0.05) in the 12L:12D group, whereas the relative abundance of Ruminococcus_torques_group was noticeably higher (P < 0.05) in the 23L:1D group. By the comprehensive analysis of the gut microbiota, the interaction of gut microbiota (Bacteroides and Ruminococcus_torques_group) and NLRP3 inflammasome may contribute to the intestinal injury under the condition of extended photoperiod.

Protective Effects of Niacin on Rumen Epithelial Cell Barrier Integrity in Heat-Stressed Beef Cattle.

The present study investigates the theoretical basis for maintaining normal physiological functions in heat-stressed beef cattle by exploring the effects of niacin supplementation on the permeability of the rumen epithelial cell barrier. Herein, 12 Jinjiang bulls with an average weight of approximately 400 ± 20.0 kg were randomly divided into three groups, thermoneutral (TN), heat-stressed (HS), and heat-stressed niacin-supplemented (HN) groups, with 4 bulls in each group. The experiment spanned 70 days, and the plasma concentrations of D-lactic acid, diamine oxidase (DAO), lipopolysaccharides (LPSs), and inflammatory cytokines were analyzed. Additionally, we assessed the gene expression of tight junction proteins to understand the effect of niacin supplementation on heat-stressed beef cattle. Our results revealed that heat stress significantly increased the D-lactic acid and LPS levels in beef cattle plasma on days 30 and 45 of the experiment (p < 0.05). Moreover, it led to a significant rise in DAO levels on day 30 (p < 0.05). Niacin supplementation significantly reduced the LPS levels on day 30 (p < 0.05). Heat stress significantly elevated the plasma concentrations of inflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-α (TNF-α) (p < 0.05), while reducing the IL-4 concentration (p < 0.05). However, niacin supplementation effectively mitigated the concentrations of these inflammatory factors by reducing IL-1β, IL-2, IL-6, and TNF-α concentrations and increasing IL-4 concentrations. The mRNA expressions of tight junction proteins zonula occluden-1 (ZO-1), claudin-1, claudin-4, and claudin-7 were significantly downregulated (p < 0.05) in the HS group compared to those in the TN group, and those of ZO-1 and occludin were significantly upregulated (p < 0.05) in the HN group compared to those in the HS group. Notably, no significant differences were observed in ruminal papillae length and width among the studied groups (p > 0.05). Our findings indicate that heat stress adversely impacted the tight junction structure of the rumen epithelium, leading to a significant reduction in the expression of tight junction protein mRNA. Consequently, heat stress impaired the rumen mucosal barrier function, resulting in increased intestinal permeability. The mechanism underlying this effect may be associated with the decreased expression of tight junction protein genes in the rumen epithelial cells. However, niacin supplementation mitigated the detrimental effects of heat stress on intestinal permeability in beef cattle and increased the expression of tight junction protein genes in the rumen epithelium, thereby effectively protecting the rumen barrier in heat-stressed beef cattle. These results highlight the potential of nicotinic acid as a protective agent against the negative impacts of heat stress on intestinal integrity in beef cattle.

Daily Cashew and Brazil Nut Consumption Modifies Intestinal Health in Overweight Women on Energy-Restricted Intervention: A Randomized Controlled Trial (Brazilian Nuts Study)

BackgroundIncreased intestinal permeability and dysbiosis are related to obesity. Nuts can provide nutrients and bioactive compounds that modulate gut microbiota and inflammation, enhancing the beneficial effects of weight loss. ObjectivesTo evaluate the effect of consuming cashew nuts (Anacardium occidentale L.) and Brazil nuts (Bertholletia excelsa H.B.K) on intestinal permeability and microbiota, fecal SCFAs and pH, inflammation, and weight loss in energy restriction condition. MethodsIn this 8-week randomized controlled trial, 40 women with overweight or obesity were assigned to energy-restricted groups (−500 kcal/d): control group (free of nuts) or Brazilian nuts group (BN: 30 g of cashew nuts and 15 g of Brazil nuts per day). Permeability was analyzed by the lactulose/mannitol test and the microbiota by sequencing the 16S gene in the V3-V4 regions. Plasma concentrations of inflammatory cytokines (TNF, IL-6, IL-10, IL-8, IL-17A) and C-reactive protein were analyzed. ResultsIn total, 25 women completed the intervention. Both groups lost weight without statistical differences. Lactulose excretion increased only in the control group (P < 0.05). The BN consumption increased fecal propionic acid and potentially beneficial bacteria, such as Ruminococcus, Roseburia, strains NK4A214 and UCG-002 from the Ruminococcaceae family, but also Lachnospiraceae family, Bacteroides, and Lachnoclostridium, when compared to the control group. Changes in intestinal permeability were correlated to a greater reduction in body fat (kg), and IL-8, and increases in Ruminococcus abundance. ConclusionOur findings demonstrate a positive impact of BN consumption within an energy-restricted context, linked to the augmentation of potentially beneficial bacteria and pathways associated with body fat reduction. Besides, BN consumption mitigated increased intestinal permeability, although its capacity to diminish permeability or enhance weight loss proved limited.This trial was registered at the Brazilian Registry of Clinical Trials as ReBEC (ID: RBR-3ntxrm).

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA.MethodsParticipants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson’s correlation analysis was applied for the correlation analysis.ResultsNORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p.ConclusionsThere is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Study of the mechanism underlying the anti-inflammatory effect of Miao medicine comprising raw and processed Radix Wikstroemia indica using the “sweat soaking method”

Ethnopharmacological relevanceTo explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the “sweat soaking method” of Radix Wikstroemia indica (RWI). Aim of the studyThe purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the “sweat soaking method.” Materials and methodsNetwork pharmacology technology was used to construct the “drug-component target-pathway–disease” network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1β, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis. ResultsEleven key anti-inflammatory targets of IL6, IL-1β, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K–Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. ConclusionsThe anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the “sweat soaking method” enhanced the anti-inflammatory effect of RWI.

Inflammatory markers for differentiation of endometritis in the mare.

Endometrial biopsy is required to diagnose mares with chronic endometritis and endometrial degenerative fibrosis. An increase in understanding of equine reproductive immunology could be utilised to create less-invasive, time-efficient diagnostic tools especially when evaluating mares for chronic endometritis. To evaluate inflammatory cytokine and chemokine concentrations in uterine fluid samples collected by low-volume lavage (LVL) as a potential screening diagnostic biomarker for endometritis. Prospective cross-sectional clinical study. Forty-six mares underwent a LVL and subsequently endometrial biopsy. Mares were split in three groups: healthy, acute endometritis, and chronic endometrial fibrosis (CEF) based on cytological and histological evaluation. A fluorescent bead-based multiplex assay for IFN-γ, IFN-α, IL-1β, IL-4, IL-10, IL-17, sCD14, TNF-α, CCL2, CCL3, CCL5 and CCL11 were carried out on the LVL fluid. The endometrial biopsy was utilised for histology and qPCR of IFN-γ, IL-1β, IL-6, IL-8, IL-17, TNF-α, CCL2 and CCL3 genes. Statistical analyses examined differences in inflammatory markers and predictive modelling for diseased endometrium. Secreted concentrations of IFN-γ were lower in LVL fluid from reproductively healthy mares compared with acute endometritis (p = 0.04) and CEF (p = 0.006). Additionally, IL-17, IL-10, IL-1β, TNF-α, CCL2, CCL3, CCL5 and CCL11 were significantly increased (p ≤ 0.04) in LVL from CEF mares compared with healthy mares. Mares with CCL2 concentrations ≥550 pg/mL (14/14) had 100% probability of having CEF and/or acute endometritis. Healthy mares had lower relative abundance of IL-17 mRNA compared with mares in CEF group [median (interquartile rage) = 14.76 (13.3, 15.3) and 12.4 (10.54, 13.81)], respectively (p = 0.02). Limited sample size: larger numbers of mares with and without endometritis are required and reference intervals in LVL samples have to be established. Inflammatory chemokines and cytokines concentrations differed between healthy mares and mares with acute endometritis or CEF in LVL.

Patients with higher numbers of allergies have lower levels of anti-inflammatory cytokines and increased pain at the time of ACL reconstruction

BackgroundSynovial fluid biomarkers are well studied indicators of inflammation and healing in the setting of orthopedic injuries. However, it has not been studied if patients with one or more allergies have a difference in the concentrations of synovial fluid inflammatory cytokines compared to patients without allergies. The purpose of the current study is to analyze the concentration of 10 pro- and anti-inflammatory cytokines in the synovial fluid of isolated ACL injury patients with and without at least one allergy. Study DesignRetrospective Case-Control. MethodsA database of patients who underwent surgery for isolated ACL injury between September 2011 and July 2023 was analyzed. All patients had SF aspirated from the operative knee prior to the surgical incision and the concentrations of pre- and anti-inflammatory biomarkers were quantified. From this cohort, 24 patients were identified to have allergies by chart review. These patients were matched 1:1 to 24 patients without allergies based on age and sex. ResultsThere were no significant differences between the allergy and no allergy cohorts with respect to age (28.5 ± 10.3 vs. 29.5 ± 8.9, p = 0.76) and sex (70.8 % female vs. 70.8 % female, p = 1.00). The allergy cohort had a decreased concentration of TIMP-1 (492.41 ± 616.20 ng/mL vs. 1041.48 ± 942.04 ng/mL, p = 0.03) and IL-1Ra (101.70 ± 93.37 pg/mL vs. 359.94 ± 399.77 pg/mL, p = 0.01) compared to patients without allergies. A linear regression analysis found a significant association between increasing number of patients reported allergies and decreasing concentration of TIMP-1 (β = -231.59, p = 0.03) and IL-1Ra (β = -71.69p = 0.03) concentrations when controlling for age and sex. Finally, the allergy cohort was found to have a significantly higher value for the VAS pain scale at the time of surgery (26.84 ± 24.73 vs. 7.37 ± 10.98, p < 0.01) compared to those without an allergy. ConclusionPatients undergoing ACL reconstruction with at least one allergy were found to have decreased concentrations of the anti-inflammatory cytokines TIMP-1 and IL-1Ra in their synovial fluid compared to those without allergies on the day of surgery. Furthermore, an increase in total number of allergies was found to be an associated with a decrease in TIMP-1 and IL-1Ra levels. Finally, the allergy cohort also had a higher value for the VAS pain scale at the time of surgery, implicating the role of a patient’s innate immune system to their biologic and symptomatic response to injury.