Levels Of Inflammatory Proteins Research Articles

Inflammatory biomarkers in the cervicovaginal fluid to identify histologic chorioamnionitis and funisitis in women with preterm labor

ObjectiveWe investigated the association between altered levels of inflammatory proteins in the cervicovaginal fluid (CVF) and acute histologic chorioamnionitis (HCA) and funisitis in women with preterm labor (PTL). MethodsIn this study, a total of 134 consecutive singleton pregnant women with PTL (at 23+0–34+0 weeks) who delivered preterm (at < 37 weeks) and from whom CVF samples were collected at admission were retrospectively enrolled. The CVF levels of haptoglobin, interleukin-6/8, kallistatin, lipocalin-2, matrix metalloproteinase (MMP)-8, resistin, S100 calcium-binding protein A8, and serpin A1 were determined using enzyme-linked immunosorbent assay. The placentas were histologically analyzed after delivery. ResultsMultiple logistic regression analyses showed significant associations between elevated CVF interleukin-8 and resistin levels and acute HCA after adjusting for baseline covariates (e.g., gestational age at sampling). CVF haptoglobin, interleukin-6/8, kallistatin, MMP-8, and resistin levels were significantly higher in women with funisitis than in those without, whereas the baseline covariates were similar between the two groups (P > 0.1). The area under the receiver operating characteristic curves of the aforementioned biomarkers ranged from 0.61 to 0.77 regarding each outcome. Notably, HCA risk significantly increased with increasing CVF levels of interleukin-8 and resistin (P for trend < 0.05). ConclusionsHaptoglobin, interleukin-6/8, kallistatin, MMP-8, and resistin were identified as potential inflammatory CVF biomarkers predictive of acute HCA and funisitis in women with PTL. Moreover, the risk severity of acute HCA may be associated with the degree of the inflammatory response in the CVF (particularly based on interleukin-8 levels).

Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease

Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n=216) and MIS-C (n=56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P=0·02) and anti-IL-22 (P=0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P=0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P=0·02); and sCD25 (P=0·009), angiopoietin-2 (P=0·001), soluble IL-33-receptor (ST2, P=0·01) and CXCL10 (P=0·02) with ICU admission in MIS-C. Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

Serum of COVID-19 patients changes neuroinflammation and mitochondrial homeostasis markers in hippocampus of aged rats.

Patients affected by COVID-19 present mostly with respiratory symptoms but acute neurological symptoms are also commonly observed. Furthermore, a considerable number of individuals develop persistent and often remitting symptoms months after infection, characterizing the condition called long-COVID. Since the pathophysiology of acute and persistent neurological manifestations is not fully established, we evaluated the expression of different genes in hippocampal slices of aged rats exposed to the serum of a post-COVID (sPC) individual and to the serum of patients infected by SARS-CoV-2 [Zeta (sZeta) and Gamma (sGamma) variants]. The expression of proteins related to inflammatory process, redox homeostasis, mitochondrial quality control and glial reactivity was determined. Our data show that the exposure to sPC, sZeta and sGamma differentially altered the mRNA levels of most inflammatory proteins and reduced those of antioxidant response markers in rat hippocampus. Furthermore, a decrease in the expression of mitochondrial biogenesis genes was induced by all serum samples, whereas a reduction in mitochondrial dynamics was only caused by sPC. Regarding the glial reactivity, S100B expression was modified by sPC and sZeta. These findings demonstrate that changes in the inflammatory response and a reduction of mitochondrial biogenesis and dynamics may contribute to the neurological damage observed in COVID-19 patients.

Early Enteral Nutrition Facilitates Postoperative Recovery and Diminishes Complications in Patients Undergoing Laparoscopic Rectal Cancer Surgery

We have examined the effect of early enteral nutrition on postoperative recovery as well as the incidence of complications in patients undergoing laparoscopic rectal cancer surgery. The control group received traditional nursing care for postoperative nutrition, whereas the treatment group received early postoperative enteral nutrition. Relative to the control group, the postoperative anal exhaust time, first defecation time, first eating of solid food time, bowel sound recovery time, and hospital stay in the treatment group were shorter (P &lt; 0.05), nutrition-related indexes including serum total protein, albumin, and prealbumin were elevated (P &lt; 0.05), levels of serum inflammatory factors C-reactive protein, interleukin-6, and tumor necrosis factor-α were lower (P &lt; 0.05), peripheral blood CD3+, CD4+, and CD4+/CD8+ cells were elevated, while CD8+ cells were decreased (P &lt; 0.05). The incidence of postoperative complications in the treatment groups was lower relative to the control group (P &lt; 0.05). To sum up, early postoperative enteral nutrition can not only promote the immune function and nutritional status of patients undergoing laparoscopic rectal cancer surgery but also help reduce the postoperative inflammatory response and promote recovery.

Omics markers of platelet transfusion in trauma patients.

Even in the era of the COVID-19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma-induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life-saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion. To bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post-hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post-hospitalization. Longitudinal plasma samples were subjected to mass spectrometry-based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions. Higher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non-recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post-PLT transfusion). The present study provides the first multi-omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry-based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

Racial and Educational Disparities in Cumulative Exposure to Hardships of the 2008 Great Recession and Inflammation.

This cross-sectional analysis examined self-reported economic hardships of the 2008 Great Recession, race/ethnicity, educational attainment, and psychological well-being (PWB) as predictors of systemic inflammatory physiology at midlife. We also tested for differential vulnerability in the relationship between recession hardship and inflammatory physiology by race/ethnicity, education, and PWB. Adults from the Midlife in the United States Refresher sample completed a survey and biomedical assessments after the recession ( n = 592 non-Hispanic White respondents, n = 158 Black/African American respondents, n = 108 respondents with other race/ethnicity). Cumulative recession hardship was the sum of financial, housing, and employment-related events. Outcomes included circulating levels of interleukin 6 and C-reactive protein. General linear regression models tested main effects interactions between primary predictor variables. Educational attainment was inversely associated with recession hardships ( b = -0.18, 95% confidence interval = -0.26 to -0.11, p < .001). Black/African American respondents reported more recession hardships than White respondents ( b = 1.17, 95% confidence interval = 0.67 to 1.68, p < .001). More recession hardships predicted higher levels of interleukin 6 ( b = 0.06, p < .001) and C-reactive protein ( b = 0.04, p = .004). Analyses did not support race/ethnicity, education, and PWB as moderators of the association between recession hardship and inflammatory markers. Race/ethnicity and education independently predicted disparities in cumulative recession hardship exposure. Recession hardship predicted higher blood levels of inflammatory proteins associated with long-term health. The lack of findings for differential vulnerability in the relationship between recession hardship and inflammatory markers by race/ethnicity, education, or PWB was possibly due to the limited sample size.

The aqueous extracts of Ageratum conyzoides inhibit inflammation by suppressing NLRP3 inflammasome activation.

Ageratum conyzoides L. (Asteraceae), a well-known and widely distributed traditional tropical medicinal herb, has been used to treat diverse diseases. Our preliminary research has shown that aqueous extracts of A. conyzoides leaf (EAC) have anti-inflammatory activity. However, the detailed underlying anti-inflammatory mechanism of EAC is still unclear. To determine the anti-inflammatory mechanism of action of EAC. The major constituents of EAC were identified by ultra-performance liquid chromatography (UPLC) combined with quadrupole-time-of-flight mass/mass spectrometry (UPLC-Q-TOF-MS/MS). LPS and ATP were used to activate the NLRP3 inflammasome in two types of macrophages (RAW 264.7 and THP-1 cells). The cytotoxicity of EAC was measured by the CCK8 assay. The levels of inflammatory cytokines and NLRP3 inflammasome-related proteins were detected by ELISA and western blotting (WB), respectively. The oligomerization of NLRP3 and ASC and the resulting inflammasome complex formation were observed by immunofluorescence. The intracellular reactive oxygen species (ROS) level was measured by flow cytometry. Finally, an MSU-induced peritonitis model was established to evaluate the anti-inflammatory effects of EAC in vivo. Twenty constituents were identified in the EAC. Kaempferol 3,7-diglucoside, 1,3,5-tricaffeoylquinic acid, and kaempferol 3,7,4'-triglucoside were found to be the most potent ingredients. EAC significantly reduced the levels of IL-1β, IL-18, TNF-α, and caspase-1 in the two types of activated macrophages, implying that EAC can inhibit the activation of the NLRP3 inflammasome. A mechanistic study revealed that EAC inhibited NLRP3 inflammasome activation by blocking NF-κB signalling pathway activation and scavenging the level of intracellular ROS to prevent NLRP3 inflammasome assembly in macrophages. Furthermore, EAC attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. Our results demonstrated that EAC inhibited inflammation by suppressing NLRP3 inflammasome activation, highlighting that this traditional herbal medicine might be used to treat NLRP3 inflammasome-driven inflammatory diseases.

Suppression of Lung Oxidative Stress, Inflammation, and Fibrosis following Nitrogen Mustard Exposure by the Selective Farnesoid X Receptor Agonist Obeticholic Acid.

Nitrogen mustard (NM) is a cytotoxic vesicant known to cause pulmonary injury that can progress to fibrosis. NM toxicity is associated with an influx of inflammatory macrophages in the lung. Farnesoid X receptor (FXR) is a nuclear receptor involved in bile acid and lipid homeostasis that has anti-inflammatory activity. In these studies, we analyzed the effects of FXR activation on lung injury, oxidative stress, and fibrosis induced by NM. Male Wistar rats were exposed to phosphate-buffered saline (vehicle control) or NM (0.125 mg/kg) by intratracheal Penncentury-MicroSprayer aerosolization; this was followed by treatment with the FXR synthetic agonist, obeticholic acid (OCA, 15 mg/kg), or vehicle control (0.13-0.18 g peanut butter) 2 hours later and then once per day, 5 days per week thereafter for 28 days. NM caused histopathological changes in the lung, including epithelial thickening, alveolar circularization, and pulmonary edema. Picrosirius red staining and lung hydroxyproline content were increased, indicative of fibrosis; foamy lipid-laden macrophages were also identified in the lung. This was associated with aberrations in pulmonary function, including increases in resistance and hysteresis. Following NM exposure, lung expression of HO-1 and iNOS, and the ratio of nitrates/nitrites in bronchoalveolar lavage fluid (BAL), markers of oxidative stress increased, along with BAL levels of inflammatory proteins, fibrinogen, and sRAGE. Administration of OCA attenuated NM-induced histopathology, oxidative stress, inflammation, and altered lung function. These findings demonstrate that FXR plays a role in limiting NM-induced lung injury and chronic disease, suggesting that activating FXR may represent an effective approach to limiting NM-induced toxicity. SIGNIFICANCE STATEMENT: In this study, the role of farnesoid-X-receptor (FXR) in mustard vesicant-induced pulmonary toxicity was analyzed using nitrogen mustard (NM) as a model. This study's findings that administration of obeticholic acid, an FXR agonist, to rats reduces NM-induced pulmonary injury, oxidative stress, and fibrosis provide novel mechanistic insights into vesicant toxicity, which may be useful in the development of efficacious therapeutics.

Dihydromyricetin suppresses inflammatory injury in microglial cells to improve neurological behaviors of Alzheimer's disease mice via the TLR4/MD2 signal.

We analyzed the role and mechanism of dihydromyricetin (DHM) in suppressing inflammatory injury in microglial cells via targeting MD2. In vitro, BV2 cells were used as the objects of study to induce inflammatory injury with LPS+ATP, then the cell apoptosis level was identified, inflammatory factor levels were measured by ELISA, TLR4 and MD2 were stained with fluorescence staining, and protein expression was determined using Western-blot (WB) assay. Afterwards, MD2 expression was knocked down n BV2 cells to construct the BV2-MD2-/- cell line, so as to detect the role of DHM on BV2-MD2-/-. Moreover, the binding of DHM to MD2 was analyzed via mall molecule-protein docking and pull-down assays. In-vivo, wild-type (WT) C67BL/6 mice and APP/PS1 (AD) mice were used as the objects of study, which were intervened with DHM to detect the changes in mouse cognition. In addition, the pathological changes of brain tissues were analyzed with H&E staining. In addition, the inflammatory factor and protein levels in brain tissues were also detected. DHM suppressed inflammatory injury in BV2 cells, reduced the cell apoptosis rate and inflammatory factor levels, and suppressed the level of TLR4 and MD2. After MD2 knockdown, DHM was unable to further suppress BV2 cell injury. Results of small molecule-protein docking and pull-down assays suggested that DHM bound to MD2 to suppress the formation of TLR4 complex. In AD mice, DHM improved the cognitive disorder in mice, suppressed inflammatory injury in brain tissues and lowered the expression of TLR4 protein. DHM targeted MD2 to suppress the formation of TLR4 protein complex, thereby suppressing inflammatory injury in microglial cells and improving the cognition in AD mice.

GSK-3β inhibition alleviates arthritis pain via reducing spinal mitochondrial reactive oxygen species level and inflammation.

Pain is the main symptom of osteoarthritis, which severely reduces the patients' quality of life. Stimulated neuroinflammation and elevated mitochondrial oxidative stress are associated arthritis pain. In the present study, arthritis model was established by intra-articular injection of complete Freund's adjuvant (CFA) on mice. Knee swelling, pain hypersensitivity and motor disability were observed in CFA-induced mice. In spinal cord, neuroinflammation was triggered and presented as severe infiltration of inflammatory cells and up-regulated expressions of glial fibrillary acidic protein (GFAP), nuclear factor-kappaB (NF-κB), PYD domains-containing protein 3 (NLRP3), cysteinyl aspartate specific proteinase (caspase-1) and interleukin-1 beta (IL-1β). Mitochondrial function was disrupted and characterized as elevated expressions of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), dihydroorotate dehydrogenase (DHODH) and cytochrome C (Cyto C), and reduced expressions of Bcl-2 and Mn-superoxide dismutase (Mn-SOD) activity. Meanwhile, as a potential target for pain management, glycogen synthase kinase-3 beta (GSK-3β) activity was up-regulated in CFA induced mice. To explore potential therapeutic options for arthritis pain, GSK-3β inhibitor TDZD-8 was intraperitoneally injected for three days on CFA mice. Animal behavioral tests found that TDZD-8 treatment elevated mechanical pain sensitivity, suppressed spontaneous pain and recovered motor coordination. Morphological and protein expression analysis indicated that TDZD-8 treatment decreased spinal inflammation score and inflammatory related protein levels, recovered mitochondrial related protein levels, and increased Mn-SOD activity. In summary, TDZD-8 treatment inhibits GSK-3β activity, reduces mitochondrial mediated oxidative stress, suppresses spinal inflammasome response, and alleviates arthritis pain.

Establishment of an artificial particulate matter-induced lung disease model through analyzing pathological changes and transcriptomic profiles in mice

Particulate matter (PM), an environmental risk factor, is linked with health risks such as respiratory diseases. This study aimed to establish an animal model of PM-induced lung injury with artificial PM (APM) and identify the potential of APM for toxicological research. APM was generated from graphite at 600 °C and combined with ethylene. We analyzed diesel exhaust particulate (DEP) and APM compositions and compared toxicity and transcriptomic profiling in lungs according to the exposure. For the animal study, C57BL/6 male mice were intratracheally administered vehicle, DEP, or APM. DEP or APM increased relative lung weight, inflammatory cell numbers, and inflammatory protein levels compared with the vehicle control. Histological assessments showed an increase in particle-pigment alveolar macrophages and slight inflammation in the lungs of DEP and APM mice. In the only APM group, granulomatous inflammation, pulmonary fibrosis, and mucous hyperplasia were observed in the lungs of some individuals. This is the first study to compare pulmonary toxicity between DEP and APM in an animal model. Our results suggest that the APM-treated animal model may contribute to understanding the harmful effects of PM in toxicological studies showing that APM can induce various lung diseases according to different doses of APM.

Increased prefrontal cortical cells positive for macrophage/microglial marker CD163 along blood vessels characterizes a neuropathology of neuroinflammatory schizophrenia

Transcript levels of cytokines and SERPINA3 have been used to define a substantial subset (40%) of individuals with schizophrenia with elevated inflammation and worse neuropathology in the dorsolateral prefrontal cortex (DLPFC). In this study, we tested if inflammatory proteins are likewise related to high and low inflammatory states in the human DLFPC in people with schizophrenia and controls. Levels of inflammatory cytokines (IL6, IL1β, IL18, IL8) and a macrophage marker (CD163 protein) were measured in brains obtained from the National Institute of Mental Health (NIMH) (N = 92). First, we tested for diagnostic differences in protein levels overall, then we determined the percentage of individuals that could be defined as “high” inflammation using protein levels. IL-18 was the only cytokine to show increased expression in schizophrenia compared to controls overall. Interestingly, two-step recursive clustering analysis showed that IL6, IL18, and CD163 protein levels could be used as predictors of “high and low” inflammatory subgroups. By this model, a significantly greater proportion of schizophrenia cases (18/32; 56.25%; SCZ) were identified as belonging to the high inflammatory (HI) subgroup compared to control cases (18/60; 30%; CTRL) [χ2(1) = 6.038, p = 0.014]. When comparing across inflammatory subgroups, IL6, IL1β, IL18, IL8, and CD163 protein levels were elevated in both SCZ-HI and CTRL-HI compared to both low inflammatory subgroups (all p < 0.05). Surprisingly, TNFα levels were significantly decreased (–32.2%) in schizophrenia compared to controls (p < 0.001), and were most diminished in the SCZ-HI subgroup compared to both CTRL-LI and CTRL-HI subgroups (p < 0.05). Next, we asked if the anatomical distribution and density of CD163+ macrophages differed in those with schizophrenia and high inflammation status. Macrophages were localized to perivascular sites and found surrounding small, medium and large blood vessels in both gray matter and white matter, with macrophage density highest at the pial surface in all schizophrenia cases examined. A higher density of CD163+ macrophages, that were also larger and more darkly stained, was found in the SCZ-HI subgroup (+154% p < 0.05). We also confirmed the rare existence of parenchymal CD163+ macrophages in both high inflammation subgroups (schizophrenia and controls). Brain CD163+ cell density around blood vessels positively correlated with CD163 protein levels. In conclusion, we find a link between elevated interleukin cytokine protein levels, decreased TNFα protein levels, and elevated CD163+ macrophage densities especially along small blood vessels in those with neuroinflammatory schizophrenia.

Characterization of the inflammatory proteome of synovial fluid from patients with psoriatic arthritis: Potential treatment targets.

1) To characterize the inflammatory proteome of synovial fluid (SF) from patients with Psoriatic Arthritis (PsA) using a high-quality throughput proteomic platform, and 2) to evaluate its potential to stratify patients according to clinical features. Inflammatory proteome profile of SF from thirteen PsA patients with active knee arthritis were analyzed using proximity extension assay (PEA) technology (Olink Target 96 Inflammation panel). Four patients with OA were included as control group. Seventy-nine inflammation-related proteins were detected in SF from PsA patients (SF-PsA). Unsupervised analyzes of the molecular proteome profile in SF-PsA identified two specific phenotypes characterized by higher or lower levels of inflammation-related proteins. Clinically, SF-PsA with higher levels of inflammatory proteins also showed increased systemic inflammation and altered glucose and lipid metabolisms. Besides, SF from PsA patients showed 39 out of 79 proteins significantly altered compared to SF-OA specifically related to cell migration and inflammatory response. Among these, molecules such as TNFα, IL-17A, IL-6, IL-10, IL-8, ENRAGE, CCL20, TNFSF-14, OSM, IFNγ, MCP-3, CXCL-11, MCP4, CASP-8, CXCL-6, CD-6, ADA, CXCL-10, TNFβ and IL-7 showed the most significantly change. This is the first study that characterizes the inflammatory landscape of synovial fluid of PsA patients by analyzing a panel of 92 inflammatory proteins using PEA technology. Novel SF proteins have been described as potential pathogenic molecules involved in the pathogenesis of PsA. Despite the flare, inflammatory proteome could distinguish two different phenotypes related to systemic inflammation and lipid and glucose alterations.

Emodin alleviates testicular ischemia-reperfusion injury through the inhibition of NLRP3-mediated pyroptosis

Ischemia-reperfusion injury (IRI) is a major cause of injury after testicular torsion and can lead to permanent impairment of spermatogenesis. Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) has potent anti-inflammatory effects and may be protective against IRI in various organs. Herein, we evaluated the effects of emodin on pyroptosis in spermatogenic cells and its role in the process of testicular IRI. A testicular torsion/detorsion (TTD) mouse model and an oxygen-glucose deprivation/reperfusion (OGD/R) germ cell model were established. Hematoxylin and eosin staining was performed to evaluate the testicular ischemic injury. The expression of pyroptosis-related proteins and reactive oxygen species production in testis tissues were detected using Western blotting, quantitative real-time PCR, malondialdehyde and superoxide dismutase assay kits and immunohistochemistry. Cell viability and cytotoxicity were evaluated using Cell Counting Kit-8 and lactate dehydrogenase assay kit. Enzyme-linked immunosorbent assay, immunofluorescence and immunoblotting were performed to assess inflammatory protein levels. The results revealed that pyroptosis and inflammation levels were upregulated after testicular IRI, and emodin inhibited inflammation and pyroptosis by acting on NOD-like receptor thermal protein domain-associated protein 3 (NLRP3). Emodin exerts protective effects on testicular IRI by acting on the NLRP3 signaling pathway and inhibiting IRI-mediated pyroptosis. Emodin treatment attenuated testicular IRI and inhibited pyroptosis. Inhibitory effects of emodin on pyroptosis were attributed to the inhibition of NLRP3 inflammasomes. Thus, emodin could be an alternative treatment for testicular IRI.

Alterations in peripheral levels of cytokines and associated inflammatory markers in acute and chronic stages of schizophrenia spectrum disorders: a systematic review and network meta-analysis

IntroductionIt has been previously identified that levels of peripheral inflammatory proteins, such as cytokines, are altered in people with schizophrenia spectrum disorders (SSD).ObjectivesAs there is considerable inconsistency in the literature with respect to how inflammatory profiles differ between acute and chronic stages of SSD, a systematic review and network meta-analysis was performed.MethodsRecords from CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and PsycINFO were systematically searched from inception until 31 March 2022 for published studies that had measured levels of inflammatory proteins in cases of SSD and healthy controls. Pairwise and network meta-analyses were performed to determine whether there were significant differences in mean peripheral protein concentrations between acute SSD, chronic SSD, and healthy controls.ResultsAfter application of the screening process, 215 articles were included for data-analysis. One group of markers were consistently elevated (p&lt;0·05) in both acute and chronic SSD, relative to healthy controls; this group comprised interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP). A second group of markers were inconsistently altered between illness stages: IL-2 and interferon (IFN)-γ were significantly elevated (p&lt;0·05) in acute SSD, whilst IL-4, IL-12 and IFN-γ were significantly decreased (p&lt;0·05) in chronic SSD.ConclusionsThese results indicate that a baseline level of inflammatory protein alteration occurs in SSD throughout the course of illness. This was evident from the group of markers that were consistently elevated in acute and chronic SSD (e.g., IL-6), representing possible trait markers. Moreover, superimposed immune activity may occur in acute SSD, given the group of possible state markers that were increased only in acute illness (e.g., IFN-γ). Further research is required to elucidate whether these peripheral changes are reflected within the central nervous system.Disclosure of InterestNone Declared

Clinical efficacy of antileukotriene therapy in children with acute bronchitis

Recurrent episodes of bronchial obstruction in preschool children are one of the important risk factors for the development of bronchial asthma.Purpose. The study aimed at investigating the clinical and immunological characteristics of children with acute bronchitis and to determine the clinical effectiveness of course anti-inflammatory therapy.Material and methods. The study was a single-center prospective cohort, including 1–5-year-old patients with acute bronchitis (main group, n = 109): a group with acute simple bronchitis (n = 34) and acute obstructive bronchitis (n = 75). Reference group: children of health group 2 (n = 29). Clinical and anamnestic and laboratory methods were used. Patients with a positive API (Asthma Predictive Index) were administered montelukast at a dose of 4 mg orally once a day for 3 months (control points at 1 and 3 months), reference patients received symptomatic therapy for respiratory infection. The end point of the study is the absence of bronchial obstruction. The effectiveness of the use of Montelukast was evaluated by calculating the clinical index, efficiency coefficient. Results. A statistically significant predominance of intoxication symptoms was found in patients with acute simple bronchitis (p = 0.02), signs of respiratory failure (p &lt; 0.001), and peripheral eosinophilia — in children with acute obstructive bronchitis (p = 0.02). In etiology, rhinovirus significantly prevailed in patients with bronchial obstruction, and RS virus prevailed in patients with acute simple bronchitis (p = 0.02). The cytokine profile of patients with acute obstructive bronchitis is characterized by a decrease in the levels of macrophage inflammatory proteins (p = 0.01) and IL-8 (p = 0.048). A prolonged course of montelukast in children with a positive API significantly reduces the severity of subsequent acute respiratory infections, reduces the frequency of bronchial obstruction and the risk of bronchial asthma (p &lt; 0.001).Conclusion. Evaluation of the results of montelukast therapy demonstrated clinical efficacy in patients with a positive API index.

Cuscutae semen alleviates CUS-induced depression-like behaviors in mice via the gut microbiota-neuroinflammation axis.

Introduction: Major depressive disorder is a mental disease with complex pathogenesis and treatment mechanisms involving changes in both the gut microbiota and neuroinflammation. Cuscutae Semen (CS), also known as Chinese Dodder seed, is a medicinal herb that exerts several pharmacological effects. These include neuroprotection, anti-neuroinflammation, the repair of synaptic damage, and the alleviation of oxidative stress. However, whether CuscutaeSemen exerts an antidepressant effect remains unknown. Methods: In this study, we evaluated the effect of CS on chronic unpredictable stress (CUS)-induced depression-like behaviors in mice by observing changes in several inflammatory markers, including proinflammatory cytokines, inflammatory proteins, and gliocyte activation. Meanwhile, changes in the gut microbiota were analyzed based on 16 S rRNA sequencing results. Moreover, the effect of CS on the synaptic ultrastructure was detected by transmission electron microscopy. Results: We found that the CS extract was rich in chlorogenic acid and hypericin. And CS relieved depression-like behaviors in mice exposed to CUS. Increased levels of cytokines (IL-1β and TNF-α) and inflammatory proteins (NLRP3, NF-κB, and COX-2) induced by CUS were reversed after CS administration. The number of astrocytes and microglia increased after CUS exposure, whereas they decreased after CS treatment. Meanwhile, CS could change the structure of the gut microbiota and increase the relative abundance of Lactobacillus. Moreover, there was a significant relationship between several Lactobacilli and indicators of depression-like behaviors and inflammation. There was a decrease in postsynaptic density after exposure to CUS, and this change was alleviated after CS treatme. Conclusion: This study found that CS treatment ameliorated CUS-induced depression-like behaviors and synaptic structural defects in mice via the gut microbiota-neuroinflammation axis. And chlorogenic acid and hypericin may be the main active substances for CS to exert antidepressant effects.

Plasma Galectin-3 and H-FABP correlate with poor physical performance in patients with congestive heart failure.

Heart failure (HF) is often associated with compromised physical capacity in patients. However, it is unclear if established HF markers correlate with the physical performance of patients with congestive HF (CHF). We assessed the left ventricular end-systolic dimension (LVESD) and ejection fraction (LVEF) and, physical performance parameters, including short physical performance battery (SPPB), gait speed (GS), and handgrip strength (HGS) in 80 patients with CHF along with 59 healthy controls. Furthermore, levels of plasma HF markers galectin-3 and heart-specific fatty acid binding protein (H-FABP) were measured in relation to the severity of HF and physical performance. Irrespective of etiology, significantly greater LVESD and lower LVEF were observed in HF patients versus controls. As expected, the levels of HF markers galectin-3 and H-FABP were upregulated in the CHF patients which were accompanied by significantly elevated levels of plasma zonulin and inflammatory marker C-reactive protein (CRP). The SPPB scores, GS, and HGS were significantly lower in the ischemic and non-ischemic HF patients than controls. The level of galectin-3 was inversely correlated with SPPB scores (r2 = 0.089, P = 0.01) and HGS (r2 = 0.078, P = 0.01). Similarly, H-FABP levels were also inversely correlated with SPPB scores (r2 = 0.06, P = 0.03) and HGS (r2 = 0.109, P = 0.004) in the patients with CHF. Taken together, CHF adversely affects physical performance, and galectin-3 and H-FABP may serve as biomarkers of physical disability in patients with CHF. The robust correlations of galectin-3 and H-FABP with the physical performance parameters and CRP in CHF patients suggest that the poor physical performance may partly be caused due to systemic inflammation.

Oral hydrogel microspheres were used for highly specific delivery of Steamed Codonopsis lanceolata to exert the protective effects on cisplatin-induced acute kidney injury in mice

Although Steamed Codonopsis lanceolata (SCL) has been shown to protect against acute kidney injury (AKI), Its poor stability and susceptibility to decomposition in the GI tract significantly reducing its therapeutic efficacy. Nanoscale/microscale drug delivery systems may overcome the difficulties of oral administration of phytochemicals and avoid premature drug release and degradation. In this study, we mainly loaded SCL into sodium alginate (SA) micron particles (SCL-SA), which showed significant gut-targeting and anti-gastric acid ability from in vitro and in vivo imaging fluorescence adhesion experiments. Our results showed that the levels of serum blood urea nitrogen (BUN) and creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by SCL-SA. Renal oxidative stress, evidenced by increasing malondialdehyde (MDA) level and decrease of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) activities, were significantly alleviated by SCL-SA pretreatment. Immunohistochemical staining showed that SCL-SA could improve cell apoptosis by decrease the expressions of BCL2-Associated X (Bax) and B-cell lymphoma-2 (Bcl-2). In addition, SCL-SA pretreatment can also inhibit the increase of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induced by cisplatin. Additionally, SCL-SA was found to reduce the expressions of nuclear factor-κB (NF-κB) signal pathways and inflammatory protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) induced by cisplatin. Meanwhile, the contents of lobetyolin and syringin in Codonopsis lanceolata were increased after steaming. In conclusion, the reduction of AKI by SCL-SA may be due to the synergistic effect of lobetyolin and syringin. Based on the advantages of microparticles, this study provides important insights into the treatment of AKI with oral natural compounds.

Abstract TP157: Interleukin Plasma Levels And Risk Of Hemorrhage In Pediatric Brain Arteriovenous Malformation Patients

Introduction: Brain arteriovenous malformations (bAVMs) are the leading cause of pediatric hemorrhagic stroke. Prior studies have implicated inflammation as a major contributor to bAVM pathogenesis, with increased inflammatory cell infiltration and IL-6 protein levels reported in bAVM tissue. However, few studies have evaluated circulating inflammatory proteins as biomarkers for bAVM or intracranial hemorrhage (ICH). Hypothesis: We hypothesized that higher plasma levels of interleukin (IL)-1B and IL-6 would be associated with bAVM ICH at initial presentation. Methods: Pediatric bAVM cases (&lt;19 years) evaluated at our institution between 2005 and 2022 were enrolled into an ongoing cohort study. Plasma samples (n=119) were collected and analyzed using the OLINK Explore 384 Inflammation panel. Protein levels were quantified based on log-log standard curves, and log 2 -transformed for analysis. Multivariable regression analysis compared plasma protein levels between cases with and without ICH presentation, adjusting for sex, race, ethnicity, age, and time between initial presentation and first plasma collection. Exponentiated coefficients are presented as proportional increase (PI). Results: Samples were collected a median of 23.5 days after presentation in the ICH group and 140 days in the non-ICH group. Plasma levels of IL-6 were higher in bAVM patients with ICH vs. those without ICH (PI=3.22, 95% CI=1.32-7.85, p=0.011), adjusting for age, sex, race and Hispanic ethnicity. After further adjustment for time to sample collection, the association between IL-6 levels and ICH was no longer significant. (PI =1.36, CI=0.57-3.29, p=0.478). There was no difference in plasma levels of IL-1B between groups (PI=0.85, 95% CI=0.65-1.12, p=0.26). Conclusion: Plasma levels of IL-6 were associated with ICH presentation in this pediatric bAVM cohort; however, this association may reflect downstream effects of the hemorrhage. Further studies are needed to help clarify whether plasma IL-6 levels can be used to predict hemorrhage risk in patients with unruptured bAVMs.