Levels Of Inflammatory Markers Research Articles

Abstract TP342: Associations Between Pericarotid Fat Density and Carotid Plaque Inflammatory Cytokine Levels

Background: Previous research has suggested pericarotid fat density to be significantly linked to atherosclerotic plaque components and cerebrovascular events. Inflammatory markers within the plaques are critical in the pathogenesis and progression of carotid artery disease. However, the association between pericarotid fat and inflammatory processes within atherosclerotic plaques remains underexplored. This study hypothesizes that pericarotid fat density is directly associated with the levels of inflammatory markers within atherosclerotic plaques. Methods: Carotid plaques were prospectively collected from patients with carotid artery disease undergoing carotid endarterectomy (CEA). The levels of inflammatory plaque cytokines (MCP-1, IL-8, IFN-γ, IL-10, IL-1β, IL-6, PDGF-AA, PDGF-AB/BB, TNF-α, VEGF) were measured in tissue homogenates using a customized 10-plex Luminex assay. Baseline demographics and clinical data of our population were extracted from electronic health records. We analyzed preoperative neck computed tomography angiography (CTA) images placing regions-of-interest (ROI) in the pericarotid fat on the slice showing maximal stenosis. For each patient, we calculated the average of Hounsfield Units (HU) within the ROI. Spearman correlation test was used to assess the correlation between variables. Results: Among the 43 patients included, the median age was 73 (67, 78) years, and 33 (76.7%) patients were male. Plaque levels of PDGF-AA and VEGF showed significant positive correlations with HU (r=0.330, p=0.030; r=0.380, p=0.011, respectively), as illustrated in Figure 1 . Although plaque levels of IFN-γ demonstrated a significant negative correlation with HU (r=-0.390, p=0.010), the most cases exhibited values close to zero. Conclusions: The assessment of pericarotid fat density on CTA may allow for the estimation of plaque inflammation, suggesting that more fat density is associated with increased inflammatory activity within atherosclerotic plaques.

Cardioprotective Potential of Moringa Oleifera Leaf Extract Loaded Niosomes Nanoparticles - Against Doxorubicin Toxicity In Rats.

Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases. The current study is intended to explore the cardioprotective effect of ethanolic Moringa oleifera extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart. It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status. Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.

The pan-PPAR agonist lanifibranor reduces portal pressure independent of fibrosis reduction through the splanchnic vasculature.

Portal hypertension (PH) can cause severe complications in patients with advanced chronic liver disease (aCLD). The pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor reduces portal pressure in preclinical models of aCLD. Since the effect on PH might be secondary to fibrosis improvement, we investigated the effect of lanifibranor on PH, hepatic and splanchnic angiogenesis in mouse models of fibrotic and prehepatic non-fibrotic PH. Mice with fibrotic PH (common bile duct ligation; CBDL) and prehepatic PH (partial portal vein ligation; PPVL) received daily lanifibranor/vehicle for 14 or 7 days, respectively. Hemodynamics, serum, hepatic and mesenteric histology, and hepatic, mesenteric and liver sinusoidal endothelial cells (LSEC) gene expression levels were analyzed. Vascular corrosion casts of the venous mesenteric and hepatic vasculature were analyzed using scanning electron microscopy and µCT. Portal pressure was increased in CBDL mice. Lanifibranor treatment demonstrated a dose-dependent trend towards decreasing the elevated portal pressure, and reduced fibrosis. Hepatic mRNA levels of inflammatory, fibrotic and angiogenic markers were significantly downregulated in lanifibranor-treated CBDL mice. LSEC dysfunction was improved by lanifibranor. Compared to CBDL mice, portal pressure was more extensively elevated in PPVL mice, which was significantly reduced by lanifibranor. Superior mesenteric artery blood flow, which was increased in vehicle-treated PPVL mice, tended to decrease by lanifibranor. The expansion of the mesenteric vasculature and mesenteric protein level of angiogenetic markers in PPVL mice were reduced after lanifibranor. In conclusion, lanifibranor improves PH, independently from fibrosis reduction, potentially through reducing the venous mesenteric vasculature expansion and intrahepatic angiogenesis, and ameliorating LSEC function.

Study of the occurrence of metabolic dysfunction-associated fatty liver disease in obstructive sleep apnea hypopnea syndrome and its risk factors

Objective: To analyze the occurrence of metabolic dysfunction-associated fatty liver disease (MAFLD) and related inflammatory indicators in obstructive sleep apnea hypopnea syndrome (OSAHS) and explore the risk factors of MAFLD. Methods: A cross-sectional study. From January 2022 to October 2024,172 patients with sleep disorders were enrolled in the First Affiliated Hospital of Soochow University,including 38 patients with non-OSAHS,53 patients with mild OSAHS,37 patients with moderate OSAHS,and 44 patients with severe OSAHS. The occurrence of MAFLD was comprehensively judged from three aspects: metabolic dysfunction-associated fatty liver (MAFL),elevated liver enzymes,and liver fibrosis. The situation of MAFLD and the level of related inflammatory markers were compared among the four groups. Binary logistic regression was used to analyze the risk factors for MAFLD in OSAHS. Results: There were significant differences in the prevalence of MAFL,the percentage of elevated liver enzymes,and interleukin-6 and tumor necrosis factor-alpha levels among the four groups (P<0.05). The differences of fibrosis-4 index and C-reactive protein among the four groups were not statistically significant (P>0.05). Binary logistic regression showed that BMI,triglycerides,longest time of sleep apnea and tumor necrosis factor-alpha were the risk factors for MAFL (P<0.05). BMI,glucose,and apnea-hypopnea index were the risk factors for elevated liver enzymes (P<0.05). Conclusions: OSAHS is strongly associated with MAFLD,and the involvement of OSAHS in the occurrence and development of MAFLD may be related to obesity,lipid metabolism disorders,insulin resistance,inflammatory responses,and intermittent hypoxia.

Association of serum levels of inflammation and oxidative stress markers with cognitive outcomes in multiple sclerosis; a systematic review.

Multiple sclerosis (MS) is an immune-mediated disease with cognitive impairment being a crucial manifestation. Oxidative stress and inflammation play significant roles in the disease's pathogenesis. This systematic review explores the association between inflammation and oxidative stress markers, with cognitive outcomes in MS patients. This study adhered to the Joanna Briggs Institute (JBI) and PRISMA 2020 methods. Eligibility criteria included studies with MS patients, evaluating serum inflammation and/or oxidative stress markers, assessing cognitive function, and examining the relationship between these factors. PubMed, Scopus, Embase, and Web of Science, were searched and the risk of bias was assessed using the JBI checklists. Out of 1609 identified records, 10 studies were included in this systematic review. The studies were published between 2006 and 2023 and involved 629 MS patients. Current evidence suggests a negative correlation between TNF-α, and cognitive outcomes in MS (reported in three out of five studies). Associations between the decreased native and total thiol levels, as well as interleukin (IL)-17A with cognitive impairment, and the correlation between IL-6 and C-reactive protein (CRP) with cognitive scores in MS are also reported (one study for each). IL-10 (four studies), glutathione peroxidase (GPX), reduced glutathione (GSH), catalase activity (CAT), ischemia-modified albumin (IMA), IL-8, IL-18, and IL-2 (one study for each) did not found to be associated with cognition in MS and evidence regarding the possible role of interferon-gamma (IFN-γ), total antioxidant capacity (TAC), and malondialdehyde (MDA) is not definitive. The review findings suggest a complex association between oxidative stress and inflammation with cognitive outcomes in MS. Diversity in study designs, participant characteristics, and assessment methods makes the findings of this study inconclusive and highlights the need for future research.

Female mice exhibit similar long-term plasticity and microglial properties between the dorsal and ventral hippocampal poles

The hippocampus is a heterogenous structure that exhibits functional segregation along its longitudinal axis. We recently showed that in male mice, microglia, the brain’s resident immune cells, differ between the dorsal (DH) and ventral (VH) hippocampus, impacting long-term potentiation (LTP) mainly through the CX3CL1-CX3CR1 signaling. Here, we assessed the specific features of the hippocampal poles in female mice, demonstrating a similar LTP amplitude in VH and DH in both control and Cx3cr1 knock-out mice. In addition, the expression levels of Cx3cr1 and Cx3cl1 mRNA do not differ between the two poles in control mice. These data support the critical role of the CX3CL1-CX3CR1 signaling in setting the physiological amount of plasticity, equally between poles in females. Although BDNF is higher in DH compared to VH, the expression levels of inflammatory markers involved in plasticity and of phagocytosis markers in microglia are comparable between the two poles. In accordance, microglia soma and arborization area/perimeter, and microglial ultrastructure are similar across regions, with the exception of microglial density, cells arborization solidity and circularity that are higher in DH. Understanding the molecular processes underlying microglial sex differences and their potential implications for plasticity in specific brain regions is of major importance in physiological and pathological conditions.

Inflammation biomarkers and neurobehavioral performance in rural adolescents

BackgroundSystemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador. MethodsWe examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes. ResultsHigher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.465 units (95% CI: -0.80, -0.13) and -0.418 units (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.112 units (-0.19, -0.03). A greater inflammatory composite variable from seven markers was associated with lower scores in language (β = -0.11, p=0.043), visuospatial processing (β= -0.15, p= 0.086), and social perception (β= -0.22, p=0.005) domains. ConclusionsHigher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

The effects and mechanisms of sivelestat in alleviating post-resuscitation brain injury

Objective: To investigate the neuroprotective effects of sivelestat (SV) in a porcine cardiac arrest-resuscitation model while exploring its association with the NF-κB/NLRP3 pathway. Methods: Fifteen healthy male pigs were randomly assigned to the sham operation group (Sham, n=5), the cardiopulmonary resuscitation group (CPR, n=5), and the CPR with SV treatment group (CPR+SV, n=5). Cardiac arrest was induced by ventricular fibrillation for 9 minutes in the CPR and CPR+SV groups, followed by 6 minutes of cardiopulmonary resuscitation to establish the experimental model. To assess the potential protective effects of SV, five minutes after successful resuscitation, the CPR+SV group received SV at 10 mg/kg via femoral vein infusion for 1 hour using a micro-infusion pump. Blood samples were collected from the femoral vein at baseline and at 0.5, 1, 2, and 4 hours post-resuscitation for serum levels of neuron-specific enolase (NSE) and S100β protein, recognized as markers of brain injury, via ELISA. Neurological function was assessed 24 hours post-resuscitation using neurological deficit scores (NDS). The animals were euthanized 24 hours post-resuscitation, and left ventricular apical myocardial and frontal lobe cortex tissues were harvested. Brain tissue levels of inflammatory markers, IL-1β and IL-18, were analyzed using Western blotting. Western blot was used to evaluate the effect of SV in reducing the expression levels of NF-κB, NLRP3, cleaved caspase-1, and GSDMD, key markers of pyroptosis, in the brain tissues of pigs after CPR. Results: Post-resuscitation, the CPR and CPR+SV groups exhibited significantly higher serum levels of NSE and S100β and elevated NDS scores compared to the Sham group (all P&lt;0.05). Nevertheless, the CPR+SV group showed significantly improved neurological scores and reduced levels of brain injury markers at all time points post-resuscitation versus the CPR group (P&lt;0.05). At 24 hours post-resuscitation, IL-1β and IL-18 levels in the brain tissues of CPR and CPR+SV groups were markedly higher than those in the Sham group (P&lt;0.05). Conversely, the levels of inflammatory factors in the CPR+SV group were significantly reduced compared to the CPR group (P&lt;0.05). At 24 hours post-resuscitation, brain tissue expression of NF-κB, NLRP3, cleaved caspase-1, and GSDMD was markedly elevated in the CPR group (P&lt;0.05). SV markedly suppressed the expression of these pyroptosis-associated proteins (P&lt;0.05), highlighting its potential role in neuroprotective via inhibition of the NF-κB/NLRP3 pathway. Conclusion: SV effectively mitigates post-resuscitation brain injury and enhances neurological outcomes, likely through its regulatory effects on the NF-κB/NLRP3 pathway.

Airway morphology, hyoid position, and serum inflammatory markers of obstructive sleep apnea in children treated with modified twin-block appliances.

To investigate the effects of modified twin-block appliances (MTBA) on obstructive sleep apnea (OSA) and mandibular retrognathia and the changes in the upper airway, hyoid bone position, and hypoxia-related inflammatory marker levels in children with OSA. This study included children with OSA and mandibular retrognathia and those with class I without mandibular retrognathia (n = 35 each). The experimental group comprised children with OSA and mandibular retrognathia managed using MTBA. Postoperative and preoperative polysomnography, lateral cephalometric radiographs, and peripheral blood samples were collected. The control group comprised children with class I without mandibular retrognathia. Following MTBA management, the experimental group exhibited decreased apnea-hypopnea index and increased lowest arterial oxygen saturation level (P < 0.05). Sella- and subspinale-nasion-supramental angles significantly increased and decreased, respectively (P < 0.05). Posterior soft palatal-posterior pharyngeal wall distance, apical palatal-middle pharyngeal wall distance, posterior airway space, epiglottis valley-hypopharyngeal wall distance, hyoid-prevertebral plane distance, and distance from the superior anterior point of the hyoid bone to the inferior anterior point of the third cervical spine significantly increased, whereas distance from the superior anterior point of the hyoid bone to the mandibular plane decreased (P < 0.05). Children with OSA (n = 35) were managed using MTBA, which relieved the mandibular retrognathia deformity, widened the upper airway space, moved the hyoid bone forward and upward, and improved the sleep monitoring indicators. Thus, MTBA can achieve satisfactory therapeutic effect in children with OSA and mandibular retrognathia with mandibular advancement.

The clinical features and outcomes of diabetes patients infected with COVID-19: a systematic review and meta-analysis comprising 192,693 patients

ObjectivesWe sought to explore the relevance of analyses that include critical laboratory parameters and drug treatment, clinical characteristics of diabetic patients who are infected with COVID-19, to the development of individualized treatment strategies for diabetic patients infected with COVID-19.MethodsWe searched Cochrane, Embase, FMRS, Pubmed, Springer, Web of Science databases for systematic reviews and meta-analyses to estimate the clinical characteristics and prognosis of confirmed covid-19 infections in patients with and without diabetes.ResultsOur meta-analysis included a total of 32 studies with 192,693 COVID-19 patients. Common comorbidities in the diabetic group were hypertension, cerebrovascular disease, chronic kidney disease and cardiovascular disease. We discovered that white blood cell count, neutrophil count, inflammatory marker levels, D-dimer, urea, precursor of the brain natriuretic peptide (Pro-BNP) increased and lymphocyte count, estimated glomerular filtration rate (eGFR), albumin decreased significantly in the diabetic group in laboratory test results. Compared with the non-diabetic group, the diabetic group had a higher incidence of complications in acute respiratory distress syndrome (ARDS), shock, acute heart injury, acute kidney injury and more regularly used oxygen therapy, invasive ventilation, non-invasive ventilation, continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO) treatment. Mortality and intensive care unit (ICU) hospitalization rates were highest in the diabetic group than in the non-diabetic group (p &amp;lt; 0.05).ConclusionDiabetic patients hospitalized with COVID-19 have an increased risk of death, lower discharge rates, and higher ICU admission rates. Their presence of hypertension, cerebrovascular disease, chronic kidney disease (CKD), higher levels of inflammatory markers. Multiple complications are all predictors of poor outcomes in people with diabetes. Our findings will help identify elevated risk factors in diabetics, which will benefit early prediction.

Disclosing the impact of metformin and methotrexate in adjuvant arthritis in female rats: molecular docking and biochemical insights on visfatin.

Rheumatoid arthritis (RA) is one of the most common systemic autoimmune inflammatory diseases, with a progressive etiology that results in serious complications and a higher chance of early death. Visfatin, an adipokine, is correlated with disease pathologic features and becomes a key biomarker and therapeutic target for RA. This study aimed to evaluate the anti-arthritic activity of metformin (an antidiabetic drug with anti-inflammatory activities) and methotrexate (the first choice for disease-modifying antirheumatic drugs in RA, with diverse adverse effects) in complete Freund's adjuvant (CFA)-induced arthritis in female rats. Treatment outcomes were assessed using arthritis severity, serum levels of inflammatory markers, and pro-inflammatory adipokine (visfatin). In addition to radiological and histopathological examination, and docking analysis. Results showed that Met, MTX, and Met/MTX significantly (p ≤ 0.05) lowered paw swelling and arthritic score, as well as attenuated serum levels of rheumatoid factor (RF), C-reactive protein (CRP), and visfatin. The combined treatment gives the best results. The previously mentioned findings were further confirmed through radiological and histopathological examinations. In conclusion, the co-administration of metformin could potentiate the anti-arthritic activity of methotrexate, providing a medical strategy for arthritis management.

Association of BCHE gene SNP rs1803274 (K-variant) and rs3495 with obesity in Pakistani population group.

Obesity plays a crucial role in the development of metabolic disorders including diabetes, coronary and renal diseases. There are several factors involved in the pathology of obesity, including chronic inflammation and exposure to environmental contaminants. Recently, the cholinergic co-hydrolyzing enzyme BChE has been associated with clinical conditions such as diabetes and obesity. This study aims to investigate the levels of BChE and inflammatory markers in the serum, as well as the association between two specific BCHE gene variants (rs1803274 and rs3495) and the risk of obesity in the Pakistani population. The study recruited 350 people with obesity and 200 volunteers with no obesity. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) levels were quantified using ELISA kits, while the analysis of BCHE gene SNPs rs1803274 (K-variant) and rs3495 was conducted using the tetra-primer amplification refractory mutation-PCR (tetra-ARM-PCR) and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. Additionally, clinico-pathological parameters HDL, LDL, BMI, Homa-IR, insulin, glucose, blood pressure was also assessed in subjects of current study. Results showed significantly higher levels of BChE, TNF-α, IL-1β, and IL-6 in the obesity group compared to the group without obesity. Furthermore, the obesity group exhibited higher blood pressure and LDL levels, as well as lower HDL levels when compared to group without obesity. Logistic regression analysis revealed a relationship between obesity and higher BChE activity, blood pressure, LDL, and lower HDL levels. The study also found a statistically significant association between the BCHE gene SNPs rs1803274 (K-variant) and rs3495 and the risk of obesity (OR = 2.01; CI = 1.21-3.33; p = 0.0063; OR = 1.80; CI = 1.09-2.96, respectively). In conclusion, the study suggests that BChE and inflammatory cytokines play a significant role in the development and pathogenesis of obesity and can also act as good diagnostic biomarkers for obesity and its related metabolic disorders.

Steady Moderate Exercise Confers Resilience Against Neurodegeneration and Neuroinflammation in a Mouse Model of Parkinson’s Disease

Intensive aerobic exercise slows the progression of movement disorders in Parkinson's disease (PD) and is therefore recommended as an important component of treatment for PD patients. Studies in animal models of PD have shown that vigorous exercise has neuroprotective effects, and emerging evidence suggests that it may be a disease-modifying treatment in humans. However, many people with PD may not be able to participate in vigorous exercise because of multiple medical conditions that severely limit their physical activity. In this study, we have shown that chronic MPTP treatment in sedentary mice resulted in loss of dopaminergic neurons in the SNpc, decreased levels of neurotrophins, BDNF and GDNF, and increased levels of inflammatory markers and pro-inflammatory changes in immunocompetent cells. Moderate exercise, initiated both before and after chronic MPTP treatment, significantly attenuated the loss of dopaminergic neurons and increased BDNF and GDNF levels even above those in sedentary control mice. No signs of inflammation were observed in MPTP-treated mice, either when training began before or after MPTP treatment. Training induced beneficial changes in the dopaminergic system, increased levels of neurotrophins and suppression of inflammation were similar for both steady moderate (present data) and intense training (our previously published data). This suggests that there is a kind of saturation when the percentage of rescued dopaminergic neurons reaches the highest possible value, and therefore further increases in exercise intensity do not enhance neuroprotection. In conclusion, our present results compared with the previous data show that increasing exercise intensity beyond the level used in this study does not increase the neuroprotective effect of aerobic training in a mouse model of Parkinson's disease.

Anti-Inflammatory and Pain-Relieving Effects of Arnica Extract Hydrogel Patch in Carrageenan-Induced Inflammation and Hot Plate Pain Models

Arnica montana (AM), which belongs to the daisy family Asteraceae, has a longstanding traditional use in Europe and North America for pain and inflammation treatment. This study investigates the inhibitory effects of ‘Arnica montana extract hydrogel patch (AHP)’ on Carrageenan-induced paw edema and hot plate-induced pain models. AHP exhibited transdermal permeability without the occurrence of issues like crystal precipitation. This study employed two animal model assessments using AHP, in comparison with Arnicare Gel (AG), to evaluate anti-inflammatory and pain relief effects. AHP treatment for 2 days showed a decrease in paw edema thickness in mice as compared to vehicle or AG groups; Carrageenan-induced swelling increased maximally at 1 h with the AHP group demonstrating a higher reduction. Thus, the AHP group exhibited a lower ratio of right/left paw thickness and a superior reduction in swelling, supportive of its ability to diminish edema. A histological analysis showed that AHP treatment reduced inflammatory cell infiltration. Consistently, the mRNA levels of inflammatory markers (tnfa, il1b, and il6) were decreased to a greater extent than the AG group. Particularly, tnfa inhibition was better in the AHP group, and the levels of il1b and il6 transcripts showed ~80% and 40% lower. Likewise, AHP reduced pain scores in a hot plate-induced rat model, although AG failed to do so. Together, these results demonstrate that AHP has long-lasting inhibitory effects on fluid effusion and edema formation, the production of inflammatory mediators, and pain-sensation, supporting its anti-inflammatory and pain-relieving pharmacological effects.

Systemic Inflammatory Diseases in Children with Sickle Cell Disease: A French Multicenter Observational Study on Diagnostic and Therapeutic Issues.

Systemic inflammatory diseases (SIDs) have been reported in patients with sickle cell disease (SCD), but clinical data in children are scarce. To identify clinical and laboratory features at diagnosis of SID in children with SCD and to describe their evolution. Data from children with SCD and SIDs were retrospectively collected in a French multicenter study from 1991 to 2018. Information included clinical characteristics, inflammatory markers, autoantibodies patterns, treatments, and complications. Inflammatory marker levels were compared at SID diagnosis and at the last follow-up. Statistical analyses were performed using Cran R software. Among a cohort of 3800 children with SCD, 43 SIDs were identified in 35 study participants: autoimmune liver disease (AILD, n = 13), inflammatory bowel disease (IBD, n = 7), juvenile idiopathic arthritis (JIA, n = 6), systemic lupus erythematosus (n = 4), autoimmune hemolytic anemia (n = 3), Sjögren syndrome (n = 1), histiocytic necrotizing lymphadenitis (n = 2), vasculitis (n = 2), myasthenia gravis (n = 1), sarcoidosis (n = 1), idiopathic inflammatory granulomatous uveitis (n = 1), mixed connective tissue disease (n = 2). Prevalence of SID was 0.9% in our cohort of children with SCD. The median time between initial symptoms and SID diagnosis was 10 (3-20) months, notably longer in children with JIA, IBD, and Sjögren syndrome. Sixteen patients (46%) exhibited hypergammaglobulinemia (>20g/L) at diagnosis. No significant differences were observed for other inflammatory parameters. Twenty-one children (60%) received systemic steroids and 13 (37%) biological therapies. Three patients (9%) underwent hematopoietic stem cell transplantation. Nine patients (26%) had severe infections; one died. Delayed diagnosis was frequent due to overlapping clinical presentations between SCD and SID. Clinicians must be aware of warning signs associated with elevated inflammatory markers, hypergammaglobulinemia, or specific antibodies. Therapeutic strategies remain challenging.

Occurrence and clinical correlates of SARS-CoV-2 viremia in two German patient cohorts

Viremia defined as detectable SARS-CoV-2 RNA in the blood is a potential marker of disease severity and prognosis in COVID-19 patients. Here, we determined the frequency of viremia in serum of two independent COVID-19 patient cohorts within the German National Pandemic Cohort Network (German: Nationales Pandemie Kohorten Netzwerk, NAPKON) with diagnostic RT-PCR against SARS-CoV-2. A cross-sectional cohort with 1,122 COVID-19 patients (German: S ektorenuebergreifende Platform, SUEP) and 299 patients recruited in a high-resolution platform with patients at high risk to develop severe courses (German: H ochaufloesende Plattform, HAP) were tested for viremia. Our study also involved a comprehensive analysis and association of serological, diagnostic and clinical parameters of the NAPKON medical dataset. Prevalence of viremia at the recruitment visit was 12,8% (SUEP) and 13% (HAP) respectively. Serological analysis revealed that viremic patients had lower levels of SARS-CoV-2 specific antibodies as well as lower neutralizing antibodies compared to aviremic patients. Viremia was associated with severity (<0.0001 SUEP; 0.002 HAP) and mortality of COVID-19 (both cohorts <0.0001) compared to aviremic patients. While rare, viremia was also detected in patients with mild disease (0.7%). In patients of the SUEP cohort with acute kidney disease (p = 0.0099) and hematooncological conditions (p = 0.0091), viremia was detected more frequently. Compared to the aviremic group, treatment with immunomodulating drugs as well as elevated levels of inflammatory markers in the blood was more frequent in the viremic group. In conclusion, our analysis revealed that detectable viremia correlates with hyperinflammatory conditions and higher risk for severe COVID-19 disease.

Association of dietary acid load with inflammatory markers, oxidative stress, and clinical features in patients with knee osteoarthritis

Knee osteoarthritis (KOA) is a prevalent chronic condition characterized by inflammation and oxidative stress, particularly in individuals over 40. Dietary factors, specifically dietary acid load (DAL), may influence these pathological processes. However, the relationship between DAL and inflammatory markers, oxidative stress, and clinical features in patients with KOA remains unexplored. This cross-sectional study involved 147 participants aged 40 and above diagnosed with moderate to severe bilateral primary KOA. Dietary intake was assessed using a validated food frequency questionnaire, and DAL was quantified using Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) indices. Clinical symptoms were evaluated using the WOMAC Index. Biochemical markers of oxidative stress and inflammation were measured from serum samples. Higher PRAL and NEAP scores were associated with increased levels of thiobarbituric acid reactive substances (TBARS) and total oxidant status (TOS), indicating elevated oxidative stress. Additionally, serum levels of inflammatory markers, including TNF-α and hs-CRP, positively correlated with higher DAL scores. Clinical assessments revealed that increased PRAL scores were related to greater severity of symptoms as measured by the WOMAC Index. This study demonstrates a significant association between dietary acid load and markers of inflammation and oxidative stress in KOA patients. These findings suggest that dietary modifications aimed at reducing acid load may serve as a beneficial adjunctive strategy in managing KOA and improving patient outcomes.

Immunopathological characteristics and therapeutic effects of UC-MSCs in a pigeon breeder's lung mouse model.

Hypersensitivity pneumonitis (HP), including pigeon breeder's lung (PBL), often progresses from acute inflammation to fibrosis, impairing lung function and limiting targeted therapeutic strategies. Mechanistic studies on PBL progression are limited by the lack of preclinical animal models and a predominant focus on patient data. This study explores the immunopathological characteristics of all stages of PBL in mice and evaluates the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) during the non-fibrotic stage. PBL models are created in A/J mice through tracheal instillation of pigeon dropping extract (PDE) protein powder. Different doses (0.4 × 10 6, 0.8 × 10 6, and 1.6 × 10 6 cells per animal) and frequencies (1-2 times) are administered to the model. The immunopathological characteristics of PBL and the therapeutic effects of UC-MSCs are assessed using micro-CT, pulmonary function, histopathology, cell counts in BALF, HYP levels, inflammatory factor levels, immunohistochemistry, and fibrosis marker expression in lung tissues. The results show that PDE exposure consistently impairs pulmonary function and increases the levels of inflammation and fibrosis markers as the disease progresses. Model mice experience non-fibrotic stages (acute inflammation) from days 0-36, mild fibrosis from days 37-77, and severe fibrosis from day 78 onwards. UC-MSCs, particularly at the highest dose (1.6 × 10 6 cells), effectively treat non-fibrotic PBL by improving pulmonary function (lung ventilation area recovers) and reducing inflammation and fibrosis. This study successfully establishes PBL mouse models reflecting both the acute (inflammatory) and chronic (fibrotic) stages, and UC-MSCs have the potential to delay fibrosis, providing new therapeutic options for PBL and other inflammation-induced lung fibrotic diseases.

P1045 Treat-smart study: Leveraging individual inflammatory markers for personalized therapy in patients with IBD

Abstract Background Diverse patient responses to treatment challenge the management of inflammatory bowel disease (IBD). This study aims to evaluate if there are differences in the inflammatory mediators among IBD patients and the treatment outcome concerning these variations. Methods This study was conducted in the IBD clinic at AL-Rajhi Hospital, Assiut University. The concentrations of TNF-α and IL-12/23 (p40) were measured in IBD patients and healthy controls using enzyme-linked immunosorbent assay (ELISA) technique. In IBD patients, marker levels were assessed before and after induction of biological therapy to evaluate changes in their levels. Biological therapies were prescribed according to the treatment protocols of the funding entities (such as health insurance). The investigators did not know the levels of inflammatory markers at the time of treatment prescription. Results From May 23, 2023, to July 16, 2024,18 IBD patients were enrolled in this study. Half of the study population were males with a median age of 27 years. The cohort included 16 patients with Ulcerative Colitis and 2 with Crohn’s disease, as shown in table 1. Before enrollment, 9 patients had failed to achieve remission on conventional therapy, and 9 had also failed on both conventional and first-line biological therapies. The analysis of the inflammatory markers at baseline showed significant variation among patients. Third of the patients (6 out of 18) showed only elevation in the TNF- α, one patient had only elevated IL 12/23, and the rest had combined elevation of both markers. Among patients with TNF-α as the predominant pathway, remission was achieved in all patients given anti-TNF-α therapy (5 out of 6 patients). In contrast, one patient with IL12/23–dominant group failed to achieve remission after receiving Ustekinumab. In the same context, another patient with elevated IL-12/23 alone failed to respond after receiving anti-TNF-α treatment. Patients with elevated levels of both TNF-α and IL 12/23 (11 patients) exhibited mixed responses. Among those treated with anti-TNF-α, only 1 achieved remission, while 7 experienced treatment failure. Using Ustekinumab in this subgroup led to remission in only 1 out of 3 cases, as shown in figure 1. Conclusion These results showed that treatment response is significantly influenced by the predominant inflammatory pathway expressed in patients with IBD. Specifically, patients with TNF-α dominant pathway showed a high remission rate with anti-TNF-α therapy. Conversely, non-specific treatments were less effective, emphasizing the importance of targeted therapy. Patients with dual-marker elevation may have better responses by combo therapy or JAK inhibitors. These results may pave the way for tailored treatment for IBD patients.

Mutual mediation effects of homocysteine and PCSK9 on coronary lesion severity in patients with acute coronary syndrome: interplay with inflammatory and lipid markers

BackgroundHomocysteine (Hcy) and the proprotein convertase subtilisin/kexin type 9 (PCSK9) significantly contribute to atherosclerosis (AS) as well as coronary lesion severity. Our previous work demonstrated that Hcy upregulates PCSK9, accelerating lipid accumulation and AS. A PCSK9 antagonist reduces plasma Hcy levels in ApoE−/− mice. These findings suggest complex roles for both Hcy and PCSK9 in AS. This study investigated the mutual mediating influence of Hcy together with PCSK9 on coronary lesion severity among individuals diagnosed with acute coronary syndrome (ACS), focusing on their interplay with inflammatory and lipid-related markers.MethodsThis cross-sectional study encompassed 617 individuals diagnosed with ACS. Baseline characteristics, including inflammatory and lipid-related markers, were compared between individuals with non-severe (SYNTAX score ≤ 22) and severe (SYNTAX score > 22) coronary lesions. To evaluate both the impacts of Hcy and PCSK9 on coronary lesions severity, multivariate logistic regression along with mediation analyses were utilized. The robustness of the findings was validated by conducting subgroup analyses and sensitivity tests.ResultsPatients with severe conditions showed higher levels of Hcy, PCSK9, and inflammatory markers compared to non-severe cases. Both Hcy and PCSK9 levels were independently linked to a heightened risk of severe coronary lesions(ORs: 1.03–1.04 and 1.01–1.02, respectively, all P < 0.001). PCSK9 mediated 34.04% of Hcy’s effect on coronary lesion severity, whereas Hcy mediated 31.39% of PCSK9’s effect, indicating significant mutual mediation between these biomarkers. Subgroup analyses revealed consistent associations, with notable interactions based on creatinine levels for Hcy and gender, smoking status, and diagnosis for PCSK9. Sensitivity analyses confirmed the robustness of the mediation effects.ConclusionsThese findings emphasize the mutual mediating effects of Hcy and PCSK9 on coronary lesion severity in patients suffering from ACS. These results highlight the complex interactions between lipid metabolism and inflammation in the pathophysiology of ACS, suggesting that targeting both Hcy and PCSK9 may offer novel therapeutic strategies to mitigate severe coronary lesions among high-risk patients.