Serum Levels Of Protein Research Articles

Association of motoric cognitive risk syndrome and high C-reactive protein serum levels with incident major neurocognitive disorder: Results from the Quebec NuAge cohort

Abstract Both motoric cognitive risk syndrome (MCR) and C-reactive protein (CRP) serum levels have been separately associated with increased risk of incident major neurocognitive disorder. The study aims to compare the CRP serum levels of older adults with and without MCR, and to examine the associations of MCR, CRP serum levels and their combination with incident major neurocognitive disorder. 915 individuals participating in an older adults population-based observational cohort study with a 3-year follow-up design, were selected. MCR and CRP serum levels were collected at baseline. Incident major neurocognitive disorder was measured at annual follow-up visits using the modified mini-mental state (≤79/100) and simplified instrumental activity daily living scale (<4/4) score values. The prevalence of MCR at baseline assessment was 3.7%. The overall incidence of major neurocognitive disorder was 3.0%. MCR alone (Hazard Ratio (HR)=28.09 with 95% Confidence Interval (CI=[7.00;112.72] and P≤0.001) and MCR with a high CRP serum level (HR=6.33, with 95% CI[1.45;27.62] and P=0.014) were significantly associated with incident major neurocognitive disorder. MCR is a significant risk factor for predicting major neurocognitive disorder in older adults, while serum CRP levels are not. In addition, serum CRP levels reduce the predictive strength of MCR for major neurocognitive disorder.

Interoperable Models for Identifying Critically Ill Children at Risk of Neurologic Morbidity.

Decreasing mortality in the field of pediatric critical care medicine has shifted practicing clinicians' attention to preserving patients' neurodevelopmental potential as a main objective. Earlier identification of critically ill children at risk for incurring neurologic morbidity would facilitate heightened surveillance that could lead to timelier clinical detection, earlier interventions, and preserved neurodevelopmental trajectory. To develop machine-learning models for identifying acquired neurologic morbidity in hospitalized pediatric patients with critical illness and assess correlation with contemporary serum-based, brain injury-derived biomarkers. This prognostic study used data from all children admitted to a quaternary pediatric intensive care unit in a large, freestanding children's hospital in Western Pennsylvania between January 1, 2010, and December 31, 2022. External model validation used data from children admitted between January 1, 2018, and December 31, 2023, to a quaternary pediatric intensive care unit in a large, freestanding children's hospital that serves as a referral center for the 5-state region of Washington, Wyoming, Alaska, Montana, and Idaho. Critical illness. The outcome was neurologic morbidity, defined according to a computable, composite definition at the development site or an order for neurocritical care consultation at the validation site. Models were developed using varying time windows for temporal feature engineering and varying censored time horizons between the last feature and the identified neurologic morbidity. A generalizable model created at the development site was optimized and assessed at an external validation site. Correlation was assessed between development site model predictions and measurements of brain biomarkers from a convenience cohort. After exclusions, there were 18 568 encounters from 2010 to 2022 in the development site generalizable model cohort (median age, 70 [IQR, 18-161] months; 8325 [45%] female). There were 6825 encounters from 2018 to 2021 at the external validation site (median age, 96 [IQR 18-171] months; 3159 [46%] female). A generalizable extreme gradient boosted model with a 24-hour time horizon and 48-hour feature engineering window demonstrated an F1 score of 0.37 (95% CI, 0.33-0.40), area under the receiver operating characteristics curve of 0.81 (95% CI, 0.78-0.83), and number needed to alert of 4 at the validation site. After recalibration at the validation site, the Brier score was 0.04. Serum levels of the brain injury biomarker glial fibrillary acidic protein significantly correlated with model output (rs = 0.34; P = .007). This prognostic study of prediction models for detecting neurologic morbidity in critically ill children demonstrated a well-performing ensemble of models with biomolecular corroboration. Prospective assessment and refinement of biomarker-coupled risk models in pediatric critical illness are warranted.

Do specific myelin autoantibodies and increased cerebral dopamine neurotrophic factor in the context of inflammation predict the diagnosis of attention deficit hyperactivity disorder in medication-free children?

BackgroundThe aim of this study was to investigate the serum levels of anti-myelin basic protein (anti-MBP), anti-myelin oligodentrocyte glycoprotein (anti-MOG), myelin-associated glycoprotein (MAG), high-sensitivity C-reactive protein (hs-CRP), cerebral dopamine neurotrophic factor (CDNF), cerebellin-1, and reelin and their relationships with clinical severity and irritability behaviours in children with attention deficit (AD) hyperactivity disorder (ADHD) and typically developing (TD) healthy controls. MethodsIn this study, 141 children with ADHD between the ages of 8 and 14 years who were medication-free and 135 TD healthy controls were included. The serum levels of anti-MBP, anti-MOG, MAG, CDNF, hs-CRP, cerebellin, and reelin were measured using enzyme-linked immunosorbent assay kits. The Turgay Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders–Parent Form (TDSM-IV-O) and the affective reactivity index (ARI) scale were used to assess clinical severity and irritability behaviours in the children. ResultsThe MAG, CDNF, hs-CRP, reelin, and cerebellin levels were significantly higher in the ADHD group than in the control group, but no significant differences in anti-MBP and anti-MOG levels were found between the groups. Compared with the controls, the patients with ADHD showed significantly higher scores on the ARI self- and parent-report scales. The reelin, hs-CRP, and MAG levels were significantly associated with the TDSM-IV-O AD scores, AD and oppositional defiant (OD) disorder scores and hyperactivity, and OD and conduct disorder scores, respectively. Hs-CRP was significantly associated with anti-MBP and cerebellin levels. In an analysis of covariance, the results were unchanged even after controlling for potential confounders such as age, body mass index, and sex. ConclusionThis study demonstrates that MAG, CDNF, hs-CRP, reelin, and cerebellin levels may play a potential role in the pathogenesis of ADHD.

Effect of Colchicine for Prevention of Recurrent Stroke in Ischemic Stroke Patients with Atrial Fibrillation: A Randomized Double-blinded Placebo-controlled Trial

Background: It has been proposed that colchicine may have the potential to prevent cardiovascular and cerebrovascular dysfunctions. Objective: This study evaluated the impact of colchicine on preventing recurrent stroke in patients with both ischemic stroke (IS) and atrial fibrillation (AF). Methods: A randomized, double-blinded, placebo-controlled trial was conducted at Golestan Hospital (Ahvaz, Iran) over one year, involving IS patients with AF. Demographic and clinical data were collected from the participants, who were then assigned to either the intervention or placebo groups. The experimental group was administered colchicine at a dosage of 0.05 mg twice daily for one year, while the control group received a placebo at a comparable dosage over the same timeframe. Results: In one year, 108 patients completed the study. There were 55 patients in the intervention group and 53 patients in the placebo group. During the second trimester of the trial, three patients in the colchicine group and 10 patients in the placebo group experienced recurrent strokes. Gastrointestinal issues were the most commonly reported complications (33 cases) among the two groups, followed by myalgia (8 patients). There were significant differences in the frequency of recurrent stroke and serum levels of C-reactive protein (CRP) between the colchicine and placebo groups (p < 0.05) after intervention. Conclusion: In this study, colchicine was effective in reducing recurrent stroke and CRP levels in IS patients with AF compared to the control group. Further randomized controlled trials with larger sample sizes and extended durations are recommended to validate the results of this trial.

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<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<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<0.05). Conversely, the levels of inflammatory factors in the CPR+SV group were significantly reduced compared to the CPR group (P<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<0.05). SV markedly suppressed the expression of these pyroptosis-associated proteins (P<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.

Hemostatic Profile and Serum Levels of Interferon Gamma-Induced Protein 10 (IP-10) in Neonates Born to Mothers with COVID-19 During the Peripartum Period

Hemostatic Profile and Serum Levels of Interferon Gamma-Induced Protein 10 (IP-10) in Neonates Born to Mothers with COVID-19 During the Peripartum Period

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.

P-441. Gut Permeability Response to Inulin Supplementation in Well-Controlled HIV Patients with Metabolic Syndrome

Abstract Background HIV infection is known to cause abnormally increased gut permeability resulting in chronic inflammation. Serum levels of Zonulin protein are elevated in persons with increased gut permeability. The objective of this study is to assess whether Inulin (fiber) supplementation will result in a decrease in gut permeability in well-controlled HIV patients with metabolic disorder as measured by baseline and post-intervention Zonulin levels. Statistical Results There was a statistically significant increase in median Zonulin levels from baseline to post-intervention (p=0.002) Methods 10 subjects were selected from patients enrolled in care at the Center for AIDS Research and Treatment (CART) based at North Shore University Hospital. Eligibility criteria included well-controlled HIV patients with evidence of metabolic syndrome. The duration of the study was 6 weeks and the intervention was Inulin supplement use. Bloodwork drawn pre- and post-intervention included Zonulin levels, A1c, Fructosamine, Cholesterol, Triglycerides, HDL, LDL, and non-HDL levels. BMI was also checked. Patients were provided with organic Inulin powder and instructed to take 1 tablespoon once a day for the first week and advance to twice a day for the rest of the study. Every week patients were contacted via telephone to assess compliance and side effects. The primary endpoint was the assessment of baseline and post-intervention Zonulin levels, with the secondary endpoint including baseline and post-intervention BMI, A1c, Fructosamine and Lipids. Descriptive statistics were computed and significance was determined via Wilcoxon signed-rank test. Pre and Post Intervention Zonulin levels in all 10 subjects Results Among the patients enrolled 80% were male, 60% were White, 80% were not Hispanic or Latino, and the median age was 60.5. Flatulence and bloating were the most frequent side effects of inulin reported. The median Zonulin levels at baseline were 177.9µg/mL, and post-intervention were 532.4µg/mL. There was a statistically significant increase in Zonulin levels from baseline to post-intervention (p=0.002). There was no significant difference between baseline and post-intervention for any of the other parameters in the dataset. Conclusion Inulin supplementation resulted in a statistically significant increase in Zonulin levels, which goes against our hypothesis. Whether this is due to underlying worsening of pre-existing gut dysbiosis or other factors needs further study. Disclosures All Authors: No reported disclosures

635. Do Necrotizing Soft Tissue Infections Behave Differently in Patients with Hematological Malignancies? A Propensity Score-Matched Retrospective Cohort Study in an Oncological Center in Mexico City

Abstract Background Necrotizing Soft Tissue Infections (NSTI) are severe clinical entities that occur in specific clinical contexts. Although, severe neutropenia related to hematological malignancies (HM) has been described in relation with NSTI, there is a paucity of published data describing its course and outcome in this populationTable 1.Population characteristics and outcomesAll values represented are N(%) unless otherwise noted with an asterisk. Variables marked with an asterisk ( * ), are represented with median(interquartile range). LRINEC score: Laboratory Risk Indicator for Necrotizing Fasciitis score, it is calculated using values of serum levels of C-reactive protein, White blood cell count, Hemoglobin, Sodium, Creatinine and Glucose. Methods We did a retrospective cohort study that included all adults with NSTI treated in the Instituto Nacional de Cancerologia in Mexico City, from 2008 to 2023. We identified all individuals with HM and matched them with individuals with non-hematological cancer using a propensity score based on age, site of infection, and the LRINEC score; and compared their clinical characteristics and outcomes. To determine if severe neutropenia was the main factor driving clinical differences amongst groups, we executed a paired sensitivity analysis comparing three groups: neutropenic adults with HM, non-neutropenic adults with HM, and adults with non-hematological cancerFigure 1.Site of NSTI and identified microbesPanel A: here we show the affected sites in each NSTI per group. There were no significant differences amongst the frequency of the affected sites when comparing both groups. Panel B: here we show the frequency of each category of bacterial isolates, and the frequency in which the isolate presented as part of a polymicrobial infection. Except for S. aureus, there were no significant differences amongst the frequency of the different bacterial isolates when comparing both groups. Results We included 31 individuals with HM and NSTI. When compared with the individuals without HM, these were more likely to have severe neutropenia during the NSTI (45.2% vs 3.7%, p< 0.001) and positive blood cultures at NSTI diagnosis (8.3% vs 63.3%, p< 0.001), and less likely to have polymicrobial (59.1% vs 14.3%, p=0.001) or Staphylococcal etiologies (22.7% vs 3.6%, p=0.039). HM patients were less likely to receive surgical treatment (81.5% vs 32.3%, p< 0.001), even though the median time from symptom onset to diagnosis was lower (4 vs 2 days, p=0.009). On the sensitivity analysis, only neutropenic patients had an increased positive yield of blood cultures (p=0.002) and were less likely to receive surgical treatment (p< 0.001). Neutropenic patients showed a higher mortality when compared with non-neutropenic HM patients (63.6% vs 27.3%, p=0.036).Figure 2.Initial antibiotic regimen Here we show the different initial antibiotic regimes per group. HM patients had a Carbapenem-based regime more frequently than Non-HM patients (p<0.001), while a regime consisting of a 3rd generation Cephalosporin and Metronidazole was less frequently used in HM patients (p<0.001). There were no significant differences amongst the frequency of additional treatment with Colistin, Amikacin or Clindamycin. Conclusion Patients with HM present with bacteriemia and monomicrobial NSTIs due to Gram-negative bacilli, which suggests bacterial translocation as the main etiology of NSTI in this population. Severe neutropenia could be the driving factor causing this phenomenon. Lack of prompt surgical interventions due to associated thrombocytopenia could explain the high mortality of NSTI in this population.Table 2.Sensitivity analysisAll values represented are N(%) unless otherwise noted with an asterisk. Variables marked with an asterisk ( * ), are represented with median(interquartile range). Neutropenia was defined as having <500 neutrophils/ml.*significant difference when compared with Non-HM users**significant difference when compared with Non-neutropenic users and Non-HM users Disclosures All Authors: No reported disclosures

Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout

Infectious diseases pose significant challenges to Norwegian Atlantic salmon aquaculture. Vaccines are critical for disease prevention; however, a deeper understanding of the immune system is essential to improve vaccine efficacy. Immunoglobulin M (IgM) is the main antibody involved in the systemic immune response of teleosts, including Atlantic salmon. In this study, we used CRISPR/Cas9 technology to knock out the two IgM genes in Atlantic salmon. High-throughput sequencing revealed an average mutagenesis efficiency of 97% across both loci, with a predominance of frameshift mutations (78%). Gene expression analyses demonstrated significantly reduced membrane-bound IgM mRNA levels in head kidney and spleen tissues. Flow cytometry revealed a 78% reduction in IgM+ B cells in peripheral blood, and Western blot analyses showed decreased IgM protein levels in serum. Notably, an upregulation of IgT mRNA was observed, suggesting a potential compensatory mechanism. This work presents the first application of CRISPR/Cas9 to disrupt an immune-related gene in the F0 generation of Atlantic salmon, and lays the foundation for generating a model completely lacking IgM+ B cells which can be used to study the role of B cells and antibodies. This study has implications for advancing immune research in teleosts and for developing strategies to improve salmon health and welfare in aquaculture.

Diagnostic Biochemical Changes Identified in a Cohort of Patients with Coronavirus-19 (COVID-19) Disease

Backgroun: SARS-CoV-2 infection was associated with inflammatory, metabolic, haematological, and immunological changes, which contributed to the increase in morbidity and mortality. Objective: To illustrate changes in some biomarkers (ESR, ferritin, CRP, D. dimer, ALT, AST, creatinine, and urea) during COVID-19 and their predictive value in the diagnosis of SARS-CoV-2 infection, especially in rural and urban areas in which sophisticated tests were not available. Materials and Methods: The study includes 154 COVID-19 patients with positive RT-PCR. Sixty age and sex-matched individuals were included as controls. The study was conducted during the period from 23rd July 2021 to the end of December 2021. The subjects with a history of liver diseases, pregnant women, an age of less than 18, and chronic renal failure were excluded. The informed consent was taken from each individual before their enrolment in the study. The study was performed in compliance with the World Medical Association Declaration of Helsinki. Venous blood samples were collected from both groups and tested for determination of creatinine, urea, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), D dimer, ferritin, and C-reactive protein (CRP) using a Mindray BS 240 chemical auto-analyzer. Results: The mean serum values were significantly higher (P= 0.01 – 0.001) in COVID-19 patients as compared to matched controls for creatinine, blood urea, ALT, AST, ESR, LDH, D- dimer, ferritin, and CRP. In addition, the mean serum levels of ALT, AST, ESR, LDH, D-dimer, ferritin, and CRP were higher than the values of normal ranges. Although, creatinine and urea mean serum values were significantly higher in COVID-19 patients, their mean values were within the normal range values. ESR was highly significantly (p < 0.001) correlated with ALT, AST, LDH, urea, ferritin, and CRP. While LDH was highly significantly correlated with creatinine, urea, ESR, ferritin, and CRP. Also, D. dimer was significantly highly correlated with ferritin, and CRP. Serum ferritin was highly significantly correlated with creatinine, urea, ESR, LDH, D. dimer, and CRP. While CRP was highly significantly correlated with creatinine, urea, ESR, LDH, D. dimer, and ferritin. Conclusion: ESR, CRP, Ferritin, D. dimer, LDH, AST, ALT, urea, and Creatinine levels in venous blood were significantly elevated in COVID-19 patients compared with controls. Sex- influenced serum levels of C-reactive protein, creatinine, and urea in this study cohort. Serum levels of tested biomarkers may be useful in the diagnosis of COVID-19 in primary healthcare centres, especially in rural areas in developing countries.

FGF21 and APOA1 mRNA-based therapies for the treatment of experimental acute pancreatitis

BackgroundAcute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.MethodsLiver-targeted lipid nanoparticles (LNP)-mRNA formulations encoding FGF21, APOA1, and a chimeric APOA1-FGF21, were first tested for protein expression and bioavailability in vitro and in mice fed a high-fat diet. Efficacy studies were performed in the caerulein-induced AP (Cer-AP) model, and a new AP model combining ethanol feeding with ethanol binge plus palmitoleic acid administration, the EtOH/POA-AP model. A single dose of the APOA1, FGF21, and APOA1-FGF21 LNP-mRNAs formulations was administered in both models. Serum levels of pancreatic lipase (LIPC), amylase (AMYL), and aspartate aminotransferase (AST), along with pancreatic tissue analyses using two histopathological scores were performed to evaluate treatment effects.ResultsIn vitro studies demonstrated the translation and secretion of APOA1, FGF21, and APOA1-FGF21 proteins encoded by the LNP-mRNAs. In vivo, LNP-mRNA administration increased serum levels of the respective proteins in metabolically impaired (i.e. high fat diet-fed) mice. In the Cer-AP model, serum markers of pancreatic injury were similarly reduced when mice were treated with APOA1, FGF21, and APOA1-FGF21 LNP-mRNA, and this effect was also observed in the histopathological analyses. The EtOH/POA-AP model was more aggressive than the Cer-AP model. FGF21 and APOA1-FGF21 LNP-mRNAs were protective according to LIPC and AMYL serum levels, while APOA1 LNP-mRNA had little effect. On the other hand, histological improvements were more evident in mice receiving APOA1 LNP-mRNA. In the EtOH/POA-AP model, FGF21 and APOA1-FGF21 LNP-mRNAs reduced serum AST levels, indicating hepatoprotective activity.DiscussionThis proof-of-concept study demonstrates the potential of mRNA-based therapies delivering FGF21 and APOA1 in experimental AP. While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. Further research is warranted to elucidate the mechanisms underlying their therapeutic efficacy and optimize treatment regimens for clinical translation.

Dietary simple sugar intake, metabolic indicators, markers of inflammation, and injury among semi-professional football players

Background: Dietary sugar intake has been implicated in the development of metabolic dysfunction, chronic inflammation, and immune dysfunction, contributing to the pathogenesis of various diseases. This study aimed to investigate the associations between dietary total simple sugar intake and glycemic markers, lipid profile, serum levels of high-sensitivity C-reactive protein (hs-CRP), and adenosine deaminase activity (ADA), among semi-professional football players. Methods: A cross-sectional study was conducted among 108 semi-professional football players. Dietary intake of simple sugars was assessed using validated dietary assessment tools, while serum levels of biochemical variables were measured using standard laboratory assays. Multinomial logistic regression analysis and partial correlation analysis were performed to examine the associations between dietary simple sugars and serum biomarkers, adjusting for confounders. Results: Strong positive associations were observed between dietary total simple sugar intake and hs-CRP and ADA levels in multinomial regression analysis. Also, among individual assessment of dietary simple sugars, dietary fructose and glucose intake were positively correlated with serum hs-CRP levels (r = 0.484, P < 0.001 and r = 0.393, P < 0.001, respectively) and serum ADA levels (r = 0.233, P = 0.001 for glucose; r = 0.188, P = 0.01 for fructose). There was no other association between dietary simple sugar intake and metabolic parameters. Conclusion: Our findings highlight the significant impact of dietary sugar intake on inflammation, as reflected by serum hs-CRP and ADA levels. Strategies aimed at reducing sugar consumption may help mitigate inflammation and improve overall health outcomes. Further research is warranted to elucidate the underlying mechanisms and to explore potential therapeutic interventions targeting dietary sugar intake for the prevention and management of chronic diseases.

Нepatoprotective еffects of lithium ascorbate on a model of nonalcoholic fatty liver disease with iron overload

Lithium ascorbate is a lithium salt with normothymic and neuroprotective properties. In an experimental model of non-alcoholic fatty liver disease with multiorgan pathology caused by combined consumption of excessive amounts of saturated fats, carbohydrates and inorganic iron salt, the use of lithium ascorbate showed pronounced hepatoprotective effects. The introduction of lithium ascorbate reduced the level of ferritin and transferrin saturation, the content of serum iron, AST, ALT, serum creatinine, leukocytes and normalized the level of serum protein and the rate of glomerular filtration. Lithium ascorbate reduced the increased content of reticulocytes and platelets to control values, restored the levels of vitamins C, B12 in the blood and reduced the number of Kupffer cells in the liver, which were overloaded with iron. The hepatoprotective effect of lithium ascorbate was confirmed histologically. The ability of the neuroprotector lithium ascorbate to reduce the level of hemosiderosis can be used in the treatment of patients with hepatic encephalopathy.

Ontogenetic features of hormonal status and metabolic profile of pigs in industrial technology

The hormonal and metabolic profile of conditionally healthy Yorkshire pigs of different age and sex groups was studied in an industrial pig farm. A statistically significant effect of age on the level of serum cortisol, triiodothyronine, and thyroxine in the studied pig groups was established. Increased cortisol levels compared to the literature data in almost all pig groups may indicate chronic stress, while increased secretion of thyroid hormones is an adaptive response associated with stress compensation. Biochemical parameters of blood serum in animals of different groups reflect age-related metabolic features. It was shown that the average parameter values for the groups as a whole are within the limits obtained by other authors. It was revealed that with age, there is a decrease in the content of glucose, triglycerides, and urea. At the same time, the level of total protein, albumins, and globulins in the blood serum of the studied pigs gradually increases with age. In some cases, reliable intersexual differences in the level of biochemical parameters were found, in particular, sows exceeded boars in cholesterol content, while the opposite pattern was noted for total protein. In general, the hormonal and metabolic profiles of the herd correspond to the “industrial” status of the complex. The ability to adapt, intensive protein, carbohydrate and fat metabolism are obviously fixed by targeted breed selection. The established reference values of the hormonal status and metabolic profile parameters can be used to characterize pigs of high-intensity meat breeds under industrial technology conditions.

The Effects of a Novel Astragalus-Based Extract (Keyfobell Powder (KFB)) on Longitudinal Bone Growth via IGF-1 Upregulation: A Potential Growth Hormone Alternative

Background/Objectives: This study evaluated the effects of a novel Astragalus extract (Keyfobell powder [KFB]) composed of Astragalus membranaceus, red ginseng (Panax ginseng C. A. Meyer), and Cervi Parvum Cornu as a potential growth hormone (GH) alternative. The primary focus was placed on its impact on longitudinal bone growth through the upregulation of circulatory insulin-like growth factor (IGF)-1. Methods: We performed in vitro and in vivo experiments using a hypothalamic cell line and Sprague–Dawley (SD) rats. Quantitative RT-PCR was performed to determine growth hormone-releasing hormone (GHRH) and ghrelin mRNA expressions in GT1-7 cells. The treatment groups were administered KFB at various dosages, and the positive controls received recombinant human GH. Body weight, bone length, and density were assessed, along with serum levels of insulin-like growth factor binding protein (IGFBP)-3 and IGF-1. Results: KFB and somatropin exhibited no cytotoxic effect in GT1-7 cells and increased GHRH and ghrelin mRNA levels in a dose-dependent manner. KFB administration resulted in a significant dose-dependent increase in body weight and bone growth (femur and tibia). Changes in IGF-1 and IGFBP-3 levels were comparable to those observed in the GH-treated group. Based on network pharmacological analysis, multiple compounds in KFB ((20S)-20-hydroxypregn-4-en-3-one, 2-isopropyl-3-methoxypyrazine, caproic acid, daidzein, furfuryl alcohol, lauric acid, octanal, and salicylic acid) may synergistically regulate the PI3K-Akt, Ras, and Rap1 signaling pathways linked to growth control and cartilage formation, leading to a possible increase in height. Conclusions: Our results suggest that KFB can function as a GH-mimetic agent that promotes bone growth through IGF-1 upregulation.

P0651 Evaluating tryptophan as a biomarker for treatment success in Inflammatory Bowel Disease patients undergoing therapy

Abstract Background Patients with inflammatory bowel disease (IBD) display heterogenous responses to different treatment modalities suggesting distinct disease pathomechanisms. Herein, tryptophan (Trp) metabolism is associated with a range of chronic inflammatory disease, but the relevance to guide treatment decision in IBD remains unclear. Here, we sought to evaluate Trp serum level as a biomarker of treatment response in IBD in comparison to established disease biomarkers. Methods We analyzed and compared the serum levels of Trp and C-reactive protein (CRP) from patients with Ulcerative Colitis (UC) (n = 15) and Crohns Disease (CD) (n = 10). Longitudinal analyses of 100 serum Trp measurements were obtained and associated with inflammatory IBD markers during the induction period of various biological agents including TNF-α inhibitors (n=2), interleukin inhibitors (n=11), JAK inhibitors (n= 8), Sphingosine modulators (n=3) and integrin inhibitors (n=1). Results As expected, we found an inverse correlation between CRP and Trp (rs = -0.219, p = 0.045), indication a weak, negative correlation between the two variables across all patients. However, while this effect was predominantly observed in UC (r = - 0.317, p = 0.003), patients with CD showed no significant correlation between CRP and Trp levels (rs = -0.082, p = 0.763). In line with these findings, the observed correlation showed significant correlation in the different treatment modalities. Patients who received either interleukin- or JAK inhibitors displayed a stronger correlation (rs = -0.542, p = 0.001 and rs = - 0.358, p = 0.007 respectively), while patients receiving TNF-α-/ integrin inhibitors or Sphingosine-1-phosphate receptor modulators did not show a significant correlation. Conclusion Highlighting the heterogeneity of responses to different biologics, we observed a correlation between high serum Trp levels and a decline in biomarkers associated with a disease flare. These observations were most pronounced in patients with UC receiving treatment with interleukin- and JAK inhibitors suggesting potential therapeutic relevance in indicating early signs of successful induction treatment. References Wang S, van Schooten FJ, Jin H, Jonkers D, Godschalk R. The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome. Nutrients. 2023 Jun 26;15(13):2886. doi: 10.3390/nu15132886. PMID: 37447212; PMCID: PMC10346271. Ding, Xueyan, Bin, Peng, Wu, Wenwen, Chang, Yajie, Zhu, Guoqiang, Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review, Mediators of Inflammation, 2020, 9706140, 10 pages, 2020. https://doi.org/10.1155/2020/9706140 Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M. Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J. Schwarz, Georg H. Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber,Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases,Gastroenterology,Volume 153, Issue 6,2017,Pages 1504-1516.e2,ISSN 0016-5085,https://doi.org/10.1053/j.gastro.2017.08.028.

DOP099 Prolonged Pharmacodynamic Effects of Risankizumab Following Withdrawal in Patients with Moderately to Severely Active Ulcerative Colitis

Abstract Background Risankizumab (RZB) is a high-affinity humanized IgG1 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine, thereby inhibiting its interaction with the IL-23 receptor.1 RZB was intentionally designed with modifications to the antibody that could contribute to prolonged half-life, low immunogenicity, and increased stability and bioavailability.1 The objective of this post-hoc analysis was to characterise the pharmacokinetic (PK) and pharmacodynamic (PD) effects of RZB following withdrawal in patients with moderately to severely active ulcerative colitis (UC). Methods In the UC maintenance trial (COMMAND, NCT03398135), 272 patients who responded to 12 weeks of intravenous (IV) RZB 1200 mg induction therapy were re-randomised to receive subcutaneous (SC) RZB maintenance dosing (180 mg or 360 mg) or placebo (PBO; RZB withdrawal).2 This analysis evaluated clinical endpoints, PK, and biomarkers of the SC PBO/withdrawal. Change from baseline in partial modified Mayo score, serum RZB concentrations and levels of high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) were assessed at each predetermined study visits throughout the maintenance trial. Results A total of 90 patients were re-randomised to receive PBO (withdrew from RZB induction) in COMMAND. Predicted PK profiles of exposure over time in the PBO/withdrawal group showed that, following the third and final RZB induction dose, residual RZB concentrations lasted for at least 16 weeks before complete washout.3 The PBO/withdrawal group did not have meaningful increases from baseline in partial modified Mayo score until after about week 24 of maintenance (36 weeks since the last dose of RZB) (Figure). Levels of hs-CRP and FCP in the PBO/withdrawal patients remained low throughout maintenance and did not meaningfully increase until week 52. Conclusion Patients with moderately to severely active UC who received IV RZB 1200 mg induction therapy and were re-randomised to PBO exhibited continued response to RZB as demonstrated by disease activity and biomarkers for at least 6 months, exceeding the time of PK washout. hs-CRP and FCP did not increase until week 52 of maintenance and remained below baseline values. This durability of response may have important clinical implications and warrants continued investigation.

P0844 Real-world effectiveness of vedolizumab in managing refractory pouchitis: a multicenter study on intravenous to subcutaneous transition

Abstract Background Chronic refractory pouchitis (RP) is a complication of ileal pouch-anal anastomosis (IPAA). Vedolizumab (VDZ) has been used in RP management, but real-world data on its effectiveness are limited. Additionally, information on switching from intravenous (IV) to subcutaneous (SC) VDZ in this context is scarce. Aims To evaluate the efficacy and safety of VDZ in RP treatment in a real-world clinical setting, to assess outcomes following a transition from IV to SC VDZ, and to compare treatment persistence and safety between IV and SC administration. Methods A multicenter Spanish study was conducted in patients with RP receiving VDZ for active pouchitis. Clinical outcomes were evaluated using the modified Pouch Disease Activity Index (mPDAI), and biomarkers such as faecal calprotectin (FC), C-reactive protein (CRP), and VDZ serum levels were monitored over one year. Patients who transitioned from IV to SC VDZ were assessed post-switch. Results A total of 47 patients were included (31 (66%) male; median age 51 [43, 64] years). Of these, 25 (53%) switched from IV to SC administration. Baseline characteristics are shown in Figure 1. Significant reductions in mPDAI scores were observed with IV VDZ, from 5 (3-7) at baseline to 3 (2-5), 3 (2-5), (2-5.8) at weeks (W) 12, 24 and 52 respectively (p<0.05). FC decreased significantly over time, from 443 µg/g (213, 746) to 329 µg/g (145-701), 193 µg/g (91-412) and 178 µg/g (101-640) at W12, 24 and 52, respectively (p<0.05), although no significant changes were observed in CRP levels. VDZ serum levels were 16,9 μg/dl (10.3-25.7), 12 μg/dl (7.3-23), 9 μg/dl (6.7-13.9) at W12, 24 and 52 respectively. After switching from IV to SC VDZ, there were no significant differences in terms of mPDAI, FC and CRP at W12 and W24. However, a significant decrease in mPAI (p=0.04) and FC levels (p=0.038) was observed at W52. FC levels also dropped significantly from 550 µg/g (145-1163) pre-swich to 264 µg/g (52-989), 129 (101-448) and 62 (31-211) at W12, 24 and 52, respectively. Notably, SC VDZ serum levels increased significantly, from 8.5 μg/dl (7.2-14) at time of switch to 22.7 μg/dl (21-27.3), 19.6 μg/dl (16.5-21), 21.6 μg/dl (17-26.2) over time. Fewer prior advanced therapies correlated with better outcomes, whereas use of corticosteroids and immunosuppressants at baseline did not. VDZ persistence was high (Figure 2) and adverse event rates were similar for IV and SC VDZ (8.5% and 12%, respectively). Conclusion VDZ was effective in achieving clinical and biological remission in patients with RP following IPAA for ulcerative colitis, particularly with early intervention. Switching from IV to SC VDZ effectively sustained long-term remission, demonstrating safety and persistence in routine clinical practice.

Association of ERAP1 and ERAP2 gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population.

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Although RA is chiefly associated with HLA class II, nevertheless some HLA class I associations have also been observed. These molecules present antigenic peptides to CD8+ T lymphocytes and natural killer cells. HLA-I molecules bind their peptide cargo (8-10 amino acids long) in the endoplasmic reticulum. Peptides longer than 10 amino acids are trimmed by the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 to fit the peptide binding groove of the HLA-I molecule. Here, we investigated the possible association of ERAP1 and ERAP2 polymorphisms with RA, and also any possible correlation between serum levels of the ERAP2 protein with disease severity. We used Real-Time PCR to genotype ERAP1 and ERAP2 and ELISA test to detect ERAP2 protein. We found significant associations of ERAP1 rs30187, rs27044, and rs26618, as well as ERAP2 rs2248374, with susceptibility to RA. ERAP1 rs26653 and ERAP2 rs2248374 were also associated with the Disease Activity Score (DAS28), and some polymorphisms were also associated with anti-citrullinated protein or anti-mutated citrullinated vimentin antibodies. RA patients secreted higher concentrations of ERAP2 than controls. Patients with mild disease activity (DAS28 < 3.2) released a concentration of ERAP2 four times lower than that of patients with severe disease activity (DAS28 > 5.1). We detected a higher level of ERAP2 in rheumatoid factor (RF)-positive patients than in RF-negative patients. ERAP2 concentration above 5.85 ng/mL indicated a severe phase of RA. Some ERAP1 and ERAP2 polymorphisms seem to be related to susceptibility to RA or the severity of the disease. The ERAP2 protein tested in serum could be a valuable biomarker of RA severity.