Serum Tumor Necrosis Factor Research Articles

Investigating Anti-Oxidative and Anti-Inflammatory Effects regarding Ethanol Extract of Allium Porrum L. in Rats with Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder worldwide. Meanwhile, Allium Porrum L. (AP) has been recognized as one of the most eminent traditional herbal medicines with substantial health benefits. The aim of the present study is to evaluate anti-oxidative and anti-inflammatory effects of ethanol extract of AP in rats with T2D. Methods: 70 male Sprague-Dawley rats were randomly divided into 7 groups of 10 animals each. The study groups were as follows: The study groups were as follows: healthy control (HC); healthy control rats receiving 100 mg/kg of AP extract (HC.AP.100); diabetic control (DC); diabetic rats receiving 10 mg/kg metformin (DT.M.10); diabetic animals receiving 50 mg/kg of AP extract (DT.AP.50); diabetic rats receiving 100 mg/kg of AP extract (DT.AP.100); and diabetic animals receiving 200 mg/kg of AP extract (DT.AP.200). Results: After 6 weeks of intervention, the level of serum malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) were significantly increased (P=0.02) and (P=0.002), respectively; while superoxide dismutase (SOD) concentration was notably reduced (P=0.04) in DC.M.10 in comparison with that of the HC.AP.100 group. Also, compared to DC.M.10 group, all rats treated with metformin and AP showed a significant decrease in the level of MDA and TNF-α, along with an enhancement of SOD concentration (All P<0.001). Moreover, in comparison with DT.M.10, DT.AP.50, and DT.AP.100 treatments, the DT.AP.200 group revealed a significantly higher improvement in serum TNF-α concentration (P=0.04, P=0.003 and P=0.003, respectively). Conclusion: The findings revealed that the use of AP extract for 6 weeks may have beneficial effects on oxidative stress and inflammatory biomarkers in T2D-induced rat models.

Effect of β-1,3-1,6-D-glukan (polysaccharide peptide) from miselia ganoderma lucidum extract as antioxidant and antiinflammation towards left ventricular systolic function in cardiometabolic patients

Background: Cardiometabolic disease (CMD) describes a metabolic condition often associated with cardiovascular disease. It has been revealed that the Ganoderma lucidum polysaccharide peptide (GLPP) possesses anti-inflammatory and antioxidant qualities. Objective: This study aimed to find out how GLPP affected oxidative stress, inflammation, and left ventricular function in individuals with cardiometabolic syndrome. Methods: A multicenter double-blinded randomized controlled trial was carried out. Subjects with cardiometabolic syndrome received either GLPP or a placebo for ninety days. Before taking the initial treatment and one day following the last treatment intake, blood samples were taken from every participant. The enzyme-linked immunosorbent assay was used to evaluate the levels of serum tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), malondialdehyde (MDA), and high-sensitivity-C-Reactive Protein (hs-CRP) while the colorimetric test was used to measure the levels of superoxide dismutase (SOD). Global longitudinal strain (GLS) and Left ventricle ejection fraction (LVEF) were measured by single echocardiographer expert validation. Results: The MDA level was decreased in the GLPP treatment group (mean 56.0 ± 71.4 ng/mL to 27.7 ± 12.0 ng/mL, p= 0.023) compared to the control group (mean 39.3 ± 29.2 ng/mL to 38.3 ± 17.7 ng/mL, p= 0.719). However, the SOD level remained constant in the GLPP treatment (mean 122.2 ± 176.1 U/mL to 93.0 ± 40.9 U/mL, p=0.925) instead of significantly declining in the control group (mean 102.0 ± 67.3 U/mL to 64.0 ± 52.0 U/mL, p=0.016). The marker of TNF-α and hsCRP were significantly decreased in all groups (both p<0.05), but IL-6 was only significantly decreased in the control group (mean 1149.3 ± 581.7 pg/mL to 744.8 ± 336.5 pg/mL, p=0.010). The GLS was significantly decreased in the GLPP treatment group (-16.1 ± 4.1 to -17.5 ± 4.8, p=0.048) but there was no difference in LVEF in both groups (p>0.05). Conclusion: Patients with cardiometabolic syndrome may benefit from GLPP treatment for 90 days in terms of reduced inflammation, oxidative stress, and improved systolic left ventricular performance. Keyword: cardiometabolic syndrome, echocardiography, ganoderma lucidum, inflammation, oxidative stress

Functional Effects of Probiotic Lactiplantibacillus plantarum in Alleviation Multidrug-Resistant Escherichia coli-Associated Colitis in BALB/c Mice Model.

Multidrug-resistant Escherichia coli (MDR-E. coli) is a global health concern. Lactic acid bacteria (LAB) are important probiotics that have beneficial effects on health, and in recent years, their influences in preventing foodborne pathogens-induced colitis have attracted much attention. Therefore, this study aimed to investigate the oral administration of Lactiplantibacillus plantarum NWAFU-BIO-BS29 as an emerging approach to alleviate MDR-E. coli-induced colitis in BALB/c mice model. To illustrate the mode of action of NWAFU-BIO-BS29 interventions with the gut microbiota and immune responses, the changes on the colonic mucosal barrier, regulatory of the gene expressions of inflammatory cytokines, re-modulating the intestinal microflora, and changes in physiological parameters were studied. The results indicated that daily supplementation of 200 µL fresh bacteria for 7days had ameliorated the associated colitis and partially prevented the infection. The modes of action by ameliorating the inflammatory response, which destructed villous and then affected the intestinal barrier integrity, reducing the secretion of interleukins (6 and β) and tumor necrosis factor (TNF-α) in serum by 87.88-89.93%, 30.73-35.98%, and 19.14-22.32%, respectively, enhancing the expressions of some epithelial integrity-related proteins in the mouse mucous layer of mucins 2 and 3, Claudin-1, and Occludin by 130.00-661.85%, 27.64-57.35%, 75.52-162.51%, and 139.36-177.73%, respectively, and 56.09-73.58% for toll-like receptor (TLR4) in colon tissues. Notably, the mouse gut microbiota analysis showed an increase in the relative abundance of beneficial bacteria, including Lactobacillus, Bacteriodales bacterium, Candidatus Saccharimonas, Enterorhabdus, and Bacilli. Furthermore, the probiotic promoted the proliferation of epithelia and goblet cells by increasing short-chain fatty acids (SCFAs) levels by 19.23-31.39%. In conclusion, L. plantarum NWAFU-BIO-BS29 has potential applications and can be considered a safe dietary supplement to ameliorate the colitis inflammation symptoms of MDR-E. coli infection.

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy.

The association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA. Serum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves. No significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients. Serum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs.

Unraveling the role of collateral circulation and serum ELAVL1 in carotid atherosclerosis and ischemic stroke: Insights from clinical observations.

The (embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) is a newly discovered protein associated with cerebral ischemic/reperfusion (I/R) injury. However, little is known of ELAVL1 in ischemic stroke patients. To investigate the clinical significance of collateral circulation and serum ELAVL1 in patients with carotid atherosclerosis (CAS) and ischemic stroke. The present prospective cohort investigation included 317 ischemic stroke patients and 300 CAS patients admitted between March 2020 and March 2022. Collateral circulation was measured using digital subtraction angiography (DSA) and graded using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading system. Enzyme-linked immunosorbent assays (ELISAs) were used to measure serum ELAVL1, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The serum levels of total cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL-C), and low-density leptin cholesterol (LDL-C) were also measured. The serum levels of ELAVL1, CRP, IL-6, TNF-α, and LDL-C were all markedly higher, while HDL-C was significantly lower in ischemic stroke patients compared to the CAS patients. Serum ELAVL1 was markedly higher in ASITN/SIR grade 0-1 patients compared to grade 2-4 patients. Also, ELAVL1 correlated positively with serum CRP, IL-6, TNF-α, TC, and LDL-C, and negatively with HDL-C. Receiver operating characteristic (ROC) curves showed that ELAVL1 and collateral circulation have the potential to be used as biomarkers for the diagnosis of ischemic stroke. Meanwhile, CRP, IL-6, TNF-α, HDL-C, ASITN/SIR grading, and ELAVL1 were independent risk factors for ischemic stroke. We found that serum ELAVL1 was associated with clinical outcomes of ischemic stroke patients, while the combination of ELAVL1 and collateral circulation could be used as a potential biomarker for ischemic stroke diagnosis.

Phytochemical Analysis, and Antioxidant and Hepatoprotective Activities of Chamaerops humilis L. Leaves; A Focus on Xanthine Oxidase.

Chamaerops humilis L. is clumping palm of the family Arecaceae with promising health-promoting effects. Parts of this species are utilized as food and employed in folk medicine to treat several disorders. This study investigated the phytochemical constituents of C. humilis leaves and their antioxidant and xanthine oxidase (XO) inhibitory activities in vitro and in vivo in acetaminophen (APAP)-induced hepatotoxicity in rats. The chemical structure of the isolated phytochemicals was determined using data obtained from UV, MS, IR, and 1H-, 13C-NMR spectroscopic tools as well as comparison with authentic markers. Eleven compounds, including tricin 7-O-β-rutinoside, vicenin, tricin, astragalin, borassoside D, pregnane-3,5,6,16-tetrol, oleanolic acid, β-sitosterol and campesterol were isolated from C. humilis ethanolic extract (CHEE). CHEE and the butanol, n-hexane, and dichloromethane fractions exhibited in vitro radical scavenging and XO inhibitory efficacies. The computational findings revealed the tendency of the isolated compounds towards the active site of XO. In vivo, CHEE ameliorated liver function markers and prevented tissue injury induced by APAP in rats. CHEE suppressed hepatic XO, decreased serum uric acid and liver malondialdehyde (MDA), and enhanced reduced glutathione (GSH), superoxide dismutase (SOD), and catalase in APAP-treated rats. CHEE ameliorated serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β in APAP-treated rats. Thus, C. humilis is rich in beneficial phytochemicals that possess binding affinity towards XO. C. humilis exhibited potent in vitro antioxidant and XO inhibitory activities, and prevented APAP hepatotoxicity by attenuating tissue injury, oxidative stress and inflammation.

Genetic variants in the TNF pathway impact TNFi response in a mixed population with rheumatoid arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies.

Serum Tumor Necrosis Factor Alpha (TNF-α) Levels in Obese and Overweight Adults: Correlations With Metabolic Syndrome and Inflammatory Markers.

Overweight and obesity are escalating public health concerns globally, and India is also experiencing a significant rise in thepopulation of overweight and obese people.Tumour necrosis factor alpha (TNF-α) is a type of cytokine that hasgarnered attention in particularly obesity-related metabolic disturbances.This study aimed to assess TNF-α levels in overweight and obese adults and explore its correlation with metabolic syndrome and associated biochemical parameters in the northeastern Indian population. A comparative study was conducted involving 200 participants divided into four groups: 50 healthy controls, 50 overweight individuals, 50 obese individuals without metabolic syndrome and 50 obese individuals with metabolic syndrome. Serum TNF-α levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Anthropometric measurements and biochemical analyses, including glucose and lipid profiles, were performed using standard methods. TNF-α levels were significantly elevated in overweight individuals (128.5±35.7 pg/ml), obese individuals without metabolic syndrome (171.5±13.6 pg/ml), and obeseindividuals with metabolic syndrome (238.6±62 pg/ml) compared to normal subjects (controls; 21.7±11.8 pg/ml). Positive correlations were observed between TNF-α and body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, glucose, cholesterol, triglycerides, and negative correlation was found high-density lipoprotein cholesterol (HDL-C). Elevated TNF-α levels in overweight and obese individuals suggest its role in metabolic disturbances and immune activation within the adipose tissue. These findings underscore the importance of monitoring TNF-α as a potential biomarker for metabolic syndrome risk, highlighting the need for targeted interventions in the northeastern Indian population to mitigate the health impacts of obesity and associated metabolic disorders.

Tirofiban influences serum inflammatory factors and neurotransmitter levels in acute cerebral infarction patients

This study investigated the effects of tirofiban on serum inflammatory factors and neurotransmitter levels in 122 patients with acute cerebral infarction (ACI) at a Nigerian teaching hospital from January 2021 to December 2023. Patients were divided into conventional and study groups, with the study group receiving tirofiban in addition to standard treatment. Clinical efficacy and levels of Interleukin 6 (IL-6), serum tumor necrosis factor (TNF-α), 5-hydroxytryptamine (5-HT), dopamine (DA), and glutamic acid (Glu) were compared. Result findings showed that the research group (RG) had a significantly higher total effective rate of treatment (93.44%) compared to the conventional group. While IL-6 and TNF-α levels were similar between groups initially and at 7 days post-treatment, they were lower in the study group at 14 days post-treatment. Levels of 5-HT, DA, and Glu did not differ initially and at 7 days post-treatment but were higher in the study group at 14 days for 5-HT and DA, while Glu was lower. In conclusion, tirofiban improved clinical efficacy, reduce serum inflammatory responses, and impact neurotransmitter levels in patients with ACI.

Clinical efficacy and safety of the self-developed Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a significant global public health issue. Modern medical treatments have both benefits and limitations, prompting increasing attention from scholars worldwide on traditional ethnic medicine, and the Zangsiwei Qingfei Mixture is a newly developed formula derived from the effective components of classical Tibetan medicine to treat chronic respiratory diseases. This study aims to investigate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Sixty AECOPD patients admitted to the Second Xiangya Hospital of Central South University from May 2021 to May 2023 were enrolled and randomly divided into 2 groups, with 30 patients in each group. The control group received conventional treatment, including bronchodilators, anti-infection agents, expectorants, and oxygen therapy. The experimental group received the Zangsiwei Qingfei Mixture in addition to conventional treatment. The treatment duration was 7 d for both groups. Baseline data such as gender, age, body mass index (BMI), smoking status, Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, COPD course, and the number of COPD exacerbations in the past year were collected. The primary efficacy indicators were assessed using the modified Medical Research Council (mMRC) dyspnea scale and the modified Borg scale. Secondary indicators included arterial lactic acid (LAC) and serum tumor necrosis factor alpha (TNF-α) levels. Safety indicators included liver and kidney function [alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (SCr), serum uric acid (SUA)], coagulation function [activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), and D-dimer]. The generalized linear mixed model (GLMM) was used to evaluate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture. Before treatment, there were no statistically significant differences in general baseline data, grading of mMRC dyspnea scale, score of modified Borg scale, arterial LAC, ALT, AST, SCr, SUA, APTT, FIB, and D-dimer between the 2 groups (all P>0.05). However, serum TNF-α and PT levels in the experimental group were significantly lower than those in the control group (both P<0.05). GLMM analysis showed that after adjusting for pre- and post-treatment, gender, age, BMI, smoking status, GOLD classification, COPD course, and the number of COPD exacerbations in the past year, the experimental group demonstrated significantly lower grading of mMRC dyspnea scale (coefficient=-0.329, P=0.036), score of modified Borg scale (coefficient=-1.077, P=0.001), serum TNF-α level (coefficient=-14.378, P<0.001), and arterial LAC level (coefficient=-0.409, P=0.012) compared to the control group. The Zangsiwei Qingfei Mixture had no significant effect on liver, kidney, or coagulation function indicators (all P>0.05). The Zangsiwei Qingfei Mixture combined with conventional treatment can improve clinical symptoms and promote homeostasis in AECOPD patients, demonstrating safety and reliability. Combining modern medicine with traditional ethnic medicine offers a feasible approach to treating chronic respiratory diseases in the future.

Adiponectin and TNFα in relation to glucometabolic control in patients with type 2 diabetes mellitus.

The correlation of adiponectin and serum tumor necrosis factor alpha (TNFα) with glucometabolic parameters in diabetes mellitus (DM) needs further studies. We aimed in this study to evaluate the relationship between adiponectin and TNFα with glucometabolic parameters in patients with type 2 DM (T2DM). We conducted a cross-sectional study in the Department of Physiology, College of Medicine, King Saud University, Saudi Arabia. The sample size was 117 from the diabetes clinic of King Abdul-Aziz University hospital through the convenience sampling technique. Subjects were grouped into control (healthy) subjects (53) with no chronic diseases and the diabetic group (64) with confirmed T2DM. Socio-demographic data were collected along with the serum blood sample to analyze the variables. Adiponectin was significantly high in healthy subjects compared to the diabetic group (control: 14.4 ± 4.3, T2DM: 11.0 ± 4.1, P = 0.000), while TNFα was higher in the T2DM group (7.8 ± 2.7) than in the control group (6.6 ± 2.9, P = 0.024). TNFα was negatively correlated with adiponectin in the control group (-0.279) and in diabetic subjects (-0.311) and positively correlated with HbA1c in the diabetic group (0.319) and triglycerides (0.252). Adiponectin was positively correlated with HDL in the control group (0.252) and in diabetic subjects (0.326). There was an inverse correlation between TNFα and adiponectin. Adiponectin is higher in healthy subjects than in diabetic patients, while TNFα is higher in diabetic patients. In addition, adiponectin is positively correlated with HDL in healthy as well as diabetic patients. TNFα is positively correlated with HbA1c and triglycerides.

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction.

Cerebral infarction (CI) is characterized by a high prevalence, disability, and mortality. Timely or improper treatment greatly affects patient prognosis. To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life (QOL), anxiety and depression in CI patients. We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group (OG) (combination therapy of aspirin and edaravone, 65 patients) or a control group (CG) (aspirin monotherapy, 59 patients). The therapeutic effects, pre- and posttreatment National Institutes of Health Stroke Scale (NIHSS) scores, activities of daily living, degree of cognitive impairment, protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and S-100B, occurrence of adverse reactions, and serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated, detected and compared between the two groups. Finally, posttreatment QOL, anxiety, and depression were assessed by the Medical Outcomes Study 36- Item Short Form Health Survey Scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), respectively. Compared with the CG, the OG had markedly better therapeutic effects, greater improvements in activities of daily living, and better alleviation in cognitive dysfunction after treatment, as well as lower posttreatment NIHSS scores and serum NSE, GFAP, S-100B, hs-CRP, IL-6, and TNF-α levels; the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL; and the OG also had lower SDS and SAS scores than the CG after treatment. Aspirin plus edaravone had a good curative effect on CI. It can reverse cranial nerve damage in patients, improve neurological function and prognosis, and alleviate inflammation, anxiety, and depression; thus, it is considered safe and worthy of clinical application.

Elevated Exposure to Air Pollutants Accelerates Primary Glomerular Disease Progression

IntroductionEnvironmental contributors to kidney disease progression remain elusive. We explored how residential air pollution impacts disease progression in patients with primary glomerulopathies. MethodsNephrotic Syndrome Study Network (NEPTUNE) and CureGlomerulonephropathy (CureGN) participants with residential census tract data and ≥2 years of follow-up were included. Using Cox proportional hazards models, the associations per doubling in annual average baseline concentrations of total particulate matter with diameter ≤ 2.5 μm (PM2.5) and its components, black carbon, and sulfate, with time to ≥40% decline in estimated glomerular filtration rate (eGFR) or kidney failure were estimated. Serum tumor necrosis factor levels and kidney tissue transcriptomic inflammatory pathway activation scores were used as molecular markers of disease progression. ResultsPM2.5, black carbon, and sulfate exposures were comparable in NEPTUNE (n=228) and CureGN (n=697). In both cohorts, participants from areas with higher levels of pollutants had lower eGFR, were older and more likely self-reported racial and ethnic minorities. In a fully adjusted model combining both cohorts, kidney disease progression was associated with PM2.5 (adjusted HR 1.55 [95% CI:1.00, 2.38], p=0.0489) and black carbon (adjusted HR 1.43 [95% CI:0.98, 2.07], p=0.0608) exposure. Sulfate and PM2.5 exposure were positively correlated with serum tumor necrosis factor (TNF) (p=0.003) and interleukin-1β levels (p=0.03), respectively. Sulfate exposure was also directly associated with transcriptional activation of the TNF and JAK-STAT signaling pathways in kidneys (r=0.55-0.67, p-value <0.01). ConclusionElevated exposure to select air pollutants is associated with increased risk of disease progression and systemic inflammation in patients with primary glomerulopathies (word count: 248).

FGF23 as a Potential Pathophysiological Factor in Peripheral Arterial Disease Associated with Chronic Kidney Disease.

Fibroblast growth factor 23 (FGF23) levels are often elevated in chronic kidney disease (CKD). FGF23 and inflammation are common characteristics in CKD, and both are associated with worse disease progression and the occurrence of complications. The existence of an interaction between FGF23 and inflammation has been suggested, each of which influences the expression and activity of the other, leading to a vicious feedback loop with adverse outcomes, including cardiovascular disease and mortality. In this work, we determined circulating FGF23 levels in a group of patients with CKD stages 3 and 4 subjected to elective femoral endarterectomy due to established peripheral artery disease (PAD), a condition resulting from an athero-inflammatory process, and we studied its associations with different inflammatory markers and mediators. We evaluated its association with serum tumor necrosis factor (TNF)α, interleukin (IL) 6, and IL10, as well as with the gene expression levels of these parameters and A disintegrin and metalloproteinase domain-containing protein (ADAM) 17 in femoral vascular tissue and peripheral blood circulating cells (PBCCs). We also analyzed its association with serum concentrations of C-reactive protein (CRP), the systemic immune inflammation index (SII), and the neutrophil-to-lymphocyte ratio (NLR). Finally, we determined the vascular immunoreactivity of protein TNFα in a subgroup of patients. FGF23 concentrations were independently associated with circulating and PBCC mRNA levels of TNFα. Worst kidney function and diabetes were also found to be contributing to FGF23 levels. Patients with higher levels of FGF23 also had greater vascular immunoreactivity for TNFα.

Effect of transcutaneous electrical acupoint stimulation on postoperative cough in lung cancer patients undergoing video-assisted thoracoscopic surgery

To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) for alleviating postoperative cough in lung cancer patients undergoing video-assisted thoracoscopic surgery. A total of 110 patients with lung cancer undergoing video-assisted thoracoscopic surgery were randomly divided into a TEAS group (55 cases, 2 cases dropped out) and a sham-TEAS group (55 cases, 4 cases dropped out). In the TEAS group, TEAS was delivered 30 min before anesthesia and on day 1 to day 4 after operation separately, with disperse-dense wave, in frequence of 2 Hz/100 Hz. The acupoints included Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Hegu (LI 4), Lieque (LU 7) and Taixi (KI 3) on the both sides. In the sham-TEAS group, at the same time points and same acupoints as the TEAS group, the electrode pads were attached to the acupoints, but without electric stimulation. The interventions were given 30 min each time, once daily in the two groups. The incidence of cough and the scores of visual analogue scale (VAS) for cough on the first day (T1), the third day (T2), the fifth day (T3), 1 month (T4) and 3 months (T5) after operation, as well as the scores of the Leicester cough questionnaire (LCQ) on T4 and T5 were compared between the two groups; the contents of serum C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were detected before surgery (T0) and at T1, T2 and T3. The first flatus time, the first defecation time, the first ambulation time, the postoperative hospital day and the incidence of postoperative nausea and vomiting were compared between the two groups. Compared with the sham-TEAS group, the cough incidence at T3 and cough VAS scores at T1 to T5 were lower in the TEAS group (P<0.05, P<0.01), and the LCQ scores at T4 and T5 were higher (P<0.05). The serum contents of CRP, IL-6 and TNF-αat T1 to T3 in the TEAS group were lower than those of the sham-TEAS group (P<0.01). The first flatus time, the first defecation time and the first ambulation time were earlier (P<0.05, P<0.01); and the postoperative hospital day was shorter (P<0.05) and the incidence of postoperative nausea and vomiting was lower (P<0.05) in the TEAS group when compared with those of the sham-TEAS group. TEAS relieves cough in lung cancer patients undergoing video-assisted thoracoscopic surgery, improves quality of life and promotes the early postoperative recovery.

185 Maternal live yeast supplementation protects newly weaned piglets against lipopolysaccharide challenge by regulating immune-associated milk proteins

Abstract Sow milk serves as a crucial source of nutritional, immunological, and growth-promoting components for the piglets. Our previous studies established that maternal live yeast (LY) supplementation altered the expression of antioxidant and immune-regulatory genes in the intestinal mucosa of suckling piglets. The current study aimed to investigate the effects of maternal LY supplementation during late gestation and lactation on milk proteomic profile in dams and health of offspring under lipopolysaccharide (LPS) challenge. On d 77 of gestation, 40 sows were allocated to 2 dietary treatments: without (CON) or with LY supplementation at 0.05% of diet during gestation and 0.1% during lactation. Milk samples were collected on d 0, 10, and 18 post-partum (n = 6), respectively. Within 24 h postweaning, piglets from the CON and LY groups were intraperitoneally injected with sterile saline or LPS [25 μg/kg body weight (BW)] and divided into four groups (n = 8): 1) saline + CON (CS), 2) saline + LY (YS), 3) LPS + CON (CLPS), and 4) LPS + LY (YLPS). Data were analyzed in a 2 × 2 factorial arrangement with main effects of maternal diet and immunological challenge. Rectal temperature was measured hourly for 4 h post-injection after which piglets were euthanized. Results showed that LPS increased concentrations of serum tumor necrosis factor (TNF) -α and interlekin (IL) -10 (P &amp;lt; 0.05) and tended to increase IL-8 in the ileal mucosa of piglets (P &amp;lt; 0.10). At 3 h post-injection, YLPS piglets tended to have a lower rectal temperature than CLPS piglets (P &amp;lt; 0.10). YLPS piglets also had decreased protein levels of TNF-α in the ileal mucosa (P &amp;lt; 0.05), with a tendency for greater protein abundance of E-cadherin but decreased mRNA abundance of catalase (P &amp;lt; 0.10) in the jejunal mucosa at 4 h post-injection (P &amp;lt; 0.05). In addition, YLPS piglets had less mRNA abundance of TLR2 and TLR4 in the liver than CLPS piglets (P &amp;lt; 0.05). With shotgun proteomics analysis, we found that milk of LY sows had more abundant proteins associated with immunity, including immunoglobulin and complement protein (Ig-like and C1q domain-containing proteins) on d 0 and d 10. Insulin-like growth factor binding protein (IGFBP) 5 was also more abundant in the d 0 milk of LY sows, whereas prostaglandin synthase was greater in d 10 and d 18 milk of CON sows. Additionally, pathway analysis showed that proteins identified in the milk of CON sows have roles in neutrophil degranulation and IL-12 signaling and production, whereas pathways associated with regulation of complement system, IGF and DHCR24 signaling, were enriched in the milk of LY sows. These results suggest that maternal LY supplementation could protect newly weaned piglets from bacteria endotoxin effect by suppressing inflammatory response, improving expression of tight junction proteins in offspring, and altering immune-associated proteins in sow milk.

Modulation of TNF Release by the Innate Fear Odorant 2-Methylthiazoline Requires TRPA1-Mediated Signaling

The innate fear odorant 2-Methylthiazoline (2-MT) elicits highly robust innate fear and defensive behaviors, such as freezing, hypothermia and bradycardia via activation of transient receptor potential ankyrin 1 (TRPA1) channels. Activation of TRPA1-expressing vagus nerve fibers also regulates IL-1β induced hypothermia and reflex anti-inflammatory responses. However, it is unclear whether 2-MT can trigger an anti-inflammatory response via TRPA1 activation. Here, we demonstrate that 2-MT attenuates endotoxin-induced tumor necrosis factor (TNF) production in wild-type mice in TRPA1-dependent manner. Exposure to 2-MT induces a significant reduction in serum TNF in wild-type mice injected with endotoxin as compared to vehicle control mice (vehicle control vs. 2-MT; 1,123 ± 32.3 pg/mL vs. 714.1 ± 58.2 pg/mL; * p=0.02). However, 2-MT exposure fails to suppress endotoxin-induced TNF-release in TrpA1-knock out mice (vehicle control vs. 2-MT; 1,123 ± 32.3 vs. 948.7 ± 99.2 pg/mL; ns p=0.89). A single exposure to 2-MT during endotoxin injection also protects animals from lethal endotoxemia and significantly improves survival as compared to vehicle-exposed endotoxemic controls (vehicle control vs. single 2-MT Odor; 26.7% vs. 66.7% survival 120 hours post LPS injection). In addition, significant improvement in disease activity is observed in mice exposed to 2-MT odorant (vehicle control vs. single 2-MT Odor; disease activity: 0.5 ± 0.2 a.u. vs. 0.3 ± 0.1 a.u., * p=0.01). Collectively, these data characterize the anti-inflammatory effcacy of 2-MT and demonstrate that the modulation of TNF release by 2-MT requires TRPA1-mediated signaling. This work is supported in part by grants from NIH, NIGMS, 1R35 GM118182 to KJT and 1R01AR083159-01 to SSC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clostridium butyricum isolated from giant panda can attenuate dextran sodium sulfate-induced colitis in mice.

Probiotics are beneficial to the intestinal barrier, but few studies have investigated probiotics from giant pandas. This study aims to explore the preventive effects of giant panda-derived Clostridium butyricum on dextran sodium sulfate (DSS)-induced colitis in mice. Clostridium butyricum was administered to mice 14 days before administering DSS treatment to induce enteritis. Clostridium butyricum B14 could more effectively prevent colitis in mice than C. butyricum B13. C. butyricum B14 protected the mouse colon by decreasing the histology index and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, which improved intestinal inflammation-related symptoms. In addition, the treatment led to the regulation of the expression of Tifa, Igkv12-89, and Nr1d1, which in turn inhibited immune pathways. The expression of Muc4, Lama3, Cldn4, Cldn3, Ocln, Zo1, Zo2, and Snai is related the intestinal mucosal barrier. 16S sequencing shows that the C. butyricum B14 significantly increased the abundance of certain intestinal probiotics. Overall, C. butyricum B14 exerted a preventive effect on colitis in mice by inhibiting immune responses, enhancing the intestinal barrier and increasing the abundance of probiotic species. Thus, C. butyricum B14 administration helps regulate the balance of the intestinal microecology. It can suppress immune pathways and enhance barrier-protective proteins.

Association between Toxoplasma gondii and gestational diabetes with regard to serum leptin and tumor necrosis factor alpha, a preliminary study

Gestational diabetes (GDM), the onset of any degree of glucose intolerance during pregnancy, increases a wide range of adverse health outcomes for both the mother and the fetus. The aim of the present study was to evaluate the association of Toxoplasma gondii infection with GDM in a case-control study with regard to the levels of leptin and tumor necrosis factor alpha (TNF-α) as two inflammatory biomarkers. Fifty-one pregnant diabetic cases and 109 controls were selected from a prenatal care clinic of a general hospital in Shiraz, southern Iran during July–November 2020. Cases and controls were similar in age, gestational age and number of parturitions. The presence of IgG antibodies against T. gondii, and serum concentrations of leptin and TNF-α were determined by ELISA. Anti-Toxoplasma antibodies were detected in 25 subjects (15.6 %, 95 % CI: 9.9–21.3). Nine (18 %) diabetic cases were infected with Toxoplasma compared to 16 (15 %) healthy controls (P = 0.63). Level of leptin was higher (P = 0.07) while TNF-α was lower in diabetic cases compared to healthy controls (P = 0.08). When subjects were classified according to the combination of GDM and T. gondii, leptin was significantly lower in healthy (non-diabetic, non-infected) subjects compared to diabetics (P = 0.026), and TNF-α was higher in healthy subjects compared to Toxoplasma-infected diabetics (P = 0.032). These findings can be interpreted as both comorbidities being individually associated with increasing serum leptin and decreasing TNF-α concentrations, with modifying effects on each other. The present study opens a new perspective on GDM and its complex pathophysiological mechanism. Future research in this area is needed to better understand the underlying pathway for the development of GDM and the role of T. gondii and inflammatory biomarkers.

Analysis of blood biochemistry and non-targeted metabolomics of endometritis in dairy cows

The incidence of bovine endometritis, which has a negative impact on the reproduction of dairy cows, has been recently increasing. In this study, the differential markers and metabolites of healthy cows and cows with endometritis were analyzed by measuring blood biochemical indicators and immune factors using biochemical and enzyme-linked immunosorbent assay kits combined with nontargeted metabolomics. The LC-QTOF platform was used to evaluate the serum metabolomics of healthy cows and cows with endometritis after 21–27 days of calving. The results showed that glucose, free fatty acid, calcium, sodium, albumin, and alanine aminotransferase levels were significantly lower in the serum of cows with endometritis than in healthy cows (P < 0.05). However, the serum potassium, interleukin-1, interleukin-6, and tumor necrosis factor levels were significantly higher in cows with endometritis (P < 0.05). In addition, the serum metabolome data analysis of the two groups showed that the expression of 468 metabolites was significantly different (P < 0.05), of which 291 were upregulated and 177 were downregulated. These metabolites were involved in 78 metabolic pathways, including amino acid, nucleotide, carbohydrate, lipid, and vitamin metabolism pathways; signal transduction pathways, and other biological pathways. Taken together, negative energy balance and immune activation, which are related to local abnormalities in amino acid, lipid, and carbohydrate metabolism, were the important causes of endometritis in dairy cows. Metabolites such as glucose, carnosine, dehydroascorbic acid, L-malic acid, tetrahydrofolic acid, and UDP-glucose may be used as key indicators in the hematological diagnosis and treatment of endometritis in dairy cows.