TNF-alpha Concentrations Research Articles

Neuroprotective effect of chelidonic acid through oxidative stress reduction in paclitaxel-induced peripheral neuropathy in rats.

The present study evaluated the effect of chelidonic acid on paclitaxel-induced neuropathy in male Wistar rats. Neuropathy was induced by administering paclitaxel (2mg/kg, i.p.) on 0, 2, 4, and 6days of the protocol. Chelidonic acid treatment (at doses of 10, 20, and 40mg/kg orally, for 21days) was initiated simultaneously with paclitaxel administration. After completion of the protocol, mechanical allodynia, hyperalgesia, and thermal hyperalgesia were measured. Additionally, nerve conduction velocity was assessed. The study investigated inflammatory cytokines, oxidative stress, and histological changes in the sciatic nerve. Furthermore, the Nrf2 was measured, and the protein expression of pAMPK and HIF-1α was assessed using western blotting. The results showed that chelidonic acid significantly normalized mechanical allodynia, hyperalgesia, and thermal hyperalgesia. It also led to a significant improvement in motor and sensory nerve conduction velocity and reduced oxidative stress compared with paclitaxel alone. Inflammatory markers such as TNF-alpha, IL-6, and IL-1β concentrations, as well as nitric oxide and C-reactive protein, were significantly decreased in the chelidonic acid-treated group. Histopathological examination revealed reduced neuronal damage, demyelination, and leukocyte infiltration with chelidonic acid treatment. Chelidonic acid treatment also resulted in a considerable rise in Nrf2 levels (p < 0.001) and increased protein expression of pAMPK in the sciatic nerve. Conversely, HIF-1α expression was significantly declined in the chelidonic acid treatment. Overall, the findings suggest that chelidonic acid treatment attenuates paclitaxel-induced neuropathic pain.

Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study.

Background/Objective: Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. Methods: We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.7 ± 3.0 kg/m2, sex F 57%) comparing the effects of daily supplementation with 20 g of LM citrus pectin versus 10 g of maltodextrin as the control (N = 15 age 43.2 ± 11 y, BMI 25.18 ± 2.0 kg/m2, sex F 66%). The effects on mood and inflammation were also tested with LM pectin at 5 g, 10 g and 15 g (2 weeks each) in an independent cohort of n = 15 healthy volunteers (age 36 ± 21 y, BMI 23.5 ± 2.4 kg/m2, sex F 80%). We assessed serum levels of TNF-alpha (downstream from TLR-2 activation), IL-1 beta, IL-6, IL-10, INF-gamma, CRP, zonulin and TLR-2 concentration which were measured using ELISA in blood samples collected at both the baseline and follow-up visits. Validated measures of anxiety and depression were collected at baseline and follow-up. Results: Supplementation with 20 g of LM pectin resulted in decreases in the pro-inflammatory markers TNF-alpha, IL-1 beta, IL-6 and INF-gamma (all p < 0.05) and an increase in anti-inflammatory marker IL-10 (p = 0.01) at the end of the 4 weeks. No such effects were observed in the control group. In addition, a significant drop in anxiety scores (from 8.38 to 4.46, p < 0.006) was found with the 20 g/day intervention but not in the control arm. In the dose-response study, anti-inflammatory effects were seen only at 15 g for TNFα (p < 0.003) and a suggestive increase in IL-10 (p = 0.08), alongside a drop in TLR-2 (p < 0.027). No significant anti-inflammatory effects were observed at 5 g and 10 g doses of LM pectin supplementation. Significant dose-dependent drops in both anxiety and depression scores were found with 10 g (p < 0.001) and 15 g per day (p < 0.0002). Conclusions: The current study identifies anxiety-reducing and anti-inflammatory effects of supplementation with 15 g/day LM pectin in healthy humans. Further research is needed to elucidate the precise mechanism and to validate the efficient dose and minimum duration of supplementation.

Inflammatory Profile of Chronic Rhinosinusitis With Nasal Polyp Patients in Brazil: Multicenter Study.

To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. Multicenter cross-sectional study involving 15 centers representing different regions of Brazil. Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund-Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund-Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF-alpha and significantly higher concentrations of IFN-gamma, CCL11/Eotaxin, CCL24/Eotaxin-2/MPIF-2, and CCL26/Eotaxin-3 versus the control group (Kruskal-Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann-Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL-6 and IL-33 (Mann-Whitney test). According to ROC curve analysis the best cut-off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund-Mackay score (Mann-Whitney test). CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut-off in nasal polyps.

The Relationship of Certain Physiological Parameters and VEGF with chronic kidney disease

Chronic kidney disease (CKD) is a major health burden affecting over 10% of the global population. As kidney function deteriorates across progressive CKD stages, systemic inflammation and cytokine activity are upregulated which further drive disease advancement. Vascular endothelial growth factor (VEGF) also becomes increasingly dysregulated with implications for vascular pathology. However, step-wise changes in these pathways correlating with declining renal filtration have not been clearly elucidated : Objective: This study aimed to evaluate the utility of estimated glomerular filtration rate (eGFR) using the MDRD equation for disease staging, and to explore potential non-invasive biomarkers, including inflammatory markers and vascular endothelial growth factor (VEGF) expression, for early prediction of renal dysfunction; Methods: 50 CKD patients categorized into stages 1-4 (n=10 each) and 10 healthy controls were recruited. Serum creatinine was measured enzymatically and eGFR calculated. Plasma TNF-alpha and CRP concentrations were determined by ELISA. Relative VEGF mRNA levels were quantified by RT-qPCR and normalized to GAPDH; Results: Advancing CKD stage showed step-wise increases in serum creatinine (p&lt;0.001) and reductions in mean eGFR (p&lt;0.001). TNF-alpha and CRP also demonstrated significant stage-dependent elevations beginning from early stage 2 disease relative to controls (p&lt;0.01). VEGF expression escalated progressively from ~3 fold in stage 2 to ~129 fold in stage 4 CKD compared to normal individuals (p&lt;0.001); Conclusions: Deteriorating renal function is associated with substantive aggravations in systemic inflammation and VEGF expression. Tracking these biomarkers could enable early detection of underlying pathology prior to onset of severe kidney impairment.

The Relationship of Certain Physiological Parameters and VEGF with chronic kidney disease

Chronic kidney disease (CKD) is a major health burden affecting over 10% of the global population. As kidney function deteriorates across progressive CKD stages, systemic inflammation and cytokine activity are upregulated which further drive disease advancement. Vascular endothelial growth factor (VEGF) also becomes increasingly dysregulated with implications for vascular pathology. However, step-wise changes in these pathways correlating with declining renal filtration have not been clearly elucidated : Objective: This study aimed to evaluate the utility of estimated glomerular filtration rate (eGFR) using the MDRD equation for disease staging, and to explore potential non-invasive biomarkers, including inflammatory markers and vascular endothelial growth factor (VEGF) expression, for early prediction of renal dysfunction; Methods: 50 CKD patients categorized into stages 1-4 (n=10 each) and 10 healthy controls were recruited. Serum creatinine was measured enzymatically and eGFR calculated. Plasma TNF-alpha and CRP concentrations were determined by ELISA. Relative VEGF mRNA levels were quantified by RT-qPCR and normalized to GAPDH; Results: Advancing CKD stage showed step-wise increases in serum creatinine (p&lt;0.001) and reductions in mean eGFR (p&lt;0.001). TNF-alpha and CRP also demonstrated significant stage-dependent elevations beginning from early stage 2 disease relative to controls (p&lt;0.01). VEGF expression escalated progressively from ~3 fold in stage 2 to ~129 fold in stage 4 CKD compared to normal individuals (p&lt;0.001); Conclusions: Deteriorating renal function is associated with substantive aggravations in systemic inflammation and VEGF expression. Tracking these biomarkers could enable early detection of underlying pathology prior to onset of severe kidney impairment.

Differential Inflammatory Responses in Adult and Pediatric COVID-19 Patients: Implications for Long-Term Consequences and Anti-Inflammatory Treatment.

BACKGROUND COVID-19 manifests with varying degrees of severity across different age groups; adults typically experience more severe symptoms than children. Matrix metalloproteinases (MMPs), known for their role in tissue remodeling and immune responses, may contribute to the pathophysiological disparities observed between these groups. We sought to delineate differences in serum MMP profiles between adult and pediatric COVID-19 patients, assess the influence of anti-inflammatory treatment on MMP levels, and examine potential implications for long-term consequences. MATERIAL AND METHODS Serum samples from adult and pediatric COVID-19 patients, alongside controls, were analyzed for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, EMMPRIN, TNF-alpha, TIMP-1, TIMP-2, TIMP-3, and TIMP-4. A subset of adult patients received treatment with glucocorticoids, tocilizumab, and convalescent plasma, and MMP levels were compared with those of untreated patients. RESULTS Elevated levels of MMP-1, MMP-7, TIMP-1, and TIMP-2 were observed in adult and pediatric patients. Adult patients displayed higher concentrations of MMP-3, MMP-8, MMP-9, TNF-alpha, and TIMP-4 than children. Post-treatment reduction in MMP-1, MMP-8, MMP-9 levels was observed, with median decreases from 21% to 70%. MMP-3 and MMP-7 remained largely unchanged, and MMP-2 concentrations increased after treatment. Notably, anti-inflammatory treatment correlated with reduced post-treatment MMP levels, suggesting potential therapeutic benefit. CONCLUSIONS Distinctive inflammatory responses in COVID-19 were evident between adults and children. While certain MMPs exhibited post-treatment reduction, the persistence of elevated levels raises concerns about potential long-term consequences, including lung fibrosis. Our findings emphasize the need for personalized treatment strategies and further investigation into the dynamics of MMP regulation in COVID-19.

JAK/STAT signaling in rheumatoid arthritis leukocytes is uncoupled from serum cytokines in a subset of patients

ObjectiveRheumatoid Arthritis (RA) is a systemic autoimmune disease involving pro-inflammatory cytokines that can be therapeutically targeted by antibodies or kinase inhibitors. Nevertheless, these drugs fail in a subset of patients independent of the abundance of the targeted cytokines. We aim to explore the cellular basis of this phenomenon by analyzing the relation of cytokine abundance and activation of downstream signaling pathways in RA. MethodsThe study included 62 RA patients and 9 healthy controls (HC). Phosphorylation of STAT 1–6 in various immune cell subsets was determined ex vivo using a novel robust flow cytometry-based protocol. Serum concentrations of IL-6, IL-10, IL-12p70, IL-17 A, interferon gamma, and TNFα in the same samples were measured using highly sensitive single molecule array (SIMOA). ResultsWe found an increase in circulating cytokines in RA patients, while STAT activity was lower in RA patients compared to HC. Based on STAT activity we determined three endotypes in active RA patients (cDAI>10, n = 28): 1) those with active STAT5a/b signaling in T cells (n = 7/28), 2) those with a low STAT activity in all assessed cell types (n = 14/28), and 3) those with active STAT1 and STAT3 signaling mainly in myeloid cells (n = 7/28). Integrating intracellular STAT activation and cytokine analysis revealed diminished JAK/STAT signaling in a subset of patients (n = 8/20) despite elevated serum cytokine concentrations. ConclusionDiminished JAK/STAT signaling in active RA may partly explain unresponsiveness to therapy targeting cytokine signaling. Analysis of JAK/STAT phosphorylation may identify patients at risk for non-response to these therapies.

Regulation of angiogenesis and inflammatory pathways by glycyrrhizic acid

Skin cancer accounts for most malignancies across the globe. They are primarily divided into melanoma and nonmelanoma skin malignancies. Nonmelanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma. Glycyrrhetinic acid (GA) is a bioactive compound extracted from licorice that exhibits an inhibition effect on various cancers. GA has been reported to have in vitro cytotoxic effects on several human cancer cells. However, reports on the mode of action and detailed mechanism of GA in vitro in skin cancer disease are limited. Hence, GA’s effect on the human skin cell line BJ and MCC13 was investigated. MTT assay showed that GA had cytotoxic effects on MCC13 cells but was non-toxic to the normal cells of BJ in a time-dose dependent manner. GA also inhibited the angiogenic sprouting of new blood vessels in tumor progression. In gene expression assay, GA induces mitochondrial apoptosis through the induction and inhibition of Cytochrome C and Bcl2 respectively. In conclusion, GA is a potent candidate to induce apoptosis and concurrently inhibit the invasion, migration, and angiogenesis of the MCC13 cell line through increasing TNF-alpha concentration resulting in the necroptotic pathway induction.

Detection and dynamics of tumor necrosis factor alpha in the diagnosis and treatment of canine heartworm disease.

The aim of this study was to determine the concentration of TNF-alpha (TNF-α) in dogs naturally infected with Dirofilaria immitis (D. immitis) and to assess whether there are any changes in TNF-α concentration and their dependence during therapy for heartworm disease (HWD). For this study, 14 client-owned dogs with HWD were selected. Clinical and parasitological examinations (modified Knott test for circulating microfilariae and SNAP Test IDEXX for circulating D. immitis antigen) had been used for diagnosing D. immitis and HWD. All dogs were treated with an alternative therapy for HWD (oral doxycycline 10 mg/kg b.w., once daily for 6 weeks, then alternately 4 weeks without and 2 weeks with the medication, and oral ivermectin 6-14 µg/kg b.w., every 2 weeks). The dogs blood sera at the moment of HWD diagnosis, during and at the end of therapy were frozen for further quantifying of TNF-α (Canine TNF-alpha ELISA kit, Thermo scientific). At the moment of HWD diagnosis TNF-α was detected in 9 dogs (7.21±12.44 pg/ml). Concentration of TNF-α was not significantly change during the therapy, neither related to the level of D. immitis antigen nor to antigen level changes. The alternative therapy for HWD has no influence on TNF-α concentration dynamics.

AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients.

Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

The Relationship of immunoglobulin-e and tumor necrosis factor in patients with allergic rhinitis in Babylon province

Abstract Background: Rhinitis is defined as inflammation of the mucous membranes of the nose usually that is accompanied by swelling of the mucosa and a nasal discharge. It is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens, smoking and alcohol use, gender, age, overweight, adoption of pets, race, educational achievement, and family history can represent a risk factor for allergic rhinitis (AR). Objectives: To find the effect of electrolytes tumor necrosis factor (TNF)-α and IgE on AR and study the influence of smoking, gender, and obesity (as a risk factor on AR) on the levels of TNF-α and IgE. Materials and Methods: Eighty subjects for this study were enrolled; 40 of those who have AR age ranged between 18 and 50 years. A control group of 40 subjects who appear to be in good health was selected. This study is a case–control study. TNF-alpha concentration and immunoglobulin-E were measured in serum by an enzyme-linked immunosorbent assay (ELISA) technique also The electrolytes concentrations were measured in the serum using an Abbott device with Integrated Chip Technology (ICT) human kit. The electrolytes were also measured in the serum using the Abbott device. Full history was taken from all patients, which include age, residence, smoking, body mass index, and family history of AR. Results: The results reveal a significant difference (P &lt; 0.05) in levels of TNF-α, Ig-E between patients and controls, There was no significant difference between smoker and non- smoker, normal weight and overweight groups in patients and controls groups.

Differential effects of heart failure with reduced ejection fraction on locomotor and respiratory muscles

Abstract Background Muscle weakness impairs quality-of-life, exercise capacity, and survival in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). However, the effects on systemic concentrations and local expression of inflammatory cytokines and myokines as well as metabolic markers might differ between locomotor and respiratory muscles. Purpose We prospectively evaluated clinical, functional, and molecular alterations of the diaphragm and the M. vastus lateralis (MVL) from HFrEF patients receiving a left ventricular assist device compared to patients without heart failure undergoing elective coronary bypass grafting (control). Methods Participants (Controls=21, HFrEF=18) underwent cardiopulmonary exercise and respiratory and leg muscle testing. Serum concentrations and local expression of inflammatory cytokines and myokines as well as key enzymes of metabolic pathways were examined in biopsies of the diaphragm and MVL. Results Exercise capacity, respiratory muscle function and endurance force of locomotor muscles were significantly reduced in HFrEF compared with controls (all p&amp;lt;0.05). The serum concentration of Il-6, Il-1beta and TNF-alpha were significantly higher or solely detectable in HFrEF compared with controls. Local mRNA expression of Il-6 was not different in MVL but 2.2-fold higher in the diaphragm of HFrEF compared with controls (p=0.013). In contrast, mRNA expression of Il-6 receptor was significantly reduced by 38% (p=0.004) in MVL of HFrEF compared with controls but comparable in the diaphragm. Serum concentrations of FGF-21 and Musclin were significantly higher in HFrEF compared with controls (all p&amp;lt;0.05). Local mRNA expression of FGF-21 was significantly lower in both MVL and diaphragm of HFrEF compared with controls. FGF-21 receptor 1 mRNA expression was reduced by 18% in the MVL of HFrEF (p=0.02), whereas co-receptor klotho was comparable to controls. In the diaphragm, FGF-21 receptor 1 mRNA expression was comparable between HFrEF and controls, but the co-receptor klotho had a 5-fold higher mRNA expression in HFrEF (p=0.002). We examined the activity of key enzymes of glucose, lipid and ketone metabolism as well as key enzymes of the Krebs cycle. The main differences were found for ß-hydroxyacyl-CoA Dehydrogenase in the diaphragm with a 1.6-fold higher activity in HFrEF compared with controls (p=0.01) and for succinyl-CoA: 3-ketoacid-coenzyme A transferase in the MVL with a 2-fold higher activity in HFrEF compared with controls (p&amp;lt;0.01) indicating a main utilization of lipids in the diaphragm and of ketones in the MVL for energy supply. Conclusions HFrEF induced divergent effects on inflammatory markers, myokine expression and metabolic parameters in locomotor and respiratory muscles in HFrEF patients compared with controls. This indicates that different molecular alterations contribute to locomotor/respiratory muscle dysfunction and reduced whole-body exercise capacity.

Molecular Characterisation of Blood Microbiome in Patients with Ankylosing Spondylitis and Healthy Controls.

In human and animal studies, ankylosing spondylitis (AS) has been increasingly linked to changes in the microbial inhabitants in the human body (microbiome). These studies have primarily now concentrated on the microbial communities that live in the gastrointestinal tract. However, evidence suggests that various molecular techniques can be used to detect microbial DNA in blood circulation. This DNA might be an unknown reservoir of biomarkers with the potential to track alterations in the microbiomes of remote locations, such as the gut. To this end, we compared the presence and identity of microbial DNA in blood samples taken from ankylosing spondylitis patients to healthy control subjects by amplifying and sequencing the bacterial 16S rRNA variable region four. The study's design is a case study based on the presence and identity of bacterial DNA in the blood of Ankylosing spondylitis (AS) patients (n = 10) and healthy control subjects (n = 10) was investigated by amplifying and sequencing the bacterial 16S rRNA gene. Blood concentrations of the cytokines TNF alpha, IL-17A, and IL-23 were determined by the Human Magnetic Luminex Screening, and data were analysed using an Unpaired T-test. Using PCR amplification, 8 of 10 AS patients (80%) and 8 of 10 healthy control samples (80%) had microbial 16S rRNA in their blood. At the phylum level, Proteobacteria (Control = 48.5%, AS = 52%), Firmicutes (Control = 27.8%, AS = 26.1%), Actinobacteria (Control = 15.4%, AS = 10.7%), and Bacteroidetes (Control = 6.5%, AS = 10%) dominated the blood microbiome. A two-tailed Mann-Whitney test found that Ankylosing Spondylitis was associated with significantly elevated Bacteroides (P < 0.05), Prevotella (P < 0.001), and Micrococcus (P < 0.01), and significantly reduced levels of Corynebacterium 1 (P < 0.001), Gemella (P < 0.01), and Alloprevotella (P < 0.05), compared to healthy controls. Additionally, it was shown that the presence of the Prevotella genus was highly positively correlated with higher levels of TNF-alpha (P < 0.05; r = 0.8) in AS patients' blood. This article reveals that a blood microbiome exists in healthy individuals and identifies particular taxa modulated in disease. These blood-derived signatures indicate that this field needs more research and may be helpful as disease biomarkers.

The p38-MITOGEN-ACTIVATED PROTEIN KINASE Signaling Pathway Is Involved in Leonurus artemisia Extract-Induced Inhibition of the Proliferation of Human Bladder Cancer BFTC-905 Cells via G1/G0 Arrest and Causes Apoptosis In Vitro.

Bladder cancer is a urothelial malignancy. Bladder cancer starts in the urothelial cells lining the inside of the bladder. The 5-year recurrence rate for bladder cancer ranges from 31% to 78%, and the progression rate is approximately 45%. To treat bladder cancer, intravesical drug therapy is often used. Leonurus artemisia extract (LaE) was obtained from medicinal samples of Chinese motherwort Scientific Chinese Medicine; L. artemisia has various biological effects. This study investigated the impact of LaE on human bladder cancer cells (the BFTC-905 cell line) and the molecular mechanism underlying apoptosis resulting from the activation of cell signal transduction pathways in bladder cancer cells. A cell counting kit-8 (CCK-8) assay was used to determine the effect of LaE on cell growth. The effect of LaE on migration ability was observed using a wound healing assay. The effects of LaE on the cell cycle, reactive oxygen species production, and apoptosis were investigated. Western blot analysis detected apoptosis-related and mitogen-activated protein kinase signaling pathway-related protein concentrations. At non-toxic concentrations, LaE inhibited the proliferation of BFTC-905 cells in a concentration-dependent manner, and the half-maximal inhibitory concentration (IC50) was 24.08172 µg/µL. LaE impaired the migration ability of BFTC-905 cells. LaE arrested the cell cycle in the G1 and G0 phases, increased reactive oxygen species production, and induced apoptosis. LaE increased Bax and p-ERK concentrations and decreased Bcl-2, cleaved caspase-3, and p-p38 concentrations. No differences in PARP, C-PARP, vimentin, e-cadherin, p-JNK, or TNF-alpha concentrations were observed. These results suggest that LaE inhibits the proliferation of human bladder cancer cells. Moreover, the mitogen-activated protein kinase signaling pathway is involved in the inhibition of the proliferation of BFTC-905 cells.

Investigating the Role of Serum and Plasma IL-6, IL-8, IL-10, TNF-alpha, CRP, and S100B Concentrations in Obstructive Sleep Apnea Diagnosis.

Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with cardiovascular diseases, depression, accidents, and stroke. There is an increasing need for alternative diagnostic tools beyond overnight sleep studies that measure the Apnea/Hypopnea Index (AHI). In this single-center, case-control study, we evaluated serum and plasma concentrations of IL-6, IL-8, IL-10, TNF-α, CRP, and S100B in 80 subjects, including 52 OSA patients (27 moderate [15 ≤ AHI ˂ 30], 25 severe [AHI ≥ 30]) and 28 non-OSA controls (AHI 0-5). Participants with OSA showed approximately 2 times higher median concentrations of CRP in plasma, and IL-6 in serum, as well as 1.3 to 1.7 times higher concentrations of TNF-α and IL-8 in plasma compared with the control group. Receiver Operator Characteristic (ROC) curve analysis was performed to evaluate the predictive capabilities of these serum and plasma biomarkers in distinguishing between the OSA and control groups, revealing varying sensitivity and specificity. In summary, in this study, serum and plasma biomarkers CRP, S100B, IL-6, TNF-α, and IL-8 have been shown to be elevated in patients with OSA, correlated positively with disease severity, age, and BMI. These results support the potential role of these biomarkers in diagnosing OSA, supplementing traditional methods such as overnight sleep studies.

Umbilical Cord Stem Cell Lysate: A New Biologic Injectate for the Putative Treatment of Acute Temporomandibular Joint Inflammation.

To compare in vivo, the acute anti-inflammatory effects of a lysate derived from human umbilical perivascular mesenchymal cells with the cells themselves in both an established hind-paw model of carrageenan-induced inflammation and also in the inflamed temporomandibular joint. Human umbilical cord perivascular cells were harvested and cultured in xeno- and serum-free conditions to P3. In addition, P3 cells were used to prepare a proprietary 0.22 micron filtered lysate. First, CD1 immunocompetent mice underwent unilateral hind-paw injections of carrageenan for induction of inflammation, followed immediately by treatment with saline (negative control), 1% cell lysate, or viable cells. The contralateral paw remained un-injected with carrageenan. Paw circumference was measured prior to injections and 48 hr later and myeloperoxidase and TNF-alpha concentrations were measured post-sacrifice in excised tissue. Second, immunocompetent Male Wistar rats underwent unilateral intra-articular temporomandibular (TMJ) injections from the same treatment groups and were sacrificed at 4 and 48 hr post-injection. The contralateral TMJ remained un-injected with carrageenan. Articular tissue and synovial aspirates, from the treated TMJ were obtained for histologic and leukocyte infiltration analyses. The lysate and cell-treated hind-paw demonstrated reduced tissue edema, and significantly lower concentrations of myeloperoxidase and TNF-alpha at 48 hr compared to untreated controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium compared to controls and histologic evidence, in the peri-articular tissue, of reduced inflammation. In this preliminary study, both the human umbilical perivascular cells and a highly diluted lysate produced therefrom were anti-inflammatory.

#3195 PATIENTS ON HD WITH CENTRAL CATHETERS LOCKED WITH TAUROLIDINE HAVE A SIMILAR INFLAMMATORY PROFILE TO SUBJECTS WITH NATIVE ARTERIOVENOUS FISTULA

Abstract Background and Aims Inflammation is a near-universal condition in haemodialysis (HD) patients, which contributes to increased complications, morbidity and mortality. The inflammatory profile is enhanced in subjects who need a central venous catheter (CVC) as vascular access in comparison with patients with native arteriovenous fistula (AVF), the optimal vascular access for HD. The aim of the present study was to analyse the inflammatory profile of HD patients according to their vascular access (CVC vs AVF), and to evaluate whether Taurolidine-citrate-heparin lock solution (TCH; taurolidine 1.35%, citrate 4% and heparin 500 IU) is able to modulate the inflammatory state of patients with CVC towards an inflammatory profile similar to that observed in subjects with AVF. Method A total of 109 patients with AVF or tunneled CVC under regular haemodialysis for more than 6 months were screened. Exclusion criteria included intercurrent infections in the previous 3 months, active inflammatory or immunologic diseases, and treatment with antibiotics or drugs affecting the immune system. Finally, 85 patients were included in the study and classified according to the vascular access: 25 patients with AVF and 60 with CVC. Subsequently, two subgroups were formed from the group of patients with tunneled CVC according to a heparin-containing catheter lock solution with (CVC-TCH) and without taurolidine-citrate (CVC-Hep). Subsequently, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) concentrations in serum and messenger ribonucleic acid (mRNA) gene expression levels of IL-6 and TNF-alpha in peripheral blood mononuclear cells (PBMC) were measured at inclusion and after three months follow-up. Results Altogether eighty-five subjects (42 males and 43 females; mean age 61 ± 9 yrs; 39% diabetics) were initially included in the study. In 25 subjects the vascular access was AVF, while the rest used tunneled CVC; of these 31 used standard CVC-Hep and 29 used CVC-TCH. Five patients dropped out the study and thus 80 patients completed the 3-month follow-up and were finally evaluated. At inclusion, patients with CVC had significantly higher serum and expression levels of inflammatory parameters compared to subjects with AVF. After 3 months, there were no significant changes in inflammatory markers in subjects with AVF compared to baseline, whereas in subjects with CVC-Hep a significant increase in serum and gene expression of IL-6 could be observed. On the contrary, subjects with CVC-TCH experienced a decrease of all parameters compared to baseline, of which differences in serum IL-6 and gene expression levels of IL-6 and TNF-alpha were significant. After 3 months of follow-up there was no significant difference in any inflammatory parameter when comparing patients with CVD-TCH with those with AVF (Table). Conclusion In patients under HD with cuffed tunneled CVC, the use of TCH lock solution after each HD session is associated with a significant improvement in the inflammatory serum and gene expression state. Thus, the inflammatory profile of patients with CVC using TCH does not differ from that of patients with native AVF after at least three months of CVC-TCH use.

Effect of Administration of Selenium Nanoparticles Synthesized Using Onion Extract on Biochemical and Inflammatory Parameters in Mice Fed with High-Fructose Diet: In Vivo and In Silico Analysis.

Fructose consumption has increased globally and has been linked to obesity, insulin resistance, and diabetes. Selenium nanoparticles (SeNPs) can regulate glucose and lipid concentrations and have immunoregulatory properties. Four study groups (n = 7/group) of eight-week-old male mice (Balb/c) were formed for this investigation. One group received a standard diet (C), another standard diet plus SeNPs (C + SeNPs), a high fructose diet (F), and a group with a high fructose diet plus SeNPs (F + SeNPs). Weight, glucose, triglycerides, and cholesterol were evaluated. In the end, mice were sacrificed, blood samples were obtained to assess cytokine profile, and liver, kidney, and pancreas were removed for histological examination. The study was complemented with an in silico analysis where the CTD, STITCH, ToppGene Suite, ShinyGO 0.76.3 databases, and Cytoscape software were implemented. The results of in vivo analysis showed that SeNPs regulated biochemical parameters and showed anti-inflammatory effects by decreasing the concentrations of TNF-alpha, IL-1beta, and IFN-gamma and increasing IL-10. No damage was observed in the studied organs. In addition, SeNPs regulate oxidative stress, preserve cell organelles, and regulate metabolic pathways to avoid the adverse effects of fructose consumption, according to bioinformatics analysis. In conclusion, SeNPs protect against the undesirable effects of a diet rich in fructose.

Effect of intermittent fasting on circulating inflammatory markers in obesity: A review of human trials.

Obesity is associated with low-grade inflammation. Weight loss, by means of dietary restriction, has been shown to reduce systemic inflammation. Intermittent fasting has recently gained popularity as a weight loss diet, but its effects on inflammatory markers in individuals with obesity have yet to be summarized. Accordingly, this review examined how the two main forms of intermittent fasting, i.e., time restricted eating (TRE) and alternate day fasting (ADF), impact body weight and key circulating inflammatory markers (i.e., C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6)), in adults with obesity. Results from this review reveal that TRE with various eating window durations (4-10 h per day) has no effect on circulating levels of CRP, TNF-alpha or IL-6, with 1-5% weight loss. As for ADF, reductions in CRP concentrations were noted when >6% weight loss was achieved. However, ADF had no effect on TNF-alpha or IL-6 concentrations, with this degree of weight loss. Thus, intermittent fasting has little or no effect on key inflammatory markers, but more research is warranted to confirm these preliminary findings.

Influence of Different Orthodontic Brackets on Cytokine and Cortisol Profile

Background and Objectives: Orthodontic tooth movement (OTM) requires bone remodeling resulting from complex processes of aseptic inflammation. Recent studies have confirmed close interaction between the immune and skeletal systems. In addition, various orthodontic appliances including fixed systems affect the sublingual microbial composition, and the likelihood of developing inflammatory reactions of the gums is high, especially early in the treatment period. It is known that these systems have both positive and negative effects on the humoral and cellular immune responses. The main aim of the study was to evaluate the influence of self-ligating and conventional brackets on the salivary concentrations of cytokines (IL-6, osteoprotegerin (OPG), TNF-alpha, and IFN-gamma) and cortisol as a marker of stress. Materials and Methods: Forty patients were analyzed at baseline (T0) and 2 months (T2) after fixing self-ligating (Ormco Damond Q) and conventional brackets (Ormco Mini Diamond). Salivary cytokine and cortisol concentrations were evaluated by commercial ELISA kits. Results: Outcomes of our study showed that after two months of treatment with either of these brackets, IFN-gamma and IL-6 levels did not change. However, TNF-alpha decreased with self-ligating brackets (13.36 to 8.32, p = 0.002). The self-ligating bracket system also affects OPG concentration and cortisol levels 2 months after orthodontic activation. The level of OPG in the group of self-ligating brackets decreased significantly (8.55 to 2.72, p = 0.003). Cortisol concentration was significantly higher in the self-ligation group (25.72 to 48.45, p = 0.001) due to the effect of sustained strength movements. Conclusions: Thus, the use of self-ligating and conventional brackets has a different effect on the concentration of cortisol and cytokines (OPG and TNF-alpha) in saliva 2 months after their fixation. Further longitudinal studies are necessary to explore why OPG levels are decreased in case of self-ligating cases and how OPG levels are related to clinical improvement.