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Intestinal permeabilization is central to the pathophysiology of chronic gut inflammation. This study investigated the efficacy of glucoraphanin (GR), prevalent in cruciferous vegetables, particularly broccoli, and its derivative sulforaphane (SF), in inhibiting tumor necrosis factor alpha (TNFα)-induced Caco-2 cell monolayers inflammation and permeabilization through the regulation of redox-sensitive events. TNFα binding to its receptor led to a rapid increase in oxidant production and subsequent elevation in the mRNA levels of NOX1, NOX4, and Duox2. GR and SF dose-dependently mitigated both these short- and long-term alterations in redox homeostasis. Downstream, GR and SF inhibited the activation of the redox-sensitive signaling cascades NF-κB (p65 and IKK) and MAPK ERK1/2, which contribute to inflammation and barrier permeabilization. GR (1 μM) and SF (0.5-1 μM) prevented TNFα-induced monolayer permeabilization and the associated reduction in the levels of the tight junction (TJ) proteins occludin and ZO-1. Both GR and SF also mitigated TNFα-induced increased mRNA levels of the myosin light chain kinase, which promotes TJ opening. Molecular docking suggests that although GR is mostly not absorbed, it could interact with extracellular and membrane sites in NOX1. Inhibition of NOX1 activity by GR would mitigate TNFα receptor downstream signaling and associated events. These findings support the concept that not only SF, but also GR, could exert systemic health benefits by protecting the intestinal barrier against inflammation-induced permeabilization, in part by regulating redox-sensitive pathways. GR has heretofore not been viewed as a biologically active molecule, but rather, the benign precursor of highly active SF. The consumption of GR and/or SF-rich vegetables or supplements in the diet may offer a means to mitigate the detrimental consequences of intestinal permeabilization, not only in disease states but also in conditions characterized by chronic inflammation of dietary and lifestyle origin.

Background: Gastrointestinal dysfunction frequently occurs following traumatic brain injury (TBI) and significantly increases posttraumatic complications. TBI can lead to alterations in gut microbiota. The neuroprotective effects of hyperbaric oxygen (HBO) have not been well recognized after TBI. The study''s aim was to investigate the impact of HBO on TBI-induced dysbiosis in the gut and the pathological changes in the brain following TBI. Methods: Anesthetized male Sprague–Dawley rats were randomly assigned to three groups: sham surgery plus normobaric air (21% oxygen at 1 atmospheres absolute), TBI (2.0 atm) plus normobaric air, and TBI (2.0 atm) plus HBO (100% oxygen at 2.0 atmospheres absolute) for 60 min immediately after TBI, 24 h later, and 48 h later. The brain injury volume, tumor necrosis factor-α expression in microglia and astrocytes, and neuronal apoptosis in the brain were subsequently determined. The V3–V4 regions of 16S ribosomal rRNA in the fecal samples were sequenced, and alterations in the gut microbiome were statistically analyzed. All parameters were evaluated on the 3rd day after TBI. Results: Our results demonstrated that HBO improved TBI-induced neuroinflammation, brain injury volume, and neuronal apoptosis. HBO appeared to increase the abundance of aerobic bacteria while inhibiting anaerobic bacteria. Intriguingly, HBO reversed the TBI-mediated decrease in Prevotella copri and Deinococcus spp., both of which were negatively correlated with neuroinflammation and brain injury volume. TBI increased the abundance of these gut bacteria in relation to NOD-lik0065 receptor signaling and the proteasome pathway, which also exhibited a positive correlation trend with neuro inflammation and apoptosis. The abundance of Prevotella copri was negatively correlated with NOD-like receptor signaling and the Proteasome pathway. Conclusions: Our study demonstrated how the neuroprotective effects of HBO after acute TBI might act through reshaping the TBI-induced gut dysbiosis and reversing the TBI-mediated decrease of Prevotella copri. [ABSTRACT FROM AUTHOR]

BACKGROUND: Molecular mechanisms targeting the miRNA/mRNA axis to regulate osteoarthritis disease process have been studied. We identified the mRNA: phospholipase C delta 3 (PLCD3) and its target miRNA(miR-34a-5p) with clinical predictive value through previous bioinformatics studies, while experiments to verify their specific roles and mechanisms in regulating osteoarthritis are still lacking. OBJECTIVE: To investigate the regulatory role and mechanism of miR-34a-5p/PLCD3 axis on osteoarthritis progression. METHODS: The synovium of 15 patients with knee osteoarthritis was selected as the osteoarthritis group, and the synovium of 15 young patients with internal fixation of patellar fracture caused by trauma during the same period was selected as the control group. The expression of PLCD3 and miR-34a-5p in the synovium was detected by real-time PCR. Human fibroblast like synovial cells-osteoarthritis (HFLS-OA) cells were treated by cell transfection and divided into miR-34a-5p mimic group, pCDH-PLCD3 group, miR-34a-5p mimic+pCDH-PLCD3 group, miR-34a-5p inhibitor group, si-PLCD3 group, and miR-34a-5p inhibitor+si-PLCD3 group. The relationship between PLCD3 and miR-34a-5p expression was detected by real-time PCR. The effects of HFLS-OA cell viability and cell migration in each group were detected by CCK-8 assay and cell scratch test. Western blot assay was used to detect the expression level of apoptosis marker protein. The expression of inflammatory factors was detected by ELISA. RESULTS AND CONCLUSION: (1) PLCD3 was a direct target of miR-34a-5p, and the expression levels of PLCD3 and miR-34a-5p were negatively correlated. (2) Upregulation of PLCD3 promoted proliferation of HFLS-OA cells and inhibited cell migration. The up-regulation of miR-34a-5p significantly inhibited the activity of HFLS-OA cells and enhanced cell migration. Overexpression of miR-34a-5p significantly increased the levels of Casp3 and Casp9 proteins in HFLS-OA cells, while overexpression of PLCD3 showed the opposite trend. (3) PLCD3 overexpression significantly increased the expression of interleukin 6 and tumor necrosis factor alpha in HFLS-OA cells, while miR-34a-5p mimics showed protective activity. (4) The miR-34a-5p/PLCD3 axis may affect the progression of osteoarthritis by regulating the inflammatory process or apoptosis of synovial cells. [ABSTRACT FROM AUTHOR]

Acute cutaneous lupus erythematosus (ACLE) is closely associated with systemic symptoms in systemic lupus erythematosus (SLE). This study aimed to identify potential biomarkers for ACLE and explore their association with SLE to enable early prediction of ACLE and identify potential treatment targets for the future. In total, 185 SLE‐diagnosed patients were enrolled and categorized into two groups: those with ACLE and those without cutaneous involvement. After conducting logistic regression analysis of the differentiating factors, we concluded that tumor necrosis factor‐alpha (TNF‐α) is an independent risk factor for ACLE. Analysis of the receiver operating characteristic revealed an area under the curve of 0.716 for TNF‐α. Additionally, both TNF‐α and ACLE are positively correlated with disease activity. TNF‐α shows promise as a biomarker for ACLE, and in SLE patients, ACLE may serve as a clear indicator of moderate‐to‐severe disease activity. [ABSTRACT FROM AUTHOR]

Background: Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression. Methods: We conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m2), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis. Results: Serum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737—0.960), sensitivity of 81%, and specificity of 71%. Conclusion: This study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system that affects the myelinated axons of the central nervous system and causes neurological deterioration. The prevalence of this disease in women is reported to be 3 times that of men. In recent years, more people with the disease have sought alternative drug therapies to manage symptoms, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. The present study was conducted with the aim of investigating the effect of eight weeks of yoga training on the serum levels of tumor necrosis factor alpha, interleukin 6, interleukin 10 and body composition in women with multiple sclerosis. Materials and Methods: In this semi-experimental study, 20 women with multiple sclerosis who were referred to the medical centers of Semnan city (mean±SD; age, 36.75±6.10 years; body mass index, 26.88±6.02 kg/m2; and with EDSS index >3.5) were selected and randomly divided into two groups of yoga training (n=10) and control (n=10). The experimental group performed yoga training for eight weeks, three sessions per week (24 sessions) in an indoor hall with a temperature of 25-26°C. The training protocol started with performing two sets of 10 seconds for 15 movements and to observe the overload principle every two weeks, 5 seconds were added for each training movement and one movement was added to the training protocol, where at the final week number of movements reached 18 movements and 15 seconds. During this period, the control group had no regular physical activity and had normal daily activities. In order to determine and control the training pressure, the Borg's rate of perceived exertion (RPE) scale was used. Statistical analysis of the data was performed by using the repeated measures of ANOVA, independent t-test and dependent t-test at a significance level of p≤0.05. Results: The results of this study showed a significant decrease in the serum levels of tumor necrosis factor alpha, interleukin 6 and interleukin 10 in the experimental group compared to the control group after eight weeks of training (p=0.001). However, no significant difference was observed in the body composition of women with multiple sclerosis compared to the control group after eight weeks of yoga (p>0.05).Conclusion: Finally, the results of this research showed that eight weeks of yoga training by reducing inflammatory cytokines and adjusting the serum index of tumor necrosis factor alpha and interleukin 6, can be used as a complementary treatment along with drug treatments for patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background: Mammary gland carcinoma is a malignant type of cancer that occurs in mammae tissue. Dimethylbenzene (α) anthracene (DMBA) is a carcinogenic agent that causes mammary cancer by damaging cellular DNA. Flavonoids found in the black soybean (Glycine max L. Merr) exhibit anti-carcinogenic effects. Aim: This study evaluated the anticarcinogenic effects of black soybean extract. Methods: The activity of flavonoid compounds in black soybean was determined in silico. Five groups of rats, four in each group, were established, consisting of a negative control, a positive control, and three treatment groups. Treatment included black soybean extract administration (i.e., T1 = 200, T2 = 400, and T3 = 800 mg of black soybean extract/kg body weight for 10 days). The observed parameters included the immunohistochemical analysis of BRCA1 and TNF-α. Results: Based on an in silico study, compounds from black soybeans are non-toxic. Functional annotation analysis revealed that most of the target proteins have a role in biological processes associated with cancer development. An in vivo analysis using an animal mammae cancer model indicated that black soybean extracts inhibited mammae cancer progression by attenuating TNF-α and BRCA1 expression. Conclusion: The most effective dosage of black soybean extract was 200 mg/kg body weight. An increase in BRCA1 and TNF-α expression may be related to the effects of catechin, daidzein, genistein, and glycitein, which are present in black soybeans. [Open Vet J 2024; 14(10.000): 2678-2686]

Abstract Background Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression. Methods We conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR

Background Acute kidney injury (AKI) is a common complication of sepsis. Immune-inflammatory markers are commonly used to assess the prognosis of these patients. However, studies evaluating microRNAs (miR) in this context are scarce, indicating a need for further clinical investigation. Objective To investigate the expression of serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and miR in pediatric patients with sepsis-induced AKI and analyze their prognostic assessment value. Methods This study included 100 pediatric patients with sepsis-induced AKI admitted to the First People's Hospital of Pingdingshan from March 2020 to March 2023 as the observation group, and 80 pediatric patients with sepsis alone as the control group. General patient data were collected, and serum levels of SAA, IL-6, and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). The relative expression of miR-21-3p, miR-182-5p, and miR-128-3p was quantified using real-time quantitative PCR. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health EvaluationⅡ (APACHE Ⅱ) score were compared between the groups. Pearson correlation analysis was used to evaluate the relationship between the levels of serum SAA, IL-6, TNF-α, and miRs and the SOFA and APACHEⅡ scores. Receiver operating characteristic (ROC) curves were plotted to explore the predictive value of these markers for mortality in pediatric patients with sepsis-induced AKI and to calculate the area under the ROC curve (AUC) . Results The observation group showed significantly higher SOFA scores, APACHE Ⅱ scores, and levels of serum SAA, IL-6, TNF-α, miR-21-3p, miR-182-5p, and miR-128-3p compared to the control group (P

Aim: systemically assessed characteristics of intestinal microbiota taxonomic composition in relation to parameters of hormonal and immune status in patients with external genital endometriosis (EGE).Materials and Methods. The controlled cross-sectional study included 33 patients with EGE comprising main group, and 30 healthy women enrolled to control group. All women underwent assessment of hormonal status and cytokine expression levels in peripheral blood. Level of blood hormones estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) was carried out using enzyme-linked immunosorbent and chemiluminescent assays. Expression levels of cytokines such as interleukin (IL) IL-6, IL-8, tumor necrosis factor alpha (TNF-α) were analyzed by an enzyme-linked immunosorbent assay. Taxonomic composition of intestinal microbiota at the level of phyla and genera was carried out by 16S ribosomal RNA gene sequencing. Microbial community a-diversity, the Chao1, ACE, and Sobs indices were used.Results. The concentration of blood E2 in main group was significantly higher compared to control group. Also, women with EGE had higher plasma concentrations for IL-6, IL-8, IL-17 and TNF-a compared to those in control group (p < 0.001). While analyzing bacterial community a-diversity in main group, Chao1 index was found to be significantly decreased. At the phylum level, the Firmicutes/Bacteroidetes ratio was increased in patients with EGE compared with that in control group. Among the 20 largest genera in patients with EGE, significant abundance was observed for Lachnospira, Blautia, Dorea, Streptococcus, Eubacterium hallii_group paralleled with significant decline in Bifidobacterium and Eubacterium eligens_group. A positive correlation was obtained between estrogen levels and the number of representatives from the genera Eubacterium hallii_group and Streptococcus, IL-8 and Streptococcus, TNF-α and Streptococcus and Lachnospira, as well as a negative correlation between TNF-α and Bifidobacterium.Conclusion. A relation between dysbiotic intestinal alterations and developing endometriosis was found. The identified correlations between altered taxonomic composition of the intestinal microflora and parameters of hormonal and immune status in patients with EGE suggest that intestinal microbiota is involved in pathophysiology of endometriosis.

Background: Periodontitis is a chronic multifactorial disease caused by microorganisms such as G-anaerobes in the periodontal tissues. It activates host defense cells and releases inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). Ganoderma lucidum is a traditional medicinal mushroom with anti-inflammatory effects against various diseases. Biologically, different levels of its active constituents, such as triterpenoids and phenolic compounds, reduce inflammation with various pathways. Furthermore, the constituents inhibit toll-like receptor 4, MyD88 receptors, and the activities of nuclear factor-kappa B, which synthesize TNF-α and PGE2. Purpose: This study aimed to analyze the extent to which G. lucidum extract can reduce TNF-α and PGE2 levels in periodontitis model Sprague Dawley rats. Methods: Thirty Sprague Dawley rats were randomly divided into six groups of five rats. Periodontitis inflammation was induced by the injection of Porphyromonas gingivalis bacteria into intrasulcular gingival incisors in the lower jaw labial section. Grouping was as follows: Group K1 (healthy control); Group K2 (negative control); Group K3 (positive control with doxycycline dose 0.27 mg/kg BW); Group P1 (G. lucidum extract dose 5 mg/kg BW); Group P2 (G. lucidum extract dose 10 mg/kg BW); and Group P3 (G. lucidum extract dose 20 mg/kg BW). Samples were taken from rat gingival tissue and the levels of TNF-α and PGE2 were examined using the enzyme-linked immunosorbent assay method. Data analysis was performed using one-way analysis of variance (ANOVA) with a confidence level of 95% (p < 0.05). Results: The levels of TNF-α and PGE2 were the highest in the K2 group and the lowest in the K1 group. One-way ANOVA showed no significant difference in TNF-α and PGE2 levels between P3 and K1 group. Conclusion: G. lucidum extract can reduce TNF-α and PGE2 levels in Sprague Dawley rats with periodontitis.

Background and Purpose: Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system that affects the myelinated axons of the central nervous system and causes neurological deterioration. The prevalence of this disease in women is reported to be 3 times that of men. In recent years, more people with the disease have sought alternative drug therapies to manage symptoms, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. The present study was conducted with the aim of investigating the effect of eight weeks of yoga training on the serum levels of tumor necrosis factor alpha, interleukin 6, interleukin 10 and body composition in women with multiple sclerosis. Materials and Methods: In this semi-experimental study, 20 women with multiple sclerosis who were referred to the medical centers of Semnan city (mean±SD; age, 36.75±6.10 years; body mass index, 26.88±6.02 kg/m2; and with EDSS index >3.5) were selected and randomly divided into two groups of yoga training (n=10) and control (n=10). The experimental group performed yoga training for eight weeks, three sessions per week (24 sessions) in an indoor hall with a temperature of 25-26°C. The training protocol started with performing two sets of 10 seconds for 15 movements and to observe the overload principle every two weeks, 5 seconds were added for each training movement and one movement was added to the training protocol, where at the final week number of movements reached 18 movements and 15 seconds. During this period, the control group had no regular physical activity and had normal daily activities. In order to determine and control the training pressure, the Borg’s rate of perceived exertion (RPE) scale was used. Statistical analysis of the data was performed by using the repeated measures of ANOVA, independent t-test and dependent t-test at a significance level of p≤0.05. Results: The results of this study showed a significant decrease in the serum levels of tumor necrosis factor alpha, interleukin 6 and interleukin 10 in the experimental group compared to the control group after eight weeks of training (p=0.001). However, no significant difference was observed in the body composition of women with multiple sclerosis compared to the control group after eight weeks of yoga (p>0.05). Conclusion: Finally, the results of this research showed that eight weeks of yoga training by reducing inflammatory cytokines and adjusting the serum index of tumor necrosis factor alpha and interleukin 6, can be used as a complementary treatment along with drug treatments for patients with multiple sclerosis.

Background and Aim: The increase in inflammatory markers, including TNF-α, contributes to the development and progression of cardiovascular complications. This study aimed to investigate the effects of six weeks of total body resistance training (TRX) and oral consumption of aqueous extract of mango leaves (Mangifera indica) on serum TNF-α level and body mass index (BMI) in overweight and obese non-athletic men. Methods: In this semi-experimental study, 48 overweight and obese non-athletes aged 20 to 25 years were randomly assigned to four groups: control, mango leaf extract, exercise + placebo, and exercise + extract. For six weeks (three sessions per week), participants engaged in total body resistance training (TRX) and consumed aqueous mango leaf extract (two capsules of 500 mg per day). Serum TNF-α level were measured 24 hours before the first session and 48 hours after the last training session using the ELISA method. Additionally, measurements for weight, BMI, and waist-to-hip ratio (WHR) were recorded. Results: After six weeks of intervention, serum TNF-α levels significantly decreased in the exercise + placebo, exercise + extract, and mango leaf extract groups compared to pre-test values (P = 0.0001). In the post-test, both the exercise + extract and exercise + placebo groups, along with the mango leaf extract group, demonstrated a significant reduction in TNF-α levels compared to the control group (P < 0.001). Furthermore, body weight, BMI, and WHR were significantly reduced in the exercise + placebo and exercise + extract groups compared to the mango leaf extract and control groups (P < 0.001). Conclusion: Six weeks of TRX training combined with the consumption of mango leaf extract may effectively reduce inflammatory markers such as TNF-α, as well as decrease BMI and WHR in young overweight and obese non-athletes. These findings suggest valuable insights for implementing effective exercise programs aimed at addressing obesity in young men.

Cutaneous papillomatosis occurs as benign tumoral skin lesions in cattle. Although this condition is most commonly observed in young animals, it can occur in cattle of any age. Although tumor necrosis factor alpha, high mobility group box-1 protein, myxovirus resistance protein-1 have been investigated in various tumoral conditions in human medicine, the relationship between these markers and other hematological indices have not been investigated in bovine papillomatosis with benign tumoral lesions. The purpose of the study is to determine the levels of these markers and their relationship with each other and with hematological indices. The study comprised two groups: the bovine papillomatosis (BP) group, consisting of animals with papillomatosis, and the control group, consisting of healthy animals. Each group consisted of 10 animals of different breeds and genders with an age of 1-2 years. In the BP group, there were significant differences in total leukocyte count, neutrophil count, monocyte count, and neutrophil-lymphocyte ratio values, which were higher, and lymphocyte-monocyte ratio values, which were lower. The levels of high mobility group box-1 protein, myxovirus resistance protein-1, and tumor necrosis factor alpha were significantly higher in the BP group compared to the control group. In conclusion, this study showed that there were significant differences in hematological, inflammation and tumor markers in cutaneous papillomatosis.

Cutaneous papillomatosis occurs as benign tumoral skin lesions in cattle. Although this condition is most commonly observed in young animals, it can occur in cattle of any age. Although tumor necrosis factor alpha, high mobility group box-1 protein, myxovirus resistance protein-1 have been investigated in various tumoral conditions in human medicine, the relationship between these markers and other hematological indices have not been investigated in bovine papillomatosis with benign tumoral lesions. The purpose of the study is to determine the levels of these markers and their relationship with each other and with hematological indices. The study comprised two groups: the bovine papillomatosis (BP) group, consisting of animals with papillomatosis, and the control group, consisting of healthy animals. Each group consisted of 10 animals of different breeds and genders with an age of 1-2 years. In the BP group, there were significant differences in total leukocyte count, neutrophil count, monocyte count, and neutrophil-lymphocyte ratio values, which were higher, and lymphocyte-monocyte ratio values, which were lower. The levels of high mobility group box-1 protein, myxovirus resistance protein-1, and tumor necrosis factor alpha were significantly higher in the BP group compared to the control group. In conclusion, this study showed that there were significant differences in hematological, inflammation and tumor markers in cutaneous papillomatosis. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic multifactorial disease caused by microorganisms such as G-anaerobes in the periodontal tissues. It activates host defense cells and releases inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). Ganoderma lucidum is a traditional medicinal mushroom with anti-inflammatory effects against various diseases. Biologically, different levels of its active constituents, such as triterpenoids and phenolic compounds, reduce inflammation with various pathways. Furthermore, the constituents inhibit toll-like receptor 4, MyD88 receptors, and the activities of nuclear factor-kappa B, which synthesize TNF-α and PGE2. Purpose: This study aimed to analyze the extent to which G. lucidum extract can reduce TNF-α and PGE2 levels in periodontitis model Sprague Dawley rats. Methods: Thirty Sprague Dawley rats were randomly divided into six groups of five rats. Periodontitis inflammation was induced by the injection of Porphyromonas gingivalis bacteria into intrasulcular gingival incisors in the lower jaw labial section. Grouping was as follows: Group K1 (healthy control); Group K2 (negative control); Group K3 (positive control with doxycycline dose 0.27 mg/kg BW); Group P1 (G. lucidum extract dose 5 mg/kg BW); Group P2 (G. lucidum extract dose 10 mg/kg BW); and Group P3 (G. lucidum extract dose 20 mg/kg BW). Samples were taken from rat gingival tissue and the levels of TNF-α and PGE2 were examined using the enzyme-linked immunosorbent assay method. Data analysis was performed using one-way analysis of variance (ANOVA) with a confidence level of 95% (p < 0.05). Results: The levels of TNF-α and PGE2 were the highest in the K2 group and the lowest in the K1 group. One-way ANOVA showed no significant difference in TNF-α and PGE2 levels between P3 and K1 group. Conclusion: G. lucidum extract can reduce TNF-α and PGE2 levels in Sprague Dawley rats with periodontitis. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionsTo reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation.This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay.The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7–2068) and 1027(453–2527), respectively], and were both significantly higher than the control group [(521.5(231.6–2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: –0.220 and p < 0.05, r: –0.252, respectively) and their DVD values (p < 0.001, r: –0.324 and p = 0.001, r: –0.299, respectively).Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients. [ABSTRACT FROM AUTHOR]

Osteoclasts are the cells primarily responsible for inflammation‐induced bone loss, as is particularly seen in rheumatoid arthritis. Increasing evidence suggests that osteoclasts formed under homeostatic versus inflammatory conditions may differ in phenotype. While microRNA‐29‐3p family members (miR‐29a‐3p, miR‐29b‐3p, miR‐29c‐3p) promote the function of RANKL‐induced osteoclasts, the role of miR‐29‐3p during inflammatory TNF‐α‐induced osteoclastogenesis is unknown. We used bulk RNA‐seq, histology, qRT‐PCR, reporter assays, and western blot analysis to examine bone marrow monocytic cell cultures and tissue from male mice in which the function of miR‐29‐3p family members was decreased by expression of a miR‐29‐3p tough decoy (TuD) competitive inhibitor in the myeloid lineage (LysM‐cre). We found that RANKL‐treated monocytic cells expressing the miR‐29‐3p TuD developed a hypercytokinemia/proinflammatory gene expression profile in vitro, which is associated with macrophages. These data support the concept that miR‐29‐3p suppresses macrophage lineage commitment and may have anti‐inflammatory effects. In correlation, when miR‐29‐3p activity was decreased, TNF‐α‐induced osteoclast formation was accentuated in an in vivo model of localized osteolysis and in a cell‐autonomous manner in vitro. Further, miR‐29‐3p targets mouse TNF receptor 1 (TNFR1/Tnfrsf1a), an evolutionarily conserved regulatory mechanism, which likely contributes to the increased TNF‐α signaling sensitivity observed in the miR‐29‐3p decoy cells. Whereas our previous studies demonstrated that the miR‐29‐3p family promotes RANKL‐induced bone resorption, the present work shows that miR‐29‐3p dampens TNF‐α‐induced osteoclastogenesis, indicating that miR‐29‐3p has pleiotropic effects in bone homeostasis and inflammatory osteolysis. Our data supports the concept that the knockdown of miR‐29‐3p activity could prime myeloid cells to respond to an inflammatory challenge and potentially shift lineage commitment toward macrophage, making the miR‐29‐3p family a potential therapeutic target for modulating inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common chronic inflammatory disorder affecting all aspects of a patient’s life. Nail involvement is frequent, but little is known about its associated inflammatory biomarker profile, including similarities or differences from cutaneous disease. Aim: We conducted this cross-sectional study to evaluate serum levels of inflammatory cytokines [tumour necrosis factor- alpha (TNF-α) and interleukin -17 (IL-17)] in patients with nail psoriasis and compared these to psoriasis patients without nail involvement, as well as in non-psoriatic healthy controls. Methods: Adult psoriasis patients with (Group I, n = 30) and without nail involvement (Group-II, n = 30) were sequentially recruited. In addition, non-psoriatic healthy controls (Group-III, n = 20) were recruited. The nail disease severity by NAPSI score was determined for patients in Group I. Cutaneous disease severity (by PASI score) and presence of psoriatic arthritis (through CASPAR criteria) were evaluated for patients in Groups I and II. Serum levels of TNF-α, IL-17, erythrocyte sedimentation rate (ESR), rheumatoid factor (RA factor), and anti-cyclic citrullinated peptide antibody (Anti-CCP) were evaluated for all three groups. Results: The median age was significantly higher for Group I as compared to Group II patients (41 ± 12.6 years vs 30 ± 12.4 years, p = 0.017). Group I patients also had higher median PASI score than Group II patients, although the difference was not statistically significant (10 ± 11.41 vs 6.50 ± 5.46, p = 0.275). The mean serum IL-17 levels were significantly higher for Group-I (113.39 ± 251.30 pg/mL) than Group II (27.91 ± 18.22 pg/mL, p = 0.002) and Group III (25.67 ± 12.08 pg/mL, p = 0.005). A weak positive correlation was found between NAPSI and serum IL-17 levels (Spearman’s Rho = 0.355) though not statistically significant (p = 0.054). Correlation between serum IL-17 and PASI was poor for Group-I patients (Spearman’s Rho = 0.13, p = 0.944) and strongly negative for Group-II patients (Spearman’s Rho = −0.368, statistically significant with p = 0.045). The mean serum levels of TNF-α were below the detection threshold of the assay kit, hence no meaningful comparison could be made. Limitations: A small sample size and low sensitivity of TNF-α assay kit. Conclusion: Our study showed that nail psoriasis could be independently associated with an elevation of IL-17. This can help choose appropriate drugs and estimate drug response in patients with nail psoriasis. [ABSTRACT FROM AUTHOR]

• Threats to social safety and inflammation is connected with risk of depression. • Inflammation has a mechanistic role in linking social threats to future depression. • Sexual minorities were more likely to display chronically elevated inflammation. • Increased coupling of inflammation and depression is more common in sexual minorities. Sexual minority individuals have a markedly elevated risk of depression compared to heterosexuals. We examined early threats to social safety and chronically elevated inflammation as mechanisms contributing to this disparity in depression symptoms, and compared the relative strength of the co-occurrence between chronic inflammation and depression symptoms for sexual minorities versus heterosexuals. To do so, we analyzed data from a prospective cohort of sexual minority and heterosexual young adults (n = 595), recruited from a nationally representative sample, that included assessments of early threats to social safety in the form of adverse childhood interpersonal events, three biomarkers of inflammation (i.e., CRP, IL-6, TNF-α) measured at two time points, and depression symptoms over four years. In pre-registered analyses, we found that sexual minorities experienced more adverse childhood interpersonal events, were more likely to display chronically elevated inflammation, and reported more severe depression symptoms than heterosexuals. Adverse childhood interpersonal events and chronically elevated inflammation explained approximately 23 % of the total effect of the association between sexual orientation and depression symptom severity. Further, there was an increased coupling of chronically elevated inflammation and depression symptoms among sexual minorities compared to heterosexuals. These results provide novel longitudinal, population-based evidence for the role of chronically elevated inflammation in linking threats to social safety during childhood with depression symptom severity in young adulthood, consistent with the primary tenets of the social signal transduction theory of depression. Our study extends this theory to the population level by finding that members of a stigmatized population (i.e., sexual minorities) experience a greater risk of depression because of their greater exposure to adverse childhood interpersonal events and the subsequent link to chronic inflammation, highlighting potential biopsychosocial intervention targets. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Introduction: Despite the established role of peripheral adenosine receptors in sepsis-induced organ dysfunction, little or no data is available on the interaction of central adenosine receptors with sepsis. The current study tested the hypothesis that central adenosine A3 receptors (A3ARs) modulate the cardiovascular aberrations and neuroinflammation triggered by sepsis and their counteraction by the cholinergic antiinflammatory pathway. Methods: Sepsis was induced by cecal ligation and puncture (CLP) in rats pre-instrumented with femoral and intracisternal (i.c.) catheters for hemodynamic monitoring and central drug administration, respectively. Results: The CLP-induced hypotension, reduction in overall heart rate variability (HRV) and sympathovagal imbalance towards parasympathetic predominance were abolished by i.v. nicotine (100 µg/kg) or i.c. VUF5574 (A3AR antagonist, 2 µg/rat). In addition, the selective A3AR agonist, 3-iodobenzyl-5'-N-methylcarboxamidoadenosine IB-MECA, 4 µg/rat, i.c.) exaggerated the hypotension and cardiac autonomic dysfunction induced by sepsis and opposed the favorable nicotine actions against these septic manifestations. Immunohistochemically, IB-MECA abolished the nicotine-mediated downregulation of NFκB and NOX2 expression in rostral ventrolateral medullary areas (RVLM) of brainstem of septic rats. The inhibitory actions of IB-MECA on nicotine responses disappeared after i.c. administration of PD98059 (MAPK-ERK inhibitor), SP600125 (MAPK-JNK inhibitor) or wortmannin (PI3K inhibitor). Moreover, infliximab (TNFα inhibitor) eliminated the IB-MECA-induced rises in RVLM-NFκB expression and falls in HRV, but not blood pressure. Conclusion: Central PI3K/MAPKs pathway mediates the A3AR counteraction of cholinergic defenses against cardiovascular and neuroinflammatory aberrations in sepsis. [ABSTRACT FROM AUTHOR]

Intestinal permeabilization is central to the pathophysiology of chronic gut inflammation. This study investigated the efficacy of glucoraphanin (GR), prevalent in cruciferous vegetables, particularly broccoli, and its derivative sulforaphane (SF), in inhibiting tumor necrosis factor alpha (TNFα)-induced Caco-2 cell monolayers inflammation and permeabilization through the regulation of redox-sensitive events. TNFα binding to its receptor led to a rapid increase in oxidant production and subsequent elevation in the mRNA levels of NOX1, NOX4, and Duox2. GR and SF dose-dependently mitigated both these short- and long-term alterations in redox homeostasis. Downstream, GR and SF inhibited the activation of the redox-sensitive signaling cascades NF-κB (p65 and IKK) and MAPK ERK1/2, which contribute to inflammation and barrier permeabilization. GR (1 μM) and SF (0.5–1 μM) prevented TNFα-induced monolayer permeabilization and the associated reduction in the levels of the tight junction (TJ) proteins occludin and ZO-1. Both GR and SF also mitigated TNFα-induced increased mRNA levels of the myosin light chain kinase, which promotes TJ opening. Molecular docking suggests that although GR is mostly not absorbed, it could interact with extracellular and membrane sites in NOX1. Inhibition of NOX1 activity by GR would mitigate TNFα receptor downstream signaling and associated events. These findings support the concept that not only SF, but also GR, could exert systemic health benefits by protecting the intestinal barrier against inflammation-induced permeabilization, in part by regulating redox-sensitive pathways. GR has heretofore not been viewed as a biologically active molecule, but rather, the benign precursor of highly active SF. The consumption of GR and/or SF-rich vegetables or supplements in the diet may offer a means to mitigate the detrimental consequences of intestinal permeabilization, not only in disease states but also in conditions characterized by chronic inflammation of dietary and lifestyle origin.

Background: 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). Methods: 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. Results: 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. Conclusion: 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.

Background. Lack of information about proinflammatory interleukins (IL) and tumor necrosis factor alpha (TNFα) levels in case of metabolic-associated liver steatosis (MALS) and their roles in its progression to steatohepatitis are key reasons for the relevance and actuality of our study. The purpose: to evaluate proinflammatory interleukins 2, 6, and TNFα levels in concomitant liver steatosis. Materials and methods. Thirty-five patients with hypertension stage II–III, type 2 diabetes mellitus were examined. All of them were treated on an outpatient basis according to the guidelines of the Ministry of Health of Ukraine and the Declaration of Helsinki. Participants were divided into the main group with MALS (n = 24, males 45.8 %, females 54.2 %; average age 55.83 ± 0.89 years) and the control group without steatosis (n = 11, males 54.5 %, females 45.5 %; average age 53.00 ± 1.55 years). In addition to standard parameters, levels of IL6, IL2, TNFα, selectin, resistin, insulin, C-peptide, glycated hemoglobin, non-esterified fatty acids were evaluated, and some indexes were calculated, including triglyceride-glucose index and Castelli indexes I and II. Results were processed statistically, with significance level of р

Background: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn's disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The single-cell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factorbinding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzymelinked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8 days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1β levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD. [ABSTRACT FROM AUTHOR]

Background: Intestinal organoids are stem cell-derived, 3D "mini-guts" with similar functions as the native intestinal epithelium such as electrolyte transport or establishment of an epithelial barrier. During intestinal inflammation, epithelial functions are dysregulated by proinflammatory cytokines like tumor necrosis factor α (TNFα) and other messengers from the immune system resulting in a loss of electrolytes and water due to an impaired epithelial barrier and higher net secretion. Methods: A murine small intestinal organoid model was established to study (long-term) effects of TNFα on the intestinal epithelium in vitro using live imaging, immunohistochemical staining and qPCR. Results: TNFα induced apoptosis in intestinal organoids as indicated by an increased number of cells with immunoreactivity for cleaved caspase 3. Furthermore, TNFα exposure led to swelling of the organoids which was inhibited by bumetanide and was concomitant with an upregulation of the bumetanide-sensitive Na+-K+-2Cl- symporter 1 (NKCC1) as shown by qPCR. Fura-2 imaging experiments revealed time-dependent changes in Ca2+ signaling consisting of a rise in the basal cytosolic Ca2+ concentration at day 1 and an increase of the carbachol-induced Ca2+ response after 3 days TNFα exposure. This was prevented by preincubation with La3+, an inhibitor of nonselective cation channels, or by using a Ca2+-free buffer indicating an enhancement of the Ca2+ influx from the extracellular side by the cytokine. No significant changes in cDNA levels of epithelial barrier proteins could be observed in the presence of TNFα. Conclusion: Intestinal organoids are a useful tool to study the mechanism underlying the TNFα-induced secretion on enterocytes such as the regulation of NKCC1 expression or the modulation of cellular Ca2+ signaling. [ABSTRACT FROM AUTHOR]

Eclampsia, a life-threatening occurrence of convulsion(s) in association with hypertension and significant proteinuria in pregnancy has remained an important public health problem, contributing to significant maternal and perinatal morbidity and mortality in Nigeria. The aim of this was to determine serum levels of tumor necrosis factor alpha in eclampsia, and to compare with those of healthy pregnant and non-pregnant controls. Enzymelinked immunoassay was used to measure the levels of tumor necrosis factor alpha in the sera of eclamptic women (n=38), normal healthy pregnant women (n=25) and healthy non pregnant controls (n=25). Data was analyzed using SPSS ver. 21.0 (Chiga, USA) and p< 0.05 is considered to be significant. The overall result of the level of tumor necrosis factor alpha (232.10±135.87 pg/ml) in eclamptic women was significantly higher than the mean values (180.58±29.18 pg/ml and 178.38±36.12 pg/ml) in pregnant and non-pregnant controls respectively. Furthermore, eclampsia had higher level of tumor necrosis factor alpha mean value compared with non-pregnant controls (P<0.05). Elevated tumor necrosis factor alpha in the maternal circulation might play a central role in the excessive systemic inflammatory response, as well as the generalized endothelial dysfunction characteristics of the maternal syndrome of eclampsia. Excessive production of tumor necrosis factor alpha may serve as immunoreactive agent responsible for clinical symptoms and fetal death recorded in women with eclampsia in this study. A further longitudinal study involving a larger population is strongly advocated to captures dangerous alterations in the levels of tumor necrosis factor alpha as they manifest in the course of pregnancy. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of idiopathic nephrotic syndrome (INS) has not been fully explained. Among the likely factors, tumor necrosis factor - alpha (TNF-α) is considered. We aimed to evaluate the TNF-α (sTNF-α, uTNF-α) levels in the serum and urine of INS children, with the aim of determining its association with proteinuria, and of determining its usefulness as a marker of the disease severity. Methods: Fifty-one examined patients were divided into subgroups depending on the number of relapses as follows: group IA—first episode; group IB—more than two relapses, and according to treatment modality; group IIA—glucocorticosteroids (GS) alone; and group IIB—GS with immunosuppressants. Healthy age-matched children served as the control group. Results: sTNF-α and uTNF-α levels were significantly increased in active phases in the whole INS group compared to the control group. They decreased in remission, but remained significantly higher when compared to the control group. During remission in the IB group, sTNF-α levels were significantly higher than in IA, whereas, in the relapse phase, these values were similar. In the IA group, a positive correlation between proteinuria and sTNF-α was demonstrated. Conclusions: Our findings suggest that TNF-α plays a role in the development of INS, and may be used as a prognostic marker, as well as an indicator for the continuation of therapy. Additional research is required to verify this statement. [ABSTRACT FROM AUTHOR]

Background. Lack of information about proinflammatory interleukins (IL) and tumor necrosis factor alpha (TNFα) levels in case of metabolic-associated liver steatosis (MALS) and their roles in its progression to steatohepatitis are key reasons for the relevance and actuality of our study. The purpose: to evaluate proinflammatory interleukins 2, 6, and TNFα levels in concomitant liver steatosis. Materials and methods. Thirtyfive patients with hypertension stage II-III, type 2 diabetes mellitus were examined. All of them were treated on an outpatient basis according to the guidelines of the Ministry of Health of Ukraine and the Declaration of Helsinki. Participants were divided into the main group with MALS (n = 24, males 45.8 %, females 54.2 %; average age 55.83 ± 0.89 years) and the control group without steatosis (n = 11, males 54.5 %, females 45.5 %; average age 53.00 ± 1.55 years). In addition to standard parameters, levels of IL6, IL2, TNFα, selectin, resistin, insulin, C-peptide, glycated hemoglobin, non-esterified fatty acids were evaluated, and some indexes were calculated, including triglyceride-glucose index and Castelli indexes I and II. Results were processed statistically, with significance level of р < 0.05. Results. Although MALS is not followed by qualitative differences in proinflammatory IL2, IL6 and TNFα compared to no steatosis, the risk of TNFα elevation was 5 times higher in patients with MALS (odds ratio 5.08; 95% confidence interval 1.02–25.17). An increase in IL2 and TNFα is unfavorable for patients with MALS, it can be considered as a marker of steatosis progression to steatohepatitis, as it is associated with transaminase activation, endogenous intoxication, lipid distress and glucose intolerance. IL6 was rather lower in patients with MALS compared to those without steatosis, but its growth was exponential and proceeded simultaneously to IL2 and TNFα. Conclusions. MALS was not associated with significant changes in IL2, IL6 and TNFα compared to no steatosis, but their elevation can be criteria for transformation into steatohepatitis due to the activation of transaminases, inflammation, endogenous intoxication, lipid distress, glucose intolerance [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions in vitro, focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6−/− and TNF-α−/− mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts in vitro. Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6−/− mice, significantly enhanced osteoclast differentiation in vitro. In contrast, supernatants from TNF-α−/− mice did not significantly affect osteoblast or osteoclast differentiation in vitro. In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of TNF-α and IL-6 genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.

Chronic inflammation can have a considerable impact on the progression of glomerular and tubulointerstitial pathologies in chronic kidney disease (CKD). As an alternative to the early detection of inflammatory markers that are most important in the progression of CKD, this study aims to analyze the association of MLR, NLR, and TNF-? with the stages of CKD. This cross-sectional study conducted at Universitas Airlangga Hospital, Surabaya, Indonesia, in mid-2023 involved 65 CKD subjects, consisting of 5 stages of CKD according to KDIGO guidelines. eGFR was calculated using the CKD-EPI creatinine equation. MLR and NLR were calculated from the differential count hematology analyzer Sysmex XN-550. TNF-α was examined using the sandwich ELISA method. Random-spot urine was used for the UACR examination (TMS 24i Premium Chemical Analyzer). There were significant differences in MLR and TNF-α at various stages of CKD (p0.05). There was a significant association between MLR (p0.05). In conclusion, MLR is better for assessing the progression of chronic kidney disease compared to NLR and TNF-α. [ J Adv Biotechnol Exp Ther 2024; 7(2.000): 346-356]

Abstract Background Osteoarthritis (OA) affects the entire joint, causing structural changes in articular cartilage, subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles that afflicts millions of people globally, leading to persistent pain and diminished quality of life. The intra-articular use of platelet-rich plasma (PRP) is gaining recognition as a secure therapeutic approach due to its potential regenerative capabilities. However, there is controversial clinical data regarding efficacy of PRP for OA treatment. In this context, gathering scientific evidence on the effects of PRP in treating OA in animal models could provide valuable insights into understanding its impact on aspects like cartilage health, synovial tissue integrity, and the inflammatory process in affected joints. Thus, the objective of this study was to assess the effects of PRP injections on inflammation and histopathological aspects of cartilage and synovium in animal models of OA through a comprehensive systematic review with meta-analysis. Methods A electronic search was conducted on Medline, Embase, Web of Science, The Cochrane Library, LILACS, and SciELO databases for relevant articles published until June 2022. A random-effects meta-analysis was employed to synthesize evidence on the histological characteristics of cartilage and synovium, as well as the inflammatory process. The GRADE approach was utilized to categorize the quality of evidence, and methodological quality was assessed using SYRCLE’s RoB tool. Results Twenty-one studies were included in the review, with twelve of them incorporated into the meta-analysis. PRP treatment demonstrated superior outcomes compared to the control group in terms of cartilage histology (very low quality; p = 0.0002), synovium histology (very low quality; p

Abstract Background Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP. Methods A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities. Results Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1β, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT. Conclusion Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.

AbstractOsteoclasts, derived from the monocyte/macrophage line of bone marrow hematopoietic stem cell progenitors, are the sole bone-resorbing cells of the body. Conventional osteoclast differentiation requires macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune disease and inflammatory arthritis characterized by bone destruction. Increased levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in the serum and joints, cause excessive bone destruction. We have recently reported that stimulation of human peripheral blood monocytes with TNF-α and IL-6 induces the differentiation of osteoclasts with bone resorption activity. This review presents the functional differences between representative osteoclasts, conventional RANKL-induced osteoclasts, and recently identified proinflammatory cytokine (TNF-α and IL-6)-induced osteoclasts in RA patients. We believe novel pathological osteoclasts associated with RA will be identified, and new therapeutic strategies will be developed to target these osteoclasts and prevent the progression of bone destruction.

Osteoclasts, derived from the monocyte/macrophage line of bone marrow hematopoietic stem cell progenitors, are the sole bone-resorbing cells of the body. Conventional osteoclast differentiation requires macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune disease and inflammatory arthritis characterized by bone destruction. Increased levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in the serum and joints, cause excessive bone destruction. We have recently reported that stimulation of human peripheral blood monocytes with TNF-α and IL-6 induces the differentiation of osteoclasts with bone resorption activity. This review presents the functional differences between representative osteoclasts, conventional RANKL-induced osteoclasts, and recently identified proinflammatory cytokine (TNF-α and IL-6)-induced osteoclasts in RA patients. We believe novel pathological osteoclasts associated with RA will be identified, and new therapeutic strategies will be developed to target these osteoclasts and prevent the progression of bone destruction. [ABSTRACT FROM AUTHOR]

Objectives TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases, but its association with idiopathic nephrotic syndrome (INS) is poorly understood. This study looked for an association of TNF- α gene polymorphisms with INS, as well as its effect on steroid responsiveness among Kuwaiti Arab children. Methods Genotypes of the TNF-a gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism in 151 INS Kuwaiti Arab patients and 64 age and sex-matched controls. Clinical data of all subjects were reviewed. Results The heterozygous AG genotype was detected in 8.6% of INS patients compared 23.4% of the controls (p  <   0.01). Comparing steroid responsiveness, AA genotype was significantly more common in steroid-sensitive nephrotic syndrome (SSNS) cases than steroid-resistant nephrotic syndrome (SRNS) patients (p  =   0.001). However, AG genotype was significantly more common in SRNS patients compared to the SSNS cases (p  =   0.001). No difference was found between these two subgroups in the GG genotype frequency. Conclusion AG genotype of TNF-a gene polymorphisms may be considered a suitable marker for INS disease among Kuwaiti children. Both AA and AG genotypes may be useful in predicting steroid responsiveness among these cases of Arab ethnicity. The findings might open the era for the use of genetic markers in the early treatment of NS. [ABSTRACT FROM AUTHOR]

Bacterial infections are characterized by an inflammatory response, which is essential for infection containment but is also responsible for negative effects on the host. The pathogen itself may have evolved molecular mechanisms to antagonize the antimicrobial effects of an inflammatory response and to enhance its pathogenicity using inflammatory response mediators, such as cytokines. Clostridioides difficile (C. difficile) infection (CDI) causes gastrointestinal diseases with markedly increasing global incidence and mortality rates. The main C. difficile virulence factors, toxin A and B (TcdA/TcdB), cause cytopathic/cytotoxic effects and inflammation. We previously demonstrated that TcdB induces enteric glial cell (EGC) apoptosis, which is enhanced by the pro-inflammatory cytokine tumor necrosis factor alpha plus interferon gamma (CKs). However, it is unknown whether CKs-enhanced TcdB cytotoxicity (apoptosis/necrosis) is affected by the timing of the appearance of the CKs. Thus, we simulated in vitro, in our experimental model with TcdB and EGCs, three main situations of possible interactions between TcdB and the timing of CK stimulation: before TcdB infection, concomitantly with infection, or at different times after infection and persisting over time. In these experimental conditions, which all represent situations of possible interactions between C. difficile and the timing of CK stimulation, we evaluated apoptosis, necrosis, and cell cycle phases. The CKs, in all of these conditions, enhanced TcdB cytotoxicity, which from apoptosis became necrosis when CK stimulation persisted over time, and was most relevant after 48 h of TcdB:EGCs interaction. Particularly, the enhancement of apoptosis by CKs was dependent on the TcdB dose and in a less relevant manner on the CK stimulation time, while the enhancement of necrosis occurred always independently of the TcdB dose and CK stimulation time. However, since in all conditions stimulation with CKs strongly enhanced the TcdB cytotoxicity, it always had a negative impact on C. difficile pathogenicity. This study might have important implications for the treatment of CDI. [ABSTRACT FROM AUTHOR]

Age impairs cognitive functions and antioxidant defenses, for example, by increasing oxidative stress and inflammation in the brain. However, to date, there are no reports on the consequences of aging on temporal patterns of lipid and protein oxidation, antioxidant enzymes activity, the endogenous clock, and proinflammatory cytokines in the prefrontal cortex (PFC). Therefore, our objectives were 1) to investigate the endogenous nature of 24-h rhythms of lipid peroxidation, protein carbonyl levels, catalase (CAT) and glutathione peroxidase (GPX) activity as well as retinoic acid-related orphan receptor a (RORa) and tumor necrosis factor alpha (TNF-α) levels, in the rat PFC, and 2) to study the consequences of aging on the circadian organization of these factors in this area. To do that, we used male Holtzman rats, maintained under constant darkness conditions for 15 days before reaching 3- and 22-mo-old, respectively. PFC samples were isolated every 4 h under dim-red light for a 24 h period. Our results revealed circadian patterns of antioxidant enzymes activity, oxidative stress, RORa and TNF-α protein levels in the PFC of young rats. The circadian distribution of the rhythms’ acrophases suggests reciprocal communication among antioxidant defenses, endogenous clock, and inflammation. Such circadian organization disappears in the PFC of aged rats. Increased oxidative stress modifies the cellular redox environment and, consequently, alters the endogenous clock activity and disrupts the circadian organization of antioxidant defenses and TNF-α in the PFC. These results might highlight novel chronobiological targets for the design of therapeutic strategies for healthy aging patients. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor α (TNFα), an inflammatory cytokine, induces lipolysis and increases circulating concentrations of free fatty acids. In addition, TNFα is the first adipokine produced by adipose tissue in obesity, contributing to obesity-associated metabolic disease. Given that benzyl isothiocyanate (BITC) is a well-known anti-inflammatory agent, we hypothesized that BITC can ameliorate TNFα-induced lipolysis and investigated the working mechanisms involved. We first challenged 3T3-L1 adipocytes with TNFα to induce lipolysis, which was confirmed by increased glycerol release, decreased protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and perilipin 1 (PLIN1), and increased phosphorylation of ERK, protein kinase A (PKA), and hormone-sensitive lipase (HSL). However, inhibition of ERK or PKA significantly attenuated the lipolytic activity of TNFα. Meanwhile, pretreatment with BITC significantly ameliorated the lipolytic activity of TNFα; the TNFα-induced phosphorylation of ERK, PKA, and HSL; the TNFα-induced ubiquitination of PPARγ; the TNFα-induced decrease in PPARγ nuclear protein binding to PPAR response element; and the TNFα-induced decrease in PLIN1 protein expression. Our results indicate that BITC ameliorates TNFα-induced lipolysis by inhibiting the ERK/PKA/HSL signaling pathway, preventing PPARγ proteasomal degradation, and maintaining PLIN1 protein expression. BITC inhibits TNFα-induced ubiquitination of PPARγ and subsequent proteasomal degradation and PPARγ is a critical transcription factor for PLIN1, which acts as a barrier to the breakdown of storage lipids. In addition, TNFα activates the ERK/PKA/HSL signaling pathway participating in lipolysis, which is suppressed by BITC. Abbreviations: BITC, benzyl isothiocyanate; DG, diglyceride; FFA, free fatty acid; HSL, hormone-sensitive lipase; MG, monoglyceride; PKA, protein kinase A; PLIN1, perilipin 1; PPARγ, peroxisome proliferator-activated receptor γ; TG, triglyceride; TNFα, tumor necrosis factor α. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: This clinical study aims to analyze the levels of cortisol, dehydroepiandrosterone (DHEA), and tumor necrosis factor alpha (TNF-α) in the gingival crevicular fluid (GCF) of persons with bruxism and to compare the efficacy of botulinum toxin (botox) and occlusal splint treatments through biomarkers. Materials and methods: A total of 40 patients with bruxism were selected according to the clinical examination and anamnesis of which 20 received occlusal splint treatment and 20 botox treatment. GCF samples were taken from the patients before and after treatment. Cortisol, DHEA, and TNF-α levels were measured by enzyme-linked immunosorbent assay test. The change in measurements between time and groups and the time-group interaction were tested by repeated measures ANOVA. Results: There was a statistically significant difference between the cortisol levels before and after treatment in both groups (p = 0.001). In individuals with bruxism, a statistically significant decrease in cortisol levels was observed after both treatments (p < 0.05), while DHEA levels increased after treatment but were not statistically significant (p > 0.05). There was no statistically significant difference between TNF-α intra-group measurements (p > 0.05). Conclusions: Stress and inflammatory biomarkers were found to be associated with bruxism. Cortisol levels decreased in people with bruxism after treatment with both occlusal splint and botox. Clinical relevance: Both splint and botox treatments were effective for bruxism by reducing the stress levels. [ABSTRACT FROM AUTHOR]

Breast cancer is the cancer with the highest incidence in women in the world. It was to investigate the mechanism of chemotactic cytokine binding protein D6 in the tumorigenicity and metastasis of breast cancer cell. The more invasive human breast cancer cell lines MDA-MB-435 and MDA-MB-231, the less invasive human breast cancer cell lines ZR-75-30 and ZR-75-1, and normal breast epithelial cells Hs578Bst and human normal breast epithelial cell line- 100 were selected for the experiments. The differences of D6 messenger ribonucleic acid levels in different cells and the effects of other factors on D6 messenger ribonucleic acid levels were explored. Then, MDA-MB-435 was selected for D6 transfection to make over expressed MDA-MB-435/D6 cells, and the effect of D6 on the tumorigenicity and metastasis of MDA-MB-435 was analyzed by comparative analysis. It revealed as the increasing cell invasion, the D6 messenger ribonucleic acid was obviously decreased; as the increasing interleukin-1 beta concentration, the D6 messenger ribonucleic acid increased clearly; as the raising tumor necrosis factor alpha concentration, the D6 messenger ribonucleic acid was clearly decreased in different degrees (p<0.05). Interferon gamma concentration had no effect on D6 messenger ribonucleic acid level (p>0.05). As against MDA-MB-435 cells, the proliferation and migration of MDA-MB-435/D6 cells were clearly decreased from the 3rd d; the concentrations of C-C motif ligand 2, C-C motif ligand 4, and C-C motif ligand 13 of D6 ligands in MDA-MB-435/D6 were clearly lower (p<0.05). Chemotactic cytokine binding protein D6 is negative regulatory in breast cancer, inhibiting the tumorigenicity and metastasis of breast cancer cell. [ABSTRACT FROM AUTHOR]

Introduction: Despite the established role of peripheral adenosine receptors in sepsis-induced organ dysfunction, little or no data is available on the interaction of central adenosine receptors with sepsis. The current study tested the hypothesis that central adenosine A3 receptors (A3ARs) modulate the cardiovascular aberrations and neuroinflammation triggered by sepsis and their counteraction by the cholinergic antiinflammatory pathway.Methods: Sepsis was induced by cecal ligation and puncture (CLP) in rats pre-instrumented with femoral and intracisternal (i.c.) catheters for hemodynamic monitoring and central drug administration, respectively.Results: The CLP-induced hypotension, reduction in overall heart rate variability (HRV) and sympathovagal imbalance towards parasympathetic predominance were abolished by i.v. nicotine (100 μg/kg) or i.c. VUF5574 (A3AR antagonist, 2 µg/rat). In addition, the selective A3AR agonist, 3-iodobenzyl-5′-N-methylcarboxamidoadenosine IB-MECA, 4 µg/rat, i.c.) exaggerated the hypotension and cardiac autonomic dysfunction induced by sepsis and opposed the favorable nicotine actions against these septic manifestations. Immunohistochemically, IB-MECA abolished the nicotine-mediated downregulation of NFκB and NOX2 expression in rostral ventrolateral medullary areas (RVLM) of brainstem of septic rats. The inhibitory actions of IB-MECA on nicotine responses disappeared after i.c. administration of PD98059 (MAPK-ERK inhibitor), SP600125 (MAPK-JNK inhibitor) or wortmannin (PI3K inhibitor). Moreover, infliximab (TNFα inhibitor) eliminated the IB-MECA-induced rises in RVLM-NFκB expression and falls in HRV, but not blood pressure.Conclusion: Central PI3K/MAPKs pathway mediates the A3AR counteraction of cholinergic defenses against cardiovascular and neuroinflammatory aberrations in sepsis.

Elevated fasting ethanol levels in peripheral blood frequently found in metabolic dysfunction-associated steatohepatitis (MASLD) patients even in the absence of alcohol consumption are discussed to contribute to disease development. To test the hypothesis that besides an enhanced gastrointestinal synthesis a diminished alcohol elimination through alcohol dehydrogenase (ADH) may also be critical herein, we determined fasting ethanol levels and ADH activity in livers and blood of MASLD patients and in wild-type ± anti-TNFα antibody (infliximab) treated and TNFα-/- mice fed a MASLD-inducing diet. Blood ethanol levels were significantly higher in patients and wild-type mice with MASLD while relative ADH activity in blood and liver tissue was significantly lower compared to controls. Both alterations were significantly attenuated in MASLD diet-fed TNFα-/- mice and wild-type mice treated with infliximab. Moreover, alcohol elimination was significantly impaired in mice with MASLD. In in vitro models, TNFα but not IL-1β or IL-6 significantly decreased ADH activity. Our data suggest that elevated ethanol levels in MASLD patients are related to TNFα-dependent impairments of ADH activity.