Serum Levels Of TNF Research Articles

Roux-en-Y gastric bypass potentially improved intestinal permeability by regulating gut innate immunity in diet-induced obese mice

Roux-en-Y gastric bypass (RYGB) has been demonstrated to be the most effective treatment for morbid obesity, yet the impact of RYGB on intestinal permeability is not fully known. In this work, we subjected obese mice to RYGB and sham operation procedures. Serum lipopolysaccharide (LPS) level, inflammatory cytokines and intestinal permeability were measured at 8 weeks post surgery. In contrast to sham surgery, RYGB reduced body weight, improved glucose tolerance and insulin resistance, and decreased serum levels of LPS, IL6 and TNFα. Intestinal permeability of the common limb and colon was significantly improved in the RYGB group compared to the sham group. The mRNA levels of IL1β, IL6, and TLR4 in the intestine were significantly decreased in the RYGB group compared with the sham group. The expression levels of intestinal islet-derived 3β (REG3β), islet-derived 3γ (REG3γ) and intestinal alkaline phosphatase (IAP) were higher in the RYGB group than in the sham group. In conclusion, in a diet-induced obesity (DIO) mouse model, both decreased intestinal permeability and attenuated systemic inflammation after RYGB surgery were associated with improved innate immunity, which might result from enhanced production of IAP and antimicrobial peptides.

Inflammatory Markers Profile in Older Adolescents During Treatment with Selective Serotonin Reuptake Inhibitors.

Objective: This study aimed to investigate the serum levels of inflammatory markers in adolescents with major depressive disorder (MDD) using selective serotonin reuptake inhibitors. Methods: This was an 8-month observational study, involving 30 adolescents with and 38 without (control) MDD diagnosis. Demographic (age and gender) and anthropometric data (weight, height, and calculated body mass index [BMI] z score) were collected. Body composition was assessed with whole-body DXA scan. Depressive and anxiety symptoms were assessed using the Beck Depression and Anxiety Inventories (BDI-II and BAI), respectively. Serum levels of interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor, monocyte chemoattractant protein-1 (MCP-1), leptin, resistin, and adiponectin were measured using Bio-Plex Multiplex Immunoassays at baseline and after 8 months. Results: At baseline, patients with MDD and controls did not differ in age, gender, BMI z score, and fat mass index (FMI) z score. At follow-up, 58.3% (21/36) of patients with MDD were in full remission. Patients with MDD had higher levels of resistin at baseline (26274.16 pg/mL [16162.68-54252.72]) than controls (21678.53 pg/mL [11221.17-37343.27]; p < 0.01). This difference remained statistically significant after adjustment for sex, age, and FMI z score. No differences in other inflammatory markers were observed between the groups. By follow up, depressive and anxiety symptom severity had decreased significantly in patients with MDD in parallel with a decrease in the serum levels of TNF (p = 0.02), IL-8 (p < 0.01) and MCP-1 (p = 0.04). Among these markers, BDI-II score was positively correlated with serum levels of MCP-1. Conclusion: These results corroborate the view of involvement of peripheral inflammatory mechanisms in the pathophysiology of MDD in adolescents. This trial is registered at ClinicalTrials.gov: NCT02147184.

Tumor necrosis factor-α gene promoter −308 and −238 polymorphisms and its serum level in psoriasis

BackgroundPsoriasis is a chronic, immune-mediated, inflammatory skin disease affecting genetically predisposed individuals and requiring long-term treatment. The etiology of psoriasis is not fully understood. This article aimed to determine association between genetic polymorphisms in tumor necrosis factor-α (TNF -α) promoter −308 (rs1800629) and −238 (rs 361,525) and its serum level in psoriasis patients. MethodsThe study was conducted on 70 patients with psoriasis and 70 age and sex-matched, healthy individuals. All patients were subjected to history taking and complete medical examination. The polymorphisms of TNF -α promoter gene −308 (rs1800629) and −238 (rs 361,525) were detected by real time PCR and Serum levels of TNF -α were measured by ELISA technique. ResultsAG polymorphism and A allele of TNF-α −238 G/A (rs 361,525) were significantly more in patients than controls, whereas AG polymorphism and A allele of TNF-α −308 G/A (rs1800629) were significantly more in controls than patients. There were significant high levels of TNF-α in serum of patients in comparison to controls. ConclusionsThe AG polymorphism and A allele of TNF-α −238G/A (rs 361,525) may act as a risk factor for occurrence of psoriasis, whereas AG polymorphism and A allele of TNF-α −308G/A (rs1800629) may have protective role. There is pivotal role of TNF-α as a pro-inflammatory mediator in pathogenesis of psoriasis.

Serum TNF\u03b1 levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study

ObjectiveTo estimate the relationship between serum TNFα, IL-6, and serum CZP levels and the clinical response to CZP in RA patients in the TSUBAME study.MethodsOne hundred patients with RA who received CZP were enrolled and multiple clinical parameters, serum TNFα, IL-6, and CZP levels, were assessed at 0, 24, and 48 h and 12 weeks after first administration of CZP.ResultsThe CZP therapy significantly improved the DAS28(ESR) at 12 weeks. Serum TNFα and IL-6 levels significantly decreased from baseline at 24 h after the first administration of CZP. Serum TNFα levels at baseline were not related to clinical parameters at baseline and improvement in DAS28(ESR) at week 12 of the CZP therapy. However, serum levels of CZP at 24 h were strongly and negatively correlated with TNFα levels at 24 h, which were negatively correlated with improved rate in DAS28(ESR) at week 12. Only serum levels of TNFα, but not IL-6, at 24 h had a negative correlation with achievement of DAS28(ESR)<2.6 at week 12 by the multivariate analysis (odds ratio 0.01, 95% confidence interval 0.04e−2–0.22, p < 0.01). A receiver operating characteristic analysis was conducted to estimate the achievement of DAS28(ESR)<2.6 at week 12 after the CZP therapy and cut-off value of 0.76 pg/ml for serum levels of TNFα at 24 h was yielded (area under the curve=0.75). DAS28(ESR)<2.6 was achieved at week 12 significantly more patients with lower serum TNF levels (≦0.76 pg/ml) at 24 h than those with higher TNF levels.ConclusionsCZP was highly effective in RA patients who had low serum TNFα levels at 24 h after the initial administration of CZP. Therefore, we propose that serum TNFα levels at 24 h could serve as a biomarker predicting effectiveness to CZP at week 12 in patients with RA.Trial registrationClinical trial registration number: UMIN ID:000022831

P302 Serum IL-6 is associated with treatment refractoriness in acute severe ulcerative colitis

Abstract Background Response to therapy in acute severe ulcerative colitis (ASUC) is highly variable ranging from steroid response to salvage therapy failure and emergency colectomy. Biomarkers that accurately predict outcomes in ASUC early in the admission may help improve its management. We aimed to ascertain whether peripheral serum cytokine levels on admission correlate with refractoriness to medical therapy. Methods Peripheral blood was collected from 34 subjects, including 29 patients with ASUC on admission (baseline) and 5 healthy controls. All patients with ASUC received intravenous steroids, with those refractory to steroids going on to receive infliximab (IFX) salvage. Eight cytokines were measured at baseline using a multiplexed cytokine assay (Bio-Rad). Clinical response to steroids and/or to the first IFX dose was assessed and used to classify patients based on increasing order of disease refractoriness (steroid-responders, IFX-responders and IFX non-responders). These groups were then evaluated to check for correlations with baseline cytokine levels. Results Our cohort consisted of steroid responders (n=9), IFX responders (n=12) and IFX non-responders (n=8). Median serum IL-6 level was 1.6 pg/mL (IQR:1.6-2.1) in healthy controls compared to 2.7 pg/mL (IQR:1.4-6.3) in ASUC (p=0.3). In patients with ASUC, there was a positive correlation between IL-6 and treatment refractoriness (Spearman’s correlation [rs]=0.56, p=0.002). Compared with steroid responders (1.36 pg/mL), serum IL-6 was significantly higher in both IFX responders and IFX non-responders (3.44 and 5.50 pg/mL, p=0.02 and p=0.009 respectively) (Fig 1). Patients with ASUC had higher serum IL-8 compared to healthy controls (17.8 vs 6.9 pg/mL, p=0.005). There was no correlation between IL-8 levels and ASUC treatment refractoriness (rs=0.22, p=0.3). Similarly, there was no difference in IL-8 levels in ASUC patients when classified by treatment response (Kruskal Wallis, p=0.5). Serum TNF level did not differ between healthy controls and patients with ASUC (19.5 and 22.2pg/mL, p=0.5). TNF levels did not correlate with treatment refractoriness in ASUC (rs=-0.06, p=0.75) and there were no differences between the ASUC response groups (p=0.6). Levels of GM-CSF, IFN-g, IL-2, IL-4 and IL-10 were predominantly below the detection limit of each assay. Conclusion In this ASUC cohort, serum IL-6 level on admission correlated with treatment refractoriness and may help identify patients at higher risk of requiring salvage therapy as well as those at higher risk of failing IFX. Further studies are needed to elucidate the function of IL-6 in ASUC and whether it may represent a potential predictor of outcomes in ASUC.

A plant-based medicinal food inhibits the growth of human gastric carcinoma by reversing epithelial\u2013mesenchymal transition via the canonical Wnt/\u03b2-catenin signaling pathway

BackgroundNatural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo.MethodsA subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of β-catenin, GSK-3β, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3β, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining.ResultsPBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3β, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of β-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3β and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues.ConclusionsThe PBMF concocted herein exerts anti-gastric cancer activities via epithelial–mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/β-catenin signaling pathway.

Anti‐Inflammatory Effects of Famotidine

The COVID-19 pandemic in the U.S. currently exceeds 21.1 million cases and 350,000 deaths. Consumption of famotidine, a histamine H2 receptor antagonist widely used to treat acid reflux and gastritis, is associated with improved survival and attenuated COVID-19 disease severity (Mather JF et al. Am J Gastroenterol. 115:1617,2020; Freedberg DE, et al. Gastroenterology 159: 1129, 2020; Janowitz T et al. Gut, 69:1592, 2020). However, the mode of action for these beneficial effects is unknown. Here we studied famotidine in mice exposed to bacterial endotoxin (lipopolysaccharide, LPS). LPS (6 mg/kg) was administered intraperitoneally in male C57BL/6 mice followed by intraperitoneal injection of famotidine (100 µg/mouse) or vehicle (PBS) twice daily for 3 days. Two-week survival was 100% in the famotidine-treated group vs. 70% in the PBS-control group (n=30/group, p < 0.05). Furthermore, famotidine administration significantly reduced serum and splenic TNF levels and serum IL-6 levels in the endotoxemic mice (p<0.05, famotidine vs. PBS). Human peripheral blood mononuclear cells co-cultured with famotidine and LPS also express significantly reduced amounts of pro-inflammatory cytokines (TNF, IL-6, HMGB1, IP-10, GM-CSF). Together these results indicate famotidine inhibits endotoxin induced cytokine storm and attenuates lethality in mice exposed to lethal endotoxemia.

Ethyl pyruvate ameliorate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in rats with acute rhinosinusitis

High mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases. The aim of this study was to establish animal model of acute rhinosinusitis (ARS), and determine whether ethyl pyruvate (EP) attenuate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in ARS animals. Thirty-six Sprague Dawley (SD) rat were used as follows: six normal controls without intervention (group 1); thirty rats were used for establishment of ARS rats model by nasal insertion of Merocel sponge, and model rats without any treatments (group 2), treated with nasal drops of sterile saline (group 3), 10 μl EP (group 4), and 20 μl EP (group 5), twice a day for 5 days, respectively. Bacterial culture was done regularly and the main bacterial strains were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. HMGB1 expression in sinonasal mucosa was detected by immunohistochemistry and RT-PCR. Serum levels of HMGB1, IL-6, and TNF-α were determined by ELISA. Data from 29 of 36 rats that had completed research were analyzed. Bacterial colony formation unit (CFU) of nasal secretion was significantly higher in each group of ARS rats compared with controls (p < 0.001). ARS rats treated with EP had only slightly decreased CFU, but significantly attenuated inflammatory response of sinonasal mucosa and decreased HMGB1 expression compared to those treated with saline alone (p < 0.001). Serum levels of HMGB1, IL-6 and TNF-α were significantly higher in ARS rats compared to controls, and decreased by EP treatments (p < 0.001). Nasal sponge packing led to acute inflammatory response of nasal sinus in rats, and increased the expression of HMGB1, IL-6, and TNF-α. Nasal drops with EP could attenuate the inflammation of sinonasal mucosa through inhibiting the expression of HMGB1, IL-6 and TNF-α in ARS rats.

Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians.

Inflammatory reactions in the body have been shown to contribute to migraine development. Therefore, genes involved in the inflammatory pathways might play a role in the susceptibility and development of migraine. In this study, polymorphisms in tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTA) genes were tested for association with migraine. A total of 398 participants (198 migraine patients and 200 controls) were recruited in the study. Serum TNF level was measured using a sandwich ELISA kit. Lymphocytes' and monocytes' counts were obtained from a differential complete blood count profile. Participants' DNA was extracted and genotyped for rs1800629 and rs1799724 in TNFα, and rs909253 in LTA. Controls had a significantly higher mean lymphocyte count (P = 0.018), while the mean monocyte count and serum TNFα levels did not differ between the two groups (P > 0.05). With respect to gene polymorphisms, the rs1800629 and rs1799724 variants showed significant association with migraine in all subjects, and in males and females when analyzed separately (P < 0.001). The rs909253 did not show any statistical difference in frequencies among the two groups (P > 0.05). Having the A allele in rs1800629 was associated with a higher risk of migraine in both male (OR, 95%; CI, G/A = 3.79 [1.87-7.69]; A/A = 14.22 [1.67-121.14]; P < 0.01) and female (OR, 95%; G/A = 2.54 [1.47-4.38]; A/A = 2.52 [1.12-5.69]; P < 0.001) subjects. In conclusion, rs1800629 and rs1799724 in TNFα showed significant association with migraine among the Jordanian population.

Relationship Between High Sensitivity TNF-? WITH clinical outcome During Admission In Acute Ischemic Stroke

Background : Tumor necrosis factor alpha (TNF-?), together with other pro-inflammatory cytokines suchas Interleukin-1b (IL-1b), IL- 6 and IL-8, play a role in the ischemic injury of the central nervous system.TNF-? has adverse effects on ischemic brain tissue. The mechanism generated is a multicomplex process. Inother studies, an increase in TNF-? can actually have neuroprotective effects. This study aims to determinethe relation between the levels of the High Sensitivity TNF-? with clinical outcome in acute ischemic stroke.Method : Thirty patients with acute ischemic stroke patients who admitted in Dr. Soetomo hospital Surabayaduring the period December 2011 to February 2012. 2 cc of vein blood for examination High sensitivityTNF-? was drawn during admission from acute ischemic stroke. Clinical outcome in acute stroke wasmeasured by NIHSS score.Results: From 30 research samples, the mean age of patients was 59.53 ± 11.51 years. The mean HighSensitivity TNF-? level in the study subjects was 2 ± 0.99 pg / ml. NIHSS examination showed the medianvalue of the NIHSS was 5 with a range of 2-19. There is a correlation but not statistically significant withthe strength is very weak between High Sensitivity TNF-? with the NIHSS in patients with acute thromboticstroke (r = 0.100 and p = 0.600).Conclusion: There is relationship between serum levels of High sensitivity TNF-? with clinical outcome inacute ischemic stroke patients.

Liver fibrosis-induced muscle atrophy is mediated by elevated levels of circulating TNF\u03b1

Liver cirrhosis is a critical health problem associated with several complications, including skeletal muscle atrophy, which adversely affects the clinical outcome of patients independent of their liver functions. However, the precise mechanism underlying liver cirrhosis-induced muscle atrophy has not been elucidated. Here we show that serum factor induced by liver fibrosis leads to skeletal muscle atrophy. Using bile duct ligation (BDL) model of liver injury, we induced liver fibrosis in mice and observed subsequent muscle atrophy and weakness. We developed culture system of human primary myotubes that enables an evaluation of the effects of soluble factors on muscle atrophy and found that serum from BDL mice contains atrophy-inducing factors. This atrophy-inducing effect of BDL mouse serum was mitigated upon inhibition of TNFα signalling but not inhibition of myostatin/activin signalling. The BDL mice exhibited significantly up-regulated serum levels of TNFα when compared with the control mice. Furthermore, the mRNA expression levels of Tnf were markedly up-regulated in the fibrotic liver but not in the skeletal muscles of BDL mice. The gene expression analysis of isolated nuclei revealed that Tnf is exclusively expressed in the non-fibrogenic diploid cell population of the fibrotic liver. These findings reveal the mechanism through which circulating TNFα produced in the damaged liver mediates skeletal muscle atrophy. Additionally, this study demonstrated the importance of inter-organ communication that underlies the pathogenesis of liver cirrhosis.

Tumor Necrosis Factor Alpha-863 C/A Single Nucleotide Polymorphisms and Nephrotic Syndrome

Introduction: Cytokines act as a mediator of inflammation in childhood nephrotic syndrome. Polymorphisms of cytokines genes may influence susceptibility to nephrotic syndrome (NS), as well as, patients’ steroid responses. Objective: To study the association of tumor necrosis factor-alpha single nucleotide polymorphisms (TNF-α SNP) (-863 C/A) with the development of NS in addition to access to their effects on serum level of TNF and the response to steroid therapy. Patients and Methods: This study included 60 patients (19 female and 41 male) with nephrotic syndrome; their ages ranged from 2 to 18 years. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess the TNF-α gene polymorphism. Results: According to the digestion pattern of RFLP-PCR products of TNF-α-863, this polymorphism had three genotypes, which were CC, CA, and AA, in both NS patients and controls. Also, the current result observed that -863 SNP do not affect the serum level of TNF-α and steroid responsiveness in patients with nephrotic syndrome. Conclusion: This polymorphism did not show any significant association with response to steroid therapy and TNF serum level neither at genotype nor at allele level.

Cytokine profile in multiple myeloma

BackgroundCytokines play a crucial role in the growth, survival and dissemination of malignant plasma cells in patients of multiple myeloma (MM). We estimated concentrations of five key cytokines: Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Tumor Necrosis Factor- alpha (TNF- α), B-cell activating factor (BAFF), and Receptor Activator of Nuclear Factor-κB ligand (RANKL) in newly diagnosed and relapsed/refractory MM (RRMM). MethodsThe study groups include 68 newly diagnosed and 21 relapsed/refractory (RR) MM patients. 32 out of 68 newly diagnosed MM patients were evaluated for serum cytokine concentrations after their treatment. For survival analysis, the various parameters were studied in relation to both progression free survival (PFS) and overall survival (OS). ResultsThe median serum levels of VEGF, IL-6, BAFF and RANKL were higher in RRMM compared with newly diagnosed patients. However, the difference was significant for BAFF levels (p = 0.04). The median serum levels of VEGF, IL-6, TNF-α, BAFF and RANKL were significantly higher in newly diagnosed and RRMM patients, compared to controls. We also observed lower plasma levels of VEGF (p=<0.0001) and BAFF (p=<0.0001) in BM compartment compared to the levels in serum from peripheral blood of newly diagnosed patients. Significant reduction in the median levels of IL-6, TNF-α, BAFF and RANKL was seen after 4–6 cycles of induction treatment in responders but not in non-responders. On survival analysis, RRMM patients had inferior median OS and PFS compared to that in newly diagnosed MM patients and found to be significantly associated with low haemoglobin representing the more aggressive disease biology in recurrent myeloma. The mean levels of IL-6 were significantly different in patients who died as compared to patients who were alive. ConclusionsThe present study demonstrates that the serum levels of VEGF, IL-6, TNF, BAFF and RANKL are significantly elevated and decrease significantly after treatment. The concentrations of circulating cytokines will reflect those of the bone marrow and could be used for subsequent analyses.

Chitosan oligosaccharide combined with running benefited the immune status of rats

Chitosan oligosaccharide (COS) degraded by chitosan, is an easily accessible and biocompatible natural molecule, which can facilitate the immune system. Running is one of the most effective forms of exercise. Persistence in running can effectively improve the body's resistance against pathogens. However, whether the combination of COS and running could benefit immune status still remains to be elucidated. We used Sprague-Dawley (SD) rats to explore the combinatory effect of COS and running. The organs and blood of the rats were collected after four weeks and the organ body mass index, biochemical and blood routine examination, cytokines, and T cells in the spleen and blood were detected and analyzed. In the group intragastric administration of COS only, the level of blood lactate dehydrogenase was increased, while the blood creatinine, red blood cells, lymphocytes, and serum TNF were decreased. Furthermore, COS combined with running promoted the development of spleen and lung, the level of lymphocytes, T cell and CD8+ T cell ratio in the blood, and serum TNF level. At the same time, the level of lactate dehydrogenase, serum IL-2, and T cell ratio in spleen were decreased. Therefore, our study indicated that COS combined with running could improve the immune status of rats.

Fermentation Production of Ganoderma lucidum by Bacillus subtilis Ameliorated Ceftriaxone-induced Intestinal Dysbiosis and Improved Intestinal Mucosal Barrier Function in Mice

ObjectiveThis study aimed to develop a type of Ganoderma lucidum (G. lucidum)-probiotic fermentation broth that can effectively improve the intestinal mucosal barrier function of mice with ceftriaxone-induced intestinal dysbiosis. MethodsBy means of absorbance of optical density (OD) value and phenol-concentrated sulfuric acid measurement of polysaccharide content, the probiotic species can grow on the medium of G. lucidum were screened out, and the concentration of the medium of G. lucidum was determined, and the fermentation broth was prepared for subsequent experiments. Thirty-two SPF grade male BALB/c mice were randomly divided into four groups (eight mice in each group), namely control group (CON), intestinal mucosal barrier damage model group (CS), fermentation broth intervention group (FT) and G. lucidum medium intervention group (GL), respectively. The intestinal dysregulation model was induced by intra-gastric administration of 0.2 mL ceftriaxone sodium (twice a day for seven consecutive days). From day 8, the FT group and GL group were gavage with 0.2 mL fermentation broth and G. lucidum medium, respectively. On day 15, all mice were sacrificed. To draw the weight curve and measure the cecal index; pathological examination of colon tissues with HE staining; serum levels of LPS, IL-10, TNF and IL-6 were detected by ELISA. Flow cytometry was used to analyze the changes of CD3 + T cells, CD4 + T cells, CD8 + T cells and macro- phages in spleen. 16S rRNA sequencing was performed to detect the intestinal microbiota structure of mice. ResultsBacillus subtilis can decompose and utilize G. lucidum fruiting body medium, and the suitable concentration of G. lucidum fruiting body medium is 33.2 mg/mL. The effect of Bacillus subtilis-G. lucidum fermentation broth on the damage of intestinal mucosal barrier caused by ceftriaxone sodium was reduced, the body weight of mice recovered and colon swellingimproved, colon histopathological injury was alleviated, inflammatory cell infiltration was alleviated, serum IL-10 increased significantly, LPS 、 TNF-α and IL-6 decreased significantly compared with model group, and the proportion of T cells and intestinal dysbiosis was improved. ConclusionsThe experimental results suggest that Bacillus subtilis-G. lucidum fermentation broth can effectively improve the intestinal barrier function damage, immune dysfunction and intestinal dysbiosis caused by antibiotic overdose, and has a certain regulatory effect on intestinal mucosal barrier function.

Subclinical inflammation in the preclinical phase of rheumatoid arthritis might contribute to articular joint damage

The first degree relatives of rheumatoid arthritis (RA) patients have a higher risk of developing RA, which is related to the expression of autoantibodies against citrullinated proteins (ACPA). Remarkably, prior to the onset of RA, cartilage damage is already initiated, whereas ACPA autoantibodies are already expressed. Here we show that both TNF-α and IL-6 are also increased prior to the onset of RA. Furthermore, when the levels of DKK1 and Sclerostin were evaluated in first degree relatives of RA patients, we found that the serum levels of TNF- α correlate with the expression levels of both DKK1 and Sclerostin. Interestingly, when the disease is already established, the correlation of TNF- α with DKK1 is lost in RA patients, whereas the correlation of Sclerostin with both TNF- α and IL-6 is further increased. Our data suggest a subclinical inflammation in patients at high risk of developing RA, which might lead to an increase in the levels of both DKK1 and Sclerostin, contributing to joint damage in the preclinical phase of the disease linked to the expression of ACPA autoantibodies.

Increased expression of in situ IL-31RA and circulating CXCL8 and CCL2 in pemphigus herpetiformis suggests participation of the IL-31 family in the pathogenesis of the disease.

Pemphigus herpetiformis (PH) is a rare clinical subtype of pemphigus with the presence of urticarial plaques, severe pruritus, rare acantholysis and eosinophilic spongiosis. The aim of this study was to investigate the influence of IL-31 and pro-inflammatory cytokines/chemokines in the pathogenesis of PH. Twenty-five patients with PH and three groups: pemphigus foliaceus (PF=14), pemphigus vulgaris (PV=15) and healthy controls (HC=20) were selected for this study. The groups were analysed by immunohistochemistry utilizing IL-31, IL-31RA, IL-4, IL-17 and TNF-α antibodies. Serum levels of IL-4, IL-13, TNF, CXCL8, CCL5 and CCL2 were evaluated by cytometric bead array. Analysis of IL-31 family of PH patients revealed the following findings: (i) Enhanced in situ expression of IL-31 in PH samples, compared to PF and to PV (epidermis); (ii) Cutaneous IL-31RA expression in PH samples was higher than in PF, PV and HC groups (epidermis and dermis); (iii) PF patients that evolved to PH showed significant increased IL-31RA epidermal expression during the PH phase. Profile of pro-inflammatory cytokines (IL-4, IL-17 and TNF-α) in PH patients' skin exhibited: (i) Enhanced IL-4 expression, when compared to patients with PF (epidermis and dermis) and with PV (epidermis); (ii) Augmented IL-17 expression than PF and PV patients (epidermis); (iii) Augmented expression of TNF-α when compared to PF at the epidermal level. Evaluation of circulating cytokines and chemokines showed higher levels of CXCL8 and CCL2 in PH sera compared to HC group. IL-31 and IL-31RA, cytokines related to pruritus, and pro-inflammatory chemokines (CXCL8 and CCL2) seem to exert a role in the pathogenesis of PH. These findings support future studies to clarify the role of IL-31 pathway as a potential therapeutic target for patients with PH.

Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial

ObjectivesThis study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19.Trial designThis study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial.ParticipantsWe are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran.The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities.The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month.Intervention and comparatorDuration of intervention: 7 days from randomizationIntervention in the treatment group:Vitamin A 25,000 IU dailyVitamin D 600,000 IU once during studyVitamin E 300 IU twice dailyVitamin C is taken four times per dayB vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg]The control group will not receive any supplements or placebo.All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand).Main outcomesWeight, height, and BMISeverity of pulmonary involvement according to CT scanRespiratory support (invasive or non-invasive)Percentage of oxygen saturation (SpO2 level)Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-αThe patient’s body temperatureThe presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys)Duration of hospitalizationMortality rateRandomizationAt baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients.Blinding (masking)Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group.Numbers to be randomized (sample size)The researchers plan to include 60 patients in total, with 30 patients in each group.Trial statusThis is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020.Trial registrationThe Iranian Registry of Clinical Trials IRCT20200319046819N1. Registered on April 4, 2020Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).

Spirulina platensis Extract Reduces Serum TNF-a, Neutrophils, and Increases Macrophage Count in Skin Incisional Mice Model

Spirulinasp.is an alga that has antioxidant and anti-inflammatory potential.Phycocyanin contained in Spirulina platensis can reduce tumor necrosis factor-? levels, neutrophils, and M2 macrophages in inflammation. This research aims to investigate the anti-inflammatory activity of S. platensisin a mice wound model. Thirty-two male Wistar rats were incised and divided into 4 groups. The first therapeutic group (X1) received S. platensisextract at a dose of 500 mg/kgBW/day, and the second therapeutic group received S. platensisextract at a dose of 750 mg/kgBW/day. The negative control group (C1) received a saline solution and the positive control group (C2) received diclofenac sodium 20mg/kgBW/day. Serum TNF-? levels examined by the Enzyme-Linked Immunosorbent Assaymethod. Neutrophils and M2 macrophages were calculated by tissue biopsy and hematoxylin-eosin (HE) staining. Data analysis was performed with ANOVA test and LSD Post-Hoc Test. The average levels of serum TNF-? on the 14-day were 394.50; 180.33; 2,980.33; and 607.42 pg/ml for X1, X2, C1 and C2, respectively. The average neutrophils number on the 14-day were 8.00; 6.83; 14.67; and 11.17 for X1, X2, C1 and C2, respectively. The average macrophage number in the 14-day was 15.50; 19.17; 6.33; and 11.17 for X1, X2, C1 and C2, respectively. We found significant differences between TNF-? levels, the number of neutrophils, and the number of M2 macrophages. The administration of S. platensisextract at a dose of 750 mg/ kgBW/day reduces serum TNF-? levels, neutrophil count, and increases M2 macrophages in skin incisional mice model.

The Effect of Vit D3 (1,25 dihydroxy cholicalciferol) on Serum Level of Human Tumor Necrosis Factor Alpha (TNF α) Following Apicoectomy

Aims: To evaluate the efficacy of Vit D3 on serum level of human TNF α in patients with chronic periapical lesion that intended to undergo apicoectomy and compare the results with a group of placebo control. Materials and Methods: The investigation was carried out on 50 subjects of different age(16- 45) and sex(27 male,23 female) complain of chronic periapical lesion were divided into two groups ) study and placebo group). Study group consist of 25 subject received Vit D3 ampoule(300000 IU) orally 24 hrs before apicoectomy procedure and placebo group consist of 25 subject received distal water ampoule orally 24 hrs before apicoectomy procedure. Peripheral venous blood samples were collected preoperatively , 3hrs postoperatively and 24 hrs postoperatively from each subject of both group to evaluate serum TNF α level by Enzyme Linked Immunosorbent Assays (ELISA) device. Patients subjectively assessed the strength the post operative pain by using Visual Analogue Scale (VAS). Data were analyzed using paired t-test and A NOVA test. Results: The results showed that the serum TNF α levels were decreased significantly in the study group after 3hrs of surgical procedure to (22.62 ± 4.58 Pg/ml) following Vit D3 treatment comparing with TNF α level pretreatment (28.33 ± 10.16 Pg/ml) whereas the TNF α level were increased from (33.38 ± 23.92 Pg/ml) preoperative to (51.11 ± 9.05 Pg/ml) 3hrs postoperative in placebo group. Serum TNF α level after 24hrs of surgical procedure in study group decreased significantly to( 28.24± 7.35Pg/ml) pg/ml) comparing with the postoperative 24 hrs TNF α of placebo group (66.15 ± 13.02 pg/ml),this indicated that the level of TNF α were increased in placebo group after 3hrs and 24hrs postoperatively in comparison to the same time of operation in study group. The number of analgesic tablet (acetaminophen) significantly decreased in study group to (1.24 ± 1.01 ) comparing with placebo group (2.24 ± 1.23). Duration of analgesia post operatively increase significantly to (308.20± 144.43) min in study group compared with placebo group (228.44 ±123.02) min. The intensity of postoperative pain decrease significantly after 8hrs (VAS1), 12 hrs (VAS2) of surgical operation in study group (1.16 ± 2.27), (0.44 ± 0.96) compared with placebo group (2.92 ± 1.87), ( 1.52 ± 1.78) respectively. Conclusion: data indicated that Vit D3 have anti inflammatory effect that can decrease level of TNF α so reduced pain and inflammation after apicoectomy .