Serum Tumor Necrosis Factor Research Articles

Eosinophil count and tumor necrosis factor α in response to phototherapy treatment of neonatal hyperbilirubinemia: a cross sectional study

BackgroundPhototherapy (PT) is the most often utilized technique for treating and preventing severe hyperbilirubinemia in the term and preterm newborns. PT's proven benefit is that it decreases the requirement for exchange transfusions. To investigate the effect of PT on allergic response mediators in neonates with hyperbilirubinemia treated by PT, eosinophil counts and tumor necrosis factor alfa levels have been assessed.MethodsThis cross-sectional study included 100 full-term infants with indirect hyperbilirubinemia in the first two weeks of life who were indicated for PT. They were investigated by tumor necrosis factor α and eosinophil counts before and 72 h after starting PT. The used tests were paired with Student’s t-test and Pearson coefficient.ResultsRelative and absolute eosinophil counts and tumor necrosis factor alfa were significantly higher after PT than before (p < 0.001). There was a significant positive correlation between total serum bilirubin and both tumor necrosis factor alfa and eosinophil % (r = 0.442 and r = 0.362, respectively, P < 0.001) before PT. There was a significant positive correlation between total serum bilirubin and both eosinophil count and eosinophil % (r = 0.281and r = 0.339), respectively (P < 0.001) after PT. There was a significant positive correlation between both tumor necrosis factor alfa and eosinophil % after PT (r = 0.545, P < 0.001).ConclusionsSerum tumor necrosis factor-alpha and eosinophilic count increased after treatment of neonatal hyperbilirubinemia by PT, which indicates an allergic response to PT in neonates.

Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study.

BACKGROUNDBiliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development.AIMTo determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.METHODSThis was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov–Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used.RESULTSPatients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage.CONCLUSIONPossible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.

TWIST1 silencing attenuates intracranial aneurysms by inhibiting NF-κB signaling

Purpose: To investigate the effect of Twist family basic helix-loop-helix transcription factor 1 (TWIST1) on intracranial aneurysms.Methods: A rat model of intracranial aneurysm was established by ligating the posterior branches of both the renal and left common carotid arteries. Pathological changes in the intracranial arterial wall were investigated using hematoxylin-eosin staining. TWIST1 expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, while vascular smooth muscle cell apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Inflammation was evaluated using enzyme-linked immunosorbent assay (ELISA).Results: Rats with intracranial aneurysms had degenerative changes in vessel wall structure. Inintracranial aneurysm rats, TWIST1 was upregulated in arterial wall sections, and TWIST1 knockdown ameliorated the pathological changes to the arterial wall. TWIST1 silencing reduced serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels and suppressed vascular smooth muscle cell apoptosis in rats with intracranial aneurysms. TWIST1 knockdown increased phospho (p)-inhibitor of nuclear factor-κB (IκB) and decreased IκB and p-p65 in intracranial aneurysm rat arterial wall sections.Conclusion: In intracranial aneurysms, silencing TWIST1 promoted vascular remodeling and suppresses vascular smooth muscle cell apoptosis and inflammation through inactivating NF-κBsignaling, revealing TWIST1 silencing as a potential treatment strategy.

Anti-inflammation effect of moxibustion for rats with diarrhea-predominant irritable bowel syndrome based on multiple miRNAs regulating NF-κB signal pathway

To observe the effect of moxibustion on the regulation of nuclear factor-kappa B (NF-κB) and inflammatory factors by multiple microRNAs (miRNAs) in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the anti-inflammatory mechanism of moxibustion on IBS-D. Twelve of 52 newborn rats were randomly selected into a normal group. The remaining rats were made into IBS-D model. A total of 36 rats with successful model were randomly divided into a model group, a medication group and a moxibustion group, 12 rats in each group. The rats in the medication group were intraperitoneally injected with pyrrolidine dithiocarbamate (PDTC). The rats in the moxibustion group were treated with moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for 20 min each time. All the intervention was given once a day for 7 days. Before and after modeling as well as after intervention, the body mass, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were measured. After intervention, the contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-8 were detected by ELISA method; the morphology of colon tissues was observed by HE staining, and the expressions of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues were detected by real-time PCR. The expressions of NF-κB p65, TNF-α, IL-1β and IL-8 protein in colon tissues were detected by immunofluorescence. After modeling, the body mass and the minimum volume threshold of AWR in the model group were lower than those in the normal group (P<0.01); the rates of loose stool in the model group were higher than those in the normal group (P<0.01); after intervention, in the model group, the inflammatory infiltration of colon tissues was obvious, and the serum levels of TNF-α, IL-1 β, IL-8 were higher than those in the normal group (P<0.05); the expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues was higher than that in the normal group (P<0.05); the protein expression of NF-κB p65, TNF-α, IL-1β, IL-8 was also higher than that in the normal group (P<0.01). After intervention, the body mass and the minimum volume threshold of AWR in the medication group and the moxibustion group were both higher than those in the model group (P<0.05); the loose stool rate in the medication group and the moxibustion group were lower than those in model group (P<0.05); the inflammatory cells infiltration in the colon tissues was less, the serum levels of TNF-α, IL-1β and IL-8 as well as the protein expression of NF-κB p65, TNF-α, IL-1β and IL-8 in the colon tissues in the medication group and the moxibustion group were lower than those in the model group (P<0.05, P<0.01). The expression of miR-125b, miR-31, miR-18a and NF-κB p65 mRNA in the medication group were lower than those in the model group (P<0.05). The expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in the moxibustion group were lower than those in the model group (P<0.05). The miR-155, miR-125b, miR-29b, miR-31, miR-18a were positively correlated with NF-κB p65 mRNA (0<r<1, P<0.01). The anti-inflammatory mechanism of moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for IBS-D rats may be related to regulating multiple miRNAs to inhibit NF-κB signal pathway and reduce the expression of inflammatory factors.

The Efficacy of Probiotic Supplementations on Glycemic Control, Lipid Profile, Inflammation Biomarkers and Anthropometric Measurements Among Type 2 Diabetes Patients

Background: Probiotics was defined as living organisms by the World Health Organization. These organisms when consumed as in food items or in the form of supplements, can lead to improvements in the health status of the host. Disturbances of intestinal biology contribute to the development of DM. Many trials have shown that the gut microbiome plays a role in the etiology and progression of type 1 and type 2 diabetes and its complications. This trial was designed to identify the effects of multi-species of probiotic supplementation on fasting blood glucose, lipid profile, inflammatory biomarkers, and in type 2 diabetic patients. Participants and methods: 65 type 2 diabetics were divided into 2 groups T (trial) and C (control) or placebo. The T group received daily one capsule of 14 differnt species of probiotic and C group received capsules filled with roasted ground chickpea. Fasting blood glucose, Serum Tumor Necrosis Factor alpha (TNFα) and C Reactive Protein (CRP), HDLC, LDLC, TG, TC levels were measured and anthropometric measurements such as weight, height, waist circumference and BMI were recorded at beginning and the end of the study which lasted for 10 weeks. Results and discussion: In the probiotic group, fasting plasma glucose decreased significantly (P &lt;0.05) compared to the control group, 131.1 ± 10.1 vs 145.7 ± 9.8 (mg/dL). Furthermore, a significant reduction was also apparent TC level in the trial group before and after supplementation (184 ± 31 vs 199 ± 21 ) the difference was significant (P &lt; 0.05). The group which received probiotic also showed significant reduction in TG (P &lt; 0.05) compare to control group ( 128 ± 23 vs 1 1 ± 32 respectively). Also, the LDL value, significantly reduced in the probiotic compared to the control group 137 ± 30 and 149 ± 31 ( P &lt; 0.05). Probiotic supplementation significantly increased HDL 41 ± 13 vs 29.8 ± 12 (P &lt; 0.05). Significant differences (P &lt;0.05) in the serum levels of inflammatory markers at the end of the study were observed. Probiotic supplementation decreases CRP (mg/dL) levels and TNFa (pg/ml) (2.11± 4.3 vs 1.68 ± 3.33 and 2.51 ±2.3 vs 2.31 ± 3.6 respectively).. A significant reduction in TNF-α level was observed. The level was 6.8 5.6 ± at the beginning of the trial and reduced to 5.4± 5.1 whereas in the control group TNF-α levels were 5.6 ± 7.6 and 5.6 ± 7.8 at the beginning and at the end of the study respectively .Probiotics supplementations reduced significantly (P &lt;0.05(BMI of participants in trial group (27.6 ± 5.2 vs 33.8 ± 10.1). Conclusion: The results obtained from this study suggest that probiotic supplementation may have positive effects and can be considered as method to control glucose levels, lipids, inflammatory biomarkers, and reduce body weight in type 2 diabetic patients.

398-P: KIM-1 and TNFR 1 and Associations with Early Diabetic Nephropathy Histology

Aim: GFR and urine albumin excretion (UAE) are prevailing measures used to detect and monitor diabetic nephropathy (DN) . We tested whether serum kidney injury molecule-1 (KIM-1) and tumor necrosis factor receptor-1 (TNFR1) , markers of DN progression, are associated with DN renal structural parameters in persons with TIDM. Methods: We measured KIM-1 and TFNR1 in 285 participants from the Renin Angiotensin System Study (RASS) . Participants had T1DM for 2-20 yrs and were free of any clinical DN. Baseline iGFR and kidney biopsies were obtained. We used linear regression to estimate cross-sectional associations of markers with renal structural measures. Results: Mean age was 30 ± yrs; mean iGFR was 125 ± 18 ml/min/1.73 m2; median UAE was 5 (IQR 4- 7) . Higher KIM-1 was associated with significantly greater mesangial fraction volume [Vv (Mes/glom) ] and the tubular atrophy (table 1) . Higher TNFR1 was associated with significantly higher Vv (Mes/glom) and glomerular basement membrane (GBM) width. Neither iGFR nor UAE were significantly associated with lesions. Conclusion: Serum KIM-1 and TNFR1 were associated with higher values for Vv (Mes/glom) , GBM, and tubular atrophy in persons with T1DM and normal kidney function, suggesting relevance as markers of early DN structural changes prior to UAE elevation or GFR decline. KIM-1 is specific to the tubules, highlighting the importance of characterizing the natural history of tubular functions in DN. Disclosure F.Tian: None. D.Prince: None. A.Doria: Research Support; Novo Nordisk Foundation. M.Mauer: None. B.Kestenbaum: Consultant; Reata Pharmaceuticals, Inc. Funding T32

Yinzhihuang oral liquid protects against non-alcoholic steatohepatitis via modulation of the gut-liver axis in mice.

BackgroundYinzhihuang (YZH) oral liquid is a traditional Chinese medicine compound that has emerged as a promising therapeutic agent for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the therapeutic effects of YZH on non-alcoholic steatohepatitis (NASH) and elucidate its underlying molecular mechanisms.MethodsMice fed on a high-fat diet plus fructose/glucose drinking water (HFGD) were treated with YZH (30 mL/kg/d). The effects of YZH on mice with NASH were assessed through serological analysis and histological examination. Microbiota analysis based on 16S ribosomal ribonucleic acid (16S rRNA) and intestinal mucosal barrier function, serum inflammatory factors, hepatic macrophage infiltration, as well as hepatic toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NFκB) pathway were carried out to explore the mechanism of YZH for treatment of NASH.ResultsResults of the current study found that YZH effectively reduced body weight gain and adiposity and alleviated hepatocyte steatosis, hepatocyte ballooning, liver tissue lobular inflammation, as well as fibrosis. It also reduced the accumulation of triglycerides, cholesterol, and free fatty acids in the liver of the treated mice and normalized serum aspartate transaminase, alanine transaminase, and glucose levels as well as lipid metabolism. Meanwhile, YZH treatment significantly decreased the abundance of harmful bacteria, such as Mucispirillum, Helicobacter, and Desulfovibrionaceae. Mechanistically, the present study found that YZH upregulated the expression of tight junction proteins, decreased serum lipopolysaccharide, interleukin 6, and tumor necrosis factor α levels, and increased interleukin 10 levels in serum. In the liver, YZH alleviated macrophage infiltration, especially that of pro-inflammatory macrophages. Moreover, it was found that YZH inhibited the canonical TLR4, MyD88, NFκB signaling pathway.ConclusionsIn conclusion, YZH may be a new agent for the prevention of NASH. Further, YZH alleviates gut microbiota dysbiosis, restores the intestinal mucosal barrier, and inhibits the canonical TLR4, MyD88, NFκB signaling pathway.

Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm

BackgroundSevere COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease, attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor (α7nAChR) signal transduction, to prevent cytokine storm.MethodsThe potential anti-inflammatory effects of famotidine and other H2R antagonists were assessed in mice exposed to lipopolysaccharide (LPS)-induced cytokine storm. As the inflammatory reflex is integrated and can be stimulated in the brain, and H2R antagonists penetrate the blood brain barrier poorly, famotidine was administered by intracerebroventricular (ICV) or intraperitoneal (IP) routes.ResultsFamotidine administered IP significantly reduced serum and splenic LPS-stimulated tumor necrosis factor (TNF) and IL-6 concentrations, significantly improving survival. The effects of ICV famotidine were significantly more potent as compared to the peripheral route. Mice lacking mast cells by genetic deletion also responded to famotidine, indicating the anti-inflammatory effects are not mast cell-dependent. Either bilateral sub-diaphragmatic vagotomy or genetic knock-out of α7nAChR abolished the anti-inflammatory effects of famotidine, indicating the inflammatory reflex as famotidine’s mechanism of action. While the structurally similar H2R antagonist tiotidine displayed equivalent anti-inflammatory activity, the H2R antagonists cimetidine or ranitidine were ineffective even at very high dosages.ConclusionsThese observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.

The role and mechanism of TLR4-siRNA in the impairment of learning and memory in young mice induced by isoflurane.

Isoflurane can significantly induce inflammation in children without surgical stress. The toll-like receptor 4 (TLR4) is closely related to noninfectious inflammation in the brain. To investigate the role of TLR4-small interfering RNA (siRNA) in learning and memory impairment in young mice induced by isoflurane. The C57 newborn mice were randomly allocated into normal control (control), isoflurane anesthesia (isoflurane), TLR4 interference empty vector+isoflurane anesthesia (siRNA-NC), and TLR4 interference+isoflurane anesthesia (TLR-siRNA) groups. Their behavior and pathological condition were detected using Morris water maze and hematoxylin and eosin (H&E) staining, respectively. The TLR4, brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element-binding protein 1 (CREB1) mRNA expressions were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 were detected by means of the enzyme-linked immunosorbent assay (ELISA). Apoptosis rate was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The TLR4, TNF-α, IL-6, BDNF, CREB1, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) protein expressions were detected using western blot (WB). Compared with the control group, the number of times the mice crossed the platform, and the time spent at the circumjacent area I and II of the platform were significantly decreased in the isoflurane group; the TLR4, TNF-α and IL-6 expressions were significantly increased in the isoflurane group, as compared to control; the results were reversed after the TLR4 interference. The hippocampal neurons in the isoflurane and siRNA-NC groups showed arrangement disorder and a high number of inflammatory infiltrates, while in the TLR-siRNA group they were closely and orderly arranged. Compared with the control group, the apoptosis rate and JNK protein expression in the isoflurane group were significantly increased, CREB1 protein expression was significantly decreased, and BDNF and ERK1/2 protein expressions showed no significant changes. Compared with the isoflurane group, the apoptosis rate of the TLR-siRNA group was significantly decreased, BDNF and CREB1 protein expressions were significantly increased, and ERK1/2 and JNK did not change significantly. Isoflurane stimulates the overexpression of inflammatory response factors, playing an important role in the cognitive impairment process. As a mediator of the innate immune inflammatory response, TLR4 plays an important role in the process of cell injury, which may be delayed by blocking the TLR4 signal.

Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan

BackgroundThe pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be associated with chronic inflammation; however, the underlying mechanism remains unclear. Recently, altered gut microbiota were found in patients with pulmonary arterial hypertension (PAH) and in experimental PAH models. The aim of this study was to characterize the gut microbiota in patients with CTEPH and assess the relationship between gut dysbiosis and inflammation in CTEPH.MethodsIn this observational study, fecal samples were collected from 11 patients with CTEPH and 22 healthy participants. The abundance of gut microbiota in these fecal samples was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Inflammatory cytokine and endotoxin levels were also assessed in patients with CTEPH and control participants.ResultsThe levels of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were elevated in patients with CTEPH. Plasma endotoxin levels were significantly increased in patients with CTEPH (P < 0.001), and were positively correlated with TNF-α, IL-6, IL-8, and MIP-1α levels. The 16S rRNA gene sequencing and the principal coordinate analysis revealed the distinction in the gut microbiota between patients with CTEPH (P < 0.01) and control participants as well as the decreased bacterial alpha-diversity in patients with CTEPH. A random forest analysis for predicting the distinction in gut microbiota revealed an accuracy of 80.3%.ConclusionThe composition of the gut microbiota in patients with CTEPH was distinct from that of healthy participants, which may be associated with the elevated inflammatory cytokines and endotoxins in CTEPH.

TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability

Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive. Using a novel humanized model of experimental colitis, we demonstrate that TNF interfered with the tissue repair program via induction of a soluble natural antagonist of IL-22 (IL-22Ra2; IL-22BP) in the colon and abrogated IL-22/STAT3-mediated mucosal repair during colitis. Furthermore, membrane-bound TNF expressed by T cells perpetuated colonic inflammation, while soluble TNF produced by epithelial cells (IECs) induced IL-22BP expression in colonic dendritic cells (DCs) and dampened IL-22-driven restitution of colonic epithelial functions. Finally, TNF induced IL-22BP expression in human monocyte-derived DCs and levels of IL22-BP correlated with TNF in sera of IBD patients. Thus, our data can explain how anti-TNF therapy induces mucosal healing by increasing IL-22 availability and implicates new therapeutic opportunities for IBD.

MiR-21 antagonist alleviates colitis and angiogenesis via the PTEN/PI3K/AKT pathway in colitis mice induced by TNBS.

BackgroundThe pathogenesis of Crohn’s disease (CD) is unknown; however, angiogenesis is known to play an important role in the disease. The present research suggests that microRNA-21 (miR-21) may play a positive regulatory role in disordered angiogenesis in CD.MethodsC57 wild-type mice were divided into 6 groups. On day 0, all mice in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) group were given an enema at the concentration of TNBS 100 mg/kg mouse body weight (solvent 50% alcohol). In the control group, the enema was performed with 50% alcohol. On day 0, 2, 4, and 6, the mice of the agomir-21 + TNBS group and the agomir control + TNBS group were injected with 200 µL, 5 nmol agomir-21 or agomir control [dissolved in ribonuclease (RNase)-free water] by tail vein injection, while the antagomir-21 + TNBS group and the antagomir control + TNBS group were injected with 200 µL, 20 nmol antagomir-21 or antagomir control (dissolved in RNase-free water). The body weight and disease activity index (DAI) score were recorded daily. The colons were obtained to assess macro and microscopic colon damage. The inferior vena cava and the accompanying abdominal aorta were chosen to detect the protein expression of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT)/vascular endothelial growth factor (VEGF) axis through western blotting. Serum interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The distribution and expression of neovascularization were demonstrated by cluster of differentiation 31 (CD31) immunohistochemistry.ResultsCompared with the only-TNBS group, the agomir-21 + TNBS group showed significantly severer colitis symptoms and more abnormal vascular hyperplasia, while the antagomir-21 + TNBS group showed symptom relief and reduced vascular hyperplasia. In addition, agomir-21 obviously inhibited the expression of PTEN and activated the PI3K/AKT/VEGF pathway in mice induced by TNBS, while antagomir-21 effectively antagonized this effect.ConclusionsmiR-21 can promote the progression of colitis in mice induced by TNBS and aggravate the disordered angiogenesis by regulating the PTEN/PI3K/AKT axis. Intravenous injection of miR-21 antagonists can effectively relieve the symptoms of colitis and inhibit colonic angiogenesis.

Inflammatory cytokines and sarcopenia in Iranian adults-results from SARIR study

Some studies suggested the effects of inflammatory cytokines in reducing muscle mass and muscle strength and, performance. This study aimed to compare pro-inflammatory cytokines in sarcopenic and non-sarcopenic subjects. 120 men and women were selected out from the cross-sectional study ‘sarcopenia and its determinants among Iranian elders’ (SARIR). Sarcopenia was defined based on the first ‘European Working Group on sarcopenia in older people’ (EWGSOP1) guidelines. A fasting blood sample was taken from each participant to measure serum high-sensitivity C-reactive protein (hs-CRP), Interleukin 6 (IL-6), and tumor necrosis factor α (TNFα). A total of 120 participants were included in this study. Mean age was 66.7 ± 7.7 years and mean body mass index (BMI) was 27.3 ± 4.2 kg/m2. Forty participants had the criteria of EWGSOP1 sarcopenia. A statistically significant difference was seen between normal and abnormal groups of muscle strength in hs-CRP (P-value = 0.04). Furthermore, we did not observe any remarkable association between inflammatory biomarkers including IL-6 (OR 1.15; 95% CI 0.31–4.28), TNF-α (OR 0.68; 95% CI 0.17–2.77), and hs-CRP (OR 2.39; 95% CI 0.87–6.55) and the presence of sarcopenia even after controlling for plausible confounders. We found that inflammatory biomarkers level was not associated with odds of sarcopenia. The lack of correlation between inflammatory cytokines and sarcopenia could be due to the participants’ age and genetics. Future studies are required to confirm these findings.

The clinical efficacy and safety of dapagliflozin in patients with diabetic nephropathy

ObjectiveTo investigate the clinical efficacy and safety of dapagliflozin in the treatment of diabetic nephropathy (DN).MethodsA total of 120 DN patients admitted to our hospital from June 2017 to March 2020 were divided into control and experimental groups, with 60 cases in each group. The control group received valsartan, and the experimental group received dapagliflozin for 3 months. Body mass index (BMI), hemoglobin A1c (HbA1c), serum creatinine (sCr), uric acid (UA), urine microalbumin (uMA), urine creatinine (uCr), and bilateral kidney function were compared before and after treatment, and adverse reactions in both groups were observed. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were also evaluated.ResultsAfter treatment, except for BMI in the control group, all indexes in both groups were significantly improved. The BMI, HbA1c, sCr, UA, and uMA/uCr ratios of the experimental group were lower than those of the control group. Serum albumin (sAlb) levels were increased in both groups, and the experimental group showed a significant difference compared with the control group. Estimated glomerular filtration rate (eGFR) levels were increased in both groups, and the experimental group was higher than the control group, with no significant differences. Serum IL-6 and TNF-α levels in both groups were lower, and the experimental group was significantly lower than the control group. No serious adverse reactions were observed in either group.ConclusionThe efficacy of dapagliflozin was demonstrated by its ability to improve diabetes, prevent nephropathy exacerbation, and reduce symptomatic reactions. The low rate of adverse reactions makes dapagliflozin a very safe medication.

The Effects of Enriched Rehabilitation on Cognitive Function and Serum Glutamate Levels Post-stroke.

AimThis study aimed to explore the effect of enriched rehabilitation (ER) on cognitive function and serum glutamate levels in patients with stroke.MethodsForty patients diagnosed with post-stroke cognitive impairment (PSCI), according to the inclusion criteria, and undergoing inpatient rehabilitation were enrolled in the study. Patients were randomly assigned to receive 8 weeks of ER treatment (ER group; n = 20) or conventional medical treatment (CM group; n = 20). In addition, 20 age-matched healthy subjects who were outpatients in our hospital during the same period formed the healthy control (HC) group. In- and between-group differences in cognitive function were assessed during pre-intervention and post-intervention based on the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT). The serum levels of glutamate, tumor necrosis factor (TNF), and malondialdehyde (MDA) levels were also detected pre-intervention and post-intervention.ResultsPre-intervention cognitive function and the levels of all the serum parameters assessed significant difference between the HC group and the PSCI group (both ER and CM groups) (p < 0.05), but not between the two groups of patients with PSCI (p > 0.05). Significant improvements were observed in cognitive function in both the ER and the CM groups post-intervention compared with pre-intervention, as evidenced by the measured improvement in MoCA, SDMT, and TMT scores. Similar improvements were seen for serum glutamate, the degree of oxidative damage, and the level of inflammation in both the treatment groups (p < 0.05). More enhancements in cognitive function, including MoCA, SDMT, TMT scores, and the serum levels of glutamate, the degree of oxidative damage, and the level of inflammation were shown in the ER group compared with the CM group post-intervention (p < 0.05).ConclusionsER can improve cognitive function in patients with PSCI. The associated mechanism may be related to the negative regulatory effect of ER on serum glutamate, TNF, and MDA levels, which is likely to enhance synaptic plasticity and alleviate oxidative stress- and inflammation-related damage, at least to some extent.

TNF-α and TGF-β Contributes in Recurrent Otorrhea of Active Mucosal Chronic Otitis Media

BACKGROUND: Active mucosal chronic otitis media (COM) is prevalent in lower-income countries and is associated with recurrent episodes of otorrhea due to chronic inflammation of the middle ear. Cytokines, which are well-known for their effects on the immune system, play an important role in the inflammatory response and tissue remodeling. The specific contributions of proinflammatory and immunoregulatory cytokines in the pathophysiology of active mucosal COM remain unclear. This study aimed to compare the levels of serum tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β in patients with active mucosal COM vs. healthy subjects.METHODS: Total 20 subjects with active mucosal COM and 20 healthy subjects participated in this study. The levels of serum TNF-α and TGF-β were measured using enzyme-linked immunosorbent assay (ELISA).RESULTS: The average level of serum TNF-α in subjects with active mucosal COM was significantly higher compare to the healthy subjects (46.373±41.76 pg/mL vs. 15.021±7.16 pg/mL; p=0.004). In contrast, the average level of serum TGF-β in subjects with active mucosal COM was lower compared to the healthy subjects, although the difference is not statistically significant (9.963±3.2 ng/mL vs. 11.78±8.48 ng/mL; p=0.552). Further analysis showed that in subjects with active mucosal COM, the levels of serum TNF-α had a medium positive correlation with the level of TGF-β (r=0.525; p=0.018).CONCLUSION: TNF-α and TGF-β, which are proinflammatory and immunoregulatory cytokines, may contribute to the pathogenesis of recurrent episodes of otorrhea in an active mucosal COM.KEYWORDS: tumor necrosis factor-α, transforming growth factor-β, active mucosal chronic otitis media

Full-fat field cricket (Gryllus bimaculatus) as a substitute for fish meal and soybean meal for weaning piglets: effects on growth performance, intestinal health, and redox status.

Full-fat field cricket meal (FCP) is an alternative protein ingredient in livestock production; however, the effects of replacing conventional protein sources with FCP in nursery diets have not been determined. In this study, the effects of the partial replacement of either fish meal or soybean meal with FCP on weaning pigs were evaluated, including the analyses of growth performance, nutrient utilization, intestinal morphology, immunity, oxidative stress, and fecal microbial counts. A total of 100 crossbred weaning pigs [(Landrace × Large White) × Duroc] were allotted to one of the following five treatments with five replicates (four pigs/pen) and fed for 28 d postweaning. Treatments were 1) a corn-soybean meal (SBM)-based diet with 5% fish meal (Positive control; PC), 2) a corn-SBM-based diet without fish meal (Negative control; NC), 3) field crickets replacing fishmeal on a total Lys basis (FCP1), 4) field crickets replacing fishmeal on a kg/kg basis (FCP2), and 5) field crickets replacing fish meal and soybean meal (FCP3). The piglets on FCP1 had a higher body weight on days 14 and 28, and an increased average daily gain over the experimental period than NC (P < 0.05); FCP2 and FCP3 were similar to the FCP1 treatment. The incidence of diarrhea was lower under an FCP-supplemented diet than under the NC diet throughout the study (P < 0.05). Pigs fed FCP1 and FCP2 had a higher digestibility of crude protein (P = 0.041), and all FCP groups increased crude fat digestibility (P = 0.024). FCP1 and FCP2 also increased jejunal villus height (P = 0.009), whereas the increase in jejunal villus-to-crypt ratios (P = 0.019) was greater in pigs fed the FCP2 diet than those fed the NC diet. Furthermore, FCP2 supplementation increased serum immunoglobulin A levels on days 14 and 28, including reduced serum interleukin-6 and tumor necrosis factor alpha levels (P < 0.05). Pigs fed an FCP2 diet had reduced malondialdehyde levels than those fed a PC diet, while pigs fed an FCP2 diet had higher superoxide dismutase and glutathione peroxidase levels, and more fecal Lactobacillus spp. than those fed an NC diet (P < 0.05). These results support the use of FCP as an alternative protein ingredient with beneficial effects on growth performance, intestinal morphology, antioxidant capacity, and intestinal microbiota. In particular, FCP can be used as a partial substitute for fish meal and soybean meal without detrimental effects on weaning pigs.

Effect of a Hemodialysis Session on Markers of Inflammation and Endotoxin.

Background People receiving hemodialysis (HD) treatment have higher cardiovascular morbidity and mortality, ascribed to an increased prevalence of traditional cardiovascular risk factors. However, the role of nontraditional risk factors, such as inflammation, has become increasingly recognized. The origin of this inflammation remains elusive and one putative cause is elevated levels of circulating bacterial endotoxin. Methods In this study, serum concentrations of endotoxin and inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1β (IL1β), ferritin and tumor necrosis factor (TNF), were measured in 30 adults receiving HD and 10 healthy individuals without kidney disease. In people receiving HD, samples were collected immediately before dialysis (preHD), after dialysis (postHD), and 48 hours after (postHD48hrs). Results Endotoxin was detectable in only 1 of 90 samples analyzed. There were no significant differences in serum hsCRP, IL1β, and IL6 levels, before and after dialysis. Serum TNF levels decreased significantly from 30.9 (8.0, 39.5) pg/mL preHD to 13.9 (8.5, 17.3) pg/mL post-HD (p=0.002) and then increased back to 27.37 (14.5, 35) pg/mL 2 days later (p < 0.001). Ferritin increased from 1153 ng/mL (782, 1458) preHD to 1313 ng/mL (657, 1638) post HD (p < 0.001) and then decreased back to 1186 ng/mL (754, 1597) (p=0.66) postHD48hrs. Compared to controls, people receiving HD had significantly elevated levels of hsCRP [6.16 mg/L (2.1, 16.8) vs. 1.1 mg/L (0.81, 3.63) p=0.015], IL1β [1.5 pg/mL (0.05, 2.51) vs. 0.5 pg/mL (1.81, 2.95) p ≤ 0.001], and ferritin [1153 (782, 1458) vs. 132.9 (111, 257) ng/mL p ≤ 0.001], but comparable levels of in IL6 [6.15 pg/mL (4.82, 9.12) vs. 7.49 pg/mL (4.56, 10.39), p=0.77] and TNF [27.35 pg/mL ± 17.48 vs. 17.87 pg/mL ± 12.28, p < 0.12]. In conclusion, people on HD have elevated levels of inflammatory biomarkers, which are not associated with endotoxemia (which is rare) or the dialysis procedure.

Correlation of Blood Biochemical Markers with Tardive Dyskinesia in Schizophrenic Patients.

Objective Oxidative stress factors and proinflammatory cytokines had been found to be involved in the pathogenesis of patients with tardive dyskinesia (TD). This study assumes that blood biochemical markers would have a link with TD in schizophrenia patients. To explore the correlation between blood biochemical markers and tardive dyskinesia in patients with schizophrenia (SCH). Methods From January 2010 to August 2021, the inpatients who met the diagnostic criteria of schizophrenia in the Chinese Classification and Diagnosis Criteria of Mental Disorders (DSM-4) and the American Diagnostic and Statistical Manual of Mental Disorders (DSM-4) were followed up in the psychiatric outpatient department of Jinxia Street Community Health Service Center, Longhu District, Shantou City. The diagnostic criteria of Abnormal Involuntary Movement Scale (AIMS) used in the TD study of Schooler and Kane were used to screen the patients. Patients were divided into the schizophrenia (SCH group) and the schizophrenia with TD groups (TD group). Oxidative stress factors including Superoxide Dismutase1 (SOD1), Glutathione Peroxidase1 (GPX1), Malondialdehyde1 (MDA1), Catalase Activity1 (CAT1), and brain-derived neurotrophic factor 1 (BDNF1) and some inflammatory cytokines including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), serum tumor necrosis factor (TNF-α), prolactin, estrogen, and cortisol were measured in 121 schizophrenic patients with tardive dyskinesia and 118 schizophrenic patients. The correlation analysis was conducted on the data. Results Age and female were immutable risk factors for the development of TD, and there were significant differences in blood biochemical indices GPX1, MDA1, CAT1, and TNF-α in schizophrenic patients with and without TD. Conclusion This study supports that oxidative stress and immune disorders are associated with TD patients. Blood biochemical markers GPX1, MDA1, CAT1, and TNF-α may play an important role in the pathogenesis of schizophrenia combined with TD patients, and they may be useful in the diagnosis of schizophrenia with tardive dyskinesia.

Influence of Foam generated in Pharmaceutical Suspensions Manufacturing Process on Active Pharmaceutical Ingredient Contents of Finished Products

Ficus erecta var. sieboldii (Miq.) King is a deciduous tree distributed on Jeju Island in Korea. The beneficial effects of F. erecta var. sieboldii have been noted in many diseases such as nephritis and arthritis. However, it is still unclear how F. erecta var. sieboldii modulates the immune response in mice; therefore, this study aimed to assess whether F. erecta var. sieboldii extracts upregulate this immune response. The administration of F. erecta var. sieboldii increased the spleen index, splenocytes proliferation, and serum tumor necrosis factor (TNF-α) and interleukin (IL)-6 levels. In addition, F. erecta var. sieboldii also increased the messenger ribonucleic acid (mRNA) expression of helper T cell-related cytokines (TNF-α, IL-6, IFN-γ, IL-17, and IL-10) and transcription factors (T-bet, RORγt, and Foxp3) in the spleen. These results suggest that F. erecta var. sieboldii can regulate the immune response in mice.