TNF-alpha Levels Research Articles

4-OCTYL ITACONATE ATTENUATES ISOPROTERENOL INDUCED MYOCARDIAL DAMAGE VIA NLRP3 INFLAMMASOME PATHWAY, NRF-2/HO-1 AND MAPK PATHWAY IN AN EXPERIMENTAL MODEL

Objective: Myocardial infarction (MI) is the major cause of morbidity and mortality worldwide. According to the World Health Organisation, more than 9 million deaths occurred due to ischemic heart disease worldwide in 2016. 4-octyl itaconate (4-OI) is a cell permeable derivative of itaconate with potent anti-oxidative, anti-inflammatory and anti-fibrotic properties. Studies have shown that 4-OI inhibits pro-inflammatory cytokines (IL6, IL1beta, TNF alpha) and activates the anti-oxidant Nrf-2/HO-1 pathway. The aim of the study was to investigate the cardio-protective effect of 4-OI in experimental model of Isoproterenol induced myocardial damage. Design and method: Adult male albino wistar rats were used in the study. They were randomly divided to five groups i.e., normal control group, isoproterenol control group, 4-OI group (2.5, 5 or 10 mg/kg) for 14 days and 4-OI perse group. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Following this, blood was withdrawn using cardiac puncture, heart was excised and preserved for analysis of biochemical, histopathological and molecular pathway studies. Results: Isoproterenol administration to rats resulted in induction of Myocardial damage as shown by impairment in hemodynamic parameters, left ventricular dysfunction and raised cardiac injury markers. Treatment with 4-OI significantly improved hemodynamic and cardiac injury markers (CKMB, LDH). Further, 4OI significantly reduced oxidative stress (enhanced levels of SOD, GSH, decreased MDA levels) and inflammation (reduced levels of TNF alpha, IL-6, IL-1beta and NLRP3). Further it activated the Nrf-2-HO-1 pathway while inhibits the inflammatory NFKB pathway. Apart from this, it also ameliorated apoptosis by decreasing the expression of Bax, caspase-3 and increasing the expression of anti-apoptotic Bcl-2. It also inhibited inflammatory MAPK proteins (JNK, phospho JNK, P38, phospho P38) while enhancing the expression of pro-survival kinases ERK1/2, and Phospho ERK1/ 2. Conclusions: Oral administration of 4-OI at a dose of 10 mg/kg ameliorated the severity of isoprotorenol-induced cardio-toxicity in rats via NLRP-3 inflammasome pathway, MAPK and Nrf-2/HO1 pathway and by maintaining morphological structure of heart tissue and oxidative stress profile along with reduced inflammation and apoptosis.

CARDIOPROTECTIVE EFFECT OF TERIFLUNOMIDE IN AN EXPERIMENTAL MODEL OF MYOCARDIAL INFARCTION

Objective: MI is a major cause of mortality worldwide. Inflammation plays a key role in the pathology of MI. Teriflunomide (TERI), an orally active Dihydroorotate Dehydrogenase inhibitor, inhibits de novo pyrimidine synthesis. It decreases production of inflammatory cytokines and suppresses the activity and proliferation of activated lymphocytes. Hypothesis: TERI, on account of its potent anti-inflammatory activity may attenuate Isoproterenol induced cardiac injury in rats. Thus, we aimed to investigate the cardio-protective effect of Teriflunomide in isoproterenol (Iso) induced myocardial infarction. Design and method: To induce myocardial infarction in rats, we administered 2 doses of Isoproterenol (85 mg/kg/day, s.c.) on days 13th and 14th, at an interval of 24 hours. Male albino Wistar rats were divided into 5 groups (n = 6); namely normal control, isoproterenol control, Teriflunomide groups to receive saline, isoproterenol, or Teriflunomide (1, 3 or 5 mg/kg/day, p.o.) for 14 days. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Blood sample was collected via cardiac puncture, heart was excised and preserved for analysis of biochemical, histopathological and ultrastructural studies. Results: Isoproterenol administration to rats resulted in induction of MI with impairment of hemodynamic parameters. Teriflunomide pretreatment showed significantly improved hemodynamic (systolic, diastolic and mean blood pressures) and cardiac function parameters (normalized ± LV dP/dt and LVEDP) with reduction in the levels of cardiac injury markers (CK-MB, LDH). Further, Teriflunomide significantly reduced oxidative stress (enhanced levels of SOD, GSH, decreased MDA levels) and inflammation (reduced levels of TNF-alpha, IL-6), led to inhibition of active JNK and p38 proteins and activation of ERK1/2, a pro-survival kinase. Furthermore, it also ameliorated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3) and increased expression of Bcl-2, an anti-apoptotic marker. In addition, pretreatment with Teriflunomide preserved morphological and ultra-structural architecture of the myocardium as seen by H & E staining and electron microscopy. Conclusions: Teriflunomide at 1 mg/kg offered cardio-protection by improving hemodynamic profile, oxidative stress profile, reduced inflammation, normalization of myocardial architecture.

Derivation of Human Corneal Keratocytes from ReLEx SMILE Lenticules for Cell Therapy and Tissue Engineering.

Fibroblasts isolated and expanded from ReLEx SMILE lenticules can be a source of human keratocytes. Since corneal keratocytes are quiescent cells, it is difficult to expand them in vitro in suitable numbers for clinical and experimental use. In the present study, this problem was solved by isolating and growing corneal fibroblasts (CFs) with a high proliferative potential and their reversion to keratocytes in a selective serum-free medium. Fibroblasts reversed into keratocytes (rCFs) had a dendritic morphology and ultrastructural signs of activation of protein synthesis and metabolism. The cultivation of CFs in a medium with 10% FCS and their reversion into keratocytes was not accompanied by the induction of myofibroblasts. After reversion, the cells spontaneously formed spheroids and expressed keratocan and lumican markers, but not mesenchymal ones. The rCFs had low proliferative and migratory activity, and their conditioned medium contained a low level of VEGF. CF reversion was not accompanied by a change with the levels of IGF-1, TNF-alpha, SDF-1a, and sICAM-1. In the present study, it has been demonstrated that fibroblasts from ReLEx SMILE lenticules reverse into keratocytes in serum-free KGM, maintaining the morphology and functional properties of primary keratocytes. These keratocytes have a potential for tissue engineering and cell therapy of various corneal pathologies.

Stem cells therapeutic effect in a reserpine-induced fibromyalgia rat model: A possible NLRP3 inflammasome modulation with neurogenesis promotion in the cerebral cortex

Fibromyalgia is a chronic pain syndrome with a multifactorial pathophysiology affecting 2–8 % of the population. AimsTo investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) against fibromyalgia-related cerebral cortex damage and the possible underlying mechanisms of action. Materials and methodsRats were randomly allocated into three groups; control, fibromyalgia and fibromyalgia treated with BMSCs groups. Physical and behavioural assessments were performed. Cerebral cortices were collected for biochemical and histological assessment. Key findingsFibromyalgia group showed behavioural changes indicating presence of pain, fatigue, depression, and sleep disturbances. Moreover, biochemical biomarkers alterations were demonstrated by a significant decrease in brain monoamines and GSH levels, but MDA, NO, TNF-alpha, HMGB-1, NLRP3, and caspase-1 levels significantly increased. Furthermore, histological assessment revealed structural and ultrastructural alterations indicating neuronal and neuroglial degeneration with microglia activation, an increase in mast cell number and IL-1β immune-expression. Additionally, a significant decrease in Beclin-1 immune-expression, and blood brain barrier disruption were noticed. Interestingly, BMSCs administration significantly improved behavioural alterations, restored the reduced brain monoamines and oxidative stress markers, and reduced TNF-alpha, HMGB-1, NLRP3, and caspase-1 levels. Profoundly, cerebral cortices demonstrated improved histological structure, significant decrease in mast cell number and IL-1β immune-expression, besides a significant increase in Beclin-1 and DCX immune-expression. SignificanceFor the best of our knowledge, this is the first study showing ameliorative effects for BMSCs treatment in fibromyalgia-related cerebral cortical damage. The neurotherapeutic effects of BMSCs could be attributed to NLRP3 inflammasome signaling pathway inhibition, mast cell deactivation, and stimulation of neurogenesis and autophagy.

Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF=HF diet mice submitted to IF; HF-T=HF diet mice submitted to ET; HF-IFT=HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.

Thyroid status and TNF-alpha in post-reproductive women with COVID-19 and 12 months after the disease

The aim. To assess the thyroid status and its relationship with tumor necrosis factor alpha (TNF-alpha) in post-reproductive women in the acute phase of the COVID-19 of moderate course and 12 months after the disease.Materials and methods. 85 women aged 45 to 69 years were divided into groups: women without COVID-19, not vaccinated, with no antibodies to COVID-19 (IgG) – control group (n = 15); women in the acute phase of COVID-19 of a moderate course, accompanied by pneumonia – main group (n = 57); patients from the main group who agreed to be examined 12 months after having COVID-19 (n = 14); women with IgG in blood who deny any symptoms of COVID-19 in the last 12 months – asymptomatic COVID-19 (n = 13). Using hormone replacement therapy and the presence of thyroid disease in history were the exclusion criteria from the study.Results. 75.4 % of patients with COVID-19 had euthyroidism, 12.3 % had subclinical hyperthyroidism. An increase of free thyroxine (free T4) level in women with COVID-19 as compared to the control group (p = 0.004) and the group with asymptomatic COVID-19 (p = 0.054) was found. There was no statistically significant difference in the level of thyroid stimulating hormone between the groups. The level of C-reactive protein in women with COVID-19 was naturally higher as compared to the control group (p = 0.009) and the group of asymptomatic patients (p = 0.001). A lower TNF-alpha level was found in the group of patients without clinical signs of COVID-19 as compared to the control group (p = 0.007) and the group with COVID-19 (p = 0.00007). The analysis of correlation relationships revealed a positive correlation between of free T4 and TNF-alpha levels in women with COVID-19 (r = 0.38, p = 0.004).Conclusions. The moderate course of COVID-19 in the post-reproductive women is associated with an increase of free T4 level, which positively correlates with TNF-alpha level. Twelve months after COVID-19, thyroid status in women remains at the level of the acute phase of the disease.

The impact glycosylated hemoglobin level on admission plasma beta amyloid in patients with acute myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by Regione Friuli Venezia Giulia (grant for the project “Lo scompenso cardiaco quale morbo di Alzheimer del cuore: opportunita ` diagnostiche e terapeutiche—HEARTzheimer”). Background A strong relationship exists between Diabetes Mellitus and Alzheimer’s disease (AD) and the most recent researches in order to underline this strong connection are talking about type 3 diabetes. Plasma beta amyloid (Aβ) has pro-atherosclerotic and pro-inflammatory traits and has been associated with AD, aging, atherosclerotic processes, depression and diabetes. Aim and Methods We aimed to study the levels of Aβ 40 in a large population of patients with acute myocardial infarction and to evaluate if any association exists with long-term glycemic control. Hemoglobin A1c, Aβ 40, Vitamin D, hs CRP and TNF alpha were measured at hospital admission. Results In this study were included 603 patients admitted for acute myocardial infarction; according to hemoglobin A1c (HbA1c level), patients were classified into three groups: group 1 including 181 patients without diabetes (HbA1C < 39 mmol/mol), group 2 with 303 patients with pre-diabetes (HbA1C 39-47 mmol/mol) and group 3 comprising 199 patients with diabetes mellitus (HbA1C ≥48 mmol/mol). The levels of Aβ 40 significantly increase through group 1 to group 3 (76.1 [48-116], Vs. 91.3 [53.3-132], Vs. 101.6 [62.6-146.5], respectively, p<0.05, Figure 1). Also the levels of inflammatory markers CRP and TNF alpha were significantly higher in the group 3 respect to the other two groups. Independent predictors of Aβ 40 levels at regression analysis were presence of diabetes mellitus (OR 12.4, CI 95% 3.2-21.6, p=0.008), Vitamin D levels (OR 0.43, CI 95% 0.09-0.78, p 0.012) and renal function (OR 33.6, 95%CI 28.7-38.5, p<0.0001). Conclusions A better glyco-metabolic control in patients with myocardial infarction may reduce the risk of low-grade inflammation and production of biomarkers such as Aβ 40, associated with worse outcome. Further studies are necessary to evaluate if Aβ 40 levels are associated with post-MI depression and therapeutic non-compliance who lead to worse outcome.

The effect of JQ1 systemic administration on oxidative stress and apoptotic markers in renal ischemic reperfusion injury in a rat model.

This study aimed to investigate the effects of JQ1 in a renal ischemia-reperfusion (IR) rat model. Twenty-four adult male Wistar Albino rats were randomly divided into four equal groups. The sham group underwent laparotomy without ischemia-reperfusion induction. The control group experienced bilateral renal ischemia for 30 minutes, followed by a 2-hour reperfusion period. The vehicle group (IR group + DMSO) and JQ1 group (same as in control IR + 25 mg/kg JQ1). Kidney and blood samples were collected 2 hours after reperfusion. Blood samples were used to analyze serum creatinine and blood urea nitrogen levels. Renal tissue was assessed for TNF-alpha, caspase-3, FOXO4, PI3K/AKT signaling pathway, and histological analysis. The control group exhibited significantly higher serum creatinine, blood urea nitrogen, caspase-3, TNF-alpha, and FOXO4 levels in renal tissue compared to the sham group. Additionally, the PI3K/AKT signaling pathway was significantly decreased in the control group. Histopathological examination revealed severe kidney damage in the control group compared to the sham group. In rats treated with JQ1, serum creatinine, BUN, caspase-3, TNF-alpha, and FOXO4 levels in renal tissue significantly improved. The PI3K/AKT signaling pathway was substantially increased (p-value 0.01) compared to the Vehicle and Control groups. The tubular severity score was also significantly reduced in the JQ1-treated groups compared to the Control and Vehicle groups. In conclusion, JQ1 significantly ameliorated renal ischemia-reperfusion injury in rats by suppressing apoptosis and inflammatory pathways.

Evaluation of leptin hormone and Tumor necrosis factor levels in patients with type two diabetes mellites

: Type 2 diabetes mellitus (T2DM) is a leading cause of mortality and morbidity worldwide. Leptin, an adipokine with the primary function of regulating energy balance, is found to mediate insulin secretion and sensitivity in peripheral tissues. Aims: Hence, we aimed to determine the role of leptin in the development of insulin resistance (IR) in newly diagnosed T2DM patients and determine tumor necrosis factoralpha (TNF-α). Materials and methods: A case control study a total of 80 patients and 50 control groups, used Cobas E311 device to measure glucose, whereas HbA1c used D-10 hemoglobin Hba1c device whereas other parameters used ELISA methods were used to analyses 130 samples Results: Highly significant increase level of Fasting blood sugar, hemoglobin A1c, Insulin, Leptin and HOMA- insulin resistance whereas significant decrease level of TNF alpha and , Plasminogen activator inhibitors -1 in patient type two diabetes mellitus compared to the control group. Conclusion: increased the level of leptin levels while TNF-α levels were decreased in type 2 diabetes patients.

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

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

Phagocyte-related S100 proteins and cytokines in acute lymphoblastic leukemia and their prognostic value

In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death. The levels of S100A9, S100A12, IL-1beta, IL-12p70, IL-13, IL-17, IL-18, and MPO serum levels increased significantly as chemotherapy was initiated. The difference was most pronounced for S100A9 and S100A12, which had strong positive correlations with the neutrophil counts. In contrast, TNF-alpha, IL-6, IL-10, CCL-2, MMP-3, and CD25 serum levels decreased after chemotherapy. Although none of these biomarkers appear to be an independent predictor of outcomes, in predictive models with MRD as the outcome, AUC increased from 76% (95% CI 68–84%) when using initial risk group stratification alone to 83% (95% CI 73–91%) in a multivariate predictive model including initial risk group stratification and the biomarkers S100A12, TNF-alpha, and IL-10.

Can montelukast sodium be an alternative treatment in the treatment of interstitial cystitis?

The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology. Our study aims to explain the role of mast cells histologically and immunohistochemically in the pathogenesis and the effectiveness of montelukast that leukotriene D4 receptor antagonist in the treatment of interstitial cystitis. Twenty-four Wistar albino adult female rats were used. Group 1 (n = 8): control (sham) group, Group 2 (n = 8): interstitial cystitis group, and Group 3 (n = 8): treatment group. Groups 2 and 3 rats were administered 75 mg/kg cyclophosphamide four times every three days intraperitoneally. The rats in the treatment group were started on montelukast sodium as 10 mg/kg, 1 × 1/day per orally after the last administration of cyclophosphamide and were given for 14 days. Mast cells in the bladder tissues were examined histologically, and the presence of IL-6, 8, VEGF, and TNF alpha was examined immunohistochemically. Thin transitional epithelium, loose connective tissue, weak smooth muscle bundles, and signs of chronic inflammation were observed in the interstitial cystitis group. Regenerated transitional epithelium, intact basement membrane, compact lamina propia, thick smooth muscle bundles, and rare inflammatory cells were observed after the treatment with the montelukast. Mast cells were decreased in bladder tissue after treatment. IL-6, IL-8, VEGF, and TNF alpha levels were significantly decreased after treatment. We found that inflammatory mediators were significantly reduced after treatment with montelukast in the interstitial cystitis group. Montelukast can be used as an effective drug in the treatment of interstitial cystitis.

CD8+ Lymphocytes from Healthy Blood Donors Secrete Antiviral Levels of Interferon-Alpha.

The adaptive immune response to viral infections features the antigen-driven expansion of CD8+ T cells. These cells are widely recognized for their cytolytic activity that is mediated through the secretion of cytokines such as perforin and granzymes. Less appreciated is their ability to secrete soluble factors that restrict virus replication without killing the infected cells. In this study we measured the ability of primary anti-CD3/28-stimulated CD8+ T cells from healthy blood donors to secrete interferon-alpha. Supernatants collected from CD8+ T cell cultures were screened for their ability to suppress HIV-1 replication in vitro and their interferon-alpha concentrations were measured by ELISA. Interferon-alpha concentrations in the CD8+ T cell culture supernatants ranged from undetectable to 28.6 pg/mL. The anti-HIV-1 activity of the cell culture supernatants was observed to be dependent on the presence of interferon-alpha. Appreciable increases in the expression levels of type 1 interferon transcripts were observed following T cell receptor stimulation, suggesting that the secretion of interferon-alpha by CD8+ T cells is an antigen-driven response. In 42-plex cytokine assays, the cultures containing interferon-alpha were also found to contain elevated levels of GM-CSF, IL-10, IL-13, and TNF-alpha. Together, these results demonstrate that the secretion of anti-viral levels of interferon-alpha is a common function of CD8+ T cells. Furthermore, this CD8+ T cell function likely plays broader roles in health and disease.

The effect of quercetin on absence epilepsy in WAG/Rij rats

ABSTRACT Aim In the present study, the effect of quercetin, a powerful antioxidant flavonoid, on genetic absence epilepsy was studied in WAG/Rij rats. Material and Method Tripolar electrodes were implanted into WAG/Rij rats. Basal electrocorticography (ECoG) was recorded following a recovery period. After basal ECoG recording, different doses of quercetin (QRC) (25, 50 and 100 mg/kg) were injected intraperitoneally (i.p.) for 30 days. ECoG recording was continued for 31 days, three hours a day. After recording, the rats were anesthetized and euthanized through cervical dislocation and their brains were excised. Biochemically, TNF-alpha, IL-6 and NO were studied in whole rat brains. Results In WAG/Rij rats, low-dose quercetin (25 mg/kg) reduced the number and duration of spike-wave discharges (SWDs) compared to the control group. However, 50 and 100 mg/kg quercetin doses increased SWDs. Duration of SWDs was prolonged only with 100 mg/kg dose. None of the quercetin doses had any effect on average amplitude of SWDs. In addition, it was observed in biochemical analyses that 25 mg/kg quercetin reduced TNF-alpha, IL-6 and NO levels compared to the control group. While TNF-alpha and IL-6 levels in rat brains were not affected by 50 or 100 mg/kg doses, both doses were found to increase NO levels in rat brains. Conclusion Based on the results of the present study, 25 mg/kg low-dose quercetin may have reduced absence seizures by reducing proinflammatory cytokines and NO, but high-dose quercetin may have increased absence seizures through increasing the NO level. This contrasting effect of quercetin on absence seizures needs to be investigated by advanced mechanisms.

Cotinus coggygria Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators.

In traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.

Empathy at school project: Effects of didactics of emotions® on emotional competence, cortisol secretion and inflammatory profile in primary school children. A controlled longitudinal psychobiological study

BackgroundThere is mounting evidence of the presence of chronic stress among children during primary school: girls and boys under the age of 15 years often experience anxiety, irritability and sleeping problems with negative consequences on scholastic climate and the spread of bullying and dropping out of school. The promotion of emotion regulation within school environment through innovative didactic methodologies represents a valuable tool for teachers and parents to reduce emotional distress and associated risk behaviours and to promote wellbeing. AimOur research aims to explore the psychological and biological consequences of teaching emotional training in an experimental group of Italian Primary School children. MethodsA sample of pupils (81 children aged between 6 and 8) was divided into an experimental group (33 subjects) and a control group (30 subjects). A further advanced group of 18 subjects, who have experienced the method in the previous school year, was also included. The experimental study lasted one school year (from October 2021 to May 2022). The following psychological tests were administered to all groups: TEC (Test of Emotion Comprehension) to measure the children's different emotional abilities and the Projective test (PT) 'A person in the rain', to identify the coping skills of children in a stressful condition. Morning salivary cortisol, IL-6 and TNF-alpha assays were conducted in all three groups. Psychological and biological tests were administered at the beginning of the study and at the end of the study. ResultsThe MR-Anova model for TEC score showed that there was not a significant group effect [Fgroup = 2.24, p = 0.114]. Pairwise comparisons showed that mean score significantly increased only in the Experimental group (pB < 0.001) and at the end of the project there was a significant difference between Experimental group and Control group (pB = 0.012). The mean score of PT test increased significantly from baseline to the end of the project for the Experimental group (pB < 0.001) and for the Advanced group (pB = 0.004). At the end of the project, there were significant differences between the Experimental group and the Control group (pB = 0.004) and between the Advanced group and the Control group (pB < 0.001). Salivary cortisol analysis revealed a significant effect between subjects [Fgroup = 9.66; p < 0.001] and significant effects within subjects with the main effect of the time [Ftime = 35.41; p < 0.001] and the significant interaction “time x group” [Ftimexgroup = 3.38; p = 0.040]. Pairwise comparisons showed that cortisol levels decreased significantly over time only in the Experimental group (pB < 0.001). Regarding to IL-6 levels, there was not a significant effect between subjects [Fgroups = 0.0481; p = 0.953]. The mean level decreased significantly for each group from baseline to post project (pB < 0.001). With respect to TNF-alpha levels, the mean levels decreased over time for all groups (pB = 0.006 for Experimental group; pB < 0.001 either for the Advanced or Control group). Conclusionthe results documented in the experimental groups who experienced didactics of emotion for at least one school year show a significant increase in children's ability to cope with reality, stress and anxiety, and an improvement of their emotional competence. Meanwhile, a significant reduction in the amount of salivary cortisol was observed in the experimental group at the end of the scholastic year; meantime a stable reduced amount of salivary cortisol in advanced group throughout the project was also observed. These findings show that an intervention through an emotional education program is able to regulate interpersonal skills and the stress axis response.

Inflammatory CSF profiles and longitudinal development of cognitive decline in sporadic and GBA-associated PD

Inflammation modifies the incidence and progression of Parkinson’s disease (PD). By using 30 inflammatory markers in CSF in 498 people with PD and 67 people with dementia with Lewy bodies (DLB) we show that: (1) levels of ICAM-1, Interleukin-8, MCP-1, MIP-1 beta, SCF and VEGF were associated with clinical scores and neurodegenerative CSF biomarkers (Aβ1-42, t-Tau, p181-Tau, NFL and α-synuclein). (2) PD patients with GBA mutations show similar levels of inflammatory markers compared to PD patients without GBA mutations, even when stratified by mutation severity. (3) PD patients who longitudinally developed cognitive impairment during the study had higher levels of TNF-alpha at baseline compared to patients without the development of cognitive impairment. (4) Higher levels of VEGF and MIP-1 beta were associated with a longer duration until the development of cognitive impairment. We conclude that the majority of inflammatory markers is limited in robustly predicting longitudinal trajectories of developing cognitive impairment.

Effect of Combination of Soybean and Phaleria macrocarpa Ethanol Extract on IL6, TNFα, VEGF and Fibroblasts in Mice Exposed to UVB

UV exposure causes inflammation and the generation of reactive oxygen species, both of which contribute to skin aging. The purpose of this research was to determine how a combination of Phaleria macrocarpa extract and soybean extract affected the number of fibroblasts, VEGF, IL-6, and TNF alpha expression, and blood levels of IL-6 and TNF alpha in UV-B-exposed mice. In this study, mice were placed into four groups: one control group, three treatment groups, and a combination of Phaleria macrocarpa:soybeans at a 1:1 ratio (com group). The mice were euthanized on days 5 and 21 for histological preparations and then examined under a light microscope. Using an Olympus C-21 microscope with an Optilab Advances camera at 1000x magnification, the fibroblast was studied by counting the number of fibroblast cells per field of view. The immunohistochemical approach was performed to analyze the expression of VEGF, IL-6, and TNF- in skin tissue. The ELISA technique was used to quantify the levels of IL-6 and TNF-alpha. SPSS ver 21 was used to analyze the data. On days 5 and 21, the number of fibroblasts and expression of VEGF, IL-6, and TNF alpha were significantly higher in the combination group than in the control, Phaleria macrocarpa, and soybean treatment groups. However, there was no significant change in IL-6 and TNF alpha levels across groups on days 5 and 21 (p > 0.05). Finally, a 1:1 mixture of Phaleria macrocarpa and soybeans reduced the number of fibroblasts and the production of VEGF, IL-6, and TNF alpha on days 5 and 21, but not in serum levels.

Daily phytate intake increases adiponectin levels among patients with diabetes type 2: a randomized crossover trial

AimAdiponectin, a major adipokine secreted by adipose tissue, has been shown to improve insulin sensitivity. Myo-inositol hexaphosphate (phytate; InsP6) is a natural compound that is abundant in cereals, legumes, and nuts that has demonstrated to have different beneficial properties in patients with diabetes type 2.MethodsWe performed a randomized crossover trial to investigate the impact of daily consumption of InsP6 on serum levels of adiponectin, TNF-alpha, IL-6, and IL-1beta in patients with type 2 diabetes mellitus (T2DM; n = 39). Thus, we measure serum levels of these inflammatory markers, classic vascular risk factors, and urinary InsP6 at baseline and at the end of the intervention period.ResultsPatients who consumed InsP6 supplements for 3 months had higher levels of adiponectin and lower HbA1c than those who did not consume InsP6. No differences were found in TNF-alpha, IL-6, and IL-1beta.ConclusionThis is the first report to show that consumption of InsP6 increases plasma adiponectin concentration in patients with T2DM. Consequently, our findings indicate that following a phytate-rich diet has beneficial effects on adiponectin and HbA1c concentrations and it could help to prevent or minimize diabetic-related complications.

The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis.

Alginate (ALG) is a biocompatible and biodegradable polymer. Mechanical weakness is one of the main problems for the alginate-based scaffolds. Various plasticizer additives or modifications tested to improve the mechanical properties. In the presented study, ALG plasticized with triacetin (TA), and tributyl citrate (TBC) than tested on bone healing. In the presented study, the alginate modified with triacetin or tributyl citrate. In-vitro, and in-vivo efficiency of the scaffolds tested on bone tissue regeneration. Scaffolds fabricated by solvent casting, and physicochemical characterizations performed. Monocytes (THP-1) cultured with scaffolds, and macrophage-released cytokines was determined. In-vivo efficacy of the scaffolds was tested in the rat drill hole model. Alginate and tributyl citrate-modified scaffolds have no cytotoxic effect on osteoblastic cells (MC-3T3). Tributyl citrate modification increased tumor necrosis factor-alpha (TNF-alpha) level but did not increase interleukin -1 beta (IL-1 beta) level. In vivo studies showed that osteoblastic growth was significant in alginate and triacetin-modified scaffolds. However, the best values for osteoclastic activity and osteoid tissue formation seen in the triacetin modification. The results demonstrated that the modified alginate scaffolds were more successful than non-modified alginate scaffolds and can used as long-term bone repairing treatments.