Multi-species synbiotic supplementation increased fecal short chain fatty acids and anti-inflammatory cytokine interleukin-10 in adult men with dyslipidemia; A randomized, double-blind, clinical trial.

BACKGROUND: Mounting evidence revealed that an imbalance of Gut Microbiota (GM) leads to metabolic disorders. Synbiotics through regulation of GM composition can be an effective intervention in the management of metabolic diseases. This study aimed to investigate the effects of multi-species synbiotic supplementation on serum interleukin10 (IL-10) and fecal Short Chain Fatty Acids (SCFAs) in patients with dyslipidemia. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, fifty-six adult men with dyslipidemia were randomly allocated to intervention and control groups and received either synbiotic or placebo powder twice a day for 12 weeks. Each synbiotic sachet contained 6 species of probiotic microorganisms with a total dose of 3 × 1010 Colony Forming Unit (CFU) and 5 gr inulin and Fructooligosaccharide (FOS) as prebiotics. Blood and stool samples were collected at the baseline and end of the study. Dietary intake, physical activity, anthropometric measurements, serum IL-10, and fecal SCFAs were assessed before and after the intervention. RESULT: There were no significant differences between the baseline characteristics of patients in the two groups. Serum IL-10 was increased in the synbiotic group (p < 0.0001). Moreover, synbiotic supplementation increased fecal concentration of acetate (p < 0.0001), butyrate (p = 0.043), propionate (p < 0.0001), and valerate (p < 0.026). A significant positive correlation was observed between the changes in fecal butyrate level and serum IL-10 concentration in the control group (r = 0.48, p = 0.01). CONCLUSIONS: A Twelve-week synbiotic supplementation increased fecal SCFAs and improved inflammation in adult men with dyslipidemia.

Long-term yogic intervention decreases serum interleukins IL-10 and IL-1ß and improves cancer-related fatigue and functional scale during radiotherapy/chemotherapy in breast cancer patients: a randomized control study.

PURPOSE: Yoga improved fatigue and immunological profile in cancer survivors and has been a promising alternative therapy. Breast cancer treatments are rapidly improving, along with their side effects. This article investigated the effect of the yogic intervention at a different time interval during radiotherapy/chemotherapy on the pro- and anti-inflammatory interleukins along with the cancer-related fatigue and functional scale among patients with stage II/III breast cancer. METHODS: A total of 96 stage II/III breast cancer patients were enrolled in this study and randomly divided into two different groups. Group I (non-Yoga) received chemotherapy and/or radiotherapy and group II (Yoga) received an additional yogic intervention. Both groups were followed up for a period of 48 weeks and blood was collected at the time of enrollment, 16, 32, and 48 weeks, and serum was isolated to measure the pro- and anti-inflammatory interleukins, fatigue, and functional scale questionnaire obtained at each time point. RESULTS: Breast cancer patients in group II showed a significant improvement (p < 0.05) in the functional scale and fatigue from baseline to 48 weeks compared to group I. The yogic intervention significantly decreased (p < 0.05) the level of pro-inflammatory interleukin IL-1ß and pleiotropic interleukin IL-10 in group II compared to group I. CONCLUSION: These finding suggested that improved fatigue and functional scale is associated with a lower level of IL-1ß and IL-10. Yoga may be an important additional therapy along with the cancer treatment to help the patients with cancer-related fatigue and improve their overall immunological profile.

The Role of Cobalamin on Interleukin 10, Osteopontin, and Related MicroRNAs in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Considering how vitamin B12 or cobalamin affects the immune system, especially inflammation and the formation of the myelin sheath, it appears as a complementary therapy for MS by affecting some signaling pathways. Recently diagnosed MS patients were divided into two groups (n=30). One group received interferon-beta (IFN-ß or Avonex), and another received IFN-ß+B12 for six months. Blood samples were taken before and after treatments.  Interleukin (IL)-10 and osteopontin (OPN) levels in the plasma were determined by the enzyme-linked immunosorbent assay (ELISA) method, and the expression of microRNA (miR)-106a, miR-299a, and miR-146a by real-time PCR. IFN-ß neither changed the IL-10 plasma levels nor miR106a and miR-299a expression, but it led to a remarkable decrease in OPN concentration and enhancement in let-7c and miR-146a expression. There was a significant decrease in IL-10, OPN plasma levels, miR-106a expression, and a substantial increase in let-7c and  miR-146a expression in IFN-ß+B12, treated group. There was no correlation between IL-10 and OPN with related miRNAs in the two treatment groups. Our study indicated that B12 could be a complementary treatment in MS that may influence the disease improvement.

Effects of photobiomodulation and a physical exercise program on the expression of inflammatory and cartilage degradation biomarkers and functional capacity in women with knee osteoarthritis: a randomized blinded study.

BACKGROUND: The knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA. METHODS: Forty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1ß, IL-6, IL-8, IL-10 e TNF-α, and CTX-II). RESULTS: An increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1ß concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups. CONCLUSION: Our data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals. TRIAL REGISTRATION: ReBEC (RBR-7t6nzr).

The effects of vitamin D supplemantation on prognosis in patients with mild obstructive sleep apnea syndrome

Background/aim: The aim of this study was to investigate the effect of vitamin D on the disease prognosis and biochemical parameters in patients with mild obstructive sleep apnea syndrome (OSAS). Materials and methods: Nineteen adult male individuals (18­65 years) who were diagnosed with mild OSAS after polysomnography and had low vitamin D levels were included in the study. Each week, patients took 50.000 IU Vitamin D3 supplementation for 8 weeks. Polysomnography, biochemical parameters FBG (fasting blood glucose), lipid profile (TG, TC, LDL-C, HDL-C, VLDL-C), calcium, phosphorus, parathormone, calcitonin, serum 25(OH)D, insulin, CRP, TNF-α, IL-6, and IL-10 of patients were evaluated at the beginning of study and at the end of the study. All assessments, including polysomnography, were repeated after 8 weeks. Results: Serum vitamin D levels were initially 19.5 ± 5.01 ng/mL and increased to 41.8 ± 10.51 ng/mL (p < 0.001) at the end of the study. FBG, TC and HOMA-IR of the patients were significantly decreased (p < 0.05). CRP, TNF-α, IL-6, and IL-10 levels were also correlated with serum vitamin D levels (p < 0.05). There was a significant decrease in number of obstructive apneas, apneas a nd hypopneas, apnea index, hypopnea index, and apnea hypopnea index of the patients (p < 0.05). Conclusion: As a result, it is thought that vitamin D supplementation may have a positive effect on the disease prognosis of mild OSAS.

Electroacupuncture inhibits IL-17/IL-17R and post-receptor MAPK signaling pathways in a rat model of chronic obstructive pulmonary disease.

OBJECTIVE: Interleukin (IL)-17, as a T-helper 17 cell (Th17) cytokine, plays a key role in chronic obstructive pulmonary disease (COPD) pathophysiology including chronic inflammation and airway obstruction, which lead to decreased pulmonary function. The aim of this study was to investigate the effect of acupuncture on IL-17, its receptor (IL-17R) and the mitogen-activated protein kinase (MAPK) signaling pathway, in a rat model of COPD. METHODS: The COPD model was induced in Sprague Dawley rats by exposure to cigarette smoke for 12 weeks. The model rats were treated with electroacupuncture (EA) at BL13 and ST36. The lung function and histology of the rats were observed. IL-17, tumor necrosis factor (TNF)-α, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and in plasma. The leukocytes and macrophages in the BALF were counted. The expression levels of IL-17R were assayed in lung tissue by real-time polymerase chain reaction (PCR), western blotting, and immunohistochemistry. MAPK signaling pathway molecules including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38, and their phosphorylated forms, were observed in the lung by western blotting. RESULTS: Compared with the control group rats, lung function decreased and there was a severe inflammatory infiltration of the pulmonary parenchyma in the COPD rats. EA effectively improved lung function and alleviated the inflammatory infiltration in the lungs of COPD rats. EA also reversed the elevated total leukocyte and macrophage counts, the high levels of IL-17 and TNF-α, and the low IL-10 content in COPD rats. Meanwhile, EA downregulated the increased mRNA and protein expression of IL-17R, and significantly inhibited the elevated levels of phosphorylated JNK, ERK1/2, and p38 in the lungs of COPD rats. CONCLUSION: Our results suggest that the protective effects of acupuncture therapy on the lungs of COPD rats are likely related to inhibition of IL-17/IL-17R and the post-receptor MAPK signaling pathways.

Effect of six weeks 1000 mg/day vitamin C supplementation and healthy training in elderly women on genes expression associated with the immune response - a randomized controlled trial.

BACKGROUND: In this study, we investigated the effects of supplementation and exercise on the expression of genes associated with inflammation like CCL2, CRP, IL1, IL6, IL10 mRNA in elderly women. METHODS: Twenty four participants divided randomly into two groups were subjected to 6 weeks of the same health training program (three times per week). SUP group (supplemented, n = 12, mean age 72.8 ± 5.26 years and mean body mass 68.1 ± 8.3 kg) received 1000 mg of Vitamin C/day during the training period, while CON group (control, n = 12, mean age 72.4 ± 5.5 years and body mass 67.7 ± 7.5 kg) received placebo. RESULTS: No significant changes in IL-1, IL-6, IL-10 and CRP mRNA were observed within and between groups. However, there was a clear tendency of a decrease in IL-6 (two-way ANOVA, significant between investigated time points) and an increase in IL-10 mRNA noted in the supplemented group. A significant decrease in CCL2 mRNA was observed only in the CON group (from 2^0.2 to 2^0.1, p = 0.01). CONCLUSIONS: It can be concluded, that 6 weeks of supplementation and exercise was too short to obtain significant changes in gene expression in leukocytes, but supplementation of 1000 mg vitamin C positively affected IL-6 and IL-10 expression - which are key changes in the adaptation to training. However, changes in body mass, IL1 and CCL2 were positive in CON group. It is possible that Vitamin C during 6 weeks of supplementation could have different effects on the expression of individual genes involved in the immune response. TRIAL REGISTRATION: Retrospectively registered.

Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Multi-vitamin supplementation blunts the circulating IL-6/IL-10 ratio increase after knee arthroplasty: A randomized, double-blind, placebo controlled study.

Circulating interleukin (IL)-6 and IL-10 concentrations can be elevated following the surgically induced trauma of total knee arthroplasty (TKA). An exaggerated increase in IL-6 relative to IL-10 (i.e., IL-6/IL-10 ratio) associates with trauma severity and indicative of pro-inflammatory predominance. Although various vitamins and minerals alter individual IL-6 and IL-10 concentrations in the blood, surprisingly, it is unknown if a multi-vitamin supplement alters the IL-6/IL-10 ratio during the systemic inflammatory response following TKA. The objective of this study was to identify if a multi-vitamin with mineral supplement taken prior to alters the circulating IL-6/IL-10 ratio following total knee arthroplasty (TKA). This study consisted of a randomized, double-blind, placebo controlled design. Twenty-one subjects undergoing elective, primary, unilateral TKA were randomly assigned to a placebo (PL, n = 11) or multi-vitamin with mineral supplement (MV, n = 10). Supplements were taken daily starting approximately 6-weeks prior to surgery. Supplements were not taken the day of surgery or during inpatient care 2-days after surgery. Circulating IL-6, IL-10, high-sensitivity CRP (hsCRP), vitamin C (ascorbic acid (AA)), vitamin D (25-hydroxyvitamin D (25(OH)D)), and vitamin E (α-tocopherol (αT)) concentrations were measured in fasting blood draw samples obtained ~6-weeks prior to surgery (and before starting supplementation), the morning of surgery, and 24-hours and 48-hours after surgery. MV supplementation tended to increase serum 25(OH)D and significantly increased plasma AA and plasma αT before surgery without mitigating the post-operative IL-6 and hsCRP increases. However, the post-operative increase in the serum IL-6/IL-10 ratio after surgery was significantly blunted in the MV group. Based on these findings, we conclude that a multi-vitamin with mineral supplement taken daily for several weeks before surgery might reduce the pro-inflammatory predominance after TKA. Future research confirming or refuting the novel data presented herein is needed.

Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: results of a pilot study.

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA. Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS. Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = -0.37, p = 0.03). Overall, n-VNS was well tolerated. Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.

Effect of Achyranthes japonica Nakai extract on immunity and anti-inflammation in dogs.

Achyranthes japonica Nakai (A. japonica) is a medicinal herb found widely distributed throughout Korea. The biological activities of A. japonica are well-documented and include anti-fungal, anti-inflammatory, and immunity enhancement. The objective of the present study was to investigate the immune-related activities of A. japonica extract in dogs. The extract was acquired by ethanol extraction and purified by filtration. To examine the effect of A. japonica extract on immune cell viability, human lymphocytes, such as Jurkat T-cells and Ramos B-cells, were exposed to the extract. After treatment with the extract, the number of Ramos B-cells was increased, whereas Jurkat T-cells remained unaffected. Griess assay revealed decreased nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated mouse macrophage Raw 264.7 cells after exposure to A. japonica extract. To evaluate the in-vivo effect in dogs, feed containing A. japonica extract was provided to 8 dogs for 2 months. Blood samples were collected before, during, and after consumption of the feed. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples and the number of T-cells and B-cells were assessed using flow cytometry with anti-dog fluorescein isothiocyanate (FITC)-conjugated CD3 and anti-dog phycoerythrin (PE)-conjugated CD21 antibodies, respectively. We observed a significant increase in the average number of B-cells in the PBMCs during ingestion of the feed containing A. japonica. In addition, enzyme-linked immunosorbent assay (ELISA) revealed a decrease in the levels of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, in 3 out of 8 dogs and increased levels of interleukin-10 (IL-10), an anti-inflammatory cytokine, in 4 out of 8 dogs. Taken together, we believe that these changes indicate that A. japonica extract is beneficial in improving the immunity of dogs by stimulating B-cells and inducing production of anti-inflammatory responses.

Achyranthes japonica Nakai (A. japonica) est une herbe médicinale retrouvée largement distribuée à travers la Corée. Les activités biologiques d'A. japonica sont bien documentées et inclus des effets antifongique, anti-inflammatoire et de stimulation de l'immunité. L'objectif de la présente étude était d'examiner les activités reliées à l'immunité d'un extrait d'A. japonica chez des chiens. L'extrait fut obtenu par extraction à l'éthanol et purification par filtration. Pour examiner l'effet de l'extrait d'A. japonica sur la viabilité de cellules immunitaires, des lymphocytes humains, tels que les cellules T Jurkat et les cellules B Ramos, furent exposés à l'extrait. Après traitement avec l'extrait, le nombre de cellules B Ramos était augmenté, alors que celui des cellules T Jurkat était inchangé. L'épreuve de Griess a révélé une diminution de production d'oxyde nitreux (NO) chez les macrophages de souris Raw 264,7 stimulés par le lipopolysaccharide (LPS) à la suite de l'exposition à l'extrait d'A. japonica. Afin d'évaluer les effets in vivo chez les chiens, de la nourriture contenant l'extrait d'A. japonica fut donnée à huit chiens pour une période de 2 mois. Des échantillons sanguins furent prélevés avant, durant et après consommation de l'aliment. Des mononucléaires du sang périphérique (PBMCs) furent isolés des échantillons sanguins et le nombre de cellules T et de cellules B fut évalué en utilisant la cytométrie de flux et des anticorps anti-CD3 de chien conjugués à l'isothiocyanate de fluorescéine (FITC) et des anticorps anti-CD21 de chien conjugués à la phycoérythrine (PE), respectivement. Nous avons observé une augmentation significative du nombre moyen de cellules B dans le PBMCs durant l'ingestion de la nourriture contenant A. japonica. De plus, une épreuve immuno-enzymatique (ELISA) a révélé une diminution des niveaux du facteur alpha nécrosant des tumeurs (TNF-α), une cytokine pro-inflammatoire, chez trois des huit chiens et des niveaux augmentés d'interleukine-10 (IL-10), une cytokine anti-inflammatoire, chez quatre des huit chiens. Pris globalement, nous croyons que ces changements indiquent qu'un extrait d'A japonica est bénéfique pour améliorer l'immunité chez les chiens en stimulant les cellules B et en induisant la production de réponses anti-inflammatoires.(Traduit par Docteur Serge Messier).

Effects of Habitual Caffeine Intake, Physical Activity Levels, and Sedentary Behavior on the Inflammatory Status in a Healthy Population.

Low-grade chronic inflammation is associated with many chronic diseases and pathological conditions. The aim of the present study was to determine the effect of regular caffeine intake, physical activity levels, and sedentary behavior on the inflammatory status in healthy participants. In total, 112 men and 132 women aged 18 to 55 years and belonging to the staff and student population of the University of the Balearic Islands volunteered to participate in this descriptive cross-sectional study. Plasma concentrations of pro-inflammatory and anti-inflammatory markers were measured. Weight, height, and body composition (bioelectrical impedance) were determined. Caffeine intake, physical activity levels and sitting time, and diet quality were determined using questionnaires. Statistical regression analysis showed that caffeine intake was a negative predictor of C-reactive protein (CRP) (p = 0.001). Body fat percentage was positively associated with CRP (p < 0.001) and inversely associated with adiponectin (p = 0.032) and interleukin (IL)-10 levels (p = 0.001). Visceral fat was the main predictor for IL-6 (p < 0.001) and tumor necrosis factor (TNF)-α (p < 0.001). Sitting time was found to be the main, inverse, predictor for IL-10 (p < 0.001), and a positive predictor for TNF-α (p < 0.001). In conclusion, regular caffeine consumption induced very limited anti-inflammatory effects. Sedentary behavior and body fat accumulation induced significant pro-inflammatory effects.

Effect of probiotic supplementation on growth performance, intestinal morphology, barrier integrity, and inflammatory response in broilers subjected to cyclic heat stress.

This study investigated the protective effects of probiotic on heat stress-induced intestinal injury and inflammatory response in broilers. A total of 180 male broilers were randomly allocated to three treatments with four replicates each from 22 to 42 days of age. The broilers were either raised under thermoneutral (TN) conditions (23 ± 1°C) or subjected to cyclic heat stress (28-35-28°C for 12 hr daily). The broilers kept at TN conditions were fed a basal diet, and those exposed to heat stress were fed basal diets supplemented with or without probiotic at a dose of 1.5 × 108  cfu/kg. Compared with the TN group, heat stress decreased (p < .05) the growth performance, reduced (p < .05) villus height and villus height: crypt depth ratio in intestinal mucosa, increased (p < .05) serum levels of D-lactic acid on day 28 and endotoxin, TNF-α and IL-6 on day 42, and decreased (p < .05) serum IL-10 content on day 42. Dietary supplementation of probiotic reversed (p < .05) all these changes except for the growth performance in heat-stressed broilers. In conclusion, dietary inclusion of probiotic could improve intestinal morphology and barrier function, alleviate inflammatory response, but exert no ameliorative effect on growth performance of broilers under cyclic heat stress.

Vitamin D Treatment Attenuates Heart Apoptosis After Coronary Artery Bypass Surgery: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Vitamin D plays an important role in immune system and in the regulation of inflammatory cytokines. Coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB) is associated with an extensive inflammatory response. The aim of this study is to examine the effect of vitamin D treatment on the apoptosis and inflammatory changes developed after CABG. METHODS: This trial was conducted on 70 patients undergoing CABG with CPB. Patients were randomly administered either in placebo or in the group of orally consuming 150 000 IU vitamin D daily for 3 consecutive days before surgery. The right atrium sample was taken to assess caspases 2, 3, and 7 activity using immunohistochemistry method. The serum level of interleukin-10 (IL-10) and insulin-like growth factor 1 (IGF-1) were compared at intervals. RESULTS: The average number of positive cells for caspases 2 and 3 were less in vitamin D group (P = .006 and P < .001, respectively). There was an increase in serum levels of IL-10 after 3 days from vitamin D treatment before surgery (vitamin D group = 4.4 ± 4.9 ng/mL and control group = 1 ± 0.5 ng/mL, P = .001). After operation, IL-10 increased in both groups, higher level in vitamin D group (P < .001). The comparison of serum IGF-1 showed significant difference after 3 days (P = .006) and remained higher in vitamin D group after CPB (P < .001). CONCLUSIONS: These findings suggest the apoptosis rate after CPB can be reduced by vitamin D. Vitamin D treatment may improve the inflammatory status before and after surgery. Further studies are needed to confirm the antiapoptotic property of vitamin D and clinical implication.

Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients.

Endemic arsenicosis is a public health problem that affects thousands of people worldwide. However, the biological mechanism involved is not well characterized, and there is no specific treatment. Exposure to arsenic may be associated with immune-related problems. In the present work, we performed an investigation to determine whether the Th17/Treg balance was abnormal in peripheral blood mononuclear cells (PBMCs) of patients with arsenicosis caused by burning coal. Furthermore, we investigated the effect of Ginkgo biloba extract (GBE) on the Th17/Treg imbalance in patients with arsenicosis. In this trial, 81 arsenicosis patients and 37 controls were enrolled. The numbers of Th17 and Treg cells, as well as related transcription factors and serum cytokines, were determined at the beginning and end of the study. Patients with arsenicosis exhibited higher levels of Th17 cells, Th17-related cytokines (IL-17A and IL-6), and the transcription factor RORγt. There were lower levels of Treg cells, a Treg-related cytokine (IL-10), and the transcription factor Foxp3 as compared with controls. There was a positive correlation between the levels of Th17 cells and IL-17A and the levels of arsenic in hair. Arsenicosis patients were randomly assigned to a GBE treatment group or a placebo group. After 3 months of follow-up, 74 patients completed the study (39 cases in the GBE group and 35 in the placebo group). Administration of GBE to patient upregulated the numbers of Treg cells and the level of IL-10 and downregulated the numbers of Th17 cells and the levels of cytokines associated with Th17 cells. The mRNA levels of Foxp3 and RORγt were increased and decreased, respectively. These results indicated that exposure to arsenic is associated with immune-related problems. The present investigation describes a previously unknown mechanism showing that an imbalance of pro- and anti-inflammatory T cells is involved in the pathogenesis of arsenicosis and that a GBE exerts effects on arsenicosis through regulation of the pro- and anti-inflammatory T cell balance.

Myrtus communis improves cognitive impairment in renovascular hypertensive rats.

Myrtus communis has anti-inflammatory, neuroprotective and anticholinesterase activities yet there have been limited studies examining effects of Myrtus communis on cognitive functions. This study investigated the possible effects of Myrtus communis on changes in the cognitive functions of experimental renovascular hypertensive rats. Fifty-six Wistar-Albino rats were equally divided into 4 groups; sham-operated control, renovascular hypertension (RVH), ramipril (RVH + Ram) and Myrtus communis extract (RVH + MC) treatment groups. Goldblatt's 2-kidney 1-clip (2K1C) method was used to induce RVH. At the end of 9 weeks of treatment, after blood pressure recording, the animals underwent new object recognition test and Morris water maze (MWM) task. Following these tests, blood brain barrier (BBB) integrity was examined in 6 animals from each group. In the others after decapitation, osteopontin and interleukin (IL)-10 levels were measured in blood samples; while matrix metalloproteinase (MMP)-13, sodium potassium adenosine triphosphatase (Na+,K+-ATPase), cluster of differentiation (CD) 36, amyloid beta (Aß), neprilysin levels, and acetylcholinesterase (AChE) activity were investigated in hippocampal tissues. In RVH group, high systolic blood pressure decreased serum IL-10 levels, increased serum osteopontin levels and also impaired BBB permeability. Hippocampal MMP-13, CD36, Aß, neprilysin levels and AChE activities were elevated, while there were decreases in Na+,K+-ATPase levels. In new objet recognition test, discrimination index (DI) was determined as lower in saline-treated RVH group compared to control animals. In MWM training trail, 4th day performance in finding platform was significantly reduced in saline-treated RVH group compared to control group. RVH also decreased the time spent in target quadrant in probe test of MWM task compared to control group. In both of the treatment groups, all biochemical parameters were restored in parallel with improvement in the behavioral test performances. The results of this study suggest that Myrtus communis extract may improve the cognitive dysfunctions in hypertension through antihypertensive, anti-inflammatory and anticholinesterase activities.

The Impact of Pre-Cooling and CoQ10 Supplementation on Mediators of Inflammatory Cytokines in Elite Swimmers.

Chronic intensive exercise and hyperthermia may cause immune system function disturbance. We aimed to investigate the effect of 14-day coenzyme Q10 (CoQ10) supplementation and pre-cooling strategy on serum changes of inflammatory cytokines [interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)], and high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO) and xanthine oxidase (XO) enzymes, leukocyte counts (WBC), and stress hormones (catecholamine and cortisol) responses in elite swimmers during competition phase. Thirty-six healthy males were randomly selected and divided into four groups of CoQ10, precooling, supplementation with precooling, and control. Blood sampling was done pre and post (before and after acute recoding bout) administration of CoQ10 and pre-cooling. There was no significant statistical difference among groups for the indices levels of IL-10, IL-8, IL-6, TNF-α, hs-CRP, catecholamine, cortisol, MPO, XO, and WBC counts at the pre sampling (P > 0.05). While, pre-cooling and control groups show a significant increase indices levels compared to the supplementation and supplementation with precooling groups in the post-sampling (two stages), (P ˂ 0.05). Short-term oral CoQ10 supplementation prevents adverse changes mediators of inflammatory cytokines following heavy swimming trainings and acute recording bout. In addition, pre-cooling strategy individually has no desired effect on the mediators of inflammatory cytokines.

Effect of Cholecalciferol Supplementation on Treatment Response and IL-10 Level in Vitamin D Deficient Parthenium Dermatitis Patients: A Randomized Double-Blind Placebo-Controlled Trial.

Allergic contact dermatitis following exposure to Parthenium is a chronic disease associated with frequent relapses and significant disturbance in the quality of life. The affected patients have lower circulating levels and decreased expression of IL-10. Hence, measures to increase its level may enhance the therapeutic outcome. The clinical trial was undertaken to evaluate the effect of cholecalciferol supplementation on treatment response and IL-10 level in Parthenium dermatitis patients with vitamin D deficiency. A total of 72 patients were recruited and randomized to receive either cholecalciferol tablet 60,000 IU per week or matching placebo for 8 weeks with standard background treatment. Eczema Area Severity Index (EASI) and Dermatology Life Quality Index (DLQI) were assessed at baseline, 4 weeks, and 8 weeks while IL-10 and serum 25-hydroxyvitamin D levels were measured at baseline and 8 weeks. Levels of 25-hydroxyvitamin D and IL-10 showed a significant rise in both placebo and vitamin D groups following the intervention. The relatively higher increase in IL-10 level observed in the vitamin D group was statistically insignificant compared to placebo group. Significant reduction in EASI, as well as DLQI scores, was noted after 1 and 2 months, but the reduction in these scales was not significantly different between the groups. Cholecalciferol supplementation for 2 months did not reduce the disease severity in clinically diagnosed Parthenium dermatitis patients. However, treatment initiation significantly improved plasma IL-10 levels after 2 months in both placebo and cholecalciferol groups.

Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation. / Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral.

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- α], transforming growth factor-b [TGF-ß],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p=.001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p=.010) and PTH decreased (p=.002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p=.001) and also TNF-α did (p=.005), on the contrary, interleukin-10 and fetuin-A increased (p=.001 for both). Anti-fibrosis marker BMP-7 increased (p=.001) and TGF-b decreased (p=.001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease.

IL-10 Cytokine as Potential Biomarkers in Women with Fibromyalgia Who Underwent to a Short Balneotherapy Treatment

Abstract Fibromyalgia (FM) is a nonarticular rheumatic syndrome that leads to diffuse myalgia, sleep disturbances and morning stiffness. Balneotherapy has been shown an effective strategy to improve the health conditions of patients; however, the treatment follow-up is based on patient report due to the lack of biomarkers. Thus, this study evaluated the application of cytokines and phosphoglycerate mutase I (PGAM-I) to monitoring FM patient underwent to balneotherapy treatment. Eleven healthy and eleven women with FM were submitted to daily sessions of balneotherapy during 10 days. Clinical and quality of life parameters were assessed through a FIQ questionnaire. Blood levels of TNF-(, interleukins (IL-1, IL-2 and IL-10) and PGAM-I expression in patients' saliva were also evaluated. Patients with FM showed significant improvements in their clinical status after treatment. Also, FM patients has IL-10 levels lower than healthy women and the balneotherapy increased the expression of this cytokine in both groups, concomitantly to pain relief. Although inflammatory cytokines (IL-1, IL-2 and TNF-() were more expressed in FM patients than healthy patients their levels did not reduce after treatment. A slight increase of PGAM-I expression was observed. In conclusion, IL-10 levels could be a useful biomarker to balneotherapy follow-up of FM patients. However, these findings must be analyzed in a larger number of patients in order to validate IL-10 as an effective biomarker.