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1.
The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1β protein.
Sabzevary-Ghahfarokhi, M, Soltani, A, Luzza, F, Larussa, T, Rahimian, G, Shirzad, H, Bagheri, N
Molecular biology reports. 2020;(9):6941-6947
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1β and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1β was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1β in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1β protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1β and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1β mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1β and increasing IL-11 production.
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Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis.
Iwaszko, M, Świerkot, J, Dratwa, M, Wysoczańska, B, Korman, L, Bugaj, B, Kolossa, K, Jeka, S, Wiland, P, Bogunia-Kubik, K
The pharmacogenomics journal. 2020;(6):760-769
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Abstract
MHC class I polypeptide-related sequence A (MICA) is a stress-induced protein involved in activation of NK and T cells through interaction with NKG2D receptor. These molecules are atypically expressed in synovium of patients diagnosed with rheumatoid arthritis (RA). A total of 279 patients with RA, qualified to TNF-blockade therapy, were genotyped for MICA rs1051792 SNP. The effectiveness of anti-TNF agents was assessed with European League Against Rheumatism criteria. Significant relationship between MICA rs1051792 and outcome of TNF-blockade therapy has been found. The MICA rs1051792 GG genotype was overrepresented in patients non-responsive to anti-TNF drugs in comparison with other genotypes (p = 0.010). On the other hand, beneficial therapeutic response was more frequently detected among RA subjects possessing heterozygous genotype than those with homozygous genotypes (p = 0.003). Furthermore, increased MICA concentrations in serum were observed in patients possessing MICA rs1051792 GG genotype as compared with those with GA or AA genotypes (p = 1.8 × 10-5). The results from this study indicate the potential influence of MICA rs1051792 polymorphism on modulation of therapeutic response to TNF-blockade treatment in RA.
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Synergism Effects of Ursolic Acid Supplementation on the Levels of Irisin, C-reactive Protein, IL-6, and TNF-α During High-intensity Resistance Training in Low Activity Men.
Asghari, E, Rashidlamir, A, Hosseini, SRA, Moazzami, M, Samarghandian, S, Farkhondeh, T
Cardiovascular & hematological disorders drug targets. 2020;(2):138-144
Abstract
BACKGROUND Ursolic Acid (UA) is a pentacyclic triterpenoid carboxylic acid which is extracted from plants. UA may enhance the effect of Resistance Training (RT) in human. OBJECTIVE Current research was designed to show the effect of High-Intensity Resistance Training (HIRT) in the presence or absence of UA on the serum levels of irisin, CRP, IL-6 and TNF-α in the low activity men. METHODS The study included twenty-two healthy male HIRT with placebo, supplementation, and HIRT in the presence of UA supplementation. The two groups received eight-week intervention including 2 sets of 8 exercises, with 8~10 repetitions at 70~75% of 1 repetition maximum and a 2 min rest interval between sets, performed 3 times/week. Placebo or UA orally was evaluated as 1 capsule 3 times/day during 8 weeks. The subsequent factors were measured post- and preintervention: C-Reactive Protein (CRP), Irisin, Tumor Necrotic Factor (TNF-α) and Interleukin-6 (IL-6). RESULTS UA supplementation significantly increased the plasma levels of irisin in the HIRT+UA group versus the HIRT+P group (p<0.05). UA treatment also dramatically decreased the plasma levels of CRP, IL-6, and TNF-α in the HIRT+UA group versus the HIRT+P group (p<0.05). CONCLUSION The current data showed that UA-induced an increase in serum irisin and reduction of CRP, IL-6, and TNF-α may have beneficial effects as a chemical for increasing of the effects of HIRT in low activity men.
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Muscle, Bone, and Fat Crosstalk: the Biological Role of Myokines, Osteokines, and Adipokines.
Kirk, B, Feehan, J, Lombardi, G, Duque, G
Current osteoporosis reports. 2020;(4):388-400
Abstract
PURPOSE OF REVIEW Skeletal muscle and bone are connected anatomically and physiologically, and play a crucial role in human locomotion and metabolism. Historically, the coupling between muscle and bone has been viewed in light of mechanotransduction, which dictates that the mechanical forces applied to muscle are transmitted to the skeleton to initiate bone formation. However, these organs also communicate through the endocrine system, orchestrated by a family of cytokines namely myokines (derived from myocytes) and osteokines (derived from bone cells). A third player in this biochemical crosstalk is adipose tissue and the secretion of adipokines (derived from adipocytes). In this review, we discuss the bidirectional effects of myokines and osteokines on muscle and bone metabolism, and the impact of adipokines on both of these secretory organs. RECENT FINDINGS Several myokines, notably, IL6, irisin, IGF-1, BDNF, myostatin, and FGF2 exert anabolic/catabolic effects on bone, while the osteokines osteocalcin and sclerostin have shown to induce muscle anabolism and catabolism, respectively. Adipokines, such as leptin, resistin, adiponectin, and TNFα (released from adipose tissue), can also modulate muscle and bone metabolism. Contrarily, exercise-mediated release of lipolytic myokines (IL6, irisin, and LIF) stimulates thermogenesis by promoting the browning of adipocytes. Myokines, osteokines, and adipokines exert autocrine/paracrine effects locally as well as through the endocrine system, to regulate muscle, bone, and fat metabolism. Reductions in physical activity and increases in energy intake, both linked with aging, leads to adipocyte hypertrophy and the recruitment of immunological cells (macrophages). In turn, this releases pro-inflammatory adipokines which induces chronic low-grade inflammation (LGI), a key player in the pathology of several diseases. However, exercise-induced stimulation of bioactive cytokines, through muscle-bone-fat crosstalk, increases muscle anabolism, bone formation, mitochondrial biogenesis, glucose utilization, and fatty acid oxidation, and attenuates chronic LGI.
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The effects of soy supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.
Asbaghi, O, Yaghubi, E, Nazarian, B, Kelishadi, MR, Khadem, H, Moodi, V, Naeini, F, Ghaedi, E
Cytokine. 2020;:155282
Abstract
BACKGROUND Soy products contain several compounds with anti-inflammatory properties like genistein and daidzein which reported to act through different pathways. Present study conducted considering the inconsistent results and lack of any comprehensive review regarding randomized controlled trials which assess the effect of soy products on inflammatory markers. METHODS Following electronic databases were searched up to March 2020: PubMed, Scopus, ISI web of science, and Cochrane Library All randomized trials which assessed the effect of soy product supplementation on c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were included for last analysis. Treatment effects were expressed as mean difference (MD) and the standard deviation (SD) of outcomes. To estimate the overall effect the random-effects model was employed. RESULTS Finally, 51 randomized trial were included for present study. Last analysis showed that soy product supplementation lead to significant reduction in CRP (MD -0.27 mg/L; 95% CI: -0.51, -0.02, p = 0.028) but it did not affect IL-6 (MD 0.0 pg/ml; 95% CI: -0.06, 0.06, p = 0.970) and TNF-α (MD = -0.04 pg/ml; 95% CI: -0.11, 0.03, p = 0.252). Subgroup analysis showed that soy supplementation had a significant impact on decreasing IL-6 and TNF-α levels when studies had a long-term intervention (≥12 weeks) and used low dose isoflavone (<100 mg/day). CONCLUSION In conclusion, present systematic review and meta-analysis found a significant reduction in CRP levels after soy supplementation whiles IL-6 and TNF-α did not affect.
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Methylglyoxal, Glycated Albumin, PAF, and TNF-α: Possible Inflammatory and Metabolic Biomarkers for Management of Gestational Diabetes.
Piuri, G, Basello, K, Rossi, G, Soldavini, CM, Duiella, S, Privitera, G, Spadafranca, A, Costanzi, A, Tognon, E, Cappelletti, M, et al
Nutrients. 2020;(2)
Abstract
BACKGROUND In gestational diabetes mellitus (GDM), pancreatic β-cell breakdown can result from a proinflammatory imbalance created by a sustained level of cytokines. In this study, we investigated the role of specific cytokines, such as B-cell activating factor (BAFF), tumor necrosis factor α (TNF-α), and platelet-activating factor (PAF), together with methylglyoxal (MGO) and glycated albumin (GA) in pregnant women affected by GDM. METHODS We enrolled 30 women whose inflammation and metabolic markers were measured at recruitment and after 12 weeks of strict dietetic therapy. We compared these data to the data obtained from 53 randomly selected healthy nonpregnant subjects without diabetes, hyperglycemia, or any condition that can affect glycemic metabolism. RESULTS In pregnant women affected by GDM, PAF levels increased from 26.3 (17.4-47.5) ng/mL to 40.1 (30.5-80.5) ng/mL (p < 0.001). Their TNF-α levels increased from 3.0 (2.8-3.5) pg/mL to 3.4 (3.1-5.8) pg/mL (p < 0.001). The levels of methylglyoxal were significantly higher in the women with GDM (p < 0.001), both at diagnosis and after 12 weeks (0.64 (0.46-0.90) μg/mL; 0.71 (0.47-0.93) μg/mL, respectively) compared to general population (0.25 (0.19-0.28) μg/mL). Levels of glycated albumin were significantly higher in women with GDM (p < 0.001) only after 12 weeks from diagnosis (1.51 (0.88-2.03) nmol/mL) compared to general population (0.95 (0.63-1.4) nmol/mL). CONCLUSION These findings support the involvement of new inflammatory and metabolic biomarkers in the mechanisms related to GDM complications and prompt deeper exploration into the vicious cycle connecting inflammation, oxidative stress, and metabolic results.
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Use of Biologics in Pityriasis Rubra Pilaris Refractory to First-Line Systemic Therapy: A Systematic Review [Formula: see text].
Naidoo, A, Sibbald, C, Fleming, PJ, Piguet, V
Journal of cutaneous medicine and surgery. 2020;(1):73-78
Abstract
Pityriasis rubra pilaris (PRP) is an uncommon, inflammatory, papulosquamous skin disease. Treatment of PRP is challenging as the disease is often refractory to conventional therapies, such as retinoids and methotrexate. There has been an increasing number of studies reporting the successful use of biologic therapy in patients with PRP; however, the data on the efficacy and safety are limited. Our objective was to evaluate the existing evidence for utilizing biologics, whether alone or in combination with established systemic therapies, in patients with treatment-resistant PRP. We systematically reviewed evidence within Medline and Pubmed databases between January 1, 2000, to March 31, 2019. Articles consisted of patients diagnosed with PRP who have failed to respond sufficiently to first-line systemic therapies, or who had comorbidities that precluded their use. In total, 363 unique articles were identified, 56 of which were considered relevant to the clinical question. Of the 56 articles highlighted, 35 met the inclusion criteria and were limited to case series and case studies. Therapy with biologics was found to be successful for both monotherapy (81.1% [27/33]) and when used in combination with existing systemic therapies (87.5% [14/16]). The existing evidence suggests that biologics may be regarded as a tool for PRP treatment alone or in combination therapy with existing treatments, although large-scale randomized clinical trials are necessary to better assess their efficacy and safety.
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Optimization of biologics to reduce treatment failure in inflammatory bowel diseases.
Bourchany, A, Gilletta De Saint-Joseph, C, Breton, A, Barreau, F, Mas, E
Current opinion in pharmacology. 2020;:51-58
Abstract
Moderate to severe inflammatory bowel disease patients can fail to respond to conventional therapy and/or to biologic treatment. In the era of TNFα antagonists and other non-anti-TNF biologic drugs, it is important to review the literature on biologic treatment failure, which could be defined as primary non-response, secondary loss of response and intolerance. Therapeutic drug monitoring (TDM), that is, drug trough level and antidrug antibodies, should enable to determine the mechanisms of treatment failure and to optimize drug efficacy. There is a consensus on reactive TDM at the time of loss of response. Proactive TDM could be of interest during induction and/or maintenance, but randomized controlled trials are required.
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Anti-inflammatory properties of Xylopia aethiopica leaves: Interference with pro-inflammatory cytokines in THP-1-derived macrophages and flavonoid profiling.
Macedo, T, Ribeiro, V, Oliveira, AP, Pereira, DM, Fernandes, F, Gomes, NGM, Araújo, L, Valentão, P, Andrade, PB
Journal of ethnopharmacology. 2020;:112312
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ethnopharmacological surveys on Guinea-Bissauan flora reveal that several species are used to treat or ameliorate the symptomatology of conditions with an inflammatory background. As such, extracts obtained from a series of plants recorded in those surveys were screened for their anti-inflammatory properties, a hydroethanolic extract obtained from the leaves of Xylopia aethiopica (Dunal) A. Rich, (Annonaceae), used on the treatment of headache, muscular pain and rheumatic pain, scoring positively and being further investigated. AIM OF THE STUDY In order to identify species with anti-inflammatory properties, extracts were screened for their ability to interfere with LPS-induced TNF-α levels. Since significant effects were recorded upon treatment with the extract of the leaves obtained from X. aethiopica, further assays were conducted to elucidate additional mechanisms underlying its anti-inflammatory potential. Since little is known on the chemical composition of the plant, we also aimed to characterise its phenolic profile. MATERIALS AND METHODS Interference with cytokines was evaluated by ELISA assay, through the quantification of TNF-α and IL-6 levels in the culture medium collected from LPS-activated THP-1-derived-macrophages. Inhibition of 5-lipoxygenase was assessed based on the oxidation of linoleic acid to 13-hydroperoxylinoleic acid. Characterization of the phenolic profile was attained by HPLC-DAD. RESULTS Evaluation of TNF-α levels in LPS-challenged THP-1 macrophages evidenced a significant inhibition (>90%) upon treatment with the hydroethanolic extract obtained from X. aethiopica leaves at a concentration of 500 μg/mL. Additional anti-inflammatory effects were recorded, including a significant decrease on IL-6 levels at 250 and 500 μg/mL. The extract proved to be active towards 5-LOX, leading to significant inhibition at concentrations ranging from 16 to 250 μg/mL (IC50 = 85 μg/mL). Phenolic profiling allowed the identification and quantitation of eight constituents, including caffeoylquinic acids (1-3), mono-O-glycosylated flavonols (5-8), and the mono-O-glycosyl flavone luteolin-7-O-glucoside (4). The main phenolic constituent, kaempferol-3-O-rutinoside (8), was found to significantly contribute to the anti-inflammatory effects, namely through the inhibition of 5-LOX. However, no effects on the decrease of TNF-α and IL-6 levels caused by this phenolic compound were found. CONCLUSION The anti-inflammatory effects of X. aethiopica leaves are demonstrated experimentally, thus substantiating its use in folk Medicine. Relevantly, the observed anti-inflammatory properties can stimulate further studies in order to fully unveil the therapeutic potential of the plant, namely as a source of phenolic compounds with a significant ability to interfere with conventional inflammatory targets.
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TNFα Mediates the Interaction of Telomeres and Mitochondria Induced by Hyperglycemia: A Rural Community-Based Cross-Sectional Study.
Lyu, L, He, S, Zhang, H, Li, W, Zeng, J, Ping, F, Li, YX
Oxidative medicine and cellular longevity. 2020;:8235873
Abstract
This study is aimed at evaluating the relationship between leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in a noninterventional rural community of China with different glucose tolerance statuses. In addition, we investigate whether the indicators of oxidative stress and inflammation were involved and identify mediators among them. A total of 450 subjects in rural China were included and divided into two groups according to a 75 g oral glucose tolerance test (OGTT): the abnormal glucose metabolism (AGM, n = 257, 57.1%) group and the normal glucose tolerance (NGT, n = 193, 42.9%) group. Indicators of oxidative stress (superoxide dismutase (SOD) and glutathione reductase (GR)) and inflammatory indices (tumor necrosis factor α (TNFα) and interleukin-6 (IL-6)) were all determined by ELISA. LTL and mtDNAcn were measured using a real-time PCR assay. Linear regressions were used to adjust for covariates that might affect the relationship between LTL and mtDNAcn. Mediation analyses were utilized to evaluate the mediators. In the AGM, LTL was correlated with mtDNAcn (r = 0.214, p = 0.001), but no correlation was found in the NGT. The association between LTL and mtDNAcn was weakened after adjusting for inflammatory factors in the AGM (p = 0.087). LTL and mtDNAcn were both inversely related to HbA1c, IL-6, TNFα, and SOD activity. Mediation analysis demonstrated that TNFα was a significant mediator in the telomere-mitochondrial interactome in the AGM. This result suggests that inflammation and oxidative stress may play a vital role in telomere shortening as well as mitochondrial dysfunction. In the subjects with hyperglycemia, a significant positive correlation is observed between LTL and mtDNAcn, which is probably mediated by TNFα. TNFα may be considered a potential therapeutic target against aging-related disease in hyperglycemia.