Effects of 1, 25-dihydroxy vitamin D3 on clinical symptoms, pro-inflammatory and inflammatory cytokines in calves with experimental pneumonia

2020 ◽  
Vol 132 ◽  
pp. 186-193
Author(s):  
Parisa Asgharpour ◽  
Mohammad Reza Mokhber Dezfouli ◽  
Mohammad Goli Nadealian ◽  
Zohre Eftekhari ◽  
Gholam Reza Nikbakht Borojeni
Keyword(s):  
Inflammatory Cytokines ◽  
Vitamin D3 ◽  
Clinical Symptoms ◽  
Experimental Pneumonia

scholarly journals Astragaloside IV Protects Against Diabetic Nephropathy by Inhibiting Pyroptosis Based on NOX4/TXNIP/NLRP3 Pathway

2020 ◽  
Author(s):  
Yudi Zhang ◽  
Chunhe Tao ◽  
Donglin Du ◽  
Chen Xuan ◽  
Wenfu Cao
Keyword(s):  
Diabetic Nephropathy ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Therapeutic Strategy ◽  
Clinical Symptoms ◽  
Collagen Iv ◽  
Tunel Staining ◽  
Astragaloside Iv ◽  
Glycation End Products

Background and Purpose: Diabetic nephropathy (DN) is a common and severe chronic complication in diabetes mellitus. The purpose of this study was to explore the effect and mechanism of Astragaloside IV (AS-IV) on renal pyroptosis in DN. Experimental Approach: High-fat diet and a small dose of streptozotocin were used to establish the DN model. Rats were treated with vehicle or AS-IV (20-, 40- and 80-mg/kg/day) or valsartan (30mg/kg/day) by gavage. After 12 weeks, animals were euthanized; samples of urine and blood were collected to examine biochemical indicators, advanced glycation end products (AGEs), inflammatory cytokines; kidney tissues were collected for histological observation, TUNEL staining, AGEs, inflammatory cytokines, redox indicators, western blot, and immunohistochemistry. Key Results: Biochemical results showed that AS-IV could significantly alleviate the degree of clinical symptoms and the levels of blood glucose, HbA1C, TG, MDA, AGEs, Interleukin (IL)-1β, and IL-18 while improving the activity of SOD and the secretion and sensitivity of insulin. Histological examination and TUNEL staining indicated that AS-IV attenuated the damage of tissues and cells in the kidney from DN rats. Western blot results revealed that AS-IV relieved the activation of NOX4/TXNIP/NLRP3 pathway and the expression of collagen IV and fibronectin in DN rats. Immunohistochemistry results showed that AS-IV attenuated collagen IV and fibronectin in the kidney from DN rats. Conclusion and Implications: The NOX4/TXNIP/NLRP3 pathway mediated renal pyroptosis could play a crucial role in kidney damage and DN development in rats. Restoration of renal pyroptosis by AS-IV be a potential therapeutic strategy against DN.

scholarly journals Protective Effect of Resveratrol Improves Systemic Inflammation Responses in LPS-Injected Lambs

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 872 ◽  
Author(s):  
Yanping Liang ◽  
Jianwei Zhou ◽  
Kaixi Ji ◽  
Hu Liu ◽  
Allan Degen ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Average Daily Gain ◽  
Clinical Signs ◽  
Blood Parameters ◽  
Mapk Signaling ◽  
Inflammatory Genes ◽  
Expression Levels ◽  
Daily Gain

Highly intensive livestock production often causes immune stress to animals, which makes them more susceptible to infections. The aim of this study was to examine whether resveratrol (Res) alleviates inflammation in lambs. In Experiment 1, 16 male lambs were injected with lipopolysaccharides (LPS) at an initial dose of 0.25, 1.25, and 2.5 μg/kg body weight (BW) for 9 days. Average daily gain and blood parameters were measured and clinical symptoms were recorded. In Experiment 2, 20 male lambs were injected intravenously with LPS (0 mg/kg) + Res (0 mg), LPS (2.5 μg /kg) + Res (0 mg, 82.5 mg, 165 mg, 330 mg), 4 h after LPS injection. Jugular blood was collected from each lamb to determine white blood cell (WBC) counts and the expression of inflammatory genes. In Experiment 1, all LPS-treated lambs showed clinical signs of sickness including rhinorrhea, lethargy, and shivering, and systemic inflammatory responses of increased inflammatory genes levels and cortisol concentration. The lambs had increased respiratory and heart rates and rectal temperature and decreased average daily gain and feed intake. In Experiment 2, resveratrol significantly reduced WBCs and the expression levels of several genes associated with inflammation response (TLR4, NF-κB, c-jun) and inhibited the signaling cascades of NF-κB and MAPKs by down-regulating the expression levels of inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, IFN-γ) induced by LPS. Resveratrol attenuated the LPS-evoked inflammatory responses in lambs by suppressing expression levels of inflammatory cytokines, and blocking NF-κB and MAPK signaling pathways.

scholarly journals NF-κB inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type

2021 ◽  
Author(s):  
Donghui Shen ◽  
Fengna Chu ◽  
Yue Lang ◽  
Chao Zheng ◽  
Chunrong Li ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
M2 Macrophage ◽  
Experimental Autoimmune Neuritis ◽  
Peak Period ◽  
Duration Of Symptoms ◽  
Beneficial Effects ◽  
M1 Macrophage ◽  
Experimental Autoimmune

Guillain–Barre’ syndrome (GBS) is an acute inflammatory and immune-mediated demyelinating disease of peripheral nervous system (PNS). Macrophages playing a central role in its animal model, experimental autoimmune neuritis (EAN) has been well-accepted. Additionally, NF-κB inhibitors has been used to treat cancers and showed beneficial effects. Here we investigated the therapeutic effect of M2 macrophage and NF-κB pathway is correlated with macrophages activation in experimental autoimmune neuritis (EAN) in C57BL/6 mice. We demonstrated that M2 macrophage transfusion can alleviate the clinical symptoms of EAN by reducing the proportion of M1 macrophage in the peak period, inhibiting the phosphorylation of NF-κB p65. The NF-κB inhibitor (BAY-11-7082) could alleviate the clinical symptoms of EAN and shorten the duration of symptoms by reducing the proportion of M1 macrophages and the expression of pro-inflammatory cytokines. Consequently, BAY-11-7082 exhibits strong potential as a therapeutic strategy for ameliorating EAN by influencing the balance of M1/M2 macrophages and inflammatory cytokines.

scholarly journals Effect of Vitamin D3 On the Expression of Antimicrobial Peptide Gene in Experimental Pneumonia in Calf

2021 ◽  
Author(s):  
Parisa Asgharpour ◽  
Zohre Eftekhari ◽  
Mohammad Goli Nadealian ◽  
Gholam Reza Nikbakht Borojeni ◽  
Mohammad Reza Mokhber Dezfouli
Keyword(s):  
Vitamin D ◽  
Treatment Group ◽  
Vitamin D3 ◽  
Pasteurella Multocida ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Cell Content ◽  
Peripheral Blood Mononuclear

Abstract Background Vitamin D3 has been identified as an immunomodulatory agent that confronts the pathogens via stimulating antimicrobial peptides (AMPs). Objective The effects of vitamin D3 on the expression of AMPs was assessed in experimental pasteurellosis in calves. Methods 10 Holstein crossbred male calves (2–4 months) were chosen and randomly divided into the two groups. Pasteurella multocida was prepared (3×109 CFU/mL) and inoculated in the trachea. Vitamin D3 was injected to the treatment group after confirming the pneumonia. Blood samples were obtained from both groups at different time intervals and the peripheral blood mononuclear cells (PBMCs) were isolated. Clinical symptoms were recorded. Broncho-alveolar lavage was performed to evaluate the lung cell content. On the other hand, 10− 6, 10− 7, and 10 − 8 molar (M) of vitamin D3, was used to evaluate the expression of CD4, BMAP34, and BNBD4 genes using PBMCs under the in vitro conditions. Results The prescription of vitamin D3 to the treatment group caused a decline in clinical signs. Following the vitamin D3 injections the treatment groups under the in vivo conditions, significant increase was observed in the expression level of Defensin (BNBD4), and CD4. Evaluation of bronchoalveolar lavage fluid (BALF) revealed that the amount of neutrophils decreased after vitamin D injection. In vitro, increased expression of Catalicidin (BMAP34), Defensin (BNBD4), and CD4 was observed at a concentration of 10− 6 M of vitamin D3. Conclusion The present study indicated that vitamin D3, exerts immunomodulatory effects on many infectious diseases via activation of VDR pathways and stimulation of AMP production.

scholarly journals Anti-inflammatory Effect of Curcumin, Homotaurine, and Vitamin D3 on Human Vitreous in Patients With Diabetic Retinopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Mariaelena Filippelli ◽  
Giuseppe Campagna ◽  
Pasquale Vito ◽  
Tiziana Zotti ◽  
Luca Ventre ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Inflammatory Cytokines ◽  
Vitamin D3 ◽  
Bioactive Molecules ◽  
Mediators Of Inflammation ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Post Hoc ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Purpose: To determine the levels of pro-inflammatory cytokines and soluble mediators (TNF-α, IL6, IL2, and PDGF-AB) in 28 vitreous biopsies taken from patients with proliferative diabetic retinopathy (PDR) and treated with increasing doses of curcumin (0. 5 and 1 μM), with or without homotaurine (100 μM) and vitamin D3 (50 nM).Materials and Methods: ELISA tests were performed on the supernatants from 28 vitreous biopsies that were incubated with bioactive molecules at 37°C for 20 h. The concentration of the soluble mediators was calculated from a calibration curve and expressed in pg/mL. Shapiro-Wilk test was used to verify the normality of distribution of the residuals. Continuous variables among groups were compared using the General Linear Model (GLM). Homoscedasticity was verified using Levene and Brown-Forsythe tests. Post-hoc analysis was also performed with the Tukey test. A p ≤ 0.05 was considered statistically significant.Results: The post-hoc analysis revealed statistically detectable changes in the concentrations of TNF-α, IL2, and PDGF-AB in response to the treatment with curcumin, homotaurine, and vitamin D3. Specifically, the p-values for between group comparisons are as follows: TNF-α: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.008, (curcumin 0.5 μM vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0004, (curcumin 0.5 μM vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.02, (curcumin 1 μM vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.025, and (homotaurine 100 μM + vitamin D3 50 nM vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.009; IL2: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0023, and (curcumin 0.5 μM vs. curcumin 0.5 μM+ homotaurine 100 μM + vitamin D3 50 nM) p = 0.0028; PDGF-AB: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.04, (untreated vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0006, (curcumin 0.5 μM vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.006, and (homotaurine 100 μM + vitamin D3 50 nM vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.022. IL6 levels were not significantly affected by any treatment.Conclusions: Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage. Multi-target treatment may provide a therapeutic strategy for diabetic retinopathy in the future.Clinical Trial Registration : The trial was registered at clinical trials.gov as NCT04378972 on 06 May 2020 (“retrospectively registered”) https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid = S0009UI8&selectaction = Edit&uid = U0003RKC&ts = 2&cx = dstm4o.

scholarly journals Safety and Efficacy of the Combination of BCc1 and Hep-S Nanochelating-Based Medicines in Hospitalized COVID-19 Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

2021 ◽  
Author(s):  
Maryam Hafizi ◽  
Somayeh Kalanaky ◽  
Saideh Fakharzadeh ◽  
Atefeh Fakharian ◽  
Somayeh Lookzadeh ◽  
...  
Keyword(s):  
Treatment Group ◽  
Inflammatory Cytokines ◽  
Clinical Symptoms ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Reduce Mortality Rate ◽  
Tnf Α

Abstract Background: The mortality and morbidity of COVID‐19 disease as well as the lack of a proper medication has forced researchers and clinicians to employ urgent efficient technologies to overcome this current pandemic. In the severe forms of COVID-19, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. The efficiency of nanomedicines - as efficient immunomodulators - that are synthesized based on nanochelating technology have been proved in the previous studies. In the present study, the therapeutic effect of the combination of BCc1 and Hep-S nanomedicines on hospitalized COVID-19 patients was evaluated.Method: Laboratory-confirmed moderate COVID-19 patients at Masih Daneshvari Hospital were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N=62) (treatment) or placebo (N=60) (placebo). The primary outcome of the study was evaluating the safety of the nanomedicines combination and its effect on the number of deceased patients, while the secondary outcome was decrease in inflammatory cytokines.Results: The evaluation of blood biochemical indices as well as clinical symptoms showed that adding the combination of BCc1 and Hep-S nanomedicines to the standard protocol of the treatment caused no adverse effects. The results analysis revealed that 28-day consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine of the patients in the treatment group (p < 0.05). In addition, the patients in the treatment group had lower TNF-α levels compared to those in the control (p > 0.05) and they also showed less need for oxygen therapy. Finally, the number of the deceased patients in the treatment group was 30% lower than that of the control (p > 0.05).Conclusion: The combination of BCc1 and Hep-S, as safe nanomedicines, inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology, and presents a promising view for immunomodulation that can manage CSS and reduce mortality rate in COVID19 patients.Trial registration IRCTID, IRCT20170731035423N2. Registered 12 Jun 2020, http://www.irct.ir/ IRCT20170731035423N2.

scholarly journals Anti-Inflammatory Effects of Mytilus coruscus Polysaccharide on RAW264.7 Cells and DSS-Induced Colitis in Mice

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 468
Author(s):  
Xing-Wei Xiang ◽  
Rui Wang ◽  
Li-Wen Yao ◽  
Yu-Fang Zhou ◽  
Pei-Long Sun ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Cytokines ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Critical Role ◽  
Intestinal Flora ◽  
Intestinal Barrier ◽  
Raw264.7 Cells ◽  
Mytilus Coruscus ◽  
Anti Inflammatory

Considerable literature has been published on polysaccharides, which play a critical role in regulating the pathogenesis of inflammation and immunity. In this essay, the anti-inflammatory effect of Mytilus coruscus polysaccharide (MP) on lipopolysaccharide-stimulated RAW264.7 cells and a dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice was investigated. The results showed that MP effectively promoted the proliferation of RAW264.7 cells, ameliorated the excessive production of inflammatory cytokines (TNF-α, IL-6, and IL-10), and inhibited the activation of the NF-κB signaling pathway. For DSS-induced colitis in mice, MP can improve the clinical symptoms of colitis, inhibit the weight loss of mice, reduce the disease activity index, and have a positive effect on the shortening of the colon caused by DSS, meliorating intestinal barrier integrity and lowering inflammatory cytokines in serum. Moreover, MP makes a notable contribution to the richness and diversity of the intestinal microbial community, and also regulates the structural composition of the intestinal flora. Specifically, mice treated with MP showed a repaired Firmicutes/Bacteroidetes ratio and an increased abundance of some probiotics like Anaerotruncus, Lactobacillus, Desulfovibrio, Alistipe, Odoribacter, and Enterorhabdus in colon. These data suggest that the MP could be a promising dietary candidate for enhancing immunity and protecting against ulcerative colitis.

scholarly journals Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

2020 ◽  
Author(s):  
William B. Grant ◽  
Henry Lahore ◽  
Sharon L. McDonnell ◽  
Carole A. Baggerly ◽  
Christine B. French ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Cytokines ◽  
Vitamin D3 ◽  
Large Population ◽  
Case Fatality ◽  
Vitamin D Supplementation ◽  
Risk Of Infection ◽  
Hydroxyvitamin D ◽  
Reduce Risk ◽  
Tract Infections

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40&ndash;60 ng/ml (100&ndash;150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

scholarly journals Vitamin D3 controls TLR4- and TLR2-mediated inflammatory responses of endometrial cells

2019 ◽  
Author(s):  
Alireza Ghanavatinejad ◽  
Nesa Rashidi ◽  
Mahroo Mirahmadian ◽  
Simin Rezania ◽  
Mahdokht Mosalaei ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Vitamin D3 ◽  
Inflammatory Responses ◽  
Female Reproductive Tract ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Tnf Α ◽  
Pre Treatment ◽  
Tract Infections ◽  
Pro Inflammatory Cytokines

Abstract Background: There is a significant association between intrauterine infection-associated inflammatory responses and such pregnancy complications as abortion and preterm labor. Here, we aimed to investigate anti-inflammatory effects of 1,25 (OH)2 D3 on pro-inflammatory cytokines secretion and expression of TLR2, TLR4 and MyD88 in endometrial stromal cells (ESCs) and whole endometrial cells (WECs). Method: WECs were treated with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) and ESCs were treated with LPS. IL-6, IL8 and TNF-α were quantified using ELISA technique. TLR2, TLR4 and MyD88 expression were assessed by RT-qPCR. TLR4 expression at the protein level was studied by Western blot technique. Results: 1,25 (OH)2 D3 significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pre-treatment increased production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pre-treatment markedly reduced LPS-induced TLR-4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pre-treated with 1,25 (OH)2 D3 before stimulation with LPS. Conclusion: 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintenance of endometrial immune homeostasis through controlling potentially harmful inflammatory responses associated with female reproductive tract infections. Key words: Vitamin D3, Endometrium, Inflammation, Toll like receptors, Pro-inflammatory cytokines

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