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2023 ◽  
Vol 83 ◽  
Author(s):  
Romina Chitsaz ◽  
Atefeh Zarezadeh ◽  
Jinous Asgarpanah ◽  
Parvaneh Najafizadeh ◽  
Zahra Mousavi

Abstract: Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin’s anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.


2022 ◽  
Author(s):  
Yanan Gao ◽  
Qingwei Meng ◽  
Xin Song ◽  
Qianqian Zhao ◽  
Baoming Shi

Abstract Background: The objective of this study was to investigate the effects of dietary resveratrol supplementation on growth performance, redox status, inflammatory state, and intestinal function of weaned piglets fed oxidized soybean oils.Methods: A total of twenty-eight castrated weaned male piglets with a similar body weight of 10.19 ±1 kg were randomly assigned to 4 dietary treatments for 28 days feeding trial with 7 replications per treatment and 1 piglet per replicate. Treatments were arranged as a 2×2 factorial with oil type [fresh soybean oils (FSOs) vs. oxidized soybean oils (OSOs)] and dietary resveratrol (RES) (0 vs. 300 mg/kg).Result: Inclusion of OSOs decreased the villus/crypt ratio (VCR), while the villus height (VH) and VCR in the jejunum of weaned piglets was increased by dietary RES (P< 0.05). The activities of lipase, chymotrypsin, and lactase were decreased by OSOs, however dietary RES supplementation increased the activities of lipase, chymotrypsin, lactase, and α-amylase in the jejunum of weaned piglets (P< 0.05). Dietary RES increased the apparent digestibility of crude fat (EE). Dietary RES supplementation in the diets supplemented with OSOs decreased the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in the plasma of weaned piglets, but failed to influence the IL-1β, IL-6, IL-8, and TNF-α level when diets supplemented with FSOs. Dietary RES alleviated the decrease of total-superoxide dismutase activity in the plasma of weaned piglets fed OSOs (P< 0.05). Dietary supplemented with OSOs and RES decreased the level of H2O2 in the plasma of weaned piglets (P< 0.05). RES alleviates the intestinal barrier damage fed OSOs in weaned piglets by increasing the mRNA expression of ZO-1 and Occludin. It is noteworthy that inclusion of OSOs in diets increased the abundance of Actinobacteria, and decreased the abundance of Tenercutes (P< 0.05). RES increased the abundance of Firmicutes, and decreased the abundance of Bacteroidetes (P< 0.05). At the genus level, RES decreased the abundance of Prevotella-1, Prevotellaceae UCG003, and Clostridium_sensu_stricto_6 in the colon. OSOs decreased the level of acetic acid, and dietary RES increased the level of acetic acid and butyric acid in the colon of weaned piglets.Conclusions: Dietary RES supplementation improved the villus-crypt structure, digestive enzyme activities and alleviated OSOs induced digestive absorption disorder. In addition, RES may alleviate OSOs immune status and energy metabolism of weaned piglets by affecting gut microbiota and its metabolite SCFAs. Notably, this positive effect of RES on OSOs may be related to decrease in the abundance of Prevotella_1 and Prevotellaceae_UCG-003.


2022 ◽  
Vol 12 ◽  
Author(s):  
Eslam E. Abd El-Fattah ◽  
Sameh Saber ◽  
Mahmoud E. Youssef ◽  
Hanan Eissa ◽  
Eman El-Ahwany ◽  
...  

HIF-1α is a key factor promoting the development of hepatocellular carcinoma (HCC). As well, AKT-AMPKα-mTOR signaling is a promising target for cancer therapy. Yet, the AKT-AMPKα-mTOR-dependent activation of HIF-1α has not been studied in livers with HCC. In addition, the mechanisms underlying the potential antineoplastic effects of sitagliptin (STGPT), an antidiabetic agent, have not yet been elucidated. For that purpose, the N-nitrosodiethylamine (NDEA)-induced HCC mouse model was used in the present study using a dose of 100 mg/kg/week, i.p., for 8 weeks. NDEA-induced HCC mice received STGPT 20, 40, or 80 mg/kg starting on day 61 up to day 120. The present study revealed that STGPT inhibited HIF-1α activation via the interference with the AKT-AMPKα-mTOR axis and the interruption of IKKβ, P38α, and ERK1/2 signals as well. Accordingly, STGPT prolonged the survival, restored the histological features and improved liver function. Additionally, STGPT inhibited angiogenesis, as revealed by a significant downregulation in the VEGF and mRNA expression of CD309 with concomitant inhibition of tissue invasion was evident by an increased ratio of TIMP-1/MMP-2. STGPT exhibited apoptotic stimulatory effect as indicated upon calculating the BCL-2/Bax ratio and by the gene expression of p53. The decrease in AFP and liver index calculation, gene expression of Ki-67 confirmed the antiproliferative activity of STGPT. The anti-inflammatory potential was revealed by the decreased TNF-α level and the downregulation of MCP-1 gene expression. Moreover, an antifibrotic potential was supported by lower levels of TGF-β. These effects appear to be GLP1R-independent. The present study provides a potential basis for repurposing STGPT for the inhibition of HCC progression. Since STGPT is unlikely to cause hypoglycemia, it may be promising as monotherapy or adjuvant therapy to treat diabetic or even normoglycemic patients with HCC.


2022 ◽  
Vol 12 (1) ◽  
pp. 477
Author(s):  
Ízola Morais de Medeiros Ramalho ◽  
Gabriela Suassuna Bezerra ◽  
Elissa Arantes Ostrosky ◽  
Márcio Ferrari ◽  
Verônica da Silva Oliveira ◽  
...  

Chrysin is a bioactive flavonoid found in pollens, passion flowers, honey, royal jelly, and propolis, which is commonly used as an ingredient in natural food supplements and is primarily responsible for their pharmacological properties. A transparent chrysin-loaded microemulsion (CS-ME) prepared through a ternary phase diagram was evaluated for use as an antihyperalgesic formulation. It was formulated with 40% Labrasol® (surfactant), 5% isopropyl myristate (oil phase) and 55% water (aqueous phase) and classified as an oil-in-water (O/W) microsized system (74.4 ± 15.8 nm). Its negative Zeta potential (−16.1 ± 1.9 mV) was confirmed by polarized light microscopy and dynamic light scattering analysis. In vitro studies in Franz-type static diffusion cells showed that chrysin release from CS-ME followed zero-order kinetics. Oral administration of CS-ME in mice resulted in a statistically significantly reduction (p < 0.05) in carrageenan-induced mechanical hyperalgesia compared to the control group. Treatment with CS-ME also showed anti-inflammatory activity by significantly decreasing the TNF-α level (p < 0.01) and increasing that of IL-10 (p < 0.05) compared to the control group. These results suggest that the proposed microsystem is a promising vector for the release of chrysin, being able to improve its capacity to modulate inflammatory and nociceptive responses.


2021 ◽  
Vol 9 (3) ◽  
pp. 195
Author(s):  
Fitratul Ramadhan ◽  
Ngakan Putu Parsama Putra ◽  
Ungky Agus Setyawan ◽  
Susanthy Djajalaksana ◽  
Aditya Sri Listyoko ◽  
...  

Tumor Necrosis Factor Alpha (TNF-α) is a pro-inflammatory cytokine that plays a crucial role in COVID-19 disease progression. N-acetylcysteine (NAC) works throughout several GSH-mediated mechanisms and is known to eliminate oxidative stress in acute respiratory distress syndrome (ARDS) in COVID-19. This study aims to analyze the effect of the N-Acetylcysteine as Adjuvant Therapy to reduce TNF-α levels and Increase SpO2/FiO2 ratio in Improving hypoxemia in COVID-19 Patients. This is a quasi-experimental, non-equivalent control group design study. There were 91 subjects selected using non-random sampling, which consisted of 75 patients in the NAC group and 16 patients in the control group. The TNF-α level was measured using the ELISA method, and SpO2/FiO2 ratio was calculated on day 1 (on admission) and day eight after NAC 5000mg/ 72 hours was given. Statistical analysis was conducted using Wilcoxon and Mann-Whitney U Test. There is a significant decrease in TNF-α level in the treatment group (median 1.49±5.22) (p=0.016) compared with the control group (median 1.64±1.99) (p=0.005). The Median SpO2/FiO2 ratio on day 1 is 163.70±69.64 in the control group and 121.49±40.41 in the treatment group (p=0.005). The Median SpO2/FiO2 ratio on day 8 is 249.69±132.26 in the control group and 151.29±59.18 in the treatment group (p=0.001). There is a positive correlation between serum TNF-α level and SpO2/FiO2 ratio after administration of adjuvant therapy NAC (r=0.240, p=0.038). There is a positive correlation and significant decrease of serum TNF-α and SpO2/FiO2 ratio after adjuvant NAC therapy, which improves hypoxemia in COVID-19 patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Feng ◽  
Yinan Ma

High-fat diet (HFD) consumption can trigger chronic inflammation in some tissues. However, it remains unclear if HFD induces chronic inflammation in the spleen. This investigation aims to address the effect of HFD consumption and exercise intervention on the level of tumor necrosis factor alpha (TNF-α) in the spleen. Rats were subjected to HFD feeding and/or moderate-intensity treadmill running. The TNF-α levels in plasma and spleen were detected by ELISA. The mass and total cell numbers of the spleen were measured. In addition, the expression of TNF-α and its relevant gene mRNAs in macrophages from the spleen were analyzed by qRT-PCR. We found that HFD consumption did not significantly affect the mass and total cell numbers of the spleen. However, HFD consumption significantly increased splenic TNF-α level, the expression of TNF-α, toll-like receptor 4, and nuclear factor κB p65 mRNAs. In contrast, the expression of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) mRNA in macrophages was downregulated. Additionally, exercise abolished the increase in splenic TNF-α level as well as the abnormal expression of TNF-α and related gene mRNAs in macrophages in HFD-fed rats. In conclusion, our results reveal that HFD consumption increases TNF-α level in the spleen, which is along with upregulation of the expression of TLR4 and NF-κB mRNAs as well as downregulation of the expression of α7nAChR mRNA in splenic macrophages in rats. Exercise abolished detrimental effects of HFD on TNF-α level in the spleen and prevented abnormal expression of these genes in the macrophages from rat spleen.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Wang ◽  
Lixiong Liu ◽  
Xiaoping Hong ◽  
Dongzhou Liu ◽  
Zeneng Cheng

Delanzomib is a novel proteasome inhibitor initially developed for treating multiple myeloma. It was found to inhibit the expression of tumor necrosis factor alpha (TNF-α). This study aimed to investigate the ameliorating effect of delanzomib on collagen-induced arthritis (CIA) and to explore the pharmacodynamics and pharmacokinetics (PK) interactions between delanzomib and adalimumab. Rats with CIA were randomly assigned to receive the treatment with delanzomib, adalimumab, delanzomib combined with adalimumab, or placebo. Visual inspection and biochemical examinations including TNF-α, interleukin 6, and C-reactive protein were performed to assess arthritis severity during the treatment. The adalimumab concentration in rats was determined to evaluate the PK interaction between delanzomib and adalimumab. Also, the levels of neonatal Fc receptor (FcRn) and FcRn mRNA were measured to explore the role of FcRn in the PK interaction between delanzomib and adalimumab. As a result, delanzomib combined with adalimumab exhibited stronger anti-arthritis activity than a single drug because both drugs synergistically reduced TNF-α level in vivo. Delanzomib also decreased adalimumab elimination in rats by increasing the level of FcRn. The slower elimination of adalimumab in rats further prolonged the anti-TNF-α effect of adalimumab. Moreover, FcRn level was increased by delanzomib via suppressing FcRn degradation rather than promoting FcRn production. In conclusion, delanzomib combined with adalimumab may be a potential therapeutic approach for treating rheumatoid arthritis. The initial finding that the PK interaction occurred between delanzomib and adalimumab may have clinical relevance for patients who simultaneously take proteasome inhibitors and anti-TNF-α therapeutic proteins.


Author(s):  
Manijeh Motevalian ◽  
Siyavash Joukar ◽  
Saeed Esmaeili-Mahani ◽  
Abdollah Karimi ◽  
Yaser Masoumi-Ardakani ◽  
...  

Abstract Objectives Given the cardiac pathological remodeling following to anabolic androgenic steroids (AASs) consumption, we examined the effect of chronic administration of nandrolone decanoate with high-intensity endurance exercise on the left ventricular hypertrophy index, levels of hydroxyproline, tumor necrosis factor-alpha (TNF-α), adiponectin (APN) and its receptors (AdipoR1 and AdipoR2) expression in rats’ hearts. Methods The male Wistar rats randomly divided to six groups included the control (CTL), exercise (Ex), nandrolone (Nan), vehicle (Arach), trained vehicle (Ex + Arach), and trained nandrolone (Ex + Nan) groups that were treated for eight weeks. Results Nandrolone consumption significantly enhanced the hypertrophy index (p<0.05) and exercise intensified this effect. It also increased the level of cardiac hydroxyproline (p<0.001), however exercise completely masked this effect. The values of TNF-α protein and AdipoR1 protein significantly increased in trained nandrolone-treated (Ex + Nan) group in comparison with CTL group (p<0.05), however, did not show significant alteration in Nan or Ex groups. High-intensity endurance exercise significantly enhanced the AdipoR2 protein (p<0.05), but, co-administration of nandrolone with exercise prevented this effect. The mRNA expression of AdipoR1 significantly reduced in the animals that received nandrolone for eight weeks and exercise recovered this effect (p<0.001). Conclusions Despite an additive effect of high-intensity endurance exercise plus nandrolone on TNF-α level, their effects on hydroxyproline and APN receptors expression is incompatible in heart of rat. It is suggests a part of beneficial regulatory role of endurance exercise against nandrolone induced heart remodeling may apply through modulation of APN system.


Mathematics ◽  
2021 ◽  
Vol 9 (22) ◽  
pp. 2858
Author(s):  
Hennie Husniah ◽  
Asep K. Supriatna

The number of failures plays an important factor in the study of maintenance strategy of a manufacturing system. In the real situation, this number is often affected by some uncertainties. Many of the uncertainties fall into the possibilistic uncertainty, which are different from the probabilistic uncertainty. This uncertainty is commonly modeled by applying the fuzzy theoretical framework. This paper aims to compute the number of failures for a system which has Weibull failure distribution with a fuzzy shape parameter. In this case two different approaches are used to calculate the number. In the first approach, the fuzziness membership of the shape parameter propagates to the number of failures so that they have exactly the same values of the membership. While in the second approach, the membership is computed through the α-cut or α-level of the shape parameter approach in the computation of the formula for the number of failures. Without loss of generality, we use the Triangular Fuzzy Number (TFN) for the Weibull shape parameter. We show that both methods have succeeded in computing the number of failures for the system under investigation. Both methods show that when we consider the function of the number of failures as a function of time then the uncertainty (the fuzziness) of the resulting number of failures becomes larger and larger as the time increases. By using the first method, the resulting number of failures has a TFN form. Meanwhile, the resulting number of failures from the second method does not necessarily have a TFN form, but a TFN-like form. Some comparisons between these two methods are presented using the Generalized Mean Value Defuzzification (GMVD) method. The results show that for certain weighting factor of the GMVD, the cores of these fuzzy numbers of failures are identical.


2021 ◽  
Vol 18 (5) ◽  
pp. 40-46
Author(s):  
А. M. Fomin

Objective: to study the effect of selective plasmadsorption (SPS) on the level of pro-inflammatory and anti-inflammatory plasma cytokines, markers of liver failure in patients with obstructive jaundice.Material and Methods. The study was conducted in 23 patients with prolonged obstructive jaundice. The baseline level of total bilirubin ranged from 285 μmol/L to 589 μmol/L. All patients were exposed to selective plasmadsorption before biliodigistic surgery and twice in the early postoperative period. Selective plasmosorption was carried using OctoNova by Asahi Kasei Medical (Japan) with the use of the sorbent based on the Plasorba BR-350 anion exchange resin. In one procedure, about two volumes of circulating plasma were treated.Results. Initial increase in the level of pro-inflammatory TNF-α, IL-1β, IL-6 cytokines as well as anti-inflammatory IL-10 cytokine was established.Following SPS, TNF-α level signifcantly decreased by 42.4% (p < 0.05). The decrease in IL-1β and IL-6 was 38.9% and 34.0%, respectively. The level of IL-10 signifcantly decreased by 30.7% (p < 0.05). A signifcant decrease in the levels of total bilirubin by 39.8 ± 3.8%, conjugated bilirubin (by 38.2%), unconjugated bilirubin (by 32.5%), ALT (by 23.5%), AST (by 37%), and bile acids (by 31.4%) was revealed by the end of the procedure. There were no hemorrhagic complications associated with SPS.Conclusions. Selective plasmosorption in complex treatment of patients with mechanical jaundice with hepatic insufciency in perioperative period reduces endotoxicosis level not only due to correction of biochemical markers of liver failure but also due to reduction of proinflammatory and anti-inflammatory cytokines.


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