scholarly journals Jinwu Jiangu Capsule affects synovial cells in rheumatoid arthritis through PI3K/Akt/mTOR signaling pathway

2021 ◽  
Author(s):  
Qiuyi Wang ◽  
Xueming Yao ◽  
Hui Xu ◽  
Daomin Lu ◽  
Ying Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signal Pathway ◽  
High Dose ◽  
Synovial Cells ◽  
Mtor Signaling Pathway ◽  
Significant Difference ◽  
Mtor Protein ◽  
Capsule Suspension ◽  
New Zealand Rabbits ◽  
Medium Dose

Jinwu Jiangu Capsule is a medicinal formula from the Chinese Miao nationality. Leflunomide is recommended in organizational guidelines for the treatment of rheumatoid arthritis (RA). To investigate the effect of Jinwu Jiangu Capsule on PI3K/Akt/mTOR signal pathway in cells taken from RA patients New Zealand rabbits were administrated with Jinwu Jiangu Capsule suspension to prepare serum containing medicine. Lyophilized powder was prepared from this serum for cell treatment. The expression of LC3-II and PI3K, AKT, mTOR were detected by IF and western blot. Moreover, the levels of Atg1, Atg5, Atg14 were detected by RT-qPCR. The results showed that the expression of LC3-II was increased, and fluorescence spot of LC3-II was obvious in high-dose of Jinwu Jiangu Capsule group. Jinwu Jiangu Capsule decreased the level of PI3k, Akt, and mTOR protein, and increased the levels of Atg1, Atg5 and Atg14. Specially, the high-dose of Jinwu Jiangu Capsule had the most obvious inhibitory and up-regulation effects. However, there was no significant difference in the expression of Akt, mTOR and Atg1 in the medium-dose of Jinwu Jiangu Capsule group compared with the leflunomide group. In conclusion, Jinwu Jiangu Capsule regulates autophagy by inhibiting the PI3K/AKT/mTOR pathway in RA.

scholarly journals Effects of Industrial Waste Fish Oil Administration on Interleukin-6 (Il-6) Expression at Mice Colon being Induced by Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS)

2021 ◽  
Vol 14 (4) ◽  
pp. 2227-2233
Author(s):  
Kevin Tjoa ◽  
Kusmardi Kusmardi ◽  
Yurnadi Hanafi Midoen
Keyword(s):  
Fish Oil ◽  
Industrial Waste ◽  
Positive Control ◽  
Negative Control ◽  
High Dose ◽  
Omega 3 ◽  
Colon Tissue ◽  
Significant Difference ◽  
Solvent Control ◽  
Medium Dose

Colorectal cancer (CRC) is the world’s third most cancer and the second highest mortality rate. The searching for new anti-inflammation substances with less adverse effects than aspirin for chemoprevention and adjuvant chemotherapy of CRC is running. The most notable one is fish oil containing omega 3. Kusmardi, et al. studied that industrial waste fish oil omega-3 level comes close enough to conventional fish oil industry. Study aims to reducing the level IL-6 on mice colon tissue being induced CRC using AOM/DSS by fish oil administration. Thirty male Swiss Webster mice are grouped into six treatments: positive control (aspirin), negative control (physiological saline), normal, high dose (fish oil 6mg/kgBW), medium dose (fish oil 3mg/kgBW), dan solvent control (corn oil). Colon tissue was stained using anti IL-6 antibody. Ten photos per slide were taken by microscope (400x), analyzed for the IL-6 expression by ImageJ®, and quantified for H-score. Data was analyzed using SPSS 24.0 (CI 95%) and p-value <0.05 is consider significant. Data are not normally distributed with median of 161.64 (119.4-260.67). Kruskal-Wallis test is significant in addition with Mann-Whitney test shows only high dose group has significant difference to negative control (p=0.008), medium dose (p=0.016) dan and solvent control (p=0.008). No significant difference reported between high dose and positive control group (p=0.69). High dose industrial waste fish oil can lower IL-6 expression in mice colon tissue induced CRC using AOM/DSS.

scholarly journals Effect of Nalbuphine Combined With Intravenous Propofol for Anesthesia During Intestinal Endoscopic Submucosal Dissection in the Elderly

2021 ◽  
Author(s):  
Jingjing Liu ◽  
Biwei Zhan ◽  
Yongjun Zeng
Keyword(s):  
Endoscopic Submucosal Dissection ◽  
Dose Group ◽  
Total Duration ◽  
The Elderly ◽  
Neurocognitive Function ◽  
High Dose ◽  
Blood Oxygen Saturation ◽  
Submucosal Dissection ◽  
Significant Difference ◽  
Medium Dose

Abstract Objective: To investigate the effects of different doses of nalbuphine combined with an intravenous propofol pump for anesthesia during intestinal endoscopic submucosal dissection (ESD) in the elderly.Methods: A total of 85 elderly patients attending the Hanchuan People's Hospital from January 2016 to January 2018 were divided into low, medium, and high dose groups according to the intravenous dosing of nalbuphine given with a continuous propofol pump.The heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SaO2) were evaluated at five different time points (T1-T2).The levels of norepinephrine (NE), cortisol and blood glucose were intervals recorded. The occurrence of adverse reactions, hospitalization days, visual analogue scale (VAS) score, Ramsay sedation, and wake score after waking from anesthesia were assessed. Neurocognitive function was assessed at discharge and after surgery using the Montreal Cognitive Assessment (MoCA). Results: MR, MAP and SaO2 decreased significantly at T0-T4 in tested groups. The levels of NE, Cor, and Glu were significantly increased in three groups at T1-T3 and decreased among the medium-dose group. There was no statistically significant difference between the three groups in the total duration of anesthesia and the operative duration. The medium-dose group was performing significantly better than the low and high dose groups in clinical indicators. The postoperative VAS and Ramsay scores were higher in the low dose group (P＜0.05). There was a significant difference in neurocognitive function scores and no significant differences in postoperative anesthesia satisfaction and hospitalization days were observed amongst the three groups (P>0.05).Conclusions: The use of nalbuphine (0.1 mg/kg) combined with propofol for anesthesia during intestinal ESD in the elderly can shorten recovery times and reduce the incidence of postoperative adverse events and neurocognitive disorders.

Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity

2021 ◽  
Author(s):  
Maihaba Muhetaer ◽  
Mei Yang ◽  
Rongxiang Xia ◽  
Jun Wu
Keyword(s):  
Gender Differences ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Arsenic Toxicity ◽  
Male And Female ◽  
Significant Difference ◽  
Medium Dose

Abstract Background: There are gender differences in the biotransformation of arsenic. We investigated the effects of gender differences on arsenic metabolism and arsenic toxicity mechanisms in rat liver tissues. Methods: Rats were treated with different amounts of arsenic compounds. Arsenic form MMA and DMA in the liver was determined by high performance liquid chromatography-hydride generation atomic fluorescence spectroscopy. SAM, ARR, NAD, PNP, PK, and MPO in rat liver were determined by enzyme-linked immunoassay. RT-qPCR was used to determine AS3MT in the liver. Results: Compared with male and female animals in the same group, MMA and DMA were statistically significant in the three groups of iAs3 + high, iAs3 + medium and iAs5+ low (P <0.05). The MMA of male rats in iAs3+ high and medium groups was higher than that of female rats, and the DMA of male rats was lower than that of female rats. As3MT mRNA in the male iAs3+ high group was higher than that of females. Besides, compared between male and female, only in iAS3+ low dose, iAS3+ medium dose, iAS5+ low dose, and iAS5+ medium dose groups, there was significant difference in SAM level (P<0.05). Compared with male and female animals in the same group, male rats had significantly higher PNP and ARR activities while lower PK activity than female rats (P<0.05). Between the male and female groups, only the iAS3+ high dose and medium dose group had a statistically significant difference (P<0.05). The NAD activity of females in iAS3+ high dose group was higher than that of males. Conclusion: Conclusively, under the same arsenic exposure, there were gender differences between female and male rats, and arsenic metabolism was more cytotoxic to male rats than to females.

Endothelin-1 Production by Human Synoviocytes

1998 ◽  
Vol 35 (2) ◽  
pp. 290-294 ◽  
Author(s):  
Hiroshi Yoshida ◽  
Yuji Imafuku ◽  
Morihiro Ohhara ◽  
Masayuki Miyata ◽  
Reji Kasukawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Arthritis ◽  
Synovial Cells ◽  
Type B ◽  
Serum Samples ◽  
Synovial Macrophage ◽  
Significant Difference ◽  
Synovial Fluids ◽  
Synovial Tissues

Immunoreactive (ir)-endothelin (ET)-l concentrations in serum samples and synovial fluids from patients with rheumatoid arthritis were higher than concentrations in sera obtained from healthy volunteers. No significant difference in ir-ET-1 concentrations in synovial fluid was observed between rheumatoid arthritis patients and osteoarthritis patients. Cultured fluids of synovial cells collected from synovial tissues and leucocytes from synovial fluids of rheumatoid arthritis patients were studied to determine the origin of ir-ET-1 in synovial fluids. Ir-ET-1 was detected in the cultured fluids of synovial macrophage-like type A cells, but not in those of fibroblast-like type B cells from the synovial tissues or leucocytes from the synovial fluids. Longitudinal studies showed that the ir-ET-1 concentration in the cultured fluid reached a peak around 24 h after starting the culture. ET-1 secreted from macrophage-like synoviocytes may be involved in the pathogenesis of inflammatory arthritis.

scholarly journals AB0126 METHOTREXATE MAINTENANCE THERAPY DURING THE TARGETED THERAPY ERA IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1092.1-1092
Author(s):  
S. Abdellaoui ◽  
S. Lefkir
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
Combination Therapy ◽  
Maintenance Therapy ◽  
Predictive Factors ◽  
Average Duration ◽  
High Dose ◽  
Average Dose ◽  
Das 28 ◽  
Significant Difference

Background:The persistence with methotrexate (MTX) at 1 year or 5 years in rheumatoid arthritis (RA) is very variable and intolerance remains the main cause of discontinuation of treatment. Changes in treatment with the strategy of adding “add-on” to a targeted therapy when the conventional DMARD becomes insufficient to optimally control the disease may decrease the maintenance MTX therapy rates, particularly for biologics with a Marketing Authorization as monotherapy.Objectives:The main objective of this study was to determine the rate of maintenance at 1 year of the combination therapy with different biologics, to compare the evaluation scores in patients receiving treatment as monotherapy (biological only) versus combination therapy with methotrexate and to analyze predictive factors for MTX maintenance therapy.Methods:We performed a descriptive study of 56 patients with RA meeting the criteria of the ACR 2010. Statistical analysis SPSS.20 Software.Results:These were 56 patients: 93% women and 7% men, mean age 46.74 years with an average duration of the disease of 14.74 years. 71.42% of patients were under corticosteroids taken for a period of 13 years with an average dose of 5.04 mg / day. BMI was highin 23.80% of patients, 30.95% had at least one associated comorbidity. The RF was positive in 61.90% and ACPA positive in 78.57% of cases. 47.62% were under MTX taken for 6.55 years with a dose of 13.03 mg / week on average: 68.75% by oral intake and 31.25% by subcutaneous intake with an average duration of setting before the switch of 8 years. 28 patients were on rituximab, 19 patients on tocilizumab and 9 patients on TNFi. 88.09% did not havenot received from bDMARD before. The mean ESR was 36.57 mm H1 and CRP was 8.56 mg / L. DAS28 at baseline was 6.81 and the current DAS 28 was 2.95 and the HAQ was 1.11. The rate of MTX maintenance therapy at 1 year was 36.84%, with rituximab, 64.28% with tocilizumab and 88% with TNFi. The comparison between the combination therapy with MTX and monotherapy groups showed a significant difference for the number of tender joints NTJ (3.5 vs 2.61), however, no significant difference concerning DAS28 value (2.98 vs 3.06), number of swollen joints NSJ (0.29 vs 0.22) and HAQ (1.09 vs 1.15). Regarding predictive factors of MTX maintenance therapy: Significant correlation was found with a high DAS 28 at baseline, however no correlation concerning the positivity of ACPA, duration of the disease, NTJ, NSJ, ESR, HAQ and the high dose of MTX. Reduction in persistence has found a significant correlation with non-naive RA of ≥ 1 bDMARD, disease activity score, type of biotherapy (antiTNF / rituximab vs Tocilizumab), young age, however no influence was found with a high BMI, HAQ, the presence of comorbidities or the withdrawal of corticosteroids. The increase in the persistence of combination therapy was associated with male gender and RF seropositivity only.Conclusion:Drug persistence is an important aspect of treatment effectiveness. For rheumatologists, knowledge of the factors that predict whether to maintain the combination therapy with methotrexate, increase or reduce the persistence is of great interest when choosing a new treatment to initiate in patients with RA.References:[1]Lavielle.M and Dougados.M. Targeted therapies in rheumatoid arthritis: Combination with conventional synthetic disease modifying antirheumatic drugs or monotherapy? Jone Bone Spine 2018;85:3-9.Disclosure of Interests:None declared

scholarly journals TNF-αDysregulation in Asthma: Relationship to Ongoing Corticosteroid Therapy

2000 ◽  
Vol 7 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Susan Waserman ◽  
Jerry Dolovich ◽  
Mary Conway ◽  
Jean S Marshall
Keyword(s):  
Corticosteroid Therapy ◽  
Mononuclear Cells ◽  
Inhaled Corticosteroids ◽  
Challenge Test ◽  
High Dose ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Significant Difference ◽  
Age And Sex ◽  
Medium Dose

BACKGROUND:Tumour necrosis factor-alpha (TNF-α) is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma. However, alterations in systemic regulation of this cytokine in asthma have not been examined in the context of corticosteroid therapy.OBJECTIVES:To examine the ability of peripheral blood mononuclear cells (PBMC) from three different groups of patients with asthma requiring varying amounts of inhaled corticosteroids (ICS) for clinical control, and to examine cells from age- and sex-matched nonasthmatic patients to produce TNF-α.DESIGN:All patients with asthma had a positive methacholine challenge test. 'High dose' ICS patients with asthma required ICS greater than or equal to 800 µg/day. 'Medium dose' patients with asthma were on less than or equal to 500 µg/day of ICS, whereas 'no ICS' patients with asthma had received no ICS for at least three months. Each patient with asthma was examined in parallel with an age- and sex-matched, nonasthmatic, nonatopic control subject. Cells were cultured (with or without the addition of potential stimulators phytohemagglutinin, lipopolysaccharide, formyl-methionine-leucine-phenylalanine or antihuman CD3), and TNF-αproduction was assessed by ELISA.MAIN RESULTS:PBMC from both high dose ICS (n=8) and no ICS (n=11) patients with asthma produced more than twice the amount of TNF-αthan cells from matched nonasthmatic control patients (P<0.01) when cultured alone or in the presence of each stimulus (P<0.05). In contrast, there was no significant difference in TNF-αproduction between medium dose ICS patients with asthma and control patients. A group of asymptomatic atopic patients (n=6) did not have an increased level of TNF-αproduction.CONCLUSIONS:Increases in TNF-αproduction within the PBMC compartment can be observed in both patients with asthma receiving high dose ICS and in a group of patients with mild asthma receiving no ICS therapy, but not in patients with asthma receiving a medium dose of ICS or atopic patients.

scholarly journals Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial

2019 ◽  
Vol 4 (3) ◽  
pp. 109-114
Author(s):  
Jie Xu ◽  
Yilong Wang ◽  
Anxin Wang ◽  
Zhiqiang Gao ◽  
Xiaoping Gao ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Multiple Dose ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Score Change ◽  
Double Blind ◽  
Significant Difference ◽  
Medium Dose

BackgroundEdaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and (+)-borneol, a food additive with an anti-inflammatory effect in animal ischaemic stroke models. This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke (AIS).MethodsIn this multicentre, randomised, double-blind, multiple-dose, active-controlled, phase II clinical trial, patients with AIS within 48 hours after stroke onset were randomly assigned (1:1:1:1) to low-dose (12.5 mg), medium-dose (37.5 mg) or high-dose (62.5 mg) Edaravone Dexborneol groups, and an active control group with edaravone (30 mg) by 30 min intravenous infusion every 12 hours, for 14 consecutive days. The primary efficacy outcome was the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days and National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 14 days after randomisation. The safety outcome included any adverse event during 90 days after treatment.ResultsOf 385 patients included in the efficacy analysis, 94 were randomised to low-dose group, 97 to medium-dose group, 98 to high-dose group and 96 to the control group. No significant difference was observed among the four groups on mRS score (mRS ≤1, p=0.4054) at 90 days or NIHSS score change at 14 days (p=0.6799). However, a numerically higher percentage of patients with mRSscore ≤1 at 90 days in the medium-dose (69.39%) and high-dose (65.63%) groups was observed than in the control group (60.64%). No significant difference in severe adverse events was found among the four groups (p=0.3815).ConclusionsCompared with edaravone alone, Edaravone Dexborneol was safe and well tolerated at all doses, although no significant improvement in functional outcomes was observed at 90days.Trial registration numberNCT01929096.

scholarly journals miR-125 regulates PI3K/Akt/mTOR signaling pathway in rheumatoid arthritis rats via PARP2

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Kai Liu ◽  
Yingang Zhang ◽  
Liang Liu ◽  
Qiling Yuan
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Normal Group ◽  
Luciferase Reporter ◽  
Synovial Cells ◽  
Reporter Assay ◽  
Mtor Signaling Pathway ◽  
Model Group ◽  
Synovial Tissues ◽  
Model C

Abstract The present study aimed to explore miR-125 effects on rheumatoid arthritis (RA) development to provide a potential target for RA. Briefly, rat RA model was established (Model group) by injection of Freund’s Complete Adjuvant into the left hind toe. Normal rats injected with saline in the same location were set as Normal group. All rats’ secondary foot swelling degree, polyarthritis index score, spleen and thymus index were measured. Synovial tissues were subjected to Hematoxylin–Eosin (HE) staining and immunohistochemistry. Synovial cells of each group were isolated and named as Normal-C group and Model-C group, respectively. Synovial cells of Model-C group further underwent cotransfection with miR-125 mimics and PARP2-siRNA (mimics+siPARP2 group) or with miR-125 negative control (NC) and PARP2-siRNA NC (NC group). Quantitative reverse transcriptase PCR (qRT-PCR), Western blot, luciferase reporter assay, ELISA, and MTT assay were performed. As a result, compared with Normal group, rats of Model group showed significantly higher secondary foot swelling degree, polyarthritis index score, spleen and thymus index (P<0.01). Down-regulated miR-125 and up-regulated PARP2 was found in synovial tissues of Model group when compared with Normal group (P<0.01). Synovial tissues of Model-C group exhibited severe hyperplasia and inflammatory cell infiltration. Luciferase reporter assay indicated that PARP2 was directly inhibited by miR-125. Compared with NC group, cells of mimics+siPARP2 group had significantly lower IL-1β, MMP-1 and TIMP-1 levels, absorbance value, and p-PI3K, p-Akt and p-mTOR relative expression (P<0.01 or P<0.05). Thus, miR-125 might attenuate RA development by regulating PI3K/Akt/mTOR signaling pathway via directly inhibiting PARP2 expression.

Change in bone mineral density with high-dose prednisone in patients with rheumatoid arthritis

2016 ◽  
Author(s):  
Linda Rasch ◽  
Tuyl Lilian van ◽  
Martijn Kremer ◽  
Irene Bultink ◽  
Maarten Boers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Bone Mineral ◽  
High Dose ◽  
Mineral Density ◽  
Dose Prednisone

Isolation of an Anti-fatigue Preparation from Cellulase-treated Maca by Hydroalcoholic Extraction

2017 ◽  
Vol 17 (1) ◽  
pp. 93-98
Author(s):  
Zheng Yue ◽  
Zhang Wen-Cheng ◽  
Wu Ze-Yu ◽  
Fu Chuan-Xiang ◽  
Gao Han ◽  
...  
Keyword(s):  
Positive Control ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Time To Exhaustion ◽  
High Dose ◽  
Hydroalcoholic Extract ◽  
Swimming Time ◽  
Significant Difference ◽  
Pre Treatment ◽  
Better Than

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.

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