T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro

Vascular ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 314-320
Author(s):  
Weiping Ci ◽  
Tian Wang ◽  
Taotao Li ◽  
Jin Wan

Objectives The effect and underlying mechanism of T-614 (iguratimod) on Takayasu’s arteritis (TA) are unknown. Here, we report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in human aortic adventitial fibroblasts (HAAFs) in vitro and explore its initial benefit in terms of vascular wall inflammation and remodeling for patients with TA. Methods HAAFs were cultured with 0, 5, 50, 100, or 250 μg/ml T-614 in the absence or presence of tumor necrosis factor-α (TNF-α) in vitro. Cell viability was determined by a modified MTT assay. Supernatant IL-8 levels were measured by enzyme-linked immunosorbent assays. Results In the presence of TNF-α, compared to that in the control group, cell viability of HAAFs significantly decreased in the 50, 100, and 250 μg/ml T-614 treatment groups (OD value: P <  0.01, P <  0.001, P <  0.001, respectively; survival fraction (SF): P <  0.05, P <  0.001, P <  0.001, respectively). However, there was no significant difference in cell viability between TNF-α-stimulated and unstimulated groups at the same concentration of T-614. In the absence or presence of TNF-α, T-614 suppressed HAAF cell viability dose-dependently (OD value: r = −0.915, P =  0.000; r = −0.926, P =  0.000, respectively; SF: r = −0.897, P =  0.000; r = −0.885, P =  0.000, respectively). Compared to that in the control group, in the absence of TNF-α, IL-8 levels in the 5 and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.05); in the presence of TNF-α, IL-8 levels in the 5, 50, and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.001, P <  0.001, P <  0.01, respectively). Further, there was a negative correlation between supernatant IL-8 levels and T-614 concentration in groups stimulated with TNF-α ( r = −0.670, P =  0.000), but there was no significant correlation between these parameters in groups that were not stimulated with TNF-α. Conclusions In the absence or presence of TNF-α, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA.

Author(s):  
Rafal J Al-Saigh ◽  
Hussam Al-Humadi

Tuberculosis(TB) is aninfectious disease caused by Mycobacterium tuberculosis. The aim was to investigate the levels of immunomodulatory markers like interluekin-6 (IL-6), tumor necrotizing factor-α (TNF- α),cell differentiation-4 (CD4) and CD8 levels in those patients with active tuberculosis (TB) disease in comparison with control group. 41 Adults diagnosed with TB were included in comparison to 32 healthy individuals at Babylon health center for pulmonary diseases and TB. Descriptive data for patients and control group werecollected by well-trained researcher following a structured questionnaire. In parallel, peripheral blood collected to determine IL-6, TNF- α,CD4 and CD8. Then the assessment for the association between clinical and descriptive data and immunomodulatory markers levels was investigated statistically. The majority of TB patients were males (56%) and 71% were resident in rural areas; 47% of them were living in middle socioeconomic state,moreover,47% of TB cases had diabetes,furthermore,51% had chronic obstructive pulmonary diseases,12% had hypertension and 39% of them had chronic anemia with 47% smokers with no significant difference versus control. Following to that,there was highly increased in IL-6 and TNF-α levels in TB patients versus control (P<0.001),with low CD4 level versus control (P<0.001). While there was no significant change shown in CD8 levels versus control and this might highly be correlated with 30% of abnormal liver function tests among TB patients. A high proportion of TB patients have low CD4 level mostly associated with active disease. Moreover,the increase of IL-6 and TNF-α levels suggests a inverse impact on CD4 level which closely associated with the outcome of the disease.


2021 ◽  
Vol 11 (12) ◽  
pp. 1282
Author(s):  
Sheng-Yu Lee ◽  
Tzu-Yun Wang ◽  
Ru-Band Lu ◽  
Liang-Jen Wang ◽  
Cheng-Ho Chang ◽  
...  

We have previously identified five candidate proteins (matrix metallopeptidase 9 (MMP9), phenylalanyl-TRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin Type 9 (PCSK9)) as potential biomarkers for bipolar II disorder (BD-II). These candidate proteins have been associated with neuroprotective factors (BDNF) and inflammatory factors (cytokines, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α)). However, the correlations between these proteins with plasma BDNF and inflammatory factors remain unknown. We recruited a total of 185 patients with BD-II and 186 healthy controls. Plasma levels of candidate proteins, BDNF, cytokines (TNF-α, CRP, and interleukin-8 (IL-8)) were assessed from each participant. The correlations between levels of candidate proteins, BDNF, and cytokines were analyzed. In the BD-II group, we found that the level of FARSB was positively correlated with the BDNF level (r = 0.397, p < 0.001) and IL-8 (r = 0.320, p < 0.001). The CA-1 level positively correlated with IL-8 (r = 0.318, p < 0.001). In the control group, we found that the FARSB level positively correlated with the BDNF level (r = 0.648, p < 0.001). The CA-1 level positively correlated with TNF-α (r = 0.231, p = 0.002), while the MMP-9 level positively correlated with the CRP level (r = 0.227, p = 0.002). Our results may help in clarifying the underlying mechanism of these candidate proteins for BD-II.


2016 ◽  
Vol 17 (6) ◽  
pp. 457-462 ◽  
Author(s):  
Isleine P Caldas ◽  
Miriam Z Scelza ◽  
Marco A Gallito ◽  
Gutemberg Alves ◽  
Licínio Silva

ABSTRACT Aims The aim of this study is to evaluate the in vitro response of human gingival fibroblasts in primary cultures to two materials for temporary relining of dentures: Temporary Soft (TDV, Brazil) and Trusoft (Bosworth, USA) for 24 hours, 7 and 30 days by using a multi-parametric analysis. Materials and methods Each material sample (TDV, TS, Polystyrene, Latex) was prepared and incubated in a culture medium for 1, 7, and 30 days at 37°C. Human gingival fibroblasts were exposed to the extracts and cell viability was evaluated by a multi-parametric assay, which allowed sequential analysis of mitochondrial activity (XTT), membrane integrity [neutral red (NR)], and cell density [crystal violet dye exclusion (CVDE)] in the same cells. Analysis of variance (ANOVA) was used to test the interactions of the three sources of variation (material, test method, and time) with the proportions of viable cells for each relining material. Results Both evaluated materials (TDV and TS) had low cytotoxic effects during 1, 7, and 30 days after manipulation of the material, as assessed by all three methods used. A statistical difference was found when comparing the negative control group (latex fragments) with the other groups, which showed high toxicity and low percentage of cell viability in all tests used. There was no significant difference among other materials (p > 0.05). Conclusion Low cytotoxicity levels were detected by representatives of the major groups of temporary prosthetic relining materials, as evaluated by multiple cellular viability parameters in human fibroblasts. Clinical significance There are various soft materials on the market for relining prostheses; however, the effects of these materials on tissues need to be clarified to avoid problems for patients. How to cite this article Caldas IP, Scelza MZ, Gallito MA, Alves G, Silva L. In vitro Analysis of Cytotoxicity of Temporary Resilient Relining Materials. J Contemp Dent Pract 2016;17(6):457-462.


2021 ◽  
Vol 18 (6) ◽  
pp. 1161-1166
Author(s):  
Zhiwen Zhou ◽  
Xiang Ren ◽  
Aiping Li ◽  
Wensheng Zhou ◽  
Li Huang

Purpose: To investigate the protective effect of floroindole against cecal ligation and puncture (CLP)- induced sepsis, as well as the underlying mechanism of action. Methods: Thirty-five 10–week-old male Wistar rats weighing 190 - 210 g (mean: 200.00 ± 10.10 g) were used for this study. The rats were randomly assigned to seven groups of five rats each, viz, normal control group, and six CLP groups. The CLP groups were those subjected to cecal ligation and puncture (CLP). The first 5 CLP groups received 2, 4, 6, 8 or 10 mg/kg floroindole, respectively, 1 h after CLP, via intraperitoneal route (i.p.) while the 6th CLP group served as untreated control. Western blotting, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) were used for the assessment of the expression levels of tumor necrosis factor-α (TNF- α), interleukn-6 (IL-6), nucleotide-binding oligomerization domain 2 (NOD2) and p-NF-κB p65. Results: Cecal ligation and puncture (CLP) significantly and time-dependently upregulated the expressions of TNF-α, IL-6 and NOD2 in intestinal tissues of rats (p < 0.05). However, treatment with floroindole significantly, and dose-dependently down-regulated CLP-induced expressions of these proteins (p < 0.05). Treatment of rats with floroindole also significantly and dose-dependently inhibited CLP-induced phosphorylation of NF-κB p65 in rat ileum (p < 0.05). Conclusion: The results obtained in this study demonstrate that floroindole confers some degree of protection against CLP-induced sepsis via inhibition of NF-κB p65 phosphorylation.


Author(s):  
Magrur Kazak DDS, PhD ◽  
Nazmiye Donmez DDS, PhD ◽  
Fatemeh Bahadori PhD ◽  
Vildan Betul Yenigun PhD ◽  
Abdurrahim Kocyigit MD, PhD

Objective: Studies have focused on use of non-expired composites. Unfortunately some clinicians still use expired composite resins without considering their effects. The objective of this in vitro preliminary research was to investigate cytotoxicity of expired(6-months) and non-expired composite resins. Materials and methods: Expired (E) and non-expired (NE) samples of one bulk-fill (Tetric N-Ceram Bulk-fill [TNB], Ivoclar Vivadent), two nano-hybrid (Tetric N-Ceram [TN], Ivoclar Vivadent; Clearfil Majesty ES-2 [CM], Kuraray) composite resins were tested on L929 fibroblast cells. Medium covering cells was removed then plastic rings (2-mm height) were filled with non-polymerized composite resins, placed in direct contact with cells and polymerized with LED light curing unit (LCU). Three samples were prepared for each group. After polymerization, removed medium was added to the cells. Cells that were left without medium (WOM) and cells that were exposed to LCU were used as positive control groups. Cells without any treatment were used as negative control group (C). Cells were incubated with tested materials for 7-days to evaluate cytotoxicity. Cell viability was calculated by sulforhodamine B test as a percentage (%). One-way ANOVA and post-hoc Tukey tests were used for statistical analyses (p<0.05). Results: Comparison between E and NE groups of same composite resins did not result in statistically significant differences (p>0.05), except between TN NE and TN E (p<0.05). TN E group was significantly more cytotoxic than TN NE group. When NE composite resin groups were compared to each other, statistically significant difference was only obtained between TNB NE and TN NE (p<0.05). Among all tested groups, TN NE group showed the least cytotoxic profile. No statistically significant differences were determined when E composite resin groups were compared to each other (p>0.05). All experimental groups compared with C group showed statistically significant cytotoxicity (p<0.05). A statistically significant difference existed between LCU and C groups (p<0.05). Conclusions: In clinical practice, expired composite resins should never be used. Although a correlation was found between expiration dates of nano-hybrid composite resins and cell viability, opposite data were obtained for bulk-fill composite resin. Researches are still required to evaluate biocompatibility of bulk-fill composite resins at various thicknesses with current LCUs.


2019 ◽  
Vol 17 ◽  
pp. 205873921983704
Author(s):  
Wentao Wang ◽  
Dequan Zhong ◽  
Hua Cheng ◽  
Chengfu Ji ◽  
Zhouming Shen ◽  
...  

The aim of this study is to investigate the efficacy of expanded endonasal approaches (EEAs) in the treatment of pituitary adenoma, and the effects of serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-12 (IL-12) in patients were further analyzed. A total of 80 cases of patients with pituitary adenoma admitted to our hospital from January 2013 to May 2015 were randomly divided into the observation group and control group, with 40 cases in each group. The observation group was treated with EEA technique, while the control group was treated with transcranial microsurgery. The prolactin (PRL), growth hormone (GH) and other endocrine hormone indexes, as well as inflammatory factors such as TNF-α, IL-6, and IL-12 were compared before and 1 week after the operation between the two groups. Moreover, the scores of Karnofsky performance status (KPS) and Mini-Mental State Examination (MMSE) at preoperative and postoperative 1 week were also compared between the two groups. The operation time, hospitalization time, and postoperative complications were compared between the two groups. And the patients were followed up for 2 years to observe the recurrence rate. The operation time and hospital stay in the observation group were 62.8 ± 9.3 min and 12.5 ± 2.1 days, respectively, while the operation time and length of stay in the control group were 105.6 ± 15.7 min and 18.2 ± 3.4 days, respectively. The operation time and hospitalization time were shorter than those in the control group, and the differences were statistically significant ( P < 0.05). Before surgery, there was no significant difference in serum levels of PRL and GH between the two groups ( P > 0.05). At 1 week after surgery, the levels of PRL and GH in the two groups were significantly lower than those before surgery ( P < 0.05). And the serum levels of PRL and GH in the observation group were significantly lower than those in the observation group at 1 week after the operation ( P < 0.05). Before operation, there was no significant difference between the two groups of KPS and MMSE scores ( P > 0.05). At 1 week after operation, the scores of KPS and MMSE in both groups were significantly higher than those before the operation ( P < 0.05), and the scores of KPS and MMSE in the observation group were significantly higher than those in the control group ( P < 0.05). Furthermore, there was no significant difference in the serum levels of IL-6, IL-12, and TNF-α between the two groups before operation ( P > 0.05). At 1 week after surgery, the serum levels of IL-6, IL-12, and TNF-α in the two groups were significantly lower than those before surgery ( P < 0.05), while the serum levels of IL-6, IL-12, and TNF-α in the observation group were evidently lower than those in the control group at 1 week after the operation. Besides, the incidence of postoperative complications in the observation group was 7.5%, which was significantly lower than that in the control group (17.5%) ( P < 0.05). All the patients in the two groups were followed up for 2 years. And there was no recurrence in the observation group and one case in the control group. The therapeutic effect of EEAs on pituitary adenoma is better. It can improve the level of high endocrine hormone in patients with pituitary adenoma, improve the functional status of the patients, reduce the serum level of inflammatory factors, and shorten the hospital stay. Meanwhile, it also has the characteristics of fewer complications and low recurrence rate, so it can be popularized in clinical practice.


2019 ◽  
Vol 12 (5) ◽  
pp. 211-218 ◽  
Author(s):  
Siwaporn Wongsen ◽  
Duangporn Werawatganon ◽  
Somying Tumwasorn

Abstract Background Salmonella typhimurium is a cause of gastroenteritis including diarrhea. Lactobacillus plantarum is a probiotic widely used to prevent and treat diarrhea. Objectives To determine the protective effects of L. plantarum B7 on diarrhea in mice induced by S. typhimurium. Methods Inhibition of S. typhimurium growth by L. plantarum B7 was determined using an agar spot method. Mice were divided into 3 groups (n = 8 each): a control group, an S group administered 3 × 109 CFU/mL S. typhimurium, and an S + LP group administered 1 × 109 CFU/mL L. plantarum B7 and 3 × 109 CFU/mL S. typhimurium daily for 3 days. Counts of S. typhimurium and percentage of fecal moisture content (%FMC) were determined from stool samples. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and CXCL1 were determined. Results L. plantarum B7 produced a clear zone on S. typhimurium. There were significantly less S. typhimurium in the feces from mice in the S+LP group than in the S group. Serum levels of TNF-α, IL-6, and CXCL1 in mice from the S group were significantly higher than levels in the S+LP and control groups. Feces from mice in the S group were soft and loose, whereas in the S+LP group they were hard and rod shaped. The %FMC in the S+LP group was significantly less than in the S group. Conclusions L. plantarum B7 can inhibit growth of S. typhimurium, decrease levels of proinflammatory cytokines, and attenuate symptoms of diarrhea induced in mice by S. typhimurium.


Author(s):  
Katarzyna Sznurkowska ◽  
Katarzyna Kaźmierska ◽  
Tomasz Śledziński ◽  
Maciej Zagierski ◽  
Anna Liberek ◽  
...  

Background: Cystic fibrosis (CF) is characterized by malnutrition and chronic inflammation predominantly occurring in lungs. Evidence suggests a relation between inflammatory activity and nutritional status. Proinflammatory cytokines, playing crucial role in pulmonary destruction in CF, are regarded as a component of the pathogenesis of illness-related malnutrition. Chemerin - a novel marker of a crosstalk between nutrition and inflammation, has not been investigated in children with cystic fibrosis. The aim of this study was to determine serum level of chemerin, interleukin-1b (IL-1b), interleukin-6 (IL-6), tumor necrosing factor α (TNF-α) and interleukin-10 (IL-10) and to verify if they correlate with the nutritional status in children with CF. Methods: The study included 72 pediatric patients with cystic fibrosis. The control group was comprised of 30 healthy children. Nutritional status parameters: Body Mass Index (BMI), fat mass percentage (FM %) and fat free mass percentage (FFM%) have been assessed in all the subjects basing on bioimpedance and anthropometry according to Slaughter. Serum concentrations of chemerin and cytokines were estimated with ELISA. Results: No statistically significant difference in serum chemerin was found between the studied and the control group. We have documented a significantly higher level of IL-1b, IL-6, TNF-α and IL-10 in CF patients when compared to healthy controls. Neither the chemerin nor the cytokine levels correlated with parameters of nutritional status in our cohort. No statistically significant correlation was found between the serum chemerin and the inflammatory cytokines: IL-1b, IL-6, and TNFα. Conclusions: Our results show that chemerin is not associated with the nutritional status in children with cystic fibrosis. Chemerin has no impact on the levels of IL-1b, IL-6, TNFα in CF patients. IL-1b, IL6, TNFα and also IL10 are upregulated in cystic fibrosis.


2019 ◽  
Vol 20 (24) ◽  
pp. 6302
Author(s):  
Jae Hyun Han ◽  
Ok-Hee Kim ◽  
Sang Chul Lee ◽  
Kee-Hwan Kim ◽  
Jung Hyun Park ◽  
...  

Tumor necrosis factor-α (TNF-α)-driven inflammatory reaction plays a crucial role in the initiation of liver fibrosis. We herein attempted to design genetically engineered adipose-derived stem cells (ASCs) producing etanercept (a potent TNF-α inhibitor), and to determine the anti-fibrotic potential of the secretome released from the etanercept-synthesizing ASCs (etanercept-secretome). First, we generated the etanercept-synthesizing ASCs by transfecting the ASCs with mini-circle plasmids containing the gene insert encoding for etanercept. We subsequently collected the secretory material released from the etanercept-synthesizing ASCs and determined its anti-fibrotic effects both in vitro (in thioacetamide [TAA]-treated AML12 and LX2 cells) and in vivo (in TAA-treated mice) models of liver fibrosis. We observed that while etanercept-secretome increased the viability of the TAA-treated AML12 hepatocytes (p = 0.021), it significantly decreased the viability of the TAA-treated LX2 HSCs (p = 0.021). In the liver of mice with liver fibrosis, intravenous administration of the etanercept-secretome induced significant reduction in the expression of both fibrosis-related and inflammation-related markers compared to the control group (all Ps < 0.05). The etanercept-secretome group also showed significantly lower serum levels of liver enzymes as well as pro-inflammatory cytokines, such as TNF-α (p = 0.020) and IL-6 (p = 0.021). Histological examination of the liver showed the highest reduction in the degree of fibrosis in the entanercept-secretome group (p = 0.006). Our results suggest that the administration of etanercept-secretome improves liver fibrosis by inhibiting TNF-α-driven inflammation in the mice with liver fibrosis. Thus, blocking TNF-α-driven inflammation at the appropriate stage of liver fibrosis could be an efficient strategy to prevent fibrosis.


Author(s):  
Rathika Rai ◽  
M. A. Easwaran ◽  
K. T. Dhivya

Aim: To evaluate the surface detail reproduction of dental stone this is immersed in different disinfectant solution and studied under stereomicroscope. Methodology: Total number of 30 specimens of dental stone (Type III) were made with measurements of 1.5cm diameter and 1cm height .This samples are divided in to 3 groups group A,B,C. were A is immersed in Distilled water which was taken as control group ;B is immersed in 2% Glutaraldehyde and C is immersed in 5%sodium hypochlorite. Each specimen were immersed in the disinfectant solution for 15 minutes and dried under room temperature for 24 hrs. After 24 hrs each specimens are studied under stereomicroscope for surface details. Result: The results showed no significant difference in the surface irregularities and porosities for a group 1 and group 2 except group 3 which showed significant increase in the porosities, surface irregularities and erosions after disinfection with 5% NaHOCl by immersion method. Conclusion: The surface detail reproduction capacity of die stone was adversely affected when 5% Sodium hypochlorite was used as disinfectant solution when compare d to control group and 2% Glutaraldehyde


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