جستجوی مقالات مرتبط با کلیدواژه « tnf-Α » در نشریات گروه « پزشکی »

Body weight loss is a common complication in hypoxic conditions. Several studies have reported that hypoxia increases the production of tumor necrosis factor-alpha (TNF-α) in in vitro and in vivo models. The present study investigates the role of circulating TNF-α concentration in body weight loss in acute and chronic systemic hypoxia.

In this experimental study, 28 adults male Wistar rats were divided into four acute or chronic control and acute or chronic hypoxia groups. Animals were exposed to room air with 21% oxygen level or hypoxia with 10-11% oxygen level in a normobaric hypoxic chamber for two days (acute) or ten days (chronic). TNF-α concentration was evaluated using the ELISA method. SPSS version 17 software was used for data analysis. The findings related to the weight of rats were used from the paired-sample t-test, and the data related to the concentration of tumor necrosis factor-alpha from the Two-tailed Student's t-test. Differences were considered significant at p>0.05 level.

The results showed that acute (p < 0.001) and chronic (p < 0.05) hypoxia caused a significant increase in the concentration of TNF-α in the serum, as well as induction of acute (p < 0.01) and chronic (p < 0.001) systemic hypoxia.) significantly decreased body weight before and after hypoxia induction.

Our findings show that acute and chronic systemic hypoxia is associated with increased serum levels of TNF-α, and acute and chronic systemic hypoxia is associated with weight loss. Due to the association of TNF-α with weight loss, the increase of TNF-α may be the reason for body weight loss in hypoxic conditions.

Interval exercises with high intensity and consumption of plant extracts probably have beneficial effects on inflammatory indicators. The aim of this study was to investigate the effect of eight weeks of High-Intensity Interval Training (HIIT) and the consumption of Loquat leaf extract on the serum levels of TNF-α and interleukin-18 in obese men with non-alcoholic fatty liver disease.

In this semi-experimental study, forty men with non-alcoholic fatty liver disease with body mass index (33.92 ± 1.82) with informed written consent were randomly selected and assigned into four groups: control, training, Extract, Extract + training (Each group of 10 people). Exercises were performed for eight weeks and three sessions per week for 60 minutes with intensity between 80-95% of the reserve heart rate. Two capsules of 250 mg of Loquat leaf extract were also prescribed daily. Paired t-test and analysis of covariance were used.

A significant decrease in the levels of TNF-α (15.3%) and interleukin 18 (14.9%) was observed in the training + extract group (P<0.05). A significant difference was observed in the levels of TNF-α (P=0.001) and interlock 18 (P=0.001) between the groups, and these changes were more significant in the Extract + training group than in the training and extract groups.

It is concluded that performing intense intermittent training along with Loquat leaf extract will be able to improve TNF-α and interleukin 18 indices related to fatty liver in people with non-alcoholic fatty liver disease. However, confirmation of this hypothesis requires more research.

 High-fat diet (HFD) intake is linked to ectopic fat deposition in the pancreas. It also causes pancreatic inflammatory lesions. trans-Chalcone is a simple chalcone with protective effects against HFD-induced metabolic disorders. This study, for the first time, explored the possible effects of this chalcone on high-fat emulsion-induced pancreatic abnormalities in rats.

 Twenty-one male rats were randomly assigned into three groups: control (received 10% tween 80); HFD (received high-fat emulsion + 10% tween 80); and HFD + chalcone (received high-fat emulsion + trans-chalcone). Real-time PCR was used to assess pancreatic mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α) in the pancreas of all rats.

 High-fat emulsion increased the mRNA expression levels of inflammatory biomarkers, including TNF-α and MCP-1 in the pancreas of rats, and treatment with trans-chalcone prevented these high-fat emulsion-induced changes.

 trans-Chalcone can protect the pancreas of male rats against HFD-induced abnormalities through its anti-inflammatory effects.

Practical Implications: 

It seems that consumption of HFD up-regulates the production of inflammatory mediators in the pancreas. On the other hand, trans-chalcone can ameliorate HFD-related pancreatic inflammation.

Abuse of anabolic steroids can lead to kidney tissue damage.The aim of this study was to investigate the effect of eight weeks of resistance training on inflammatory markers and antioxidant indices of kidney tissue of male rats following testosterone enanthate abuse.

In this experimental study, 24 male Wistar rats were randomly divided into three groups: 1) Control, 2) Training and 3) Training + Testosterone. Rats in groups 2 and 3 performed resistance training five sessions a week for eight weeks. Moreover, group 3 received 20 mg/kg of testosterone enanthate intramuscularly three days a week. The activity levels of Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) were measured by spectrophotometric method and the gene expression of Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) were measured by Real Time PCR method. The data were analyzed using SPSS version 16 software. To analyze the findings, To analyze the findings, one-way analysis of variance was used (P≥0.05).

Resistance training caused a significant decrease in GPx activity (P=0.001) compared to the control group. IL-6 gene expression in the training + testosterone group was significantly more than the training group (P=0.04) and the control group (P=0.001). Training + testosterone caused a significant increase in TNF-α gene expression compared to the training group (P=0.02) and the control group (P=0.008). Furthermore, the level of GPx activity in the training + testosterone group was significantly lower than the control group (P=0.001), but no significant difference was observed in the training + testosterone groups and the training group (P=0.93).

It seems that testosterone abuse along with intense resistance training is associated with a decrease in the function of the antioxidant system and increase in inflammatory markers in the kidney tissue.

Today, natural compounds such as peptides and probiotics can be mentioned as a supplement to the treatment of diseases such as cancer. These compounds may be effective in preventing the progression or treatment of cancer by affecting some molecular pathways including inflammation. The aim of this study was to investigate the effect of D-peptide-B and B.bifidum probiotic lysate on the expression of TNF-α and IL-1 genes in gastric cancer cells of AGS cell line.

In this study, AGS and HEK cells were cultured in DMEM medium with 10% bovine serum. The cells were treated with different concentrations of D-peptide-B and B.bifidum lysate and were incubated for 24 hours. The cell viability was checked by MTT. For molecular investigations, after RNA extraction and cDNA synthesis, the relative expression of TNF-α and IL-1 genes was evaluated using Real time PCR, and the data were analyzed using statistical methods One-way ANOVA.

The MTT results indicated that the AGS cancer cells’ survival rate decreased after treatment with dipeptide-B and lysate of B.bifidum as compared to HEK control cells. Furthermore, the study found that the expression levels of TNF-α and IL-1 genes in gastric cancer cells were significantly higher after treatment with D-Peptide-B, bacterial lysate, or both, when compared to normal HEK cells (P≤0.05). Specifically, the IL-1 gene expression increased by 300% (4 times) for peptide treatment, 100% (2 times) for bacterial treatment, and 650% (7.5 times) for combined treatment. Similarly, the TNF-α gene expression increased by 350% for peptide treatment, 100% for bacterial treatment, and 520% for combined treatment. These results suggest that these compounds may have induced cell death in cancer cells by affecting other molecular pathways.

Considering that D-peptide-B and B.bifidum lysate had no significant toxicity on normal cells and caused a significant decrease in the survival of cancer cells and this toxicity was dose dependent, therefore, consideration might be given to these natural compounds in treatment of gastric cancer.

Cytokine levels increase in response to air pollution. Air pollution is one of the most important factors affecting the general health of society and has become a concern in large and industrial cities. One of the        air- polluting components is sulfur dioxide (SO2). Based on epidemiological studies, SO2 aggravates various diseases such as cardio- pulmonary, cancer, progressive neurological diseases such as Alzheimer's, etc. The purpose of this study was to investigate the effects of sulfur dioxide gas on the level of pro- inflammatory cytokines IL-6 and TNF-α and hippocampal cell changes in mice.

This research was based on an experimental-laboratory study. Twenty- Four mice were randomly divided into 4 groups (control, Experimental (a) once with a high dose, Experimental (b) one week every day for 5 minutes with a low dose, Experimental (c) 3 weeks every day for 5 minutes with a low dose). In order to expose the animals to SO2 gas, a chamber was used. After the period, the mice were anesthetized and blood samples weretaken from the heart to analyze the inflammatory factors. After the perfusion, the brain was removed from the skull and entered the passage stages. Then cutting and staining the tissue slices, the neuronal density of different hippocampus regions was examined by the dissector method, and the data were analyzed by one- way ANOVA and Tukey's supplementary test.

The results showed that the amount of IL-6 in the experimental group b (P < 0.05) and c (P < 0.001) increased significantly compared to the control group. In addition, the amount of TNF-α also increased significantly in experimental group B (P < 0.05) and C (P < 0.001) compared to the control group. Also, the neuronal density of different areas of the hippocampus decreased in all groups compared to the control group, which is more significant in the experimental group (c) (P < 0.05).

It seems that the amount of IL-6, TNF-α increased in the experimental groups that were exposed to gas. Also, the neuronal density in all areas of the hippocampus of rats in the experimental groups was lower than in the control group.

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic form of interstitial lung disease, characterized by an inflammatory infiltrate, deposition of extracellular matrix (ECM) components like collagen, and change in the architectural lung parenchyma. IPF has a poor prognosis and is lethal, with a median survival of 2 to 3 years. The etiology of the disease is obscure; however, several studies indicated that the disease is initiated by inflammation and the release of profibrotic growth factor, namely transforming growth factor β (TGF-β). The definitive treatment for patients has not yet been approved. Although. However, evidence suggests that inflammation plays an essential role in the development and pathogenesis of IPF as a stimulus. However, inflammation is sometimes referred to as a secondary event in fibrosis, partly due to the failure of anti-inflammatory drugs in clinical trials. Therefore, more studies are needed to evaluate the effectiveness of anti-inflammatory therapies. In primary injury or inflammation, TGF-β, a critical cytokine and regulator of fibrosis, promotes inflammation and increases the activity and proliferation of fibroblasts at the site of inflammation, differentiation into myofibroblasts, and production of extracellular matrix, leading to severe pulmonary fibrosis. As a downstream mediator, the connective tissue growth factor (CTGF) is induced by TGF-β and promotes its fibrotic effects, enhancing lung fibrosis through fibroblast proliferation and collagen deposition. Evidence has shown that CTGF expression is increased in fibroblasts of IPF patients. In addition, Endothelin-1 (ET-1) is another downstream mediator of TGF-β fibrogenic responses in fibroblasts, which produces an extracellular matrix and differentiates fibroblasts into myofibroblasts. Also, the expression of tumor necrosis factor-alpha (TNF-α), which in addition to its inflammatory properties, also has fibrogenic properties, is significantly increased in the lungs of IPF patients. This expression is associated with increased fibroblasts and the deposition of extracellular matrix proteins in the interstitial region of the lung. In general, these findings indicatthat these factors are reasonable targets for designing treatment strategies or evaluating the effect of proposed drugs in the treatment of IPF.Broad-acting anti-inflammatory molecules, including glucocorticoids like Dexamethasone, were considered potential therapy. Glucocorticoids are anti-inflammatory agents that can reduce pro-inflammatory molecules by suppressing cellular and humoral immunity. Dexamethasone is one of the most potent glucocorticoid drugs; however, despite the various investigations on the inhibition of pulmonary fibrosis, its anti-fibrosis effects are still debated, and there are contradictory findings in this regard. Also, the underlying mechanism of its impact on IPF is not clear. Therefore, in this study, the therapeutic effect of Dexamethasone on pulmonary fibrosis was scrutinized, based on the impact of various players of this scenario, namely the expression of TGF-β, TNF-α, CTGF, ET-1and hydroxyproline.

6 to 8 week-old male mice were used in this study. All animal care conditions, including temperature, light, and humidity, were observed. Mice aged 8-10 weeks were randomly divided into the following groups, and ten mice were placed in each group.1.  Control group treated with normal saline (Control) 2.  Bleomycin inoculated group on day one (BLM)3.  Bleomycin inoculated on day one and dexamethasone-treated for 14 days (BLM+DEXA)The experiments were performed according to the approved guideline from the Faculty Ethics Committee (IR.IUMS.FMD.REC1396.9511127007). Lung fibrosis was induced intratracheal in anesthetized mice using 50 µL bleomycin (5mg/kg) by a single dose. The intervention with Dexamethasone (1mg/Kg/day) was done by 14 days intraperitoneal injection under sterile conditions. The mice were euthanized on day 21 under deep anesthesia, and their lungs were extracted. For evaluation, architectural changes occurred in the lungs based on bleomycin administration and dexamethasone intervention; the left lungs were fixed in formalin. The right lungs were frozen in liquid nitrogen for RNA extraction, gene expression analysis, ELISA, and hydroxyproline assay and were stored at -80 ºC. After 24 hours of immersion in formalin, paraffin blocks were prepared from the left lungs, and tissue incisions were made and transferred to the slide. After paraffin removal and leaching of slides, pathological examinations were performed using Masson Trichrome staining. The amount of hydroxyproline was measured using a hydroxyproline kit. Quantitative measurement of mRNA from CTGF and ET-1 genes in the lungs of mice was performed using real-time PCR. Data analysis of different groups was performed using Prism software and one-way ANOVA and Tukey multiple comparison test.In order to evaluate the anti-fibrotic effect of Dexamethasone in IPF, the bleomycin-induced mouse model was treated with Dexamethasone. After fibrosis was induced by intratracheal BLM administration, histopathological evaluation and hydroxyproline assay, ELISA for measurement of TGF-β and TNF-α, and RT-PCR were performed to evaluate the expression CTGF and ET-1 genes.

Histological examination indicated the deposition of collagen after administration of one dose of Bleomycin; an enzymatic analysis of hydroxyproline showed that administration of a single dose of BLM intratracheally leads to extensive fibrosis in the lungs of C57BL/6 mice on day 21. In comparison, 14 days of intraperitoneal treatment with Dexamethasone reduced the severity of fibrosis. Histological examination of Mason trichrome-stained tissue sections from lungs of control mice (receiving saline intratracheally) showed normal lung structure including no extracellular matrix deposition (based on the absence of blue color in the interstitium) and the alveolar space was distinct. While the lung tissue sections of BLM mice showed histopathological changes, including increased fibrotic areas and increased collagen deposition (based on increased blue color), and decreased alveolar spaces compared to the control group. However, lung tissue sections from dexamethasone-treated mice (BLM+DEXA group) showed only mild fibrosis. Dexamethasone treatment reduced the amount of hydroxyproline compared to the Bleomycin treated group; however, this reduction was not statistically significant (P> 0.05). Dexamethasone treatment significantly reduced TGF-β levels in the lungs of the BLM + DEXA group compared with the BLM group (P <0.001). Further, treatment of received Bleomycin (BLM) received mice with Dexamethasone (BLM + DEXA) reduced the amount of TNF-α when compared with Bleomycin received only group nevertheless, this reduction was not statistically significant to mice but statistically significant (P <0.05). The levels of TNF-α and TGF-β in the lungs of Bleomycin treatment mice (BLM) were higher when compared with Normal saline-treated mice (Control) (P <0.001). Dexamethasone treatment can induce its effect by inhibiting a prominent signaling pathway, namely TGF-β. Further, Dexamethasone treatment of Bleomycine received mice significantly reduced the expression of CTGF gene (P <0.001). CTGF expression occurs before the TGF- β cytokine is expressed during the phenomenon of fibrosis. It seems that CTGF is responsible for extracellular accumulation in the fibrosis pathway. In addition, 14 days of treatment of Bleomycin received mice with Dexamethason reduced ET-1 genes in the lungs of the BLM+DEXA group compared with the BLM group (P <0.001). ET1 gene is responsible for the differentiation of fibroblasts to myofibroblasts.It is known that Dexamethasone can ameliorate fibrosis; however, it is not known how this steroid can induce its effect or whether its impact is based on its role in the inhibition of inflammation

Our findings showed that intratracheal inoculation of Bleomycin in mice resulted in extensive accumulation of extracellular matrix in the lungs of C57BL/6 mice. Our study demonstrated that administration of Dexamethasone attenuated Bleomycin-induced pulmonary fibrosis in C57BL/6 mice by reducing hydroxyproline, production of two critical cytokines, the TGF-β and TNF-α, also by reduction of CTGF and ET-1 gene expression. Still, further investigations are required to understand how this compound can reduce fibrosis.

Nowadays, synthetic drugs used to treat inflammatory diseases are of the slightest interest due to their potential side effects and serious adverse effects. Therefore, finding new treatment approaches, especially herbal medicines, could help manage inflammation disorders. Olive and its products (oleuropein), as both antioxidants and inflammatory inhibitors, can effectively reduce the inflammatory process. This study aimed to investigate the effects of oleuropein on the cytokines profile of peripheral blood mononuclear cells of rheumatoid arthritis patients.

A 5 ml blood sample was taken from 40 patients with RA. Peripheral blood mononuclear cells (PBMCs) were isolated from each sample using Ficoll. Then, it cultured in 24 well tissue culture plates with and without oleuropein and phytohemagglutinin (PHA). The concentration of TNF-α and IL-4 was evaluated in the supernatant of treated and non-treated cells using immunoassay after 72 hours. The results were analyzed using t-test and ANOVA.

The results revealed a significant reduction of TNF-α in treated PBMCs with oleuropein compared to non-treated cells, especially in the 100 mg/ml of oleuropein (P<0.0001). In addition, a significant increase in IL-4 in a dose-dependent manner was indicated (P<0.0001).

Our findings demonstrated that oleuropein could effectively reduce the inflammation of inflammatory diseases, especially rheumatoid arthritis, by increasing the anti-inflammatory factor IL-4 production and decreasing the level of TNF-α.