جستجوی مقالات مرتبط با کلیدواژه "nf-" در نشریات گروه "پزشکی"

The present study aimed to estimate the potential and the molecular mechanism of the hydro-ethanolic extract of O.floribundum against acetaminophen (AC) induced hepatotoxicity. Four groups of female Wistar rats (n=6) was formed to study the hepatoprotective effect of O.floribundum extract against acetaminophen overdose (2 g/kg): Groups N and AC received orally tap water for 03 days and Groups O. floribundum + AC and N+O.floribundum: received orally O. floribundum extract (400 mg/kg). After 1hour (h) of the last dose administered, the paracetamol solution (2 g/kg) is administered orally for group AC and O. floribundum + AC. The hydroethanolic extract of O. floribundum shows strong antioxidant activity "in-vitro". After 24 h, asingle dose of acetaminophen increased significantly serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the activity of alkaline phosphatase (ALP) significantly and decreased total protein and albumin levels compared to the normal group. These alterations are confirmed by histological observations with inflammation markers (congestion, inflammatory cells infiltration). These observed effects are mainly due to the over-expression of the CYP2E1 and NF_κB genes marked in this study by quantitative RT-PCR. Also, acetaminophen overdose leads to activation of the mitochondrial permeability transition (MPT). leading to hepatocyte necrosis. Pretreatment with O.floribundum before acetaminophen administration removes all previously observed biochemical, histological. and mitochondrial manifestations. These results suggest that O.floribundum has a potent antioxidant power and an interesting hepatoprotective activity against acetaminophen toxicity partly due to the inhibition of CYP2E1 and NF_κB genes expression.

TNF-α, as a pro-inflammatory cytokine in the tumor microenvironment is able to regulate the expression and function of various ATP binding cassette (ABC) transporters involved in clinical drug resistance and among them, ABCC2 transporter is represented to contribute to cancer multidrug resistance (MDR) by drug efflux.

In this study, we aimed to evaluate the effects of TNF-α and/or E2 (17β-estradiol) on the mRNA and protein expression levels of ABCC2 and NF-κB (p65) transcription factor in estrogen receptor positive (ER+) MCF-7 cells by QRT-PCR and Western blot analysis. Also, we used MTT assay to study the cell sensitivity against the active form of tamoxifen (4OH-TAM), a hypothetical substrate and Cisplatin (Cis), a well-known substrate for ABCC2 used in endocrine and chemo-therapy of breast cancers, respectively. Data were analyzed by one-way ANOVA and Tukey tests. Significance was considered in P-values < 0.05.

The expression levels of ABCC2 and the active form of NF-κB (p65) were significantly increased following 20-day concomitant treatment with TNF-α and E2, compared to untreated cells as control. Also, the viability assay showed that 20-day TNF-α+E2 treatment led to more sensitivity reduction of MCF-7 cells to Cis and 4OH-TAM compared to E2-treated and untreated cells.

Based on our findings, there is a positive correlation between ABCC2 overexpression, over-activity of NF-ҡB/p65 and decreasing the sensitivity of MCF-7 cells to Cis and 4OH-TAM following TNF-α treatment in MCF-7 cells. Further experiments are needed to elucidate possible mechanistic relationship of these findings and their clinical significance in order to circumvent the drug-resistance in breast tumors.

Gastric cancer (GC) is regarded as the fifth most common cancer and the third cause of cancer-related deaths worldwide. Mechanism of GC pathogenesis is still unclear and relies on multiple factors, including environmental and genetic characteristics. One of the most important environmental factors of GC occurrence is infection with Helicobacter pylori that is classified as class one carcinogens. Dysregulation of several genes and pathways play an essential role during gastric carcinogenesis. Dysregulation of developmental pathways such as Wnt/β-catenin signaling, Hedgehog signaling, Hippo pathway, Notch signaling, nuclear factor-kB, and epidermal growth factor receptor have been found in GC. Epithelial-mesenchymal transition, as an important process during embryogenesis and tumorigenesis, is supposed to play a role in initiation, invasion, metastasis, and progression of GC. Although surgery is the main therapeutic modality of the disease, the understanding of biological processes of cell signaling pathways may help to develop new therapeutic targets for GC.

Daunorubicin (DNR) is capable of killing the human acute myeloid leukemia cells through apoptosis or necrosis with arresting cell cycle and various mechanisms. The response of AML cells to DNR associated with defect and or defiance in survival has been a consideration subject.
We have represented the transcription gene profile of some critical prosurvival proteins by qRT - PCR, including osteopontin (OPN), AKT1, mTOR, β - catenin, and NF - kB/RelB.
The U937 cells were treated with DNR with clinically achievable concentrations for MTT assay, annexin V (AV) /Propidium iodide (PI), and cell cycle analysis. QRT - PCR was performed, using primers of OPN, NF - kB/RelB, AKT1, mTOR, PTEN, and β - catenin.
The AV/PI assay displayed that DNR - induced death in cells was a dose - dependent and necrotic manner. Cell cycle distribution following treatment with DNR exhibited a relatively lower chromatin of S phase than untreated cells. OPN gene expression was significantly attenuated. NF - kB/RelB, mTOR, β - catenin, as well as PTENgenes showed unchanged or non - significant increase in expression. However, AKT1increased significantly.
U937 sensitivity to DNR could be due to the targeting of anti-apoptotic proteins in the transcriptional stages. The decrease in OPNlevels appears to play a significant role in the death of the observed by DNR.

The inhibition of the inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and nuclear factor-κB (NF-κB) production are research targets of attract in the field of antiinflammatory drug development. Therefore, this study was designed to investigate the anti-inflammatory effects of novel thiazolidinone derivatives using a cellular model of lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7. In the present study, five new derivatives (A to E) of thiazolidinone were synthesized and screened for anti-inflammatory activities. Cell viability of LPS-stimulated RAW 264.7 macrophages clearly decreased in >55 μg/mL of synthesized A-E compounds especially in the presence of C; therefore, up to 50 μg/mL of compounds were selected for the subsequent analysis. A majority of these compounds showed significant inhibition on the production of NO in LPS-stimulated macrophages in a dose-dependent manner. Compounds B and D (10-50 μg/mL) significantly inhibited LPSinduced NF-κB (p65) production in a dose-dependent manner. The effects of B and D on iNOS and COX-2 mRNA and protein expression in LPS-stimulated RAW 264.7 cells were detected by real time-PCR and western blot. B derivative significantly suppressed the iNOS and COX-2 mRNA level and as well as protein expression. Taken together, these results reveal that compound B as new thiazolidinone derivative decreased expression of the inflammatory-related signals (NO, iNOS and COX-2) through regulation of NF-κB; hence, this compound could be suggested as a novel therapeutic strategy for inflammation-associated disorders.

Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy. This study examined the relationship between U266 cells and MSCs.
U266 cells were cultured with Umbilical Cord Blood derived-MSCs (UCBMSCs) and Conditioned Medium (C.M). Effect of UCB-MSCs and C.M on proliferation rate and CD54 expression of U266 cells were examined with MTT assay and Flowcytometry respectively. Furthermore, expression of CXCL1, PECAM-1, JUNB, CCL2, CD44, CCL4, IL-6, and IL-8 were analyzed by Real Time-PCR (RT-PCR). Moreover, status of p65 protein in NF-kβ pathway assessed by western blotting.
Our findings confirm that UCB-MSCs support U266 cells proliferation and they increase CD54 expression. In addition, we demonstrate that UCB-MSCs alter the expression of CCL4, IL-6, IL-8, CXCL1 and the levels of phosphorylated p65 in U266 cells.
Our study provides a novel sight to the role of MSCs in the activation of NFkβ signaling pathway. So, NF-kβ signaling pathway will be targeted in future therapies against MM.

The aim of the present work was to assess the feasibility of Acconon MC8-2 EP/NF as a bioadhesive material for developing controlled release gastroretentive microsponges of loratadine. Modified emulsion-solvent diffusion method was employed for the preparation of microsponges (F1-F9) based on 32 factorial design. The amount of ethyl cellulose (EC) and polyvinyl alcohol (PVA) were selected as independent variables while particle size, entrapment efficiency and %CDR were designated as dependent variables. The formulation (F1) with least particle size of 54 ± 2.37µm, entrapment efficiency of 65.98 ± 2.21 % and CDR of 88.15 ± 1.59% at 8 h that followed zero order release kinetics was selected as optimized formulation. F1 was re-fabricated as bioadhesive microsponges (BF1) using Acconon MC 8-2 and assessed. The particle size of BF1increased to 84 ± 2.29 µm whereas the entrapment efficiency lowered to 55.19 ± 1.36% in comparison to F1. However, the CDR8h from BF1 (81.65 ± 3.37%) was comparable to F1. Dynamic in vitro bioadhesion test confirmed the bioadhesive property of BF1. Ex vivo permeation across gastric mucin depicted 52.87% CDP8h that followed zero order kinetics (r2 = 0.9885). Scanning electron microscopy revealed spherical and highly porous surface. The FTIR studies revealed no chemical interaction between drug and excipients. Hence, the study affirmed the bioadhesive characteristics of Acconon MC 8-2 EP/NF for development of controlled release biaodhesive floating microsponges of loratadine.

The objective of this study was to investigate the hepatoprotective effect of licochalcone B (LCB) in a mice model of carbon tetrachloride (CCl4)-induced liver toxicity.
Hepatotoxicity was induced in mice by a single subcutaneous injection (SC) of CCl4. The LCB was administered orally once a day for seven days (PO) as pretreatment at three doses of 1, 5, and 25 mg/kg/day. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. The protein expression degrees of p38 mitogen activated protein kinases (p38) and nuclear factor-k-gene binding (NF-κB) were assayed by western blotting.
CCl4-induced hepatotoxicity was manifested by an increase in the levels of ALT, AST, MDA, IL-6, CRP, and TNF-ɑ, and a decrease in the SOD level and GSH/GSSG ratio in the serum. The histopathological examination of the liver sections revealed necrosis and inflammatory reactions. Pretreatment with LCB decreased the levels of ALT, AST, MDA, GSSG, IL-6, CRP, TNF-ɑ, and the protein expression of p38 and NF-κB, increased the level of SOD and GSH, and normalized the hepatic histo-architecture.
LCB protected the liver from CCl4-induced injury. Protection may be due to inhibition of p38 and NFκB signaling, which subsequently reduced inflammation in the liver.

Nuclear factor-kappa B (NF-B) activation and its inhibition by NF-B inhibitor (IB) have been functionally linked to germ cell apoptosis, which may affect human infertility. We hypothesized a possible relationship between the NF-𝜅B1-94ins/del ATTG (rs28362491) and NF-𝜅BIA 3’UTR A→G (rs696) polymorphism, which are common polymorphisms and the susceptibility to oligospermia in the context of the sperm apoptosis.
In order to evaluate this association, we studied the polymorphisms and sperm apoptosis rates of 114 men with idiopathic oligospermia, as well as 130 normospermic men, using PCR-RFLP and TUNEL staining methods, respectively.
Univariate analysis revealed that heterozygous ID genotype at the NF-𝜅B1 -94ins/del ATTG polymorphism is associated with an approximately 2.4-fold reduced risk of oligospermia (P = 0.006, 95% confidence intervall = 1.34 – 4.13). However, the genotype and allele frequencies of NF-𝜅BIA 3’UTR A→G polymorphism, and the genotype frequencies of all possible rs28362491/rs696 genotype combinations did not show any significant differences between oligospermic and normospermic men. Furthermore, neither polymorphism appeared to affect sperm apoptosis, although the sperm apoptosis index was detected to be significantly higher in the oligospermic patients compared with those in the controls (P Our findings suggested that the heterozygosity of rs28362491 in the NF-𝜅B1 gene may have a protective effect against oligospermia and could modify the susceptibility of oligospermia in a group with idiopathic male infertility in a Turkish population.

The purpose of the current study was to evaluate the anti-inflammatory activity of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells (SMC), lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were isolated from oxazolone-induced colitis and normal mice. The colitis cells treated by oxazolone were randomly divided into model, low dose, middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the oxazolone-induced group was lower than that in the normal group. Compared with model group, apoptotic rate of SMC was significantly increased in the high dose group, while the apoptotic rate of LPMC in the middle dose group was increased. Compared with SMC, LPMC and PBMC of normal group, the mRNA level of nuclear factor kappa B (NF-kB), transcription factor-activated protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT) were higher in model group. Tetramethylpyrazine inhibited the increase of NF-kB, AP-1 and NF-AT mRNA induced by oxazolone. For SMC, LPMC and PBMC there was significant difference in the mRNA level of AP-1 among the three different doses of tetramethylpyrazine treated groups. However, no significant difference was observed in the mRNA levels of NF-AT and NF-κB between normal and middle groups. Tetramethylpyrazine promoted the apoptotic rate of SMC and LPMC in-vitro, and suppressed the expression of transcription factors in SMC, LPMC and PBMC isolated from oxazolone-induced colitis mice. The study provides a novel insight into the mechanism behind the effect of etramethylpyrazine on colitis.

The purpose of the present study is to evaluate the expression of miR-146a gene, its adaptor genes (TRAF6, NF-KB, and IRAK1), and possible changes in the cellular signaling pathway in diabetic hippocampus tissue.
Male Sprague–Dawley rats are randomly selected and divided into control and diabetic (n=6) groups. Diabetes induced by the single-dose injection of nicotinamide [110 mg/kg, (i.p.)], 15 min before streptozotocin (50 mg/kg; i.p.) in 12-h fasted rats. The rats are kept at the laboratory for two months. After anaesthetization, hippocampus of the rats was removed in order to measure the expression of miR-146a, NFK-B, IRAK1, and TRAF6 genes using real-time PCR and activity of NF-KB as well as amount of apoptosis rate using ELISA.
The results indicated a reduction in expression of miR-146a and an increase in expression of IRAK1, NF-KB, and TRAF6 genes in the hippocampus of diabetic rats compared to control. Also it reveals an increase in the activity of NF-KB and apoptosis rate in the hippocampus of diabetic rats.
Our results report the probability that reduction of miR-146a expression in the negative feedback loop between miR-146a and NF-KB increases NF-kB expression and thus intensifies inflammation and apoptosis in hippocampus.

Multi-drug resistance (MDR) is a controversial issue in traditional chemotherapy of aggressive cancers, including hepatocellular carcinoma. The major cause of MDR is suggested to be the aberrant activation of the main signaling pathways such as Wnt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) which have key roles in the maintenance of cancer stem cells (CSCs). Therefore, the evaluation of their alterations could be essential in chemo-resistant cancers such as Hepatocellular carcinoma. The main purpose of this study was to investigate the alteration of the mentioned pathways in the chemotherapy resistant cancer cells by assessing their major molecular parameters. In this experimental study, methylthiazol tetrazolium (MTT) assay, acridine orange/ethidium bromide (AO/EtBr) and Hoechst 33342 staining, DNA fragmentation and colony formation methods were employed to investigate the cytotoxic effects of methotrexate (MTX) and doxorubicin (DOX) on PLC/PRF/5 cells. Moreover, the expression of 11 important genes involved in MDR was performed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). PLC/PRF/5 cells (Alexander) were sensitive to DOX and normally resistant to MTX. In addition, the results obtained from RT-PCR analysis revealed that β-catenin expression was significantly reduced and ABCG2 significantly overexpressed 4.85 and 3.34 times (P value<0.05) in DOX and MTX treated cells, respectively. Furthermore, a considerable expression of HIF-1α and p65 were detected only in MTX-resistant cells. Anti-cancer drugs may have more than one target in tumor cells. They not only participate in deregulation of Wnt but also alter NF-κB activation. Moreover, HIF-1α was the only anti-apoptotic protein that was significantly induced in the chemoresistant cells.

To study the effect of cardiopulmonary bypass (CPB) on nuclear factor-kappa B (NF-кB) and cytokine expression and pulmonary function in dogs. Twelve male mongrel dogs were divided into a methylprednisolone group (group M) and a control group (group C). All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated. The activity of NF-кB and myeloperoxidase (MPO), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8, and the wet/dry (W/D) weight ratio were significantly higher after CPB than before CPB in both groups (P<0.01), with the lower values in group M than in group C, at different time points (P<0.01). Histological evaluation revealed neutrophilic infiltration and thickening of the alveolar interstitium in both groups; however, the degree of pathological changes was significantly lower in group M than in group C. The alveolar–arterial O2 tension difference (PA-aDO2) was significantly higher after CPB than before CBP (P<0.01), and lower in group M than in group C (P<0.01). The pulmonary compliance after removal of the aortic clamp obviously decreased in group C (P<0.05), with no significant change in group M. CPB can significantly enhance the activation of NF-кB in lung tissues and increase the expression of inflammatory cytokines, thus inducing lung injury. Methylprednisolone can inhibit the NF-кB activation, thus inhibiting the release of cytokines and protecting the lung function.

Microglial cells act as the sentinel of the central nervous system. They are involved in neuroprotection but are highly implicated in neurodegeneration of the aging brain. When over-activated, microglia release pro-inflammatory factors, such as nitric oxide (NO) and cytokines, which are critical in eliciting neuroinflammatory responses associated with neurodegenerative diseases. This study examined whether bromelain, the pineapple-derived extract, may exert an anti-inflammatory effect in primary microglia and may be neuroprotective by regulating microglial activation. Following the isolation of neonatal rat primary microglial cells, the activation profile of microglia was investigated by studying the effects of bromelain (5, 10, 20, and 30 µg/ml) on the levels of NO, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) in microglia treated with lipopolysaccharide (LPS) (1 µg/ml). Data were analyzed using Student's t-test. P values less than 0.05 were considered to be statistically significant, compared with the LPS-treated group without bromelain. Results showed that pretreatment of rat primary microglia with bromelain, decreased the production of NO induced by LPS (1 µg/ml) treatment in a dose-dependent manner. Bromelain (30 µg/ml) also significantly reduced the expression of iNOS at mRNA level and NF-κB at protein level. Moreover, the study of mitochondrial activity in microglia indicated that bromelain had no cytotoxicity at any of the applied doses, suggesting that the anti-inflammatory effects of bromelain are not due to cell death. Bromelain can be of potential use as an agent for alleviation of symptoms in neurodegenerative diseases.

Regular aerobic exercise improves the inflammatory status in different lung diseases. However, the effects of long-term aerobic exercise on the lung response have not been investigated. The present study evaluated the effect of aerobic exercise on the lung inflammatory. 12 adult male Wistar rats were divided to 2 groups: A: control (n=6), B: aerobic exercise (five times per week for 4 week; n=6). The gene expression of NF-κB and TNF-α were analyzed in lung tissue by Real time–PCR. In order to determine the significant differences between groups independent t-test were used. Aerobic exercise inhibited the gene expression of NF-κB and TNF-α. But there was no significant difference between A and B groups for TNF-α and NF-κB. We conclude that four week aerobic exercise decrease inflammatory status in lung tissue. Our results indicate a need for human studies that evaluate the lung responses to aerobic exercise.

Recent developments in the field of cell therapy have led to a renewed interest in treatment of acute kidney injury (AKI). However, the early death of transplanted mesenchymal stem cells (MSCs) in stressful microenvironment of a recipient tissue is a major problem with this kind of treatment. The objective of this study was to determine whether overexpression of a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2), in MSCs could protect rats against AKI. The Nrf2 was overexpressed in MSCs by recombinant adenoviruses, and the MSCs were implanted to rats suffering from cisplatin-induced AKI. The obtained results showed that transplantation with the engineered MSCs ameliorates cisplatin-induced AKI. Morphologic features of the investigated kidneys showed that transplantation with the MSCs in which Nrf2 had been overexpressed significantly improved the complications of AKI. These findings suggested that the engineered MSCs might be a good candidate to be further evaluated in clinical trials. However, detailed studies must be performed to investigate the possible carcinogenic effect of Nrf2 overexpression.

Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body’s resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor κB kinase-β (IKK-β)/nuclear factor-κB (NF-κB) and transforming growth factor beta 1 (TGF-β1)/Smad signaling pathways to elucidate whether FZHY could attenuate nutritional steatohepatitis and fibrosis in mice. C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice. The effects of FZHY alone and in combination with hemin were assessed by comparing the severity of hepatic injury, activation of hepatic stellate cells (HSCs), and the expression of oxidative stress, inflammation and fibrogenesis related genes. Administration of FZHY, hemin and FZHY plus hemin significantly ameliorated liver injury. Additionally, our analysis indicated that administration of these agents significantly attenuated oxidative stress, downregulated the expression of pro-inflammatory and pro-fibrotic genes, including IKK-β, NF-κB, monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle actin (α-SMA), TGF-β1, Smad3 and Smad4, and upregulated the expression of the antifibrogenic gene Smad7 (P< 0.001). FZHY-containing therapies prevented nutritional steatohepatitis and fibrosis through modulating the expression of factors associated with the IKKβ/NF-κB and TGF-β1/Smad signaling pathways and oxidative stress related genes.

Alcoholic liver disease (ALD) is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), IL-6, IL-8, adhesion molecules (ICAM, VCAM) and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.