جستجوی مقالات مرتبط با کلیدواژه "mapk" در نشریات گروه "پزشکی"

Stools from colorectal cancer patients are noninvasive samples that could be used to compare the frequency of hotspot mutations between two different ethnic cohorts.

We collected stool samples from the Iranian cohort (52 patients and 49 controls) and the Finnish cohort (40 patients and 14 controls). Following stool DNA extraction, we used the AmpliSeq Colon and Lung Cancer panel to prepare DNA libraries before sequencing.

The Iranian cohort exhibited 35 hotspot mutations in the BRAF, ERBB4, FBXW7, FGFR1, FGFR3, KRAS, MAP2K, MET, NRAS, PIK3C, SMAD4, and TP53 genes. In the Finnish cohort, 13 hotspot mutations were found in the AKT1, APC, KIT, KRAS, SMO, STK11, and TP53 genes. Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort.

Genes involved in MAPK and PI3K‑MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.

This research aimed to investigate the effect of 8 weeks of interval training and the use of cineole, linalool, and bourbonene on MAPK/Arc gene expression and learning in Alzheimer’s disease (AD) rats.

In this experimental study, 40 AD rats were randomized into eight groups, including (1) control, (2) AD, (3) AD+aerobic training (AT), (4) AD+linalool, cineole, and bourbonene (LCB), (5) AD+AT+LCB, (6) AT+AD, (7) LCB+AD, and (8) AT+LCB+AD. AD was induced by injecting amyloid-beta (Aβ1)-42 into the hippocampus of rats. The interval training protocol was performed five days per week for eight weeks before and after AD induction. Linalool at a concentration of 25 mg/kg, cineole at a concentration of 10 µM, and β-bourbonene at a concentration of 10 µg/mL were used for eight weeks. One-way analysis of variance was used for between-group comparisons, and Tukey’s test was used for pairwise comparisons at P≤0.05.

AD induction caused a significant decrease in MAPK/Arc gene expression in hippocampal tissue (P=0.001). Interval exercise and consumption of three herbal drugs significantly increased gene expression of Arc (P=0.001) and MAPK (P=0.001). AD induction decreased learning (P=0.001). Interval exercise and consumption of three herbal medicines caused a significant increase in learning (P=0.001).

Interval exercise and using three herbal medicines have more favorable effects on improving MAPK/Arc gene expression and learning in AD than each alone.

Stools from colorectal cancer patients are noninvasive samples that could be used to compare the frequency of hotspot mutations between two different ethnic cohorts.

We collected stool samples from the Iranian cohort (52 patients and 49 controls) and the Finnish cohort (40 patients and 14 controls). Following stool DNA extraction, we used the AmpliSeq Colon and Lung Cancer panel to prepare DNA libraries before sequencing.

The Iranian cohort exhibited 35 hotspot mutations in the BRAF, ERBB4, FBXW7, FGFR1, FGFR3, KRAS, MAP2K, MET, NRAS, PIK3C, SMAD4, and TP53 genes. In the Finnish cohort, 13 hotspot mutations were found in the AKT1, APC, KIT, KRAS, SMO, STK11, and TP53 genes. Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort.

Genes involved in MAPK and PI3K?MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.

 Since EGFR inhibitors show a limited therapeutic effect on Glioblastoma multiforme patients, the EGFR/MAPK/STAT5/FN14 signaling pathway becomes vulnerable to the invasive GBM cell population and may be a suitable target for the treatment of GBM. Nanocurcumin consumption and exercise training are probably effective interventions in this signaling pathway.

 This study aimed to investigate the simultaneous effects of exercises training and Nanocurcumin consumption on the EGFR/MAPK/STAT5/FN14/FN14 pathway in the tumor tissue of GBM model rats.

 In this study, 40 male Wistar rats were randomly assigned to five groups: 1- control (CON), 2- glioblastoma multiform (GBM), 3- glioblastoma multiform+concurrent training (GBM+CT), 4- glioblastoma multiform+nanocurcumin (GBM+NC), and 5- glioblastoma multiform+nanocurcumin+concurrent training (GBM+NC+CT) groups. The target groups performed aerobic training (20 - 35 minutes at 18 m/min) along with resistance training (climbing the ladder in three sets repeated four times) and received Nanocurcumin at the rate of 100 mg.kg-1.day-1 for four weeks. Gene expression was measured by real-time PCR. Two-way analysis of variance was used for analyzing data.

 According to our study results, concurrent training significantly reduced the expressions of EGFR, MAPK, STAT5, and Fn14, mRNA compared with GBM group (P < 0.05). Furthermore, nanocurcumin significantly reduced the expressions of EGFR, MAPK, as well as Fn14, mRNA compared with GBM group (P < 0.05). Nanocurcumin+Concurrent training decreased the expressions of EGFR, MAPK, STAT5 as well as Fn14, and mRNA compared with the GBM group (P < 0.05). A significant reduction was recorded for all mRNA expression levels in the GBM+NC+CT group compared with those in the GBM+NC group (P < 0.05).

 In sum, combined exercises and nano curcumin consumption may have been adopted as a non-pharmacological strategy to modulate the expression of EGFR/MAPK/STAT5/FN14 genes in tumor tissue of glioblastoma multiform.

To clarify therapeutic potential of albiflorin and its intrinsic mechanisms against dextran sulfate sodium (DSS)-induced Ulcerative colitis (UC) mice.

Sixty male C57BL/6 mice were randomly divided into five groups: negative control, positive, albiflorin low-dose group, albiflorin high-dose group and treatment control (Salicylazosulfapyridine “SASP”, 100 mg/kg) group. Acute colitis was induced in all groups except NC by administration of 3% DSS for 7 days. Albiflorin and SASP were administered via the intragastric route twice a day for 7 days. The changes of colon tissue were assessed by disease activity index (DAI), HE staining, and ELISA. Adrenodoxin expressions of UC colon tissues were evaluated by immunohistochemistry. Western blotting was performed to investigate related protein of the NF-κB and MAPK signaling pathways. 

It has been found that the albiflorin shares similar influences as the SASP in ameliorating the DSS-induced UC. The reduced DAI and alleviated colon tissue damage were observed in albiflorin intervened groups. Moreover, albiflorin significantly inhibited myeloperoxidase activities and attenuated immuno-inflammatory response and elevated Foxp3 mRNA in colon tissue. Furthermore, investigations revealed that albiflorin could inhibit adrenodoxin isoform and activate activated phosphorylated NF-κB p65 and IκBα, which consequently suppressed phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK).

These findings showed that albiflorin could alleviate DSS-induced murine colitis by activating inhibiting NF-κB and MAPK signaling pathways. It might be a potential therapeutic reagent for UC treatment.

Quinacrine (QC), an attractive anticancer drug, has been forwarded for clinical evaluation in various cancer types due to its tremendous safety data accumulated since World War II. Its shotgun nature makes it unmissable as a chemotherapy drug that traps and activates multiple pathways.

Recently, QC has been shown to block malignancy by affecting pathways, including RHO signaling, G1/S arrest, ROS emission, and cell death through autophagy. In this review, we have extensively studied QC as an anticancer agent that affects various signaling pathways. We have documented activity via WNT, NOTCH, HEDGEHOG, MAPK, EGFR, P53, RHO, AKT, NF-k and TGF pathways and reformed the already established mode of action of QC.

QC’s effects on multiple key signaling pathways, implicated in the malignant progression of numerous cancer types, make it an exciting candidate as a chemotherapeutic agent for new combination treatments and therapies.

Acute kidney injury (AKI) is a major component of isoproterenol (ISO) induced cardiorenal syndrome. In this study, we investigated the effect of TLR4‐IN‐C34 as a toll-like receptor (TLR)-4 inhibitor on ameliorating ISO-induced AKI and the possible molecular underlying pathways. 

The study included 4 groups: control group, ISO group (rats received 100 mg/kg ISO in 2 doses 24 hr apart, SC), ISO+C341 and ISO+C343 groups (rats received 1 or 3 mg/kg TLR4‐IN‐C34 respectively twice one hour before each ISO injection, IP). 

Obtained results showed that TLR4‐IN‐C34 injection prior to ISO decreased serum creatinine level (P<0.05). Renal tissue histopathologic changes were markedly decreased by TLR4‐IN‐C34. Renal relative expression of MAPK and MyD88 mRNA decreased significantly in both ISO+C341 and ISO+C343 groups compared with the ISO group (P<0.05). Furthermore, TLR-IN-C34 lowered the inflammatory cytokines IL-8, IL-1β, and IL-12 renal levels (P<0.05). Immunostained kidney sections showed a marked decrease in NF-κb positive cells in addition to the apoptotic marker Bax (P<0.05) by the two tested doses of TLR4‐IN‐C34. On the other hand, the expression of the antiapoptotic marker Bcl-2 by renal cells was markedly increased. 

It can be concluded that TLR4-IN-C34 ameliorates ISO-induced AKI through anti-inflammatory anti-apoptotic effects and modulation of TLR4 signaling pathways.

Hyperinsulinemia, secondary to insulin resistance, may lead to vascular smooth muscle cell dysfunction. In the present research, we aimed to investigate the effect of Chemokine receptor 8 (CCR8) on angiotensin II (Ang II)-induced dysfunction of vascular smooth muscle cells (VSMCs) and to explore the underlying molecular mechanism. 

The expression of CCR8 was analyzed in diabetics and normal people by RT-PCR and ELISA. CCK-8 assay and transwell were used to explore cell proliferation and migration, and ELISA was used to measure the content of IL-6 and TNF-α. Reactive oxygen species (ROS) kit was employed to measure ROS generation. 

The results revealed that CCR8 was highly expressed in diabetics and Ang Ⅱ-induced VSMCs. Further studies found that interfering with the expression of CCR8 significantly reduced the production of ROS and the levels of inflammatory factors in AngⅡ-induced VSMCs. Interfering with CCR8 increased the glucose uptake induced by AngⅡ+IR. More importantly, inhibition of CCR8 alleviated Ang II-induced dysfunction of VSMCs. Inhibition of CCR8 inactivated the MAPK/NF-κB signaling pathway.

Inhibition of CCR8 attenuates Ang II-induced VSMCs injury by inhibiting the MAPK/NF-κB pathway. CCR8 may be a new biomarker related to hypertension and insulin resistance and is a new target for the treatment of human cardiovascular diseases.

Adipose-derived stem cells (ADSCs) are one of the most well-known and accessible sources of stem cells that can be used for the treatment of neurodegenerative diseases. On the other hand, previous studies have suggested that selegiline, as an irreversible inhibitor of monoamine oxidase, affects stem cells’ differentiation into neurons. This study was conducted to investigate the involvement in phosphatidylinositol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in ADSCs differentiation to neuron-like cells using selegiline as inducer.

ADSCs were isolated from male rats, cultured in DMEM and then treated with selegiline (10-7 M) for 24h. Real-time PCR for nestin and neurofilament-68 (NF-68) was performed from the negative control (ADSCs at the 3rd passage), positive control (ADSCs were treated with 10-7 M selegeline for 24h, PI3AKT inhibitor (ADSCs were pretreated with treated with 10µM LY294002 for 3h, then10-7 M selegeline for the next 24h, and MAPK inhibitor (ADSCs were pretreated with treated with 10µM PD98059 for 3h, then10-7 M selegeline for the next 24h).

Nestin and NF-68 genes have been over-expressed in the selegiline-treated ADSCs. The PD98059 and LY294002 significantly down-regulated the selegiline-induced over-expression of nestin and NF-68; however, PI3K inhibition did not return the genes expression to control level. ADSCs were immunoreactivefor nestin and NF-68 about 98% and 95% respectively.

According to the results, selegilinecan induce the gene expression of neural stem cell biomarkers in ADSCs through MAPK pathway activating and so differentiating them into neuron-like cells.

Paracetamol is the most implicated xenobiotic in inducing hepatotoxicity. Our study aimed to determine the impact of some kaempferol glycosides isolated from the leaves of Cedrela odorata L. on paracetamol hepatotoxicity.

The methanolic extract of dried leaves of C. odorata L. was subjected to the combination of spectroscopic methods (1H and 13CNMR). Six kaempferol glycosides were isolated: kaempferol-3-O--D-glycopyranoside (astragalin), kaempferol-3-O--L-rhamnopyranoside, kaempferol-3-O--D-rutinoside, kaempferide-3-O--D-rutinoside, kaempferide-3-O--Drutinosyl-7-O--Drhamnopyranoside, and kaempferol-3-O--D- rutinosyl-7-O-α-D-arabinopyranoside. Fifty-four female Swiss Albino mice were divided randomly into 9 groups including (1) control negative (1 mL/kg saline; IP), (2) control positive (paracetamol 300 mg/kg; IP), (3) silymarin 50 mg/kg (IP). Animals of groups 4-9 were injected with 6 different samples of isolated compounds at 100 mg/kg (IP). One h later, groups 3-9 were injected with paracetamol (300 mg/kg IP). Two h later, tissue samples were taken from all animals to assess nitrotyrosine, c-Jun N-terminal protein kinase (c-JNK), Raf -1kinase, and oxidative stress biomarkers viz. reduced glutathione (GSH) and malondialdehyde (MDA).

Isolated glycosides had a prominent anti-apoptotic effect via inhibition of c-JNK and Raf1 kinase. They also exerted a powerful antioxidant effect by modulating the oxidative stress induced by paracetamol via increasing GSH, reducing MDA and nitrotyrosine concentrations compared to positive control. The glycoside (1) showed a better effect than silymarin (standard) in ameliorating the formation of nitrotyrosine, Raf-1 kinase, c-JNK, and GSH.

Kaempferol glycosides isolated for the first time from C. odorata L. leaves exerted antioxidant and antiapoptotic effects via amelioration of oxidative stress and inhibition of Raf/ MAPK pathway.

 Hepatic stellate cells (HSCs) are liver-specific pericytes that transform into myofibroblasts, which are involved in pathological vascularization in liver fibrosis. We previously suggested that A20 overexpression suppresses lipopolysaccharide (LPS)-induced inflammation in HSC. We aimed to determine the mechanisms of the anti-inflammatory role of A20 in LX-2 cells.

 LX-2 cells were transfected with A20-siRNA or control-siRNA and control adenovirus or A20-carrying adenovirus. Quantitative reverse transcription PCR (RT-qPCR) analysis was employed to quantify mRNA levels of α-SMA, col-I, col-III, IL-6, TGF-β, and PDGF in A20-siRNA LX-2 cells stimulated with LPS. Multiple molecular indices of MAPK/ERK/JNK signal pathway were performed by using gene transfection and Western blotting.

 Relative to control, the fibrosis-related mRNA levels of α-SMA, col-I, and col-III were increased in A20-siRNA LX-2 cells. Meanwhile, A20-siRNA cells significantly increased IL-6, TGF-β, and PDGF mRNA levels. Relative to controls, stimulating A20 overexpressing LX-2 cells with LPS for 5 and 30 minutes significantly reduced the levels of phosphorylated ERK and JNK, respectively. A20 knockdown in LX-2 cells promotes phosphorylated ERK and JNK levels with LPS for 30 minutes.

 Our data indicate that A20 could be functional in HSCs through the MAPK/ERK/JNK signaling pathway, highlighting a potential novel therapeutic strategy against liver fibrosis.

Kainic Acid (KA) is an ionotropic glutamate receptor agonist. KA can induce neuronal overactivity and excitotoxicity. Rosmarinic Acid (RA) is a natural polyphenolic compound with antioxidant, anti-apoptotic, anti-neurodegenerative, and anti-inflammatory properties. This study aimed to assess the effect of RA on apoptosis, nNOS-positive neurons number, as well as Mitogen-Activated Protein Kinase (MAPK) and Cyclooxygenase-2 (COX-2) immunoreactivity, following intrahippocampal Kainic acid injection in rats. 

The study rats were randomly assigned to three groups of sham, KA (KA was injected into the right side of the hippocampus) and KA+RA (a dose of 10 mg/kg/day through a gavage needle for one week before KA injection). Then, histopathological changes, including apoptosis [Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay], nNOS-positive neurons number, as well as COX-2 and MAPK immunoreactivity were evaluated in the hippocampus. 

In the RA pretreated group, nNOS-positive neurons and TUNEL- positive cells were significantly reduced compared to the KA group (P<0.05). COX-2and MAPK immunoreactivity demonstrated no significant changes compared to the KA group. They indicated a significant higher reactivity for COX-2 (P<0.01) and MAPK (P<0.005) versus the sham group. 

RA had neuroprotective effects, compared to KA, through reduced apoptosis and nNOS-positive neurons, but not MAPK and COX-2.

It is generally believed that the inflammatory response in bone marrow mesenchymal stem cells (BMSCs) transplantation leads to poor survival and unsatisfactory effects, and is mainly mediated by cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α). In this study, we explored the mechanisms underlying the TNF-α-induced inflammatory response in BMSCs. We treated BMSCs with TNF-α (1 and 10 ng/ml) for 5 days. The expression levels of key inflammatory mediators were evaluated by Real-time PCR. Intracellular ROS level was measured by using a 2, 7-dichlorofluorescein diacetate (DCF-DA). We found that TNF-α treatment dramatically increased the expression levels of some key inflammatory mediators, including IL-6, IL-1β, IFN-γ and transforming growth factor β (TGF-β). Moreover, TNF-α induced intracellular oxidative stress by elevating intracellular reactive oxygen species (ROS) level, which is due to the increase of lipid peroxidation, the reduction of antioxidant Glutathione (GSH) levels and the inhibition of many antioxidant enzyme activities in BMSCs. Interestingly, 5 µM curcumin, a ROS scavenger, dramatically lowered the TNF-α-induced inflammatory response in BMSCs. In addition, TNF-α induced the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), p38 and their down-stream transcription factors nuclear factor kappa B (NF-κB) pathway. ROS mediated the TNF-α-induced inflammatory response via MAPK and NF-κB pathway, and may provide a novel strategy to prevent the inflammatory-dependent impairments in BMSCs.

To reveal the detailed mechanism underlying the functions of salidroside on the inflammation of intestinal epithelial cells during IBD. Quantitative real-time PCR was employed to assess the expression of IL-6, IL-10, and α-defensins 5 and 6. ELISA assay was performed to measure the secretion of IL-6 and IL-10. MTT assay was used to determine the cell viability and proliferation. Western blot was used to assess the phosphorylation of NF-kB, Erk1/2, JNK, P38, JAK2, and STAT3. Salidroside impaired the proliferation of intestinal epithelial cells at high concentrations (P< 0.05) and down-regulated interleukin-6 (IL-6) production induced by LPS (P<0.05). Western blot results showed that salidroside repressed the phosphorylation of NF-kB, Erk1/2, JNK, P38, JAK2 and STAT3 (P<0.05) and attenuated the activation of NF-κB, MAPK, and STAT3 pathways. Moreover, the expressions of α-defensin 5 and 6 were rescued by salidroside after LPS or SAC triggering (P<0.05). In summary, salidroside suppressed the expression of IL-6 and elevated the expression of defensins in LPS-activated intestinal epithelial cells through NF-κB/MAPK and STAT3 pathways. The mechanism revealed here may be potentially useful for the treatment of IBD with salidroside

We aimed to investigate the participation of adiponectin in preeclampsia, and to explore the possible mechanism. A total of 52 patients with preeclampsia and 30 normal women with full-term pregnancy were enrolled. Immunohistochemistry was used to detect the localization of MAPK and STAT5. RT-PCR was used to detect the expression of adiponectin mRNA in placental tissue of patients with preeclampsia and normal pregnant women. Western blot was used to detect the expression of adiponectin protein, MAPK, p-MAPK, STAT5 and p-STAT5 in placental tissue of patients with preeclampsia and normal pregnant women. p-p38 was highly expressed in placental trophoblasts of patients with preeclampsia, while p-STAT5 was less expressed. Expression level of p-p38 and p-STAT5 in patients with preeclampsia were significantly different from those in normal pregnant women (P<0.01). Expression level of adiponectin mRNA was significantly lower in patients with preeclampsia than in normal pregnant women (P<0.05). Level of p-p38 expression was negatively correlated with levels of adiponectin expression (r=-0.413, P<0.05). Expression level of p-STAT5 was positively correlated with expression level of adiponectin (r=0.526, P<0.01). Adiponectin participates in preeclampsia by regulating the biological function of placental trophoblasts through p38 MAPK-STAT5 pathway.

Resveratrol (RSV) provides several important biological functions in wide variety of cells. In this study, we investigated the molecular mechanisms underlying anti-inflammatory effect of RSV on HepG2 cells by assessing the gene expression of RelA and c-Jun- subunits of NF-κB and AP-1 transcription factors.

HepG2 cells were settled in a serum- free medium with high concentrations of glucose (30 mM) and insulin (1 µM) overnight and were then incubated with RSV (5, 10, and 20 µM) for 24 and 48 hours. Real time quantitative polymerase chain reaction (qRT-PCR) was used to determine RelA and c-Jun expression.

RSV diminished hyperglycemia/hyperinsulinemia stimulated expression of c-Jun dose- dependently after 24 and 48 hours (p The findings of the present study demonstrated that RSV may be considered as a preventative and therapeutic agent for antagonizing inflammation in Hepatocellular carcinoma (HCC).

In traditional Chinese medicine, gamboge can detoxify bodies, kill parasites, and act as a hemostatic agent. Recent studies have demonstrated that gambogic acid (GBA) suppressed inflammation in arthritis, and also presented antitumor effect. Thus, this study investigated the new biological properties of GBA on macrophages.
RAW 264.7 cells were pretreated with GBA at different concentrations (10, 20, 40, 80, 160, 320 nM) for 24 hrs, and then cell viability was measured using Cell Counting Kit (CCK)-8 assays. Pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were determined using ELISA kits and qPCR. Then nitrite concentration was calculated according to a standard curve. At last, the effect of GBA on MAPK and NF-κB signaling pathways was assessed by western blot and luciferase reporter gene assay.
GBA (IC50: 260 nM) suppressed the TNF-α, IL-6 and IL-1β expression induced by lipopolysaccharide (LPS) in RAW 264.7 cells. The expression of TNF-α, IL-6 and IL-1β decreased to 30-50% and 70-75% in the high-dose (160 nM) and low-dose (40 and 80 nM) GBA groups, respectively. Furthermore, the nitric oxide (NO) production and the activation of NF-κB, ERK, and JNK pathways were significantly reduced in high-dose (160 nM) GBA only, while p38 pathway was inhibited at both low (40 and 80 nM) and high (160 nM) concentration of GBA.
These data suggested that GBA inhibited LPS-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β mainly through the suppression of the p38 pathway.