The Literatures on mechanism of acupuncture from the aspect of mitogen-activated protein kinase (MAPK) signal transduction pathways are analyzed in this paper. And the result shows that many acupuncture effects are closely related with the regulation of MAPK signal transduction pathway. However, the current studies only cover limited aspects, and there problems still existed in the experiment designation. Acupuncture and electroacupuncture are often adopted for the treatment group, while moxibustion is not applied for most of them. There are not unified wave model, frequency and stimulation period for electroacupuncture. And the studies still remain in simple confirmation and proper inference. In the future, the domain of researches should be further wid ened and the experiment designation further perfected. Therefore, the therapeutic effect of acupuncture in clinic will be greatly improved through researches on MAPK signal transduction pathway and the production mechanism of acupuncture effect.
Acupuncture Therapy ; Animals ; Humans ; MAP Kinase Signaling System ; Moxibustion

27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determine roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors. Treatment with LY294002 or U0126 resulted in recovery of endocytic activity which was reduced by 27OHChol. CD197 expression and cell adherence enhanced by 27OHChol were attenuated in the presence of the inhibitors. Transcription and surface expression of CD molecules involved in atherosclerosis such as CD105, CD137 and CD166 were also significantly decreased by treatment with LY294002 and U0126. These results mean that the PI3K and the ERK signaling pathways are necessary for differentiation of monocytic cells into mDCs and involved in over-expression of atherosclerosis-associated molecules in response to 27OHChol.
Atherosclerosis ; Dendritic Cells ; MAP Kinase Signaling System ; Up-Regulation

BACKGROUND/AIMS: DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. METHODS: Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. RESULTS: The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. CONCLUSIONS: DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.
Animals ; Blotting, Western ; Dextrans ; Fluorescein ; Indomethacin ; Inflammation ; Intestine, Small ; MAP Kinase Signaling System ; Permeability* ; Phosphotransferases ; Rats

Objective: To investigate the cell cycle and apoptosis in hydroquinone (HQ) -induced malignant transformation of TK6 cells and its related regulatory mechanisms. Methods: TK6 cells were exposed to 20 μmol/L HQ, 24 h/time, once a week, for 19 weeks as experimental group and TK6 cells treated with phosphate buffer (PBS) for 19 weeks was used as control group from March 2014. In regulatory mechanism research, the cells were divided into four groups: control group, experimental group, control inhibitor group and experimental inhibitor group (inhibitor groups were added 10 μmol/L P600125) . Cell cycle and apoptosis were detected by flow cytometry. The protein expression of cell cycle-related proteins and JNK signaling pathway proteins were detected by Western blot. Results: Flow cytometry showed that compared with control group, the ratio of cells in the G0/G1 phase of the experimental group was significantly decreased (P=0.001) , and the ratio of cells in the S phase was significantly increased (P=0.002) . Western blotting demonstrated that the protein expressions of p-Rb (Ser780) , E2F1, Cyclin D1, p-p16 (Ser152) , JNK1, p-JNK1 (Thr183/Tyr185) , c-jun, p-c-jun (Ser63) (P=0.015, 0.021, 0.001, 0.001, 0.005, 0.001, 0.039, 0.003) were up-regulated, while the protein expressions of Rb (P=0.048) and p16 (P=0.002) were significantly down-regulated. After exposed to SP600125, compared with experimental group, there were no significant changes in cell cycle distribution (P=0.946) and apoptosis rate (P=0.923) in experimental inhibitor group. The expression of c-jun (P=0.040) protein was down-regulated, while the expression of Rb (P=0.027) protein was up-regulated in experimental inhibitor group. Conclusion: In HQ-induced TK6 cells malignant transformation, the cell cycle is arrested in the S phase, and the p16/pRb signaling pathway is inhibited, while the JNK signaling pathway is activated. However, the activated JNK signaling pathway may not be involved in the regulation of cell cycle.
Humans ; Hydroquinones/toxicity* ; MAP Kinase Signaling System ; Cell Cycle ; Cell Transformation, Neoplastic ; Apoptosis

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

JNK signaling pathway plays an important role in regulation of cell growth, proliferation, differentiation, migration and apoptosis. Studies have shown that JNK signaling pathway is closely related to autophagy, but the underlying mechanisms are not clear. Clarification of the correlation between the JNK signaling pathway and autophagy may provide opportunities for identifying potential molecular targets for the treatment of diseases associated with autophagy.
Autophagy ; Humans ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System

Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family which plays roles in the nucleus as a nuclear factor and is released by damaged or necrotic cells to act as a cytokine. It can be released via damaged or necrotic cells and functions as a cytokine. The released IL-33 activates the downstream NF-κB and MAPKs signaling pathways through the isomers of the specific receptor ST2 and the interleukin-1 receptor accessory protein (IL-1RAcP), resulting in danger signals and the activated multiple immune responses. IL-33 is abnormally expressed in various tumors and involves in tumorigenesis, development, and metastasis. Moreover, IL-33 can play both pro-tumor and anti-tumor roles in the same type of tumor.
Cytokines ; Humans ; Interleukin-33/genetics* ; MAP Kinase Signaling System ; NF-kappa B/metabolism* ; Neoplasms

RASopathies are a group of disorders caused by germline variants of genes involved in RAS/MAPK pathway with overlapping features which may complicate their diagnosis. Since almost all RASopathies are autosomal dominant inherited disorders, the affected families may give birth to multiple children with the disease. Owning to the advance in sequencing technology, the genotype-phenotype correlation of RASopathies has become clearer in recent years, and genetic testing is now available in many places, which make prenatal diagnosis for couples with increased risk possible. For de novo variants of RASopathies, prenatal diagnosis is still difficult as the findings in routine ultrasonography are not specific enough. Nevertheless, certain findings may still be used as clues for prenatal diagnosis. This article overviews the common disorders of RASopathies, with an emphasis on the features that can be used as clues for the prenatal diagnosis of RASopathies.
Female ; Genes, ras ; Humans ; MAP Kinase Signaling System/genetics* ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To investigate the effect of galectin-1 on biological behaviors of lung adenocarcinoma cells and the underlying mechanism. METHODS: The expression levels of galectin-1 mRNA were detected in 8 pairs of lung adenocarcinoma tissues and adjacent normal tissues and in lung adenocarcinoma cell lines A549 and H1299 and normal bronchial epithelial cell line BEAS-2b using qRT-PCR. The effect of galectin-1 knockdown by RNA interference on the proliferation, invasion and migration abilities and apoptosis of lung adenocarcinoma cells were examined using CCK8 assay, Transwell assay, scratch assay and flow cytometry. Western blotting was performed to detect the expressions of apoptosis-related proteins BAX, BCL-2, and caspase-3 and the proteins involved in the AKT and ERK pathways. RESULTS: The mRNA expression of galectin-1 was significantly increased in lung cancer tissues and lung adenocarcinoma cell lines (P < 0.05). In lung adenocarcinoma cells, galectin-1 knockdown significantly inhibited cell proliferation, migration and invasion and obviously increased cell apoptosis rate (P < 0.05), causing also significant reduction of the phosphorylation level of ERK signaling pathway (P < 0.05). CONCLUSION Galectin-1 knockdown inhibits proliferation, migration, and invasion and promotes apoptosis of lung adenocarcinoma cells, and this effect is mediated probably by inhibition of the phosphorylation levels of the ERK pathway.
Humans ; Adenocarcinoma of Lung ; Apoptosis ; Lung Neoplasms ; MAP Kinase Signaling System ; Cell Proliferation

Mitogen-activated protein kinase (MAPK) cascade system is one of the highly conserved signal systems in eukaryotic cells, which participates in the regulation of many biological processes. Under the stimulation of different signals (such as cytokines, neurotransmitters, and hormones), MAPK cascade activates downstream targets and controls a variety of cellular processes, including growth, immunity, inflammation, and stress response. In different cells, the effects of MAPK cascade on cells vary with the stimuli and the duration of stimulation. MAPK cascade induces Th differentiation and participates in T cell receptor signal pathway and B cell receptor signal pathway. MAPK cascades regulate various cellular activities related to the occurrence and development of cancer. A thorough and systematic understanding of the specific regulatory effects of MAPK cascade on various cellular processes will provide theoretical guidance for treating various diseases.
Humans ; MAP Kinase Signaling System ; Signal Transduction ; Cell Cycle ; Neoplasms ; Inflammation