The expression of intracellular cytokines of decidual natural killer cells in unexplained recurrent pregnancy loss.

OBJECTIVE: This study aims to investigate the expression levels of TNF-α, IFN-γ, IL-4, and IL-10 in dNK cells and determine whether or not the MAPK signal pathway is involved in the regulation of cytokine secretion by dNK cells at the maternal-fetal interface. METHODS: In this study, we collected decidua specimens from patients with apparently normal pregnant and unexplained recurrent pregnancy loss (URPL) and extracted dNK cells by enzymatic digestion. Then the expression of cytokines were analyzed by flow cytometry and Real-Time PCR respectively. RESULTS: The secretions of both IFN-γ and TNF-α in dNK cells in URPL were significantly higher than those in normal pregnancy. Furthermore, p38/MAPK inhibitors can inhibit the secretion of four cytokines in normal pregnancy, while in URPL cases, p38/MAPK inhibitors only significantly inhibit the secretion of IL-4 and IFN-γ. ERK inhibitors had no effect on the expression of all four cytokines and JNK/MAPK inhibitors varied on different cytokines. CONCLUSION: URPL is associated with a NK1 cytokine profile. MAPK signaling pathway is involved in the regulation of cytokine secretion by decidual NK cells at maternal-fetal interface.

Research progress on the regulation of craniofacial development and malformation by fibroblast growth factor 8 / 口腔疾病防治

@#Fibroblast growth factor 8 (FGF8) is a kind of secretory polypeptide that has crucial roles in the development of various tissues and organs. Current studies have found that FGF8 can regulate the differentiation of cranial neural crest cells by activating the mitogen-activated protein kinase (MAPK) signaling pathway and affect the establishment of mandibular arch polarity and the development of craniofacial symmetry by regulating the expression of target genes. Cleft lip with or without cleft palate, ciliopathies, macrostomia and agnathia are four developmental malformations involving the craniofacial region that seriously affect the quality of life of patients. The abnormal FGF8 signal caused by gene mutation, abnormal protein conformation or expression is closely related to the occurrence of craniofacial malformations, but the molecular mechanism and signaling pathway underlying these malformations have not been fully elucidated. Craniofacial development is a complex process mediated by a variety of signaling molecules. In the future, the role of various signaling molecules in craniofacial development and malformations need to be explored to provide a new perspective and vision for the prevention and treatment of these craniofacial malformations.

Regulation of HtrA2 on WT1 gene expression under imatinib stimulation and its effects on the cell biology of K562 cells.

The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis. Subsequent to treatment with drugs and UCF-101, the proliferative function of K562 cells was detected using MTT assays, and the rate of apoptosis was detected using Annexin V with propidium iodide flow cytometry in K562 cells. The protein levels in the signaling pathway were analyzed using western blotting following treatment with imatinib and UCF-101. In K562 cells, imatinib treatment activated HtrA2 gene at a transcription level, while the WT1 gene was simultaneously downregulated. Following HtrA2 inhibitor (UCF-101) treatment, the downregulation of WT1 increased gradually. At the protein level, imatinib induced the increase in HtrA2 protein level and concomitantly downregulated WT1 protein level. Subsequent to HtrA2 inhibition by UCF-101, the WT1 protein level decreased temporarily, but eventually increased. Imatinib induced apoptosis in K562 cells, but this effect was attenuated by the HtrA2 inhibitor UCF-101, resulting in the upregulation of the WT1 protein level. However; UCF-101 did not markedly change the proliferation inhibition caused by imatinib. Imatinib activated the p38 mitogen activated protein kinase (p38 MAPK) signaling pathway in K562 cells, and UCF-101 affected the activation of imatinib in the p38 MAPK signaling pathway. Imatinib inhibited the extracellular signal-related kinase (ERK1/2) pathway markedly and persistently, but UCF-101 exhibited no notable effect on the inhibition of the ERK1/2 pathway. HtrA2 and its regulatory effect on WT1 may affect the sensitivity of BCR/ABL(+) cell lines to target therapy drugs through different mechanisms. Regulation of WT1 by HtrA2 occurs in K562 cells, and the regulation may affect the apoptosis of K562 cells under the stress caused by chemotherapeutic treatment. The p38 MAPK signaling pathway, which serves an important role in cell apoptosis, is a downstream pathway of this regulation.

Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways.

2-Chloroethanol (2-CE) is one of the reactive metabolites of 1,2-DCE in vivo, which might contribute to brain edema formation induced by 1,2-dichloroethane (1,2-DCE) poisoning. Thus, the purpose of this study was to explore the roles of mitogen-activated protein kinase (MAPK) signal pathways in upregulation of matrix metalloproteinase-9 (MMP-9) in 2-CE exposed rat astrocytes. Expression of p38 MAPK (p38), extracellular signal regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and MMP-9 at both protein and gene levels in rat astrocytes were determined using western blot and real-time RT-PCR methods. The results showed that both protein and mRNA levels of MMP-9 in 2-CE exposed astrocytes significantly increased. Meanwhile, protein levels of phosphorylated p38 (p-p38), ERK1/2 (p-ERK1/2) and JNK1/2 (p-JNK1/2) in 2-CE exposed astrocytes also significantly increased. In addition, both protein and mRNA levels of MMP-9 significantly decreased in response to reduced protein levels of p-p38, p-ERK1/2 and p-JNK1/2 achieved by supplement with their specific inhibitors, indicating that activation of MAPK signal pathways might play an important role in upregulation of MMP-9 expression at the transcriptional level in 2-CE exposed astrocytes. Furthermore, since pretreatment of n-acetyl-l-cysteine (NAC), a powerful antioxidant amino acid, could attenuate the elevated levels of MMP-9, p-p38, p-ERK2 and p-JNK1/2 in 2-CE exposed astrocytes, activation of MAPK signal pathways in 2-CE exposed astrocytes could be mediated partially by reactive oxygen species (ROS), which was most likely generated in the metabolism of 2-CE.

Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway.

The histamine receptor antagonists in the treatment of allergic disease have limitations. The treatments of Chinese herbs have some curative effects on allergic skin lesions. Present research indicates that the mitogen-activated protein kinase (MAPK) signaling pathway might be equally important in allergic reactions. It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms, and some herbs can inhibit the MAPK pathway, which yields anti-allergy effects. Chinese medicines (CMs) have immense potential in the development of treatments for allergic disease.

Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway / 中国结合医学杂志

The histamine receptor antagonists in the treatment of allergic disease have limitations. The treatments of Chinese herbs have some curative effects on allergic skin lesions. Present research indicates that the mitogen-activated protein kinase (MAPK) signaling pathway might be equally important in allergic reactions. It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms, and some herbs can inhibit the MAPK pathway, which yields anti-allergy effects. Chinese medicines (CMs) have immense potential in the development of treatments for allergic disease.