Influence of electroacupuncture on mitogen-activated protein kinase signal transduction in a rat model of cerebral ischemia/reperfusion

Following electroacupuncture at Baihui （DU 20） and Dazhui （DU 14） in a rat model of cerebral ischemia/reperfusion, extracellular-signal-regulated kinase expression in cerebral cortex and corpus striatum, serum glutathione reductase, glutathione peroxidase activity, and serum glutathione content were elevated, and neurobehavioral scores improved. However, these effects were antagonized by mitogen-activated protein kinase inhibitor PD98059. Results indicated that electroacupuncture reversed free radical chain reactions and oxidative stress injury caused by cerebral ischemia/reperfusion, thereby providing neuroprotection. This process could correlate with the mitogen-activated protein kinase signal transduction pathway.

Mitogen activated protein kinase signaling pathways participate in the active principle region of Buyang Huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells

Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively, mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction.

Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer

AIM: To investigate the expression of mitogen-activated protein kinases (MAPKs) and its upstream protein kinase in human gastric cancer and to evaluate the relationship between protein levels and clinicopathological parameters. METHODS: Western blot was used to measure the expression of extracellular signal-regulated kinase (ERK)-1, ERK-2, ERK-3, p38 and mitogen or ERK activated protein kinaseMEK-1 proteins in surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 42 patients. Immunohistochemistry was employed for their localization. RESULTS: Compared with normal tissues, the protein levels of ERK-1 (integral optical density value 159 526?5 760 vs 122 807±65 515, P= 0.001), ERK-2 (168 471±95 051 vs 120 469±72 874, P<0.001), ERK-3 (118 651±71 513 vs 70 934±68 058,P<0.001), P38 (104 776±51 650 vs 82 930±40 392, P= 0.048) and MEK-1 (116 486±45 725 vs 101 434±49 387, P = 0.027) were increased in gastric cancer tissues. Overexpression of ERK-3 was correlated to TNM staging [average ratio of integral optic density (IOD)tumor: IODnormal in TNM I, II, III, IV tumors was 1.43±0.34, 5.08±3.74, 4.99±1.08, 1.44±1.02, n = 42, P= 0.023] and serosa invasion (4.31±4.34 vs 2.00±2.03, P = 0.037). In poorly differentiated cancers (n = 33), the protein levels of ERK-1 and ERK-2 in stage III and IV tumors were higher than those in stage I and II tumors (2.64+3.01 vs 1.01±0.33, P= 0.022; 2.05±1.54 vs1.24±0.40, P= 0.030). Gastric cancer tissues with either lymph node involvement (2.49±2.91 vs1.03±0.36, P= 0.023; 1.98±1.49vs1.24±0.44, P= 0.036) or serosa invasion (2.39±2.82 vs 1.01±0.35, P= 0.022; 1.95±1.44 vs1.14±0.36, P=0.015) expressed higher protein levels of ERK-1 and ERK-2. In Borrmann II tumors, expression of ERK-2 and ERK-3 was increased compared with Borrmann III tumors (2.57±1.86 vs1.23±0.60, P= 0.022; 5.50±5.05 vs1.83±1.21, P= 0.014). Borrmann IV tumors expressed higher p38 protein levels. No statistically significant difference in expression of MAPKs was found when stratified to tumor size or histological grade (P>0.05). Protein levels of ERK-2, ERK-3 and MEK-1 in metastatic lymph nodes were 2-7 folds higher than those in adjacent normal mucosa. The immunohistochemistry demonstrated that ERK-1, ERK-2, ERK-3, p38 and MEK-1 proteins were mainly localized in cytoplasm. The expression of MEK-1 in gastric cancer cells metastasized to lymph nodes was higher than that of the primary site. CONCLUSION: MAPKs, particularly ERK subclass are overexpressed in the majority of gastric cancers. Overexpression of ERKs is correlated to TNM staging, serosa invasion, and lymph node involvement. The overexpression of p38 most likely plays a prominent role in certain morphological subtypes of gastric cancers. MEK-1 is also overexpressed in gastric cancer, particularly in metastatic lymph nodes. Upregulation of MARK signal transduction pathways may play an important role in tumorigenesis and metastatic potential of gastric cancer.

Role of Activator Protein-1 in the Transcription of Interleukin-5 Gene Regulated by Protein Kinase C Signal in Asthmatic Human TLymphocytes

Summary: In order to explore the role of activator protein-1 (AP-1) in the transcription of interleukin-5 (IL-5) gene regulated by protein kinase C (PKC) signal in peripheral blood T lymphocytes from asthmatic patient, T lymphocytes were isolated and purified from peripheral blood of each asthmatic patient. The T lymphocytes were randomly divided into 4 groups: group A (blank control), group B (treated with PKC agonist phorbol 12-myristate 13-acetate (PMA)), Group C (treated with PMA and AP-1 cis-element decoy oligodeoxynucleotides (decoy ODNs)), and group D (treated with PMA and AP-1 mutant decoy ODNs). The ODNs were transfected into the T cells of group C and D by cation liposome respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to assess IL-5 mRNA expression, and electrophoretic mobility shift assays (EMSA) for the activation of AP-1. The results showed that the activation of AP-1 (88 003.58±1 626.57) and the expression of IL-5 mRNA (0.8300±0.0294) in T lymphocytes stimulated with PMA were significantly higher than these in blank control (20 888.47±1103.56 and 0.3050±0.0208, respectively, P< 0.01), while the indexes (23 219.83±1 024.86 and 0.3425±0.0171 respectively) of T lymphocytes stimulated with PMA and AP-1 decoy ODNs were significantly inhibited, as compared with group B (P< 0.01). The indexes (87 107.41±1 342.92 and 0.8225±0.0222, respectively) in T lymphocytes stimulated with PMA and AP-1 mutant decoy ODNs did not exhibit significant changes, as compared with group B (P>0.05). The significant positive correlation was found between the activation of AP-1 and the expression of IL-5 mRNA (P< 0.01). It was concluded that AP-1 might participate in the signal transduction of PKC-triggered transcription of IL-5 gene in asthmatic T lymphocytes. This suggests the activation of PKC/AP-1 signal transduction cascade of T lymphocytes may play an important role in the pathogenesis of asthma.

Effect of cigarette smoke extract on lipopolysaccharide-activated mitogen-activated protein kinase signal transduction pathway in cultured cells

Background Lipopolysaccharide （LPS） forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflammation of respiratory passage. The mitogen-activated protein kinase （MAPK） signal transduction pathway of the airway epithelia is intimately associated with the action of LPS. The chronic inflammation of respiratory tract and smoking are interrelated and entwined in the development and progression of chronic lung diseases. This study was designed to examine the effects of cigarette smoke extract （CSE） and LPS on MAPK signal transduction pathway in order to further understand the roles CSE and LPS play in chronic lung inflammation. Methods Cultured primary human epithelial cells of airway were divided into four groups according to the stimulants used： blank control group, LPS-stimulation group, CSE-stimulation group and CSE plus LPS group. Western blotting was employed for the detection of phosphorylation level of extracellular-signal-regulated-kinase （ERK1/2）, p38 MAPK and c-Jun N-terminal kinase （JNK）. The expression of cytokines of MAPK transduction pathway （granulocyte-macrophage colony stimulating factor （GM-CSF） and mRNA of IL-8） in the primary epithelial cells of respiratory tract was also determined. Results Western blotting revealed that the phosphorylation levels of ERK1/2, p38 MAPK and JNK were low and 2 hours after the LPS stimulation, the phosphorylation of ERK1/2, p38 MAPK and JNK were all increased. There was a significant difference in the phosphorylation between the LPS-stimulation group and blank control group （P〈0.05）; no significant difference was found between CSE-stimulation group and blank control group （P〉0.05）; there was a significant difference between CSE ＋ LPS group and blank control group and between CSE ＋ LPS group and LPS group （P〈0.05）. The phosphorylation of CSE-LPS group was higher than that of blank control group but lower than that of LPS group. In blank control group, the expression of IL-8 and GM-CSF mRNA was low in the epithelial cells of airway and the release of IL-8 and GM-CSF was also at a low level. One hour after LPS stimulation, the level of IL-8 mRNA increased （P〈0.05） and reached a peak after 2 hours. On the other hand, GM-CSF mRNA level increased 2 hours after the stimulation （P〈0.05） and reached the highest level 4 hours after the stimulation. Two hours after LPS stimulation, IL-8 and GM-CSF protein level began to rise （P〈0.05）, and the level was the highest 8 hours after the stimulation （P〈0.01）. Stimulation with CSE alone had no effect on the release of IL-8 and GM-CSF and expression of IL-8 mRNA （P〉0.05）, but pre-treatment with CSE could delay the LPS-induced release of IL-8 and GM-CSF and the expression of IL-8 mRNA and its peak was lower. Conclusions LPS stimulation can significantly increase the phosphorylation of ERK1/2, p38 MAPK and JNK in the epithelial cells of airway and activate the MAPK transduction pathway, thereby can activate the downstream signal transduction pathway, and can ultimately result in the release of cytokines by the epithelial cells of airway. CSE can partially abolish the LPS-induced activation of MAPK signal transduction pathway and the expression of cytokines of the pathway, which might contribute to the development and progression of the inflammatory reactions in COPD patients.

The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

Protein kinase C epsilon(PKCε)is one of major isoforms in novel PKC family.Although it has been extensively characterized in the past decade,the role of PKCεin neuron is still not well understood.Advances in molecular biology have now removed significant barriers to the direct investigation of PKCεfunctions in vivo,and PKCεhas been increasingly implicated in the neural biological functions and associated neurogenic diseases.Recent studies have provided important insights into the influence of PKCεon cortical processing at both the single cell level and network level.These studies provide compelling evidence that PKCεcould regulate distinct aspects of neural signal transduction and suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of PKCεsignal pathway in the developing brain.

Modulating protein kinase D1 signal transduction

Protein kinase C （PKC） consists of a family of serine/threonine kinases that are identified by the presence of two copies of the C1 domain, which form the diacylglycerol （DAG）-binding module. According to their enzymatic activities PKCs are sub-divided into conventional isozymes （PKCα, β and γ; calcium, phospholipid and DAG-activated kinases）, novel isozymes （PKCδ, ε, η, μ and θ; calcium-insensitive, phospholipid-dependent and DAG-dependent）, and atypical isozymes （PKCζ and λ; calcium-insensitive and DAG-insensitive enzymes）. Human protein kinase Cμ and its mouse homolog, protein kinase D1 （PKD1）, which has been under intense investigation in recent years, is a DAG-dependent, Ca^2＋-independent serine/threonine protein kinase as a novel PKC isoform. Recently PKDs were classified as a novel subgroup of the calcium/calmodulin-dependent protein kinase （CAMK） family, based on sequence similarities of the kinase domain; the catal^ctic domain of PKD1 has the highest homology to CAMK. PKD1 has three main pathways for activation. One is DAG-phospholipase C （PLC）-PKC-dependent activation of PKD1. In this model, PKD 1 not only acts as a direct DAG target but also lies downstream of PKCs to regulate biological processes in cells.

CIPK9: a calcium sensor-interacting protein kinase required for low-potassium tolerance in Arabidopsis

Potassium is one of the major macro-nutrients essential for a number of cellular processes in plants. Low potassium level in the soil represents a limiting factor for crop production. Recent studies have identified potassium transporters that are involved in potassium acquisition, and some of them are critical for potassium nutrition under low potassium conditions. However, little is understood on the molecular components involved in low potassium signaling and responses. We report here the identification ofa calcineurin B-like protein-interacting protein kinase （CIPK9） as a critical regulator of low potassium response in ,Arabidopsis. The CIPK9 gene was responsive to abiotic stress conditions, and its transcript was inducible in both roots and shoots by potassium deprivation. Disruption of CIPK9 function rendered the mutant plants hypersensitive to low potassium media. Further analysis indicated that K^＋ uptake and content were not affected in the mutant plants, implying CIPK9 in the regulation of potassium utilization or sensing processes.

INHIBITION OF IL-6-INDUCED STAT3 ACTIVATION IN MYELOMA CELLS BY PROTEIN KINASE A

Objective: To investigate the regulation effect of protein kinase A on IL-6-induced STAT3 activation in myeloma cells. Methods: Two human myeloma cell lines-Sko-007 and U266 were pretreated with Forskolin, a protein kinase A antagonist, and then stimulated by IL-6. The activation state of STAT3 in these two cells were examined by electrophoretic mobility shift assay (EMSA). Results: Although PKA pathway itself doesn’t participate in IL-6 signal transduction in Sko-007 and U266 cells, activation of protein kinase A can inhibit IL-6-induced STAT3 activation in these two cell lines. Conclusion: There exists an inhibitory effect of protein kinase A on STAT3 activation in human myeloma cells treated by IL-6.

Telencephalin protects PAJU cells from amyloid beta protein-induced apoptosis by activating the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway

Telencephalin is a neural glycoprotein that reduces apoptosis induced by amyloid beta protein in the human neural tumor cell line PAJU. In this study, we examined the role of the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway in this process. Western blot analysis demonstrated that telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidylinositol-3-kinase/protein kinase B were not expressed in PAJU cells transfected with empty plasmid, while they were expressed in PAJU cells transfected with a telencephalin expression plasmid. After treatment with 1.0 nM amyloid beta protein 42, expression of telencephalin and phosphorylated phosphatidylinositol-3-kinase/protein kinase B in the transfected cells gradually diminished, while levels of phosphorylated ezrin/radixin/moesin increased. In addition, the high levels of telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidylinositol-3-kinase/protein kinase B expression in PAJU cells transfected with a telencephalin expression plasmid could be suppressed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings indicate that telencephalin activates the ezrin/radixin/moesin family/phosphatidylinositol-3-kinase/protein kinase B pathway and protects PAJU cells from amyloid beta protein-induced apoptosis.

Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives

Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription(JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.

Bornyl acetate extracted from Sharen(Fructus Amomi)inhibits proliferation,invasion and induces apoptosis by suppressing phosphatidylinositol-3-kinase/protein kinase B signaling in colorectal cancer

OBJECTIVE:To investigate the antitumor effects of bornyl acetate(BA)isolated from Sharen(Fructus Amomi)in colorectal cancer(CRC)and the underlying mechanisms.METHODS:SW480 and HT29 cells were treated with increasing doses of BA in order to determine its antitumor effects in vitro.Cell viability,colony formation,cell cycle,and apoptosis as well as migration and invasion were assessed using various assays.In addition,the in vivo antitumor effects of BA were assessed using a xenograft mouse model.We then assessed the mechanism of action of BA by conducting pathway activator-mediated rescue experiments and assessed the protein levels by Western blot analysis.RESULTS:BA showed anti-CRC tumor activities in vitro by suppressing cell proliferation and colony formation,inducing apoptosis,blocking cell cycle,and inhibiting migration and invasion.These effects were mediated via suppression of the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway.In the tumor xenograft experiment,BA was found to repress tumor growth in vivo with low toxicity.CONCLUSIONS:The results demonstrated that BA exerts antitumor effects by suppressing the PI3K/AKT pathway,with low toxicity.Thus,BA might be a potential novel therapeutic agent for CRC.

Electroacupuncture stimulating Zusanli(ST36),Sanyinjiao(SP6)in mice with collagen-induced arthritis leads to adenosine A2A receptor-mediated alteration of p38αmitogen-activated protein kinase signaling and inhibition of osteoclastogenesis

OBJECTIVE:To observe the effect of electroacupuncture(EA)stimulating Zusanli(ST36),Sanyinjiao(SP6)on inhibition of osteoclastogenesis and the role of the adenosine A2A receptor(A2AR)and the p38αMitogen-Activated Protein Kinase(MAPK)signaling pathway in mediating this effect.METHODS:Mice with collagen induced arthritis(CIA)received different treatments.Immunohistochemistry and western blotting were used to determine the levels of multiple signaling molecules in these joints[receptor activator of nuclear transcription factor-κB(NF-κB)ligand(RANKL),receptor activator of NF-κB(RANK),tumor necrosis factor receptor associated factor 6(TRAF6),p38α,NF-κB,and nuclear factor of activated T cells C1(NFATc1)].Osteoclasts were identified using tartrate-resistant acid phosphatase(TRAP)staining.RESULTS:The immunohistochemistry results indicated upregulation of p38α,NF-κB,and NFATc1 in the CIA-control and CIA-EA-SCH58261 groups,but reduced levels in the CIA-EA group.Western blotting indicated upregulation of RANKL,RANK,TRAF6,p38α,NF-κB,and NFATc1 in the CIA-control and CIA-EA-SCH58261 groups,but reduced expression in the CIA-EA group.Osteoclasts were more abundant in the CIA-control and CIA-EA-SCH58261 groups than in the CIA-EA group.CONCLUSIONS:EA treatment enhanced the A2AR activity and inhibited osteoclast formation by inhibition of RANKL,RANK,TRAF6,p38α,NF-κB,and NFATc1.SCH58261 reversed the effect of EA.These results suggest that EA regulated p38α-MAPK signaling by increasing A2AR activity,which inhibited osteoclastogenesis.

Ginsenoside Rb1 alleviates chronic intermittent hypoxia-induced diabetic cardiomyopathy in db/db mice by regulating the adenosine monophosphate-activated protein kinase/Nrf2/heme oxygenase-1 signaling pathway

OBJECTIVE:To examine the protective effect of ginsenoside Rb1(Rb1),the main component of Renshen(Radix Ginseng),on cardiomyopathy in db/db mice exposed to chronic intermittent hypoxia(CIH)and explore the potential underlying mechanism of Rb1 in treating diabetic cardiomyopathy(DCM).METHODS:The db/db mice were randomly separated into five groups:normal control group,model group,Rb120 mg/kg group,Rb140 mg/kg group,and glucagon-like peptide-1(GLP-1)group.Mice were exposed to aircondition or CIH for 8 weeks,and Rb1 and GLP-1 were administrated before CIH exposure every day.Oral glucose tolerance test(OGTT),intraperitoneal insulin tolerance test(IPITT),total cholesterol(TC),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)were detected to evaluate glycolipid metabolism.The level of insulin was detected by a mouse enzyme-linked immunosorbent assay(ELISA).Cardiac function was detected by echocardiography,and myocardial pathology was observed by hematoxylin-eosin and Masson staining.The expression of collagenⅠand collagenⅢwas detected by immunohistochemistry.Adenosine monophosphate-activated protein kinase(AMPK)/Nrf2/heme oxygenase-1(HO-1)signaling pathway was detected by Western blot and immunofluorescence.RESULTS:Rb1 treatment could improve glucose tolerance and the level of cardiac function indexes,and inhibit the level of oxidative stress indexes and the expression of collagenⅠand collagenⅢ.Moreover,Rb1 treatment enhanced AMPK phosphorylation and increased Nrf2 and HO-1 expression.CONCLUSION:Rb1 treatment alleviated CIH-induced diabetic cardiomyopathy and glycolipid metabolism disorders in db/db mice by inhibiting oxidative stress and regulating the AMPK/Nrf2/HO-1 signaling pathway.

一个新的鼠STE20家族激酶的克隆和鉴定

从鼠肝ｃＤＮＡ文库克隆了一个新的ＳＴＥ２０ 类蛋白激酶， Ｍｅｓｓ１． 其ｃＤＮＡ长１７ ｋｂ， 编码了一个４９７ 个氨基酸残基的多肽， 与人ＭＳＴ２ 具有９５％ 的氨基酸相同． Ｍｅｓｓ１ 蛋白氨基末端激酶催化区的序列与ＳＴＥ２０ 同源，其羧基末端包含了一簇丝氨酸／苏氨酸和谷氨酸丰富的序列， 被认为具有介导与ＳＨ２ 功能区结合的作用． ＭＥＳＳ１可能通过与含有ＳＨ２

Protein kinase-based neural signaling pathways for ginsenosides:a retrospective review

Ginsenosides are the main active components of ginseng,which have been reported to target brain tissues and produce multiple neuroprotective effects.Ginsenosides have been shown to improve learning ability and memory in normal aged animals,and in an animal model of memory impairment.However,its underlying pharmacological mechanisms are very complicated,especially with regard to its effects on the activation of protein kinases in neurons.Previous reports have shown that some protein kinases may be affected by ginsenosides,including protein kinase C,calcium/calmodulin-dependent protein kinase Ⅱ,c-Jun-N terminal kinase,and protein tyrosine kinase.In this paper,protein kinases that may underlie the mechanisms of ginsenosides will be discussed.

Mitogen-activated protein kinase cascades in plant signaling

Mitogen-activated protein kinase(MAPK)cascades are key signaling modules downstream of receptors/sensors that perceive either endogenously produced stimuli such as peptide ligands and damage-associated molecular patterns(DAMPs)or exogenously originated stimuli such as pathogen/microbe-associated molecular patterns(P/MAMPs),pathogen-derived effectors,and environmental factors.In this review,we provide a historic view of plant MAPK research and summarize recent advances in the establishment of MAPK cascades as essential components in plant immunity,response to environmental stresses,and normal growth and development.Each tier of the MAPK cascades is encoded by a small gene family,and multi ple members can function redundantly in an MAPK cascade.Yet,they carry out a diverse array of biological functions in plants.How the signaling specificity is achieved has become an interesting topic of MAPK research.Future investigations into the molecular mechanism(s)underlying the regulation of MAPK activation including the activation kinetics and magnitude in response to a stimulus,the spatiotemporal expression patterns of all the components in the signaling pathway,and functional characterization of novel MAPK substrates are central to our understanding of MAPK functions and signaling specificity in plants.

Pingchuan formula(平喘方) improves allergic asthma in mice through inhibiting nuclear factor-kappa B/mitogen-activated protein kinase signaling pathway

OBJECTIVE:To examine the role and decipher the mechanism of Pingchuan formula(平喘方,PCF)in treating allergic asthma.METHODS:The mice were treated with saline,dexamethasone(DXM)and PCF for 1 week after the asthma model was established and their respiratory function including respiratory resistance(RI),pulmonary dynamic compliance(Cdyn)and maximum voluntary ventilation(MVV)were measured.In addition,cellular changes in bronchoalveolar lavage fluid(BALF)and pathological changes in lung biopsy as well as the expression level ofα-smooth muscle actin(α-SMA),transforming growth factor-beta1(TGF-β1)in BALF and interleukin-5(IL-5),interleukin-13(IL-13),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),nuclear factor-kappa B-p65(NF-κBp65),inhibitor-αof nuclear transcription factorκB(IκBα),p38 mitogen-activated protein kinase(p38 MAPK),c-jun n-terminal kinase(JNK)and its phosphorylated proteins in lung tissue were also examined and compared among different groups.RESULTS:Our data suggested that the respiratory functions were significantly improved and the pathological changes ameliorated in the DXM group and the PCF group compared to the model group.Both DXM and PCF effectively decreased the number of eosinophils,lymphocytes,and neutrophils in BAL as well as the secretion ofα-SMA and TGF-β1,IL-5,IL-13,while increased the expression of TNF-αand IFN-γ.Furthermore,our study indicated that the NF-κBp65,IκBα,p38 MAPK and JNK pathways were inhibited under the treatment of PCF.CONCLUSION:Our data indicated that PCF can attenuate the inflammatory response in asthma through inhibiting the NF-κB/MAPK signaling pathway.This study not only supported the use of PCF in allergic asthma in clinic but also shed light upon afurther understanding of the disease pathogenesis.

Receptor-like protein kinase-mediated signaling in controlling root meristem homeostasis

Generation of the root greatly benefits higher plants living on land.Continuous root growth and development are achieved by the root apical meristem,which acts as a reservoir of stem cells.The stem cells,on the one hand,constantly renew themselves through cell division.On the other hand,they differentiate into functional cells to form diverse tissues of the root.The balance between the maintenance and consumption of the root apical meristem is governed by cell-to-cell communications.Receptor-like protein kinases(RLKs),a group of signaling molecules localized on the cell surface,have been implicated in sensing multiple endogenous and environmental signals for plant development and stress adaptation.Over the past two decades,various RLKs and their ligands have been revealed to participate in regulating root meristem homeostasis.In this review,we focus on the recent studies about RLK-mediated signaling in regulating the maintenance and consumption of the root apical meristem.

Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway

OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent protein kinase(c GMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFp EF rat models using the abdominal aorta constriction method. These rats in the HFp EF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin lowdose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, lowdose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide(NT-pro BNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the c GMP-PKG pathway. Natriuretic peptide receptor A(NPRA) and guanylate cyclase(GC) were detected by immunohistochemistry, and e NOS, phosphodiesterase 5A(PDE5A), and c GMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole(IVSd) and the thickness of the posterior wall at the end of diastole(PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced(P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased(P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P < 0.01). Compared to the model group, the expressions of e NOS and PKG I increased(P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group(P < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFp EF. It increases the expression of NPRA, GC, and e NOS in the myocardial cell c GMP-PKG signaling pathway, upregulates c GMP expression, decreases PDE5A expression to reduce the c GMP degradation. Thus, the c GMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFp EF rats.