Using multi-omics analysis to explore diagnostic tool and optimize drug therapy selection for patients with glioma based on cross-talk gene signature

Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.

基于肠源性高密度脂蛋白调控脂多糖介导Kupffer-肝细胞Cross-Talk探讨脾虚膏脂转输障碍的分子生物学基础

脾虚膏脂转输障碍是血脂异常的关键病机。脾失健运引起肝脏代谢功能障碍可能导致血脂异常。肠道功能紊乱是脾虚膏脂转输障碍的启动因素,以其介导“炎症-代谢”紊乱为切入点,深入揭示血脂异常疾病发病机制以提高中西医结合防治水平逐渐成为基础和临床研究焦点和热点。从肠源性高密度脂蛋白(high-density lipoprotein 3,HDL3)调控脂多糖(lipopolysaccharide,LPS)介导Kupffer-肝细胞cross-talk的角度,深入分析脾虚膏脂转输障碍的分子生物学机制,揭示健脾化浊法的效应机制,为临床防治血脂异常提供科学依据。

Integration of root architecture,root nitrogen metabolism,and photosynthesis of‘Hanfu’apple trees under the cross-talk between glucose and IAA

Sugars and auxin have important effects on almost all phases of plant life cycle,which are so fundamental to plants and regulate similar processes.However,little is known about the effect of cross-talk between glucose and indole-3-acetic acid(IAA)on growth and development of apple trees.To examine the potential roles of glucose and IAA in root architecture,root nitrogen(N)metabolism and photosynthetic capacity in‘Hanfu’(Malus domestica),a total of five treatments was established:single application of glucose,IAA,and auxin polar transport inhibitor(2,3,5-triiodobenzoic acid,TIBA),combined application of glucose with TIBA and that of glucose with IAA.The combined application of glucose with IAA improved root topology system and endogenous IAA content by altering the mRNA levels of several genes involved in root growth,auxin transport and biosynthesis.Moreover,the increased N metabolism enzyme activities and levels of genes expression related to N in roots may suggest higher rates of transformation of nitrate(NO3--N)into amino acids application of glucose and IAA.Contrarily,single application of TIBA decreased the expression levels of auxin transport gene,hindered root growth and decreased endogenous IAA content.Glucose combined with TIBA application effectively attenuated TIBA-induced reductions in root topology structure,photosynthesis and N metabolism activity,and mRNA expression levels involved in auxin biosynthesis and transport.Taken together,glucose application probably changes the expression level of auxin synthesis and transport genes,and induce the allocation of endogenous IAA in root,and thus improves root architecture and N metabolism of root in soil with deficit carbon.

内质网应激下肝癌细胞Akt和ERK通路间的cross-talk研究

目的研究内质网应激介导的肝癌细胞PI3K/AKt和M EK/ER K途径间的信号交流。方法采用PI3K抑制剂LY 294002/Akt激活型突变载体m yr-Akt和M EK抑制剂U 0126分别阻断/激活内质网应激介导的Akt和ER K活化,并利用W estern blot分析内质网应激条件下PI3K/Akt和M EK/ER K途径间的信号交流。结果阻断PI3K/Akt明显促进内质网应激介导的M EK/ER K活化,而过度激活PI3K/Akt则抑制内质网应激介导的M EK/ER K活化。阻断M EK/ER K对内质网应激介导的PI3K/Akt活化无影响。结论 PI3K/Akt和M EK/ER K信号途径间在内质网应激肝癌细胞中存在信号交流。

基于GEO芯片联合网络药理学探讨当归饮子治疗慢性荨麻疹的cross-talk及miRNA-mRNA机制

目的采用GEO芯片联合网络药理学的研究方法,初步探讨当归饮子治疗慢性荨麻疹(CU)的cross-talk及miRNA-mRNA机制,为后续实验研究提供理论基础。方法采用R语言limma包对GSE57178芯片进行差异分析;采用TCMSP、TCMID、PubChem、String、DAVID、TargetScan数据库对当归饮子有效成分、潜在靶点、PPI、KEGG、cross-talk及miRNA-mRNA机制进行预测分析。结果GSE57178差异分析得出257个差异基因,其中240个基因表达上调(如:HIF1A、MMP12、STAT3等);有17个基因表达下调(如:FABP7、KRT15、LGR5等),其中有36个当归饮子治疗慢性荨麻疹的潜在靶点,拓扑分析出24个关键靶点基因在其中发挥重要作用;cross-talk分析得出1个靶点(SELE)在TNF通路与细胞粘附分子(CAMs)2条通路中“串话”;1个靶点(ITGB2)在吞噬体与CAMs 2条通路中“串话”;2个靶点(CTSL、CTSS)在抗原处理表达、吞噬体与溶酶体3条通路中“串话”;2个靶点(VCAM1、ICAM1)在NF-kappa B、TNF与CAMs 3条通路中“串话”;1个靶点(TLR4)在HIF-1、NF-kappa B、吞噬体3条通路中“串话”;miRNA-mRNA预测分析得出24个潜在靶点mRNA,构成了477组miRNA-mRNA模式,在CU炎症反应中发挥作用。结论本研究从基因、分子角度预测和分析了当归饮子治疗CU的多靶点、多cross-talk、多miRNA-mRNA作用机制,为后续研究提供了依据,可成为未来机制研究的新方向。

TLRs信号通路和TLRs的Cross-talk在炎症性疾病中作用的研究进展

Toll样受体(TLRs)是一种重要的模式识别受体(PRR),主要通过2条信号通路向下游传递信号以发挥免疫学效应。经过下游分子诱导的TLR通过和其他PRR(包括其他TLRs)、免疫分子和蛋白酶类的交叉作用,即Cross-talk,与炎症性疾病的发生发展过程密切相关。TLR信号通路包括MyD88依赖信号通路和MyD88非依赖性信号通路(TRIF通路),其下游的信号分子肿瘤坏死因子受体相关因子3(TRAF3)和肿瘤坏死因子受体相关因子6(TRAF6),在引导信号传导方向的过程中起重要作用。TLRs信号通路能完全激活炎症,而TLRs的Cross-talk参与各种炎症性疾病的预后和转归。TLRs的Cross-talk在系统性红斑狼疮、急性肺损伤和脓毒症等炎症性疾病的发生过程中通过增加细胞因子的分泌、激活蛋白酶使免疫细胞过度活化和增强免疫细胞的趋化作用加速相关疾病进程,甚至在炎症末期因机体免疫分子及免疫细胞消耗过度而引发免疫抑制,这阻碍了机体免疫稳态的维持。现对炎症性疾病进程中组织和细胞中TLRs信号通路分子的表达变化及其Cross-talk作用的分子机制进行综述,深入了解TLRs的Cross-talk在炎症发生发展中的作用机制,为治疗炎症性疾病提供新的策略和靶标。

Signaling cross-talk between TGF-β/BMP and other pathways

Transforming growth factor-beta （TGF-β）/bone morphogenic protein （BMP） signaling is involved in the vast majority of cellular processes and is fundamentally important during the entire life of all metazoans. Deregulation of TGF-β/ BMP activity almost invariably leads to developmental defects and/or diseases, including cancer. The proper functioning of the TGF-β/BMP pathway depends on its constitutive and extensive communication with other signaling pathways, leading to synergistic or antagonistic effects and eventually desirable biological outcomes. The nature of such signaling cross-talk is overwhelmingly complex and highly context-dependent. Here we review the different modes of cross-talk between TGF-β/BMP and the signaling pathways of Mitogen-activated protein kinase, phosphatidylinositol-3 kinase/ Akt, Wnt, Hedgehog, Notch, and the interleukin/interferon-gamma/tumor necrosis factor-alpha cytokines, with an emphasis on the underlying molecular mechanisms.

表达HCV NS3蛋白肝细胞中ERK与NF-κB信号转导通路间的cross-talk研究

目的:研究表达丙型肝炎病毒非结构蛋白3(hepatitis C virus non-structural protein3,HCVNS3)的肝细胞中细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)与核因子κB(nuclear fac-torκB,NF-κB)信号转导通路间的cross-talk。方法:真核表达质粒pcDNA3.1-NS3转染人源永生化肝细胞系QSG7701,建立稳定表达HCV NS3蛋白的细胞株QSG7701/NS3。在丝裂原活化蛋白激酶的激酶(MAP kinase kinase,MEK)抑制剂PD98059(0,30,50,100μmol/L)处理细胞QSG7701/NS3前后,利用Western免疫印迹检测ERK的磷酸化水平及细胞周期素D1(cyclin D1)蛋白的表达;凝胶电泳阻滞迁移试验检测转录激活因子1(activator protrin1,AP-1)、NF-κB等转录因子活性的改变;流式细胞术检测细胞周期各期百分数的改变;MTT比色法观察其对细胞增殖的影响。结果:HCV NS3蛋白能上调QSG7701细胞的ERK磷酸化水平及cyclin D1的表达水平;PD98059抑制HCV NS3蛋白介导的细胞增殖,下调AP-1和NF-κB的活性及cyclin D1的表达。结论:在表达HCV NS3蛋白的肝细胞中,ERK抑制剂能抑制肝细胞增殖,并呈明显的剂量依赖关系。ERK与NF-κB信号转导通路间可能存在cross-talk,并在肝细胞的增殖和恶性转化中发挥协同作用。

Cross-talk between T-cells and gut-microbiota in neurodegenerative disorders

The emerging role of gut microbiota as a key player in the development of neurodegenerative disorders: Mammals have evolved together with commensal microbiota to establish a symbiotic relationship in which they regulate reciprocally by synthesizing and responding to several common chemical substances. In this regard, gut microbiota constitutes a consortium of bacteria that not only participates in the degradation of nutrients, but also produces metabolites, fatty acids and neurotransmitters that can act on the enzymes and receptors expressed in eukaryotic cells, which considerably affects the physiology of the host and contribute to maintaining homeostasis (Lyte, 2013).

The cross-talk between family and pediatrician: The case of bronchial asthma

Today the most important challenge facing the pediatrician is the increasing prevalence of chronic diseases. With this regard, pediatricians play a key role in the management of these conditions. The closeness with the family, the knowledge of the clinical case and the care continuity allow the pediatrician to acquire a position of director of every case. When pathological events have a chronic feature, suddenly the quality of life of the whole family changes. For this reason the first communication of chronic disease is very important and the task of the pediatrician should be to provide a positive message to help the family in facing the difficulty of this new challenge. The bronchial asthma is the most common chronic disease worldwide. The incidence, the prevalence, and the mortality of the disease have increased in children over the past decades. These trends are particularly marked above all in preschool children. The success reached by Pediatricians is closely related to the compliance and the implementation of the therapy followed by the little patient and his family. With this regard authors, in this review, focus on the illustration of several strategies, based on the pediatrician’ skills and medicine documents, that can be used for the improvement of communication among pedia- trician-family and child, never forgetting the hu- man aspect of the same doctor, that should con- ciliate with the scientific knowledge in the taking care of a specific chronic disease.

Testing Cross-Talk Induced Delay Faults in Digital Circuit Based on Transient Current Analysis

The delay fault induced by cross-talk effect is one of the difficult problems in the fault diagnosis of digital circuit. An intelligent fault diagnosis based on IDDT testing and support vector machines （SVM） classifier was proposed in this paper. Firstly, the fault model induced by cross-talk effect and the IDDT testing method were analyzed, and then a delay fault localization method based on SVM was presented. The fault features of the sampled signals were extracted by wavelet packet decomposition and served as input parameters of SVM classifier to classify the different fault types. The simulation results illustrate that the method presented is accurate and effective, reaches a high diagnosis rate above 95%.

Cross-Talk between Extracellular S1P/S1P2 and P42/44 MAPK in bcr/abl Positive Chronic Myeloid Leukemia Cells

Objective： BCR/ABL oncoprotein-expression is associated with uncontrolled cell growth. Sphingosine kinase 1 （SPK1） regulates the production of sphingosine 1-phosphate （S1P）, a key lipid signal molecular in cell proliferation and survival. The objective of this study was to elucidate the roles of S1P and its receptors in bcr/abl positive chronic myeloid leukemia （CML） cells. Methods： The expressions of SIP receptors： S1P1, S1P2 and S1P3 in CML cells were detected by RT-PCR. SPK1 expression, activity and extracellular S1P were determined in ECV304 and HL-60 cells which were transfected with bcr/abl gene. To elucidate the relationship between the BCR/ABL, ERK/MAPK （extracellular signal-regulated kinase/mitogen-activated protein kinase）, SPK/S 1P and S 1P/S 1 P2 signal pathways, bcr/abl positive CML cell line K562 was treated with STI571, PD98059, N,N-dimethyl sphingosine （DMS） and JTE-013. Results： Retrovirus-mediated overexpression of bcr/abl gene in ECV304 and HL-60 cells resulted in upregulation of the expression, activity of SPK1 and increase of the secretion of SIP, whereas treatment of STI571 and PD98059 decreased the BCR/ABL-induced S1P secretion. Treatment of DMS reduced S1P secretion and P42/44MAPK phosphorylation. S1P2-selective antagonist JTE-013 could also decrease P42/44MAPK phosphorylation. Conclusion： These results suggest that BCR/ABL up-regulates extracellular sphingosine 1-phosphate through sphingosine kinase 1 and there is cross-talk between SPK1/S1P/S1P2 and P42/44MAPK in bcr/abl positive CML cells.

一种6信道声光调制器

介绍了一种6信道声光调制器。通过在换能器上制备电极阵列,设计独立的阻抗匹配电路和电输入端口,将6个声光互作用单元集成在一起,实现了对6束激光的并行、独立调制。经测试,该6信道声光调制器工作波长为355 nm,工作频率为220 MHz,单信道衍射效率>75%,全局串扰<0.5%。

Nonaqueous potassium-ion full-cells:Mapping the progress and identifying missing puzzle pieces

This review addresses the growing interest for potassium-ion full-cells(KIFCs)in view of the transition from potassium-ion half-cells(KIHCs)toward commercial K-ion batteries(KIBs).It focuses on the key parameters of KIFCs such as the electrode/electrolyte interfaces challenge,major barriers,and recent advancements in KIFCs.The strategies for enhancing KIFC performance,including interfaces co ntrol,electrolyte optimization,electrodes capacity ratio,electrode material screening and electrode design,are discussed.The review highlights the need to evaluate KIBs in full-cell configurations as half-cell results are strongly impacted by the K metal reactivity.It also emphasizes the importance of understanding solid electrolyte interphase(SEI)formation in KIFCs and explores promising nonaqueous as well as quasiand all-solid-state electrolytes options.This review thus paves the way for practical,cost-effective,and scalable KIBs as energy storage systems by offering insights and guidance for future research.

各向同性弹性波逆时偏移

为了得到物理意义明确、地质可解释的偏移成像结果,当前的弹性波逆时偏移方法需要在偏移过程中对外推的弹性波场进行P/S波分解,以消除物理上相互不匹配的波型在偏移成像结果中产生的交叉噪声.给定具有地震波运动学特征准确的地下介质光滑模型,本文首先给出了作为地震数据线性反演的偏移所对应的一般正演表达式;再利用各向同性弹性波方程,推导出了适合弹性介质光滑模型的P/S波解耦的弹性波方程,即纵波弹性波方程和横波弹性波方程;最后对各向同性弹性波逆时偏移提出了新方法和新认识.对于纯P(或S)波震源激发得到的地震数据的各向同性弹性波逆时偏移,提出了对外推的弹性波场无需进行P/S波分解,在偏移成像结果中也不会出现交叉噪声的新方法;对于P/S波复合震源激发得到的地震数据的各向同性弹性波逆时偏移,提出了即使对外推的弹性波场进行P/S波分解,在偏移成像结果中还会出现交叉噪声的新认识.

Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity

BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.

超低本底流气式正比计数器在样品总α/β测量中串道影响修正

超低本底流气式正比计数器是样品总α/β测量的理想探测器,但本身具有较强的串道现象,影响样品测量的准确性。系统研究了流气式正比计数器在同一质量厚度、不同241 Am和40 K质量分数下α→β、β→α串道影响,建立了总α/β串道修正的二元方程,并与遮盖修正法进行对比,对自制的25组α/β模拟粉末样品进行了测量和串道修正。结果显示α→β串道影响较大,修正因子随着α计数率的变化并非恒定值;β→α串道修正因子影响较小,其平均值为0.001;遮盖修正法对模拟粉末样品中β测量结果的修正效果较差,其相对偏差绝对值介于1.4%~45.0%;二元方程修正法对模拟粉末样品中β测量结果的修正效果较好,其相对偏差绝对值介于0~5.5%。

MicroRNAs and Their Cross-Talks in Plant Development

Plant development is a complex process influenced by exogenous and endogenous elements.A series of postembryonic developmental events is involved to form the final architecture and contend with the changing environment.MicroRNA（miRNA） is one of endogenous non-coding RNAs,which plays an important role in plant developmental regulation.In this review,we summarized 34 miRNA families that are closely associated with plant development.Among these families,nine are expressed only in specific organs,whereas 20 families are expressed in at least two different organs.It is known that some miRNAs are expressed across most processes of plant growth,while some appear only at particular developmental stages or under special environmental conditions such as drought,waterlogging and short-day time.These miRNAs execute their diverse functions by regulating developmental gene expression levels,interacting with phytohormone signaling response,participating in the biogenesis of ta-siRNAs and affecting the production of miRNAs.

Cross-talk between NMDA and GABA_A receptors in cultured neurons of the rat inferior colliculus

Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system,respectively.Currently,cross-talk between the NMDA receptor and the GABAA receptor,particularly in the central auditory system,is not well understood.In the present study,we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus,which is an important nucleus in the central auditory system.We found that the currents induced by aspartate at 100 μmol L-1 were suppressed by the pre-perfusion of GABA at 100 μmol L-1,indicating cross-inhibition of NMDA receptors by activation of GABAA receptors.Moreover,we found that the currents induced by GABA at 100 μmol L-1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L-1 aspartate,but those induced by GABA at 3 μmol L-1 were suppressed,indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors.In addition,inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+,however,CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L-1 BAPTA,a membrane-permeable Ca2+ chelator,suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors,rather than voltage-dependent Ca2+ channels.Finally,KN-62,a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII),reduced the inhibition of IGABA by aspartate,indicating the involvement of CaMKII in this cross-inhibition.Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats.The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.

Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats

Background Signaling pathways that regulate the production of cytokines and destructive enzymes have been implicated in rheumatoid arthritis （RA） pathogenesis. There are co-relations between signaling pathways. The aim of this study was to investigate interactions and cross-talks between MEK1/2-extracellular signal-related kinase （ERK1/2） signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis （CIA） rats by the stimulation of interleukin-1 （IL-1）, U0126, isoprenaline hydrochloride and aminophyline respectively. Methods Twenty Sprague-Dawley （SD） rats were induced by chicken type II collagen. Synoviocytes of CIA rats were isolated and cultured. The expressions of Gi, phosphorylated MEK1/2 （p-MEK1/2） and phosphorylated ERK1/2 （p-ERK1/2） were detected by Western blotting, cAMP level and protein kinase A （PKA） activity were measured by radioimmunoassay and kinase-glo luminescent kinase assay respectively. Results There was remarkable inflammation in CIA rats accompanied by swelling paws, hyperplastic synovium, pannus and cartilage erosion, cAMP level and PKA activity of synoviocytes decreased. Gi, p-ERK1/2 and p-MEK1/2 increased, rlL-la improved the expression of Gi, p-ERK1/2 and p-MEK1/2, cAMP and PKA increased with stimulation of rlL-1α. U0126 inhibited Gi, cAMP and PKA of synoviocytes stimulated by rlL-la. Isoprenaline hydrochloride enhanced Gi, cAMP and PKA, but had no effects on p-MEK1/2 and p-ERK1/2. Aminophyline increased cAMP and PKA, but inhibited p-MEK1/2 and p-ERK1/2. Conclusions Mitogen-activated protein kinases （MAPKs） and G protein-couple signaling are associated with synovitis. There are cross talks between MAPKs and G protein-couple signaling. The two signaling pathways represent potential therapeutic targets for RA.