Molecular mechanisms involved in epidermal growth factor receptor-mediated inhibition of dopamine D₃ receptor signaling

Sun, Ningning,Zhang, Xiaowei,Guo, Shuohan,Le, Hang Thi,Zhang, Xiaohan,Kim, Kyeong-Man Elsevier 2018 Biochimica et biophysica acta, Molecular cell rese Vol.1865 No.9

<P><B>Abstract</B></P> <P>The phenomenon wherein the signaling by a given receptor is regulated by a different class of receptors is termed transactivation or crosstalk. Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs) is highly diverse and has unique functional implications because of the distinct structural features of the receptors and the signaling pathways involved. The present study used the epidermal growth factor receptor (EGFR) and dopamine D<SUB>3</SUB> receptor (D<SUB>3</SUB>R), which are both associated with schizophrenia, as the model system to study crosstalk between RTKs and GPCRs. Loss-of-function approaches were used to identify the cellular components involved in the tyrosine phosphorylation of G protein-coupled receptor kinase 2 (GRK2), which is responsible for EGFR-induced regulation of the functions of D<SUB>3</SUB>R. <I>SRC</I> proto-oncogene (Src, non-receptor tyrosine kinase), heterotrimeric G protein Gβγ subunit, and endocytosis of EGFR were involved in the tyrosine phosphorylation of GRK2. In response to EGF treatment, Src interacted with EGFR in a Gβγ-dependent manner, resulting in the endocytosis of EGFR. Internalized EGFR in the cytosol mediated Src/Gβγ-dependent tyrosine phosphorylation of GRK2. The binding of tyrosine-phosphorylated GRK2 to the T142 residue of D<SUB>3</SUB>R resulted in uncoupling from G proteins, endocytosis, and lysosomal downregulation. This study identified the molecular mechanisms involved in the EGFR-mediated regulation of the functions of D<SUB>3</SUB>R, which can be extended to the crosstalk between other RTKs and GPCRs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Stimulation of EGFR results in the tyrosine phosphorylation of GRK2. </LI> <LI> Gβγ, Src, and endocytosis of EGFR are required for the tyrosine phosphorylation of GRK2. </LI> <LI> Tyrosine phosphorylated GRK2 binds to T142 of D<SUB>3</SUB>R. </LI> <LI> GRK2-bound D<SUB>3</SUB>R is uncoupled from G proteins to result in signaling inhibition. </LI> <LI> GRK2-bound D<SUB>3</SUB>R undergoes endocytosis and degradation through lysosomal pathway. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Levonorgestrel-releasing intrauterine system-based therapies for early- stage endometrial cancer: a systematic review and meta-analysis

Hongyi Wei,Ningning Pan,Wen Zhang,Guangwu Xiong,Wenping Guo,Zhe Dong,Caihong Ma 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.2

Objective: To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens. Methods: The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate. Results: A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%–73.2%), with 29.6% (95% CI=23.3%–36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m2 who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%–88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%–53.9%) and 39.3% (95% CI=24.0%–57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups. Conclusion: LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.

Multiple Mixed Modes: Single-Channel Blind Image Separation

Tiantian Yin,Yina Guo,Ningning Zhang 한국정보처리학회 2023 Journal of information processing systems Vol.19 No.6

As one of the pivotal techniques of image restoration, single-channel blind source separation (SCBSS) iscapable of converting a visual-only image into multi-source images. However, image degradation often resultsfrom multiple mixing methods. Therefore, this paper introduces an innovative SCBSS algorithm to effectivelyseparate source images from a composite image in various mixed modes. The cornerstone of this approach is anovel triple generative adversarial network (TriGAN), designed based on dual learning principles. The TriGANredefines the discriminator's function to optimize the separation process. Extensive experiments havedemonstrated the algorithm's capability to distinctly separate source images from a composite image in diversemixed modes and to facilitate effective image restoration. The effectiveness of the proposed method isquantitatively supported by achieving an average peak signal-to-noise ratio exceeding 30 dB, and the averagestructural similarity index surpassing 0.95 across multiple datasets.

A combined application of molecular docking technology and indirect ELISA for the serodiagnosis of bovine tuberculosis

Song, Shengnan,Zhang, Qian,Yang, Hang,Guo, Jia,Xu, Mingguo,Yang, Ningning,Yi, Jihai,Wang, Zhen,Chen, Chuangfu The Korean Society of Veterinary Science 2022 Journal of Veterinary Science Vol. No.

Background: There is an urgent need to find reliable and rapid bovine tuberculosis (bTB) diagnostics in response to the rising prevalence of bTB worldwide. Toll-like receptor 2 (TLR2) recognizes components of bTB and initiates antigen-presenting cells to mediate humoral immunity. Evaluating the affinity of antigens with TLR2 can form the basis of a new method for the diagnosis of bTB based on humoral immunity. Objectives: To develop a reliable and rapid strategy to improve diagnostic tools for bTB. Methods: In this study, we expressed and purified the sixteen bTB-specific recombinant proteins in Escherichia coli. The two antigenic proteins, MPT70 and MPT83, which were most valuable for serological diagnosis of bTB were screened. Molecular docking technology was used to analyze the affinity of MPT70, MPT83, dominant epitope peptide of MPT70 (M1), and dominant epitope peptide MPT83 (M2) with TLR2, combined with the detection results of enzyme-linked immunosorbent assay to evaluate the molecular docking effect. Results: The results showed that interaction surface Cα-atom root mean square deviation of proteins (M1, M2, MPT70, MPT83)-TLR2 protein are less than 2.5 A, showing a high affinity. It is verified by clinical serum samples that MPT70, MPT83, MPT70-MPT83 showed good diagnostic potential for the detection of anti-bTB IgG and M1, M2 can replace the whole protein as the detection antigen. Conclusions: Molecular docking to evaluate the affinity of bTB protein and TLR2 combined with ELISA provides new insights for the diagnosis of bTB.

A combined application of molecular docking technology and indirect ELISA for the serodiagnosis of bovine tuberculosis

Song, Shengnan,Zhang, Qian,Yang, Hang,Guo, Jia,Xu, Mingguo,Yang, Ningning,Yi, Jihai,Wang, Zhen,Chen, Chuangfu The Korean Society of Veterinary Science 2022 Journal of Veterinary Science Vol.23 No.3

Background: There is an urgent need to find reliable and rapid bovine tuberculosis (bTB) diagnostics in response to the rising prevalence of bTB worldwide. Toll-like receptor 2 (TLR2) recognizes components of bTB and initiates antigen-presenting cells to mediate humoral immunity. Evaluating the affinity of antigens with TLR2 can form the basis of a new method for the diagnosis of bTB based on humoral immunity. Objectives: To develop a reliable and rapid strategy to improve diagnostic tools for bTB. Methods: In this study, we expressed and purified the sixteen bTB-specific recombinant proteins in Escherichia coli. The two antigenic proteins, MPT70 and MPT83, which were most valuable for serological diagnosis of bTB were screened. Molecular docking technology was used to analyze the affinity of MPT70, MPT83, dominant epitope peptide of MPT70 (M1), and dominant epitope peptide MPT83 (M2) with TLR2, combined with the detection results of enzyme-linked immunosorbent assay to evaluate the molecular docking effect. Results: The results showed that interaction surface Cα-atom root mean square deviation of proteins (M1, M2, MPT70, MPT83)-TLR2 protein are less than 2.5 A, showing a high affinity. It is verified by clinical serum samples that MPT70, MPT83, MPT70-MPT83 showed good diagnostic potential for the detection of anti-bTB IgG and M1, M2 can replace the whole protein as the detection antigen. Conclusions: Molecular docking to evaluate the affinity of bTB protein and TLR2 combined with ELISA provides new insights for the diagnosis of bTB.

Research on the Axial Magnetic Levitation Force Acting on the Ring Magnet Suspended in Magnetic Fluid : Considering a Radial Eccentricity

Jun Yu,Decai Li,Nannan Di,Ningning Guo 한국자기학회 2019 Journal of Magnetics Vol.24 No.2

The self-suspension of magnet in magnetic fluid has been widely used in micromechanical systems, sensors, and dampers. The magnetic field associated with the ring magnet is obtained by numerical calculation and simulation through which the axial magnetic levitation force is calculated, and the numerical calculation, simulation, and experimental results agree with each other. The influence of the radial eccentricity of the ring magnet on the axial magnetic levitation force is studied, the ring magnet will experience a maximum axial magnetic levitation force without radial eccentricity. With the increase of radial eccentricity and the decrease of the distance between the bottom of the ring magnet and container, the axial magnetic levitation force will continue to decrease. But it is worth noting that the magnitude of the change caused by radial eccentricity is negligible compared to that of the axial magnetic levitation force.