1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.
2.Effects and mechanism of paeoniflorin on oxidative stress of ulcerative colitis mice
Xin DAI ; Ying WANG ; Xinyue REN ; Dingxing FAN ; Xianzhe LI ; Jiaxuan FENG ; Shilei LOU ; Hui YAN ; Cong SUN
China Pharmacy 2025;36(4):427-433
OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis (UC) mice based on adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. METHODS Male BALB/c mice were randomly divided into control group, model group, inhibitor group (AMPK inhibitor Compound C 20 mg/kg), paeoniflorin low-, medium- and high-dose groups (paeoniflorin 12.5, 25, 50 mg/kg), high- dose of paeoniflorin+inhibitor group (paeoniflorin 50 mg/kg+Compound C 20 mg/kg), with 8 mice in each group. Except for the control group, mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently, mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally, once a day, for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration, colon length, malondialdehyde (MDA) content, and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in colon tissues were measured; histopathological morphology of colon tissues, tight junctions between intestinal epithelial cells, and histopathological scoring were all observed and evaluated; the mRNA expressions of AMPK and Nrf2, as well as the protein expressions of heme oxygenase-1(HO-1), occludin and claudin-1, were all determined in colon tissue. RESULTS Compared with model group, paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue, as well as improved tight junction damage between intestinal epithelial cells. Additionally, significant increases or upregulations were observed in body weight, colon length, activities of SOD and GSH-Px, phosphorylation level of AMPK, and protein expression of Nrf2, HO-1, occludin, claudin-1, and mRNA expressions of AMPK and Nrf2; concurrently, MDA content and histopathological scores were significantly reduced (P< 0.05 or P<0.01). In contrast, the inhibitor group showed comparable (P>0.05) or worse (P<0.05 or P<0.01) indicators compared to the model group. Conversely, the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin (P<0.01). CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice, improve tight junctions between epithelial cells, upregulate the expression of related proteins, and promote the expression and secretion of antioxidant-promoting molecules, thereby ameliorating UC; its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.
3.Construction of Tax-PC/SDC/PVP-K30 micelles and their protective effect on alcoholic liver injury
Shi-yu ZHANG ; Jing-meng SUN ; Dong-dong LI ; Xin ZHANG ; Jia-hui ZHANG ; Wei-yu ZHANG
Acta Pharmaceutica Sinica 2025;60(2):488-497
Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by
4.Surveillance results of respiratory syncytial virus outbreaks in kindergarten and school in Shenzhen, 2017-2023
WANG Xin, FANG Shisong, WU Weihua, LIU Hui, SUN Ying, ZOU Xuan, TANG Xiujuan
Chinese Journal of School Health 2025;46(3):435-437
Objective:
To analyze respiratory syncytial virus(RSV) outbreaks surveillance results and the epidemiological characteristics in kindergarten and school in Shenzhen during 2017-2023 , so as to provide a scientific reference for control and prevention of RSV.
Methods:
Epidemiological data and surveillance results of RSV outbreaks in kindergarten and school from 2017 to 2023 were collected for descriptive analyses.
Results:
A total of 31 RSV outbreaks were identified in kindergarten and school in 2017-2023 in Shenzhen, 346 cases were reported, the average incidence rate was 22.02%. The most annual RSV outbreaks were reported in 2020 with 14 outbreaks, followed by 8 outbreaks in 2023. A total of 64.52% of RSV outbreaks were identified in kindergarten with rest occurring in primary school or middle school. The greatest monthly count of outbreak was 18 (58.06%) in September, followed by 3 outbreaks (9.68%) in March and October. A total of 244 swab samples were collected, 169 samples were positive for respiratory viruses, the positive rate was 69.26%, 121 samples were positive for RSV,from 31 respiratory syncytical virus outbreaks 57 and samples were positive for other respiratory viruses(9 samples were positive for two respiratory viruses). A toral of 14(45.16%) outbreaks are caused by RSV alone, 17 outbreaks (54.84%) were caused by RSV and other respiratory viruses.
Conclusions
Most RSV outbreaks in kindergarten and school are reported after 2020 in Shenzhen, most RSV outbreaks occur in kindergarten, peak seasons of RSV outbreaks are autumn and spring.
5.Effect of Yishen Tongluo Prescription on Sperm DNA Fragmentation Index and Sperm Mitochondrial Membrane Potential in Patients with Asymptomatic Idiopathic Asthenospermia Infertility
Gaoli HAO ; Xin HE ; Lipeng FAN ; Jianshe CHEN ; Xun LI ; Hui ZHANG ; Xiang CHEN ; Shuilin LYU ; Xiaojun FU ; Zixue SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):145-151
ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index (DFI) and sperm mitochondrial membrane potential (MMP) in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group (64 cases) and a control group (64 cases). The experimental group received Yishen Tongluo prescription, while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate, sperm progressive motility (PR), total sperm motility (PR+NP), sperm function (sperm tail hypotonic swelling rate, sperm acrosin activity), sperm DFI, and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study, and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study, including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% (9/61), higher than that in the control group at 6.67% (4/60), though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group (P<0.05). Compared with the results before treatment, sperm PR, PR + NP, sperm tail hypotonic swelling rate, sperm acrosin activity, sperm DFI, and sperm MMP were significantly improved in both groups after treatment (P<0.05), with greater improvements in the experimental group (P<0.05). However, there was no significant change in sperm concentration in either group after treatment. During the study, no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility, increase spouse pregnancy rate, enhance sperm function, and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.
6.Research Advance on Smartphone-based Visual Biosensor in Point-of-Care Testing
Xian-Xin XIANG ; Hua-Yue SUN ; Hui-Ning CHAI ; Kun YU ; Li-Jun QU ; Guang-Yao ZHANG ; Xue-Ji ZHANG
Chinese Journal of Analytical Chemistry 2024;52(2):145-156
Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.
7.Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum
Xin-yue HU ; Xiao-li DING ; Yue SUN ; Hui ZHANG ; Jing LI ; Cheng-gang LINAG
Acta Pharmaceutica Sinica 2024;59(1):188-197
The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.
8.A new pyrazine from Hypecoum erectum L.
Yun LIU ; Meng-ya HU ; Wen-jing ZHANG ; Yu-xin FAN ; Rui-wen XU ; Deng-hui ZHU ; Yan-jun SUN ; Wei-sheng FENG ; Hui CHEN
Acta Pharmaceutica Sinica 2024;59(1):183-187
Four pyrazines were isolated from the
9.Analysis of human metapneumovirus outbreaks in kindergartens and schools in Shenzhen, 2017-2023
WANG Xin, FANG Shisong, WU Weihua, LIU Hui, SUN Ying, ZOU Xuan, TANG Xiujuan
Chinese Journal of School Health 2024;45(12):1789-1791
Objective:
To analyze the monitoring results and characteristics of human metapneumovirus (HMPV) outbreaks in Shenzhen in kindergartens and schools during 2017-2023, so as to provide a evidence for prevention and control of respiratory diseases.
Methods:
Based on the epidemiological data and laboratory test results of HMPV outbreaks in kindergartens and schools of Shenzhen during 2017 to 2023, collected from the influenza monitoring network platform, Mann Kendall test was applied for trend analysis pf HMPV.
Results:
A total of 11 HMPV outbreaks were identified in kindergartens and schools from 2017 to 2023 for 128 cases with an average incidence rate of 26.61% in 2018. The most yearly HMPV outbreaks were reported in 2020 being 4 outbreaks, followed by 2 outbreaks in 2018. A total of 72.73% (8 outbreaks) of HMPV outbreaks were identified in kindergartens with 27.27% (3 outbreaks) occurring in primary schools. The monthly greatest count of outbreak was 3(27.27%) in March and December, followed by 2 outbreaks (18.18%) in April and June. A total of 98 swab samples were collected, and 80 samples were positive for respiratory viruses with a positive rate of 81.63%; among them, 67 samples were positive for HMPV alone, 10 samples were positive for other respiratory viruses alone, and 3 samples were positive both for HMPV and other respiratory virus. Among the 11 human metalung virus cases, 6 HMPV outbreaks were caused by human metapneumovirus alone, and 5 outbreaks were caused by HMPV and other respiratory viruses. Except for 2020, the percentage of HMPV outbreaks in influenza like illness outbreaks increased with year ( Z=2.25, P =0.02).
Conclusion
HMPV outbreaks have been reported every year from 2017 to 2023 in kindergartens and schools in Shenzhen, most of HMPV in kindergartens, and the peak seasons of HMPV outbreaks are spring and winter.
10.Assessment of respiratory protection competency of staff in healthcare facilities
Hui-Xue JIA ; Xi YAO ; Mei-Hua HU ; Bing-Li ZHANG ; Xin-Ying SUN ; Zi-Han LI ; Ming-Zhuo DENG ; Lian-He LU ; Jie LI ; Li-Hong SONG ; Jian-Yu LU ; Xue-Mei SONG ; Hang GAO ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(1):25-31
Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60%participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10%participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.


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