1.Natural products for the treatment of age-related macular degeneration:New insights focusing on mitochondrial quality control and cGAS/STING pathway
Xuelu XIE ; Shan LIAN ; Wenyong YANG ; Sheng HE ; Jingqiu HE ; Yuke WANG ; Yan ZENG ; Fang LU ; Jingwen JIANG
Journal of Pharmaceutical Analysis 2025;15(5):956-973
Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
2.Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway.
Xuelu XIE ; Shan LIAN ; Wenyong YANG ; Sheng HE ; Jingqiu HE ; Yuke WANG ; Yan ZENG ; Fang LU ; Jingwen JIANG
Journal of Pharmaceutical Analysis 2025;15(5):101145-101145
Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
3.Improving effect of astragalus polysaccharide on recurrent spontaneous abortion rats by regulating PI3K/AKT signaling pathway
Xuemei CHEN ; Yi YANG ; Jingqiu GUO ; Zhengyan ZHU
Chinese Journal of Immunology 2025;41(10):2348-2353
Objective:To investigate improvement effect of astragalus polysaccharides(APS)on recurrent spontaneous abor-tion(RSA)in rats and its mechanism.Methods:Pregnant rats were randomly grouped into control group,RSA group,dexamethasone group,APS low,medium,high doses groups and LY294002 group.A RSA rat model was constructed,uterine organ index and embryo loss rate were calculated.HE staining was applied to observe histopathology changes of decidua.ELISA was applied to detect serum levels of estradiol(E2),progesterone(P),prolactin(PRL),cytokines such as IFN-γ,TNF-α,IL-4 and IL-10.Immunohisto-chemistry was applied to detect expression of decidua progesterone receptor(PR).Western blot was applied to detect expression of PI3K/AKT signaling pathway proteins of decidua.Results:Compared with control group,desquamated cells of rats in RSA group exhibit edema,disordered arrangement,nuclear pyknosis and disappearance,and decidua reduced interstitial blood vessels,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously reduced,embryo loss rate,IFN-γ and TNF-α levels were obviously increased(P<0.05);compared with RSA group,morphology of decidual cells and interstitial blood vessels in dexamethasone group and APS low,medium and high doses groups were improved,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously increased,embryo loss rate,serum IFN-γ and TNF-α levels were obviously reduced(P<0.05);LY294002 reversed improvement effect of high-dose APS on adverse pregnancy out-comes in RSA rats(P<0.05).Conclusion:APS can reduce miscarriage rate of RSA rats,regulate Th1/Th2 balance,whose mecha-nism may be related to activation of PI3K/AKT.
4.Improving effect of astragalus polysaccharide on recurrent spontaneous abortion rats by regulating PI3K/AKT signaling pathway
Xuemei CHEN ; Yi YANG ; Jingqiu GUO ; Zhengyan ZHU
Chinese Journal of Immunology 2025;41(10):2348-2353
Objective:To investigate improvement effect of astragalus polysaccharides(APS)on recurrent spontaneous abor-tion(RSA)in rats and its mechanism.Methods:Pregnant rats were randomly grouped into control group,RSA group,dexamethasone group,APS low,medium,high doses groups and LY294002 group.A RSA rat model was constructed,uterine organ index and embryo loss rate were calculated.HE staining was applied to observe histopathology changes of decidua.ELISA was applied to detect serum levels of estradiol(E2),progesterone(P),prolactin(PRL),cytokines such as IFN-γ,TNF-α,IL-4 and IL-10.Immunohisto-chemistry was applied to detect expression of decidua progesterone receptor(PR).Western blot was applied to detect expression of PI3K/AKT signaling pathway proteins of decidua.Results:Compared with control group,desquamated cells of rats in RSA group exhibit edema,disordered arrangement,nuclear pyknosis and disappearance,and decidua reduced interstitial blood vessels,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously reduced,embryo loss rate,IFN-γ and TNF-α levels were obviously increased(P<0.05);compared with RSA group,morphology of decidual cells and interstitial blood vessels in dexamethasone group and APS low,medium and high doses groups were improved,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously increased,embryo loss rate,serum IFN-γ and TNF-α levels were obviously reduced(P<0.05);LY294002 reversed improvement effect of high-dose APS on adverse pregnancy out-comes in RSA rats(P<0.05).Conclusion:APS can reduce miscarriage rate of RSA rats,regulate Th1/Th2 balance,whose mecha-nism may be related to activation of PI3K/AKT.
5.DNA oxidative damage induced by natural pyrethrins in human liver cells
Yun YANG ; Mengchao YING ; Jingqiu SUN ; Yijie SHA ; Xinyu HONG ; Ping XIAO ; Gonghua TAO
Journal of Environmental and Occupational Medicine 2024;41(6):681-686
Background Natural pyrethrins have long been widely used in the fields of environmental and household hygiene. Studies have reported that natural pyrethrins have potential liver toxicity, but their specific mechanisms are still unclear yet. Objective To explore the effect of natural pyrethrins on DNA damage in human liver cells. Methods This study used human liver cell QSG7701 as an in vitro testing model. After exposure to DMSO and a series of concentrations of natural pyrethrins (5, 10, 20, and 40 μg·mL−1) for 6 and 24 h, reactive oxygen species (ROS) was detected by fluorescence microscopy using a fluorescence probe, thiobarbituric acid reactive substance (TBARS) by colorimetric method using a microplate reader, DNA damage by comet assay through observing DNA fragment migration under microscope, and phospho H2AX (γH2AX) and 8-oxoguanine (8-oxoG) by immunofluorescence assay using a laser confocal microscope. Results As the exposure concentration of natural pyrethrins increased, the fluorescence intensity of ROS significantly increased in a concentration-dependent manner. The differences in ROS between the 10 μg·mL−1 and above groups and the control group were statistically significant (P<0.01), and the ROS levels in the 20 μg·mL−1 and 40 μg·mL−1 treatment groups were 2.17 and 3.05 times higher than that in the control group respectively. The TBARS level increased in a concentration-dependent manner in natural pyrethrins treated cells (P<0.01), and the levels in the 20 μg·mL−1 and 40 μg·mL−1 treatment groups were 2.46 and 3.01 times higher than that in the control group respectively. The results of comet assay showed trailing formation of cellular DNA in each dose group; as the exposure concentration of natural pyrethrins increased, indicators such as tail DNA content (TDNA%), tail length (TL), tail moment (TM), and Olive tail moment (OTM) increased in a concentration-dependent manner. Compared with the control group, the differences in the indicators between the 20 μg·mL−1 and above groups and the control group were statistically significant (P<0.01), especially in the 40 μg·mL−1 treatment groups, where TDNA%, TL, TM, and OTM were (46.92 ± 3.52) %, (64.67± 4.16) μm, 30.96 ± 2.94, and 22.64 ± 3.89, respectively. The cellular immunofluorescence results showed that natural pyrethrins induced the formation of γH2AX and 8-oxoG, the fluorescence intensities of γH2AX and 8-oxoG increased in a concentration-dependent manner, and the differences between the 10 μg·mL−1 and above groups and the control group were statistically significant (P<0.01). Conclusion Natural pyrethrins could induce DNA damage in human liver cells, and ROS-mediated oxidative stress may play an important role in its liver cell genotoxicity.
6.The mediating effect of balanced time perspective between negative evaluation fear and mobile phone addiction among vocational school students
Hao ZHANG ; Jiaxin YANG ; Tianling ZHANG ; Jingqiu ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(5):431-435
Objective:To explore the relationship between negative evaluation fear and mobile phone addiction, and the mediating role of balanced time perspective.Methods:In April 2021, totally 1 158 secondary vocational school students were investigated by scales of fear of negative evaluation(FNE), mobile phone addiction index(MPAI)and Zimbardo time perspective inventory(ZTPI). The balanced time perspective was calculated by deviation from the balanced time perspective(DBTP). SPSS 20.0 statistical software was used for descriptive statistical analysis and correlation analysis of the data.Bootstrap method was used to test the mediating effect.Results:(1) Negative evaluation fear(37.87±7.71)was significantly positively correlated with balanced time perspective(4.50±0.75)( r= 0.379, P<0.01) and mobile phone addiction(46.11±11.92)( r=0.437, P<0.01). The balanced time perspective was significantly positively correlated with mobile phone addiction( r=0.475, P<0.01). (2) Negative evaluation fear directly and positively predicted mobile phone addiction( β=0.300, 95% CI=0.248-0.352). The balanced time perspective played a partial mediating role between negative evaluation fear and mobile phone addiction, and the mediating effect value was 0.137, accounted for 31.31%(0.137/0.437) of the total effect. Conclusion:The fear of negative evaluation can directly affect the mobile phone addiction behavior of secondary vocational students, and can also indirectly affect the mobile phone addiction by affecting the balanced time perspective.Good balanced time perspective can reduce the risk caused by the fear of negative evaluation.
7.Comparison on Skin Permeability of Corydalis Rhizoma Total Alkaloid Patches at Shenque Acupoint and Non-acupoint Administration
Mingrui JIANG ; Zhicheng WANG ; Zhuzhu YUE ; Jingqiu ZHANG ; Peihua WANG ; Guimei ZHANG ; Huinan WANG ; Ziye YANG ; Mengyu CHEN ; Yingzi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(19):148-153
ObjectiveTo compare the differences in resistance and structure of skin between acupoints and non-acupoints, and to study the difference in skin permeability characteristics of Corydalis Rhizoma total alkaloid patches (CTTP) after administration at Shenque acupoint and non-acupoint, so as to provide experimental support for its clinical acupoint application to prevent and treat chronic pain. MethodTaking corydaline (CD), tetrahydropalmatine (THP) and corydalis L (CDL) as evaluation indexes, and the quantitative analysis was carried out by high performance liquid chromatography (HPLC). The mobile phase was methanol-0.04 mol·L-1 phosphoric acid aqueous solution (70∶30, pH 6.0 adjusted with triethylamine), the detection wavelength was 281 nm. In vitro transdermal test in Franz diffusion cell and in vivo transdermal test were used to study the skin permeability characteristics of CTTP through Shenque acupoint and non-acupoint administration. At the same time, the skin resistance between Shenque acupoint and non-acupoint was measured before and after the administration, and the distribution of the drug in each layer of the skin was compared by freezing sectioning, and visual verification was performed with fluorescence inverted microscope. ResultAfter 24 h of administration, the results of in vivo and in vitro experiments showed that the cumulative permeation and retention of CD, THP and CDL at Shenque acupoint skin were higher than those at non-acupoint skin (P<0.05, P<0.01), the skin resistance of Shenque acupoint was lower than that of non-acupoint at all time points. The fluorescence microscopic observation results showed that the drug content of each layer of the skin was all Shenque acupoint>non-acupoint, indicating that the skin of Shenque acupoint had better effect on drug penetration and storage than non-acupoint. ConclusionThe 24 h cumulative permeation and retention of CTTP in Shenque acupoint skin are higher than those in non-acupoint skin, and the mechanism may be related to the thin skin, low electrical resistance and large number of hair follicle bodies at Shenque acupoint.
8.A comparison of 20-MHz and 50-MHz ultrasonography in imaging and measuring the skin
Menglong RAN ; Dehua LIU ; Jingqiu ZHANG ; Ping TU ; Shuxia YANG ; Hang LI
Chinese Journal of Dermatology 2017;50(7):482-486
Objective To investigate imaging characteristics of human skin in different sites by using 20-MHz and 50-MHz high-frequency ultrasonography,and to compare the reliability of skin thickness measurement by the above two approaches of ultrasonography.Methods A total of 39 healthy volunteers aged 18-39 years were enrolled into this study.Then,20-MHz and 50-MHz ultrasonography were separately performed to image 20 different sites on the body,and the thickness of the epidermis and dermis were measured and evaluated by 3 dermatologists independently.The ultrasonic images were analyzed,and the intraclass correlation coefficient (ICC) was used to assess and compare the reliability of skin thickness measurement by 20-MHz and 50-MHz ultrasound.Results The ICC values were less than or close to 0.7 in epidermal thickness measurement at almost all the tested sites between 20-MHz and 50-MHz ultrasonography,suggesting poor reliability.However,20-MHz and 50-MHz ultrasonography showed excellent reliability in dermal thickness measurement with the ICC greater than 0.75 at almost all the tested smooth and flat body sites.The 20-MHz ultrasound could provide clear images of the dermis and subcutaneous tissue,while 50-MHz ultrasound could only provide clearer images of the dermis in details.In some uneven sites with complex anatomical structures,20-MHz and 50-MHz ultrasound probes had their own advantages and disadvantages in imaging depth and detail resolution.Conclusions The 20-MHz and 50-MHz ultrasono-graphy both can serve as non-invasive imaging techniques to show structures of the epidermis and dermis better.In different parts of human body,ultrasound frequencies should be selected according to their imaging characteristics.
9.Real-time shear wave elastography in evaluation of elasticity of gastrocnemius muscle in patients with lumbar disc herniation
Lintong SONG ; Jing DU ; Yongping LU ; Jingqiu ZHANG ; Hanning YANG
Chinese Journal of Medical Imaging Technology 2017;33(11):1696-1699
Objective To explore the value of real-time shear wave elastography in evaluating gastrocnemius muscle elasticity in patients with lumbar disc herniation.Methods One hundred patients with clinically diagnosed unilateral lumbar disc herniation were selected.Selective nerve root block combined with ozone ablation and pulsed radiofrequency therapy via the lateral crypt was performed.The real-time shear wave elastography was applied to detect the mean elastic modulus (Mean) and the maximum elastic modulus (Max) of bilateral tense gastrocnemius muslcs (kPa) before and after treatment.Statistical analysis was done.Results The EMean and EMax values of ipsilateral tension in gastrocnemius muscle before treatment were (11.28±2.60)kPa and (15.26±2.63)kPa,lower than those of contralateral (EMean:[16.284-5.25]kPa,EMax:[21.13±6.62]kPa;t=78.241,64.634,both P<0.001).The EMean and EMax values of ipsilateral tension in gastrocnemius muscle after treatment were (13.18±2.38)kPa and (17.63± 2.73)kPa,higher than those before treatment (t=6.407,14.815,both P<0.001).In different strength condition,EMean and EMax of gastrocnemius muscle before and after treatment were statistically significant (all P<0.001).With the myodynamia increasing,EMean and EMax also increased before and after treatment.The differences between patients with any two different myodynamia were statistically different (all P<0.05).Conclusion The muscle tissue recovery can be evaluated quantitatively by detecting EMean and EMax of tense gastrocnemius in patients with lumbar disc herniation using real-time shear wave elastography before and after treatment.
10.In vivo biocompatibility of whole-kidney acellular matrix scaffolds prepared by perfusion method
Jie CHEN ; Jingqiu YANG ; Chunxiao LIU
Chinese Journal of Tissue Engineering Research 2015;19(16):2529-2533
BACKGROUND:The whole-kidney acelular matrix scaffold in rats prepared by perfusion method is proved to have goodin vitro biocompatibility, butin vivo biocompatibility is stil unclear. OBJECTIVE:To produce a whole-kidney acelular matrix scaffold in rats by perfusion method and to evaluate the in vivo biocompatibility of the scaffold. METHODS:The whole-kidney acelular matrix scaffold in Wistar rats was prepared by perfusion method and evaluated with the folowing tests. (1) Acute toxicity test: mice were subject to intraperitoneal injection of whole-kidney acelular matrix scaffold extract liquid, normal saline and phenol. (2) Hemolytic test: Anticoagulant blood samples from New Zealand rabbits were mixed with whole-kidney acelular matrix scaffold extract liquid, normal saline and distiled water, respectively. (3) Pyrogen test: Whole-kidney acelular matrix scaffold extract liquid was injected into the ear vein of New Zealand rabbits. (4) Intracutaneous stimulation test: Whole-kidney acelular matrix scaffold extract liquid was injected subcutaneously into New Zealand rabbits for observing whether there was a skin stimulus response. (5) Subcutaneous implantation test: The whole-kidney acelular matrix scaffold was implanted subcutaneously into the back of New Zealand rabbits. RESULTS AND CONCLUSION:There was no cel residual in the whole-kidney acelular matrix scaffold preparedby perfusion method, and no acute systemic toxicity, hemolytic reaction, pyrogen response, and skin stimulus respons, indicating the scaffold has a good histocompatibility in the rabbits. These findings suggest that the whole-kidney acelular matrix scaffolds in Wistar rats prepared by perfusion method have goodin vivo biocompatibility.

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