1.Interplay Between Interferon Stimulatory Pathways and Organellar Dynamics
Jin-Ru LI ; Yu DUAN ; Xin-Gui DAI ; Yong-Ming YAO
Progress in Biochemistry and Biophysics 2025;52(7):1708-1727
Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.
2.Research progress on impacts of air pollutants, gut microbiota, and seminal microbiota on semen quality
Wenchao XIA ; Jiahua SUN ; Yuya JIN ; Ruixin LUO ; Ruyan YAN ; Yuming GUI ; Yongbin WANG ; Fengquan ZHANG ; Wei WU ; Weidong WU ; Huijun LI
Journal of Environmental and Occupational Medicine 2025;42(8):1003-1008
In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.
3.Clinical trial of bevacizumab combined with paclitaxel and carboplatin in the treatment patients with of recurrent/metastatic cervical cancer
Yang XIANG ; Jin-Long CAO ; Gui-Mei NIE ; Ying LI ; Yan-Ying SUN ; Shu WANG ; Ping-Rong XIE
The Chinese Journal of Clinical Pharmacology 2024;40(8):1121-1125
Objective To analyze the efficacy of bevacizumab combined with paclitaxel+carboplatin in the treatment of recurrent/metastatic cervical cancer,and to explore the influence on survival prognosis of patients.Methods Patients with recurrent/metastatic cervical cancer were divided into control group and treatment group according to different treatment methods.The control group received paclitaxel combined with carboplatin chemotherapy regimen(intravenous infusion of 170 mg·m-2 paclitaxel and carboplatin(AUC=5 mg·mL-1·min)for 3 weeks as a course of chemotherapy),and the treatment group was given bevacizumab on the basis of control group,intravenous infusion of 15 mg·kg-1 bevacizumab,once every 3 weeks.Both groups were treated for 3 cycles of treatment by taking 3 weeks as 1 treatment cycle.The clinical efficacy,levels of serum tumor markers,quality of life,survival prognosis and occurrence of drug-related adverse reactions during treatment were compared between the two groups.Results There were 41 cases in treatment group and 48 cases in control group.After treatment,the overall response rate(ORR)of treatment group and control group were 31.71%(13 cases/41 cases)and 14.58%(7 cases/48 cases),with no statistical significance(P>0.05).After treatment,the disease control rate(DCR)in control group and treatment group were 62.50%(30 cases/48 cases)and 82.93%(34 cases/41 cases);the squamous cell carcinoma antigen(SCCA)levels were(3.58±0.73)and(2.52±0.57)ng·mL-1;carbohydrate antigen 19-9(CA19-9)levels were(23.60±4.29)and(19.19±3.72)U·mL-1;carbohydrate antigen 15-3(CA15-3)levels were(27.13±5.36)and(22.86±3.94)U·mL-1;carbohydrate antigen 125(CA125)levels were(39.24±6.88)and(26.47±5.09)U·mL-1;the overall improvement rates of quality of life were 41.67%(20 cases/48 cases)and 73.17%(30 cases/41 cases),the progression-free survival times were 8.67 months(95%CI:7.82-9.53)and 10.25 months(95%CI:9.68-10.81),the total survival times were 9.96 months(95%CI:9.13-10.79)and 11.47 months(95%CI:11.00-11.93),all with significant difference(all P<0.05).There were no statistically significant differences in the incidence of nausea and vomiting,leukopenia,thrombocytopenia and liver-kidney function impairment between both groups(all P>0.05).Conclusion Bevacizumab combined with chemotherapy has significant efficacy in the treatment of recurrent/metastatic cervical cancer,and it can reduce the levels of serum tumor markers,enhance the quality of life,and improve the survival prognosis,and it has good safety.
4.Inhibitory effect of miR-133a on liver cancer through tar-geted regulation of G6PD expression
Ya-Dong WANG ; Xue-Jun SUN ; Chun-Yu YANG ; Gui-Ping WANG ; Ming JIN ; He LI ; Jia-Jun YIN
Chinese Journal of Current Advances in General Surgery 2024;27(1):25-29
Objective:To explore if miR-133a is involved in the occurrence and development of hepatocellular carcinoma(HCC)via regulating G6PD.Methods:Bioinformatics analysis predicted the binding sites of miR-133a and G6PD;RT-PCR or western blot was used to assess the expres-sion of miR-133a and G6PD in HCC tissues and the adjacent normal tissues;CCK-8 and flow cy-tometry assays were performed to evaluate the effects of miR-133a/G6PD on cell proliferation,apop-tosis;Fluorescent reporter gene and western blot assays were used to assess the effect of miR-133a on G6PD expression.Results:miR-133a expression was decreased in HCC tissues while G6PD was increased(P0.01);Up-regulation of miR-133a significantly reduced G6PD expression(P<0.01);up-reg-ulation of miR-133a inhibited cell growth and promoted cell apoptosis(P<0.05),whereas these effects induced by miR-133a over-expression were all abolished when G6PD was up-regulated(P<0.01).Conclusion:miR-133a represses the occurrence and development of HCC via targeting G6PD.
5.Correlation of CD200-CD200R axis and diseases and its research progress
Han XU ; Yu-xin BI ; Gui-xia LI ; Jian LI ; Liu-li WANG ; Rui-jia HAO ; Xue-min ZHENG ; Rui-jing HUANG ; Jin HAN ; Fei LI ; Gen-bei WANG
Acta Pharmaceutica Sinica 2024;59(4):822-830
CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.
6.Protective effects of cinnamaldehyde on benzene-induced immune and oxidative stress injury in mice
Mengyang LI ; Gui WANG ; Yamei QIAO ; Pingyu WANG ; Min JIN ; Dong YANG ; Junwen LI
Military Medical Sciences 2024;48(1):44-51
Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.
7.Study on clinical effect of reversely opening anterior circulation tandem lesions under protection of distal stents
Gui TONG ; Zhiqiang WANG ; Jin FAN ; Xi LI
Chongqing Medicine 2024;53(16):2467-2471
Objective To investigate the safety and efficacy of the surgical strategy of reversely opening under the protection of distal thrombectomy stent on anterior circulation tandem lesions.Methods A total of 42 patients with acute ischemic stroke with anterior circulation tandem lesions receiving opening surgery from January 2018 to December 2023 were selected as the study subjects.According to the surgical strategy,the pa-tients were divided into the observation group (n=23,adopting the distant stent protection) and the control group (n=19,adopting the protective umbrella protection).The intraoperative thrombus escape rate,inci-dence rate of 24 h symptomatic intracranial hemorrhage (SICH),successful opening rate,total operation time,good prognosis rate and mortality rate on postoperative 90 d were compared between the two groups. Results All patients in the both groups were successfully opened,and the opening rate was 100%.There were no statistically significant differences in the 90 d good prognosis rate and mortality rate,SICH incidence rate at postoperative 24 h and total operation duration between the both groups (P>0.05).The thrombus distal end escape rate in the observation group was lower than that in the control group with statistically significant difference (4.3% vs. 26.3%,P=0.043).Conclusion In the opening operation of anterior circulation tandem lesions,adopting the reverse opening surgical strategy under the distal stents protection has a lower thrombus escape rate,which is comparable to that of reverse opening under the traditional carotid artery protective um-brella in the aspects of effect and safety.
8.Clinical trial of N-acetylcysteine in the treatment of children with respiratory tract infection
Jin-Tao SONG ; Yong ZHAO ; Hong-Chen DAI ; Gui-Tao LI
The Chinese Journal of Clinical Pharmacology 2024;40(20):2915-2919
Objective To observe the application effect of N-acetylcysteine in children with respiratory tract infection.Methods According to random number table method,children with respiratory tract infection were divided into control group and treatment group.The control group was given intravenous injection of ceftazidime(30-100 mg·kg-1,q12 h)on basis of routine symptomatic treatment,while treatment group was given aerosol inhalation of N-acetylcysteine solution(0.3 g∶3 mL,qd)on basis of control group.All patients were treated for 7 d.The clinical curative effect,remission time of symptoms,changes of chest X-ray,lung function[forced expiratory volume in 1 second(FEV1),tidal volume(VT),peak expiratory flow(PEF)],serum inflammatory factors,immune function and adverse drug reactions in the two groups were compared.Results In the trial,there were 28 cases excluded due to shedding and loss of follow-up,and there were 40 cases in treatment group and 52 cases in control group,respectively.After treatment,total clinical response rates in treatment group and control group were 92.50%(37 cases/40 cases)and 76.92%(40 cases/52 cases),the difference was statistically significant(P<0.05).After treatment,disappearance time of fever in treatment group and control group were(2.96±0.65)and(4.83±0.81)d;remission time of cough were(5.58±1.08)and(7.45±1.24)d;remission time of asthma were(3.23±0.54)and(4.72±0.75)d;disappearance time of lung rales were(4.66±0.72)and(5.94±0.87)d;FEV1 were(2.26±0.25)and(1.79±0.21)L;VT were(13.76±1.32)and(10.27±1.17)mL·kg-1;PEF were(5.78±0.68)%and(4.92±0.62)%;levels of serum C-reactive protein(CRP)were(7.68±1.18)and(9.41±1.29)mg·L-1;levels of interleukin-6(IL-6)were(18.76±3.24)and(22.75±3.85)ng·mL-1;levels of tumor necrosis factor α(TNF-α)were(8.93±1.51)and(15.46±2.24)ng·mL-1;CD4+/CD8+were 1.35±0.29 and 1.20±0.30.There were statistically significant differences in the above indexes between the treatment group and the control group(all P<0.05).In treatment group,there were 3 cases with nausea,1 case with vomiting and 1 case with diarrhea.In control group,there were 3 cases with vomiting and 2 cases with diarrhea.There was no significant difference in incidence of adverse drug reactions between treatment group and control group[12.50%(5 cases/40 cases)vs 9.62%(5 cases/52 cases),P>0.05].Conclusion Curative effect of N-acetylcysteine combined with ceftazidime is significant in children with respiratory tract infection,which can effectively improve lung function,relieve airway inflammation and enhance immune function,with good safety.
9.Clinical trial of parecoxib sodium combined with dexmedetomidine for surgery in patients with osteoporotic compression fractures
Kai LUO ; Qing WANG ; Gao-Ju WANG ; Jin YANG ; Guang-Zhou LI ; Shi-Jie SONG ; Shun-Gui CAI
The Chinese Journal of Clinical Pharmacology 2024;40(20):2963-2967
Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P<0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82%and 9.76%,without statistically significant difference(P>0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.
10.Morphological classification and molecular identification of Hyalomma asiaticum in parts of Xindi Township,Xinjiang
Xiao-Qing ZAN ; Qiao-Yun REN ; Jin LUO ; Yan-Long WANG ; Pei-Wen DIAO ; Li-Yan CHE ; Jian-Xun LUO ; Hong YIN ; Gui-Quan GUAN ; Guang-Yuan LIU ; Hong-Xi ZHAO
Chinese Journal of Zoonoses 2024;40(4):289-294
The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

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