1.miR-207 targets autophagy-associated protein LAMP2 to regulate the mechanism of macrophage-mycobacterium tuberculosis interaction.
Wenya DU ; Yumei DAI ; Linzhi YUE ; Tao MA ; Lixian WU
Chinese Journal of Cellular and Molecular Immunology 2025;41(2):97-104
Objectives miR-207 has been identified as being expressed in natural killer (NK) cell exosomes that play a role in disease progression; however, to date, there are no studies specifically linking miR-207 to tuberculosis (TB). Methods Bioinformatics methods employed for prediction, followed by a dual luciferase reporter assay to determine whether lysosome-associated membrane protein 2 (LAMP2) is targeted by miR-207. The experiments were divided into four groups using the liposome transfection method (OP-LAMP2 group: co-transfected with miR-207 mimics and LAMP2 overexpression plasmid; EP group: co-transfected with mimics NC and null-loaded plasmid; siLAMP2 group: transfected with siLAMP2; and siLAMP2-NC group: transfected with siLAMP2-NC). TB infection was modeled using H37Ra-infected Ana-1 cells. The impact of LAMP2 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria were assessed by tuberculosis colony-forming unit counting. Flow cytometry was used to assess the total apoptosis rate. Real-time fluorescent quantitative PCR was conducted to determine the relative expression of LAMP2, apoptosis genes, pyroptosis genes, and autophagy genes. Western blot analysis was performed to measure the relative expression of LAMP2 proteins, apoptosis proteins, pyroptosis proteins, and autophagy proteins. Results Dual luciferase reporter assay test showed that there was a targeting relationship between LAMP2 and miR-207. The transfection model was successfully constructed under real-time fluorescent quantitative PCR and Western blot statistical analysis, and microscopic observation. The infection model was successfully established under microscopic observation. Colony forming unit counting revealed that the number of colonies in the OP-LAMP2 group was lower than that in the EP group, while the number of colonies in the siLAMP2 group was higher than that in the siLAMP2-NC group. Flow cytometry assay revealed that the total apoptosis in OP-LAMP2 group was lower than that in EP group, and the total apoptosis in siLAMP2 group was higher than that in siLAMP2-NC group. Real-time fluorescence quantitative PCR and Western blot analysis revealed that the relative expression of apoptosis and pyroptosis-related proteins and genes in the control group was lower in the OP-LAMP2 group compared to the EP group, and higher in the siLAMP2 group compared to the siLAMP2-NC group. Real-time fluorescence quantitative PCR detected that the relative expression of autophagy positively regulated genes Microtubule-associated protein 1 light chain 3(LC3)and Beclin1 in the OP-LAMP2 group was higher in the OP-LAMP2 group compared to the EP group, and lower in the siLAMP2 group compared to the siLAMP2-NC group, while the relative expression of negatively regulated autophagy genes followed the opposite trend to that of autophagy positively regulated genes. The relative expression of autophagy-related proteins was consistent with the trend of autophagy genes. Conclusions miR-207 enhances macrophage apoptosis, cellular pyroptosis and inhibits autophagy, promoting survival of Mycobacterium tuberculosis by targeting the autophagy-related protein LAMP2, thus offering a novel therapeutic direction for tuberculosis.
Lysosomal-Associated Membrane Protein 2/metabolism*
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MicroRNAs/metabolism*
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Mycobacterium tuberculosis/physiology*
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Autophagy/genetics*
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Humans
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Macrophages/metabolism*
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Apoptosis/genetics*
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Tuberculosis/metabolism*
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Cell Line
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Pyroptosis/genetics*
2.Advances in the study of exosomes derived from mesenchymal stem cells in the treatment of pulmonary diseases.
Tao MA ; Linzhi YUE ; Yumei DAI ; Wenya DU ; Lixian WU
Chinese Journal of Cellular and Molecular Immunology 2025;41(3):278-282
Pulmonary diseases, as a prevalent category of respiratory system disorders, have become a significant global public health concern. The increasing incidence of these diseases, caused by environmental pollution and occupational hazards, poses a substantial threat to human health and the overall quality of life. Mesenchymal stem cells (MSCs) are known for their remarkable immunomodulatory, anti-bacterial, and anti-apoptotic capabilities. Exosomes derived from MSCs, carrying a diverse array of proteins, lipids, nucleic acids, and other bio-active molecules, have demonstrated considerable therapeutic potential in treating pulmonary diseases, and have come to the forefront of medical research. This review summarized the therapeutic role of exosomes derived from various sources of mesenchymal stem cells in the context of pulmonary diseases, aiming to provide a robust foundation for their clinical application in diagnosis and treatment.
Exosomes/transplantation*
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Humans
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Mesenchymal Stem Cells/metabolism*
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Lung Diseases/therapy*
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Animals
3.Association of sperm aneuploidy with unexplained spontaneous recurrent abortion
Jie YANG ; Weiyi WU ; Linzhi MA ; Ruyue LIU ; Qinli MA ; Zhou ZHANG
Chinese Journal of Clinical Laboratory Science 2025;43(6):423-427
Objective To investigate the correlation of sperm aneuploidy with unexplained recurrent spontaneous abortion(URSA).Methods Thirty-four male partners of couples diagnosed with URSA in the Center of Reproductive Medicine of Northwest Women's and Children's Hospital from November 2021 to December 2023 were enrolled as the experimental group,after excluding chromosomal structural or numerical abnormalities in either partner of the couples,female age≥37 years,and other known female-related causes of miscarriage.Meanwhile,30 men,who had given birth to healthy children,or were infertile only due to female factors and had normal semen parameters,were selected as control group.Fluorescence in situ hybridization(FISH)was used to detect sperm aneuploidy after routine semen analysis for the males of the two groups.Results There were no significant differences in male age,semen volume,sperm concentration,percentage of progressively motile sperm,and percentage of sperm with normal morphology between the two groups(all P>0.05).However,in the experimental group,the total nullisomy rate(2.10±1.93)% versus(0.54±0.27)%,total dip-loidy rate(0.25±0.27)% versus(0.05±0.05)%,and disomy rate of chromosome 18(0.77±1.15)% versus(0.18±0.21)%,sex chromosomes(2.79±2.38)% versus(0.78±0.52)%,chromosome 13(0.79±0.99)% versus(0.21±0.22)%,and chromosome 21(1.24±1.68)% versus(0.22±0.19)% were significantly higher than those in the control group(P<0.05).When the the mean aneu-ploidy rate in the control group(x+2s)was set as the upper limit of the normal reference value,the proportions of disomy rates of chro-mosomes 18,13,21 and sex chromosomes,as well as the total diploidy rate exceeding the threshold in the experimental group were 41.18%,35.29%,41.18%,55.88%,and 47.06%,respectively,with the proportion of abnormal disomy rate of sex chromosomes be-ing the highest.Conclusion The aneuploidy rate of sperm may be a related factor leading to unexplained recurrent spontaneous abor-tion in females,which has certain clinical significance for the assessment of male fertility and the diagnosis of male infertility.
4.Association of sperm aneuploidy with unexplained spontaneous recurrent abortion
Jie YANG ; Weiyi WU ; Linzhi MA ; Ruyue LIU ; Qinli MA ; Zhou ZHANG
Chinese Journal of Clinical Laboratory Science 2025;43(6):423-427
Objective To investigate the correlation of sperm aneuploidy with unexplained recurrent spontaneous abortion(URSA).Methods Thirty-four male partners of couples diagnosed with URSA in the Center of Reproductive Medicine of Northwest Women's and Children's Hospital from November 2021 to December 2023 were enrolled as the experimental group,after excluding chromosomal structural or numerical abnormalities in either partner of the couples,female age≥37 years,and other known female-related causes of miscarriage.Meanwhile,30 men,who had given birth to healthy children,or were infertile only due to female factors and had normal semen parameters,were selected as control group.Fluorescence in situ hybridization(FISH)was used to detect sperm aneuploidy after routine semen analysis for the males of the two groups.Results There were no significant differences in male age,semen volume,sperm concentration,percentage of progressively motile sperm,and percentage of sperm with normal morphology between the two groups(all P>0.05).However,in the experimental group,the total nullisomy rate(2.10±1.93)% versus(0.54±0.27)%,total dip-loidy rate(0.25±0.27)% versus(0.05±0.05)%,and disomy rate of chromosome 18(0.77±1.15)% versus(0.18±0.21)%,sex chromosomes(2.79±2.38)% versus(0.78±0.52)%,chromosome 13(0.79±0.99)% versus(0.21±0.22)%,and chromosome 21(1.24±1.68)% versus(0.22±0.19)% were significantly higher than those in the control group(P<0.05).When the the mean aneu-ploidy rate in the control group(x+2s)was set as the upper limit of the normal reference value,the proportions of disomy rates of chro-mosomes 18,13,21 and sex chromosomes,as well as the total diploidy rate exceeding the threshold in the experimental group were 41.18%,35.29%,41.18%,55.88%,and 47.06%,respectively,with the proportion of abnormal disomy rate of sex chromosomes be-ing the highest.Conclusion The aneuploidy rate of sperm may be a related factor leading to unexplained recurrent spontaneous abor-tion in females,which has certain clinical significance for the assessment of male fertility and the diagnosis of male infertility.
5.Research progress on the role of ferroptosis in infectious diseases
Linzhi YUE ; Tao MA ; Yumei DAI ; Wenya DU ; Guofu WANG ; Lixian WU
Chinese Journal of Comparative Medicine 2024;34(7):175-180
Ferroptosis is a newly discovered mode of programmed cell death characterized by the accumulation of intracellular iron-dependent lipid peroxidation.Current research has mainly focused on the role of ferroptosis in the field of cancer,but increasing evidence shows that ferroptosis is also related to the occurrence of infectious diseases.Ferroptosis has accordingly been detected in cases of COVID-19,tuberculosis,and cryptococcal meningitis,as well as other diseases.This article reviews the role of ferroptosis in infectious diseases,to provide new ideas for the prevention and treatment of ferroptosis-related infectious diseases.
6.Mechanistic study of miR-207 regulation of Mycobacterium tuberculosis survival in macrophages
Wenya DU ; Yumei DAI ; Linzhi YUE ; Tao MA ; Lixian WU
Chinese Journal of Comparative Medicine 2024;34(12):41-49
Objective miR-207 is differentially expressed in many diseases.We investigated the mechanism by which miR-207 overexpression regulates the survival of Mycobacterium tuberculosis(H37Ra)in macrophages,to provide a theoretical basis for the targeted therapy of tuberculosis.Methods Macrophages were divided into four groups:blank(Ana-1 cells),control(cells infected with H37Ra),mi(infected with H37Ra and transfected with miRNA-207 mimics),and mi-NC(infected with H37Ra and transfected with NC mimics)groups.A model of tuberculosis infection was established using H37Ra-infected Ana-1 cells,and miRNA-207 and NC mimics were transfected into Ana-1 cells using the liposome transfection method.Tuberculosis colony-forming units were counted to assess the effect of miR-207 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria.The total apoptosis rate was detected by flow cytometry.The relative expression levels of miR-207 and apoptosis,pyroptosis,inflammation,and autophagy genes were measured by quantitative real-time polymerase chain reaction(qPCR).Relative expression levels of apoptosis,pyroptosis,and autophagy proteins were detected by Western blot.Fluorescence microscopy and multifunctional enzyme labeling were used to detect the fluorescence intensity of intracellular reactive oxygen species(ROS)and lactate dehydrogenase(LDH).Results Successful establishment of the infection model was observed under the microscope.qPCR showed that miR-207 expression was lower in the control compared with the blank group(P<0.01),indicating differential expression between these two groups.miR-207 expression was significantly higher in the mi compared with the mi-NC group(P<0.0001),indicating successful establishment of the transfection model.The number of colonies and total apoptosis were both higher in the mi group compared with the mi-NC and control groups(P<0.001).qPCR and Western blot showed that the relative expression levels of apoptotic genes and proteins were higher in the control group than in the blank group(P<0.05),and higher in the mi group than in the mi-NC group(P<0.05).The relative expression levels of inflammatory genes were higher in the control than in the blank group(P<0.001).The relative expression levels of inflammatory genes were higher in the mi group than in the mi-NC group(P<0.05),and the relative expression levels of pyroptosis genes and proteins were higher in the control group compared with the blank group(P<0.01)and higher in the mi group compared with the mi-NC group(P<0.05).The relative expression levels of the autophagy positively-regulated genes LC3 and Beclin1 were higher in the control compared with the blank group(P<0.0001),and lower in the mi than in the mi-NC group(P<0.05),while negatively-regulated autophagy genes showed the opposite trend.Autophagy-related proteins showed similar trends to the autophagy genes.ROS fluorescence intensity was higher in the control compared with the blank group(P<0.05),and higher in the mi compared with the mi-NC group(P<0.001).LDH content was higher in the control than in the blank group(P<0.01),but there was no significant difference between the mi and mi-NC groups(P>0.05).Conclusions miR-207 overexpression promotes apoptosis,cellular pyroptosis,and inflammation,inhibits autophagy,and favors H37Ra survival.These result provide a potential new direction for the treatment of tuberculosis.
7.Mechanistic study of miR-207 regulation of Mycobacterium tuberculosis survival in macrophages
Wenya DU ; Yumei DAI ; Linzhi YUE ; Tao MA ; Lixian WU
Chinese Journal of Comparative Medicine 2024;34(12):41-49
Objective miR-207 is differentially expressed in many diseases.We investigated the mechanism by which miR-207 overexpression regulates the survival of Mycobacterium tuberculosis(H37Ra)in macrophages,to provide a theoretical basis for the targeted therapy of tuberculosis.Methods Macrophages were divided into four groups:blank(Ana-1 cells),control(cells infected with H37Ra),mi(infected with H37Ra and transfected with miRNA-207 mimics),and mi-NC(infected with H37Ra and transfected with NC mimics)groups.A model of tuberculosis infection was established using H37Ra-infected Ana-1 cells,and miRNA-207 and NC mimics were transfected into Ana-1 cells using the liposome transfection method.Tuberculosis colony-forming units were counted to assess the effect of miR-207 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria.The total apoptosis rate was detected by flow cytometry.The relative expression levels of miR-207 and apoptosis,pyroptosis,inflammation,and autophagy genes were measured by quantitative real-time polymerase chain reaction(qPCR).Relative expression levels of apoptosis,pyroptosis,and autophagy proteins were detected by Western blot.Fluorescence microscopy and multifunctional enzyme labeling were used to detect the fluorescence intensity of intracellular reactive oxygen species(ROS)and lactate dehydrogenase(LDH).Results Successful establishment of the infection model was observed under the microscope.qPCR showed that miR-207 expression was lower in the control compared with the blank group(P<0.01),indicating differential expression between these two groups.miR-207 expression was significantly higher in the mi compared with the mi-NC group(P<0.0001),indicating successful establishment of the transfection model.The number of colonies and total apoptosis were both higher in the mi group compared with the mi-NC and control groups(P<0.001).qPCR and Western blot showed that the relative expression levels of apoptotic genes and proteins were higher in the control group than in the blank group(P<0.05),and higher in the mi group than in the mi-NC group(P<0.05).The relative expression levels of inflammatory genes were higher in the control than in the blank group(P<0.001).The relative expression levels of inflammatory genes were higher in the mi group than in the mi-NC group(P<0.05),and the relative expression levels of pyroptosis genes and proteins were higher in the control group compared with the blank group(P<0.01)and higher in the mi group compared with the mi-NC group(P<0.05).The relative expression levels of the autophagy positively-regulated genes LC3 and Beclin1 were higher in the control compared with the blank group(P<0.0001),and lower in the mi than in the mi-NC group(P<0.05),while negatively-regulated autophagy genes showed the opposite trend.Autophagy-related proteins showed similar trends to the autophagy genes.ROS fluorescence intensity was higher in the control compared with the blank group(P<0.05),and higher in the mi compared with the mi-NC group(P<0.001).LDH content was higher in the control than in the blank group(P<0.01),but there was no significant difference between the mi and mi-NC groups(P>0.05).Conclusions miR-207 overexpression promotes apoptosis,cellular pyroptosis,and inflammation,inhibits autophagy,and favors H37Ra survival.These result provide a potential new direction for the treatment of tuberculosis.
8.The relationship between triglyceride glucose index and risk of cardiovascular disease among Kazakh and Uygur population in Xinjiang: a retrospective cohort analysis
Linzhi YU ; Rulin MA ; Xianghui ZHANG ; Jia HE ; Heng GUO ; Yunhua HU ; Xinping WANG ; Lati MU ; Yizhong YAN ; Shuxia GUO
Chinese Journal of Preventive Medicine 2022;56(6):800-805
Objective:To analyze whether triglyceride-glucose (TyG) index is associated with increased risk of cardiovascular diseases (CVD) and the value of TyG index in predicting CVD risk among Kazakh and Uighur population of Xinjiang.Methods:In this study, 5 375 Kazakh and Uygur people of Xinyuan county and Jiashi county were selected as the research objects. Subjects were divided into four groups based on the quartile of the TyG index level. Cox regression model was used to analyze the association between TyG index with the risk of CVD. The dose-response relationship between TyG index and CVD risk was described by restricted cubic splines. The area under the receiver operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to estimate the value of TyG index for predicting CVD. Mediating effect analysis was conducted to analyze the mediating effect of TyG index in the association between body mass index and CVD.Results:The age of subjects was 41.06(30.11,53.00)years old, with 46.30%(2 489/5 375)was male. After multivariate adjustment, there was an increasing trend between the risk of CVD and the higher TyG index Ptrend<0.001, compared with subjects of TyG index in Q1, the HR (95% CI) of Q2, Q3, and Q4 groups was 1.53, 1.23 and 1.73, respectively. Restricted cubic splines showed that TyG index was the linearly associated with the risk of CVD. TyG index could improve the prediction ability of Framingham model for the risk of CVD (NRI=0.106, P=0.010; IDI=0.003, P=0.030). The mediating effect analysis showed that in the relationship between body mass index and CVD, the TyG index had a mediating effect ( P<0.001), and the ratio of mediating effect was 12.69%. Conclusion:TyG index is an independent predictor of CVD risk among kazakh and Uygur population in Xinjiang and has a good predictive value for the risk of CVD.
9.The relationship between triglyceride glucose index and risk of cardiovascular disease among Kazakh and Uygur population in Xinjiang: a retrospective cohort analysis
Linzhi YU ; Rulin MA ; Xianghui ZHANG ; Jia HE ; Heng GUO ; Yunhua HU ; Xinping WANG ; Lati MU ; Yizhong YAN ; Shuxia GUO
Chinese Journal of Preventive Medicine 2022;56(6):800-805
Objective:To analyze whether triglyceride-glucose (TyG) index is associated with increased risk of cardiovascular diseases (CVD) and the value of TyG index in predicting CVD risk among Kazakh and Uighur population of Xinjiang.Methods:In this study, 5 375 Kazakh and Uygur people of Xinyuan county and Jiashi county were selected as the research objects. Subjects were divided into four groups based on the quartile of the TyG index level. Cox regression model was used to analyze the association between TyG index with the risk of CVD. The dose-response relationship between TyG index and CVD risk was described by restricted cubic splines. The area under the receiver operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to estimate the value of TyG index for predicting CVD. Mediating effect analysis was conducted to analyze the mediating effect of TyG index in the association between body mass index and CVD.Results:The age of subjects was 41.06(30.11,53.00)years old, with 46.30%(2 489/5 375)was male. After multivariate adjustment, there was an increasing trend between the risk of CVD and the higher TyG index Ptrend<0.001, compared with subjects of TyG index in Q1, the HR (95% CI) of Q2, Q3, and Q4 groups was 1.53, 1.23 and 1.73, respectively. Restricted cubic splines showed that TyG index was the linearly associated with the risk of CVD. TyG index could improve the prediction ability of Framingham model for the risk of CVD (NRI=0.106, P=0.010; IDI=0.003, P=0.030). The mediating effect analysis showed that in the relationship between body mass index and CVD, the TyG index had a mediating effect ( P<0.001), and the ratio of mediating effect was 12.69%. Conclusion:TyG index is an independent predictor of CVD risk among kazakh and Uygur population in Xinjiang and has a good predictive value for the risk of CVD.

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