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.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.
4.Core competency of doctors at tertiary public hospitals in regions of different income levels in China: a cross-sectional survey
Zitang HE ; Yue LI ; Yaoda HU ; Guojie ZHANG ; Li LI ; Jialin SUN ; Linzhi LUO ; Zhenlong WU ; Guangliang SHAN ; Shuyang ZHANG
Chinese Journal of Hospital Administration 2023;39(6):442-448
Objective:To explore the core competency of doctors in tertiary public hospitals in regions of different income levels in China, and provide reference for promoting such competency and related policy formulation.Methods:Using multi-stage stratified cluster sampling method, 195 tertiary public hospitals in 16 provinces of China were selected from November 2021 to March 2022. 200 doctors were sampled from each hospital. A self-designed questionnaire was used to investigate the status of doctors′ core competencies, as well as the status of their postgraduate medical education and continuing medical education. According to the per capita gross regional product of each province in China Statistical Yearbook 2022, each province was divided into high, middle and low income regions, and the questionnaire data were descriptively analyzed, while χ2 test was used to compare the differences between groups. Results:A total of 32 673 valid questionnaires were collected. There were 12 135 doctors (37.14%) in China who had received comprehensive education and training of core competency in all dimensions. Among the dimensions of self-rated core competency of the surveyed doctors, there were 10 019 doctors (30.66%) with insufficient teaching ability and 438 (1.34%) with insufficient professional quality, and there was no significant difference between regions ( P>0.05). There were 2 385 (27.08%), 2 528 (27.55%) and 3 646 (24.82%) doctors in high-, middle- and low-income regions with insufficient lifelong learning ability, respectively. The proportion of doctors in middle- and high-income regions was higher than that in low-income ones ( P<0.05). There were 1 317 (15.57%), 1 290 (14.06%) and 2 719 (18.51%) doctors with insufficient knowledge and skills in high-, middle- and low-income areas, respectively. The proportion of doctors in low-income regions was higher than that in middle- and high-income regions ( P<0.05). The proportion of doctors who did not receive any kind of postgraduate medical education or continuing medical education in low-income regions was 7.33% (1 077 people), higher than that in high-income and middle- income ones ( P<0.05); 50.44% (4 442 people) of surveyed doctors in high-income regions believed that for standardized training of resident physicians (hereinafter referred to as residential training), the clinical teachers were " overworked to take this job", which was higher than that in middle- and low-income regions ( P<0.001); In middle-income regions, 46.16% (4 235 people) and 43.46% (3 987 people) believed that the salary residents and specialized physicians in standardized training (hereinafter referred to as specialized training) was too low, while 42.47% (3 897 people) and 30.44% (2 793 people) believed that the clinical practice opportunities of students were limited, both of which were higher than those in high-income and low-income regions ( P<0.001); 34.91% (5 128 people) of surveyed doctors in low-income regions believed that the investment was insufficient for training bases of residential training, 27.81% (4 085 people) of those held that training bases for specialized training were unevenly distributed, and 33.19% (4 876 people) of those held that continuing medical education was plagued by " insufficient promotion coverage, and insufficient opportunities for primary doctors", all of which being higher than those in high- and middle-income regions ( P<0.001). Conclusions:There is an obvious need to improve the core competence of doctors in the teaching ability dimension of tertiary public hospitals in China, especially in middle- and high-income regions for lifelong learning, and in low-income regions for knowledge and skills; There are differences between postgraduate medical education and continuing medical education systems in regions of different income levels in China. It is necessary to improve the competency oriented postgraduate medical education and continuing medical education systems.
5.Electroacupuncture ameliorated neuropathic pain induced by chronic constriction injury via inactivation of PI3K/AKT pathway
Yu Zhao ; Wenxue He ; Yong Wu ; Yang Liu ; Chang Yang ; Linzhi Wu ; Bin Liu
Neurology Asia 2019;24(4):317-326
Objective: To explore the analgesic effect of electroacupuncture on neuropathic pain and the role of
PI3K/AKT pathway in microglial activation in spinal cord.
Methods: Chronic constriction injury model was established using Sprague-Dawley rats to mimic
neuropathic pain. The pain intensity was then detected by paw withdrawal threshold and thermal
withdrawal latency. Real-time quantitative PCR (qRT-PCR), Western blot were used to evaluate the
activation of PI3K/AKT pathway as well as microglia in L4-5 of all rats. Proinflammatory cytokines
TNF-α and IL-6 were analyzed by Enzyme-linked immunosorbent assay (ELISA). Results: It was
demonstrated that chronic constriction injury-induced hyperalgesia was significantly improved by
LY294002 intrathecal administration and electroacupuncture stimulation at “Zusanli” 足三里 (ST36)
and “Yanglingquan” 阳陵泉 (GB34). Also, treatment with electroacupuncture significantly reduced
the activation of microglia and downregulated the levels of TNF-α and IL-6, which was similar to the
outcomes of LY294002 intrathecal administration. Furthermore, the expression and phosphorylation
of PI3K/AKT signaling was markedly suppressed by electroacupuncture treatment.
Conclusions: These findings indicated that electroacupuncture exhibited the analgesic effect on CCI
rats by inhibiting the activation of microglia and production of proinflammatory cytokines in spinal
cord through blocking the microglial PI3K/AKT signaling activation
6.Change trends of pathogen of severe hand, foot and mouth disease in Chaoshan area during 2011 to 2015
Xiaoying CAI ; Linzhi YANG ; Guangyu LIN ; Chuangxing LIN ; Paizhen CHEN ; Jiamin WU ; Jieling CHEN ; Xuedong LU
Chinese Pediatric Emergency Medicine 2018;25(1):27-31
Objective To discuss the change trends of pathogen of severe hand,foot and mouth dis-ease(HFMD) in Chaoshan area during 2011 to 2015. Methods All 1410 throat swabs of cases who were diagnosed as HFMD were collected from children hospitalized in our hospital during May 2011 to August 2015. Enterovirus were detected by nest RT-PCR,and the results of these positive cases diagnosed as severe HFMD were analyzed. Results (1) There were 216 positive cases(67. 29%,216/321) diagnosed as severe HFMD,including 53. 70% ( 116/216 ) enterovirus 71 ( EV71 ), 19. 91% ( 43/216 ) coxsackievirus A16 (CA16),12. 04%(26/216) CA6,8. 80%(19/216) CA10,3. 24%(7/216) CA4,0. 93%(2/216) coxsack-ievirus B5, 0. 46% ( 1/216 ) enteric cytopathogenic human orphan virus and 0. 93% ( 2/216 ) unclassified samples were unclassified to species. (2) Five cases of critical HFMD were all caused by EV71. (3) The EV71 positive samples were given priority to severe cases ( 51. 79%,116/224 ) and the non EV71 positive samples were given priority to mild cases ( 82. 08%, 458/558 ) , the difference was statistically significant (χ2 =91. 68,P<0. 001). (4) The change trends of severe HFMD year by year were consistent with the change trends of EV71 composition,and were highly correlated(Rs=0. 9,P=0. 037). (5) Severe HFMD caused by non EV71 virus gradually increased. Conclusion Severe HFMD in Chaoshan area during 2011 to 2015 were mainly caused by EV71,non EV71 viruses including CA16,CA6,CA10,CA4,coxsackievirus B5, enteric cytopathogenic human orphan virus 6 could also develop to severe HFMD. The composition ratio of severe HFMD increased accordingly in the year of EV71 as the dominant pathogen. The proportion of severe HFMD caused by non EV71 virus gradually increased after 2013 year.


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