1.TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis
Jingyi HAN ; Xue ZHANG ; Menghua CAI ; Feng TIAN ; Yi XU ; Hui CHEN ; Wei HE ; Jianmin ZHANG ; Hui TIAN
Chinese Medical Journal 2024;137(13):1592-1602
Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.
2.Preparation and application of PRRSV MS2 armored virus-like particles qualityas control products
Jiamin HE ; Xuanfei PANG ; Lyu LUO ; Jiazhen YANG ; Baozhen ZHANG ; Jianmin WU ; Wenna LIU ; Zhongsheng LI ; Yiquan BAI
Chinese Journal of Veterinary Science 2024;44(11):2316-2323
In order to develop a positive quality control products for the detection of porcine repro-ductive and respiratory syndrome virus(PRRSV)nucleic acid by real-time fluorescent quantitative PCR(RT-qPCR),the positive quality control products of PRRSV-1 and PRRSV-2 M genes were prepared using armored RNA technology of MS2 phage.PRRSV-1 and PRRSV-2 M genes were amplified,purified and recovered,and ligated into pET28b vector containing MS2 mature enzyme protein gene and capsid protein.After transformed into BL21(DE3),the gene products were in-duced by IPTG and purified by PEG6000 precipitation method to prepare the armored RNA virus-like particles(AR-PRRSV)containing PRRSV M gene.Following the performance evaluation,as the positive quality control products of PRRSV-1 and PRRSV-2 M genes,AR-PRRSV1M and AR-PRRSV2M were calculated using YY/T 1652-2019 standard.Results showed that it had a good u-niformity,stable storage for the armored virus-like particles at-20,4,25 ℃ for 60 d,and 37 ℃ for 30 d.The prepared armored virus-like particles AR-PRRSV1M and AR-PRRSV2M were deter-mined by digital quantitative PCR(ddPCR)after preliminary quantification by RT-qPCR.The 104 copies/μL of AR-PRRSV1M and AR-PRRSV2M ddPCR fixation was(1.33+0.50)× 104 cop-ies/μL.The above results indicates that the AR-PRRSVM can be used as the quality control of the whole detection process(nucleic acid extraction,reverse transcription and RT-qPCR).
3.Research progress in tumor infiltrating lymphocyte therapy
Hourui TAN ; Ruiqi LIU ; Peng DONG ; Jianmin ZHANG ; Wei HE ; Hui CHEN
Chinese Journal of Microbiology and Immunology 2024;44(9):741-751
Tumor-infiltrating lymphocytes (TILs), derived from the solid tumor microenvironment, have significant advantages in adoptive cell therapy for solid tumors as they are believed to have more specific antitumor activity than peripheral lymphocytes. TILs was first reported in 1986. With the development and improvement of isolation and activation techniques, TILs-based adoptive cell therapy has shown long-term clinical benefit in phase Ⅱ/Ⅲ trials for advanced melanoma in recent years, and the first TILs-based therapy has been approved for market. Gene editing technology has improved the antitumor activity of TILs and made TILs widely used in other solid tumors besides advanced melanoma, such as head and neck cancer, breast cancer, non-small cell lung cancer, and ovarian cancer. In addition, TILs-based adoptive cell therapy used in combination with other tumor therapies has shown promising therapeutic potential in a variety of solid tumors. This review summarizes the significant progress of TILs-based therapy in basic research, clinical trials, and industrial application in the past two years, and analyzes the challenges and development trends, hoping to provide reference for further development in this field.
4.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy.
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans
;
Receptors, Antigen, T-Cell, gamma-delta
;
Immunotherapy, Adoptive
;
T-Lymphocytes
;
Immunotherapy
;
Neoplasms/therapy*
5.Effects of icariin-astragaloside IV-puerarin mixture on cognitive function and ferroptosis amino acid metabolism pathway in APP/PS1 HAMP-/-mice
Shan LIU ; Xiaoping HE ; Yan ZHAO ; Jianmin ZHONG ; Yehua ZHANG ; Yiming LIU ; Jiaxuan LI ; Xianhui DONG
Chinese Journal of Pathophysiology 2024;40(3):502-510
AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P<0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P<0.05),the brain neurons were seri-ously damaged(P<0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P<0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P<0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P<0.05),the brain neurons were seriously damaged(P<0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P<0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P<0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P<0.05),the brain neuron damage was alleviated(P<0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P<0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.
6.Level of injury first aid skills among parents of preschool children in Dongxihu District
XIA Lin ; HE Jianmin ; NING Jingming ; LI Yilin
Journal of Preventive Medicine 2024;36(8):718-722
Objective:
To investigate the level of injury first aid skills and its influencing factors among parents of preschool children in Dongxihu District, Wuhan City, so as to provide insights into carrying out targeted health education work.
Methods:
Parents of preschool children from kindergarten in Dongxihu District were selected using multi-stage stratified cluster sampling method. Basic information of preschool children, parents' demographic information, and parents' knowledge of injury first aid skills were collected through questionnaires. The level of injury first aid skills among parents was analyzed and its influencing factors were identified using a multivariable logistic regression model.
Results:
A total of 1 148 questionnaires were allocated and 1 131 valid questionnaires were recovered, with an effective recovery rate of 98.52%. The respondents included 242 men (21.40%) and 889 women (78.60%). The parents surveyed were mainly mothers, with 862 accounting for 76.22%. The level of injury first aid skills was 39.43%. Among the individual injury first aid skills, the proportions of mastering the treatment of cardiac arrest and arm fracture were relatively high, which were 94.69% and 94.16%, respectively, while the proportion of mastering the correct steps of cardiopulmonary resuscitation was the lowest, at 31.21%. Multivariable logistic regression analysis showed that the grade of children (middle class, OR=1.374, 95%CI: 1.021-1.847; senior class, OR=1.561, 95%CI: 1.147-2.125), age (30 to 34 years old, OR=1.712, 95%CI: 1.170-2.505), education level (high school/technical secondary school and below, OR=0.664, 95%CI: 0.515-0.857), and having learned injury first aid skills (OR=1.653, 95%CI: 1.284-2.129) were influencing factors of injury first aid skills among parents of preschool children.
Conclusions
The level of injury first aid skills among parents of preschool children is relatively low. The first aid ability of parents whose children are in small classes, older, less educated, and have not learned injury first aid skills should be specifically improved.
7.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
8.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
9.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
10.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.


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