1.Induction of tumor immunogenic cell death by low-temperature plasma
Xiangni WANG ; Jinren LIU ; Yixin CUI ; Jiajia LU ; Zhirou HE ; Yulin XU ; Rongrong LI ; Xingmin SHI ; Xili WU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):20-27
Objective To compare the induction effects of direct treatment with low-temperature plasma(LTP)and treatment with plasma-activated medium(PAM)on immunogenic cell death(ICD)of melanoma cells.Methods After direct treatment of melanoma cell line B16F10 with LTP and treatment of it with PAM for 24 hours,cell viability was detected by MTT assay.Flow cytometry was used to detect cell apoptosis and the expression of calreticulin(CRT)on the cell surface.The adenosine triphosphate(ATP)content in the culture medium was detected by an ATP detection kit.The content of high-mobility group box 1(HMGB1)in the cell culture medium was detected by ELISA.B16F10 cells treated with LTP were co-cultured with immature dendritic cells(DC)DC2.4 cell line,and flow cytometry was used to detect DC surface molecules CD80 and CD86.Results Compared with the control group,both direct treatment and indirect treatment could lead to a decrease in the viability of B16F10 cells,an increase in the apoptosis rate,an increase in intracellular ROS,an increase in CRT expression,and an increase in the secretion of ATP and HMGB1(P<0.05).At the same treatment time,the expression of CRT and the release of ATP in B16F10 cells directly treated with LTP were higher than those indirectly treated with PAM(P<0.05).Compared with the DC2.4 group,the expression proportion of the DC cell maturation marker molecule CD80 was significantly increased in LTP-120s group,LTP-180s group,PAM-120s group,and PAM-180s group.The expression proportion of the DC cell maturation marker molecule CD86 was significantly increased in LTP-120s group,LTP-180s group,and PAM-180s group,and the difference was statistically significant(P<0.05).Conclusion Both direct treatment with LTP and indirect treatment with PAM can induce ICD in melanoma cells.The direct treatment with LTP has a better induction effect.
2.Targeting copper homeostasis: Akkermansia-derived OMVs co-deliver Atox1 siRNA and elesclomol for cancer therapy.
Muhammad HAMZA ; Shuai WANG ; Hao WU ; Jiayi SUN ; Yang DU ; Chuting ZENG ; Yike LIU ; Kun LI ; Xili ZHU ; Huiying LIU ; Lin CHEN ; Motao ZHU
Acta Pharmaceutica Sinica B 2025;15(5):2640-2654
Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.
3.Research Progress on Immunomodulatory Activity and Mechanism of Polygonatum sibiricum
Jinyu LI ; Ningning QIU ; Chang YI ; Mengqin ZHU ; Yanfeng YUAN ; Guang CHEN ; Xili ZHANG ; Wenlong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):298-306
Polygonatum sibiricum, as a traditional Chinese medicine with both medicinal and edible properties, has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs, tonifying the spleen and benefiting Qi, and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system, effectively enhancing and improving the morphology and function of immune organs, stimulating the proliferation and activation of immune cells, and regulating the secretion and release of immune factors, thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum, there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore, this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years, and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects: including increasing the organ index of the spleen and thymus, increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells, improving intestinal flora imbalance, regulating the quantity and proportion of T lymphocyte subsets, increasing the level of immunoglobulin, promoting the proliferation of macrophages, enhancing the activity of natural killer cells, increasing the number of white blood cells, and promoting the maturation of dendritic cells, providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum, and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.
4.Induction of tumor immunogenic cell death by low-temperature plasma
Xiangni WANG ; Jinren LIU ; Yixin CUI ; Jiajia LU ; Zhirou HE ; Yulin XU ; Rongrong LI ; Xingmin SHI ; Xili WU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):20-27
Objective To compare the induction effects of direct treatment with low-temperature plasma(LTP)and treatment with plasma-activated medium(PAM)on immunogenic cell death(ICD)of melanoma cells.Methods After direct treatment of melanoma cell line B16F10 with LTP and treatment of it with PAM for 24 hours,cell viability was detected by MTT assay.Flow cytometry was used to detect cell apoptosis and the expression of calreticulin(CRT)on the cell surface.The adenosine triphosphate(ATP)content in the culture medium was detected by an ATP detection kit.The content of high-mobility group box 1(HMGB1)in the cell culture medium was detected by ELISA.B16F10 cells treated with LTP were co-cultured with immature dendritic cells(DC)DC2.4 cell line,and flow cytometry was used to detect DC surface molecules CD80 and CD86.Results Compared with the control group,both direct treatment and indirect treatment could lead to a decrease in the viability of B16F10 cells,an increase in the apoptosis rate,an increase in intracellular ROS,an increase in CRT expression,and an increase in the secretion of ATP and HMGB1(P<0.05).At the same treatment time,the expression of CRT and the release of ATP in B16F10 cells directly treated with LTP were higher than those indirectly treated with PAM(P<0.05).Compared with the DC2.4 group,the expression proportion of the DC cell maturation marker molecule CD80 was significantly increased in LTP-120s group,LTP-180s group,PAM-120s group,and PAM-180s group.The expression proportion of the DC cell maturation marker molecule CD86 was significantly increased in LTP-120s group,LTP-180s group,and PAM-180s group,and the difference was statistically significant(P<0.05).Conclusion Both direct treatment with LTP and indirect treatment with PAM can induce ICD in melanoma cells.The direct treatment with LTP has a better induction effect.
5.Analysis and comparison of health education on respiratory infectious diseases at home and abroad
Yan GUAN ; Xili CHEN ; Wenxi WANG ; Ming LI ; Yueming SU ; Zhenyu LIANG ; Dongying ZHANG
Chinese Journal of Health Management 2024;18(11):869-875
Objective:To analyze and compare the health education efforts of respiratory infectious diseases at home and abroad.Methods:The literature related to health education and popular science of respiratory infectious diseases included in the databases of China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) from January 1, 2003 to December 31, 2023 was searched. A total of 4 686 articles were retrieved in CNKI, 1 540 articles unrelated to the theme were excluded, and 3 146 Chinese articles were obtained. In the WOS database, 7 724 articles were retrieved, 3 685 articles about the clinical mechanism of diseases, pharmacology, and other research topics were excluded, and 4 039 English articles were obtained. The information of annual publications, institutions, authors and keywords was analyzed by using CiteSpace visualization software, and the publication status, research hotspots and development trends of health education related to respiratory infectious diseases at home and abroad were analyzed.Results:Since 2003, the number of publications in health education on respiratory infectious diseases at home and abroad had shown a fluctuating growth trend, and in 2020, the field showed a sharp growth trend at home and abroad. There was no core author group in this field in China, and the network density of domestic authors was 0.006 5, and the network density of foreign authors was 0.009 6. The domestic institutions were mainly the Center for Disease Control and Prevention and medical institutions, including Guangzhou Chest Hospital (29 articles) and the Chinese Center for Disease Control and Prevention (10 articles); Foreign research institutions were mainly higher education institutions, including the University of London (91 articles) and Harvard University (67 articles). The network density of domestic was 0.001 3, and the network density of foreign publishing institutions was 0.026 3, the network density was greater than that of Chinese publishing institutions. The emergence of "COVID-19" "Avian influenza" "Knowledge, Attitude, Practice" and "mental health" in China had strong burst (burst intensity: 46.41, 12.12, 10.33, 8.5); "Coronavirus" "coverage" "Avian influenza" and "COVID-19 vaccine" in foreign countries had strong burst (burst intensity: 14.34, 11.06, 10.73, 10.02).Conclusions:At present, the health education of respiratory infectious diseases at home and abroad has received great attention. But the cooperation between domestic authors and research institutions is loose, and the close collaboration needs to be strengthened. There are differences in the research focus of health education on respiratory infectious diseases at home and abroad.
6.Analysis of plasma amino acid profiles in adolescents and adults with atopic dermatitis
Xili XU ; Dongning LI ; Han DUAN ; Fei WANG
Chinese Journal of Dermatology 2023;56(8):742-750
Objective:To analyze changes in plasma amino acid profiles in adolescents and adults with atopic dermatitis (AD) by targeted metabolomics, to further analyze differences in plasma amino acid profiles between AD patients with elevated total IgE levels and those with normal total IgE levels, as well as between AD patients with and without allergic rhinitis, and to explore the pathogenesis of AD from the perspective of metabolic pathways.Methods:From December 2021 to June 2022, 40 AD patients aged > 12 years were collected as research subjects from the Department of Dermatology, the First Affiliated Hospital of Jinzhou Medical University, and 30 healthy checkup examinees served as a control group at the same time. Plasma samples were obtained from the subjects, and high-performance liquid chromatography-mass spectrometry was performed to detect levels of metabolites in the plasma samples. Principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were carried out to analyze data and screen out differential metabolites with the variable weight value (VIP) of the first principal component being > 1 in the OPLS-DA model and the P value being < 0.05 in the t test. Possible abnormal metabolic pathways were analyzed using MetaboAnalyst 5.0 software, and differential metabolic pathways were defined as those with an impact value of > 0.1 and a P value of < 0.05. Results:PCA and OPLS-DA model analysis showed that metabolites were well differentiated among the groups, and differential metabolites and metabolic pathways were screened out. Concretely speaking, 12 differential metabolites and 8 differential metabolic pathways were identified by comparing the AD group with the control group, among which differential metabolites included arginine (metabolic levels: 28.257 ± 11.517 μmol/L vs. 21.038 ± 8.500 μmol/L, VIP = 1.32, P = 0.001), ornithine (47.597 ± 18.158 μmol/L vs. 36.937 ± 5.813 μmol/L, VIP = 1.26, P < 0.001) and histidine (78.322 ± 14.971 μmol/L vs. 100.694 ± 32.419 μmol/L, VIP = 1.33, P < 0.001), and differential metabolic pathways included arginine biosynthesis (impact = 0.482, P < 0.001) and histidine metabolism (impact = 0.221, P < 0.001). Comparisons between the AD group with elevated IgE levels and those with normal IgE levels showed 5 differential metabolites and 3 differential metabolic pathways, among which differential metabolites included lysine (313.998 ± 61.252 μmol/L vs. 285.330 ± 58.388 μmol/L, VIP = 2.25, P < 0.001) and glycine (200.807 ± 53.320 μmol/L vs. 187.056 ± 50.941 μmol/L, VIP = 1.40, P = 0.014), and differential metabolic pathways included the glyoxylate and dicarboxylate metabolic pathway (impact = 0.105, P = 0.001) ; by comparing the AD group with and without allergic rhinitis, 6 differential metabolites and 3 differential metabolic pathways were identified, among which the arginine biosynthesis metabolic pathway was highlighted (impact = 0.116, P < 0.001) . Conclusion:The plasma amino acid metabolites in adolescents and adults with AD were different from those in healthy controls, and elevated plasma levels of arginine and ornithine and decreased plasma level of histidine may be involved in the pathogenesis of AD; increased plasma levels of lysine and glycine were associated with AD with elevated IgE levels; the arginine biosynthetic metabolic pathway was related to AD complicated by allergic rhinitis.
7.The role of natural killer cells in anti-infection and tumor therapy.
Xili FENG ; Huihui WANG ; Mengzhu WANG ; Feiyang PU ; Zeyang ZHAO ; Yicong LI ; Xiaoxia MA ; Zhongren MA ; Jianhua ZHOU
Chinese Journal of Cellular and Molecular Immunology 2023;39(10):952-958
Natural killer (NK) cells are an important part of the body's innate immune system. As the first line of defense against pathogens, they need to be transformed into a mature state under the control of various cell signaling molecules and transcription factors to play cytotoxic and immune regulatory roles. Under the interaction of activated receptors and inhibitory receptors, NK cells are activated to perform a direct cell killing effect by secreting perforin and granzyme, or indirectly eliminate pathogenic microorganisms in the body by secreting various cytokines, such as type I and type II interferons. These functions of NK cells play a very important role in antiviral and anti-autoimmune diseases, especially in anti-tumor.
Humans
;
Killer Cells, Natural
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Interferon-gamma
;
Apoptosis
;
Autoimmune Diseases
;
Cytokines
8.Analysis of Key Points of Technical Review of Traditional Chinese Medicine Fumigation Treatment Device.
Guoyong LI ; Wenlong XIA ; Xili REN ; Liguo ZHAO ; Hongzhong CHEN ; Ou CHEN
Chinese Journal of Medical Instrumentation 2023;47(5):562-565
Traditional Chinese medicine fumigation device is the carrier of traditional Chinese medicine fumigation treatment. In recent years, with the rapid development of new technology and new materials, the development of fumigation device changes with each passing day, and a variety of new products continue to emerge. However, at present, the lack of corresponding evaluation norms, resulting in some difficulties in the registration, marketing, quality control, evaluation scale and other aspects of the product. Some products have many disadvantages in clinical use. From the perspective of technical review, this paper elaborates and analyzes the main concerns in technical review, such as product structure, main risks, performance requirements, clinical evaluation, etc., in order to provide a basis for the design, development, production, registration, use and post-marketing supervision of the devices.
Fumigation
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Medicine, Chinese Traditional
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Marketing
;
Quality Control
9.The components transitive regularity of three dosage forms of Liuwei Dihuang Fufang
ZHU Junping ; ZHANG Xili ; ZHAO Jing ; LIANG Huihui ; LI Yuanhua ; LIU Wenlong
Digital Chinese Medicine 2022;5(1):68-74
Objective To explore the transitive regularity of holistic constituents from the crude slices of the medicinal raw materials (MCS) to the formula granules (FG), fufang decoction (FD), and finally, the concentrated pills (CP) of Liuwei Dihuang Fufang (六味地黄复方, LWDHF). Methods Samples for MCS, FG, FD, and CP of LWDHF were obtained, and a fingerprint database was established using high-performance liquid chromatography (HPLC), by separating the samples in an XB-C18 column and analyzing the transitive regularity of components using the total quantum statistical moment (TQSM), including total quantum zero moment (AUCT), total quantum first moment (MRTT), total quantum second moment (VRTT), and its similarity approach. The AUCT, MRTT, and VRTT were calculated based on the representative HPLC chromatograms of FG, FD, and CP of LWDHF. Results AUCT of FG, FD, and CP of LWDHF was 71 804, 46 553, and 144 646 µV·s, respectively; MRTT was 14.43, 14.54, and 18.85 min, respectively; and VRTT was 106.98, 112.84, and 269.12 min2, respectively. Comparing the similarity of FG/FD, FG/CP and FD/CP of LWDHF, the TQSM similarity values were 98.66%, 76.62%, and 75.37%, respectively, whereas the traditional similarity evaluation values were 98.68%, 85.43%, and 85.60%, respectively. Conclusion The results perform little distinction in the total composition between FG and FD, whereas some distinction existed between FD and CP. Experimental evidence, therefore indicates that FG could be used as the alternative of MCS in clinical applications.
10.Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization.
Yongcun QU ; Qi CHEN ; Shanshan GUO ; Chiyuan MA ; Yonggang LU ; Junchao SHI ; Shichao LIU ; Tong ZHOU ; Taichi NODA ; Jingjing QIAN ; Liwen ZHANG ; Xili ZHU ; Xiaohua LEI ; Yujing CAO ; Wei LI ; Wei LI ; Nicolas PLACHTA ; Martin M MATZUK ; Masahito IKAWA ; Enkui DUAN ; Ying ZHANG ; Hongmei WANG
Protein & Cell 2021;12(10):810-817
Animals
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Antigens, Surface/genetics*
;
Cell Communication/genetics*
;
Copulation/physiology*
;
Fallopian Tubes/metabolism*
;
Female
;
Fertilization/genetics*
;
GPI-Linked Proteins/genetics*
;
Gene Expression Regulation
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Genes, Reporter
;
Green Fluorescent Proteins/metabolism*
;
Litter Size
;
Luminescent Proteins/metabolism*
;
Male
;
Mice
;
Mice, Inbred C57BL
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Mice, Knockout
;
Mitochondria/metabolism*
;
Reproduction/genetics*
;
Signal Transduction
;
Sperm Count
;
Sperm Motility/genetics*
;
Spermatozoa/metabolism*
;
Uterus/metabolism*

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