2.ADAR1 Regulates the ERK/c-FOS/MMP-9 Pathway to Drive the Proliferation and Migration of Non-small Cell Lung Cancer Cells.
Li ZHANG ; Xue PAN ; Wenqing YAN ; Shuilian ZHANG ; Chiyu MA ; Chenpeng LI ; Kexin ZHU ; Nijia LI ; Zizhong YOU ; Xueying ZHONG ; Zhi XIE ; Zhiyi LV ; Weibang GUO ; Yu CHEN ; Danxia LU ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2025;28(9):647-657
BACKGROUND:
Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.
METHODS:
Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism.
RESULTS:
ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression.
CONCLUSIONS
High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans
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Lung Neoplasms/physiopathology*
;
Adenosine Deaminase/genetics*
;
Matrix Metalloproteinase 9/genetics*
;
Cell Proliferation
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Carcinoma, Non-Small-Cell Lung/physiopathology*
;
Cell Movement
;
Animals
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Mice
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RNA-Binding Proteins/genetics*
;
Female
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Male
;
Cell Line, Tumor
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Proto-Oncogene Proteins c-fos/genetics*
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Middle Aged
;
MAP Kinase Signaling System
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Gene Expression Regulation, Neoplastic
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Mice, Nude
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Extracellular Signal-Regulated MAP Kinases/genetics*
3.Experimental study to construct the three-dimensional scaffold of rabbit cartilage-shedding cells and evaluate their compatibility with stem cells
Juju XU ; Yanyan XIE ; Zhiyi GUO ; Yukai MA ; Linhong WANG ; Meirong YANG ; Zhaoling DENG ; Baolai HUA ; Zhenyu YAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):1012-1022
Objective To prepare decellularized scaffolds from rabbit cartilage at various concentrations and assess their physicochemical properties and compatibility with stem cells to provide an experimental basis for cartilage repair.Methods Bone marrow mesenchymal stem cells(BMSCs)were cultured using the Percoll density gradient separation method,and this was followed by flow cytometric analysis and testing of their osteogenic and chondrogenic differentiation capabilities.Cartilage pieces were excised from rabbit knees and hip joints and subjected to physical crushing,repeated freeze-thaw cycles,and mixed enzymatic digestion for decellularization.To compare and observe the physicochemical properties of the decellularized scaffolds at different concentrations,three groups of scaffolds(labelwd A,B,and C)were designed with concentrations of 100%,50%and 30%,with three replicates each.Third-generation PKH26-labeled BMSCs were seeded onto optimally concentrated scaffolds and cultured for 1 week to observe cell growth.Results Flow cytometry detected BMSC surface antigens with positive expression of CD44 and CD90 and negative expression of CD45.Osteogenic induction stained with alizarin red showed red calcific nodules,and chondrogenic induction stained with alcian blue showed blue cartilaginous nodules.No apparent cell morphology was observed in the three groups of scaffolds stained with hematoxylin-eosin,and toluidine blue.There was a significant difference in DNA concentration between decellularized samples and non-decellularized scaffolds(P<0.05).The content of glycosaminoglycans was slightly lower than the normal values.Significant differences were observed between the three groups of scaffolds in terms of pore size,water absorption,porosity,tensile strength,and Young's modulus(P<0.05).After co-cultivation of stem cells with the scaffolds,cell adhesion was found to be good.Conclusions Percoll density gradient separation can obtain high-purity rabbit BMSCs,and the mixed decellularization method is superior.Group B scaffolds were the most suitable for tissue-engineered cartilage repair.BMSCs cultured in vitro grew well on Group B scaffolds.
4.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
5.Impact of autologous hematopoietic stem cell transplantation on the efficacy of CAR-T treatment of relapsed/refractory multiple myeloma
Meijing DING ; Xingxing JIE ; Hujun LI ; Zhiyi XU ; Li NIAN ; Kunming QI ; Zhiling YAN ; Feng ZHU ; Jiang CAO ; Huanxin ZHANG ; Kailin XU ; Hai CHENG ; Zhenyu LI
Chinese Journal of Internal Medicine 2024;63(6):587-592
Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.
6.Blinding Designs and Critical Issues in Acupuncture Clinical Trials
Tinglan LIU ; Haoran ZHANG ; Xiaoyu LIU ; Zhiyi XIONG ; Chengyi SUN ; Shiyan YAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(7):1765-1770
Blinding is an important method to control the measure bias in clinical trials.As a complex and invasive intervention,acupuncture has more difficulty in blinding implementation compared to drugs and has a higher risk of unblinding breakage.This article provides an overview of the blinding in acupuncture clinical study and summarized the key aspects,including:there is no standard for the application and reporting of sham acupuncture design and blinding measures,appropriate sham acupuncture devices still need to be developed,currently there are no effective methods of operator blinding,blinding assessment has not been given due attention,sham acupuncture design should be standardized and reported.Researchers should conduct further studies to address critical questions and challenges to provide methodological support to improve and promote the quality of acupuncture clinical research.
7.SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice.
Lingling GAO ; Zhi XIE ; Shouheng LIN ; Zhiyi LV ; Wenbin ZHOU ; Ji CHEN ; Linlin ZHU ; Li ZHANG ; Penghui ZENG ; Xiaodan HUANG ; Wenqing YAN ; Yu CHEN ; Danxia LU ; Shuilian ZHANG ; Weibang GUO ; Peng LI ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2023;26(10):753-764
BACKGROUND:
The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex.
METHODS:
The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases.
RESULTS:
WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group.
CONCLUSIONS
This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals
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Mice
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Carcinoma, Non-Small-Cell Lung/genetics*
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Lung Neoplasms/genetics*
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Mutation
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Liver Neoplasms/genetics*
8.Understanding health literacy from a traditional Chinese medicine perspective.
Zhiyi QIAN ; Grace Y WANG ; Marcus HENNING ; Yan CHEN
Journal of Integrative Medicine 2023;21(3):215-220
Health literacy is critical to improving individual and public health. However, indigenous perceptions of health are largely absent from Western-derived measurements, contributing to disparities in health outcomes between indigenous and non-indigenous populations. China is the country with the world's largest population and only officially introduced the term "health literacy" in 2008. Current measures of health literacy in China are primarily based on Western-derived constructs, which have been shown to have poor comparability to the unique dual medical system in China. Given its significant importance to health management globally, understanding health perceptions from a traditional Chinese medicine perspective is essential. This review explores the concept and core elements of indigenous health literacy, evaluates the existing definitions and measurement tools as applied to the concept, and proposes a new model of traditional Chinese medicine health literacy. Please cite this article as: Qian Z, Wang GY, Henning M, Chen Y. Understanding health literacy from a traditional Chinese medicine perspective. J Integr Med. 2023; 21(3): 215-220.
Medicine, Chinese Traditional
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Health Literacy
;
China
9.Comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma
Yang MAN ; Zhiyi LIN ; Zhang MIAO ; Lerong YAN ; Xiao CHENG ; Renyi JING ; Rong BAI ; Pingwen HUANG ; Hongwei ZHANG ; Xinyu PENG
Journal of Clinical Hepatology 2022;38(3):601-605
Objective To investigate the comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma, and to lay a foundation for further research on the influence of hepatic cystic echinococcosis on HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma. Methods A retrospective analysis was performed for the data of 401 patients with hepatic cystic echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from 2003 to 2019, and the state of comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma was clarified. The patients with hepatic cystic echinococcosis and chronic HBV/HCV infection were selected as comorbidity group, and the patients with HBV/HCV infection alone were matched as control group. The chi-square test and the Fisher's exact test were used to analyze the state of viral infection and the disease composition of liver cirrhosis and hepatocellular carcinoma. Results Of all 401 patients, 38(9.5%) were included in the comorbidity group and 2(0.5%) had liver cirrhosis after HBV/HCV infection, while no patient had hepatocellular carcinoma after HBV/HCV infection. Among the patients with chronic hepatitis B virus infection in the comorbidity group, non-active HBsAg carriers accounted for 81%, HBeAg-positive chronic hepatitis B patients accounted for 9.5%, and HBeAg-negative chronic hepatitis B patients accounted for 9.5%; among the patients with hepatitis B virus infection in the control group, non-active HBsAg carriers accounted for 43%, HBeAg-positive chronic hepatitis B patients accounted for 33%, and HBeAg-negative chronic hepatitis B patients accounted for 19%, with a significant difference between the two groups ( P =0.033). There was a significant difference in the HBV RNA clearance rate of the patients with HCV infection between the comorbidity group and the control group ( χ 2 =4.447, P =0.035). In the comorbidity group, the patients with liver cirrhosis accounted for 5.2% and there were no patients with hepatocellular carcinoma, while in the control group, the patients with liver cirrhosis accounted for 18.4% and those with hepatocellular carcinoma accounted for 5.2%; the comorbidity group had significantly lower proportions than the control group ( P =0.048). Conclusion The proportion of liver cirrhosis patients with hepatic cystic echinococcosis and HBV/HCV infection is lower than that of liver cirrhosis patients with viral hepatitis alone, and there are no cases of hepatocellular carcinoma after HBV/HCV infection. Further multicenter studies are needed to investigate the influence of hepatic cystic echinococcosis on chronic HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma.
10.Recommendations on the diagnosis and treatment of osteoarthritis in China
Yanping ZHAO ; Zhiguo LIN ; Shudian LIN ; Liping XIA ; Zhiyi ZHANG ; Yan ZHAO
Chinese Journal of Internal Medicine 2022;61(10):1136-1143
Osteoarthritis (OA) is the most common form of arthritis and the leading cause of old age disability, affecting an estimated 302 million people worldwide. OA is seriously overlooked in the world. The awareness of OA and the popularization of standardized diagnosis and treatment are all lacking. Knees, hips, and hands are the most commonly affected joints in OA. Based on the experience of diagnosis and treatment, consensus and guidelines, we formulated this diagnosis and treatment standard in order to standardize the diagnosis and treatment of OA. We hope that our standard can reduce misdiagnosis and mistreatment and improve the prognosis of OA.

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