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BTG2 interference ameliorates high glucose-caused oxidative stress, cell apoptosis, and lipid deposition in HK-2 cells

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BIOCELL 2024年第9期48卷 1379-1388页

作者： Zhu, Wenjuan Ju, Zhengzheng Cui, Fan first peoples hosp wuhu Dept Blood Transfus Wuhu 241000 Peoples R China first peoples hosp wuhu Dept Clin Lab Wuhu 241000 Peoples R China

Objective: Diabetic nephropathy (DN) is a deleterious microangiopathy of diabetes, constituting a critical determinant of fatality in diabetic patients. This work is purposed to disclose the effects and modulatory mechanism of BTG anti-proliferation factor 2 (BTG2) during the pathological process of DN. Methods: BTG2 expression in kidney tissues of diabetic mice and high glucose (HG)-exposed human proximal tubular cell line HK-2 was assessed with Western blot and RT-qPCR. The diabetic mice model was constructed by streptozotocin injection and con fi rmed by the blood glucose level beyond 16.7 mmol/L. Hematoxylin and eosin (H&E) staining and measurement of kidney function hallmarks were conducted to assess kidney injury. Cell counting kit (CCK)-8 method and TUNEL assay appraised cell activity and apoptosis. Oil red O staining assayed lipid accumulation. Relevant commercial kits were used to estimate oxidative stress-related factors. Co-immunoprecipitation (Co-IP) assay testi fi ed the binding relationship of BTG2 with protein arginine methyltransferase 1 (PRMT1). Results: BTG2 expression was signi fi cantly raised in renal tissues of diabetic mice and HK-2 cells exposed to HG. BTG2 de fi ciency improved viability and extenuated the apoptosis, lipid deposition as well as oxidative stress in HK-2 cells following HG exposure. In addition, PRMT1 was also overexpressed in HK-2 cells exposed to HG. BTG2 interacted with PRMT1 and positively modulated PRMT1 expression. The effects of BTG2 interference on viability, apoptosis, lipid deposition, and oxidative stress in HG-challenged HK-2 cells were partially abrogated by PRMT1 overexpression. Conclusion: Altogether, BTG2 might aggravate HK-2 cell injury in response to HG by binding with PRMT1, providing a novel target for the therapeutic strategy of DN.

关键词： BTG2 Diabetic nephropathy Lipid deposition Oxidative stress PRMT1 PRMT1 GENE

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Prevalence and influencing factors of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer

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CURRENT UROLOGY 2024年第2期18卷 98-103页

作者： Fang, Xiao Ren, Kong Li, Yan Meng, Qiao Li, Mingyue Miao, Miao Zhan, Jing Wang, Xia Wu, Fei Zhang, Meixia Shandong first Med Univ & Shandong Acad Med Sci Shandong Med Univ 1 Shandong Prov Hosp Dept Urol 324Jingwu Rd Jinan 250021 Peoples R China Binzhou Med Univ Clin Med Coll 2 Dept Urol Yantai Peoples R China Shandong first Med Univ Dept Hematol Affiliated Hosp 1 Jinan Peoples R China Shandong Prov Qianfoshan hosp Jinan Peoples R China

Objectives: This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors. Materials and methods: A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study. To assess the patients, several questionnaires were used. These included the General Situation Questionnaire, General Alienation Scale, Social Impact Scale, Modified Memorial Anxiety Scale for Prostate Cancer, and Perceived Social Support Scale. Pearson correlation analysis was conducted to examine the relationships between variables, whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy. Results: Patients who underwent radical prostatectomy had a mean total score of 44.13 +/- 7.24 on the Social Alienation Scale. The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support (r = -0.627, p < 0.05) and positive associations with age, disease stigma, and anxiety (r = 0.325, 0.575, 0.421, all p's < 0.01) among patients who underwent radical prostatectomy. The findings from multiple linear regression analysis demonstrated that educational level, age, urinary incontinence, disease stigma, anxiety, and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy (p < 0.05). Conclusions: Elderly patients who undergo radical prostatectomy often experience social alienation. This study found that social alienation was associated with factors such as educational level, age, urinary incontinence, social support, anxiety, and disease stigma. Consequently, healthcare providers should actively monitor the degree of social alienation in elderly patients after radical p

关键词： Prostate cancer Social alienation Disease stigma Social support Nursing BREAST SCALE MANAGEMENT ANXIETY STIGMA LIFE MEN

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Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography

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FRONTIERS OF MEDICINE 2024年第4期18卷 649-663页

作者： Wang, Yingbin Zhang, Yu Yao, Guihua Tang, Hong Chen, Lixin Yin, Lixue Zhu, Tiangang Yuan, Jianjun Han, Wei Yang, Jun Shu, Xianhong Yang, Ya Wei, Yulin Guo, Yanli Ren, Weidong Gao, Dongmei Lu, Guilin Wu, Ji Yin, Hongning Mu, Yuming Tian, Jiawei Yuan, Lijun Ma, Xiaojing Dai, Hongyan Ding, Yunchuan Ding, Mingyan Zhou, Qing Wang, Hao Xu, Di Zhang, Mei Zhang, Yun Chinese Minist Educ State Key Lab Innovat & Transformat Luobing Theory Jinan 250012 Peoples R China Chinese Minist Educ Chinese Natl Hlth Commiss Key Lab Cardiovasc Remodeling & Funct Res Jinan 250012 Peoples R China Chinese Acad Med Sci Jinan 250012 Peoples R China Shandong Univ Dept Cardiol Qilu Hosp Jinan 250012 Peoples R China Shandong Univ Qingdao Dept Cardiol Qilu Hosp Qingdao 266000 Peoples R China Sichuan Univ West China Hosp Dept Ultrasonog Chengdu 610041 Peoples R China Jinan Univ Shenzhen Peoples Hosp Dept Ultrasonog Clin Med Coll 2 Shenzhen 518020 Peoples R China Elect Sci & Technol Univ China Affiliated Sichuan Prov Peoples Hosp Dept Ultrasonog Chengdu 610072 Peoples R China Peking Univ Dept Cardiol Peoples Hosp Beijing 100044 Peoples R China Henan Prov peoples hosp Dept Ultrasonog Zhengzhou 463599 Peoples R China Harbin Med Univ Dept Cardiol Affiliated Hosp 1 Harbin 150007 Peoples R China China Med Univ Dept Echocardiol Affiliated Hosp 1 Shenyang 110001 Peoples R China Fudan Univ Zhongshan Hosp Dept Echocardiol Shanghai 200032 Peoples R China Capital Med Univ Beijing Anzhen Hosp Dept Echocardiol Beijing 100029 Peoples R China Sun Yat Sen Univ Sun Yat Sen Mem Hosp Dept Cardiol Guangzhou 510120 Peoples R China Southwest hosp AMU Dept Ultrasonog Chongqing 400038 Peoples R China China Med Univ Dept Ultrasonog Shengjing Hosp Shenyang 110136 Peoples R China Jilin Univ Dept Ultrasonog China Japan Union Hosp Changchun 130033 Peoples R China Shihezi Univ Affiliated Hosp 1 Sch Med Dept Ultrasonog Shihezi 832000 Peoples R China Guangxi Med Univ Dept Ultrasonog Affiliated Hosp 1 Nanning 537406 Peoples R China Hebei Med Univ Dept Echocardiol Hosp 2 Shijiazhuang 050061 Peoples R China Xinjiang Med Univ Dept Ultrasonog Affiliated Hosp 1 Urumqi 830054 Peoples R China Harbin Med Univ Dept Ultrasonog Affiliated Hosp 2 Harbin 150088 Peoples R China Air Force Med Univ PLA Dept Ultrasonog Tangdu Hosp Xian 710038 Peoples R China

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

关键词： three-dimensional echocardiography left ventricle left atrium normal reference values Chinese adults NORMAL VALUES EUROPEAN ASSOCIATION AMERICAN SOCIETY REFERENCE RANGES QUANTIFICATION NATIONWIDE CONSENSUS

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DAPK2 promotes autophagy to accelerate the progression of ossification of the posterior longitudinal ligament through the mTORC1 complex

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BIOCELL 2024年第9期48卷 1389-1400页

作者： Shi, Lei Yin, Jianshi Chen, Yu Shi, Jiangang Miao, Jinhao Shanghai Changzheng hosp Dept Spine Surg Shanghai 200003 Peoples R China Chinese peoples Liberat Army Hosp 967 Dept Orthoped Dalian 116000 Peoples R China

Background: Ossification of the posterior longitudinal ligament (OPLL) is a prevalent condition in orthopedics. While death-associated protein kinase 2 (DAPK2) is known to play roles in cellular apoptosis and autophagy, its specific contributions to the advancement of OPLL are not well understood. Methods: Ligament fibroblasts were harvested from patients diagnosed with OPLL. Techniques such as real-time reverse transcriptasepolymerase chain reaction (RT-qPCR) and Western blot analysis were employed to assess DAPK2 levels in both ligament tissues and cultured fibroblasts. The extent of osteogenic differentiation in these cells was evaluated using an alizarin red S (ARS) staining. Additionally, the expression of ossification markers and autophagy markers was quantified. The autophagic activity was further analyzed through LC3 immunofluorescence and transmission electron microscopy (TEM). An in vivo heterotopic bone formation assay was conducted in mice to assess the role of DAPK2 in ossification. Results: Elevated DAPK2 expression was confirmed in both OPLL patient tissues and derived fibroblasts, in contrast to non-OPLL controls. Silencing of DAPK2 significantly curtailed osteogenic differentiation and autophagy in these fibroblasts, evidenced by decreased levels of LC3, and Beclin1, and reduced autophagosome formation. Additionally, DAPK2 was found to inhibit the mechanistic target of the rapamycin complex 1 (mTORC1) complex's activity. In vivo studies demonstrated that DAPK2 facilitates ossification, and this effect could be counteracted by the mTORC1 inhibitor rapamycin. Conclusion: DAPK2 enhances autophagy and osteogenic processes in OPLL through modulation of the mTORC1 pathway.

关键词： Ossification fi cation of the posterior longitudinal ligament DAPK2 Autophagy mTORC1 IMPACT

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Moderate expression of CD39 in GPC3-CAR-T cells shows high efficacy against hepatocellular carcinoma

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FRONTIERS OF MEDICINE 2024年第4期18卷 708-720页

作者： Zou, Fan Wei, Jialiang Zhuang, Jialang Liu, Yafang Tan, Jizhou Huang, Xianzhang Liu, Ting Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Guangdong Cardiovasc Inst Guangzhou 510080 Peoples R China Southern Med Univ Guangdong Prov Peoples Hosp Med Res Inst Guangdong Acad Med Sci Guangzhou 510080 Peoples R China Guangzhou Univ Chinese Med Guangdong Prov Hosp Chinese Med State Key Lab Tradit Chinese Med Syndrome Dept Lab MedClin Med Coll 2 Guangzhou 510120 Peoples R China Guangxi Med Univ Affiliated Hosp 1 Dept Med Oncol Nanning 530021 Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Dept Stomatol Guangzhou 510080 Peoples R China Shenzhen Polytech Univ Sch Food & Drug Shenzhen 518055 Peoples R China Shenzhen Univ Affiliated Hosp 1 Shenzhen Peoples Hosp 2 Shenzhen 518055 Peoples R China

CD39 serves as a crucial biomarker for neoantigen-specific CD8+ T cells and is associated with antitumor activity and exhaustion. However, the relationship between CD39 expression levels and the function of chimeric antigen receptor T (CAR-T) cells remains controversial. This study aimed to investigate the role of CD39 in the functional performance of CAR-T cells against hepatocellular carcinoma (HCC) and explore the therapeutic potential of CD39 modulators, such as mitochondrial division inhibitor-1 (mdivi-1), or knockdown CD39 through short hairpin RNA. Our findings demonstrated that glypican-3-CAR-T cells with moderate CD39 expression exhibited a strong antitumor activity, while high and low levels of CD39 led to an impaired cellular function. Methods modulating the proportion of CD39 intermediate (CD39int)-phenotype CAR-T cells such as mdivi-1 and CD39 knockdown enhanced and impaired T cell function, respectively. The combination of mdivi-1 and CD39 knockdown in CAR-T cells yielded the highest proportion of infiltrated CD39int CAR-T cells and demonstrated a robust antitumor activity in vivo. In conclusion, this study revealed the crucial role of CD39 in CAR-T cell function, demonstrated the potential therapeutic efficacy of combining mdivi-1 with CD39 knockdown in HCC, and provided a novel treatment strategy for HCC patients in the field of cellular immunotherapy.

关键词： CD39 CAR-T cells mdivi-1 hepatocellular carcinoma antitumor activity CD73

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Efficacy of acupuncture in refractory irritable bowel syndrome patients: a randomized controlled trial

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FRONTIERS OF MEDICINE 2024年第4期18卷 678-689页

作者： Zhao, Jun Zheng, Hui Wang, Xin Wang, Xuefei Shi, Yunzhou Xie, Chaorong Tao, Qingfeng Li, Da Sun, Jingwen Tian, Junjian Gao, Junxia Liu, Huimin Shi, Suhua Ni, Jinxia Xue, Rongdan Hu, Hui Chen, Min Yu, Shuguang Li, Zhigang Beijing Univ Chinese Med Sch Acupuncture Moxibust & Tuina Beijing 100029 Peoples R China Sichuan Univ West China Hosp Dept Integrated Tradit & Western Med Chengdu Peoples R China Chengdu Univ Tradit Chinese Med Hosp 3 Acupuncture & Tuina Sch Chengdu 610000 Peoples R China Capital Med Univ Beijing Hosp Tradit Chinese Med Beijing 100010 Peoples R China Beijing Univ Chinese Med Dept Acupuncture & Moxibust Dongzhimen Hosp Beijing 100700 Peoples R China Beijing Univ Chinese Med Affiliated Hosp 3 Dept Rehabil Beijing 100029 Peoples R China Beijing Univ Chinese Med Dongfang Hosp Dept Acupuncture & Moxibust Beijing 100078 Peoples R China hosp Chengdu Univ Tradit Chinese Med Anorectal Dis Dept Chengdu 610075 Peoples R China

Previous studies have confirmed that acupuncture for irritable bowel syndrome (IBS) provided an additional benefit over usual care alone. Therefore, we performed a multicenter, randomized, sham-controlled trial to assess the efficacy and safety of acupuncture versus sham acupuncture for refractory IBS in patients in the context of conventional treatments. Patients in the acupuncture and sham acupuncture groups received real or sham acupuncture treatment in 3 sessions per week for a total of 12 sessions. The primary outcome was a change in the IBS-Symptom Severity Scale (IBS-SSS) score from baseline to week 4. A total of 521 participants were screened, and 170 patients (85 patients per group) were enrolled and included in the intention-to-treat analysis. Baseline characteristics were comparable across the two groups. From baseline to 4 weeks, the IBS-SSS total score decreased by 140.0 (95% CI: 126.0 to 153.9) in the acupuncture group and 64.4 (95% CI: 50.4 to 78.3) in the sham acupuncture group. The between-group difference was 75.6 (95% CI: 55.8 to 95.4). Acupuncture efficacy was maintained during the 4-week follow-up period. There were no serious adverse events. In conclusion, acupuncture provided benefits when combined with treatment as usual, providing more options for the treatment of refractory IBS.

关键词： acupuncture functional gastrointestinal disorders irritable bowel syndrome clinical trial

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Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac

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FRONTIERS OF MEDICINE 2024年第4期18卷 744-751页

作者： Long, Zhangbiao Jiang, Suyu Xin, Honglei Zhang, Lu Lu, Ruinan Liu, Fengqi Xu, Yong Wang, Linv Wang, Jun Zhang, Xuezhong Liao, Hui Shi, Jinning Yan, Xue Zhu, Xiang Shao, Ruonan Li, Zijian Zhu, Yilin Yan, Han Wu, Jiao Fang, Chao Xi, Xiaodong Shi, Xiaofeng Anhui Med Univ Affiliated Hosp 1 Dept Hematol Hefei 230022 Peoples R China Nanjing Med Univ Affiliated Hosp 2 Dept Hematol Nanjing 210003 Peoples R China Nanjing Med Univ Jiangsu Prov Hosp Affiliated Hosp 1 Dept Hematol Nanjing 210029 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Affiliated Hosp Dept HematolMed Sch Nanjing 210008 Peoples R China Nanjing Univ Chinese Med Affiliated Hosp Clin Med Coll 1 Dept Hematol Nanjing 210009 Peoples R China Southeast Univ Zhongda Hosp Dept Hematol Nanjing 210044 Peoples R China Nanjing Med Univ Nanjing Hosp 1 Dept Hematol Nanjing 210006 Peoples R China Air Force hosp Eastern Theater Command Dept Hematol Nanjing 210016 Peoples R China Nanjing Med Univ Affiliated Jiangning Hosp Dept Hematol Nanjing 211199 Peoples R China Nanjing hosp Chinese Med Dept Hematol Nanjing 210006 Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Basic Med Dept Pharmacol Wuhan 430030 Peoples R China Huazhong Univ Sci & Technol State Key Lab Diag & Treatment Severe Zoonot Infec Key Lab Drug Target Res & Pharmacodynam Evaluat Hu Wuhan 430030 Peoples R China Shanghai Jiao Tong Univ Ruijin Hosp Sch Med State Key Lab Med GenomShanghai Inst Hematol Shanghai Peoples R China

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including ***2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors' knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.

关键词： thrombotic thrombocytopenia purpura (TTP) corona virus disease 2019 (COVID-19) CoronaVac acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine

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Advanced strategies for 3D-printed neural scaffolds: materials, structure, and nerve remodeling

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BIO-DESIGN AND MANUFACTURING 2024年第5期7卷 747-770页

作者： He, Jian Qiao, Liang Li, Jiuhong Lu, Junlin Fu, Zhouping Chen, Jiafang Zhang, Xiangchun Hu, Xulin Henan Univ Sci & Technol Coll Basic Med & Forens Med Luoyang 471023 Peoples R China Henan Univ Sci & Technol Affiliated Hosp 1 Coll Clin Med Luoyang 471003 Peoples R China Chinese Acad Agr Sci Tea Res Inst Hangzhou 310008 Peoples R China Chengdu Univ Affiliated Hosp Clin Med Coll Chengdu 610081 Peoples R China Sichuan Univ West China Hosp Dept Cardiovasc Surg Dept BiotherapyCanc Ctr Chengdu 610041 Peoples R China Sichuan Univ West China Hosp State Key Lab Biotherapy Chengdu 610041 Peoples R China Sichuan Univ West China Hosp Dept Neurosurg Chengdu 610041 Peoples R China

Nerve regeneration holds significant potential in the treatment of various skeletal and neurological disorders to restore lost sensory and motor functions. The potential of nerve regeneration in ameliorating neurological diseases and injuries is critical to human health. Three-dimensional (3D) printing offers versatility and precision in the fabrication of neural scaffolds. Complex neural structures such as neural tubes and scaffolds can be fabricated via 3D printing. This review comprehensively analyzes the current state of 3D-printed neural scaffolds and explores strategies to enhance their design. It highlights therapeutic strategies and structural design involving neural materials and stem cells. first, nerve regeneration materials and their fabrication techniques are outlined. The applications of conductive materials in neural scaffolds are reviewed, and their potential to facilitate neural signal transmission and regeneration is highlighted. Second, the progress in 3D-printed neural scaffolds applied to the peripheral and central nerves is comprehensively evaluated, and their potential to restore neural function and promote the recovery of different nervous systems is emphasized. In addition, various applications of 3D-printed neural scaffolds in peripheral and neurological diseases, as well as the design strategies of multifunctional biomimetic scaffolds, are discussed.

关键词： Nerve regeneration 3D printing based neural scaffolds Biomaterials Nervous system Design strategies SPINAL-CORD-INJURY PERIPHERAL-NERVE STEM-CELLS 3D FABRICATION DIFFERENTIATION INKS

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Apatinib reduces liver cancer cell multidrug resistance by modulating NF-κB signaling pathway

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BIOCELL 2024年第9期48卷 1331-1341页

作者： He, Xiaoxiao Zhou, Xueqing Zhang, Jinpeng Zhang, Mingfei Zeng, Danhong Zhang, Heng Yang, Shucai Huazhong Univ Sci & Technol Cent Hosp Wuhan Tongji Med Coll Dept Gastroenterol Wuhan 430022 Peoples R China Southern Med Univ Pingshan Hosp Pingshan Dist Peoples Hosp Shenzhen Dept Clin Lab Shenzhen 518118 Peoples R China

Objectives: This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro. Methods: To establish a Hep3B/5-Fu resistant cell line, 5-Fu concentrations were gradually increased in the culture media. Hep3B/5-Fu cells drug resistance and its alleviation by apatinib were confirmed via flow cytometry and Cell Counting Kit 8 (CCK8) test. Further, Nuclear factor kappa B (NF-kappa B) siRNA was transfected into Hep3B/5-Fu cells to assess alterations in the expression of multidrug resistance (MDR)-related genes and proteins. Nude mice were injected with Hep3B/5-Fu cells to establish subcutaneous xenograft tumors and then categorized into 8 treatment groups. The treatments included oxaliplatin, 5-Fu, and apatinib. In the tumor tissues, the expression of MDRrelated genes was elucidated via qRT-PCR, immunohistochemistry, and Western blot analyses. Results: The apatinibtreated mice indicated slower tumor growth with smaller size compared to the control group. Both the in vivo and in vitro investigations revealed that the apatinib-treated groups had reduced expression of MDR genes GST-pi, LRP, MDR1, and p-p65. Conclusions: Apatinib effectively suppresses MDR in human hepatic cancer cells by modulating the expression of genes related to MDR, potentially by suppressing the NF-kappa B signaling pathway.

关键词： Apatinib Liver cancer Multidrug resistance NF-kappa B signaling pathway DRUG-RESISTANCE CHEMOTHERAPY SENSITIVITY EXPRESSION ADENOCARCINOMA PROGRESS THERAPY GENE

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RNF26 up-regulates PD-L1 to regulate the cancer immune response in ccRCC

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BIOCELL 2024年第9期48卷 1323-1330页

作者： Ren, Weigang Li, Jing Zeng, Ruijiang Zhu, L. iang Hunan Normal Univ Hunan Prov Peoples Hosp Dept Urol Changsha 410000 Peoples R China Cent South Univ Second Xiangya Hosp Dept Rehabil Changsha 410000 Peoples R China Cent South Univ Second Xiangya Hosp Dept Urol Changsha 410000 Peoples R China Cent South Univ Urooncol Inst Changsha 410000 Peoples R China

Background: Clear cell renal cell carcinoma (ccRCC) stands as the most prevalent form of kidney cancer, accounting for a significant proportion of malignancies affecting the kidneys. ccRCC is well known as a type of tumour with immunogenicity. Immune checkpoint inhibitors (ICIs) aim to enhance the anticancer immune response in ccRCC by blocking programmed cell death 1 ligand 1/programmed death 1 (PD-L1/PD-1) pathways. In a previous study, we showed that RING finger protein 26 (RNF26) degrades chromobox 7 (CBX7) to activate the tumor necrosis factor (TNF) in ccRCC. Methods: We analyzed The Cancer Genome Atlas (TCGA) database using the R package ESTIMATE and found that RNF26 was significantly associated with ccRCC immune infiltration. The relationship between RNF26 and the PD1 checkpoint signaling pathway was detected by enrichment analysis. In addition, the molecular mechanism of RNF26 up-regulation of PD-L1 was detected by transcriptome sequencing, RT-qPCR, and Western Blot in ccRCC cell lineages 786-O and A498 cells. The transplantation tumor experiments in C57BL/6 mice were used to test the efficacy of anti-PD1 and knockdown of RNF26 in vivo. Results: We showed that RNF26 suppressed the immune response to ccRCC. Next, we revealed that RNF26 activated the PD-1 checkpoint pathway to suppress the immune response to ccRCC, possibly via the CBX7/PD-L1 axis. Conclusion: The suggestion derived from our results is that targeting RNF26 holds the potential to amplify the efficacy of anticancer immunotherapies in the treatment of ccRCC.

关键词： Clear cell renal cell carcinoma Ring fi nger protein 26 chromobox 7 PD-L1 RENAL-CELL CARCINOMA PROTEIN INSIGHTS

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