1.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
2.Beyond cancer: The potential application of CD47-based therapy in non-cancer diseases.
Wei-Qing DENG ; Zi-Han YE ; Zhenghai TANG ; Xiao-Lei ZHANG ; Jin-Jian LU
Acta Pharmaceutica Sinica B 2025;15(2):757-791
CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.
3.Study on the Genotoxicity of Graphene Artificial Nerve Sheath Conduit
Ling-xiao SUN ; Bing-bing SUN ; Yue QIN ; Guo-wei WANG ; Luan-luan WANG ; Zi-yi YANG ; Zi-ye WANG ; Xiao-tian ZHAO ; Xiao-jing LI ; Cheng-hu LIU
Progress in Modern Biomedicine 2025;25(14):2250-2258
Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5%,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.
4.Study on the Genotoxicity of Graphene Artificial Nerve Sheath Conduit
Ling-xiao SUN ; Bing-bing SUN ; Yue QIN ; Guo-wei WANG ; Luan-luan WANG ; Zi-yi YANG ; Zi-ye WANG ; Xiao-tian ZHAO ; Xiao-jing LI ; Cheng-hu LIU
Progress in Modern Biomedicine 2025;25(14):2250-2258
Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5%,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.
5.Percutaneous coronary intervention for the treatment of non-ST-segment elevation myocardial infarction combined with Lambl's excrescences on the aortic valve:a case report
Meng-qi YE ; Bang-guo YANG ; Zi-wei ZHANG ; Jiang WANG ; Jie BAI
Chinese Journal of Interventional Cardiology 2025;33(3):176-180
The Lambl's excrescences(LEs)are elongated valvular fronds with excessive mobility,commonly found at the closure lines of heart valves.These filiform projections are thin and long,exhibiting undulating independent motion.LEs predominantly occur on the ventricular side of the aortic valve and on the atrial side of the mitral valve,although there have been documented cases involving tricuspid,pulmonic,and prosthetic valves.To detect LEs,transesophageal echocardiography is often recommended.The high stress experienced by left-sided valves during closure can lead to tears or lesions in the endocardium that initiate LEs pathogenesis.In this particular case study,we present a patient who presented with acute non-ST-segment elevation myocardial infarction alongside LEs located on the non-coronary cusp of the aortic valve.This specific anatomical location posed significant challenges during percutaneous coronary intervention(PCI),as it required direct contact between the guiding catheter and the aortic valve,thereby increasing the risk of dislodging the LEs.Fortunately,our team successfully performed PCI without encountering any notable complications or embolic events.
6.LncRNA GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and Invasion of lung squamous carcinoma cells
Yu-ning HU ; Yan-lei GE ; Ye JIN ; Jun-qing GAN ; Wei-nan YAO ; Ya-nan WU ; Xuan ZHENG ; Zi-qing LIU ; Xin SU ; Guo-gui SUN
Chinese Pharmacological Bulletin 2025;41(8):1531-1541
Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P<0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P<0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P<0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P<0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P<0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P<0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P>0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.
7.Perioperative electroacupuncture for early gastrointestinal function recovery after colorectal cancer surgery:a pilot study protocol
Jiaojiao WU ; Xuqiang WEI ; Shouquan FENG ; Qunhao GU ; Jing LI ; Zi YE ; Chenchen FENG ; Lijuan PEI ; Yanbin PENG ; Jia ZHOU
Journal of Acupuncture and Tuina Science 2025;23(3):239-249
Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.
8.Selection of exosomal microRNA biomarkers for brucellosis diagnosis and construction of a potential miRNA-mRNA regulation network
Jin ZHAO ; Zhi-qiang CHEN ; Bing-Li WANG ; Shu-ling LI ; Xiao-yu ZHU ; Jin-tong JIA ; Ye-zi LIU ; Zhi-wei LI
Chinese Journal of Zoonoses 2025;41(3):269-277
This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P<0.05),hsa-miR-199a-5p(P<0.05),and hsa-miR-148a-5p(P<0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.
9.Perioperative electroacupuncture for early gastrointestinal function recovery after colorectal cancer surgery:a pilot study protocol
Jiaojiao WU ; Xuqiang WEI ; Shouquan FENG ; Qunhao GU ; Jing LI ; Zi YE ; Chenchen FENG ; Lijuan PEI ; Yanbin PENG ; Jia ZHOU
Journal of Acupuncture and Tuina Science 2025;23(3):239-249
Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.
10.Study of debridement effects of multi shapes of plasma scalpels in explosion injury model
Hong-ye ZHENG ; Yu LI ; Zi-heng XU ; Yu-fan WEI ; Bo-ya ZHANG ; Yan LI ; Li ZHU ; Xi-ru LI
Chinese Medical Equipment Journal 2025;46(2):31-38
Objective To explore the debridement effects of 3 types of plasma scalpels for the animal model of explosion injury,and to compare them with the steel scalpel and high-frequency electrosurgical scalpel.Methods Firstly,blast wounds were constructed in the right inguinal regions of 9 Landrace pigs by high-pressure gas impact combined with preset metal shrapnel.Secondly,debridement was carried out in experimental groups with wide-,arrow-or needle-type plasma scalpel and in control groups with steel and high-frequency electrisurgical scalpel,with the operating temperature and debridement time recorded during the procedure and trauma specimens analyzed pathologically after the debridement;comparisons were performed among the five types of scalpels in terms of debridement effect,and among the four ones in terms of maximum operating temperature and depth of tissue thermal damage under electrocutaneous cutting and electrocoagulation modes with the steel scalpel excluded because it did not generate any heat.GraphPad Prism 9.5.1 software was used for statistical analysis.Results There were no significant differences in debridement effect found between the three plasma scalpels and the steel and high-frequency electrosurgical scalpels(P>0.05).The three types of plasma scalpels had the maximum operating temperature lower significantly than that of the high-frequency electrosurgical scalpel during debridement(P<0.05).Under electrosection and electrocoagulation modes the three plasma scalpels had the depths of tissue thermal damage statistically less than that by the high-frequency electrosurgical scalpel under electrosection and electrocoagulation modes(P<0.05).The depths of tissue thermal damage by the four scalpels under electrocoagulation mode were obviously greater than those under electrosection mode(P<0.05).Conclusion Multi shapes of plasma scalpels behave well in debridement with low operating temperature,little tissue thermal damage and high efficiency for wound protection and the same efficacy with the steel scalpel and high-frequency electrosur-gical scalpel.[Chinese Medical Equipment Journal,2025,46(2):31-38]

Result Analysis
Print
Save
E-mail