1.Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma
Shan LI ; Jie HU ; Yihan YAN ; Xinrui LIU ; Xiao DONG ; Huijun LIANG ; Xin TANG ; Junji TAO ; Rong ZHANG ; Yuan HU ; Ailong HUANG ; Kai WANG ; Ni TANG
Clinical and Molecular Hepatology 2026;32(2):661-682
Background/Aims:
Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial.
Methods:
A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining.
Results:
Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth.
Conclusions
These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.
2.Analysis of toxic material basis of Dryopteris crassirhizoma by UPLC-ESI-MS/MS
Rong-hui ZHENG ; Cui-jie WEI ; Fei-fei XIE ; Xin-ya WAN ; Xiao-jie LIANG ; Zhi-wen DUAN ; Dong-mei SUN ; Xiang-dong CEHN
Chinese Traditional Patent Medicine 2025;47(10):3305-3314
AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95%ethanol cold soaked ultrasonic extract(EC),95%ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2%formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.
3.Effect of 3D laparoscopic radical prostatectomy on urinary control and sexual function of patients with prostate cancer
Jie XIE ; Zhen-jia DONG ; Qiang-dong WANG ; Yao YAN ; Xu XIAO
National Journal of Andrology 2025;31(8):703-708
Objective:To investigate the effects of 3 D laparoscopic radical resection prostatectomy(LRP)on urinary control and sexual function of patients with prostatic cancer.Methods:A total of 268 patients who were treated with LRP in the Fifth People's Hospital of Huai an City from January 2019 to May 2022 were selected and divided into 2 groups according to surgical methods,with 134 cases in each group.The patients in the control group were treated with traditional LRP,and the 3D LRP was used in the observa-tion group.The clinical effects of the two groups were compared.Results:The patients in observation group had less blood loss([135.62±13.58]mL vs[143.18±14.89]mL)and shorter indwelling catheter time([8.26±1.47]d vs[9.78±1.73]d)compared with control group,but the operation time([160.52±10.78]min vs[154.47±10.41]min)was longer than that in the control group(P<0.05).The recovery of sexual function and urinary control in the observation group was better than that in the con-trol group after 3,6 and 12 months of the surgery(P<0.05).After one month of surgery,the scores of ICIQ-SF and 1 h urine pad test were lower than those of the control group.The EPIC-UIN score([72.63±6.85]points vs[67.15±5.09]points)of the observation group was higher than that of the control group(P<0.05).The patients in the observation group had lower level of residual urine volume([60.26±6.63]mL vs[76.89±7.89]mL),higher maximum urine flow rate([7.52±0.46]mL/s vs[6.17±0.43]mL/s)and detrusor pressure([85.19±7.18]mL vs[76.29±6.85]mL)at maximum urine flow rate compared with the control group(P<0.05).There was no difference in the incidence of complications between the observation group and the control group(5.97%vs 8.27%,P>0.05).The recurrence rate of tumor 3 years after operation in the observation group was lower than that in the control group(11.94%vs 29.10%,x2=12.102,P<0.05).Conclusion:3D LRP has obvious advantages in surgical clarity and preci-sion,which reduces the risk of postoperative complications and improves urinary control ability and sexual function of patients.
4.Correlation between serum creatinine-to-cystatin C ratio and muscle mass and strength in peritoneal dialysis patients
Nan ZHANG ; Xinqiu LI ; Xiao XU ; Jie DONG
Chinese Journal of Nephrology 2025;41(5):325-331
Objective:To explore the correlation between serum creatinine/cystatin C ratio (Scr/CysC) and muscle mass and muscle strength, and evaluate the predictive value of Scr/CysC for all-cause mortality in peritoneal dialysis patients.Methods:It was a prospective cohort study. The patients who received regular peritoneal dialysis treatment for more than 3 months and had stable conditions in the Renal Division of Peking University First Hospital from April 1, 2011 to August 1, 2012 were included, and the clinical data were collected. The patients were divided into the male group and the female group, and the differences of clinical data between the two groups were compared. The lean body mass (LBM) directly measured by the dual-energy X-ray absorptiometry (LBM-DEXA) was used as the reference gold standard and compared with the LBM estimated by the creatinine method (LBM-CK) and the anthropometric method (LBM-A). Muscle strength was measured by a grip strength meter for the dominant hand grip strength. Pearson correlation and multiple linear regression analysis method were used to analyze the correlations between Scr/CysC and LBM as well as grip strength, and subgroup analyses were conducted according to gender groups. Cox regression model was used to analyze the value of Scr/CysC in predicting all-cause mortality in peritoneal dialysis patients.Results:A total of 213 peritoneal dialysis patients were included in this study, including 95 males (44.6%) and 118 females (55.4%). The age was (56.46±12.42) years old. The dialysis age was 24.0 (9.0, 52.5) months. The baseline Scr/CysC was (1.77±0.73). LBM-DEXA ( t=-17.764, P<0.001), LBM-CK ( t=-7.702, P<0.001), LBM-A ( t=-16.813, P<0.001), grip strength ( t=-11.083, P<0.001) and Scr/CysC ( t=-2.965, P=0.003) in the male group were all significantly higher than those in the female group. Pearson correlation analysis showed that Scr/CysC was positively correlated with LBM-DEXA ( r=0.204, P=0.003), LBM-CK ( r=0.279, P<0.001), LBM-A ( r=0.198, P=0.004), and grip strength ( r=0.341, P<0.001). Multiple linear regression analysis showed that Scr/CysC wasn't independently correlated with LBM-DEXA, but was independently correlated with grip strength ( β=0.134, P=0.006). Cox regression analysis showed that baseline Scr/CysC was not an independent influencing factor of all-cause mortality in peritoneal dialysis patients ( HR=1.005, 95% CI 0.751-1.346, P=0.972). Conclusion:Scr/CysC is associated with muscle mass and muscle strength in peritoneal dialysis patients, but has no value in predicting all-cause mortality in peritoneal dialysis patients.
5.Mechanism of Polygonum capitatum on atherosclerosis based on data mining
Zi YE ; Yun-pei WANG ; Yu-hui WANG ; Xun-de XIAN ; Xiao-jie LI ; Chun-hua HUANG ; Yuan-zhu LIAO ; Di-dong LOU ; Yi-xia ZHOU
Chinese Pharmacological Bulletin 2025;41(12):2369-2378
Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.
6.Novel Structural Features of Isoflavone Synthase from Medicago truncatula Shed Light on Its Unique Enzymatic Mechanism
Chao SHI ; Zhao-Yang YE ; Fei XU ; Xiang-Ning DU ; Zhang-Xin CHEN ; Ming-Yue GU ; Jie DENG ; Wei WANG ; Liang-Yu LIU ; Mei-Ying WANG ; Xiao-Dong SU ; He-Li LIU ; Ming-Ying SHANG ; Li-Xin HUANG ; Zhen-Zhan CHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1204-1213,中插1-中插6
Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.
7.Analysis of magnetic resonance imaging features of spinal adnexal tuberculosis
Yuan TIAN ; Ning WU ; Jie-ai LIU ; Mei TIAN ; Yue DENG ; Shan YU ; Xiao-dong YUAN
Chinese Medical Equipment Journal 2025;46(1):55-59
Objective To summarize the magnetic resonance imaging(MRI)features of spinal adnexal tuberculosis in order to improve its early diagnosis.Methods Totally 21 spinal adnexal tuberculosis patients confirmed at some hospital from January 2019 to October 2023 had their clinical data and MRI images analyzed retrospectively to determine the basic clinical characteristics and MRI features.Results Of the 21 patients,8 ones had sudden lower extremity weakness and pyramidal tract signs,and the remaining 13 ones had no significant symptoms of neurologic deficit.The lesion involvement ranged from C4 to L5 vertebrae,with the involvement of lumbar segments in 13 cases,thoracic segments in 6 cases and cervical segments in 2 cases.There were 15 cases that had tuberculosis involving in only a single spinal adnexa and peripheral soft tissue,4 cases in 2 vertebrae and 2 cases in 3 vertebrae.There were 9 cases involving in pedicles,8 cases in vertebral plates and some cases involving in sphenoid process,transverse process or facet joints.The MRI features of spinal adnexal tuberculosis included the tuberculosis-infected bone showing slightly low signals on T1WI while slightly high signals on T2WI,edge enhancement by enhanced scan and edema and abscess of paravertebral soft tissue and intra-and extradural tuberculous abscess displayed clearly by the fat suppression and diffusion weighted imaging sequences of T2WI.Conclusion MRI effectively detects the abnormal signs of bone and soft tissue of spinal adnexal tuberculosis.The MRI findings of spinal adnexal tuberculosis are of characteristics,and MRI can be used as the first choice for imaging examination and differential diagnosis to realize early detection of spinal adnexal tuberculosis.[Chinese Medical Equipment Journal,2025,46(1):55-59]
8.Effects of fangchinoline derivative LYY-32 on biological properties of BLM DNA helicase
Wang-ming ZHANG ; Qin-ying FENG ; Xiao-yu SONG ; Xin-zhong ZHOU ; Juan LU ; Wan-qing XIE ; Zhi-wen LAI ; Wei-dong PAN ; Jie-lin LIU
Chinese Pharmacological Bulletin 2025;41(9):1680-1686
Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17%.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49%.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3%at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100%.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.
9.Detection and Transfusion Strategy of Mimicking Antibodies
Hui ZHANG ; Jie-Wei ZHENG ; Sha JIN ; Wei SHEN ; Shan-Shan LI ; Xiao-Wen CHENG ; Dong XIANG
Journal of Experimental Hematology 2025;33(4):1168-1172
Objective:To explore serological detection and blood transfusion strategies of mimicking antibodies,so as to provide appropriate transfusion strategies.Methods:Detailed serological tests,including ABO blood group,Rh typing,antibody specificity,etc,were performed on two patients with autoimmune hemolytic anemia(AIHA).Meanwhile,the references about blood transfusion from mimicking antibody patients published from 1977 to 2024 in China and abroad were retrospectively summarized and analyzed.Results:The patient 1 blood type was AB,CCDee and the antibody is mimicking anti-e,transfusion the e-negative red blood cells(RBCs)was effective.After two transfusions of e-RBCs,hemoglobin levels significantly increased from 48 g/L to 91 g/L,with complete resolution of hemolytic symptoms.The patient 2 blood type was O,CcDee,and the antibody was mimicking anti-c,the patient was diagnosed with AIHA and treated with hormone.No blood products were transfused during hospitalization,and his hemolysis was relieved.Conclusion:Strictly grasping the indication of blood transfusion,blood transfusion should not be performed in the unnecessary conditions,and the corresponding antigen-negative RBC should be screened for transfusion in the necessay conditions.
10.Correlation between serum creatinine-to-cystatin C ratio and muscle mass and strength in peritoneal dialysis patients
Nan ZHANG ; Xinqiu LI ; Xiao XU ; Jie DONG
Chinese Journal of Nephrology 2025;41(5):325-331
Objective:To explore the correlation between serum creatinine/cystatin C ratio (Scr/CysC) and muscle mass and muscle strength, and evaluate the predictive value of Scr/CysC for all-cause mortality in peritoneal dialysis patients.Methods:It was a prospective cohort study. The patients who received regular peritoneal dialysis treatment for more than 3 months and had stable conditions in the Renal Division of Peking University First Hospital from April 1, 2011 to August 1, 2012 were included, and the clinical data were collected. The patients were divided into the male group and the female group, and the differences of clinical data between the two groups were compared. The lean body mass (LBM) directly measured by the dual-energy X-ray absorptiometry (LBM-DEXA) was used as the reference gold standard and compared with the LBM estimated by the creatinine method (LBM-CK) and the anthropometric method (LBM-A). Muscle strength was measured by a grip strength meter for the dominant hand grip strength. Pearson correlation and multiple linear regression analysis method were used to analyze the correlations between Scr/CysC and LBM as well as grip strength, and subgroup analyses were conducted according to gender groups. Cox regression model was used to analyze the value of Scr/CysC in predicting all-cause mortality in peritoneal dialysis patients.Results:A total of 213 peritoneal dialysis patients were included in this study, including 95 males (44.6%) and 118 females (55.4%). The age was (56.46±12.42) years old. The dialysis age was 24.0 (9.0, 52.5) months. The baseline Scr/CysC was (1.77±0.73). LBM-DEXA ( t=-17.764, P<0.001), LBM-CK ( t=-7.702, P<0.001), LBM-A ( t=-16.813, P<0.001), grip strength ( t=-11.083, P<0.001) and Scr/CysC ( t=-2.965, P=0.003) in the male group were all significantly higher than those in the female group. Pearson correlation analysis showed that Scr/CysC was positively correlated with LBM-DEXA ( r=0.204, P=0.003), LBM-CK ( r=0.279, P<0.001), LBM-A ( r=0.198, P=0.004), and grip strength ( r=0.341, P<0.001). Multiple linear regression analysis showed that Scr/CysC wasn't independently correlated with LBM-DEXA, but was independently correlated with grip strength ( β=0.134, P=0.006). Cox regression analysis showed that baseline Scr/CysC was not an independent influencing factor of all-cause mortality in peritoneal dialysis patients ( HR=1.005, 95% CI 0.751-1.346, P=0.972). Conclusion:Scr/CysC is associated with muscle mass and muscle strength in peritoneal dialysis patients, but has no value in predicting all-cause mortality in peritoneal dialysis patients.

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