1.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
2.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
3.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
4.Identification of HMA gene family and response to cadmium stress in Ophiopogon japonicas.
Zhihui WANG ; Erli NIU ; Yuanliang GAO ; Qian ZHU ; Zihong YE ; Xiaoping YU ; Qian ZHAO ; Jun HUANG
Chinese Journal of Biotechnology 2025;41(2):771-790
Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]4P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism*
;
Adenosine Triphosphatases/metabolism*
;
Ophiopogon/drug effects*
;
Soil Pollutants/toxicity*
;
Plant Proteins/metabolism*
;
Stress, Physiological
;
Multigene Family
;
Gene Expression Regulation, Plant
5.Value of prealbumin-to-total bilirubin ratio in predicting the short-term prognosis of patients with HBV-related acute-on-chronic liver failure
Wenjuan LI ; Weifeng ZHAO ; Xiaoping HUANG
Journal of Clinical Hepatology 2025;41(11):2272-2277
ObjectiveTo investigate the value of prealbumin-to-total bilirubin (PA/TBil) ratio on admission in predicting 90-day mortality or liver transplantation in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF), as well as the effect of its combination with Model for End-Stage Liver Disease (MELD) score on the predictive performance for short-term prognosis. MethodsA retrospective analysis was performed for the clinical data of 216 HBV-ACLF patients who were admitted to Department of Infectious Diseases in the First Affiliated Hospital of Soochow University from April 2020 to May 2025, and the patients were followed up for 3 months. According to the outcome, the patients were divided into survival group with 104 patients and death/transplantation group with 112 patients. The Kolmogorov-Smirnov test was used to check whether the continuous data was in accordance with the normal distribution; the two-independent-samples t test was used for comparison of normally distributed continuous data between two groups, while the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups. The chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate binary Logistic regression analyses were used to investigate the influencing factors for prognosis, and the receiver operating characteristic (ROC) curve was used to analyze the performance of each indicator in predicting the prognosis of ACLF. The area under the ROC curve (AUC) was calculated, and the Delong test was used for comparison of AUC. ResultsA total of 216 patients were enrolled in this study, with a 90-day survival rate of 48.15% (104/216). Compared with the death/transplantation group, the survival group had significantly higher platelet count, lymphocyte count, albumin, and PA/TBil ratio (all P<0.05) and significantly lower age, white blood cell count, neutrophil count, prothrombin time, international normalized ratio, aspartate aminotransferase, total bilirubin, creatinine, and MELD score (all P<0.05). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=1.05, 95% confidence interval [CI]: 1.02 — 1.09, P<0.001), PA/TBil ratio (OR=0.16, 95%CI: 0.05 — 0.46, P<0.001), and MELD score (OR=1.09, 95%CI: 1.01 — 1.17, P=0.024) were independent influencing factors for 90-day prognosis in HBV-ACLF patients. PA/TBil ratio and MELD score used alone or in combination had an AUC of 0.760, 0.779, and 0.811, respectively, in predicting the prognosis of HBV-ACLF patients, and PA/TBil ratio combined with MELD score had a better AUC than PA/TBil ratio or MELD score used alone (Z=-2.058 and 2.017, both P<0.05). ConclusionBoth serum PA/TBil ratio and MELD score can effectively predict the prognosis of patients with HBV-ACLF, and a combination of the two indicators had a better predictive performance than MELD score alone, which provides an important reference for clinical risk stratification management and timely intervention.
6.Research Progress on Mitophagy and Energy Metabolism in Digestive Tract Tumors
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(6):935-944
Mitophagy is an evolutionarily highly conserved selective autophagy process that maintains cellular homeostasis and mitochondrial quality control by specifically recognizing and removing damaged or superfluous mitochondria. During tumorigenesis, mitophagy eliminates damaged mitochondria and reduces the accumulation of reactive oxygen species (ROS), thereby helping to sustain cellular homeostasis. Energy metabolism refers to the core biological process through which cells convert chemical energy from nutrients into adenosine triphosphate (ATP) via biochemical pathways such as glycolysis and oxidative phosphorylation, providing energy for cellular activities. While research on gastrointestinal tumors is advancing rapidly, a major bottleneck lies in their complex metabolic adaptations and therapeutic resistance. Targeting the interplay between mitophagy and energy metabolism has emerged as a promising therapeutic strategy for this disease. Current research on mitophagy and energy metabolism in gastrointestinal tumors, including the molecular mechanisms of their bidirectional regulatory network and applications in targeted therapies, remains to be systematically elucidated. Therefore, this review summarizes the implications of the mitophagy-energy metabolism interplay in gastrointestinal tumors, with the aim of providing insights for future research.
7.Bionic design,preparation and clinical translation of oral hard tissue restorative materials
Han ZHAO ; Yan WEI ; Xuehui ZHANG ; Xiaoping YANG ; Qing CAI ; Chengyun NING ; Mingming XU ; Wenwen LIU ; Ying HUANG ; Ying HE ; Yaru GUO ; Shengjie JIANG ; Yunyang BAI ; Yujia WU ; Yusi GUO ; Xiaona ZHENG ; Wenjing LI ; Xuliang DENG
Journal of Peking University(Health Sciences) 2024;56(1):4-8
Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.
8.Study on the differential markers of Morus alba leaves before and after baked with honey based on fingerprint and chemometrics
Beibei YAN ; Xiaoping ZHANG ; Huanyun QIN ; Xiangjun ZHAO ; Bingmei SHAO ; Jingzhen TIAN ; Dalong MA
China Pharmacy 2024;35(10):1198-1202
OBJECTIVE To compare the changes of chemical components of Morus alba leaves, screen differential markers, and determine their contents, so as to provide reference for quality control of M. alba leaves before and after baked with honey. METHODS The fingerprints of M. alba leaves before and after baked with honey were established by high-performance liquid chromatography (HPLC). The common peaks of the fingerprints were identified and the similarity was evaluated. The differential markers of M. alba leaves before and after baked with honey were screened by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) using common peak are of raw material and product baked with honey of M. alba leaves as index. The quantitative analysis was carried out. RESULTS Twenty-three and twenty-four common peaks were identified from the HPLC fingerprint spectra of ten batches of raw material and ten batches of product baked with honey of M. alba leaves, respectively. The similarities of HPLC fingerprints for raw material and product baked with honey of M. alba leaves were all greater than 0.97. The results of PCA showed that raw material and product baked with honey of M. alba leaves could be divided into two categories. The results of OPLS-DA showed that the variable importance in projection of peak 2, peak H (5- hydroxymethylfurfural), peak 1, peak 17 (isochlorogenic acid C) and peak 16 were all greater than 1. The average contents of differential marker of isochlorogenic acid C in raw material and product baked with honey of M. alba leaves were 0.093 6 and 0.127 8 mg/g, respectively; there was statistical significance (P<0.05). CONCLUSIONS Five differential markers such as isochlorogenic acid C are obtained. The content of isochlorogenic acid C in M. alba leaves is significantly increased after baked with honey.
9.Comparative analysis of small shadow morphology between chest CT and DR images of patients with occupational pneumoconiosis
Zhongxue LI ; Xiazi ZHAO ; Yongzhong TANG ; Qianchang LI ; Shiwen HUANG ; Feifei LI ; Xiaoping LI ; Kunhai QIU
China Occupational Medicine 2024;51(3):303-307
Objective To compare the morphology differences in small shadows of occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") between computed tomography (CT) and digital radiography (DR) imaging. Methods A total of 1 010 pneumoconiosis patients were selected as the research subjects using a judgment sampling method. Chest DR imaging and CT imaging were performed on patients, and the differences in small shadow morphology between the two images were compared. Results In both DR and CT images of patients, circular small shadows identified as p, q, and r shapes accounted for 76.2%, 11.5%, and 1.3%, respectively, while irregular small shadows were identified in 1.8% of cases. There was medium high consistency between DR and CT in detecting these four types of small shadow morphology (Kappa=0.72, P<0.01). The detection rate of irregular small shadows (including interlobular septal thickening, ground-glass opacity, and/or centrilobular emphysema) by CT images was 54.0% (545/1 010), with 88.6% (483/545) of these cases also showing small circular shadows. Irregular small shadows in CT images were mostly identified as p small circular shadows in DR images, accounting for 88.8% (484/545). The results of DR and CT images for p/p, p/q, q/p, q/q, q/r, r/q and r/r in small circular shadows showed medium high consistency (Kappa =0.52, P<0.01). Conclusion The results of CT and DR imaging for pneumoconiosis with small shadow were of medium high consistency, with CT demonstrating advantages in detecting irregular small shadow morphology of pneumoconiosis. CT images can be used to describe the shape of circular small shadow as DR images, and irregular small shadow can be described as interlobular septal thickening, ground-glass opacity, and/or centrilobular emphysema.
10.Screening of aldosterone-specific antibodies based on phage display technology
Sujuan WANG ; Xiaoping TIAN ; Qiaohui ZHAO ; Tianyun WANG
Journal of Xinxiang Medical College 2024;41(3):214-220
Objective To screen out specific aldosterone(ALD)antibodies using phage display technology and recom-binant antibody technology,providing raw materials for the research and development of ALD diagnostic kits.Methods Five healthy and clean New Zealand white rabbits were selected and immunized for the first time against the diluted ALD-keyhole limpet hemocyanin antigen(2 mg·L-1)using a multi-point injection method on the back,with a dose of 1 mg per rabbit.Immunization was administered again every 2 weeks,with a 50%reduction in dose.Starting from the third immunization,the ear vein blood of the rabbits was collected one week after each immunization.A chemiluminescent plate coated with 0.25 mg·L-1 ALD-bovine serum albumin antigen was used to measure serum titers via indirect and competitive methods.After the 5th immunization,the rabbit with high serum titers and good specificity was selected,and its spleen and bone marrow were removed.The spleen tissue was grinded,and RNA was extracted using TRIzol reagent in one step to obtain gene sequences in the variable region of light chain(VL)and the variable region of heavy chain(VH).The single-chain variable fragment(ScFv)was connected through the linker and constructed into the bacteriophage vector Pcomb3xss;then,it was carried to Escherichia coli TG1 through electrotransformation,and the ALD ScFv phage display library was constructed accordingly.Three to five rounds of enrichment screening were performed against the library.Monoclonal clones,identified by enzyme-linked immunosorbent assay(ELISA)competitive method,were selected for phage supernatant preparation,and a highly competitive clone sequence was obtained.The screened clone sequence was inserted into the pCMV3 expression vector,and the HEK293 cell was transfected using the transient transfection method after the plasmid was extracted.One week later,the supernatant was collected,and its purity and expression were identified by affinity chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE).Results After the 5th immunization,the serum titers of 5 rabbits were indirectly tested,and the results showed that the serum titers of 4# and 5# white rabbits were still greater than 10,000 after being diluted by 32,000 times.The test results based on the competitive method showed that the ratio of low to high values in the plasma sample of 5#white rabbit was 2∶1,superior to that of other white rabbits.The 5# white rabbit was selected for phage library construction.The VL and VH gene fragments were amplified by conventional polymerase chain reaction,and then bridged into ScFv(VL+VH).The agar gel electrophoresis analysis showed that the size of the band was about 750 bp,which was consistent with the size of the originally designed fragment.ScFv was cleaved and electroporated into Escherichia coli TG1 to construct a phage library with a storage capacity of 4.73 × 108 cfu·mL-1.After 3 rounds of washing,300 monoclonal clones were selected from the outbound petri dishes to prepare monoclonal bacteriophages.The ELISA results showed a positive rate of 100%among the 300 clones,and 42 clones were tested positive for calibration competition,with a screening rate of 14%.The 42 positive clones were further subjected to clinical sample competition testing,and 16 monoclonal strains that met the requirements were screened.The 16 strains were retested,and the results of the two tests were consistent.After sequencing,6 antibody sequences were selected for construction and expression.After purification,SDS-PAGE reduced gel electrophoresis results showed that there were bands at positions 50,000 on the heavy chain and 25,000 on the light chain.Six highly affinitive and competitive rabbit ALD monoclonal antibodies were obtained.Conclusion Six highly affinitive and competitive rabbit ALD antibodies are successfully screened using phage display technology,which provides a reference method for the discovery of small molecule antibodies.The screened AD1 85 and AD277 antibodies show a competitive advantage twice that of the positive control in the competition of calibration and clinical samples,providing a possibility for the development of raw materials for ALD detection kits.

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