1.Nanoengineered cargo with targeted in vivo Foxo3 gene editing modulated mitophagy of chondrocytes to alleviate osteoarthritis.
Manyu CHEN ; Yuan LIU ; Quanying LIU ; Siyan DENG ; Yuhan LIU ; Jiehao CHEN ; Yaojia ZHOU ; Xiaolin CUI ; Jie LIANG ; Xingdong ZHANG ; Yujiang FAN ; Qiguang WANG ; Bin SHEN
Acta Pharmaceutica Sinica B 2025;15(1):571-591
Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.
2.Study on sepsis induced by liver abscess in mice due to hypervirulent Klebsiella pneumoniae
Ziwen XIE ; Liming FAN ; Weiyu JIANG ; Keyi GONG ; Xingdong ZHANG ; Jiadong WANG ; Ziyan JIANG ; Qiang WANG ; Jiaqi FANG
Chinese Journal of Microbiology and Immunology 2025;45(3):231-238
Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.
3.Synergistic diagnostic potential of novel biomarkers SYWC and ADA for tuberculous pleural effusion
Chunhong FAN ; Wenlong HU ; Limei ZHU ; Ruifu YANG ; Daxia CAI ; Shaohua LU ; Xingdong CAI
The Journal of Practical Medicine 2025;41(15):2406-2411
Objective To evaluate the respective or synergistic value of cytoplasmic tryptophan-tRNA ligase(WARS1/SYWC)and adenosine deaminase(ADA)in diagnosing tuberculous pleural effusion(TPE).Methods A retrospective analysis was conducted on 120 patients with pleural effusion(64 cases of TPE,56 cases of non-TPE)admitted to the First Affiliated Hospital of Jinan University and its affiliated Shunde Hospital from January 2020 to December 2024.Pleural fluid SYWC levels were identified using enzyme-linked immunosorbent assay(ELISA).Univariate and multivariate logistic regression analyses were performed to identify diagnostic predictors,while receiver operating characteristic(ROC)curves were plotted to assess the diagnostic perfor-mance of individual and combined biomarkers.Results Compared to the non-TPE group,TPE group exhibited significantly younger age,lower pleural CEA,less serum CEA,and lower neutrophil-to-lymphocyte ratio(NLR),but significantly higher levels of pleural ADA,total protein,SYWC,and serum CRP(all P<0.05).Univariate analysis identified age,pleural CEA,carbohydrate antigen 199,ADA,SYWC,serum CEA,and NLR as potential predictors.Multivariate analysis confirmed pleural ADA(OR=1.064,95%CI:1.017~1.228)and SYWC(OR=6.695,95%CI:2.794~16.04)as independent diagnostic factors.At optimal cutoffs,SYWC(16.94 μg/L)demonstrated a sensitivity of 71.80%and specificity of 98.21%,while ADA(36.5 U/L)showed a sensitivity of 93.75%and a specificity of 89.29%.Combined detection increased the sensitivity to 95.56%,the specificity to 98.0%,and the accuracy to 97.87%.ROC analysis revealed an AUC of 0.973(95%CI:0.943~1.000)for the combination,outperforming ADA(0.897)and SYWC(0.938)alone.Conclusion The combi-nation of SYWC and ADA notably enhances diagnostic efficacy for TPE,providing high sensitivity and specificity as a reliable tool for clinical differentiation.
4.Synergistic diagnostic potential of novel biomarkers SYWC and ADA for tuberculous pleural effusion
Chunhong FAN ; Wenlong HU ; Limei ZHU ; Ruifu YANG ; Daxia CAI ; Shaohua LU ; Xingdong CAI
The Journal of Practical Medicine 2025;41(15):2406-2411
Objective To evaluate the respective or synergistic value of cytoplasmic tryptophan-tRNA ligase(WARS1/SYWC)and adenosine deaminase(ADA)in diagnosing tuberculous pleural effusion(TPE).Methods A retrospective analysis was conducted on 120 patients with pleural effusion(64 cases of TPE,56 cases of non-TPE)admitted to the First Affiliated Hospital of Jinan University and its affiliated Shunde Hospital from January 2020 to December 2024.Pleural fluid SYWC levels were identified using enzyme-linked immunosorbent assay(ELISA).Univariate and multivariate logistic regression analyses were performed to identify diagnostic predictors,while receiver operating characteristic(ROC)curves were plotted to assess the diagnostic perfor-mance of individual and combined biomarkers.Results Compared to the non-TPE group,TPE group exhibited significantly younger age,lower pleural CEA,less serum CEA,and lower neutrophil-to-lymphocyte ratio(NLR),but significantly higher levels of pleural ADA,total protein,SYWC,and serum CRP(all P<0.05).Univariate analysis identified age,pleural CEA,carbohydrate antigen 199,ADA,SYWC,serum CEA,and NLR as potential predictors.Multivariate analysis confirmed pleural ADA(OR=1.064,95%CI:1.017~1.228)and SYWC(OR=6.695,95%CI:2.794~16.04)as independent diagnostic factors.At optimal cutoffs,SYWC(16.94 μg/L)demonstrated a sensitivity of 71.80%and specificity of 98.21%,while ADA(36.5 U/L)showed a sensitivity of 93.75%and a specificity of 89.29%.Combined detection increased the sensitivity to 95.56%,the specificity to 98.0%,and the accuracy to 97.87%.ROC analysis revealed an AUC of 0.973(95%CI:0.943~1.000)for the combination,outperforming ADA(0.897)and SYWC(0.938)alone.Conclusion The combi-nation of SYWC and ADA notably enhances diagnostic efficacy for TPE,providing high sensitivity and specificity as a reliable tool for clinical differentiation.
5.Study on sepsis induced by liver abscess in mice due to hypervirulent Klebsiella pneumoniae
Ziwen XIE ; Liming FAN ; Weiyu JIANG ; Keyi GONG ; Xingdong ZHANG ; Jiadong WANG ; Ziyan JIANG ; Qiang WANG ; Jiaqi FANG
Chinese Journal of Microbiology and Immunology 2025;45(3):231-238
Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.
6.Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).
Qing ZHAO ; Tong WANG ; Hongbin WANG ; Peng CAO ; Chengyu JIANG ; Hongzhi QIAO ; Lihua PENG ; Xingdong LIN ; Yunyao JIANG ; Honglei JIN ; Huantian ZHANG ; Shengpeng WANG ; Yang WANG ; Ying WANG ; Xi CHEN ; Junbing FAN ; Bo LI ; Geng LI ; Bifeng LIU ; Zhiyang LI ; Suhua QI ; Mingzhen ZHANG ; Jianjian ZHENG ; Jiuyao ZHOU ; Lei ZHENG ; Kewei ZHAO
Chinese Herbal Medicines 2024;16(1):3-12
To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
7.Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine.
Xingdong ZHOU ; Hui WANG ; Qun JI ; Mingjuan DU ; Yuexia LIANG ; Huanhuan LI ; Fan LI ; Hang SHANG ; Xiujuan ZHU ; Wei WANG ; Lichun JIANG ; Alexey V STEPANOV ; Tianyu MA ; Nanxin GONG ; Xiaodong JIA ; Alexander G GABIBOV ; Zhiyong LOU ; Yinying LU ; Yu GUO ; Hongkai ZHANG ; Xiaoming YANG
Protein & Cell 2021;12(10):818-823
8.Oral health in China: from vision to action.
Xuedong ZHOU ; Xin XU ; Jiyao LI ; Deyu HU ; Tao HU ; Wei YIN ; Yujiang FAN ; Xingdong ZHANG
International Journal of Oral Science 2018;10(1):1-1
Chinese president Xi Jinping made clear at the National Health and Wellness Conference that health is the prerequisite for people's all-around development and a precondition for the sustainable development of China. Oral health is an indispensable component of overall health in humans. However, the long neglect of oral health in overall health agendas has made oral diseases an increasing concern. With this perspective, we described the global challenges of oral diseases, with an emphasis on the challenges faced by China. We also described and analyzed the recently released health policies of the Chinese government, which aim to guide mid-term and long-term oral health promotion in China. More importantly, we called for specific actions to fulfill the larger goal of oral health for the nation. The implementation of primordial prevention efforts against oral diseases, the integration of oral health into the promotion of overall health, and the management of oral diseases in conjunction with other chronic non-communicable diseases with shared risk factors were highly recommended. In addition, we suggested the reform of standard clinical residency training, the development of domestic manufacturing of dental equipment and materials, the revitalization traditional Chinese medicine for the prevention and treatment of oral diseases, and integration of oral health promotion into the Belt and Road Initiative. We look forward to seeing a joint effort from all aspects of the society to fulfill the goal of Healthy China 2030 and ensure the oral health of the nation.
China
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Health Policy
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Humans
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National Health Programs
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Oral Health
9.A review of research progress on biological effects about nanometer scaffold for bone tissue engineering.
Bo LI ; Huawei HE ; Xiaoling LIAO ; Hongsong FAN ; Xingdong ZHANG
Journal of Biomedical Engineering 2011;28(5):1035-1039
Quite a few orthopedics experts have fabricated some novel bone scaffolds with nanotechnology and have carried out some researches on nano-biological effects. The study of the biological effects about nano-biomaterials can facilitate the understanding of the interaction between the biomaterials and the organism, and provide research ideas and direction to construct new biomaterials with physiological function. To better understand the interaction of nano biomaterials with protein, cells and bio-security, this review presents recent advances of biological effects about nano scaffold for bone tissue engineering.
Biocompatible Materials
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metabolism
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Bone Substitutes
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Bone and Bones
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Humans
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Nanostructures
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Nanotechnology
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Surface Properties
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Tissue Engineering
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methods
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Tissue Scaffolds
10.Preliminary clinical utility of ROI volume measurement for the oral and maxillofacial AVM before embolization
Journal of Interventional Radiology 1994;0(03):-
Objective To evaluate the clinical utility of ROI(region of intest)volume measurement for interventional embolization of the oral and maxillofacial AVM before intervention.Methods four patients with oral and maxillofacial AVM were undertaken,ROI volume measurement of AVM by GE AW 4.1 software based on the MRI and MSCT imaging data,and the quantity of embolic agent was administered correspondingly to the measured volume of AVM lesion and then,the therapeutic effect was observed.Results In 3 cases of this series,the volume of AVM lesions obtained by ROI volume measurement based on the imaging data were 7.515 cm3,1.195 cm3 and 10.714 cm3,respectively;gaining all the therapeutic satisfactory effects.However,the volume of the other case was not achieved because of the bilateral diffuse AVM with previous ligation of feeding arteries.Conclusions Soft tissue AVM can be best demonstrated on MRI and MSCT therefore can display AVM of jaw clearly.Pre-embolization of oral and maxillofacial AVM,the quantity of embolic agent(especially the liquid agent) can be estimated correctly by the ROI volume measurement used GE AW 4.1 software.

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