1.Carnosic acid inhibits osteoclast differentiation by inhibiting mitochondrial activity
Haishan LI ; Yuheng WU ; Zixuan LIANG ; Shiyin ZHANG ; Zhen ZHANG ; Bin MAI ; Wei DENG ; Yongxian LI ; Yongchao TANG ; Shuncong ZHANG ; Kai YUAN
Chinese Journal of Tissue Engineering Research 2025;29(2):245-253
BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.
2.Discussion on the meaning of "yinluo" in Suwen: Shuire Xue Lun.
Haoji WU ; Rui LI ; Zixuan ZHU ; Weijie QIU ; Shangjin LIU
Chinese Acupuncture & Moxibustion 2025;45(2):249-252
By analyzing the understandings of water points (acupoints connected with the kidney) and its association with water (kidney), zangfu organs and meridian-collateral recorded in Suwen: Shuire Xue Lun (Discussion on Water and Heat Diseases in Plain Question), it is found that the recognition on the water points is different from that on water diseases in Huangdi Neijing (the Yellow Emperor 's Inner Classic). The recognition on the water points focuses on the core theory, "rooted at the kidney", to explain the water diseases. Besides, in association with the study on the connotation of "luo" in Huangdi Neijing, it is discovered that "yinluo" discussed in water points is actually the misunderstanding of "zang zhi yinluo" that means "the connection by the kidney". It is shown that the discussion of water points refer to the elaboration of zangfu organs and 57 acupoints connected with water (the kidney), rather than the theory of collaterals. The characteristics of these 57 acupoints involved and the related needling techniques provide a new approach to the treatment of zangfu diseases.
Acupuncture Points
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Humans
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Meridians
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China
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History, Ancient
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Medicine in Literature
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Medicine, Chinese Traditional/history*
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Acupuncture Therapy/history*
3.Analysis and reinterpretation of chongmai diseases and their pathological manifestations.
Weijie QIU ; Rui LI ; Yu GONG ; Zixuan ZHU ; Haoji WU ; Shangjin LIU
Chinese Acupuncture & Moxibustion 2025;45(12):1839-1845
The diseases and pathological manifestations associated with chongmai (thoroughfare vessel) are the representative in the practical applications of chongmai theory. Elucidating this theory serves as a prerequisite of acupuncture and moxibustion therapy. Based on literature analysis, the diseases and clinical manifestations of chongmai recorded in the time of Huangdi Neijing (The Yellow Emperor's Inner Classic) were analyzed so as to reinterpret the diagnostic process, pathological characteristics, and clinical manifestations of disorders, and evaluate the value of chongmai theory. Chongmai diseases were identified from the palpation initially, known as the "palpation on abdominal pulse". The "qi reversion" of chongmai represents a typical clinical manifestation of chongmai diseases, such as ji (abdominal mass), jia (abdominal hematoma), and shan (hernia), occurring in different sites of the abdomen and in different pathological stages. A part of distribution of chongmai is considered in clinical manifestation, diagnosis and treatment of acupuncture and moxibustion. To emphasize the significance of chongmai in modern acupuncture-moxibustion theory and practice, the diagnostic and therapeutic patterns of the related disorders should be considered in clinical practice. The characteristics of chongmai are reflected in three aspects: qi, blood and abdomen, which are determined by both its inherent properties and the clinical manifestations of related diseases.
Humans
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Acupuncture Therapy
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Moxibustion
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History, Ancient
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Meridians
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Medicine, Chinese Traditional
4.Progress and challenges of functionalized bacterial encapsulation: A novel biotechnology for next-generation biotherapeutics.
Ying ZHANG ; Yuwei WU ; Xinyu ZHAO ; Qinghua YE ; Lulu CAO ; Ming LIU ; Bao GAO ; Qinya NIU ; Nuo CHEN ; Zixuan DUAN ; Yu DING ; Juan WANG ; Moutong CHEN ; Ying LI ; Qingping WU
Acta Pharmaceutica Sinica B 2025;15(10):5167-5191
The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.
5.Curvularin derivatives from hydrothermal vent sediment fungus Penicillium sp. HL-50 guided by molecular networking and their anti-inflammatory activity.
Chunxue YU ; Zixuan XIA ; Zhipeng XU ; Xiyang TANG ; Wenjuan DING ; Jihua WEI ; Danmei TIAN ; Bin WU ; Jinshan TANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):119-128
Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, 13C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC50 values ranging from 0.44 to 4.40 μmol·L-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry*
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Mice
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Animals
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Anti-Inflammatory Agents/isolation & purification*
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RAW 264.7 Cells
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Nitric Oxide/metabolism*
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Hydrothermal Vents/microbiology*
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Macrophages/immunology*
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Molecular Structure
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Nitric Oxide Synthase Type II/immunology*
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Cyclooxygenase 2/immunology*
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Geologic Sediments/microbiology*
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NF-kappa B/immunology*
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NLR Family, Pyrin Domain-Containing 3 Protein/immunology*
6.Meta analysis on randomized controlled trials of efficacy of long-term or short-term breathing training in patients with different chronic non-specific low back pain
Shanlin WU ; Hui ZHANG ; Tingting LI ; Mingchen ZHANG ; Jinchao DU ; Zixuan ZHANG ; Qi WANG ; Xiaowen WANG
Chongqing Medicine 2024;53(11):1705-1710,1716
Objective To study the efficacy of breathing training in the patients with chronic non-spe-cific low back pain (CNLBP).Methods The databases of Pubmed,Embase,Web of Science,Cochrane Librar-y,CNKI,China Biomedical Literature Database,Wanfang Database and VIP Database were searched for obtai-ning relevant trials of respiratory-related training for treating CNLBP.The retrieval time limit was from the database establishment to October 2022.The quality assessment was performed by using the Cochrane Manual for Systematic Reviews,and the data analysis was performed by using StataSE15.1 software.Results Nine-teen articles were finally obtained,involving in 1011 cases.The meta analysis showed that the visual analogue scale (VAS) score or pain numerical scale (NRS) score in the experiment group were lower than those in the control group (MD=-1.19,95%CI:-1.51 to-0.87,P<0.05),and the Oswestry dysfunction index (ODI) score was lower than that in the control group (MD=-0.64,95%CI:-0.91 to-0.38,P<0.05). For different types of the patients,the improvement effects of VAS score for different types of patients with CNLBP from high to low were in turn postpartum patients (MD=-1.89,95%CI:-2.51 to-1.27,P<0.05),athletes (MD=-1.46,95%CI:-1.79 to-1.13,P<0.05) and general population (MD=-1.01,95%CI:-1.40 to-0.61,P<0.05).Conclusion Thebreathing training has the improvement effect for pain,dysfunction,proprioception and posture control in various populations with CNLBP.
7.Role of macrophages in fungal keratitis
Yanting LUO ; Junming YANG ; Yaqi LUO ; Shunliang WU ; Zixuan PENG ; Hong HE ; Xingwu ZHONG
International Eye Science 2024;24(10):1582-1587
Fungal keratitis is a serious blinding eye disease. The development of fungal infections depends primarily on the interaction of fungal virulence with host immune defense factors. The cornea is considered an immune-privileged organ, and resident macrophages are the main immune cells that respond to the heterogeneity exhibited by the microenvironment with their polarization. In the early stage of infection, macrophages polarize towards M1, which promotes inflammation and facilitates fungal clearance but produces a cellular storm that exacerbates immune damage; in the late stage of infection, macrophages polarize towards M2, which suppresses the inflammatory response and facilitates tissue repair, but may be immunosuppressed or even immune escape to the detriment of pathogen clearance. The balance between pro-inflammatory and anti-inflammatory responses is key to maintaining the functional integrity of the cornea. Current antifungal drug therapy is limited, so it is particularly important to find a therapeutic target for the inflammatory response triggered by the immune response in addition to antifungal therapy. In this review, the functional and phenotypic characterization of macrophage subsets associated with fungal keratitis was reviewed, more in-depth research is needed to explore the specific mechanisms by which macrophage polarization and their impact on fungal keratitis. Targeted regulation of macrophage differentiation based on their phenotype and function could be an effective approach to treat and manage fungal keratitis in the future.
8.Prevalence of caries among children and adolescents in China: a meta-analysis
SHEN Rongfan ; LI Weiping ; DONG Zixuan ; WU Jiamin ; HE Minmei
Journal of Preventive Medicine 2024;36(12):1092-1096
Objective:
To systematically evaluate the prevalence of caries among children and adolescents in China, so as to provide the basis for the prevention and intervention of caries among children and adolescents.
Methods:
Literature on caries among children and adolescents aged 3 to 18 years was collected through SinoMed, CNKI, Wanfang Data, VIP, PubMed and Web of Science published from January 1, 2020 to December 31, 2023. A meta-analysis was performed using R 4.4.0 software. Literature were excluded one by one for sensitivity analysis. Publication bias was assessed using Egger's test and Begg rank correlation test.
Results:
Totally 561 publications were retrieved, and 26 eligible literature were enrolled in the final analysis. The survey period spanned from 2020 to 2023. The survey sites for 14, 4 and 8 eligible literature were eastern, central and western regions, respectively. A total of 95 594 individuals were included, with 45 004 cases of caries. Meta-analysis showed that the prevalence of caries among children and adolescents was 48.11% (95%CI: 41.58%-54.65%). Subgroup analysis results showed that there were no statistically significant differences in the prevalence of dental caries across different genders, regions, educational stages, urban-rural areas, and regional economic levels (all P>0.05). After sequentially excluding publications, the prevalence of caries ranged from 41.58% to 54.65%, indicating that the research results were relatively stable. Begg rank correlation test and Egger's test indicated no publication bias (all P>0.05).
Conclusion
The prevalence of caries among children and adolescents in China ranged from 41.58% to 54.65% from 2020 to 2023.
9.Relationship between blood indicators and course of nontraumatic osteonecrosis of femoral head in different stages:multiple logistic regression analysis
Zixuan WU ; Shiyi SUN ; Cheng ZHANG ; Guangyi ZHANG ; Tongjie YANG ; Haijun HE
Chinese Journal of Tissue Engineering Research 2024;28(36):5865-5871
BACKGROUND:Up to now,there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages.It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE:To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous(ARCO),thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS:This study used a retrospective study design.A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database,and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria.Patient age,gender,body mass index,and blood laboratory test results were collected.Blood laboratory tests included low-density lipoprotein,total cholesterol,triglycerides,high-density lipoprotein,apolipoprotein β,apolipoprotein α1,uric acid,total protein quantitative,alkaline phosphatase,activated partial thromboplastin time,prothrombin time,prothrombin time International Normalized Ratio,prothrombin time activity,fibrinogen quantitative,coagulation time of thrombin,D-dimer,total iron binding capacity,and platelet count.The indicators of patients with different age groups and different ARCO stages were compared,and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION:(1)There were statistical differences in total cholesterol,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer among ARCO stages in the young group(P<0.05).Among young patients in ARCO stage II,total cholesterol levels were higher than those in ARCO stage III(P<0.05).Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III(P<0.05).Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II(P<0.05).(2)There were statistically significant differences in high-density lipoprotein,coagulation time of thrombin,and D-dimer among ARCO stages in the middle-aged group(P<0.05).Among middle-aged patients in ARCO stage IV,high-density lipoprotein levels were higher than those in ARCO stages II and III(P<0.05).Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III(P<0.05).(3)The uric acid,activated partial thromboplastin time,D-dimer,and platelet count in the elderly group showed statistically significant differences(P<0.05).The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group(P<0.05),while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group(P<0.05).The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group(P<0.05).The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group(P<0.05).(4)Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head.(5)It is indicated that total cholesterol,high-density lipoprotein,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer are statistically significant among patients with different ARCO stages.Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head.
10.The association of intestinal microbiota with hepatobiliary and pancreatic malignancies:a review of research progress
Hongmei YANG ; Zixuan FENG ; Zixun XU ; Gangyi WANG ; Huan WU ; Rui FANG ; Ping CHEN
Chinese Journal of General Surgery 2024;33(10):1724-1730
The gut microbiota plays a crucial role in maintaining overall health.Dysbiosis of the gut microbiota can promote the occurrence and progression of tumors,especially hepatobiliary and pancreatic tumors,by affecting intestinal homeostasis,gut metabolism,and immune function.Therefore,a better understanding of the role of the gut microbiome in the development and progression of hepatobiliary and pancreatic tumors may provide opportunities for developing new prevention and treatment strategies for patients with these malignancies.This article reviews recent research on the role of gut microbiota in the development and progression of hepatobiliary and pancreatic malignancies,aiming to provide a reference for future studies.


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