1.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
2.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
3.Stem cell-based therapeutic strategies for liver aging
Huan NIU ; Yan-Nan WANG ; Yu DING ; Yu-Qing LIN ; Jian QIN ; Jian-Cheng WANG
Liver Research 2025;9(2):118-131
Aging is characterized by a gradual deterioration of the physiological integrity of cells,tissues,and or-gans,resulting in a decrease in the body's physiological functions and an acceleration of the onset of age-related diseases,ultimately leading to death.The aging of the liver,which is a critical metabolic organ,is closely linked to various chronic liver diseases,such as hepatitis,liver fibrosis,and cirrhosis,and it ex-acerbates their prognosis and is a primary risk factor for their development at all stages.Therefore,a comprehensive understanding of the causes,mechanisms,and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases.Stem cells,which are potential anti-aging agents,present a promising and effective alternative for managing liver aging.In this review,we systematically assess the driving factors,characteristics,and underlying mechanisms of liver aging.We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases.The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.
5.Era Implications,Development Trends,and Implementation Strategies of Ideological and Political Education in the Curriculum of Higher Institutions of Traditional Chinese Medicine
Xuebin QIAO ; Zhipeng CHEN ; Hao NIU ; Wankun DING
Journal of Traditional Chinese Medicine 2025;66(23):2406-2410
Ideological and political education within the curriculum of higher institutions of traditional Chinese medicine (TCM) not only bears the important responsibility of promoting China's outstanding traditional culture but also serves as a vital domain for upholding integrity and innovation in medical education. These institutions must profoundly comprehend the contemporary significance of curriculum-based ideological and political education, clarify its core role in talent cultivation, leverage the distinctive advantages of TCM culture, and promote the organic integration of ideological education and professional training. By reviewing the current situation and development trends of ideological and political education in the curriculum of higher TCM institutions, this paper has analyzed the challenges in teaching design, teachers' ideological and political literacy and competence, and the integration of ideological content with specialized courses, and has proposed implementation strategies such as using TCM culture as a guiding force, strengthening teachers' teaching capacity in ideological and political education, developing distinctive educational resources, and improving evaluation and incentive mechanisms. These strategies aim to effectively enhance the impact of ideological and political education in the new era, fostering well-rounded TCM talents with both moral integrity and professional competence.
6.Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.
Li QUAN ; Wen-Hao NIU ; Fu-Peng YANG ; Yan-da ZHANG ; Ru DING ; Zhi-Qing HE ; Zhan-Hui WANG ; Chang-Zhen REN ; Chun LIANG
Chinese journal of integrative medicine 2025;31(4):299-310
OBJECTIVE:
To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC).
METHODS:
The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups.
RESULTS:
After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01).
CONCLUSIONS
YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans
;
Microcirculation/drug effects*
;
Drugs, Chinese Herbal/administration & dosage*
;
Stomach Neoplasms/physiopathology*
;
Emulsions
;
Male
;
Plant Oils/administration & dosage*
;
Brucea/chemistry*
;
Middle Aged
;
Female
;
Drug Combinations
;
Human Umbilical Vein Endothelial Cells/metabolism*
;
Seeds/chemistry*
;
Injections
;
Vascular Endothelial Growth Factor A/metabolism*
;
Aged
;
Network Pharmacology
7.A chromosome-level Dendrobium moniliforme genome assembly reveals the regulatory mechanisms of flavonoid and carotenoid biosynthesis pathways.
Jiapeng YANG ; Qiqian XUE ; Chao LI ; Yingying JIN ; Qingyun XUE ; Wei LIU ; Zhitao NIU ; Xiaoyu DING
Acta Pharmaceutica Sinica B 2025;15(4):2253-2272
Dendrobium moniliforme (D. moniliforme) is a traditional medicinal herb widely cultivated in Asia. Flavonoids, one of the largest groups of secondary metabolites in plants, are significant medicinal components in Dendrobium species. Several subgroups of R2R3-MYB proteins have been validated to directly regulate flavonoid biosynthesis. Using PacBio sequencing technology, we assembled a high-quality chromosome-level D. moniliforme genome with a total length of 1.20 Gb and a contig N50 of 3.97 Mb. The BUSCO assessment of genome annotation was 91.4%. By integrating the genome and transcriptome, we identified biosynthesis pathway enzyme genes related to flavonoids, polysaccharides, carotenoids, and alkaloids. A total of 90 R2R3-MYBs were identified in D. moniliforme and classified into 21 subgroups. Studies on the functions of R2R3-MYB transcription factors revealed that R2R3-MYB in SG6 can up-regulate flavonoid biosynthesis. Various validation experiments, including subcellular localization, transient overexpression, UPLC-MS/MS, HPLC, yeast one-hybrid, and dual-luciferase assays, demonstrated that DMYB69 directly up-regulates the expression of enzyme genes involved in flavonoid biosynthesis, increasing the content of flavonoids such as anthocyanin, flavone, and flavonol. Additionally, DMYB44 was shown to directly up-regulate the expression of carotenoid biosynthesis enzyme genes, thereby increasing carotenoid content. This study provides an essential genome resource and theoretical basis for molecular breeding research in D. moniliforme.
8.Tranexamic acid-fatty alcohol polyoxyethylene ether conjugation/PVA foam for venous sclerotherapy via vascular damage and inhibiting plasmin system.
Jizhuang MA ; Keda ZHANG ; Wenhan LI ; Yu DING ; Yongfeng CHEN ; Xiaoyu HUANG ; Tong YU ; Di SONG ; Haoran NIU ; Huichao XIE ; Tianzhi YANG ; Xiaoyun ZHAO ; Xinggang YANG ; Pingtian DING
Acta Pharmaceutica Sinica B 2025;15(6):3291-3304
Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEOx-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEOx) by ester bonds. AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEOx-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEOx-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.
9.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.
10.Construction of stable BHK-21 cell lines overexpressing APN of different species and the susceptibility to different coronaviruses
Dan WANG ; Hengjie ZHANG ; Yuyang TIAN ; Xiaohan HOU ; Zeao CHEN ; Ying HU ; Wenchao ZHANG ; Jianle REN ; Ying WANG ; Yujun ZHAO ; Ding ZHANG ; Bo YANG ; Wenxia TIAN ; Sheng NIU
Chinese Journal of Veterinary Science 2025;45(10):2095-2101
This study aims to establish BHK-21 stable cell lines expressing APN from four species(human,pig,dog,and cat),the APN fragments were amplified from pEGFP-C1-APN plasmids of the four species stored in the laboratory to generate the recombinant plasmids pcDNA4.0-APN.Af-ter the recombinant plasmids were transfected into BHK-21 cells,the stable BHK-21 cell lines ex-pressing the APNs were selected by two rounds of limited dilution.The constructed BHK-21 cell lines were identified by indirect immunofluorescence assay(IFA),and their susceptibility to PD-CoV and TGEV was tested for these four cell lines.Virus infection experiments revealed that PD-CoV infected cells expressing human,pig,and dog APNs,while it did not infect cells expressing cat APN.Simultaneously,TGEV infected cells expressing pig,dog,and cat APNs,but did not infect cells expressing human APN.The results suggest that the risk of cross-species infection for different coronaviruses and the established cell line can be used effectively to evaluate the virus in-fection.The findings also revealed that PDCoV has the potential risk of cross-species infection of human and dog,and TGEV has the potential risk of cross-species infection of dog and cat.These results provide a basis for the prevention and control strategy of coronaviruses.

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