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Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy:a novel delivery system candidate for tumor vaccines

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Science China(Life Sciences) 2024年第4期67卷 680-697页

作者： Nan Li Yun Zhang Miaomiao Han Tian Liu Jinjia Wu Yingxia Xiong Yikai Fan Fan Ye Bing Jin Yinghua Zhang Guibo Sun Xiaobo Sun Zhengqi Dong State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS)Institute of Medicinal Plant Development(IMPLAD)Beijing 100193China Key Laboratory of Bioactive Substances and Resources Utilization of chinese Herbal medicine from Ministry of Education Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine(Natural Medicine)and Translational MedicineKey Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription from Chinese Academy of Medical SciencesCAMSIMPLADBeijing 100193China Department of Pharmaceutics School of Pharmaceutical SciencesHeilongjiang University of Chinese MedicineHarbin 150036China Jilin Academy of chinese medicine Sciences Changchun 130012China Joint Research center for chinese Medicinal Herbs IMPLADABRC&ACCLBeijing 100193China

The study of tumor nanovaccines(NVs)has gained interest because they specifically recognize and eliminate tumor ***,the poor recognition and internalization by dendritic cells(DCs)and insufficient immunogenicity restricted the vaccine ***,we extracted two molecular-weight Astragalus polysaccharides(APS,12.19 k D;APSHMw,135.67 k D)from Radix Astragali and made them self-assemble with OVA257–264directly forming OVA/APS integrated nanocomplexes through the microfluidic *** nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve *** in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor *** optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline *** FITC-OVA in APS-NVs could be effectively taken up by DCs,and APS-NVs could stimulate the maturation of DCs,improving the antigen cross-presentation efficiency in *** possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and *** accumulation of APS-NVs both in draining and distal lymph nodes were observed following *** APS-NVs could easily access the lymph ***,APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T *** addition,APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment *** antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor ***,the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by ***,this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

关键词： Astragalus polysaccharides nanovaccines OVA immunotherapy self-adjuvant

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A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT

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chinese Journal of Natural medicines 2024年第2期22卷 112-126页

作者： REN Boxue LI Yang DI Lei CHENG Ranran LIU Lijuan LI Hongmei LI Yi TANG Zhangrui YAN Yongming LU Tao FU Rong CHENG Yongxian WU Zhaoqiu State Key Laboratory of Natural medicines Department of PharmacologySchool of PharmacyChina Pharmaceutical UniversityNanjing 211198China Institute for Inheritance-based Innovation of chinese medicine School of Pharmaceutical SciencesShenzhen University Health Science CenterShenzhen 518060China

The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in *** study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant ***22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 *** interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal ***22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling ***,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal ***,LZ22 administration in tumor-bearing mice did not manifest notable side *** findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.

关键词： LZ22 Wild-type p53 p53 Reactivator Snail-driven EMT Tumor growth and metastasis

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Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions

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chinese Journal of Integrative medicine 2024年第6期30卷 565-576页

作者： KE Jun-yu SONG Jin-bin LI Long HE Zhen-fan HUANG Zhuo-jian LIU Zheng-lin CHEN Gui-rong WANG Hai-yan WEN Su-ru ZHOU Heng-li MA Hui-lin DU Qun WU Yong-qiang LI Yan-wu CHEN Xin-lin School of Basic Medical Sciences Guangzhou University of Chinese MedicineGuangzhou510006China Department of Surgery II Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese MedicineGaozhou525200China Science and Technology Innovation center Guangzhou University of Chinese MedicineGuangzhou510405China The First Clinical Medical College of Guangzhou University of Traditional chinese medicine Guangzhou510405China

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

关键词： macrophage ulcerative colitis colon cancer chinese medicine

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern chinese medicine Resources Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China center for evidence‑based and Translational medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

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chinese Journal of Integrative medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min WANG Xia LIU Xia ZHAO Juan Medical Examination center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

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Network Pharmacology and Molecular Docking Analysis of the Mechanisms of Combined Radix Bupleuri(Chai-Hu) and Radix Paeoniae Alba(Bai-Shao) Treatment in the Prevention and Treatment of Alzheimer's Disease

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World Journal of Traditional chinese medicine 2024年第2期10卷 254-262页

作者： Zhao-Han Huang Yuan Fang Qi Yu Tong Wang College of Traditional chinese medicine Beijing University of Chinese MedicineBeijingChina Shanghai center for Women and Children's Health ShanghaiChina

Objective: Radix Bupleuri and Radix Paeoniae Alba are referred to as Chai-Hu and Bai-Shao, respectively, in chinese. We used molecular docking and network pharmacological approaches to explore the active components of this chinese herb combination which is commonly used for treating Alzheimer's disease(AD), the Chai-Hu and Bai-Shao pair(CBP). Materials and Methods: The active compounds and action targets of Chai-Hu and Bai-Shao were identified in the Traditional chinese medicine Systems Pharmacology database, and the Therapeutic Target Database, Drug Bank, Gen Cards, Dis Ge NET, and Online Mendelian Inheritance in Man databases were used to identify therapeutic targets in patients with AD. To identify a common target of CBP in the treatment of AD, we used the Metascape tool to perform Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. In addition, CBP-AD protein–protein interaction(PPI) and herb-component-target networks were created using Cytoscape 3.8.2. Molecular docking was verified using Auto Dock tools. Results: We identified 20 active compounds of CBP, 202 active targets, 1,323 disease targets, and 117 active compound disease intersection targets;the PPI network showed that the top eight key targets were AKT1, interleukin(IL) 6, JUN, MAPK1, tumor necrosis factor, TP53, vascular endothelial growth factor, and epidermal growth factor. These act mainly on the fluid shear stress, atherosclerosis, IL-17, hypoxia-inducible factor-1, and nonalcoholic fatty liver disease pathways, among others, which control immune inflammation, cell proliferation, and apoptosis. based on molecular docking results, the active components of CBP bind well to its key targets. Conclusion: Our results indicated that CBP was effective for treating AD by reducing the expression of inflammatory factors, promoting cell proliferation and differentiation, and preventing nerve cell death and anti-neuronal cell apoptosis.

关键词： Alzheimer's disease Bai-Shao Chai-Hu molecular docking network pharmacology

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2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu Peng Minru Liao Wenke Jin Wei Liu Zixiang Li Zhichao Fan Ling Zou Siwei Chen Lingjuan Zhu Qian Zhao Gu Zhan Liang Ouyang Cheng Peng Bo Han Jin Zhang Leilei Fu West China School of Pharmacy and Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Engineering Research center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern chinese medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China School of Traditional chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with *** activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIRT3 homeostasis metabolism

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Effects of anterior sciatic nerve acupuncture on lower limb paralysis after cerebral infarction:study protocol for a randomized controlled trial

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Journal of Traditional chinese medicine 2024年第1期44卷 205-211页

作者： LI Menghan WANG Yu RAN Dawei YANG Xinming DENG Shizhe SHI Lei MENG Zhihong Department of Acupuncture First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300193China National Clinical Research center for chinese medicine Acupuncture and Moxibustion Tianjin 300193China Graduate department Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Massage and Rehabilitation Second Affiliated Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300250China

Stroke is the main cause of disability in the middle and old ***,especially lower limb paralysis,often leads to the loss of self-care ability and a series of secondary *** main method to improve hemiplegic limb movement is exercise therapy,but there are still many patients with disabilities after rehabilitation *** one of the non-pharmacological therapies for stroke,acupuncture has been recognized to improve motor function in ***,we propose a new method,anterior sciatic nerve acupuncture,which can stimulate both the femoral nerve and the sciatic *** designed this study to determine the effect of this method on lower limb motor *** participants recruited with hemiplegia after cerebral infarction will be randomly assigned to the test group or control group in a 1:1 *** control group will receive Xingnao Kaiqiao acupuncture,and the test group will receive anterior sciatic nerve acupuncture on this *** participants will get acupuncture treatment once a day,6 times a week for 2 *** primary outcome is Fugl-Meyer Assessment of Lower Extremity and the secondary outcomes are Modified Ashworth Scale and Modified Barthel *** will be collected before treatment,1week after treatment,and 2 weeks after treatment,and then statistical analysis will be *** study can preliminarily verify the effect of anterior sciatic nerve acupuncture on improving lower limb motor function in patients with cerebral infarction,which may provide an alternative approach for clinical treatment of hemiplegia.

关键词： anterior sciatic nerve acupuncture paralysis cerebral infarction Xingnao Kaiqiao clinical protocols

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Effect of pediatric Tuina on children's recurrent acute respiratory tract infections: a retrospective cohort study in Southern China

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Journal of Traditional chinese medicine 2024年第3期44卷 586-594页

作者： YIN Lingjia ST?LSBY LUNDBORG Cecilia WU Darong YANG Jinghua ALVESSON Helle M?lsted CAI Jianxiong LU Taoying XIE Qianwen MARRONE Gaetano Department of Global Public Health Karolinska Institutet State Key Laboratory of Dampness Syndrome of chinese medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Outcome Assessment Research Team in chinese medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Health Construction Administration Centre Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Key Laboratory of Clinical Research on Traditional chinese medicine Syndrome the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Department of Pediatrics the Second Affiliated Hospital of Guangzhou University of Chinese Medicine

OBJECTIVE: To determine the effectiveness of pediatric Tuina(PT) in preventing recurrent acute respiratory tract infections(ARTIs) in children. METHODS: This is a retrospective cohort study based on the electronic medical records of children with recurrent ARTIs in 2016. Children were divided into a PT group or a non-PT group, according to whether they had received PT or not in 2016. The primary outcome was the number of ARTI episodes in 2017 and 2018. The secondary outcomes were the number of ARTIs leading to outpatient department visits and outpatient antibiotic prescriptions due to ARTIs in the same time period. Negative binomial regressions were used to detect the association between PT and the outcomes. RESULTS: A total of 2303 children were included in the analysis, including 94 in the PT group and 2209 in the non-PT group. Children who received PT six or more times in 2016 had fewer episodes of ARTIs in 2017 [incidence rate ratio(IRR): 0.59, 95% confidence interval(CI)(0.42-0.84)] and 2018 [IRR: 0.58, 95% CI(0.36-0.94)] and fewer outpatient department visits due to ARTIs in 2017 [IRR: 0.56, 95% CI(0.38-0.83)] than children who had not received PT in 2016. There was no significant difference in the number of outpatient antibiotic prescriptions between the two groups. CONCLUSIONS: Receiving PT six or more times within one year is associated with a decrease in recurrent ARTIs in children in the following two years. Randomized controlled trials are needed for effect evaluation prior to establishing PT as a method for preventing recurrent ARTIs among children.

关键词： child massage pediatric Tuina respiratory tract infections

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