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Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents

World Journal of Traditional Chinese Medicine 2020年第1期6卷 12-25页

作者： Xi-Lin Li Xiao-Qing Guo Hai-Rong Wang Tao Chen Nan Mei Division of Genetic and Molecular Toxicology National Center for Toxicological ResearchJeffersonARUSA Tianjin center for New drug safety Assessment and research TianjinChina

Aristolochic acid(AA)is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal *** is a causative agent for Chinese herbs nephropathy,a term replaced later by AA *** indicates that AA is nephrotoxic,genotoxic,and carcinogenic in humans;and it also induces tumors in the forestomach,kidney,renal pelvis,urinary bladder,and lung of rats and ***,plants containing AA have been classified as carcinogenic to humans(Group 1)bytheInternational *** our laboratories,we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 *** results demonstrated that AA treatments induced DNA adducts and mutations in the kidney,liver,and spleen of rats,as well as significant alteration of gene expression in both its target and nontarget *** treatments altered mutagenesis-or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression *** also applied benchmark dose(BMD)modeling to the 3-month AA-induced genotoxicity *** obtained BMDL10(the lower 95%confidence interval of the BMD10 that is a 10%increase over the background level)for AA-induced mutations in the kidney of rats was about 7μg/kg body weight per *** review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression,microRNA expression,and proteomics;and presents updated information focused on AA-induced genotoxicity in rodents.

关键词： Aristolochic acid benchmark dose genotoxicity mutation toxicogenomics

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Synthesis of New Thiazine and Thiosemicarbazone Derivatives from D-Xylose

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Chinese Chemical Letters 2006年第12期17卷 1563-1565页

作者： Xiao Ming JI He Ping SUN Hai Wei XU Hong Min LIU New drug research ＆ Development center Zhenzhou University Zhengzhou 450052

1,2-O-Isopropylidene-5-O-p-toluenesulfonyl-α-D-erythro-pentofuranos-3-ulose 1 was treated with thiourea and aminothiourea to give a D-ribose derivative 2 bearing a 2-amino 1,3-thiazine ring and a thiosemicarbazone derivative 5, respectively. 2 was acylated with Ac20 and propandioic acid to afford two acylation derivatives 3 and 4, respectively. Reduction of 5 with NaBH4 in methanol produced a hydrothiosemicarbazone derivative 6. The absolute configuration of 2 was confirmed by X-ray crystallographic analysis. The structures of all products were elucidated by IR, NMR and HRMS spectra.

关键词： Thiourea aminothiourea thiazine D-xylose synthesis.

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Optimization of Caesalpinia sappan L. heartwood extraction procedure to obtain the highest content of brazilin and greatest antibacterial activity

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Journal of Integrative Medicine 2019年第5期17卷 351-358页

作者： Sukanya Settharaksa Chaowalit Monton Laksana Charoenchai drug and Herbal Product research and Development center College of Pharmacy Rangsit University

Objective: The objective of the work was to optimize the extraction conditions of Caesalpinia sappan *** in order to maximize the brazilin content and antibacterial activity of the ***: Two independent factors were studied: extraction temperature(45–95 °C) and extraction time(30–60 min). In addition, five dependent factors were monitored, including extraction yield, brazilin content, and clear zones against Staphylococcus aureus TISTR 1466, Staphylococcus epidermidis TISTR 518 and Propionibacterium acnes DMST 14961. The brazilin content was quantified by high-performance liquid chromatography and antibacterial activity was determined by disk diffusion ***: The high temperature provided high total extract yield as well as brazilin content, while extraction time had little effect on yield or brazilin content. Extraction time had a positive effect, while extraction temperature had little effect on clear zone against S. aureus. The largest clear zone against S. epidermidis was achieved at low extraction temperature and long extraction time. Conversely, short extraction time and high extraction temperature provided the largest clear zone against P. acnes. The optimal conditions providing the highest brazilin content was an extraction temperature and extraction time of 95 °C and 30 min, *** same optimal conditions also provided the simultaneous greatest antibacterial activity against the three bacteria. Modeled optimal conditions were validated be conducting extraction using these values. Yield and antibacterial activity of the resulting extract demonstrated that the model had a low percentage ***: The optimal condition will be used as a standard condition for extraction of C. sappan heartwood to maximize brazilin content and antibacterial activity.

关键词： Antibacterial activity Brazilin Caesalpinia sappan Optimization

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Rh(Ⅲ)-Catalyzed Diverse C-H Functionalization of Iminopyridinium Ylides

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Chinese Journal of Chemistry 2021年第9期39卷 2489-2494页

作者： Zhenzhen Dong Pengfei Li Xingwei Li Bingxian Liu NMPA Key Laboratory for research and evaluation of Innovative drug Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsSchool of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiangHenan 453007China

Divergent synthesis of useful skeletons has been realized via rhodium(Ⅲ)-catalyzed C-H activation of iminopyridinium ylides and coupling with various unsaturated coupling *** and isoquinolones were obtained via cleavage of the C-N or N-N bond in the ylidic di recti ng group,while fluorinated alkenes were delivered with the di recti ng group in *** reactions occurred with wide substrate scopes and good efficiency under redox-neutral and air-tolerant *** products exhibit solid-state fluoresce nt property and bioactivity of in hibiti on toward huma n cancer cells.

关键词： C-H functionalization Iminopyridinium ylide Diverse transformation Redox-neutral Ylidic directing group

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Combination of Shengmai San and Radix puerariae ameliorates depression-like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression

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Animal Models and Experimental Medicine 2023年第3期6卷 211-220页

作者： Ayaz Ahmed Guirong Zeng Mudassar Azhar Fengzhong Wang Jingru Wang Bei Fan Xinmin Liu Dejiang Jiang Qiong Wang Institute of Food Science and Technology Chinese Academy of Agricultural SciencesBeijingChina Hunan Key Laboratory of Pharmacodynamics and safety evaluation of New drugs&Hunan Provincial research center for safety evaluation of drugs ChangshaChina Dr.Panjwani center for Molecular Medicine and drug research International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan Institute of drug Discovery Technology Ningbo UniversityNingboChina research center for Pharmacodynamic Material Basis and Mechanism of ActionCollege of PharmacyGuizhou University of Traditional Chinese MedicineGuiyangChina Sino-Portugal TCM International Cooperation center The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouChina

Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as *** individuals are more vulnerable to experience depression compared to the normal ***,novel treatment approaches are required to reduce depressive symptoms among diabetic *** Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient ***:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic *** antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])***:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the *** with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel *** with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in ***:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.

关键词： BDNF depression Shengmai San STZ induced diabetes traditional Chinese medicine

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Aerobic respiration Lactococcus lactis ameliorate Salmonella induced infection and intestinal dysfunctions by oxygen-scavenging and maintaining immune balance and regulating intestinal microbiota

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Food Science and Human Wellness 2024年

作者： Yulong Zhang Han Yang Zhiliang Cheng Hui Ha Fei Liu Yuehua Jiao Key Laboratory of Dairy Science， Ministry of Education， Food College， Northeast Agricultural University center of drug safety evaluation， Heilongjiang University of Chinese Medicine

Salmonella grows better under aerobic conditions as a facultative anaerobic foodborne pathogenic bacteria. The oxygen-scavenging activity of Lactococcus lactis in the intestinal tract is a promising strategy for preventing Salmonella infection. In this study， the aerobic respiration requirement and preventive mechanism of Lactococcus lactis subsp. lactis (L. lactis) KLDS 4.0325 in murine models infected by Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) SL1344 were investigated. Results indicate that L. lactis KLDS 4.0325 is capable of aerobic respiratory metabolism in the host intestine when exogenous heme exists， and decrease intestinal oxygen concentration， which in turn trigger autophagy of intestinal cells to reduce S. Typhimurium load， improve gut microbiota composition， alleviate intestinal barrier injury and inflammation response. These results suggest that aerobic respiration L. lactis KLDS 4.0325 can prevent S. Typhimurium infection in a new way in which by restoring intestinal cell hypoxia， maintaining immune balance and regulating intestinal flora.

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Asymmetric Synthesis and Antitumor Activity of Spiro- Oxadiazole Derivatives from 1,4：3,6-Dianhydro-D-fructose

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Chinese Journal of Chemistry 2017年第9期35卷 1437-1444页

作者： Wenke Xu Yongxun Ge Yu Hou Yingju Liu Yingchun Hua Weiwei Han Zhiyan Qin Fengwu Liu School of Pharmaceutical Sciences Zhengzhou University Zhengzhou Henan 450001 China Collaborative Innovation center of Henan New drug research and safety evaluation Zhengzhou Henan 450001 China Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou Henan 450007 China Oepartment of Medicine Kaifeng University Kaifeng Henan 475000 China

A series of spiro-oxadiazoles were synthesized from 1,4：3,6-dianhydro-D-fructose and hydrazides via a stereoselective two-step reaction sequence. The structures of newly synthesized compounds were established by spectral analysis. The absolute configuration of compound 2a was further confirmed by single crystal X-ray analysis. All the synthesized compounds were screened for their in vitro antitumor activity, showing that these compounds have poor inhibitory activities against A549, MGC-803 tumor cells.

关键词： 1,4:3,6-dianhydro-D-froctose spiro-oxadiazole single crystal X-ray analysis antitumor activity

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Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 542-549页

作者： Yang Liu Juan Li Zhi Li Xing Tang Zhenzhong Zhang School of Pharmacy Shenyang Pharmaceutical University103Wenhua RoadShenyang 110016China School of Pharmaceutical Sciences Zhengzhou University100 Kexue AvenueZhengzhou 450001China Collaborative Innovation center of New drug research and safety evaluation Henan ProvinceZhengzhou 450001China

A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.

关键词： Pharmacokinetics 10-Hydroxycamptothecin Conjugate Nano-micelle PH-responsive

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Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit

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Science China Life Sciences 2025年

作者： Ruyu Wang Tianxiao Wang Ziyu Chen Jiandong Jiang Yifei Du Hua Yuan Yongchu Pan Yuli Wang Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University Department of Stomatology Chongzhou People's Hospital Medical Basic research Innovation Centre for Cardiovascular and Cerebrovascular Diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical University Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College Department of Orthodontic The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University

Delayed tooth extraction socket(TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils(ANs), and neutrophil extracellular traps(NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium(CM) collected from berberine-treated human bone marrow mesenchymal stem cells(BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

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STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy

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National Science Review 2023年第10期10卷 123-138页

作者： Lei Zhou Wenzhe Yi Zehong Zhang Xiaoting Shan Zitong Zhao Xiangshi Sun Jue Wang Hao Wang Hualiang Jiang Mingyue Zheng Dangge Wang Yaping Li State Key Laboratory of drug research & center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of Sciences China State Institute of Pharmaceutical Industry Univerisity of Chinese Academy of Sciences drug Discovery and Design center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Precision research center for Refractory Diseases Shanghai General HospitalShanghai Jiao Tong University School of Medicine Shandong Laboratory of Yantai drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery

Messenger RNA(mRNA) vaccine is revolutionizing the methodology of immunization in ***,mRNA immunization is drastically limited by multistage biological barriers including poor lymphatic transport,rapid clearance,catalytic hydrolysis,insufficient cellular entry and endosome ***,we design a mRNA nanovaccine based on intelligent design to overcome these *** efficient nanovaccines are carried out with machine learning techniques from datasets of various nanocarriers,ensuring successful delivery of mRNA antigen and cyclic guanosine monophosphate-adenosine monophosphate(cGAMP) to *** activates stimulator of interferon genes(STING),promotes mRNA-encoded antigen presentation and boosts antitumour immunity in vivo,thus inhibiting tumour growth and ensuring long-term survival of tumour-bearing *** work provides a feasible and safe strategy to facilitate STING agonist-synergized mRNA immunization,with great translational potential for enhancing cancer immunotherapy.

关键词： vaccine mRNA STING cancer immunotherapy nanoparticles

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