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Journal of Pharmaceutical Analysis 2024年第4期14卷 483-505页

作者： Karolina Zuchowska Wojciech Filipiak Department of pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089 BydgoszczPoland

Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted ***,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these ***,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are *** this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical *** also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.

关键词： Volatile organic compounds Pathogenic bacteria metabolites Metabolomics Microextraction techniques Gas chromatography-mass spectrometry In vivo breath analysis In vitro model

Commentary:brain endothelial GSDMD as a novel target for brain disorders associated with BBB damage

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Chinese Journal of Natural Medicines 2024年第7期22卷 580-581页

作者： LIU Kui PANG Tao State Key Laboratory of Natural Medicines New Drug Screening and Pharmacodynamics Evaluation CenterChina Pharmaceutical UniversityNanjing 210009China

The blood-brain barrier(BBB)is a highly selective and critical interface between the blood and the central nervous system(CNS),essential for maintaining the microenvironment necessary for normal brain function and homeostasis[1].The BBB is primarily formed by brain endothelial cells(bECs),pericytes,and astrocytes,and it operates in concert with microglia/macrophages and neurons[2,3]to constitute the neurovascular unit(Fig.1).Disruption of the BBB or the presence of systemic inflammation can precipitate or exacerbate various CNS pathologies,including Alzheimer’s disease[4],amyotrophic lateral sclerosis[5],Huntington’s disease[6]and multiple sclerosis.

关键词： Brain endothelial cells GSDMD Blood-brain barrier Natural products Neuroinflammation Brain disorders

Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer:A systematic review

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Journal of Integrative Medicine 2024年第2期22卷 137-162页

作者： Bizhar Ahmed Tayeb Ikhwan Yuda Kusuma Alaa A.M.Osman Renáta Minorics Institute of pharmacodynamics and Biopharmacy Faculty of PharmacyUniversity of Szeged6720 SzegedHungary Institution of Clinical Pharmacy Faculty of PharmacyUniversity of Szeged6725 SzegedHungary Department of Clinical Pharmacy and Pharmacy Practice Faculty of PharmacyUniversity of Gezira20 Wad MadaniSudan Pharmacy Study Program Facuity of HealthUniversitas Harapan BangsaPurwokerto 53182Indonesia

Background:The field of personalized medicine has gained increasing attention in cancer care,with the aim of tailoring treatment strategies to individual patients for improved *** medicine,with its long-standing historical use and extensive bioactive compounds,offers a rich source of potential treatments for various diseases,including ***:To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer ***,to explore the general characteristics of the studies included in the analysis,focusing on their key features and *** strategy:A comprehensive literature search was conducted from multiple online databases,including Pub Med,Scopus,Web of Science,and *** search strategy was designed to identify studies related to personalized cancer medicine and herbal *** criteria:Publications pertaining to cancer research conducted through in vitro,in vivo,and clinical studies,employing natural products were included in this *** extraction and analysis:Two review authors independently applied inclusion and inclusion criteria,data extraction,and assessments of methodological *** quality assessment and biases of the studies were evaluated based on modified Jadad scales.A detailed quantitative summary of the included studies is presented,providing a comprehensive description of their key features and ***:A total of 121 studies were included in this review for *** of them were considered as comprehensive experimental investigations both in vitro and in *** majority(n=85)of the studies included in this review were conducted in vitro,with 44 of them specifically investigating the effects of herbal medicine on animal ***,7 articles with a combined sample size of 31,271 patients,examined the impact of herbal medicine in clinical ***:Personal

关键词： Cancer Herbal medicine Personalized medication Active phytochemicals Natural compound

Beyond boundaries:Neuroprotective effects of steroids and ecdysteroids in SH-SY5Y cells-A systematic review

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Neuroprotection 2024年第2期2卷 151-166页

作者： Bizhar Ahmed Tayeb Isaac Kinyua Njangiru Renata Minorics Institute of pharmacodynamics and Biopharmacy Faculty of PharmacyUniversity of SzegedSzegedHungary

Steroids and ecdysteroids have been shown to exhibit a range of biological effects,including anti-inflammatory,anticancer,and *** systematic review aims to highlight the evidence-based neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y neuroblastoma cells.A comprehensive literature search was conducted on May 11,2023,without publication source restrictions,using various electronic databases,including PubMed,Web of Science(WoS),Scopus,and Cumulative Index toNursing and Allied Health *** 103articles,only20 studies were included for investigating the neuroprotective effects of steroids and ecdysteroids in SH-SY5Y cells exposed to oxidative stress or neurotoxic *** risk of bias and quality assessment of the included studies were evaluated in accordance with the Nature Publication Quality Improvement Project specific *** selected studies reported the antioxidant effects of the tested compounds on SH-SY5Y cells and demonstrated their ability to scavenge free radicals and prevent lipid *** findings suggest that neurosteroids have potential therapeutic applications for the prevention and treatment of neurodegenerative diseases characterized by oxidative stress and neuronal *** studies have investigated the molecular mechanisms underlying the neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y *** mechanisms include the activation of antioxidant enzymes,such as superoxide dismutase and glutathione peroxidase,and the modulation of various signaling pathways,including the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated kinase *** review provides evidence that the tested compounds have remarkable neuroprotective and antioxidant effects in human neuroblastoma SH-SY5Y cells.

关键词： antiapoptotic cytoprotective neuroblastoma neurosteroids oxidative stress SH-SY5Y cells

Biomarkers of Neurotoxicity: An Overview

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Biomedical and Environmental Sciences 1991年第1期4卷 192-196页

作者： WILLIAM SLIKKER JR chief pharmacodynamics branch Division of Reproductive and Developmental Toxicology National Center for Toxicological Research JeffersonDepartments of Pharmacology and Toxicology and Pediatrics University of Arkansas for Medical Sciences and Arkansas Children's Hospital Little Rock Arkansas 72079 Arkansas 72205

Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. Neurotoxic effects may be permanent or reversible, produced by neuropharmacological or neurodegenerative properties of a neurotoxicant, or the result of direct or indirect actions on the nervous system (ICON, 1990). Adverse effects include side effects (unwanted effects) or effects due to overdosing; functional or structural responses that promote compensation to restore normal function; or any

关键词： An Overview Biomarkers of Neurotoxicity

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological ***,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains ***,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH *** the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH *** of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)***’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 *** findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

Pharmacokinetics and pharmacodynamics of Subcutaneous Single Doses of Pegylated Human G-CSF Mutant(PEG30-rhG-CSF) in Beagle Dogs

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Chinese Journal of Clinical Oncology 2008年第5期5卷 326-332页

作者： Yongming Cai Zhengmin Chen Ling Jiang Ming Li Changxiao Liu State Key Laboratory of Pharmacokinetics and pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin 300193 China.

OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage, and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzymeqinked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software. RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows： the mean elimination half-life （t1/2ke） was 40.6 h （33.5-45.4 h）; the mean time to reach peak concentration （Tmax） was 19.2 h （11.7-24.0 h）; the drug clearance from the serum （CL） was decreased with increasing doses; the peak concentration （Cmax） and the area under the serum concentration-time curve （AUC） were increased with increasing doses. For PEG20-rhG- CSF, the half-life was shorter （12 h） and Tmax was achieved much earlier （10 h） relative to PEG30-rhG-CSF. The AUC of PEG30- rhG-CSF was much greater than that of PEG20-rhG-CSF, and the relative bioavailability with a subcutaneous injection was 158.7%. Administration of single doses of PEG30-rhG-CSF resulted in substanti

关键词： PEG30-rhG-CSF PEG20-rhG-CSF pharmacoki-netics pharmacodynamics ANC ELISA beagle dogs.

Drug metabolism in drug discovery and development

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Acta Pharmaceutica Sinica B 2018年第5期8卷 721-732页

作者： Zhoupeng Zhang Wei Tang Department of Pharmacokinetics Pharmacodynamics and Drug Metabolism Merck Sharp & Dohme Corp. Shanghai ChemPartners

Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics(PK), pharmacodynamics(PD), and safety should be carefully considered. This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates; these include, but are not limited to, collaboration with medicinal chemists on structure–activity relationships(SAR) to overcome high clearance, using deuterium replacement to further optimize a lead, prodrug approaches to circumvent formulation and delivery difficulties, and addressing issues such as species differences in metabolism,drug–drug interactions(DDI) and formation of reactive metabolites.

关键词： Bioactivation Drug discovery and development Drug metabolism Metabolite Pharmacokinetics pharmacodynamics Safety Toxicity

Photosafety testing of dermally-applied chemicals based on photochemical and cassette-dosing pharmacokinetic data

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 237-238页

作者： Hiroto Ohtake Yukiko Suzuki Masashi Kato Yoshiki Seto Satomi Onoue Department of Pharmacokinetics and pharmacodynamics School of Pharmaceutical Sciences University of Shizuoka

Drug-induced phototoxicity is elicited by exposure of skin and/or eyes to topical or systemic administration of chemicals,followed by exposure to *** photosafety testing,a new screening strategy,employing in vitro photochemical/photobiological and in vivo cassette-dosing pharmacokinetic(PK)studies,was proposed[1,2].The screening system provided reliable phototoxic predictions of tested chemicals at least within the same chemical series;however,the applicability of the proposed strategy is not fully understood.

关键词： Photosafety assessment Phototoxicity Photoreactivity Pharmacokinetics

Nutritional and Antioxidant Evaluation and Effect of Eggplant Consumption on Anthropometric and Hematologic Parameters in Wistar Rats

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Food and Nutrition Sciences 2024年第4期15卷 245-262页

作者： Elenga Michel Nkouka Rhode Gouollaly Tsiba Wossolo Stephane Itoua Okouango Yvon Simplice Mananga Vital Multi-field Team of Research in Feeding and Nutrition (Eprancongo) Faculty of Sciences and Technology Marien Ngouabi University Brazzaville Republic of the Congo Laboratory of Human Nutrition and Feeding (LaNAH) Faculty of Sciences and Technology Marien Ngouabi University Brazzaville Republic of the Congo Department of Pharmacopeia and Traditional Medicine National Institute of Health Science & Research (IRSSA) Scientific City of Brazzaville Brazzaville Republic of the Congo Laboratory of pharmacodynamics and Experimental Pathophysiology (L2PE) Faculty of Sciences and Technology Marien Ngouabi University Brazzaville Republic of the Congo

The aim of the present study was to evaluate the nutritional quality of green and purple eggplant, their antioxidant activity and their nutritional efficacy on Wistar rats. For nutritional quality, the parameters measured are dry matter, protein, lipid, ash, carbohydrate, iron, phosphorus, calcium, magnesium and energy content. For antioxidant activity, the parameters measured are 50% DDPH free radical inhibition concentration and total polyphenol content. Nutritional efficacy was evaluated in rats fed the control diet and in rats fed the three treated diets containing eggplant meal obtained by replacing 5%, 10%, and 15% of the control diet. The parameters measured are the amount consumed, the weight of the animal and target organs, and hematologic parameters. The results of the nutritional analysis show the following values: 13.31% protein, 2.66% lipids, 0.84% calcium, 0.12% magnesium, 0.43% phosphorus for the Solanum aethiopicum L. species and 13.47% protein, 3.66% lipids, 0.36% calcium, 0.22% magnesium, 0.35% phosphorus for the Solanum melongena L. species. In terms of antioxidant activity, we obtained DDPH inhibition percentages of 40.28 mg/ml for Solanum aethiopicum L. and 12.42 mg/ml for Solanum melongena L., respectively. Finally, hematologic and anthropometric tests showed that for the different diets used, weight loss and an increase in hematologic parameters were observed in the rats tested. This study showed that eggplant has interesting nutritional characteristics and antioxidant activity, contributing to an increase in weight and anthropometric parameters.

关键词： Fruit Vegetables Eggplant Solanum aethiopicum L. Solanum melongena L. Antioxidants Polyphenols