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Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from transient cerebral ischemic injury by increasing the expression of antioxidant enzymes

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Neural Regeneration Research 2017年第2期12卷 220-227页

作者： Bai Hui Chen Joon Ha Park Ji Hyeon Ahn Jeong Hwi Cho In Hye Kim Jae Chul Lee Moo-Ho Won Choong-Hyun Lee In Koo Hwang Jong-Dai Kim Il Jun Kang Jun Hwi Cho Bich Na Shin Yang Hee Kim Yun Lyul Lee Seung Min Park Department of Histology and Embryology Institute of NeuroscienceWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym UniversityChuncheonSouth Korea Department of Neurobiology School of MedicineKangwon National UniversityChuncheonSouth Korea Department of pharmacy College of PharmacyDankook UniversityCheonanSouth Korea Department of Anatomy and Cell Biology College of Veterinary Medicineand Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea Division of Food Biotechnology School of BiotechnologyKangwon National UniversityChuncheonSouth Korea Department of Food Science and Nutrition Hallym UniversityChuncheonSouth Korea Department of Emergency Medicine School of MedicineKangwon National UniversityChuncheonSouth Korea Department of Physiology College of Medicineand Institute of Neurodegeneration and NeuroregenerationHallym UniversityChuncheonSouth Korea Department of Surgery School of MedicineKangwon National UniversityChuncheonSouth Korea Department of Emergency Medicine Sacred Heart HospitalCollege of MedicineHallym UniversityAnyangSouth Korea

Quercetin（QE; 3,5,7,3′,4′-pentahydroxyflavone）, a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprotective mechanisms of QE after ischemic insults. Therefore, in this study, we investigated the effects of QE on ischemic injury and the expression of antioxidant enzymes in the hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, pretreatment with QE significantly increased the expression levels of endogenous antioxidant enzymes Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic injury. These findings demonstrate that pretreated QE displayed strong neuroprotective effects against transient cerebral ischemia by increasing the expression of antioxidant enzymes.

关键词： nerve regeneration flavonoids transient cerebral ischemia Cu/Zn superoxide dismutase catalase Mn superoxide dismutase glutathione peroxidase neural regeneration

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Ethnobotanical Studies on Dwarf Palm (<i>Nannorhops ritchieana</i>(Griff.) Aitchison) and Date Palm (<i>Phoenix dactylifera</i>L.) in Dera Ismail Khan, KPK, Pakistan

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American Journal of Plant Sciences 2012年第8期3卷 1162-1168页

作者： Sarfaraz Khan Marwat Khalid Usman Ejaz Ahmad Khan Said Ghulam Jalaluddin Baloch Abdul Manan Tauqeer Fazal Ur Rehman Department of Economics Gomal University Dera Ismail Khan Pakistan Faculty of Agriculture Gomal University Dera Ismail Khan Pakistan Faculty of pharmacy Gomal University Dera Ismail Khan Pakistan University WENSAM college Gomal University Dera Ismail Khan Pakistan

This paper is based on research work conducted during 2008-2010 in Dera Ismail Khan (D. I. Khan) District, Pakistan, to investigate Socio-Economic Impacts of Dwarf Palm (Nannorhops ritchieana) and Date Palm (Phoenix dactylifera) on the local inhabitants. A questionnaire for data collection of Dwarf Palm was designed and local people were interviewed. The main Dwarf Palm (Mazri) areas are lying between the Koh-i-Surkh and Marwat hill and yielding about 1000 tons of mazri leaves annually. Date Palm plantations are concentrated in Paniala, Paharpur, Chawdwan and Dhakki. The prominent varieties grown in the area are Dhakki, Shakri, Gulistan, Zaidi, Hillawi, Basra, Azadi and khudarawi. Dhakki Dates are well-known among all other varieties. Total area under dates cultivation in the district is 100,000 hectares, with total production of 11,000 tons dates. An average yield of Dhakki-Dates y-1 ranges from 6500 to 7000 tons i.e., 75% of the total production of dates in the area and dried dates production ranges from 800 - 1000 tons·year-1. A significant population is involved in processing of mazri and date palm leaves to prepare different products. Dates have a tremendous potential for economic uplift of the people. But growers face limitations and challenges regarding lack of information about customers and markets, harvesting, processing, and packaging techniques and infrastructure for producing good quality fresh dates. Fruit dropping in date palm particularly in Dhakki variety has become a serious concern. More than 70% date fruits drop before maturity. If production and processing constraints are properly handled, this may have significant socio-economic impact on local inhabitants.

关键词： Mazri Palm Date Palm Arecaceae Socio-Economic Impact

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Actinidia deliciosa as a complemental therapy against nephropathy and oxidative stress in diabetic rats

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Food Science and Human Wellness 2023年第6期12卷 1981-1990页

作者： Ali Y.Naoom Wenyi Kang Nora F.Ghanem Mohamed M.Abdel-Daim Fatma M.El-Demerdash Department of Medical Laboratory Techniques Imam Ja'afar Al-Sadiq UniversityAl-Muthanna 66002Iraq National R&D Center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Department of Zoology Faculty of ScienceKafr ElSheikh UniversityKafr El Sheikh 33516Egypt Department of Pharmaceutical Sciences Pharmacy ProgramBatterjee Medical CollegeJeddah 21442Saudi Arabia Pharmacology Department Faculty of Veterinary MedicineSuez Canal UniversityIsmailia 41522Egypt Department of Environmental Studies Institute of Graduate Studies and ResearchAlexandria UniversityAlexandria 21526Egypt

This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa(kiwifruits)aqueous extract in streptozotocin-treated *** were distributed into;control,*** aqueous extract(ADAE;1 g/kg orally),streptozotocin(STZ;50 mg/kg,i.p,single dose),and STZ plus ADAE,*** showed that ADAE had high antioxidant and radical scavenging *** in blood sugar level,lipid peroxidation(LPO),kidney function biomarkers,and perturbations in hematological parameters were observed in diabetic ***,enzymatic and non-enzymatic antioxidants,protein content,and alkaline phosphatase(ALP)activity ***,histological,immunohistochemical alpha-smooth muscle actin immunoreactivity(α-SMA-ir)and histochemical(collagen,total protein,DNA,and RNA)alterations were observed in rat ***,STZ produced upregulation of inflammatory associated genes(tumor necrosis factor-alpha;TNF-αand transforming growth factorβ1;TGF-β1)and triggered apoptosis by upregulating apoptotic related gene[Bcl2-associated X protein(Bax)]and downregulating anti-apoptotic related gene B-cell lymphoma-2(Bcl-2)based on real-time PCR ***,diabetic rats administered with ADAE showed significant restoration in LPO,antioxidant status,and biochemical indices besides tissue architecture,and genes improvement regarding STZ ***,*** has a valuable ameliorative infl uence and can restore glucose levels and improve kidney dysfunction in diabetic rats.

关键词： Diabetes mellitus Actinidia deliciosa Inflammation Apoptosis Oxidative stress Nephropathy

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Population Pharmacokinetics of Methotrexate in Egyptian Children with Lymphoblastic Leukemia

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Pharmacology & pharmacy 2013年第2期4卷 139-145页

作者： Ehab Said EL Desoky Mohamed H. Ghazal Rajendra P. Singh Omnia N. Abdelhamid Hartmut Derendorf Department of Pharmaceutics College of Pharmacy University of Florida Gainesville USA harmacology Department Faculty of Medicine Assiut University Assiut Egypt Pediatric Department Assiut University Hospital Assiut University Assiut Egypt Upper Egypt Oncology Unit Assiut University Assiut Egypt

Background: Individualization of high dose regimen of methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia based on pharmacokinetic (PK) parameters can help in optimization of the dose and better control of the disease. Building up of a pharmacokinetic model can help dose optimization. Objectives: A NONMEM based population (POP) PK model has been subsequently developed to evaluate the effect of demographics as covariates to address variability in pharmacokinetics of MTX. Method: Forty one patients (24 males & 17 females) with ranges of age, body weight and height of 3 - 15 years, 13 - 54 kg and 100 - 177 cm respectively and diagnosed as acute lymphoblastic leukemia (ALL) were involved in the study. MTX was administered as i.v. infusion at a dose of 2 gm/m2 over a period of two hour and its plasma concentrations were determined primarily at 24 hr post-dose to be utilized in the building-up of PK *** initial/prior estimates of volumes of central (V1) and peripheral compartments (V2) and clearance (CL) and inter-compartmental clearance (Q2) for MTX were extracted from literature. The inter-subject variability was estimated for V1 & CL. The influence of different covariates on model performance and parameter estimates was assessed by evaluating the difference in objective function value. The final POP PK model was validated by bootstrap re-sampling procedures (1000 runs) and the 95% confidence intervals for the estimates were calculated. Results: The POP estimates for CL, V1 and V2 were 2.18 L/h, 5.74 L and 11.2 L respectively. The inter-individual variability for the CL and V1 was 23% and 30% respectively. The covariates analysis showed effect of body surface area and sex on the CL and weight on V1. Conclusions: The POP-PK model developed adequately defines the population PK of MTX in pediatric patients with lymphoblastic leukemia. The model showed effect of body surface area and sex on clearance and weight on volume of distribution of the M

关键词： Methotrexate Population Pharmacokinetics Leukemia

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The Prevalence of Hyponatremia in Pulmonary Tuberculosis Patients, a Tertiary Care Hospital Experience from Pakistan

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Journal of Tuberculosis Research 2019年第4期7卷 259-266页

作者： Afshan Nisar Amanullah Lail Darkhshan Nisar Syed Abdul Waheed Nausheen Saifullah Ghulamullah Lail Department of Chest Medicine Jinnah Postgraduate Medical Centre Karachi Pakistan Department of Pediatrics Dow University Hospital Karachi Pakistan Department of pharmacy (Pharmacology) Hamdard University Hospital Karachi Pakistan Department of Medicine and Allied Jinnah Medical and Dental College Karachi Pakistan

Introduction: Tuberculosis (TB) is one of the major public health problems in Pakistan. Our country ranks fifth in tuberculosis high-burden countries worldwide. Hyponatremia is considered as one of the most common and important electrolyte abnormality in Pulmonary TB (PTB) patients. This study will show the prevalence of hyponatremia in PTB in our population. Objective: To evaluate the prevalence of hyponatremia in pulmonary tuberculosis patients. Study Design: Cross-sectional, descriptive study at Jinnah postgraduate medical centre Karachi from August 2017 to August 2018. Material and Methods: In this cross-sectional study, all patients with TB admitted in chest ward were enrolled. Patients having tuberculous meningitis, syndrome of inappropriate Ant diuretic hormone (SIADH), Renal failure, pneumonia, Cirrhosis taking medicines (diuretics, ACEI, and ARBs) were excluded. A pre-designed questionnaire was used to assess hyponatremia and its potential causes other than TB. Chi-square or Fischer exact test was used to identify factors associated with hyponatremia. Results: Ninety-six patients with mean age were 40.14 ± 13.02 years (ranging 18 - 65 years). Predominantly, patients were females 50 (52.08%). Overall Serum Na, Mean ± SD was 130.53 ± 6.99 (Ranging 110 - 146). Sixty one patients (63.5%) were younger than 40 years. Forty patients (41.66%) were smokers: 16 (16.7%) had diabetes mellitus (DM), and 15 (15.6%) had hypertension. Sixty-nine (71.87%) patients had hyponatremia of which 45 (73.77%) were less than 40 years (p = 0.375). Diabetes mellitus, female gender, smoking, hypertension and duration of disease were not associated with increased risk of hyponatremia having P Values: p = 0.082, p = 0.39, p = 0.57, p = 0.20 and p = 0.45 respectively. Conclusion: Hyponatremia is associated with tuberculosis and is more common with diabetes, hypertension, smoking and young age.

关键词： Hyponatremia Tuberculosis Electrolyte Imbalance

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Single-cell RNA sequencing reveals the dynamics of hepatic non-parenchymal cells in autoprotection against acetaminophen-induced hepatotoxicity

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药物分析学报:英文版 2023年第8期13卷 926-941页

作者： Lingqi Yu Jun Yan Yingqi Zhan Anyao Li Lidan Zhu Jingyang Qian Fanfan Zhou Xiaoyan Lu Xiaohui Fan Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Future Health Laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxingZhejiang314100China Innovation Center in Zhejiang University State Key Laboratory of Component-Based Chinese MedicineHangzhou 310058China School of pharmacy The University of SydneySydney2006Australia Jinhua Institute of Zhejiang University JinhuaZhejiang321016China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou310058China Engineering Research Center of Innovative Anticancer Drugs Ministry of EducationHarbin150023China

Gaining a better understanding of autoprotection against drug-induced liver injury(DILI)may provide new strategies for its prevention and ***,little is known about the underlying mechanisms of this *** used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells(NPCs)in autoprotection against DILI,using acetaminophen(APAP)as a model *** was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice,followed by a higher dose in a secondary *** subsets and dynamic changes were identified in the APAP(hepatotoxicity-sensitive)and APAP-resistant(hepatotoxicity-resistant)groups.A chemokine(C-C motif)ligand 2^(+)endothelial cell subset almost disappeared in the APAP-resistant group,and an R-spondin 3^(+)endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP ***,the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of ***-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant *** addition,the natural killer cell subsets NK-3 and NK-4 and the Sca-1^(-)CD62L^(+)natural killer T cell subset may promote autoprotection through interferon-γ-dependent ***,macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP ***,this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

关键词： Single-cell RNA sequencing Drug-induced liver injury Autoprotection against APAP hepatotoxicity Endothelial cells Dendritic cells

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PEP06 polypeptide 30 is a novel clusterdissociating agent inhibiting αv integrin/FAK/Src signaling in oral squamous cell carcinoma cells

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1163-1173页

作者： Gulnara Tuguzbaeva Er Yue Xi Chen Lina He Xinlei Li Jiaming Ju Ying Qin Valentin Pavlov Yanjie Lu Wenting Jia Yunlong Bai Yumei Niu Baofeng Yang Central Laboratory of Scientific Research Bashkir State Medical UniversityUfa 450008Russian Federation Department of Pharmacology(State-Province Key Laboratories of BiomedicineePharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbin 150081China Department of Endodontics the First Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Department of Orthopedic Dentistry and Maxillofacial Surgery Bashkir State Medical UniversityUfa 450008Russian Federation

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial *** oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be *** to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of *** study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in ***,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human *** study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous *** PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly ***,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC ***06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in ***,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

关键词： Oral squamous cell carcinoma Tumor cell clusters Collective migration Metastasis αv integrin/FAK/RC signaling RGD

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Clitocine induces drug-resistant cancer cells apoptosis in vitro through repression of Mcl-1 and growth inhibition in vivo

Clitocine induces drug-resistant cancer cells apoptosis in v...

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生态文明建设中的植物学：现在与未来——中国植物学会第十五届会员代表大会暨八十周年学术年会

作者： Jian-guo Sun Hua Li Xia Li Xueli Zeng Ping Wu Kwok-Pui Fung Fei-yan Liu Zhejiang University Research Centre of Siyuan Natural Pharmacy and BiotoxicologyCollege of Life SciencesZijinggang Campus Zhejiang University Zhejiang University The State Key Laboratory of Plant Physiology and BiochemistryCollege of Life SciencesZijinggang Campus School of Biomedical Sciences(SBS) The Chinese University of Hong Kong

Clitocine is an amino nucleoside that has been shown to inhibit human cancer cell ***,we reported that Clitocine effectively induced drug-resistant human cancer cells apoptosis in vitro and tumor growth suppression in vivo for the first *** treatment inhibited tumor cell growth in vitro in a dose-and time-dependent *** analysis revealed that Clitocine induced tumor cell growth inhibition was associated with activation of caspases 3,8 and 9,PARP cleavage,cytochrome C release and Bax,Bak activation,suggesting that Clitocine inhibits tumor cell growth through inducing *** of apoptosis regulatory genes indicated that Mcl-1 was dramatically decreased in tumor cells after Clitocine *** of Mcl-1 blocked Clitocine-induced apoptosis and reversed the activation of Bak,suggesting that Clitocine induced the drug-resistant cancer cell apoptosis through decreasing Mcl-1 *** with the in vitro apoptosis induction activity,Clitocine significantly suppressed the drug-resistant hepatocellular carcinoma xenograft *** together,we demonstrated that Clitocine holds great promise for further development as an effective agent to overcome drug resistance in cancer therapy.

关键词： Clitocine cancer drug resistance apoptosis Mcl-1.

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Multidrug Resistance-associated Protein 1（MRP 1） Targeted Photoimmunotherapy（PIT） for the Treatment of Drug Resistant Carcinoma

Multidrug Resistance-associated Protein 1（MRP 1） Targeted ...

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2018年第十二届中国药物制剂大会

作者：李芳 Chengqiong Mao Junbo Xin Xin Ming 江苏医药职业学院药学院 Department of Cancer Biology & Comprehensive Cancer Center Wake Forest University School of Medicine School of pharmacy Jiangsu Vocational College of Medicine

Drug resistance remains an enormous challenge to cancer therapy. Multidrug resistanceassociated protein 1（MRP 1） contributes to multidrug resistance in numerous carcinomas by pumping out anticancer agents in cancer cells. Strategies to surmount drug resistance have been long pursued;however, unfortunately clinical solutions do not exist yet. The main cause for the failure is deficiency of cancer specificity of small-molecule MRP 1 inhibitors, thus inducing serious toxicity in normal tissues. In present study, MRP 1-targeted photoimmunotherapy（PIT） was established to achieve superior cancer specificity through antibody targeting and locoregional light irradiation. Thus, a MRP 1 monoclonal antibody was chemically linked with IR700, a water soluble porphyrin photosensitizer. In vitro studies showed that the antibody-photosensitizer conjugates specifically accumulated in MRP 1-expressing drug resistant cancer cells, and caused conspicuous cytotoxicity upon near infrared light irradiation. We then examined our MRP 1-targeted approach in mouse xenograft model of chemoresistant small cell lung cancer. In vivo data indicated that targeted PIT produced rapid tumor shrinkage, and remarkably prolonged survival of tumorbearing mice. We conclude that our targeted PIT approach produces molecularly targeted and spatially selective ablation of chemoresistant tumors, and thereby provides an efficacious strategy to overcome MRP 1-mediated multidrug resistance in cancer, where conventional approaches have failed.

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Inhibitory effects of recombinant IL-4 and recombinant IL-13 on UHMWPE-induced bone destruction in the murine air pouch model

Inhibitory effects of recombinant IL-4 and recombinant IL-13...

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中华医学会第五次中青年骨质疏松和骨矿盐疾病学术会议

作者： Yang Wang Ning-Ning Wu Yu-Qin Mou Liang Chen Zhong-Liang Deng Department of Orthopaedic Surgery The Second Affiliated Hospital Chongqing Medical University Ministry of Education Key Laboratory Department of Clinical Laboratory Testing DiagnosticsChongqing Medical University college of pharmacy Chongqing Medical University

Purpose We administered recombinant interleukin(IL)-4 and recombinant IL-13 locally into the air pouch of mice to improve bone resorption induced by ultra-high-molecular-weight polyethylene (UHMWPE) particles. Methods...

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