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Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2009年第3期10卷 172-179页

作者： Dao-fa TIAN Ying-chun HE Fang-guo LU Fa-qing TANG faculty of Integrative medicine Changsha 410007 China) faculty cf basic medicine Chinese Medicine University of Hunan Changsha 410007 China Department of Clinical Laboratory the First Xiangya Hospital Central South University Changsha 410008 China

Objective： To investigate the enhancive effect ofN, N′-dinitrosopiperazine （DNP） on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN（p53mt-LMP1）/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma （NPC）. Methods： TgN（p53mt-LMP1）/HT transgenic mice and the same strain of C57BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN（p53mt-LMP1）/HT cancerous lesion-inducing group （T1）, TgN（p53mt-LMP1）/HT control group （TC）, C57BL/6J cancerous lesion-inducing group （CI）, and C57BL/6J control group （CC）. TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as *** the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by hacmatoxylin and eosin （HE） staining and for determination on the expression ofTRAF2, c-Jun, and p 16 by immunohistochemistry. Results： Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 （P〈0.01） respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-0-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor （TNF） receptor-associated factor 2 （TRAF2） and c-Jun in these samples were significantly up-regulated in TI （P〈0.0 I）, while tbe expression of p16 was significantly lower in TI than in the other groups （P〈0.01）. Conclusion： TgN（p53mt-LMPI）/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN（p53mt-LMP1）/HT mice should be closely associated with abn

关键词： Nasal epithelia Nasopharyngeal epithelia Precancerous lesions N N′-dinitrosopiperazine (DNP) Activator protein-1(AP- 1) pathway Signal transduction

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ALTERATION IN CHROMATIN CONFORMATION OF PROLIFERATING AND DIFFERENTIATING ENZYME GENES IN NORMAL MOUSE LIVER AND ASCITES HEPATOMA CELLS AND ITS RELATION TO THE GENE EXPRESSION OF ENZYMES

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Science in China,Ser.B 1988年第11期31卷 1319-1324页

作者：李士谔马恩陵吴石君 faculty of basic medicine Beijing Union Medical University Institute of basic Medical Sciences Chinese Academy of Medical Sciences BeijingFaculty of Basic Medicine Beijing Union Medical University

Nuclei from the normal mouse liver were partially digested with micrococcal nuclease, followed by DNA extraction, agarose gel clectrophoresis and dot blot hybridization with 32P-labeled cDNA probes of CPS1 and ACT complex, It was clearly shown that the CPS1 genes were distributed on the monomer, dimer. and trimer of nucleosomes, while the genes coding for ACT complex were distributed on the condensed oligonucleosomes. An opposite manner of distribution of CPS1 and ACT complex genes was, however, noted in the case of ascites hepatoma cells, in which the specific activity of ACT was 13 times higher than that in the normal liver, while that of CPS1 was remarkably reduced. Similar patterns of change in mRNA level of CPS1 and ACT complex were observed in the normal mouse liver and ascites hepatoma cells, indicating a close relationship between chromatin structure and gene expression of these enzymes.

关键词： gene expression chromatin conformation CPS1 ACT hepatoma.

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Endothelium-derived Relaxing Factor Activates Calcium-activated Potassium Channels of Resistance Vessel Smooth Muscle Cells

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Science China Chemistry 1993年第4期36卷 439-450页

作者：汤云贵郑永芳 Department of Physiology Institute of Basic Medical Sciences CAMS Faculty of Basic Medicine PUMC Beijing 100005 PRC

Direct observation was made by using the patch-clamp technique with a specially designed microperfusion system to investigate the effect of acetylcholine (Ach 10^(-6) mol/L) elicited endothelium-derived relaxing factor (EDRF) on the calcium-activated potassium channel (IK(Ca))in the smooth muscle cells of mesenteric resistance vessels in Wistar rats. Activation of IK(Ca) was firstly observed by inducing the elicited EDRF or sodium nitroprusside (SNP 10^(-8) mol/L) under various clamping voltages in cell-attached configuration. While the pipette solution contained KCl 126 mmol/L and the bath solution contained KCl 5.9 mmol/L, two types of conductances of calcium-activated potassium current being 76.4±2.3 pS(mean±S.E. n = 7) and 160.3±7.5 pS (mean±S.E. n= 7) were recorded during the EDRF activation, one type of conductance being 100.5±2.8 pS (mean±S.E. n = 6) was activated by nitric oxide (NO) which is an effective component from SNP. Differences in kinetic characteristics of these channels between EDRF and NO activation were found, particularly the probability of the channel being open in EDRF activation was obviously greater than that in NO stimulation. It has been shown that the potassium channel mechanisms involved in the EDRF and NO actions might be different.

关键词： endothelium-derived relaxing factor (EDRF) calcium-activated potassium channel (IK(Ca)) mesenterie resistance vessel smooth muscle patch-clamp technique open microperfusion system.

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Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery

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Acta Pharmaceutica Sinica B 2018年第1期8卷 51-63页

作者： Xinyi Ma Qingxiang Song Xiaoling Gao Department of Pharmacology and Chemical Biology Faculty of Basic Medicine Shanghai Jiao Tong University School of Medicine

High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient *** on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.

关键词： Biomimetic nanocarrier Reconstituted high-density lipoprotein Biological barriers Efficient targeting Nanodrug delivery systems

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The transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines

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Asian Journal of Andrology 2019年第5期21卷 460-467页

作者： Octavio Orellana-Serradell Daniela Herrera Enrique A Castellon Hector R Contreras Department of basic and Clinical Oncology Faculty of MedicineUniversity of ChileIndependenciaSantiago 8380453Chile

One of the factors promoting tumoral progress is the abnormal activation of the epithelial-mesenchymal transition(EMT)program which has been associated with chemoresistance in tumoral *** transcription factor zinc finger E-box-binding homeobox 1(ZEB1),a key EMT activator,has recently been related to docetaxel resistance,the main chemotherapeutic used in advanced prostate cancer *** mechanisms involved in this protective effect are still *** a previous work,we demonstrated that ZEB1 expression induced an EMT-like phenotype in prostate cancer cell *** this work,we used prostate cancer cell lines 22Rvl and DU145 to study the effect of ZEB1 modulation on docetaxel resistance and its possible *** results showed that ZEB1 overexpression conferred to 22Rvl cell resistance to docetaxel while its silencing made DU145 cells more sensitive to *** of resistance markers showed no presenee of ATP-binding cassette subfamily B member 1(MDR1)and no changes in breast cancer resistance protein(BCRP)or ATP-binding cassette subfamily C member 10(MRP7).However,a correlation between ZEB1,multidrug resistance-associated protein 1(MRP1),and ATP-binding cassette subfamily C member 4(MRP4)expression was ***4 inhibition,using MK571,resensitized cells with ZEB1 overexpression to docetaxel *** addition,modulation of ZEB1 and subsequent change in MRP4 expression correlated with a lower apoptotic response to docetaxel,characterized by lower B-cell lymphoma 2(Bcl2),high BCL2-associated X protein(Bax),and high active caspase 3 *** response to docetaxel in our model seems to be mediated mainly by activation of the apoptotic death *** results showed that modulation of MRP4 could be a mediator of ZEBl-related resistance to docetaxel in prostate cancer,making it a possible marker for chemotherapy response in patients who do not express MDR1.

关键词： chemoresistance prostate cancer ZEB1

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Therapeutic and regenerative potential of different sources of mesenchymal stem cells for cardiovascular diseases

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BIOCELL 2024年第4期48卷 559-569页

作者： YARA ALZGHOUL HALA J.BANI ISSA AHMAD K.SANAJLEH TAQWA ALABDUH FATIMAH RABABAH MAHA AL-SHDAIFAT EJLAL ABU-EL-RUB FATIMAH ALMAHASNEH RAMADA R.KHASAWNEH AYMAN ALZU’BI HUTHAIFA MAGABLEH Department of basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbidJordan

Mesenchymalstemcells(MSCs)*** the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart *** can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental *** from various sources differ in their regenerative and therapeutic abilities for cardiovascular *** this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.

关键词： Bone marrow mesenchymal stem cells Adipose tissue mesenchymal stem cells Dental pulp stem cells Umbilical cord mesenchymal stem cells Cardiomyocytes Regeneration Myocardial infarction Mesenchymal stem cells Differentiation Immunomodulation

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Hepatoprotective and in vivo antioxidant activities of the hydroethanolic leaf extract of Mucuna pruriens (Fabaceae) in antitubercular drugs and alcohol models

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Chinese Journal of Natural medicines 2014年第4期12卷 273-283页

作者： Mercy B.Obogwu Abidemi J.Akindele Olufunmilayo O.Adeyemi Department of Pharmacology Faculty of Basic Medical Sciences College of Medicine University of Lagos

AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. METHOD: In each of the models used, seven groups were allotted. The different groups received normal saline(10 mL·kg-1, p.o.); hepatotoxicant(isoniazid-rifampicin, INH-RIF, 100 mg·kg-1, i.p. or 20% ethanol 5 g·kg-1, p.o.) and normal saline(10 mL·kg-1, p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg-1 p.o.; hepatotoxicant and silymarin 50 mg·kg-1 p.o.; and extract at 400 mg·kg-1 p.o.. On the 21st day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. RESULTS: The hepatotoxicants significantly(P < 0.05-0.001) increased the levels of alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), bilirubin, and malondialdehyde(MDA); and reduced the levels of catalase(CAT), superoxide dismutase(SOD), glutathione peroxidase(GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed(P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract(200 and 400 mg·kg-1) significantly reversed(P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens(100-400 mg·kg-1) elicited significant reduction(P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.

关键词： Mucuna pruriens Fabaceae Hepatoprotective Antioxidant Alcohol Antitubercular drugs

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Mechanisms of analgesic effect of mesenchymal stem cells in osteoarthritis pain

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World Journal of Stem Cells 2023年第4期15卷 196-208页

作者： Fatimah Almahasneh Ejlal Abu-El-Rub Ramada R Khasawneh basic Medical Sciences Faculty of Medicine-Yarmouk UniversityIrbid 21163Jordan

Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health *** is the most common and bothersome presentation of OA,but its treatment is still suboptimal,due to the short-term action of employed analgesics and their poor adverse effect *** to their regenerative and anti-inflammatory properties,mesenchymal stem cells(MSCs)have been extensively investigated as a potential therapy for OA,and numerous preclinical and clinical studies found a significant improvement in joint pathology and function,pain scores and/or quality of life after administration of *** a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by *** this paper,we review the evidence reported in literature that support the analgesic action of MSCs in OA,and we summarize the potential mechanisms of these antinociceptive effects.

关键词： Osteoarthritis Pain Inflammation Mesenchymal stem cells Regeneration Analgesic mechanisms

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The transcription factor ZEB1 promotes an aggressive phenotype in prostate cancer cell lines

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Asian Journal of Andrology 2018年第3期20卷 294-299页

作者： Octavio Orellana-Serradell Daniela Herrera Enrique A Castellon Hector R Contreras Department of basic and Clinical Oncology Faculty of Medicine University of Chile Independencia Santiago 8380453 Chile.

It has been reported that one of the factors that promotes tumoral progression is the abnormal activation of the epithelial-mesenchymal transition program. This process is associated with tumoral cells acquiring invasive and malignant properties and has the transcription factor zinc finger E-box-binding homeobox 1 （ZEB1） as one of its main activators. However, the role of ZEB1 in promoting malignancy in prostate cancer （PC, a） is still unclear. Here, we report that ZEB1 expression correlates with Gleason score in PCa samples and that expression of ZEB1 regulates epithelial-mesenchymal transition and malignant characteristics in PCa cell lines. The results showed that ZEB1 expression is higher in samples of higher malignancy and that overexpression of ZEB1 was able to induce epithelial-mesenchymal transition by upregulating the mesenchymal marker Vimentin and downregulating the epithelial marker E-Cadherin. On the contrary, ZEB 1 silencing repressed Vimentin expression and upregulated E-Cadherin. ZEB1 expression conferred enhanced motility and invasiveness and a higher colony formation capacity to 22Rvl cells whereas DU145 cells with ZEB1 silencing showed a decrease in those same properties. The results showed that ZEB1 could be a key promoter of tumoral progression toward advanced stages of PC, a.

关键词： epithelial-mesenchymal transition prostate cancer transcriptional repression ZEB1

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Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the Achang population of southwestern China

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Science China(Life Sciences) 2007年第4期50卷 479-485页

作者： YANG YinFeng, ZHU YueChun, LI DanYi, LI ZhiGang, Lü HuiRu, WU Jing, TANG Jing & TONG ShuFen Department of Biochemistry, faculty of basic medicine, Kunming University of Medical Sciences, Kunming 650031, China These authors contributed equally to this work Department of Biochemistry Faculty of Basic Medicine Kunming University of Medical Sciences Kunming China

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its gene mutations were studied in the Achang population from Lianghe County in Southwestern China. We found that 7.31% (19 of 260) males and 4.35% (10 of 230) females had G6PD deficiency. The molecular analysis of G6PD gene exons 2―13 was performed by a PCR-DHPLC-Sequencing or PCR-Sequencing. Sixteen inde-pendent subjects with G6PD Mahidol (487G>A) and the new polymorphism IVS5-612 (G>C), which combined into a novel haplotype, were identified accounting for 84.2% (16/19). And 100% Achang G6PD Mahidol were linked to the IVS5-612 C. The percentage of G6PD Mahidol in the Achang group is close to that in the Myanmar population (91.3% 73/80), which implies that there are some gene flows between Achang and Myanmar populations. Interestingly, G6PD Canton (1376G>T) and G6PD Kaiping (1388G>A), which were the most common G6PD variants from other ethnic groups in China, were not found in this Achang group, suggesting that there are different G6PD mutation profiles in the Achang group and other ethnic groups in China. Our findings appear to be the first documented report on the G6PD genetics of the AChang people, which will provide important clues to the Achang ethnic group origin and will help prevention and treatment of malaria in this area.

关键词： glucose-6-phosphate dehydrogenase deficiency Achang population G6PD Mahidol gene mutation Myanmar population

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