Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Publication year range
1.
J Alzheimers Dis ; 48(1): 89-104, 2015.
Article in English | MEDLINE | ID: mdl-26401931

ABSTRACT

Truncation of tau protein is considered an early event in Alzheimer's disease (AD) and is believed to play a major pathogenic role in sporadic AD. However, causative factors that trigger tau truncation in AD remain poorly understood. In the present study, we demonstrate that CXCL1 (C-X-C motif ligand 1), a specific ligand for the chemokine receptor CXCR2, induced cleavage of tau at ASP421 in a caspase-3-dependent manner in long-term but not short-term cultured neurons. The cleaved tau formed varicosities or bead-like structures along the neurites, an abnormal distribution of tau induced by CXCL1 that has not been observed previously. CXCL1-induced activation of GSK3ß and the subsequent phosphorylation of tau preceded and were required for caspase-3 activation and tau cleavage. Moreover, intrahippocampal microinjection of lentiviral CXCL1 induced tau cleavage in hippocampal neurons in aged (15-18 months of age) but not adult mice (5-10 months of age). Our data highlight a new role of CXCR2 in tau cleavage and suggest that targeting CXCR2 may offer therapeutic benefits to patients with AD and potentially other tauopathies.


Subject(s)
Aging , Caspase 3/metabolism , Chemokine CXCL1/pharmacology , Hippocampus/cytology , Neurons/drug effects , tau Proteins/metabolism , Animals , Cells, Cultured , Chemokine CXCL1/blood , Chemokine CXCL1/cerebrospinal fluid , Chemokine CXCL1/genetics , Embryo, Mammalian , Female , Mice , Mice, Inbred C57BL , Microinjections , Microtubule-Associated Proteins/metabolism , Mutation/genetics , Neurons/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Time Factors , Transfection , tau Proteins/genetics
2.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(2): 191-6, 2014 Feb.
Article in Chinese | MEDLINE | ID: mdl-24672944

ABSTRACT

OBJECTIVE: To discuss the effect of Taohong Siwu Decoction (TSD) in regulating functions of endothelial cells and treating arteriosclerosis obliterans (ASO). METHODS: The ASO model was prepared by using high-fat diet plus intimal injury. They were randomly divided into the model group (n = 10), the normal control group (n = 9), the low dose TSD group (group A, n = 12), the middle dose TSD group (group B, n = 10), and the high dose TSD group (group C, n = 9). Eight weeks after modeling, the limb blood perfusion was observed using laser Doppler flowmetry. The arterial morphology was observed using light microscope and transmission electron microscope. The number of circulating endothelial cells (CECs) was determined using Percoll density gradient centrifugation method. Serum levels of TNF-alpha, IL-1, ET-1, and NO were detected using double antibody sandwich assay of enzyme linked immunosorbent assay (ELISA). RESULTS: The ASO rat model was successfully established. Blood lipids levels significantly increased, the blood perfusion of left hind limbs significantly decreased, the number of CECs in the peripheral blood significantly increased, the arterial lumen was irregularly narrowed, the ultra-structure of vessel walls was damaged, serum levels of TNF-alpha, IL-1, and ET-1 significantly increased, and the serum level of NO significantly decreased in the model group, showing statistical difference when compared with the normal control group (P < 0.01). Compared with the model group, significant improvement in the aforesaid indices was shown in group B and C (P < 0.05, P < 0.01). CONCLUSIONS: The injury and abnormal functions of endothelial cells is an important pathological process of ASO. As an effective recipe for treating ASO, TSD could protect vascular endothelial cells and improve the secretion function of vascular endothelial cells.


Subject(s)
Arteriosclerosis Obliterans/blood , Drugs, Chinese Herbal/pharmacology , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Animals , Arteriosclerosis Obliterans/drug therapy , Diet, High-Fat/adverse effects , Drugs, Chinese Herbal/therapeutic use , Endothelin-1/blood , Interleukin-1/blood , Male , Nitric Oxide/blood , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/blood
3.
J Urol ; 187(4): 1466-72, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22341810

ABSTRACT

PURPOSE: Abnormal miRNA expression is associated with prostate cancer progression. However, the relationship between miRNA and biochemical recurrence after radical prostatectomy is not well established. Thus, we evaluated the miRNA miR-21 as a biomarker to predict the risk of biochemical failure, and as a potential drug target for prostate cancer therapy. MATERIALS AND METHODS: miR-21 levels were assayed using locked nucleic acid in situ hybridization coupled with tissue microarray techniques in 169 radical prostatectomy tissue samples. The Cox proportional hazard model was used to analyze miR-21 expression as an independent predictor of biochemical recurrence. The association of miR-21 with recurrence was estimated using the Kaplan-Meier method. miR-21 was also evaluated as a potential drug target for prostate cancer therapy. RESULTS: miR-21 expression in prostate cancer tissue samples was significantly associated with pathological stage, lymph node metastasis, capsular invasion, organ confined disease, Gleason score, biochemical recurrence and patient followup. Multivariate analysis also indicated that miR-21 expression could be an independent predictor of biochemical recurrence. The 5-year recurrence-free probability for patients positive vs negative for miR-21 expression was 33.9% vs 44.5%. In vivo treatment with antagomir-21 also repressed the tumor growth of DU145 cells in nude mice. CONCLUSIONS: Positive miR-21 expression was associated with poor biochemical recurrence-free survival and predicted the risk of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Accordingly gene therapy using miR-21 inhibition strategies may prove useful for prostate cancer therapy.


Subject(s)
Biomarkers, Tumor/biosynthesis , MicroRNAs/biosynthesis , Neoplasm Recurrence, Local/metabolism , Prostatic Neoplasms/metabolism , Animals , Biomarkers, Tumor/analysis , Biomarkers, Tumor/antagonists & inhibitors , Humans , Male , Mice , Mice, Nude , MicroRNAs/analysis , MicroRNAs/antagonists & inhibitors , Neoplasm Recurrence, Local/chemistry , Neoplasm Recurrence, Local/drug therapy , Predictive Value of Tests , Prostatic Neoplasms/chemistry , Prostatic Neoplasms/drug therapy , Risk Assessment
4.
Contraception ; 84(6): 642-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22078196

ABSTRACT

BACKGROUND: This study was conducted to observe the in vivo effect of 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) on embryo implantation in rats and its in vitro effect on cell adhesion. STUDY DESIGN: The anti-implantation efficacy of AEBSF in rats was determined by counting the number of visible implanted embryos on day 8 of pregnancy following intrauterine (5 mg and 10 mg AEBSF per horn) or tail vein (10 mg AEBSF per rat) administration on day 3 of pregnancy. The effects of AEBSF on cell adhesion were detected, respectively, by using the mouse blastocysts-endometrial cells or the human umbilical vein endothelial cells (HUVECs)-HeLa cells co-culture model. The alteration in protein secretion pattern of HUVECs and HeLa cells was detected by the proteome analysis. RESULTS: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride showed an in vivo inhibitory effect on embryo implantation in rat. In vitro, AEBSF could disturb the growth of blastocysts on endometrial cells and inhibit the adhesion of HeLa cells on HUVECs. The treatment of AEBSF could alter the protein secretion pattern of co-cultured HUVEC-HeLa cells. CONCLUSION: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride might be a potential leading compound for novel contraceptives, and its inhibitory effect on implantation might result from the interference in extracellular matrix remodeling process.


Subject(s)
Embryo Implantation/drug effects , Serine Proteinase Inhibitors/pharmacology , Sulfones/pharmacology , Administration, Intravaginal , Animals , Blastocyst/drug effects , Cell Adhesion/drug effects , Cells, Cultured , Coculture Techniques , Contraceptives, Postcoital, Synthetic/administration & dosage , Contraceptives, Postcoital, Synthetic/pharmacology , Dose-Response Relationship, Drug , Endometrium/cytology , Endometrium/drug effects , Female , HeLa Cells , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Injections, Intravenous , Mice , Mice, Inbred ICR , Pregnancy , Random Allocation , Rats , Rats, Sprague-Dawley , Serine Proteinase Inhibitors/administration & dosage , Sulfones/administration & dosage
5.
Int J Cancer ; 127(3): 707-17, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-19950222

ABSTRACT

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in Western male population. Previous studies have demonstrated that differential display code 3 (DD3 or DD3(PCA3)) is one of the most PCa-specific genes; therefore, it has been used as a clinical diagnostic marker for PCa. In this study, we constructed an oncolytic adenovirus Ad.DD3-E1A by using the minimal DD3 promoter to replace the native viral promoter of E1A gene. In addition, Ad.DD3-E1A was armed with therapeutic gene IL-24 to enhance its antitumor activity. The resulting adenovirus, Ad.DD3-E1A-IL-24, demonstrated PCa specificity and excellent antitumor effect. Further analyses on its antitumor mechanism revealed that it has the capacity to induce apoptosis in PCa cells and inhibit angiogenesis. These results suggest that Ad.DD3-E1A-IL-24 is a promising antitumor agent that may be able to be used in the future as a treatment for PCa.


Subject(s)
Antigens, Neoplasm/genetics , Genetic Therapy , Interleukins/genetics , Oncolytic Virotherapy , Prostatic Neoplasms/therapy , Animals , Apoptosis , Base Sequence , Blotting, Western , Cell Line, Tumor , Combined Modality Therapy , DNA Primers , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Polymerase Chain Reaction , Prostatic Neoplasms/pathology
6.
J Urol ; 182(5): 2511-7, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19765770

ABSTRACT

PURPOSE: We developed an organotypic genital tubercle culture system in vitro and used it to investigate the direct effects of the hyperestrogenic state on fetal mouse penile and urethral development. MATERIALS AND METHODS: Genital tubercles were dissected from embryonic day 14.5 C57B/L6 male mouse fetuses and cultured using an air-liquid interface on a microporous membrane support soaked in synthetic medium. Cultures were separated into 4 groups. Groups 1 to 3 were supplied with 10 nM dihydrotestosterone, estradiol and 10 nM dihydrotestosterone plus estradiol, respectively. Group 4 was cultured in hormone-free medium. After 36 to 72-hour culture morphological, histological, proliferation, apoptosis, androgen signaling and activating transcription factor 3 analyses were done. RESULTS: The physiological concentration of 10 nM dihydrotestosterone was essential for genital tubercle growth in vitro. Androgen induced growth and urethral development were significantly suppressed by high dose estrogen. Concurrently we observed increased apoptosis and decreased proliferation in the mesenchyma. Androgen signaling was disrupted and activating transcription factor 3, a factor related to hypospadias genesis, was up-regulated. CONCLUSIONS: High dose estrogen suppressed male genital tubercle development in vitro. The organotypic genital tubercle culture system in vitro consisting of urethral epithelial and mesenchymal cells can recapitulate the hormonal sensitivity of fetal penile and urethral development. This method is potentially useful for studying the effects of various factors, particularly endocrine disruptors.


Subject(s)
Estrogens/pharmacology , Genitalia, Male/drug effects , Genitalia, Male/embryology , Penis/drug effects , Penis/embryology , Urethra/drug effects , Urethra/embryology , Animals , Male , Mice , Organ Culture Techniques
7.
Asian J Androl ; 11(4): 484-91, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19448646

ABSTRACT

Asthenozoospermia (AS) is a common cause of human male infertility. In one study, more than 80% of the samples from infertile men had reduced sperm motility. Seminal plasma is a mixture of secretions from the testis, epididymis and several male accessory glands, including the prostate, seminal vesicles and Cowper's gland. Studies have shown that seminal plasma contains proteins that are important for sperm motility. To further explore the pathophysiological character of AS, we separated the seminal plasma proteins from AS patients and healthy donors using sodium dodecyl sulfate polyacrylamide gel electrophoresis and in-gel digestion, and then subjected the proteins to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. A total of 741 proteins were identified in the seminal plasma, with a false discovery rate of 3.3%. Using spectral counting, we found that 45 proteins were threefold upregulated and 56 proteins were threefold downregulated in the AS group when compared with the control. Most of these proteins originated from the epididymis and prostate. This study identified a rich source of biomarker candidates for male infertility and indicates that functional abnormalities of the epididymis and prostate can contribute to AS. We identified DJ-1-a protein that has been shown elsewhere to be involved in the control of oxidative stress (OS)-as a downregulated protein in AS seminal plasma. The levels of DJ-1 in AS seminal plasma were about half of those in the control samples. In addition, the levels of reactive oxygen species were 3.3-fold higher in the AS samples than in the controls. Taken together, these data suggest that downregulation of DJ-1 is involved in OS in semen, and therefore affects the quality of the semen.


Subject(s)
Asthenozoospermia/metabolism , Oxidative Stress , Proteins/metabolism , Proteomics , Semen/metabolism , Blotting, Western , Chromatography, Liquid , Humans , Male , Reactive Oxygen Species/metabolism , Tandem Mass Spectrometry
8.
Reprod Biol Endocrinol ; 7: 12, 2009 Feb 11.
Article in English | MEDLINE | ID: mdl-19208265

ABSTRACT

BACKGROUND: Sec63 is a key component of the protein translocation machinery in the mammalian endoplasmic reticulum (ER), and involved in the post-translation processing of secretory proteins. The aim of this study was to determine the expression pattern of SEC63 gene in mouse uterus during the early pregnancy. METHODS: Real-time quantitative PCR and Western blot analyses were used to evaluate the alteration in levels of uterine SEC63 gene expression during the peri-implantation period in mice. Further, both in situ hybridization and immunohistochemical analyses were performed to examine the spatial localization of SEC63 gene expression in mouse uterine tissues. The presence of Sec63 protein in human uterine tissue was also detected by immunohistochemical analysis. Statistical analysis was carried out using Tukey test. RESULTS: Uterine SEC63 gene expression was up-regulated and predominantly localized in mouse decidual cells during days 5-8 of pregnancy. More interestingly, Sec63 protein was also detected in human decidua of 10-week pregnancy, whereas was not observed in human endometrial tissues both at proliferative and secretory phases of menstrual cycle. CONCLUSION: The pattern of SEC63 gene expression is consistent with a possible role for SEC63 in decidualization.


Subject(s)
Embryo Implantation/genetics , Up-Regulation , Uterus/metabolism , Animals , Embryo Implantation/physiology , Female , Humans , Immunohistochemistry , In Situ Hybridization , Membrane Proteins/metabolism , Mice , Mice, Inbred ICR , Molecular Chaperones , Oviducts/metabolism , Pregnancy , RNA, Messenger/metabolism , RNA-Binding Proteins
9.
Zhonghua Nan Ke Xue ; 13(8): 696-9, 2007 Aug.
Article in Chinese | MEDLINE | ID: mdl-17918707

ABSTRACT

OBJECTIVE: To investigate the expression of ARA55 mRNA in the prostate carcinoma tissues and its clinical significance. METHODS: Real-time RT-PCR was used to examine the expression of ARA55 mRNA in the samples of the prostate carcinoma tissues from 32 patients. RESULTS: ARA55 mRNA expressed in different degrees in all the samples. The Ct values were 20.57 +/- 0.20 and 16.33 +/- 0.31 at T1-T2 and T3-T4 stages, 23.13 +/- 0.13 and 17.3 +/- 0.19 for those with Gleason score < or =7 and >7, 24.70 +/- 0.27 and 17.21 +/- 0.34 for those with PSA < or =10 microg/L and >10 microg/L, and 23.82 +/- 0.21 and 16.71 +/- 0.32 for those that responded to endocrinological therapy and those that failed to, respectively. There was a significant difference between the former and the latter. CONCLUSION: ARA55 mRNA expression is significantly correlated with the clinical characteristics of the patient. And ARA55 can be regarded as a prognostic molecular marker for prostate carcinoma as well as a predictor of endocrinological therapeutic effect on the disease.


Subject(s)
Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/genetics , Prostatic Neoplasms/pathology , RNA, Messenger/metabolism , Aged , Aged, 80 and over , Follow-Up Studies , Humans , LIM Domain Proteins , Male , Middle Aged , Neoplasm Staging , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...