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1.
Biol Pharm Bull ; 38(6): 827-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25787895

RESUMO

Dendritic cell (DC)-based vaccines are a promising therapeutic modality for cancer. Results from recent trials and approval of the first DC vaccine by the U.S. Food and Drugs Administration for prostate cancer have paved the way for DC-based vaccines. A total of 21 hormone refractory prostate cancer (HRPC) patients with a life expectancy >3 months were randomised into two groups. DC loaded with recombinant Prostate Specific Membrane Antigen (rPSMA) and recombinant Survivin (rSurvivin) peptides was administered as an subcutaneous (s.c.) injection (5×10(6) cells). Docetaxel (75 mg/m(2) intravenous (i.v.)) and prednisone (5 mg, bis in die (b.i.d.)) served as control. Clinical and immunological responses were evaluated. Primary endpoints were safety and feasibility; secondary endpoint was overall survival. Responses were evaluated on day 15, day 30, day 60, and day 90. DC vaccination was well tolerated with no signs of grade 2 toxicity. DC vaccination induced delayed-type hypersensitivity reactivity and an immune response in all patients. Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumours (RECIST) was 72.7% (8/11) versus 45.4 (5/11) in the docetaxel arm and immune related response criteria (irRC) was 54.5% (6/11) compared with 27.2% (3/11) in the control arm. The DC arm showed stable disease (SD) in 6 patients, progressive disease (PD) in 3 patients, and partial remission (PR) in two patients compared to SD in 5 patients, PD in 6 patients, and PR in none in the docetaxel arm. There was a cellular response, disease stabilization, no adverse events, and partial remission with the rPSMA and rSurvivin primed DC vaccine.


Assuntos
Antineoplásicos/uso terapêutico , Vacinas Anticâncer , Células Dendríticas , Proteínas Inibidoras de Apoptose/uso terapêutico , Antígeno Prostático Específico/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Vacinação , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias , Antineoplásicos/farmacologia , Docetaxel , Humanos , Hipersensibilidade Tardia/imunologia , Proteínas Inibidoras de Apoptose/farmacologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias , Antígeno Prostático Específico/farmacologia , Neoplasias da Próstata/imunologia , Survivina , Taxoides/farmacologia , Taxoides/uso terapêutico
2.
Int J Gen Med ; 15: 3143-3154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342305

RESUMO

Background: The aim of this study was to identify novel genetic features of Hunner's lesion interstitial cystitis (HIC) via comprehensive analysis of the Gene Expression Omnibus (GEO) database. Methods: The GSE11783 and GSE28242 datasets were downloaded from GEO for further analysis. Differentially expressed genes (DEGs) were identified and analyzed for functional annotation. The diagnostic markers for HIC were screened and validated using the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms. Finally, the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was adopted to investigate the correlation between immune cell infiltration and diagnostic markers in HIC. Results: A total of 7837 DEGs were identified in GSE11783 and 1583 DEGs in GSE28242. Venn diagrams were used to obtain 16 overlapping upregulated and 67 overlapping downregulated DEGs separately. The LASSO logistic model and SVM-RFE algorithm were used to identify 6 genes including KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 from DEGs as diagnostic markers for HIC. Their diagnostic potential in HIC and bladder pain syndrome/interstitial cystitis (BPS/IC) were acceptable. PLAC8 exhibited the best diagnostic performance in BPS/IC with an area under the curve of 0.916. The results of immune infiltration involving GSE11783 revealed that the plasma cell ratio (p = 0.017), activated memory CD4+ T cells (p = 0.009), activated dendritic cells (p = 0.01), eosinophils (p = 0.004), and neutrophils (p = 0.03) were significantly higher in HIC than in normal samples, in contrast to resting mast cells (p = 0.022). A positive correlation existed between diagnostic markers and infiltrating immune cells. Conclusion: KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 represent novel and potent diagnostic markers for HIC. They also exhibit certain diagnostic potential in BPS/IC. Immune cell infiltration might play a key role in the pathogenesis and progression of BPS/IC.

3.
J Biol Chem ; 285(18): 13874-84, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-20194495

RESUMO

The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist of residues Met-Lys-His-Met (MKHM) corresponding to human PrP-(109-112). This assumption is based mainly on the observation that 3F4 reacts with human and hamster PrP but not with PrP from mouse, sheep, and cervids, in which Met at residue 112 is replaced by Val. Here we report that, by brain histoblotting, 3F4 did not react with PrP of uninfected transgenic mice expressing elk PrP; however, it did show distinct immunoreactivity in transgenic mice infected with chronic wasting disease. Compared with human PrP, the 3F4 reactivity with the recombinant elk PrP was 2 orders of magnitude weaker, as indicated by both Western blotting and surface plasmon resonance. To investigate the molecular basis of these species- and conformer-dependent preferences of 3F4, the epitope was probed by peptide membrane array and antigen competition experiments. Remarkably, the 3F4 antibody did not react with MKHM but reacted strongly with KTNMK (corresponding to human PrP-(106-110)), a sequence that is also present in cervids, sheep, and cattle. 3F4 also reacted with elk PrP peptides containing KTNMKHV. We concluded that the minimal sequence for the 3F4 epitope consists of residues KTNMK, and the species- and conformer-dependent preferences of 3F4 arise largely from the interactions between Met(112) (human PrP) or Val(115) (cervid PrP) and adjacent residues.


Assuntos
Anticorpos Monoclonais/química , Especificidade de Anticorpos , Epitopos/química , Príons/química , Animais , Bovinos , Cricetinae , Epitopos/genética , Epitopos/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Príons/genética , Príons/metabolismo , Conformação Proteica , Ovinos , Especificidade da Espécie
4.
J Urol ; 185(5): 1578-82, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21419437

RESUMO

PURPOSE: The indication for laparoscopic total or partial adrenalectomy in patients with aldosterone producing adrenal adenoma remains controversial. We compared retroperitoneoscopic partial and total adrenalectomy for aldosterone producing adrenal adenoma in a prospective, randomized, multicenter trial. MATERIALS AND METHODS: Patients with aldosterone producing adrenal adenoma were randomized to retroperitoneoscopic partial or total adrenalectomy. Patient characteristics, surgical data, complications and postoperative clinical results were analyzed statistically. RESULTS: From July 2000 to March 2004, 212 patients were enrolled in this study, including 108 and 104 who underwent total and partial adrenalectomy, respectively. The 2 groups were comparable in patient age, gender, body mass index and tumor site. Mean followup was 96 months in each group. No conversion to open surgery was needed and no major complications developed. Partial adrenalectomy required a shorter operative time than total adrenalectomy but this did not attain statistical significance. Intraoperative blood loss in the partial adrenalectomy group was significant higher than in the total adrenalectomy group (p <0.05) but no patient needed blood transfusion. All patients in each group showed improvement in hypertension, and in all plasma renin activity and aldosterone returned to normal after surgery. No patient required potassium supplements postoperatively. In the total and partial adrenalectomy groups 32 (29.6%) and 29 patients (27.9%), respectively, were prescribed a decreased dose of or fewer antihypertensive medicines at final followup. CONCLUSIONS: Retroperitoneoscopic partial adrenalectomy is technically safe. It has therapeutic results similar to those of total adrenalectomy in patients with primary aldosteronism due to aldosteronoma.


Assuntos
Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Hiperaldosteronismo/cirurgia , Adenoma/complicações , Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Aldosterona/metabolismo , Feminino , Humanos , Hiperaldosteronismo/etiologia , Laparoscopia , Masculino , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do Tratamento
5.
J Toxicol Environ Health A ; 74(22-24): 1493-503, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22043910

RESUMO

Prion diseases are a group of incurable transmissible neurodegenerative disorders. The key molecular event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrP(C)) into its pathological isoform (PrP(Sc)), accompanied by a conformational transition of α-helix into ß-sheet structure involving the structured α-helix 1 domain from residues 144-154 of the protein (PrP144-154). Blocking the accessibility of PrP144-152 with anti-PrP antibody 6H4 was found to prevent PrP conversion and even to cure prion infection in cell models ( Enari et al. 2001 ). Previously, Yuan et al. (2005 ) demonstrated that the reduction and alkylation of PrP induced concealment of the 6H4 epitope. This study examined the ability of mechlorethamine (MCT), an alkylating antitumor drug, to conceal the 6H4 epitope and block PrP conversion in the presence of a reducing reagent. Mechlorethamine treatment significantly decreased in vitro amplification of PrP(Sc) in the highly efficient protein misfolding cyclic amplification system. Our findings suggest that MCT may serve as a potential therapeutic agent for prion diseases.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Mecloretamina/farmacologia , Proteínas PrPC/antagonistas & inibidores , Proteínas PrPC/química , Animais , Antineoplásicos Alquilantes/uso terapêutico , Epitopos/imunologia , Epitopos/metabolismo , Humanos , Mecloretamina/uso terapêutico , Proteínas PrPC/metabolismo , Doenças Priônicas/tratamento farmacológico , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Dobramento de Proteína/efeitos dos fármacos , Isoformas de Proteínas , Estrutura Secundária de Proteína/efeitos dos fármacos
6.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34132366

RESUMO

The long non-coding RNA 00858 (LINC00858) has been reported to be an oncogene for various cancer diseases, including osteosarcoma and colorectal cancer. However, the expression pattern and function of LINC00858 in bladder cancer remain largely unknown. The expression level of LINC00858 was measured in tumor tissues and cell lines by RT-qPCR. The role of LINC00858 in bladder cancer cells were studied by gain- and loss-of-function strategies in vitro. Cell proliferation, migration and invasion were assessed by CCK-8, colony formation, wound healing and Transwell chamber assays. At the molecular level, dual luciferase reporter and RNA RIP assays were performed to identify the interaction among LINC00858, microRNA (miR)-3064-5p and cellular communication network factor 2 (CTGF). The results revealed that the expression level of LINC00858 was upregulated in bladder cancer tissues and cell lines including T24, J82 and 5637. Moreover, knockdown of LINC00858 suppressed cell proliferation, migration and invasion in vitro. Mechanistically, LINC00858 functioned as a competitive RNA to increase the expression level of oncogene CTGF by sequestering miR-3064-5p. In conclusion, LINC00858 knockdown inhibited the proliferation, migration and invasion of bladder cancer cells via regulation of the miR-3064-5p/CTGF axis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Adulto , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade
7.
World J Clin Cases ; 8(10): 2050-2055, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32518800

RESUMO

BACKGROUND: A vascular tumor is a benign tumor with unique clinical and pathological features. Perirenal vascular tumor is extremely rare and has not yet been reported. Clinically, it manifests as soreness and swelling. Color ultrasound and renal angiography illustrated the perirenal mass, which was closely connected with the kidney and the surrounding tissues and organs. Histology showed extensive embedded perirenal fat, and thin-walled vascular tissue displayed a pink stain due to red blood cells. CASE SUMMARY: Herein, a case of robot-assisted retroperitoneal laparoscopic excision of a perirenal vascular tumor is reported. Analysis of the clinical, biological, and histological features of the perirenal vascular tumor can provide an in-depth understanding of the disease, which provides a theoretical and practical basis for better diagnosis and treatment. CONCLUSION: This study contributes to a practical basis for the diagnosis and treatment of perirenal hemangiom.

8.
EPMA J ; 10(3): 249-259, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31462942

RESUMO

OBJECTIVE: The amplitude of low-frequency fluctuation (ALFF) fMRI technique was used to study the changes of spontaneous brain activity in patients with diabetic retinopathy and nephropathy (DRN), and to explore the application of ALFF technique in the potential prediction and the targeted prevention of diabetic microangiopathy. METHODS: Nineteen patients with diabetic retinopathy and nephropathy and 19 healthy controls (HCs) were matched for age and gender. Spontaneous cerebral activity variations were investigated using the ALFF technique. The average ALFF values of the DRN patients and the HCs were classified utilizing receiver operating characteristic (ROC) curves. RESULTS: In contrast to the results in the HCs, the patients with DRN had significantly higher ALFF values in the cerebellum (bilaterally in the posterior and anterior lobes) and the left inferior temporal gyrus, but the ALFF values of the bilateral medial frontal gyrus, right superior temporal gyrus, right middle frontal gyrus, left middle/inferior frontal gyrus, bilateral precuneus, and left inferior parietal lobule were lower. ROC curve analysis of each brain region showed the accuracy of AUC was excellent. However, the mean ALFF values in the different regions did not correlate with clinical performance. The subjects showed abnormal neuronal synchronization in many areas of the brain, which is consistent with cognitive and visual functional deficits. CONCLUSION: Abnormal spontaneous activity was detected in many areas of the brain, which may provide useful information for understanding the pathology of DRN. Abnormal ALFF values of these brain regions may be of predictive value in the development of early DRN and be a targeted intervention indicator for individualized treatment of diabetic microvascular diseases.

9.
Cell Signal ; 56: 1-14, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30465826

RESUMO

As the most commonly occurring form of primary renal tumor, renal cell carcinoma (RCC) is a malignancy accompanied by a high mortality rate. 3-phosphoinositide-dependent protein kinase 1 (PDK1) has been established as a protein target and generated considerable interest in both the pharmaceutical and academia industry. The aim of the current study was to investigate the effect of si-PDK1 on the RCC cell apoptosis, proliferation, migration, invasion and epithelial mesenchymal transition (EMT) in connection with the PI3K-PDK1-Akt pathway. Microarray analysis from the GEO database was adopted to identify differentially expressed genes (DEGs) related to RCC, after which the positive expression of the PDK1 protein in tissue was determined accordingly. The optimal silencing si-RNA was subsequently selected and RCC cell lines 786-O and A498 were selected and transfected with either a si-PDK1 or activator of the PI3K-PDK1-Akt pathway for grouping purposes. The mRNA and protein expressions of PDK1, the PI3K-PDK1-Akt pathway-, EMT- and apoptosis-related genes were then evaluated. The effect of si-PDK1 on cell proliferation, apoptosis, invasion and migration was then analyzed. Through microarray analysis of GSE6344, GSE53757, GSE14762 and GSE781, PDK1 was examined. PDK1 was determined to be highly expressed in RCC tissues. Si-PDK1 exhibited marked reductions in relation to the mRNA and protein expression of PDK1, PI3K, AKT as well as Vimentin while elevated mRNA and protein expressions of E-cadherin were detected, which ultimately suggested that cell migration, proliferation and invasion had been inhibited coupled with enhanced levels of cell apoptosis. While a notable observation was made highlighting that the PI3K-PDK1-Akt pathway antagonized the effect of PDK1 silencing. Taken together, the key observations of this study provide evidence suggesting that high expressions of PDK1 are found in RCC, while highlighting that silencing PDK1 could inhibit RCC cell proliferation, migration, invasion and EMT by repressing the PI3K-PDK1-Akt pathway.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Carcinoma de Células Renais/patologia , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Renais/patologia , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/biossíntese , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Adulto , Idoso , Antígenos CD/metabolismo , Apoptose/genética , Caderinas/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Vimentina/metabolismo
10.
Indian J Surg ; 80(3): 252-258, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29973756

RESUMO

The present study aims to compare the operative outcomes following the use of robot-assisted retroperitoneal partial nephrectomy (RARPN) with radius, exophytic/endophytic, nearness to sinus, anterior/posterior, and location (RENAL) scoring or laparoscopic retroperitoneal partial nephrectomy (LRPN) for the treatment of renal tumors. Eighty-three nephron-sparing surgery (NSS) procedures performed between January 2013 and December 2015 were reviewed. The study set consisted of 26 robot-assisted retroperitoneal laparoscopes, of which 3 were high risk (RENAL score ≥10), 11 were medium risk (RENAL score ≥7 < 9), and 12 were low risk (RENAL score <7) and 57 laparoscopic retroperitoneal partial nephrectomy procedures (7 high, 22 medium, and 28 low risk). All surgeries were successful in the absence of conversion or transfusion. Operative times were 96.0 ± 16.9 and 110.0 ± 19.4 min for RARPN and LRPN, respectively (P < 0.05). Warm ischemia times (WITs) were 17.6 ± 3.1 and 22.8 ± 3.5 min, respectively (P < 0.05). Estimated blood losses (EBLs) were 45 ± 15 and 97 ± 25 mL, respectively (P < 0.05). No statistical significance was found in duration of drainage, intestinal recovery time, hospital stay, serum creatinine, and perioperative complications (P > 0.05). RARPN affords significant advantages in outcomes of WIT, EBL, and recovery time over conventional LRPN owing to an increased accuracy in excision and suturing. Patients bearing high-risk renal tumors (RENAL score ≥10) are suitable candidates for RARPN.

11.
Sci Transl Med ; 9(417)2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29167394

RESUMO

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible through iatrogenic routes due to abundant infectious prions [misfolded forms of the prion protein (PrPSc)] in the central nervous system (CNS). Some epidemiological studies have associated sCJD risk with non-CNS surgeries. We explored the potential prion seeding activity and infectivity of skin from sCJD patients. Autopsy or biopsy skin samples from 38 patients [21 sCJD, 2 variant CJD (vCJD), and 15 non-CJD] were analyzed by Western blotting and real-time quaking-induced conversion (RT-QuIC) for PrPSc Skin samples from two patients were further examined for prion infectivity by bioassay using two lines of humanized transgenic mice. Western blotting revealed dermal PrPSc in one of five deceased sCJD patients and one of two vCJD patients. However, the more sensitive RT-QuIC assay detected prion seeding activity in skin from all 23 CJD decedents but not in skin from any non-CJD control individuals (with other neurological conditions or other diseases) during blinded testing. Although sCJD patient skin contained ~103- to 105-fold lower prion seeding activity than did sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated with sCJD skin homogenates from two sCJD patients succumbed to prion disease within 564 days after inoculation. Our study demonstrates that the skin of sCJD patients contains both prion seeding activity and infectivity, which raises concerns about the potential for iatrogenic sCJD transmission via skin.


Assuntos
Síndrome de Creutzfeldt-Jakob/patologia , Príons/patogenicidade , Pele/patologia , Idoso , Animais , Bioensaio , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Humanos , Técnicas In Vitro , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Doenças Priônicas/patologia
12.
Zhonghua Yi Xue Za Zhi ; 86(6): 403-6, 2006 Feb 14.
Artigo em Zh | MEDLINE | ID: mdl-16677551

RESUMO

OBJECTIVE: To evaluate the feasibility and effect of mesenchymal stem cells (MSCs)-poly (lactic-co-glycolic acid) (PLGA) scaffold as transplant in repair of skin damage. METHODS: MSCs were isolated from the bone marrow of femur of a one-month-old New Zealand rabbit, cultured, and labeled with diamidino-phenyl-indole (DAPI). Porous foam scaffolds were made with PLGA. MSCs of 2 - 3 passages were seeded on the scaffolds. Fluorescence microscopy and scanning electron microscopy were used to observe the growth of the MSCs. Six pieces of skin 2 cm x 2 cm in size were cut from the backs of five 5-month-old new Zealand rabbits and then 4 pieces of MSCs- PLGA scaffolds and 2 pieces of porous foam PLGA scaffolds of the size similar to these of the cut skin were transplanted to the skin wounds. The wound healing was observed. Five days after the operation, samples of newly-grown skin were taken to undergo HE staining, VG staining, and microscopy. Immunofluorescence histochemistry was used to detect the cytokeratin AE1/AE3. RESULTS: Scanning electron microscopy showed that holes were distributed evenly on the surface of and inside the porous foam PLGA scaffolds Fluorescence microscopy and scanning electron microscopy showed that the MSCs grew well on the porous foam PLGA scaffolds and the number of MSCs increased gradually. Animal experiment showed that with the degradation of the polymer scaffolds the wounds were gradually covered by newly grown skin similar to the normal skin. Immunofluorescence histochemistry showed fluorescence positive cells in the stratum corneum and follicles. The wounds transplanted only with porous foam PLGA scaffolds formed new skin too, however, in the dermis of the new skin only thickened fibrous scars and a few follicles were seen. CONCLUSION: The compound of MSCs-PLGA polymer is effective in wound healing.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Ácido Láctico/farmacologia , Transplante de Células-Tronco Mesenquimais , Ácido Poliglicólico/farmacologia , Polímeros/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Imunofluorescência , Queratinas/análise , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Pele/química , Pele/lesões , Engenharia Tecidual , Alicerces Teciduais
13.
Oncotarget ; 6(2): 642-50, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25460507

RESUMO

In transmission studies with Alzheimer's disease (AD) animal models, the formation of Aß plaques is proposed to be initiated by seeding the inoculated amyloid ß (Aß) peptides in the brain. Like the misfolded scrapie prion protein (PrPSc) in prion diseases, Aß in AD shows a certain degree of resistance to protease digestion while the biochemical basis for protease resistance of Aß remains poorly understood. Using in vitro assays, histoblotting, and electron microscopy, we characterize the biochemical and morphological features of synthetic Aß peptides and Aß isolated from AD brain tissues. Consistent with previous observations, monomeric and oligomeric Aß species extracted from AD brains are insoluble in detergent buffers and resistant to digestions with proteinase K (PK). Histoblotting of AD brain tissue sections exhibits an increased Aß immunoreactivity after digestion with PK. In contrast, synthetic Aß40 and Aß42 are soluble in detergent buffers and fully digested by PK. Electron microscopy of Aß40 and Aß42 synthetic peptides shows that both species of Aß form mature fibrils. Those generated from Aß40 are longer but less numerous than those made of Aß42. When spiked into human brain homogenates, both Aß40 and Aß42 acquire insolubility in detergent and resistance to PK. Our study favors the hypothesis that the human brain may contain cofactor(s) that confers the synthetic Aß peptides PrPSc-like physicochemical properties.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Príons/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos
14.
PLoS One ; 10(9): e0136923, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26327228

RESUMO

The cellular prion protein (PrPC), a protein most noted for its link to prion diseases, has been found to play a protective role in ischemic brain injury. To investigate the role of PrPC in the kidney, an organ highly prone to ischemia/reperfusion (IR) injury, we examined wild-type (WT) and PrPC knockout (KO) mice that were subjected to 30-min of renal ischemia followed by 1, 2, or 3 days of reperfusion. Renal dysfunction and structural damage was more severe in KO than in WT mice. While PrP was undetectable in KO kidneys, Western blotting revealed an increase in PrP in IR-injured WT kidneys compared to sham-treated kidneys. Compared to WT, KO kidneys exhibited increases in oxidative stress markers heme oxygenase-1, nitrotyrosine, and Nε-(carboxymethyl)lysine, and decreases in mitochondrial complexes I and III. Notably, phosphorylated extracellular signal-regulated kinase (pERK) staining was predominantly observed in tubular cells from KO mice following 2 days of reperfusion, a time at which significant differences in renal dysfunction, histological changes, oxidative stress, and mitochondrial complexes between WT and KO mice were observed. Our study provides the first evidence that PrPC may play a protective role in renal IR injury, likely through its effects on mitochondria and ERK signaling pathways.


Assuntos
Rim/metabolismo , Príons/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase-1/metabolismo , Nefropatias/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Tirosina/análogos & derivados , Tirosina/metabolismo
15.
Hepatobiliary Pancreat Dis Int ; 3(4): 620-2, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15567759

RESUMO

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) with portal-enteric drainage is physiological effective in treatment of patients with diabetes mellitus complicated by end-stage renal disease. A case is reported with a review of our clinical experience. METHODS: A patient with type 2 diabetes complicated by renal failure was subjected to SPK transplantation with portal-enteric drainage. Pancreaticoduodenal allograft procured from corpse was transplanted to recipient's right abdomen with donor's portal vein anastomosed to recipient's superior mesenteric vein. Donor's plastic pancreas artery was anastomosed to recipient's right common iliac artery and donor's duodenum anastomosed to recipient's jejunum. The kidney allograft was transplanted ectopically to the contralateral iliac fossa. Postoperative immunosuppression includes tacrolimus (TAC)/mycophenolate mofetil (MMF)-based regimen and methylprednisolone or prednisone. RESULTS: On the 5th postoperative day, the level of blood creatinine decreased from 590 micromol/L to normal. Daily urine volume was about 2500 ml. On the 18th postoperative day, insulin was given up, and the levels of fasting blood-glucose and after meal blood-glucose were kept normal. No acute rejection symptoms or other complications were observed except infection of Pseudomonas aeruginosa. CONCLUSION: Combined pancreas and kidney transplantation with portal-enteric drainage is a physiological effective treatment for diabetic patients with end-stage renal disease.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/cirurgia , Drenagem , Intestinos/irrigação sanguínea , Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Pâncreas , Sistema Porta , Adulto , Nefropatias Diabéticas/etiologia , Humanos , Falência Renal Crônica/etiologia , Masculino , Resultado do Tratamento
16.
J Clin Cell Immunol ; 5(4)2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25419482

RESUMO

Differentiating iatrogenic Creutzfeldt-Jakob disease (iCJD) from sporadic CJD (sCJD) would be useful for the identification and prevention of human-to-human prion transmission. Currently, the diagnosis of iCJD depends on identification of a recognized source of contamination to which patients have been exposed, in addition to fulfilling basic requirements for the establishment of diagnosis of CJD. Attempts to identify differences in clinical manifestations, neuropathological changes and pathological prion protein (PrPSc) between iCJD and sCJD have been unsuccessful. In the present study, using a variety of more sophisticated methods including sucrose step gradient sedimentation, conformational stability immunoassay, protein misfolding cyclic amplification (PMCA), fragment-mapping, and transmission study, we show no significant differences in gel profiles, oligomeric state, conformational stability and infectivity of PrPSc between iCJD and sCJD. However, using PMCA, we find that convertibility and amplification efficiency of PrPSc is greater in iCJD than in sCJD in a polymorphism-dependent manner. Moreover, two protease-resistant PrP C-terminal fragments (termed PrP-CTF12/13) were detected in all 9 cases of sCJD but not in 6 of 8 cases of iCJD tested in this study. The use of fragment mapping- and PMCA-based assays thus provides a means to distinguish most cases of iCJD from sCJD.

19.
Ai Zheng ; 22(6): 607-11, 2003 Jun.
Artigo em Zh | MEDLINE | ID: mdl-12948410

RESUMO

BACKGROUND & OBJECTIVE: PTEN is a tumor suppressor gene with phosphatase activity. It had been proved the aberrant expression and mutation of PTEN in diverse types of human cancer; PTEN is closely associated with occurrence and development of malignant tumor. This study was conducted to investigate the expression of PTEN/MMAC1/TEP1 gene product in human renal cell carcinoma (RCC) and the correlation between the expression of PTEN and the biological behaviors of RCC. METHODS: The PTEN protein of 44 cases of RCC tissues confirmed by pathology after operation, 15 cases of adjacent normal renal tissues, and 10 cases of non-tumor normal renal tissues were assessed using immunohistochemical technique (SP). Fifteen RCC tissues and 10 normal renal tissues selected respectively from the renal tissues whose PTEN protein expression were positive as well as those from the negative were made to be the cell suspension mingled with paraffin. The proliferative index and the apoptosis incidence were examined by flow cytometry and the correlation between PTEN protein and the proliferation and apoptosis were analyzed. RESULTS: The expression of PTEN protein was mostly located in the renal cell plasma. The positive incidence of expression PTEN protein in RCC was 36.3% which was prominently lower than those in the adjacent normal tissues (77.3%) and the normal tissues (100.00%) (P< 0.01). There was no significant difference between the different sorts of tissues (P >0.05). The expression of PTEN in stage I, II is much higher than that in stage III, IV(P< 0.05). The proliferative index of RCC whose expression of PTEN protein was positive (5.6+/-0.8)% was significantly lower than that of negative (15.6+/-1.6)% (P< 0.01). While the apoptosis incidence was (6.5+/-1.9)%,which was much higher than that of RCC whose expression was (2.9+/-1.6)% (P< 0.01). CONCLUSION: The positive expression incidence of PTEN protein significantly decreases in RCC tissues. PTEN protein suppresses carcinoma by inducing the cell cycle to be blocked up in G1 phase and increasing the apoptosis incidence. The assessment of the expression PTEN protein is one of the important indexes of the development and prognosis of RCC.


Assuntos
Apoptose , Carcinoma de Células Renais/genética , Genes Supressores de Tumor , Neoplasias Renais/genética , Monoéster Fosfórico Hidrolases/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Carcinoma de Células Renais/patologia , Divisão Celular , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/análise , Prognóstico , Proteínas Supressoras de Tumor/análise
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