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1.
Chem Biodivers ; : e202401034, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109873

RESUMEN

The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1 a-h), dithiocarbamate-Cu(II) complexes (2 a-hCu) and disulfide derivatives (2 a-e, 2 i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7, and 15.1-111 µM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1 g may be a partial reversible inhibitor, while 2 d and 2 f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2 d, 2 f-Cu, and 1 g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2 f-Cu and 2 d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2 f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2 d and 1 g exhibit low cytotoxicity, whereas 2 f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.

2.
World J Clin Cases ; 12(19): 3950-3955, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38994291

RESUMEN

BACKGROUND: We report a case of eye-penetrating injury in which a massive silicone oil migration into the patient's subconjunctival space and orbit occurred after vitrectomy. CASE SUMMARY: A 30-year-old male patient sought medical attention at Ganzhou People's Hospital after experiencing pain and vision loss in his left eye due to a nail wound on December 9, 2023. Diagnosis of penetrating injury caused by magnetic foreign body retention in the left eye and hospitalization for treatment. On December 9, 2023, pars plana vitrectomy was performed on the left eye for intraocular foreign body removal, abnormal crystal extraction, retinal photocoagulation. Owing to the discovery of retinal detachment at the posterior pole during surgery, silicone oil was injected to fill the vitreous body, following which upper conjunctival bubble-like swelling was observed. Postoperative orbital computed tomography (CT) review indicated migration of silicone oil to the subconjunctival space and orbit through a self-permeable outlet. On December 18, 2023, the patient sought treatment at the First Affiliated Hospital of Nanchang University, China. The patient presented with a pronounced foreign body sensation following left eye surgery. On December 20, 2023, the foreign body was removed from the left eye frame and an intraocular examination was conducted. The posterior scleral tear had closed, leading to termination of the surgical procedure following supplementary laser treatment around the tear. The patient reported a significant reduction in ocular surface symptoms just one day after surgery. Furthermore, a notable decrease in the migration of silicone oil was observed in orbital CT scans. CONCLUSION: The timing of silicone oil injection for an eye-penetrating injury should be carefully evaluated to avoid the possibility of silicone oil migration.

3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(5): 796-800, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34728042

RESUMEN

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Preparaciones Farmacéuticas , Inhibidores de la Angiogénesis/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular/uso terapéutico
4.
Int J Ophthalmol ; 13(1): 141-148, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31956583

RESUMEN

AIM: To compare the anatomic and functional outcomes between vitrectomy with internal limiting membrane (ILM) peeling and internal ILM flap insertion technique for high myopia macular hole (MH). METHODS: PubMed, Cochrane Library, EMBASE, and CNKI were systematically searched, and all studies involved MH were included. The closure rate of MH and the postoperative best-corrected visual acuity (BCVA) at 6mo after the initial surgery were the primary measures. All statistical tests were performed in Review Manager 5.3. RESULTS: Five studies that included 151 eyes of 151 patients were finally included, all of which were retrospectively comparative studies. Between the pars plana vitrectomy (PPV) with ILM peeling surgery and the ILM insertion technique, the latter had significantly better efficacy with respect to the closure rate of MH (OR=21.32, 95%CI=7.25-62.67, P<0.001); However, regarding BCVA at 6mo after the initial surgery in MH, there was no statistical significance between the groups (OR=-0.04, 95%CI=-0.22-0.14, P=0.66). In addition, regarding the rate of retinal reattachment after the initial surgery, the two different methods were not significantly different (OR=2.22, 95%CI=0.34-14.32, P=0.4). CONCLUSION: Both ILM peeling and ILM insertion technique could significantly improve anatomic outcomes of MH in high myopia with or without retinal detachment (RD), and anatomic outcomes are more effective. However, there is no statistical significance in BCVA at 6mo after the initial surgery in MH, or in the rate of retinal reattachment after the first surgery, between the two methods.

5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(3): 402-407, 2019 Jun 30.
Artículo en Chino | MEDLINE | ID: mdl-31282337

RESUMEN

Ocular myasthenia gravis(OMG)is an autoimmune disease caused by neuromuscular junction transmission disorders and manifested mainly as fluctuating blepharoptosis and diplopia,with the extraocular muscles as the main involveed sites.While the pathogenesis of OMG remains unclear,some antibodies,complements,and cytokines may be the contributing factors.The diagnosis and treatment of OMG have been defined in recent years.This article reviews the pathogenesis,diagnosis,and treatment of OMG.


Asunto(s)
Miastenia Gravis/diagnóstico , Miastenia Gravis/patología , Miastenia Gravis/terapia , Músculos Oculomotores/patología , Anticuerpos , Proteínas del Sistema Complemento , Citocinas , Humanos
6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 261-266, 2019 Apr 28.
Artículo en Chino | MEDLINE | ID: mdl-31060684

RESUMEN

Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-ß,polyunsaturated fatty acids,and ß-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.


Asunto(s)
Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/cirugía , Niño , Humanos , Recién Nacido , Recien Nacido Prematuro , Neovascularización Patológica/terapia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
7.
Chemosphere ; 227: 289-298, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30999170

RESUMEN

Residual dichlorodiphenyltrichloroethane (DDT) in the environment and a continuously increasing atmospheric carbon dioxide (CO2) concentration are two issues that have received a lot of attention. This study was conducted using a pot experiment to investigate the interactive effects of elevated CO2 and DDT on the uptake of DDT, the physiological responses and the resulting health risks in three vegetables. These vegetables included Brassica juncea var. foliosa Bailey (B. Bailey), Brassica campestris L. var. communis Tsen et Lee Suzhou Qing (B. Lee) and Brassica campestris L. ssp. pekinensis (Lour.) Olsson Chun Dawang (B. Olsson). Two levels of CO2 and four DDT treatment levels were set up. Results showed 5 mg kg-1 DDT significantly reduced the shoot biomass of B. Bailey when compared to 0 mg kg-1 DDT treatment under ambient CO2 condition. Elevated CO2 concentration stimulated the growth of B. Bailey and B. Lee, increased the DDT uptake in the shoots of both vegetables and the values of some photosynthesis indices, and triggered the activity of peroxidase and catalase in the shoots when compared to the related ambient CO2 treatment. Elevated CO2 concentration increased the values of hazard indexes for non-carcinogenic and cancer risks of all vegetables when compared to the individual ambient CO2 treatment (each of vegetable has an ambient CO2 treatment), especially for B. Bailey (increase amplitude of 123.81%-127.78% at 5 mg kg-1 DDT). Long-term ingestion with these DDT-polluted vegetables might result in an elevated carcinogenic risk and elevated atmospheric CO2 may enhance the non-carcinogenic and carcinogenic risks.


Asunto(s)
Brassica/toxicidad , Dióxido de Carbono , Exposición a Riesgos Ambientales/efectos adversos , Residuos de Plaguicidas/toxicidad , Hojas de la Planta/toxicidad , Verduras/toxicidad , Dióxido de Carbono/efectos adversos , Dióxido de Carbono/metabolismo , DDT/efectos adversos , Contaminación Ambiental/efectos adversos , Contaminación de Alimentos , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Medición de Riesgo
8.
Shanghai Kou Qiang Yi Xue ; 28(6): 610-615, 2019 Dec.
Artículo en Chino | MEDLINE | ID: mdl-32346705

RESUMEN

PURPOSE: To investigate the mechanism of endothelial progenitor cells(EPCs) bone remodeling during orthodontic tooth movement. METHODS: Experimental tooth movement model was established. EPCs were isolated, cultured, and labeled with 10 µmol/L Brdu and injected into rats through tail vein to observe the distribution in periodontal tissue. VEGF was added to EPCs culture medium, cell proliferation ability was measured by MTT assay, cell adhesion was observed under microscope. Transwell assay was used to observe cell migration ability, and VEGF immunohistochemical staining sections of model rats at different time points were made. The expression of VEGF in periodontal tissues at different time points was defected. All data were imputed into SPSS 20.0 software package for statistical analysis. RESULTS: A rat model of tooth movement was successfully established. EPCs were isolated from cardiac blood. Some spindle-shaped EPCs were observed under microscope and injected into model rats using Brdu-labeled EPCs. With the increase of time, the intensity of fluorescence gradually increased. In the 3d specimen, the fluorescence intensity reached the strongest. The gap between the first and second molars in the experimental group was lower than that in the control group at each time point, with significant difference(P<0.05). The results of VEGF immunohistochemical staining showed that both the tension side and the pressure side of the experimental group were significantly higher than the control group(P<0.05). The expression of VEGF in both osteoblasts and osteoclasts reached a maximum at 14 days. EPCs proliferation and adhesion experiments demonstrated that VEGF promoted proliferation of EPCs and enhanced their adhesion. Transwell experiments showed that VEGF promoted chemotaxis of EPCs.VEGF regulated the biological effects of EPCs. CONCLUSIONS: EPCs can be accumulated in periodontal tissues and participate in periodontal bone remodeling. After EPCs chemotizing to periodontal tissues, they participate in the remodeling of periodontal tissues through mutual regulation of VEGF and other factors, and promote periodontal tissue repair and bone remodeling.


Asunto(s)
Células Progenitoras Endoteliales , Técnicas de Movimiento Dental , Animales , Osteoclastos , Ligamento Periodontal , Ratas , Factor A de Crecimiento Endotelial Vascular
9.
Oncotarget ; 7(25): 38004-38009, 2016 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-27191742

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy. The molecular pathogenesis of ccRCC remains unclear and biomarkers for daily practice were still limited. We performed an integrative analysis of two public ccRCC microarray datasets, E-GEOD-22541 and E-MTAB-1050, The candidate differential expression genes (DEG) were then confirmed in the E-GEOD-53757 dataset. In addition, an independent cohort of 50 ccRCC and 36 non-tumor kidney tissues were analyzed to examine the selected DGEs by qRT-PCR. We identified and validated two DEGs, namely GFOD1 and peejar, which were significantly up-regulated in ccRCC compared with normal renal tissues (p < 0.001). Moreover, the expression of these two genes are related to histological grade and stage and decrease of their expression correlated with disease progression (p < 0.05). Furthermore, we found the expression of peejar was positively correlated with the expression of GFOD1 in ccRCC tissue, with Pearson correlation coefficiency reaching 0.939 (p < 0.001). GFOD1 and peejar were novel genes correlated with ccRCC disease progression and patients' poor prognosis.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Conjuntos de Datos como Asunto , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Estadificación de Neoplasias , Pronóstico
10.
Artículo en Inglés | MEDLINE | ID: mdl-26360502

RESUMEN

Renal angiomyolipoma may sometimes require surgical intervention. In this paper, we present a case of renal angiomyolipoma which infiltrated the sinus and extended into the inferior vena cava. He was successfully treated with a combined approach of laparoscopic radical nephrectomy, extracorporeal workbench tumor resection, and autotransplantation. Three months postoperatively, no evidence of tumor recurrence or presence of thrombus in the inferior vena cava was noted. Our experience represents the successful application of a combined nephron-sparing approach in the management of angiomyolipoma with extension into a major blood vessel.


Asunto(s)
Angiomiolipoma/patología , Angiomiolipoma/cirugía , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Vena Cava Inferior/patología , Adulto , Circulación Extracorporea , Humanos , Laparoscopía/métodos , Masculino , Nefrectomía/métodos , Trasplante Autólogo
11.
World J Surg Oncol ; 13: 159, 2015 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-25897659

RESUMEN

BACKGROUND: The aim of this study was to investigate the minimally invasive cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) approach in the management of renal cell carcinoma (RCC) with level III or IV inferior vena cava (IVC) thrombus and evaluate the survival outcomes. METHODS: We performed a retrospective analysis on 32 RCC patients with IVC thrombus that underwent nephrectomy and thrombectomy via the minimally invasive CPB/DHCA approach between January 2007 and December 2013. Perioperative variables (for example, operative time, CPB duration, and circulatory arrest duration), estimated blood loss, hospital stay, perioperative complications, and survival data were recorded and analyzed. RESULTS: Thirty-two patients (median age: 56 years) were treated surgically using the CPB and DHCA approach for RCC with a level III (n=25) or level IV (n=7) tumor thrombus. The median operation time was 360 min (interquartile range (IQR): 300 to 435 min) with median CPB and DHCA durations of 149 min and 23 min, respectively. The median estimated blood loss was 2,500 ml. Four complications were observed but no deaths occurred perioperatively. The median follow-up was 25 months (range: 4 to 64 months). The mean overall survival (OS) was 28.2±4.6 months while the disease-free survival (DFS) was 19.5±11.6 months. In patients with M0 disease, ten patients developed metastases and were treated with sorafenib as an adjuvant therapy. The mean OS and DFS of this subgroup were 25.4±12.8 months and 16.0±14.2 months, respectively. CONCLUSIONS: Radical nephrectomy and thrombectomy using CPB and DHCA to treat RCC is a relatively safe approach associated with low morbidity and mortality. This minimally invasive procedure may help minimize surgical trauma and improve perioperative outcomes.


Asunto(s)
Carcinoma Papilar/cirugía , Carcinoma de Células Renales/cirugía , Puente Cardiopulmonar/métodos , Paro Circulatorio Inducido por Hipotermia Profunda/métodos , Neoplasias Renales/cirugía , Trombosis/cirugía , Vena Cava Inferior/cirugía , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nefrectomía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trombectomía , Trombosis/mortalidad , Trombosis/patología , Vena Cava Inferior/patología
12.
Mol Cancer Res ; 12(10): 1365-76, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24874433

RESUMEN

UNLABELLED: Mitochondrial targeted Szeto-Schiller (SS) peptides have recently gained attention for their antioxidative stress ability; however, the functional variations between normal and cancer cells have not been determined. Here, we report the results of such experiments conducted with a newly designed class of peptide called RY4, which is based on SS peptide sequence characteristics. The RY4 peptide exhibits distinct differences in antioxidative stress response between normal and cancer cells when challenged with chemotherapeutics like the glycolytic inhibitor dichloroacetate (DCA), the platinating agent carboplatin, and the DNA damage inducer doxorubicin. Interestingly, only normal human cells were protected by the RY4 peptide and catalase (CAT) activity was significantly enhanced in normal but not tumor cells when incubated with RY4. Pull-down, coimmunoprecipitation, and LC/MS-MS proteomic analysis demonstrated that RY4 and catalase are capable of forming protein complexes. Finally, in vivo efficacy was evaluated by intraperitoneal administration of RY4 into a lung cancer xenograft model, which revealed significant myocardiocyte protection from doxorubicin-induced cardiotoxicity without diminishing doxorubicin's tumoricidal effects. Taken together, RY4 offers selective protection to normal cells from chemotherapy-induced toxicity by enhancing the activity of cellular antioxidant enzymes. IMPLICATIONS: RY4 peptides selectively reduce chemotherapeutic-induced oxidative stress and represent a new class of chemoprotective agents with clinical potential.


Asunto(s)
Antineoplásicos/farmacología , Citoprotección/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Péptidos/farmacología , Péptidos/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Antioxidantes/farmacología , Carboplatino/farmacología , Catalasa/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ácido Dicloroacético/farmacología , Doxorrubicina/farmacología , Humanos , Ratones Desnudos , Miocardio/patología , Neoplasias/patología , Estrés Oxidativo/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteómica , Ratas , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Diagn Pathol ; 8: 206, 2013 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-24330589

RESUMEN

BACKGROUND: Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited. MATERIAL AND METHOD: In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K. RESULTS: A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis. CONCLUSIONS: The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Neoplasias Renales/patología , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/clasificación , Adenocarcinoma Mucinoso/cirugía , Adulto , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma de Células Renales/patología , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/química , Neoplasias Renales/clasificación , Neoplasias Renales/cirugía , Laparoscopía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nefrectomía/métodos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral
14.
Toxicology ; 312: 108-14, 2013 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-23973255

RESUMEN

Benzene is a common occupational hazard as well as a widespread pollutant. Its metabolites play important roles in its toxicity to the hematopoietic system, but little is known about how benzene metabolites affect erythropoiesis. Our previous study demonstrated that benzene metabolites, including phenol and hydroquinone, inhibited hemin-induced erythroid differentiation of K562 cells. In present study, to elucidate the role of DNA methylation in benzene metabolites-induced inhibition on erythroid differentiation, it was investigated whether DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), was able to prevent benzene metabolites inhibiting hemin-induced erythroid differentiation in K562 cells, and the methylation levels of erythroid-specific genes in benzene metabolites-treated K562 cells were analyzed by Quantitative MassARRAY methylation analysis platform. It was found that treatment of K562 cells with 5-aza-CdR completely prevented phenol and hydroquinone inhibiting hemin-induced hemoglobin synthesis and hemin-induced expression of erythroid specific genes, including α- and ß-globin, erythroid porphobilinogen deaminase and GATA binding protein 1 (GATA-1). Consistently, the exposure to benzene metabolites caused an increase in DNA methylation levels at a few CpG sites in some erythroid specific genes, including α-globin gene and α-cluster HS40 element, ß-globin gene and HS core sequence in LCR of ß-globin gene cluster, erythroid porphobilinogen deaminase gene, and GATA-1 gene. These results indicated that DNA methylation played a role in benzene metabolites inhibiting hemin-induced erythroid differentiation of K562 cells via down-regulating transcription of some erythroid related genes.


Asunto(s)
Metilación de ADN , Células Eritroides/efectos de los fármacos , Hidroquinonas/toxicidad , Fenol/toxicidad , Azacitidina/farmacología , Diferenciación Celular/efectos de los fármacos , Islas de CpG , Eritropoyesis/efectos de los fármacos , Factor de Transcripción GATA1/genética , Humanos , Hidroximetilbilano Sintasa/genética , Células K562 , Globinas beta/genética , gamma-Globinas/genética
15.
Int J Mol Med ; 32(2): 347-54, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23695304

RESUMEN

Nerve growth factor (NGF) is a polypeptide growth factor with specific trophic function in nerve cells and was initially investigated for its role as a key player in the regulation of peripheral innervations. The aim of this study was to examine the NGF-induced transdifferentiation of adrenal medullary cells, and to screen the major candidate differentially expressed proteins involved in the transdifferentiation. NGF was used to treat primary cultures of neonatal calf adrenal medullary cells and the effects of transdifferentiation were determined in association with cellular morphology, ultrastructure and changes in endocrine function. Differentially expressed proteins were screened and identified through two-dimensional gel electrophoresis and mass spectrometry. The protein spots showing differential expression were verified by western blot analysis. We observed neurite outgrowth in the adrenal medullary cells treated with NGF under a phase contrast microscope. Ultrastructure analysis revealed that there were rich drumstick-like and villiform processes on the cell membranes and vesicles were formed near the cell membranes. The cytoplasm was rich in mitochondria and the secretion of epinephrine was decreased. Two-dimensional gel electrophoresis revealed that among the differentially expressed proteins, 48 protein spots showed an upregulated expression and 37 protein spots showed a downregulated expression, and no 'all-or-none' spots with significant differences in expression were found. Fourteen protein spots with an upregulated expression and 6 with a downregulated expression were randomly selected for identification by mass spectrometry. Western blot analysis revealed that ras homologus oncogene (Rho) GDP dissociation inhibitor α (RhoGDIα) protein expression was significantly downregulated and peripherin protein expression was significantly upregulated. In brief, our data demonstrate that NGF can induce the differentiation of adrenal medullary cells into neurons, and that RhoGDIα and peripherin may play important roles in this process.


Asunto(s)
Médula Suprarrenal/citología , Médula Suprarrenal/metabolismo , Transdiferenciación Celular/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Proteómica , Animales , Animales Recién Nacidos , Bovinos , Epinefrina/metabolismo , Proteómica/métodos , Reproducibilidad de los Resultados , Inhibidor alfa de Disociación del Nucleótido Guanina rho/metabolismo
16.
Med Oncol ; 30(1): 346, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23263830

RESUMEN

Forkhead box protein M1 (FoxM1) is crucial in the regulation of various biological processes, including cell proliferation, organogenesis, and angiogenesis. Overexpression of FoxM1 is associated with carcinogenesis. In this study, immunohistochemistry was carried out to examine FoxM1 expression in clear cell renal cell carcinoma (ccRCC), and these data were examined for correlation with clinicopathological parameters and prognosis. FoxM1 protein had high expression in 37 of 87 cases of ccRCC (42.5 %), which was significantly higher than in normal tissues, and FoxM1 overexpression was significantly associated with tumor stage (P = 0.005) and recurrence (P = 0.027). The Kaplan-Meier survival analysis demonstrated that FoxM1 expression was significantly associated with shorter recurrence-free survival and overall survival (P = 0.007 and P = 0.008, respectively). Multivariate analysis further demonstrated that FoxM1 was an independent prognostic factor for patients with ccRCC. So FoxM1 might be a potential molecular marker to predict the prognosis of patients with ccRCC.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/metabolismo , Factores de Transcripción Forkhead/biosíntesis , Neoplasias Renales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Femenino , Proteína Forkhead Box M1 , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Adulto Joven
17.
Toxicol Appl Pharmacol ; 265(1): 43-50, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23022512

RESUMEN

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, ß-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, ß-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes.


Asunto(s)
Catecoles/farmacología , Diferenciación Celular/efectos de los fármacos , Metilación de ADN , Células Eritroides/efectos de los fármacos , Diferenciación Celular/genética , Supervivencia Celular/efectos de los fármacos , Islas de CpG/efectos de los fármacos , Hemina/farmacología , Hemoglobinas/biosíntesis , Hemoglobinas/metabolismo , Humanos , Células K562 , Familia de Multigenes , Reacción en Cadena de la Polimerasa , Regulación hacia Arriba/efectos de los fármacos
18.
Toxicol Lett ; 203(3): 190-9, 2011 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-21414390

RESUMEN

Benzene is a common occupational hazard and a ubiquitous environmental pollutant. Benzene exposure at the levels even below 1ppm still showed hematotoxicity. It is widely accepted that the metabolites of benzene play important roles in the benzene toxicity to the hematopoietic system, but little is known about the effects of benzene metabolites on erythropoiesis. In present study, erythroid progenitor-like K562 cells were used to determine the effects of phenolic metabolites of benzene, including phenol, hydroquinone and 1,2,4-benzenetriol, on the erythroid differentiation. After the treatment with these benzene metabolites at the concentrations with no obvious cytotoxicity, the hemin-induced hemoglobin synthesis in K562 cells decreased in a concentration- and time-dependent manner, and the expression of CD71 and GPA protein on the surface of K562 cells was also inhibited. The reverse transcription-PCR was used to determine the mRNA level of the erythroid related genes in the K562 cells that were treated with benzene metabolites. The hemin-induced expression of globin genes, including α-, ß- and γ-globin genes, and the gene encoding the heme synthesis enzyme porphobilinogen deaminase was inhibited by benzene metabolites. When the K562 cells were pretreated with benzene metabolites, the hemin-induced expression of two transcription factor genes GATA-1 and NF-E2 was distinctly reduced, and the pre-treatment with benzene metabolites promoted the decrease of the mRNA level of transcription factor gene GATA-2 by hemin. These results indicated that benzene metabolites inhibited the hemin-induced erythroid differentiation through affecting the transcription of the erythroid related genes.


Asunto(s)
Benceno/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Precursoras Eritroides/efectos de los fármacos , Hidroquinonas/toxicidad , Fenol/toxicidad , Antígenos CD/análisis , Células Precursoras Eritroides/citología , Factor de Transcripción GATA1/genética , Factor de Transcripción GATA2/genética , Glicoforinas/análisis , Hemina/farmacología , Hemoglobinas/biosíntesis , Humanos , Hidroquinonas/química , Células K562 , Fenol/química , Receptores de Transferrina/análisis
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 39(3): 461-3, 2008 May.
Artículo en Chino | MEDLINE | ID: mdl-18575342

RESUMEN

OBJECTIVE: To study the early indicators for renal damages in mercury workers and the clinical significance. METHODS: Eighty-five mercury workers were divided into 2 experimental groups: the normal & subject-under-surveillance group and the mercury-poisoning group. Sixty-five healthy adults with no mercury exposure history were assigned as the control group. Any subjects with history of renal diseases or concurrent renal diseases were excluded. The results from physical examinations and measurements of HgU, B-Cr, U-Cr, BUN, N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin (beta2-MG), urinary alpha1-microglobulin (alpha1-MG), and retinol-binding protein (RBP) in all the groups were analyzed. RESULTS: The levels of HgU, NAG, alpha1-MG, beta2-MG, and RBP were significantly higher in the experimental groups than in the control group. The levels of NAG, beta2-MG and RBP were significantly higher in the nomal & subject-under-surveillance group than in the control group. However, there was no statistically significant difference between the levels of B-Cr and BUN in the experimental groups and those of the control group. CONCLUSIONS: Long-term exposure to mercury can cause renal damages. The level of NAG, alpha1-MG, beta2-MG, and RBP can be used as sensitive indicators for detecting early renal damages caused by mercury.


Asunto(s)
Enfermedades Renales/diagnóstico , Intoxicación por Mercurio/diagnóstico , Enfermedades Profesionales/diagnóstico , Exposición Profesional/análisis , Acetilglucosaminidasa/orina , Adulto , Anciano , Diagnóstico Precoz , Femenino , Humanos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/orina , Masculino , Tamizaje Masivo , Intoxicación por Mercurio/orina , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/orina , Adulto Joven , Microglobulina beta-2/orina
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