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1.
Ecotoxicol Environ Saf ; 233: 113342, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35228028

RESUMEN

The objective of this study was to investigate the effects of co-exposure of iron and microplastics (MPs) on the cognitive function of aged humans and animals. It was already known that individual iron or MPs exposure can initiate potential neurotoxicity. However, the combined effect of MPs and iron remained to be elucidated. In this study, the toxicity of iron, MPs, co-treatment of MPs & iron, and the underlying mechanisms were evaluated in vivo. Our findings suggest that 5 µm MPs could enter the aging mice brain and accumulate in cortex and hippocampus. In addition, MPs and iron have a good binding ability, therefore, co-exposure of MPs & iron cause significant iron overload and cognitive deficits as compared to control and individual treatments of iron and MPs. Moreover, the lipid peroxidation and inflammation, which are involved in ferroptosis, get significantly elevated by co-exposure of iron and MPs. Taken together, our results provide compelling evidence that co-exposure of iron and MPs could aggravate the cognitive impairment via disturbing brain iron homeostasis and inducing ferroptosis in cognitive-related brain areas, what's more, the results warn that MPs may act as vectors of pollutants (mostly heavy metals) increasing the health burden on body.


Asunto(s)
Disfunción Cognitiva , Ferroptosis , Contaminantes Químicos del Agua , Envejecimiento , Animales , Disfunción Cognitiva/inducido químicamente , Hierro/toxicidad , Ratones , Microplásticos , Plásticos , Poliestirenos/toxicidad , Contaminantes Químicos del Agua/toxicidad
2.
Neurochem Res ; 43(7): 1308-1316, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29868983

RESUMEN

Lead (Pb2+) is a well-known type of neurotoxin and chronic exposure to Pb2+ induces cognition dysfunction. In this work, the potential role of early growth response gene 1 (EGR1) in the linkage of Pb2+ exposure and disrupted in scherophernia-1 (DISC1) activity was investigated. Human neuroblastoma cell line SH-SY5Y was subjected to different concentrations of lead acetate (PbAc) to determine the effect of Pb2+ exposure on the cell viability, apoptosis, and activity of EGR1 and DISC1. Then the expression of EGR1 in SH-SY5Y cells was knocked down with specific siRNA to assess the function of EGR1 in Pb2+ induced activation of DISC1. The interaction between EGR1 and DISC1 was further validated with dual luciferase assay, Supershift electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP)-PCR. Administration of PbAc decreased cell viability and induced apoptosis in SH-SY5Y cells in a dose-dependent manner. Additionally, exposure to PbAc also up-regulated expression of EGR1 and DISC1 at all concentrations. Knockdown of EGR1 blocked the effect of PbAc on SH-SY5Y cells, indicating the central role of EGR1 in the function of Pb2+ on activity of DISC1. Based on the results of dual luciferase assay, Supershift EMSA, and ChIP-PCR, EGR1 mediated the effect of Pb2+ on DISC1 by directly bound to the promoter region of DISC1 gene. The current study elaborated the mechanism involved in the effect of Pb2+ exposure on expression of DISC1 for the first time: EGR1 activated by Pb2+ substitution of zinc triggered the transcription of DISC1 gene by directly binding to its promoter.


Asunto(s)
Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Neuroblastoma/metabolismo , Compuestos Organometálicos/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Proteína 1 de la Respuesta de Crecimiento Precoz/agonistas , Humanos , Factores de Transcripción/metabolismo
3.
Tumour Biol ; 37(4): 4655-63, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26508030

RESUMEN

High-risk human papillomavirus (HPV) infection may play an important role in non-small cell lung carcinoma (NSCLC) development. However, some recent studies have proved that it was not directly associated with lung cancer. The aim of this study was to evaluate the underlying molecular mechanism that HPV16 regulate the expression of GLUT1 and may promote the development of lung cancer. HPV16, HIF-1α, and GLUT1 were detected in pleural effusions of patients with lung cancer (n = 95) and with benign lung disease (n = 55) by immunocytochemistry. Western blotting and qRT-PCR were used to detect the expression chances of HPV16 E6/E7, HIF-1α, and GLUT1 in lung cancer cells. HPV16, HIF-1α, and GLUT1 were significantly more likely to be expressed in the malignant group than in the benign group as detected by immunocytochemistry (ICC), and HIF-1α was significantly correlated with HPV16 or GLUT1 in the malignant group (P < 0.01). Expression changes of E6 and E7 significantly promoted the protein expression of HIF-1α, the expression of both protein and mRNA of GLUT1, but had no effect on the expression of HIF-1α mRNA in lung cancer cells. After inhibition of HIF-1α, it obviously downregulated the expression of both protein and mRNA of GLUT1 in lung cancer cells. E6 and E7 regulated the expression of GLUT1 may be due to the mediation of HIF-1α in lung cancer cells. These results suggest that both E6 and E7 play the important role in the regulation of Warburg effect and may be a valuable therapeutic target for HPV-related cancer.


Asunto(s)
Adenocarcinoma/genética , Transportador de Glucosa de Tipo 1/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Neoplasias Pulmonares/genética , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/genética , Proteínas Represoras/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/virología , Adulto , Anciano , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Transportador de Glucosa de Tipo 1/metabolismo , Papillomavirus Humano 16/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/virología , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Proteínas Represoras/metabolismo , Activación Transcripcional , Regulación hacia Arriba
4.
BMC Anesthesiol ; 15: 53, 2015 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-25895497

RESUMEN

BACKGROUND: Bleeding during functional endoscopic sinus surgery is a challenge for the quality of the surgical field for surgeons. This study aimed to evaluate the effect of desmopressin premedication on blood loss and the quality of the surgical field in endoscopic sinus surgery. METHODS: A total of 90 American Society of Anesthesiologists physical status I-II patients underwent endoscopic sinus surgery for chronic sinusitis. They were randomly allocated to receive either desmopressin 0.3 µg/kg or saline before the operation. Management of anesthesia was achieved with propofol and remifentanil infusions, with moderate, controlled hypotension. Blood loss and quality of the surgical field were assessed after surgery. Effects of desmopressin on anesthetic requirements and hemodynamic variables were analyzed. RESULTS: Blood loss was significantly less in the desmopressin group (mean ± SD, 42 ± 8.7 ml) than in the control group (70 ± 9.2 ml, P < 0.001). Surgeons were more satisfied with the surgical field in the desmopressin group than in the control group (median score, 4 [3-5] vs. 7 [6-9], P < 0.001). Requirements for remifentanil and esmolol were lower in the desmopressin group than in the control group. CONCLUSIONS: Premedication with desmopressin 0.3 µg/kg can effectively reduce bleeding during endoscopic sinus surgery.


Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Desamino Arginina Vasopresina/farmacología , Endoscopía/métodos , Sinusitis/cirugía , Adulto , Desamino Arginina Vasopresina/administración & dosificación , Femenino , Hemostáticos/administración & dosificación , Hemostáticos/farmacología , Humanos , Masculino , Persona de Mediana Edad , Piperidinas/administración & dosificación , Propofol/administración & dosificación , Estudios Prospectivos , Remifentanilo , Método Simple Ciego , Adulto Joven
5.
Eur Arch Otorhinolaryngol ; 271(1): 171-9, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23625387

RESUMEN

Increased expression of aldehyde dehydrogenase 1 (ALDH1) has recently been reported in several cancers. However, whether member A1 of aldehyde dehydrogenase 1 (ALDH1A1) is involved in the formation of nasopharyngeal carcinoma (NPC) remains unknown. To investigate the expression of ALDH1A1 in NPC and its association with the tumorigenesis of NPC, we examined the expression of ALDH1A1 in NPC specimens using immunohistochemistry (IHC), quantitative RT-PCR (qRT-PCR) and Western blot. Moreover, we sorted ALDH1A1(high) cells from NPC cell line CNE-2 by flow cytometry and examined the expression of primitive embryonic stem cell markers OCT4, SOX2 and Nanog. Finally, we investigated the capacities of growth, proliferation, colony- formation and tumorigenesis of ALDH1A1(high) cells in vitro and in vivo. We found ALDH1A1 was significantly increased in human NPC samples via IHC, qRT-PCR and Western blot (p < 0.05). ALDH1A1(high) cells sorted from NPC cell line CNE-2 by flow cytometry had higher expression of primitive embryonic stem cell markers OCT4, SOX2 and Nanog, and showed enhanced capacities of growth, proliferation, colony formation and tumorigenesis in vitro and in vivo when compared with ALDH1A1(low) cells (p < 0.05). Our findings indicated that increased expression of ALDH1A1 in NPC was associated with enhanced invasiveness.


Asunto(s)
Aldehído Deshidrogenasa/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Familia de Aldehído Deshidrogenasa 1 , Animales , Pruebas de Carcinogenicidad , Proliferación Celular , Citometría de Flujo , Inmunohistoquímica , Ratones , Ratones Desnudos , Invasividad Neoplásica , Retinal-Deshidrogenasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
6.
Acta Pharmacol Sin ; 34(10): 1317-24, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23933652

RESUMEN

AIM: To investigate the effects of the PPAR-γ agonist rosiglitazone on acute lung injury induced by the herbicide paraquat (PQ) and the underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were injected with PQ (20 mg/kg, ip). Rosiglitazone (3 or 10 mg/kg, ip) was administered 1 h before PQ exposure. Peripheral blood was collected at 4, 8, 24 and 72 h after PQ exposure for measuring the levels of MDA, TNF-α and IL-1ß, and the SOD activity. Lung tissues were collected at 72 h after PQ exposure to determine the wet-to-dry (W/D) ratios and lung injury scores, as well as the protein levels of NF-κBp65, PPAR-γ, Nrf2, IκBα and pIκBα. RESULTS: At 72 h after PQ exposure, the untreated rats showed a 100% cumulative mortality, whereas no death was observed in rosiglitazone-pretreated rats. Moreover, rosiglitazone pretreatment dose-dependently attenuated PQ-induced lung edema and lung histopathological changes. The pretreatment significantly reduced the levels of TNF-α, IL-1ß and MDA, increased SOD activity in the peripheral blood of PQ-treated rats. The pretreatment also efficiently activated PPAR-γ, induced Nrf2 expression and inhibited NF-κB activation in the lung tissues of PQ-treated rats. Furthermore, the pretreatment dose-dependently inhibited IκB-α degradation and phosphorylation, thus inhibiting NF-κB activation. CONCLUSION: Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-γ, inducing Nrf2 expression and inhibiting NF-κB activation.


Asunto(s)
Lesión Pulmonar Aguda/prevención & control , PPAR gamma/agonistas , Paraquat/toxicidad , Tiazolidinedionas/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/fisiopatología , Animales , Relación Dosis-Respuesta a Droga , Herbicidas/toxicidad , Interleucina-1beta/sangre , Masculino , Malondialdehído/sangre , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/metabolismo , Edema Pulmonar/fisiopatología , Edema Pulmonar/prevención & control , Ratas , Ratas Sprague-Dawley , Rosiglitazona , Superóxido Dismutasa/metabolismo , Tiazolidinedionas/administración & dosificación , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangre
7.
iScience ; 26(10): 107463, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37720094

RESUMEN

Nasopharyngeal carcinoma (NPC) is known for high curability during early stage of the disease, and early diagnosis relies on nasopharyngeal endoscopy and subsequent pathological biopsy. To enhance the early diagnosis rate by aiding physicians in the real-time identification of NPC and directing biopsy site selection during endoscopy, we assembled a dataset comprising 2,429 nasopharyngeal endoscopy video frames from 690 patients across three medical centers. With these data, we developed a deep learning-based NPC detection model using the you only look once (YOLO) network. Our model demonstrated high performance, with precision, recall, mean average precision, and F1-score values of 0.977, 0.943, 0.977, and 0.960, respectively, for internal test set and 0.825, 0.743, 0.814, and 0.780 for external test set at 0.5 intersection over union. Remarkably, our model demonstrated a high inference speed (52.9 FPS), surpassing the average frame rate (25.0 FPS) of endoscopy videos, thus making real-time detection in endoscopy feasible.

8.
Bioact Mater ; 6(9): 2927-2945, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33732964

RESUMEN

Sterilization is the process of killing all microorganisms, while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores. Biomaterials involved in cell experiments, animal experiments, and clinical applications need to be in the aseptic state, but their physical and chemical properties as well as biological activities can be affected by sterilization or disinfection. Decellularized matrix (dECM) is the low immunogenicity material obtained by removing cells from tissues, which retains many inherent components in tissues such as proteins and proteoglycans. But there are few studies concerning the effects of sterilization or disinfection on dECM, and the systematic introduction of sterilization or disinfection for dECM is even less. Therefore, this review systematically introduces and analyzes the mechanism, advantages, disadvantages, and applications of various sterilization and disinfection methods, discusses the factors influencing the selection of sterilization and disinfection methods, summarizes the sterilization and disinfection methods for various common dECM, and finally proposes a graphical route for selecting an appropriate sterilization or disinfection method for dECM and a technical route for validating the selected method, so as to provide the reference and basis for choosing more appropriate sterilization or disinfection methods of various dECM.

9.
Acta Biomater ; 134: 160-176, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34303866

RESUMEN

Adhesion often occurs after tendon injury, and results in sliding disorder and movement limitation with no ideal solution for it in clinic. In this study, an anti-adhesion membrane, i.e., decellularized tendon matrix (DTM) for tendon is successfully prepared by an optimized tendon decellularization method from homologous extracellular matrix. Microsection technology has been used to optimize the method of decellularization in order to better preserve the bioactive components in tissues and reduce the chemical reagent residues on the premise of effective decellularization with relatively shorter time and less reagents for decellularization. The physic-chemical properties and biological functions of DTM are evaluated, and high-throughput and high-precision tandem mass tags (TMT) labeling proteomics technology is used to analyze protein components of DTM, which may provide the scientific support for application of the innovative product. In vitro biosafety tests show that DTM not only is non-toxic but also promote cell proliferation. Subcutaneous implantation test confirms that DTM is completely degraded after 12 weeks and there is no obvious inflammatory reaction. The results of Achilles tendon repair in rabbits show that DTM can not only prevent tendon adhesion but also improve the quality of tendon repair, which demonstrates its tremendous application potential. STATEMENT OF SIGNIFICANCE: There is no ideal solution for adhesion after tendon injury. In this study, a dense tendon anti-adhesion membrane (DTM) was successfully prepared from homologous extracellular matrix (ECM). This DTM could effectively retain bioactive ingredients, and prevent adhesion as well as improve the quality of tendon repair in vivo. An optimized decellularization method was used which could effectively decellularize tendon in a short time, better preserve bioactive components, and reduce reagent residues. For the first time, high-throughput and high-precision tandem mass tags (TMT) labeling proteomics technology was used to qualitatively and quantitatively analyze the protein composition of fresh tendon, acellular tendon and DTM, which provided not only scientific support for the application of DTM, but also comprehensive and accurate data support for related research of bovine tendons and decellularization.


Asunto(s)
Traumatismos de los Tendones , Andamios del Tejido , Animales , Bovinos , Proliferación Celular , Matriz Extracelular , Conejos , Tendones , Ingeniería de Tejidos
10.
Artículo en Inglés | MEDLINE | ID: mdl-20332659

RESUMEN

OBJECTIVES: To clarify the utility of a safe and effective endoscopic procedure for closing frontal sinus cerebrospinal fluid (CSF) leaks. METHODS: A retrospective review of all 15 patients seen at our hospital from 2002 to 2008 whose CSF leak originated within the frontal sinus or frontal recess. A transnasal endoscopic or combined transfrontal endoscopic approach was used to repair the CSF leak. RESULTS AND SURGICAL OUTCOMES: Four defects originated in the frontal recess and 11 involved the posterior wall of the frontal sinus. Nine patients were repaired by a direct endoscopic approach and 4 patients were repaired after widening the frontal recess endoscopically. Two patients were repaired using the combined transfrontal and transnasal approach. The leak was stopped in 14 cases (93%) after the first operation. One patient (7%) required a second repair 1 month after initial surgery and has remained well after 27 months. Complications included a frontal lobe abscess and a frontal sinus obstructive mucocele. These 2 patients were successfully treated without further complications. Patient follow-up ranged from 4 to 44 months (mean 30 months). CONCLUSIONS: Most frontal CSF leaks can be successfully closed by an endoscopic surgical approach.


Asunto(s)
Rinorrea de Líquido Cefalorraquídeo/cirugía , Endoscopía/métodos , Seno Frontal/cirugía , Adolescente , Adulto , Rinorrea de Líquido Cefalorraquídeo/diagnóstico por imagen , Niño , Femenino , Seno Frontal/diagnóstico por imagen , Humanos , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
11.
J Immunol Res ; 2018: 7213760, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29967801

RESUMEN

Abdominal aortic aneurysm (AAA), a deadly vascular disease in human, is a chronic degenerative process of the abdominal aorta. In this process, inflammatory responses and immune system work efficiently by inflammatory cell attraction, proinflammatory factor secretion and subsequently MMP upregulation. Previous studies have demonstrated various inflammatory cell types in AAA of human and animals. The majority of cells, such as macrophages, CD4+ T cells, and B cells, play an important role in the diseased aortic wall through phenotypic modulation. Furthermore, immunoglobulins also greatly affect the functions and differentiation of immune cells in AAA. Recent evidence suggests that innate immune system, especially Toll-like receptors, chemokine receptors, and complements are involved in the progression of AAAs. We discussed the innate immune system, inflammatory cells, immunoglobulins, immune-mediated mechanisms, and key cytokines in the pathogenesis of AAA and particularly emphasis on a further trend and application of these interventions. This current understanding may offer new insights into the role of inflammation and immune response in AAA.


Asunto(s)
Aneurisma de la Aorta Abdominal/etiología , Aneurisma de la Aorta Abdominal/metabolismo , Inmunidad , Inmunomodulación , Inflamación/complicaciones , Inflamación/inmunología , Animales , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/terapia , Citocinas/metabolismo , Humanos , Inmunidad Innata , Inmunoglobulinas/inmunología , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Terapia Molecular Dirigida , Receptores Toll-Like/metabolismo
12.
Polymers (Basel) ; 9(9)2017 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-30965706

RESUMEN

Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs) with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment.

13.
Mol Med Rep ; 16(4): 4455-4462, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28791384

RESUMEN

Angiogenesis is an important process in the pathogenesis of aortic aneurysm. The aim of the present study was to investigate the angiogenic balance and the expression of vascular endothelial growth factor (VEGF) in thoracic aortic aneurysm (TAA). A previous study demonstrated that curcumin exerts a marked effect on aortic aneurysm development. Therefore, the present study determined whether curcumin is able to modulate angiogenesis and inflammatory signaling in TAA by collecting human TAA samples and establishing a rat TAA model using periaortic application of CaCl2. TAA rats were treated with curcumin or 1% carboxymethyl cellulose and were sacrificed 4 weeks after the operation. All tissue specimens were analyzed by histological staining, immunohistochemistry and western blotting. Human TAA samples exhibited increased neovascularization and VEGF expression when compared with normal aortic walls. In rat tissues, treatment with curcumin resulted in reduced aneurysm size and restored the wavy structure of the elastic lamellae. In addition, curcumin decreased neovascularization and the expression of VEGF. Immunohistochemical analysis indicated that curcumin significantly inhibited infiltration of cluster of differentiation (CD)3+ and CD68+ cells in TAA. Furthermore, curcumin treatment decreased the expression of vascular cell adhesion molecule­1, intracellular adhesion molecule­1, monocyte chemoattractant protein­1 and tumor necrosis factor­α. Collectively, the results demonstrated that angiogenesis and VEGF expression were increased in the aortic wall in TAA. Treatment with curcumin inhibited TAA development in rats, which was associated with suppression of VEGF expression. In addition, curcumin attenuated inflammatory cell infiltration and suppressed inflammatory factor expression in the periaortic tissue of TAA.


Asunto(s)
Aneurisma de la Aorta Torácica/etiología , Aneurisma de la Aorta Torácica/patología , Curcumina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Sustancias Protectoras/farmacología , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Animales , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/prevención & control , Biomarcadores , Biopsia , Curcumina/uso terapéutico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Sustancias Protectoras/uso terapéutico , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo
14.
PLoS One ; 12(8): e0182775, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28813465

RESUMEN

HPV 16 E6 upregulates hTERT expression in lung cancer cells. However, the underlying molecular mechanism is unclear. In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR. The mRNA expression levels of E6, SP1, and hTERT were significantly increased in the malignant group compared with the benign group (P < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (P < 0.01). Furthermore, the correlation between E6, Sp1, hTERT, and LKB1 was performed, our results indicated that E6, Sp1, and hTERT with positive, but LKB1 with negative correlation (P < 0.01). To investigate the potential relationship between these genes, using double directional genetic manipulation, we showed that overexpression of E6 in H1299 cells down-regulated LKB1 mRNA and protein expression but up-regulated SP1 and hTERT as well as the transcriptional activity of Sp1. In contrast, knockdown of E6 in A549 cells by short-interference RNAs (siRNAs) up-regulated LKB1 expression, but down-regulated SP1 and hTERT expression as well as Sp1 activity. LKB1 loss upregulated both SP1 and hTERT at the protein and mRNA level as well as SP1 activity. To verify that the role of E6 on hTERT was mediated by SP1, siRNA knockdown of SP1 was performed on both H1299 and A549 cell lines. Inhibition of SP1 downregulated hTERT expression. Our results indicate that HPV16 E6 indirectly upregulated the expression of hTERT by inhibition of LBK1 expression and upregulation of Sp1 expression, thus suggesting a HPV-LKB1-SP1-hTERT axis for the tumorigenesis of lung cancer. Our study also provides new evidence to support the critical role of SP1 and LKB1 in the pathogenesis of HPV-related lung cancer, and suggests novel therapeutic targets.


Asunto(s)
Neoplasias Pulmonares/metabolismo , Proteínas Oncogénicas Virales/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Represoras/metabolismo , Telomerasa/metabolismo , Factor de Transcripción AP-1/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Línea Celular Tumoral , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes Reporteros , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Proteínas Represoras/genética , Telomerasa/genética , Factor de Transcripción AP-1/genética
15.
Chin Med J (Engl) ; 130(15): 1816-1823, 2017 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-28748855

RESUMEN

BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. METHODS: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.


Asunto(s)
Cuerpos Extraños/cirugía , Órbita/cirugía , Base del Cráneo/cirugía , Adolescente , Adulto , Preescolar , Endoscopios , Femenino , Humanos , Masculino , Estudios Retrospectivos
16.
Mol Med Rep ; 13(1): 874-80, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26647781

RESUMEN

PIWIs have been shown to be abnormally expressed in a variety of cancers and may be important in the maintenance and invasion of cancer cells. The high expression of PIWIL2 contributed to the resistance effect of cisplatin in colon cancer cells, and the knockout of the PIWIL2 gene reduced the aggressive nature and malignant degree of colon cancer cells. Sodium orthovanadate (SOV) is a vanadium compound, and exhibited antineoplastic activity in certain types of human cancer cells, including lung, kidney and prostate cancer cells. However, its effects in human neuroblastoma (NB) cells have not yet been reported. The objective of this study was to investigate the effect of SOV on the apoptosis of NB cells and to explore how PIWIL2 is involved in the mechanism underlying this effect. In the present study, SH­SY5Y cells were treated with SOV and the optimal concentration was determined for further assays. Cell apoptosis, cell count, viability, the cell cycle, and the expression of PIWIL2 mRNA and protein were then determined. The results showed that SOV could induce cell apoptosis, reduce the percentage of viable cells, induce accumulation of SH­SY5Y cells at the G2/M and S phase of the cell cycle, and inhibit the expression of PIWIL2 and Bcl­2 mRNA and protein. The results suggested that the underlying mechanisms may be, at least in part, due to SOV inhibiting the expression of PIWIL2. These findings demonstrated the effect of SOV and supported its further evaluation as a treatment for human NB.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas Argonautas/antagonistas & inhibidores , Vanadatos/farmacología , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Recuento de Células , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fase G2/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Mitosis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
17.
PLoS One ; 11(2): e0148536, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26918963

RESUMEN

Chronic inflammation and degradation of elastin are the main processes in the development of abdominal aortic aneurysm (AAA). Recent studies show that zinc has an anti-inflammatory effect. Based on these, zinc may render effective therapy for the treatment of the AAA. Currently, we want to investigate the effects of zinc on AAA progression and its related molecular mechanism. Rat AAA models were induced by periaortic application of CaCl2. AAA rats were treated by daily intraperitoneal injection of ZnSO4 or vehicle alone. The aorta segments were collected at 4 weeks after surgery. The primary rat aortic vascular smooth muscle cells (VSMCs) were stimulated with TNF-α alone or with ZnSO4 for 3 weeks. The results showed that zinc supplementation significantly suppressed the CaCl2-induced expansion of the abdominal aortic diameter, as well as a preservation of medial elastin fibers in the aortas. Zinc supplementation also obviously attenuated infiltration of the macrophages and lymphocytes in the aortas. In addition, zinc reduced MMP-2 and MMP-9 production in the aortas. Most importantly, zinc treatment significantly induced A20 expression, along with inhibition of the NF-κB canonical signaling pathway in vitro in VSMCs and in vivo in rat AAA. This study demonstrated, for the first time, that zinc supplementation could prevent the development of rat experimental AAA by induction of A20-mediated inhibition of the NF-κB canonical signaling pathway.


Asunto(s)
Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/prevención & control , Proteínas de Unión al ADN/metabolismo , FN-kappa B/metabolismo , Sulfato de Zinc/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/etiología , Células Cultivadas , Modelos Animales de Enfermedad , Elastina/metabolismo , Quinasa I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Inflamación/metabolismo , Inflamación/prevención & control , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Inhibidor NF-kappaB alfa , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
18.
Materials (Basel) ; 9(10)2016 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-28773924

RESUMEN

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

19.
Am J Rhinol Allergy ; 30(2): 143-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26980396

RESUMEN

BACKGROUND: Functional endoscopic sinus surgery (FESS) is considered to be the standard procedure for chronic rhinosinusitis with nasal polyps (CRSwNP). However, for CRSwNP that accompanies asthma, the results are not satisfying. Extensive endoscopic sinus surgery (EESS) aimed at reducing the inflammatory load has been indicated as a viable option for refractory chronic rhinosinusitis. OBJECTIVE: To evaluate the clinical outcomes and safety of EESS (middle turbinate and superior turbinate resection and total ethmoidectomy) for patients with CRSwNP and with asthma. METHODS: This was a prospective, single-institute cohort study conducted in a tertiary teaching hospital. Patients with CRSwNP and with asthma who were proceeding to surgery were enrolled. There were 23 patients in the EESS group and 24 patients in the FESS group. The preoperative disease severity was evaluated by the visual analog scale (VAS), Lund-Kennedy (L-K) endoscopy score, computed tomography Lund-Mackay score, asthma control test (ACT), and pulmonary function test. Clinical outcomes were comparatively evaluated between the two groups after a 1-year follow-up by using the VAS score, the postoperative endoscopic score (E score), L-K score, ACT score, and pulmonary function test. RESULTS: The disease severity (general VAS score, endoscopic L-K score, computed tomography score, ACT score) showed no significant differences between the two groups before surgery (p > 0.05). One year after surgery, both groups achieved significant improvement in the VAS score and endoscopic L-K score. The EESS group showed better improvement in the olfactory VAS score and E score compared with the FESS group (mean [standard deviation] change of olfactory VAS, 6.00 ± 3.67 versus 3.30 ± 3.44, p = 0.015; mean [standard deviation] E score, 0.31 ± 0.18 versus 0.66 ± 0.26, p < 0.001). No significant differences were found in the change of general nasal symptom VAS score, other individual VAS scores (nasal congestion, discharge, headache and/or facial pain), L-K score, ACT score, and pulmonary function between the two groups (p > 0.05). CONCLUSION: EESS for patients with CRSwNP and with asthma may help to improve the subjective olfaction and endoscopic appearance.


Asunto(s)
Asma/cirugía , Pólipos Nasales/cirugía , Rinitis/cirugía , Rinoplastia , Sinusitis/cirugía , Cornetes Nasales/cirugía , Adulto , Anciano , Asma/complicaciones , Enfermedad Crónica , Estudios de Cohortes , Endoscopía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Estudios Prospectivos , Pruebas de Función Respiratoria , Rinitis/complicaciones , Sinusitis/complicaciones , Olfato , Tomografía Computarizada por Rayos X , Cornetes Nasales/diagnóstico por imagen
20.
Zhongguo Fei Ai Za Zhi ; 8(3): 195-7, 2005 Jun 20.
Artículo en Zh | MEDLINE | ID: mdl-21190618

RESUMEN

BACKGROUND: Immunocytochemistry is valuabale in differentiating malignant fluids from benign ones. However, the diagnostic value of a single tumor marker is limited. The aim of this study is to evaluate the clinical value of capture of cancer cells in pleural fluids of patients with lung cancer by cytochip. METHODS: A new pattern cytochip was developed to immunize hybridization of cells in pleural fluids of patients with 42 lung cancers and with 20 lung benign lesions. Ten antibodies were fixed on the cytochip, they were epithelial specific antigen (ESA), CD44V6, ND-1, T cell (CD3), CD45RO, B cell (CD20), CD79a, Hodgkin's cell (CD15), CD30 and macrophage (CD68). RESULTS: The point of positive hybridization showed round distribution with clear border, and the shape of cell displayed well. The positive numbers of ESA, CD44V6, ND-1 were 35, 30, 38 respectively in pleural fluids of 42 patients with luog cancers; lymphocytes and neutrophils were found on the 1 ESA and 1 ND-1 respectively, and only lymphocytes were found on the 3 CD44V6 in 20 ones with lung benign lesions; the other 7 antibodies did not capture cancer cells except for lymphocytes, neutrophils and macrophages from two pleural fluids. CONCLUSIONS: The cytochip could be an important practical foreground in clinic for diagnosing cancer cells in pleural fluids of patients with lung cancer.

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