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1.
Genes Dev ; 37(19-20): 883-900, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37890975

RESUMEN

Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance and its DNA binding, and G118E mice manifest RTT-like symptoms seen in the patient, affirming the pathogenicity of this mutation. Using live-cell and single-molecule imaging, we found that G118E mutation alters MeCP2's chromatin interaction properties in live neurons independently of its effect on protein levels. Here we report the generation and characterization of RTT models of a male hypomorphic variant and reveal new insight into the mechanism by which this pathological mutation affects MeCP2's chromatin dynamics. Our ability to quantify protein dynamics in disease models lays the foundation for harnessing high-resolution single-molecule imaging as the next frontier for developing innovative therapies for RTT and other diseases.


Asunto(s)
Cromatina , Síndrome de Rett , Femenino , Humanos , Masculino , Ratones , Animales , Cromatina/metabolismo , Encéfalo/metabolismo , Proteína 2 de Unión a Metil-CpG/genética , Síndrome de Rett/genética , Mutación , Neuronas/metabolismo
2.
Nature ; 628(8009): 818-825, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38658687

RESUMEN

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2-6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.


Asunto(s)
Trastorno Autístico , Síndrome de QT Prolongado , Oligonucleótidos Antisentido , Sindactilia , Animales , Femenino , Humanos , Masculino , Ratones , Empalme Alternativo/efectos de los fármacos , Empalme Alternativo/genética , Trastorno Autístico/tratamiento farmacológico , Trastorno Autístico/genética , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo L/genética , Movimiento Celular/efectos de los fármacos , Dendritas/metabolismo , Exones/genética , Síndrome de QT Prolongado/tratamiento farmacológico , Síndrome de QT Prolongado/genética , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Oligonucleótidos Antisentido/farmacología , Oligonucleótidos Antisentido/uso terapéutico , Organoides/efectos de los fármacos , Organoides/metabolismo , Prosencéfalo/metabolismo , Prosencéfalo/citología , Sindactilia/tratamiento farmacológico , Sindactilia/genética , Interneuronas/citología , Interneuronas/efectos de los fármacos
3.
Nature ; 622(7982): 359-366, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37758944

RESUMEN

The assembly of cortical circuits involves the generation and migration of interneurons from the ventral to the dorsal forebrain1-3, which has been challenging to study at inaccessible stages of late gestation and early postnatal human development4. Autism spectrum disorder and other neurodevelopmental disorders (NDDs) have been associated with abnormal cortical interneuron development5, but which of these NDD genes affect interneuron generation and migration, and how they mediate these effects remains unknown. We previously developed a platform to study interneuron development and migration in subpallial organoids and forebrain assembloids6. Here we integrate assembloids with CRISPR screening to investigate the involvement of 425 NDD genes in human interneuron development. The first screen aimed at interneuron generation revealed 13 candidate genes, including CSDE1 and SMAD4. We subsequently conducted an interneuron migration screen in more than 1,000 forebrain assembloids that identified 33 candidate genes, including cytoskeleton-related genes and the endoplasmic reticulum-related gene LNPK. We discovered that, during interneuron migration, the endoplasmic reticulum is displaced along the leading neuronal branch before nuclear translocation. LNPK deletion interfered with this endoplasmic reticulum displacement and resulted in abnormal migration. These results highlight the power of this CRISPR-assembloid platform to systematically map NDD genes onto human development and reveal disease mechanisms.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Trastornos del Neurodesarrollo , Femenino , Humanos , Recién Nacido , Embarazo , Movimiento Celular/genética , Sistemas CRISPR-Cas/genética , Interneuronas/citología , Interneuronas/metabolismo , Interneuronas/patología , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Organoides/citología , Organoides/embriología , Organoides/crecimiento & desarrollo , Organoides/metabolismo , Organoides/patología , Retículo Endoplásmico/metabolismo , Prosencéfalo/citología , Prosencéfalo/embriología , Prosencéfalo/crecimiento & desarrollo , Prosencéfalo/metabolismo , Prosencéfalo/patología , Transporte Activo de Núcleo Celular
4.
BMC Surg ; 23(1): 1, 2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36600246

RESUMEN

OBJECTIVE: To investigate the effect of laparoscopic purse-string sutures in adult complicated appendicitis treatment. METHODS: The data of 568 adult cases of complicated appendicitis treated by laparoscopic appendectomy at the Hefei Second People's Hospital, Anhui Province, China, from September 2018 to September 2021 were analysed retrospectively. The patients were divided into two groups: 295 cases in the laparoscopic purse-string suture treatment group (observation group) and 273 cases in the simple Hem-o-lok® clamp treatment group (control group). The baseline data collected included age, gender, preoperative body temperature, leukocyte count and percentage of neutrophils and the surgery time. The postoperative data collected included antibiotic treatment duration, drainage tube placement time and the incidence of complications. RESULTS: There were no significant differences in the baseline data of the two groups, including age, gender, preoperative body temperature, leukocyte count and neutrophil percentage (all P > 0.05). Compared with the control group, the postoperative hospital length of stay, duration of antibiotic treatment, the recovery time of peripheral white blood cell and neutrophil counts and the incidence of postoperative complications in the observation group were significantly decreased (P < 0.05). CONCLUSION: Purse-string sutures can effectively reduce the incidence of postoperative complications after a laparoscopic appendectomy for adult acute complicated appendicitis. There was faster postoperative recovery when patients' appendiceal stumps were treated with laparoscopic purse-string sutures.


Asunto(s)
Apendicitis , Laparoscopía , Humanos , Adulto , Apendicitis/cirugía , Técnicas de Sutura/efectos adversos , Estudios Retrospectivos , Apendicectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Laparoscopía/efectos adversos , Suturas/efectos adversos , Tiempo de Internación
5.
Acta Biochim Biophys Sin (Shanghai) ; 53(4): 454-462, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33686422

RESUMEN

Circular RNAs (circRNAs) play either oncogenic or tumor suppressive roles in gastric cancer (GC). A previous study demonstrated that circ_002059, a typical circRNA, was downregulated in GC tissues. However, the role and mechanism of circ_002059 in GC development are still unknown. In this study, the levels of circ_002059, miR-182, and metastasis suppressor-1 (MTSS1) were examined by real-time quantitative polymerase chain reaction and western blot analysis. Cell proliferation and migration were evaluated by MTT assay and Transwell migration assay, respectively. The interactions between miR-182 and circ_002059 or MTSS1 were analyzed by dual-luciferase reporter assay. A GC xenograft model was established to validate the role of circ_002059 in GC progression in vivo. Overexpression of circ_002059 significantly inhibited, whereas knockdown of circ_002059 notably facilitated, cell proliferation and migration in GC cells. MTSS1 was found to be a direct target of miR-182 and circ_002059 upregulated MTSS1 expression by competitively sponging miR-182. Transfection with miR-182 mimic and MTSS1 silencing abated the inhibitory effect of circ_002059 on GC progression. Circ_002059 inhibited GC cell xenograft tumor growth by regulating miR-182 and MTSS1 expression. Collectively, Circ_002059 inhibited GC cell proliferation and migration in vitro and xenograft tumor growth in mice, by regulating the miR-182/MTSS1 axis.


Asunto(s)
Movimiento Celular , Proliferación Celular , MicroARNs/metabolismo , Proteínas de Microfilamentos/metabolismo , Proteínas de Neoplasias/metabolismo , ARN Circular/metabolismo , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Humanos , MicroARNs/genética , Proteínas de Microfilamentos/genética , Proteínas de Neoplasias/genética , ARN Circular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología
6.
Pak J Pharm Sci ; 34(3(Special)): 1227-1231, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34602393

RESUMEN

This study designed to evaluate efficacy and safety profile of Mesenchymal stem cells (MSCs) versus Acetyl cysteine (NACys) in the Chinese patients with Chronic renal failure (CRF). The CRF patients having eGFR less than 60ml per minute per 1.73m2 randomly assigned to MSCs (N=100) or NACys (N=100) (1:1) for 8 weeks. MSCs administered as intravenous infusion of marrow-derived autologous MSCs (1 × 106 to 2 × 106/kg) reperfusion, whereas, another group received NACys 600mg orally twice a day for 8 weeks. The efficacy variables include: creatinine; cystatin C; TGF-ß levels; oxidants/reactive oxygen species production induced by TGF-ß; collagen levels (type 1 and 4); urinary albumin/creatinine ratio and Glomerular area. Safety was also assesed. Both the treatments significantly decreased creatinine, cystatin C and reactive oxygen species from baseline, however, reduction in creatinine, cystatin C, and reactive oxygen species level from baseline was significantly higher in patient treated with MSCs (N=100) as compared to NACys (N=100). Moreover, improvement in renal and systemic functional parameters from baseline was significantly higher in patient treated with MSCs as compared to NACys. Overall, MSCs offer significantly greater improvement in renal function as compared to NACys in Chinese CRF patients.


Asunto(s)
Acetilcisteína/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Fallo Renal Crónico/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Anciano , China , Creatinina/metabolismo , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trasplante Autólogo/métodos , Resultado del Tratamiento
7.
Med Sci Monit ; 25: 3014-3025, 2019 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-31017126

RESUMEN

BACKGROUND Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved. MATERIAL AND METHODS Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3ß-ß/catenin pathway was detected by western blot. RESULTS OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3ß-ß/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells. CONCLUSIONS OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3ß-ß/catenin pathway.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Células Madre Neoplásicas/metabolismo , Osteopontina/metabolismo , Anciano , Apoptosis/fisiología , Diferenciación Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Células Madre Neoplásicas/patología , Osteopontina/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Transducción de Señal , beta Catenina/metabolismo
8.
Phytother Res ; 33(1): 174-186, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30346067

RESUMEN

Human enterovirus 68 (EVD68) is a primary causative agent for respiratory illness worldwide. Until now, there has been no available medication for treating EVD68-related diseases. Rheum emodin, artemisinin, astragaloside, pseudolaric acid B, oridonin, and erianin are natural extracts from Chinese herbs that have traditionally been used for the treatment and prevention of epidemic diseases. Our results showed that pseudolaric acid B protected cells from EVD68-induced cytopathic effects and decreased viral production. However, the same effects were not observed with rheum emodin, astragaloside, or artemisinin. Pseudolaric acid B inhibited EVD68 production by manipulating the host cell cycle in G2/M phase. Further, either oridonin or erianin related G2/M arrest also inhibited viral production. Due to inducing G2/M phase arrest, pseudolaric acid B, oridonin, and erianin might be good candidates for inhibiting EVD68 production, and Chinese herbs with natural compounds inducing G2/M arrest should be considered for the treatment of EVD68-related diseases.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Enterovirus Humano D/patogenicidad , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Humanos
9.
Dig Dis Sci ; 62(11): 3021-3028, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28258379

RESUMEN

BACKGROUND: PVT1 was up-regulated in patients with gastric cancer (GC) and might be as a novel biomarker for predicting GC. However, the exact mechanism of PVT1 exerting functions in GC was still poorly understood. Emerging evidence suggests that long noncoding RNAs may act as endogenous microRNA (miRNA) sponges to bind to miRNAs and regulate their function. AIM: This study aimed to determine the function of PVT1 on miR-152 expression in GC cells. METHODS: The levels of PVT1 and miR-152 were determined in GC tissues by quantitative real-time PCR. The expression of miR-152 was detected in GC cells transfected with PVT1 plasmid or siPVT1. Luciferase assay was performed to verify the regulation of miR-152 to CD151 or FGF2 expression and PVT1 to miR-152 expression. The effects of PVT1 on the expression of CD151 and FGF2 were evaluated by Western blot. RESULTS: PVT1 was up-regulated in GC tissues than that in the matched normal tissues, and mRNA level of miR-152 was decreased. MiR-152 was negatively associated with PVT1 expression in GC tissues. Based on the in silico analysis, we found that PVT1 have three binding sequences for miR-152. Moreover, PVT1 might inhibit the expression of miR-152 and increased the expression of CD151 and FGF2 through regulating miR-152. PVT1 was positively associated with CD151 and FGF2 expression in GC tissues. CONCLUSIONS: PVT1 might act as a "sponge" to inhibit miR-152 in gastric cancer cells. PVT1 is a promising molecular target to improve the diagnosis and therapy of GC.


Asunto(s)
MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Sitios de Unión , Línea Celular Tumoral , Biología Computacional , Simulación por Computador , Bases de Datos Genéticas , Femenino , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , ARN Largo no Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Tetraspanina 24/genética , Tetraspanina 24/metabolismo , Transfección
10.
Med Sci Monit ; 23: 1385-1393, 2017 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-28321112

RESUMEN

BACKGROUND The aim of this study was to characterize the expression and secretion of hepatitis B surface-antigen (HBsAg) in the hepatocytes of hepatitis B virus (HBV)-infected patients at different phases of infection; as such, the association of intrahepatic HBsAg expression with virological markers and the histological characteristics were analyzed. MATERIAL AND METHODS 302 chronic HBV infection patients who had not received antiviral therapy were stratified by HBeAg status. The proportion of HBsAg-positive cells was used as an indicator for HBsAg expression level. RESULTS In HBeAg-positive patients, there was a significant correlation between serum HBsAg and serum HBV DNA levels (r=0.569, p<0.001). Intrahepatic HBsAg expression and serum HBsAg level in HBeAg-positive patients were higher than those in HBeAg-negative patients (p=0.002 and p<0.001, respectively). A significant correlation between serum HBsAg level and intrahepatic HBsAg expression was found in HBeAg-negative patients (r=0.377, p<0.001), but not in HBeAg-positive patients (r=0.051, p=0.557). Very interestingly, the correlation between serum HBsAg level and HBsAg expression in hepatocytes gradually increased along with disease progression through the immune-tolerant, immune-clearance, inactive, and recovery phases of HBV infection (r=-0.184, 0.068, 0.492, and 0.575; and p=0,238, 0,722, 0.012, and 0.002, respectively). CONCLUSIONS Different mechanisms may be involved in HBsAg synthesis and secretion in different phases of chronic HBV infection.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/biosíntesis , Antígenos de Superficie de la Hepatitis B/fisiología , Antígenos e de la Hepatitis B/fisiología , Adulto , Biomarcadores/sangre , ADN Viral/sangre , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/sangre , Hepatocitos/patología , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Carga Viral
11.
Opt Lett ; 41(10): 2221-4, 2016 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-27176967

RESUMEN

A photoacoustic cell containing an infrared active gas and equipped with a pair of infrared transmitting windows that alternately views two bodies at different temperatures through a pair of chopping wheels acts as a differential detector of the radiation emitted by the two bodies. A theory for the photoacoustic signal shows that the device acts to monitor the difference in the incidances between the two bodies integrated over the absorptions of the gas in the cell. Experiments are reported showing that the response of the pyrometer depends on the relative temperatures of heated bodies, the absorption coefficient of the gas in the cell, and the modulation frequency of the chopping wheels. The instrument is shown to be a sensitive detector of a null in the integrated incidance of the two bodies.

12.
Pak J Pharm Sci ; 29(5): 1473-1482, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27731799

RESUMEN

We and others have shown that Astragalus extract (AE) regulates various cellular processes including inflammation and apoptosis. It remains elusive whether and how AE modulates apoptosis in gastric cancer cells in vitro and in vivo. The objective of this study is to determine the effects and mechanisms of AE on the proliferation and apoptosis of human gastric cancer SGC-7901 cells and on tumor growth in orthotopic transplantation gastric tumor model in nude mice. Human gastric adenocarcinoma SGC-7901 cells and nude mice implanted with gastric cancer cells were treated with different concentration of AE and 5-fluorouracil as control. Cellular proliferation, apoptosis and tumor growth as well as interleukin (IL)-6/signal transducer and activator of transcription (Stat) 3 signals pathway were determined. We found that AE inhibited proliferation but caused apoptosis in human gastric cancer cells. Furthermore, the tumor growth and volume were reduced by AE administration in nude mice implanted with gastric cancer cells. In addition, treatments with AE decreased the expression of Bcl-2 proteins, whereas the expression of Bax was increased after AE treatment in tumor tissues of nude mice transplanted with human gastric cancer cells. This was associated with AE-mediated reduction of IL-6, phosphorylated Stat3, survivin and vascular endothelial growth factor. Overall, AE enhances apoptosis in gastric cancer cells in vitro and in vivo, which is associated with decreased activation of IL-6/Stat3 signals.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Planta del Astrágalo/química , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Survivin , Carga Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
13.
J Cardiovasc Pharmacol ; 65(6): 571-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25636074

RESUMEN

Ca is a crucial factor in the regulation of smooth muscle contraction. Store-operated Ca entry (SOCE) is one pathway that mediates Ca influx and smooth muscle contraction. Vessel contraction function usually alters with aging to cause severe vascular-related diseases. However, the underlying mechanism is still not fully understood. Here, we assessed intracellular Ca and vessel tension and found that SOCE and SOCE-mediated contraction of vascular smooth muscle cells (VSMCs) was reduced in aorta but increased in mesenteric arteries from aged rats. The results of Western blot and immunofluorescence staining show that the expression levels of Orai1, a store-operated Ca channel, were increased in VSMCs of mesenteric arteries but were reduced in VSMCs of aorta with aging. In conclusion, we demonstrated that the changing pattern of SOCE and SOCE-mediated contraction of VSMCs is completely reversed in mesenteric arteries and aorta with aging, providing a potential therapeutic target for clinical treatment in age-related vascular diseases.


Asunto(s)
Envejecimiento/metabolismo , Aorta Torácica/efectos de los fármacos , Agonistas de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Glicoproteínas de Membrana/agonistas , Arterias Mesentéricas/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Factores de Edad , Envejecimiento/sangre , Animales , Aorta Torácica/metabolismo , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Canales de Calcio/metabolismo , Glicoproteínas de Membrana/metabolismo , Arterias Mesentéricas/metabolismo , Proteína ORAI1 , Estrés Oxidativo , Ratas Sprague-Dawley , Molécula de Interacción Estromal 1 , Superóxido Dismutasa/metabolismo , Factores de Tiempo
14.
Hepatogastroenterology ; 62(139): 615-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26897940

RESUMEN

BACKGROUND/AIMS: Dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-134 has been found in some types of cancer. However, miR-134 expression and its clinical significance in colorectal cancer (CRC) have not been explored. The aim of this study was to explore the effects of miR-134 in CRC tumorigenesis and development. METHODOLOGY: Quantitative RT-PCR was performed to evaluate miR-134 levels in CRC cell lines and 168 pairs of CRC specimens and adjacent noncancerous tissues. The association of miR-134 expression with clinicopathological factors and prognosis was also analyzed. Further, the effects of miR-134 on the biological behavior of CRC cells were investigated. RESULTS: MiR-134 expression was significantly downregulated in CRC cancer tissues and cell lines. Decreased miR-134 expression was significantly associated with large tumor size, positive lymph node metastasis, and advanced clinical stage Low miR-134 expression in CRC was an independent predictor of poor survival. Moreover, over-expression of miR-134 inhibited SW620 cell proliferation, invasion, and migration, and promoted cell apoptosis in vitro. CONCLUSIONS: These findings indicate that miR 134 may act as a tumor suppressor in CRC and would serve as a novel therapeutic agent for miR-based therapy.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , MicroARNs/genética , Apoptosis , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Factores Protectores , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Transfección , Carga Tumoral
15.
Tumour Biol ; 35(4): 3431-8, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24338709

RESUMEN

Published data on the relationship between T309G polymorphism in the murine double minute 2 (MDM2) gene and susceptibility of digestive tract cancers (DTC) are inconclusive. Thus, the aim of this study is to determine whether MDM2 T309G polymorphism is associated with the risk of diverse DTC, including esophagus, stomach, liver, bile duct, pancreas, and colorectum cancers. Relevant studies were identified up to October 1, 2013. Crude odds ratio (OR) and 95% confidence interval (CI) were used as a measure of the strength of the association. The pooled result based on all studies showed that there was a statistically significant link between MDM2 T309G polymorphism and DTC susceptibility (T vs. G: OR = 0.82, 95%CI = 0.76-0.88). When stratified by race, significant associations were observed for all genetic models among Asians (especially in Chinese population), but not among Caucasians. Subgroup analyses according to tumor location indicated that the genetic variant was associated with esophageal (OR = 0.88, 95%CI = 0.81-0.96 for T vs. G), hepatocellular (OR = 0.69, 95%CI = 0.57-0.84 for T vs. G) and pancreatic cancer risk but not associated with cholangiocarcinoma or colorectum cancer susceptibility. Meanwhile, the G allele was also suggested to be associated with increased gastric cancer risk (OR = 0.68, 95%CI = 0.54-0.87 for TT + TG vs. GG for intestinal type of gastric cancer and OR = 0.18, 95%CI = 0.06-0.50 for TT vs. GG for Helicobacter pylori infection positive stomach cancer). Our study indicates that the MDM2 T309G polymorphism may be an ethnicity-dependent risk factor for DTC, especially for the upper gastrointestinal tract malignancies.


Asunto(s)
Neoplasias del Sistema Digestivo/etnología , Neoplasias del Sistema Digestivo/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-mdm2/genética , Neoplasias del Sistema Digestivo/etiología , Genes p53 , Genotipo , Humanos , Factores de Riesgo
16.
Tohoku J Exp Med ; 233(1): 65-72, 2014 05.
Artículo en Inglés | MEDLINE | ID: mdl-24827382

RESUMEN

Gastrointestinal stromal tumors (GISTs) are the most common among gastrointestinal mesenchymal tumors, but its prognosis has not been accurately predicted by the current risk stratification guidelines, National Institutes of Health classification. In this study, we evaluated the predictive factors for GIST prognosis in a retrospective analysis of 332 patients. The data collected included tumor sites, including the esophagus, stomach, duodenum, small intestine, and extragastrointestinal sites; tumor size; microscopic indicators for malignant tumor behavior, such as the number of dividing cells, cell necrosis, atypical morphology, and invasion into the muscular or mucous layer; and previously established immunohistochemical indicators, CD117, CD34, and discovered on GIST-1 (DOG-1). No single occurrence of any microscopic indicators correlated with the prognosis of GIST; however, the total number of microscopic indicators was a significant prognostic factor of GIST (P < 0.001). Regarding the tumor sites, the order of prognostic risk (from the lowest to the highest) was as follows: the esophagus, stomach, duodenum, small intestine, extragastrointestinal sites, and colorectum. The association between tumor sites and prognosis was significant (P < 0.001). On the other hand, the expression of CD117 or CD34 was not associated with the risk of GIST. Importantly, 91% of the patients (302/332) showed the expression of DOG-1, and the lack of DOG-1 expression was associated with poor prognosis (P < 0.05). In conclusion, both tumor sites and total number of microscopic indicators are independent risk factors associated with the prognosis of GIST. The lack of DOG-1 expression may be predictive of malignant outcome.


Asunto(s)
Tumores del Estroma Gastrointestinal/patología , Tracto Gastrointestinal/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Adulto Joven
17.
Zhonghua Yi Xue Za Zhi ; 94(4): 293-5, 2014 Jan 28.
Artículo en Zh | MEDLINE | ID: mdl-24731498

RESUMEN

OBJECTIVE: To explore the safety in inguinal incarcerated hernia repair without use of antibiotics. METHODS: Retrospective statistical analysis was performed for a total 326 patients with inguinal incarcerated hernia repair at our hospital from January 2011 to July 2013. They were divided into 2 groups of non-using (n = 192) and using (n = 134) antibiotics. Statistical analysis of early postoperative infection was performed for two groups. RESULTS: The total incision infection had no statistical difference between two groups (7.29% (14/192) vs 3.73% (5/134), 0.52% (1/192) vs 1.49% (2/134), both P > 0.05). Further comparison of leukocyte count and neutrophil count at Day 3 showed no inter-group statistical difference ((7.9 ± 0.6) ×10(9) vs (7.8 ± 0.7) ×10(9)/L, (4.9 ± 0.5)×10(9) vs (5.0 ± 0.5) ×10(9)/L; U = 1.344, 1.777; P = 0.180, 0.077). CONCLUSION: It is unnecessary to use preventive antibiotics in patients undergoing tension-free repair with incarcerated inguinal hernia without high-risk infection or bowel necrosis.


Asunto(s)
Profilaxis Antibiótica , Hernia Inguinal/cirugía , Mallas Quirúrgicas , Adulto , Antibacterianos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
18.
Oncol Lett ; 26(6): 516, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37927411

RESUMEN

[This corrects the article DOI: 10.3892/ol.2018.9494.].

19.
Clin Exp Pharmacol Physiol ; 39(3): 227-32, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22211760

RESUMEN

The currently available chemotherapeutic regimens against gastric cancer are not very effective, leading to high recurrence and poor survival. Resveratrol is a naturally occurring polyphenol with potent apoptosis-inducing activity. However, the mechanism underlying its actions remains unknown. In the present study, human gastric adenocarcinoma SGC7901 cells were treated with resveratrol (0, 25, 50, 100 and 200 µmol/L) for 48 h, and cellular apoptosis DNA damage were determined. In certain experiments, cells were incubated with superoxide dismutase (100 U/mL), catalase (300 U/mL) or sirtinol (10 µmol/L) to determine the role of reactive oxygen species (ROS) and sirtuin1 in resveratrol-induced cellular apoptosis. Treatment with resveratrol (50-200 µmol/L) for 48 h significantly induced apoptosis and DNA damage in human gastric cancer SGC7901 cells. This was due to the increased generation of ROS following resveratrol treatment because incubation of cells with superoxide dismutase (100 U/mL) or catalase (300 U/mL) attenuated resveratrol-induced cellular apoptosis. Interestingly, treatment with resveratrol (25-200 µmol/L) did not affect the level and activity of sirtuin1, whereas the sirtuin1 inhibitor sirtinol (10 µmol/L) significantly reduced sirtuin1 activity. Furthermore, treatment with sirtinol (10 µmol/L) did not have any effect on apoptosis induced by resveratrol. These data provide evidence that resveratrol induces apoptosis via ROS, but independent of sirtuin1, in the human gastric cancer cell line SGC7901.


Asunto(s)
Apoptosis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/fisiología , Estilbenos/farmacología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Resveratrol , Estilbenos/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Células Tumorales Cultivadas
20.
Zhonghua Yi Xue Za Zhi ; 92(48): 3426-8, 2012 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-23327705

RESUMEN

OBJECTIVE: To explore the clinical characteristic and therapeutic strategies of acute appendicitis after radical gastrectomy for gastric carcinoma. METHODS: The clinical data of 31 patients with acute appendicitis after radical gastrectomy for gastric carcinoma from January 2006 to January 2012 was analyzed retrospectively. The profiles of previous operations, symptoms, physical signs, disease duration, progression time, examination results, peri-operative complications, results of bacterial culture and use of antibiotics were used to evaluate the clinical characteristics and therapeutic strategies. RESULTS: There were 19 males and 12 females with a mean age of (61 ± 4) years. Gastric cancer postoperative acute appendicitis lacked typical symptoms. The presenting symptoms were persistent and progressive severe right lower abdominal pains (n = 31, 100.0%), associated, with fever (n = 27, 87.1%) nausea or vomiting (n = 11, 35.5%), abdominal distension (n = 9, 29.0%), intestinal obstruction (n = 21, 67.7%) and abdominal purulent exudate (n = 31, 100.0%). The average onset time from abdominal pain to peritonitis was (15 ± 4) hours. Perforated appendix occurred in 16 cases (51.6%). Seven patients had no increase of the total number of WBC or percentage of neutrophils (22.6%). Exploratory laparotomy was performed in 17 cases, and the rate of delayed diagnosis was 54.8%. And 31 patients were cured by surgery and anti-infection treatment. There was no intraoperative death. CONCLUSIONS: Because of rapidly spreading abdominal infection, peritonitis occurs early with a high incidence rate. Early diagnosis, early operation and rational use of antibiotics are the most important therapeutic modalities of acute postoperative appendicitis in patients with gastric cancer.


Asunto(s)
Apendicitis/diagnóstico , Apendicitis/etiología , Gastrectomía/efectos adversos , Complicaciones Posoperatorias , Neoplasias Gástricas/cirugía , Enfermedad Aguda , Anciano , Apendicitis/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
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