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1.
Genes Dev ; 37(19-20): 883-900, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890975

RESUMO

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.


Assuntos
Cromatina , Síndrome de Rett , Feminino , Humanos , Masculino , Camundongos , Animais , Cromatina/metabolismo , Encéfalo/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome de Rett/genética , Mutação , Neurônios/metabolismo
2.
Nature ; 628(8009): 818-825, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38658687

RESUMO

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.


Assuntos
Transtorno Autístico , Síndrome do QT Longo , Oligonucleotídeos Antissenso , Sindactilia , Animais , Feminino , Humanos , Masculino , Camundongos , Processamento Alternativo/efeitos dos fármacos , Processamento Alternativo/genética , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/genética , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/genética , Movimento Celular/efeitos dos fármacos , Dendritos/metabolismo , Éxons/genética , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/genética , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/uso terapêutico , Organoides/efeitos dos fármacos , Organoides/metabolismo , Prosencéfalo/metabolismo , Prosencéfalo/citologia , Sindactilia/tratamento farmacológico , Sindactilia/genética , Interneurônios/citologia , Interneurônios/efeitos dos fármacos
3.
Nature ; 622(7982): 359-366, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37758944

RESUMO

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.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Transtornos do Neurodesenvolvimento , Feminino , Humanos , Recém-Nascido , Gravidez , Movimento Celular/genética , Sistemas CRISPR-Cas/genética , Interneurônios/citologia , Interneurônios/metabolismo , Interneurônios/patologia , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Organoides/citologia , Organoides/embriologia , Organoides/crescimento & desenvolvimento , Organoides/metabolismo , Organoides/patologia , Retículo Endoplasmático/metabolismo , Prosencéfalo/citologia , Prosencéfalo/embriologia , Prosencéfalo/crescimento & desenvolvimento , Prosencéfalo/metabolismo , Prosencéfalo/patologia , Transporte Ativo do Núcleo Celular
4.
BMC Surg ; 23(1): 1, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600246

RESUMO

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.


Assuntos
Apendicite , Laparoscopia , Humanos , Adulto , Apendicite/cirurgia , Técnicas de Sutura/efeitos adversos , Estudos Retrospectivos , Apendicectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Laparoscopia/efeitos adversos , Suturas/efeitos adversos , Tempo de Internação
5.
Acta Biochim Biophys Sin (Shanghai) ; 53(4): 454-462, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33686422

RESUMO

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.


Assuntos
Movimento Celular , Proliferação de Células , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Circular/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Proteínas dos Microfilamentos/genética , Proteínas de Neoplasias/genética , RNA Circular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
6.
Pak J Pharm Sci ; 34(3(Special)): 1227-1231, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602393

RESUMO

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.


Assuntos
Acetilcisteína/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Falência Renal Crônica/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Idoso , China , Creatinina/metabolismo , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transplante Autólogo/métodos , Resultado do Tratamento
7.
Med Sci Monit ; 25: 3014-3025, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31017126

RESUMO

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.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Osteopontina/metabolismo , Idoso , Apoptose/fisiologia , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células-Tronco Neoplásicas/patologia , Osteopontina/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transdução de Sinais , beta Catenina/metabolismo
8.
Phytother Res ; 33(1): 174-186, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30346067

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Enterovirus Humano D/patogenicidade , Infecções Respiratórias/tratamento farmacológico , Humanos
9.
Dig Dis Sci ; 62(11): 3021-3028, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28258379

RESUMO

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.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Biologia Computacional , Simulação por Computador , Bases de Dados Genéticas , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Tetraspanina 24/genética , Tetraspanina 24/metabolismo , Transfecção
10.
Med Sci Monit ; 23: 1385-1393, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28321112

RESUMO

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.


Assuntos
Antígenos de Superfície da Hepatite B/biossíntese , Antígenos de Superfície da Hepatite B/fisiologia , Antígenos E da Hepatite B/fisiologia , Adulto , Biomarcadores/sangue , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatócitos/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Carga Viral
11.
Opt Lett ; 41(10): 2221-4, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-27176967

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-27731799

RESUMO

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.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Astrágalo/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Survivina , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Cardiovasc Pharmacol ; 65(6): 571-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25636074

RESUMO

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.


Assuntos
Envelhecimento/metabolismo , Aorta Torácica/efeitos dos fármacos , Agonistas dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Glicoproteínas de Membrana/agonistas , Artérias Mesentéricas/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Fatores Etários , Envelhecimento/sangue , Animais , Aorta Torácica/metabolismo , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Canais de Cálcio/metabolismo , Glicoproteínas de Membrana/metabolismo , Artérias Mesentéricas/metabolismo , Proteína ORAI1 , Estresse Oxidativo , Ratos Sprague-Dawley , Molécula 1 de Interação Estromal , Superóxido Dismutase/metabolismo , Fatores de Tempo
14.
Hepatogastroenterology ; 62(139): 615-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26897940

RESUMO

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.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , MicroRNAs/genética , Apoptose , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Proteção , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Transfecção , Carga Tumoral
15.
Tumour Biol ; 35(4): 3431-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24338709

RESUMO

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.


Assuntos
Neoplasias do Sistema Digestório/etnologia , Neoplasias do Sistema Digestório/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias do Sistema Digestório/etiologia , Genes p53 , Genótipo , Humanos , Fatores de Risco
16.
Tohoku J Exp Med ; 233(1): 65-72, 2014 05.
Artigo em Inglês | MEDLINE | ID: mdl-24827382

RESUMO

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.


Assuntos
Tumores do Estroma Gastrointestinal/patologia , Trato Gastrointestinal/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
17.
Zhonghua Yi Xue Za Zhi ; 94(4): 293-5, 2014 Jan 28.
Artigo em Zh | MEDLINE | ID: mdl-24731498

RESUMO

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.


Assuntos
Antibioticoprofilaxia , Hérnia Inguinal/cirurgia , Telas Cirúrgicas , Adulto , Antibacterianos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Oncol Lett ; 26(6): 516, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37927411

RESUMO

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

19.
Clin Exp Pharmacol Physiol ; 39(3): 227-32, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22211760

RESUMO

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.


Assuntos
Apoptose/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/fisiologia , Estilbenos/farmacologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Resveratrol , Estilbenos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Células Tumorais Cultivadas
20.
Zhonghua Yi Xue Za Zhi ; 92(48): 3426-8, 2012 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-23327705

RESUMO

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.


Assuntos
Apendicite/diagnóstico , Apendicite/etiologia , Gastrectomia/efeitos adversos , Complicações Pós-Operatórias , Neoplasias Gástricas/cirurgia , Doença Aguda , Idoso , Apendicite/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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