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2.
Dev Cell ; 59(3): 384-399.e5, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38198890

RESUMO

Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In humans and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acid supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration in mice. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake.


Assuntos
Ácidos Graxos , Lipoilação , Músculo Esquelético , Proteínas Qa-SNARE , Regeneração , Animais , Humanos , Camundongos , Transporte Biológico , Antígenos CD36/metabolismo , Membrana Celular/metabolismo , Ácidos Graxos/metabolismo , Músculo Esquelético/lesões , Músculo Esquelético/fisiologia , Proteínas Qa-SNARE/metabolismo
3.
Acta Pharm Sin B ; 13(10): 4060-4088, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37799384

RESUMO

Protein-protein interactions (PPIs) are fundamental to many biological processes that play an important role in the occurrence and development of a variety of diseases. Targeting the interaction between tumour-related proteins with emerging small molecule drugs has become an attractive approach for treatment of human diseases, especially tumours. Encouragingly, selective PPI-based therapeutic agents have been rapidly advancing over the past decade, providing promising perspectives for novel therapies for patients with cancer. In this review we comprehensively clarify the discovery and development of small molecule modulators of PPIs from multiple aspects, focusing on PPIs in disease, drug design and discovery strategies, structure-activity relationships, inherent dilemmas, and future directions.

4.
BMC Oral Health ; 23(1): 683, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730562

RESUMO

OBJECTIVE: This study aimed to provide evidence for the clinical application of single short implants by establishing an anisotropic, three-dimensional (3D) finite element mandible model and simulating the effect of crown-to-implant ratio (CIR) on biomechanics around short implants with different osseointegration rates. METHODS: Assuming that the bone is transversely isotropic by finite element method, we created four distinct models of implants for the mandibular first molar. Subsequently, axial and oblique forces were applied to the occlusal surface of these models. Ultimately, the Abaqus 2020 software was employed to compute various mechanical parameters, including the maximum von Mises stress, tensile stress, compressive stress, shear stress, displacement, and strains in the peri-implant bone tissue. RESULTS: Upon establishing consistent osseointegration rates, the distribution of stress exhibited similarities across models with varying CIRs when subjected to vertical loads. However, when exposed to inclined loads, the maximum von Mises stress within the cortical bone escalated as the CIR heightened. Among both loading scenarios, notable escalation in the maximum von Mises stress occurred in the model featuring a CIR of 2.5 and an osseointegration rate of 25%. Conversely, other models displayed comparable strength. Notably, stress and strain values uniformly increased with augmented osseointegration across all models. Furthermore, an increase in osseointegration rate correlated with reduced maximum displacement for both cortical bone and implants. CONCLUSIONS: After fixing osseointegration rates, the stress around shorter implants increased as the CIR increased under inclined loads. Thus, the effect of lateral forces should be considered when selecting shorter implants. Moreover, an implant failure risk was present in cases with a CIR ≥ 2.5 and low osseointegration rates. Additionally, the higher the osseointegration rate, the more readily the implant can achieve robust stability.


Assuntos
Implantes Dentários , Osseointegração , Humanos , Dente Molar , Mandíbula , Coroas
5.
J Cell Sci ; 136(15)2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37461827

RESUMO

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidence reveals that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane (PM). Through shRNA screening, we identified ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from the Golgi to the PM. We found that the N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids in cell culture revealed that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our study has thus identified a sorting mechanism for targeting palmitoylated proteins from the Golgi to the PM.


Assuntos
Complexo de Golgi , Proteínas de Membrana , Membrana Celular/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Membrana/metabolismo , Transporte Proteico
6.
Cancer Chemother Pharmacol ; 92(1): 71-81, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37272931

RESUMO

PURPOSE: Tumor-promotive tumor-associated macrophages (TAMs) and the CXCL16/CXCR6 axis have been reported to be correlated with the limited efficacy of chemotherapy in ovarian cancer (OC). However, the role of TAM-secreted CXCL16 and the mechanism by which it affects the cisplatin (DDP) resistance of OC cells remain elusive. METHODS: We induced human THP-1 monocytes to differentiate into macrophages. Next, SKOV3 and TOV-112D cells were co-cultured with the macrophages, followed by incubation with increasing concentrations of DDP. The effects of CXCL16, CXCR6, and WTAP on the DDP resistance of OC cells were investigated using the CCK-8 assay, colony formation assay, flow cytometry, and TUNEL staining. CXCL16 concentrations were determined by ELISA. Quantitative real-time PCR and western blotting were used to examine related markers. RESULTS: Our results showed that after being co-cultured with TAMs, the DDP resistance of OC cells was significantly enhanced and their CXCL16 levels were elevated. Acquired DDP resistance was characterized by an increased IC50 value for DDP, the formation of cell colonies, and decreased levels of cell apoptosis, which were accompanied by reduced levels of caspase-3 and Bax expression, and increased levels of Bcl-2, PARP1, BRCA1, and BRCA2 expression. Either CXCL16 knockdown in TAMs or CXCR6 knockdown in OC cells suppressed the DDP resistance of OC cells that had been co-cultured with TAMs. Knockdown of CXCL16 affected m6A RNA methylation in OC cells, as reflected by decreased YTHDF1/WTAP expression and increased ALKBH5 expression. WTAP overexpression and knockdown promoted and suppressed the DDP resistance of OC cells, respectively. CONCLUSION: Tumor-associated macrophages promote the cisplatin resistance of OC cells by enhancing WTAP-mediated N6-methyladenosine RNA methylation via the CXCL16/CXCR6 axis.


Assuntos
Cisplatino , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Macrófagos Associados a Tumor , Metilação , Neoplasias Ovarianas/tratamento farmacológico , RNA/farmacologia , RNA/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Proliferação de Células , Receptores CXCR6 , Fatores de Processamento de RNA , Proteínas de Ciclo Celular
7.
BMC Oral Health ; 23(1): 220, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-37061667

RESUMO

OBJECTIVE: This experiment aimed to investigate the effects of bone conditions and osseointegration rates on the stress distribution of short implants using finite element analysis and also to provide some reference for the application of short implants from a biomechanical prospect. MATERIALS AND METHODS: Anisotropic jaw bone models with three bone conditions and 4.1 × 6 mm implant models were created, and four osseointegration rates were simulated. Stress and strain for the implants and jaws were calculated during vertical or oblique loading. RESULTS: The cortical bone area around the implant neck was most stressed. The maximum von Mises stress in cortical bone increased with bone deterioration and osseointegration rate, with maximum values of 144.32 MPa and 203.94 MPa for vertical and inclined loading, respectively. The osseointegration rate had the greatest effect on the maximum principal stress in cortical bone of type III bone, with its value increasing by 63.8% at a 100% osseointegration rate versus a 25% osseointegration rate. The maximum and minimum principal stresses under inclined load are 1.3 ~ 1.7 and 1.4 ~ 1.8 times, respectively, those under vertical load. The stress on the jaw bone did not exceed the threshold when the osseointegration rate was ≥ 50% for Type II and 100% for Type III. High strain zones are found in cancellous bone, and the maximum strain increases as the bone condition deteriorate and the rate of osseointegration decreases. CONCLUSIONS: The maximum stress in the jaw bone increases as the bone condition deteriorates and the osseointegration rate increases. Increased osseointegration rate reduces cancellous bone strain and improves implant stability without exceeding the yield strength of the cortical bone. When the bone condition is good, and the osseointegration ratio is relatively high, 6 mm short implants can be used. In clinical practice, incline loading is an unfavorable loading condition, and axial loading should be used as much as possible.


Assuntos
Implantes Dentários , Osseointegração , Humanos , Análise de Elementos Finitos , Arcada Osseodentária , Estresse Mecânico , Análise do Estresse Dentário/métodos , Simulação por Computador , Planejamento de Prótese Dentária
8.
Histol Histopathol ; 38(4): 475-485, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36264049

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are widely involved in cell metabolism, and their abnormal expression is involved in the regulation of ovarian cancer development, metastasis, and recurrence. The current study aimed to explore the potential mechanism and prognostic value of miRNAs related to the targeted regulation of oxidized low-density lipoprotein receptor 1 (OLR1) expression in ovarian cancer. METHODS: A prospective study was conducted including 132 ovarian cancer patients. Patients were followed up for 36 months. The dual-luciferase reporter gene detection was used to verify the targeting relationship between miRNA and OLR1. Cell Counting Kit-8 assay, flow cytometric analysis, transwell migration, and invasion assays were performed to address the malignant biological behaviors of ovarian cancer cells. RESULTS: OLR1 protein and gene expression levels were significantly higher in ovarian cancer tissues and cell lines than in adjacent tissues and normal ovarian epithelial cells. OLR1 depletion facilitated apoptosis and impeded cell proliferation, migration, and invasion in ovarian cancer. Predictive software and dual-luciferase reporter assays showed that miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465 targeted OLR1 expression. Functionally, the introduction of miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465 mimics abrogated the aggressive phenotype in ovarian cancer cells. Lastly, compared with adjacent tissues, the levels of miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465 in cancer tissues were significantly lower (P<0.001). Compared with high miR-106b-5p, high miR-93-5p, high miR-3129-5p, high miR-199b-3p, high miR-4465 group and low OLR1 group, the low miR-106b-5p, low miR-93-5p, low miR-3129-5p, low miR-199b-3p, low miR-4465 group and high OLR1 group have significantly higher recurrence (all P<0.05) and higher mortality (all P<0.05). The identification value of recurrence assessment model [Y = 4.267+0.336*(miR-106b-5p)+0.168*(miR-93-5p)+1.847*(miR-3129-5p)+2.119*(miR-199b-3p)+0.872*(miR-4465)-3.408*(OLR1)] was high with an AUC of 0.918. The prognosis assessment model [Y = 3.914+0.143*(miR-106b-5p)+0.102*(miR-93-5p)+0.115*(miR-3129-5p)+1.369*(miR-199b-3p)+0.186*(miR-4465)-0.334*(OLR1)] also had high identification value with an AUC of 0.934. CONCLUSION: The combined detection of miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, miR-4465, and OLR1 is expected to become a molecular biomarker for the long-term prognostic assessment of ovarian cancer.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Feminino , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Prognóstico , Estudos Prospectivos , Regulação para Cima
9.
Nat Commun ; 13(1): 6004, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224181

RESUMO

Aberrant activation of EGFR due to overexpression or mutation is associated with poor prognosis in many types of tumors. Here we show that blocking the sorting system that directs EGFR to plasma membrane is a potent strategy to treat EGFR-dependent tumors. We find that EGFR palmitoylation by DHHC13 is critical for its plasma membrane localization and identify ARF6 as a key factor in this process. N-myristoylated ARF6 recognizes palmitoylated EGFR via lipid-lipid interaction, recruits the exocyst complex to promote EGFR budding from Golgi, and facilitates EGFR transporting to plasma membrane in a GTP-bound form. To evaluate the therapeutic potential of this sorting system, we design a cell-permeable peptide, N-myristoylated GKVL-TAT, and find it effectively disrupts plasma membrane localization of EGFR and significantly inhibits progression of EGFR-dependent tumors. Our findings shed lights on the underlying mechanism of how palmitoylation directs protein sorting and provide an potential strategy to manage EGFR-dependent tumors.


Assuntos
Fatores de Ribosilação do ADP , Neoplasias , Fatores de Ribosilação do ADP/metabolismo , Membrana Celular/metabolismo , Receptores ErbB/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Lipídeos , Neoplasias/metabolismo , Transporte Proteico
10.
Am J Transl Res ; 14(4): 2402-2409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559408

RESUMO

OBJECTIVE: To clarify the effects of total laparoscopic hysterectomy (TLH) on sex hormone levels, quality of life (QOL) and complications such as lower-extremity deep vein thrombosis (DVT) in patients with uterine fibroids (UFs). METHODS: In this retrospective study, 136 patients with UFs treated in Hainan General Hospital from March 2018 to December 2020 were collected as research participants, of which 65 patients received total abdominal hysterectomy (TAH) were included in the control group and 71 patients who received TLH were assigned to the research group. The two groups were compared regarding the following items: response rate, surgical indexes, rehabilitation indicators, changes in sex hormone levels and QOL, and the occurrence of lower-extremity DVT. RESULTS: The research group showed a significantly higher response rate, and better indicators of surgical treatment and rehabilitation than the control group (P<0.05). The sex hormones in the research group were more stable than that in the control group. The QOL was also significantly better and the incidence of total complications was statistically lower in the research group compared with the control group (both P<0.05). CONCLUSIONS: TLH is a feasible and safe alternative than traditional TAH for UFs, as it can effectively improve patients' sex hormone levels and QOL, and reduce the incidence of complications, which is worthy of clinical promotion.

12.
Phytomedicine ; 93: 153798, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34673348

RESUMO

BACKGROUND: NLRP3 inflammasome activation and pyroptosis play an important role in myocardial ischemia/reperfusion injury (MI/RI). Cinnamomi ramulus (CR), is an important folk medicinal plant in China, which derived from the dried twig of Cinnamomum cassia (L.) Presl, has function of "warming and tonifying heart yang", and traditionally utilized to treat the cold, blood-cold amenorrhea, phlegm, edema, arthralgia, and palpitations as well as improve blood circulation. The aqueous extract of C. ramulus was reported to show significant therapeutic potential for treating MI/RI. Whereas, there are no previous investigations in China or abroad has reported the cardioprotective effects and underlying mechanism of the ethyl acetate extract of C. ramulus (CREAE) and its bioactive substance cinnamic acid (CA) in triggering NLRP3 inflammasome activation and subsequent pyroptosis. PURPOSE: The present study aimed to assess the cardioprotective function of CREAE and CA against the MI/RI in rats and involved the underlying mechanisms. METHODS: The MI/RI model was established in male SD rats by occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min, respectively. The rats were intragastrically administered with CREAE (74 and 37 mg/kg) and CA (45 mg/kg) for 7 successive days before vascular ligation. The cardioprotective effects of CREAE and CA against myocardial injury of rats were detected by HE staining, TTC staining, echocardiograms, and myocardial enzymes detections. Serum levels of inflammatory factors, such as IL-6, IL-1ß, and TNF-α, were analyzed by ELISA kits to evaluate the effects of CREAE and CA. The protein and gene expression levels of NLRP3 and the pyroptosis-related factors in heart tissue were conducted by western blot and RT-qPCR. RESULTS: Our results showed that CREAE and CA decrease myocardial infarct size and improve cardiac function, mitigate myocardial damage, and repress inflammatory response in rats after I/R. Mechanistically, our results revealed that CREAE and CA can dramatically suppress the activation of NLRP3 inflammasome and subsequent cardiomyocyte pyroptosis in myocardial tissues that as evidenced by downregulating the protein and gene expressions of NLRP3, ASC, IL-1ß, caspase-1, gasdermin D, and N-terminal GSDMD. CONCLUSIONS: Our data indicated that CREAE and CA may attenuate MI/RI through suppression of NLRP3 inflammasome and subsequent pyroptosis-related signaling pathways.


Assuntos
Traumatismo por Reperfusão Miocárdica , Piroptose , Acetatos , Animais , Inflamassomos , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ratos Sprague-Dawley
13.
BMC Nephrol ; 22(1): 305, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496793

RESUMO

BACKGROUND: Albumin is the primary body protein, which can predict the poor prognosis of several critical diseases. However, there are a few scientific studies on the relationship between albumin and the prognosis of dialysis patients. This study aims to explore the impact of hypoalbuminemia on the prognosis of critically ill patients with acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). METHODS: This was a secondary study. Clinical, biochemical, and 28-day and 90-day mortality rates for critical patients with AKI who received CRRT between 2009 and 2016 were searched from the database to determine the effect of hypoalbuminemia on poor outcomes by univariate, multivariate, smooth curve fitting, and subgroup analysis. RESULTS: A total of 837 participants were enrolled in this study. Multivariate Cox proportional hazard regression analysis showed that hypoalbuminemia was associated with both 28-day and 90-day mortality risks after full adjustment for confounding variables, with an adjusted hazard ratio (95% confidence interval) of 0.63 (0.50-0.80) and 0.63 (0.51-0.78), respectively for each 1 g/dL increase of albumin. Stratified analysis showed that hypoalbuminemia was not associated with poor prognosis in oliguria. CONCLUSION: Hypoalbuminemia is associated with poor prognosis in critically ill AKI patients with CRRT; therefore, measuring albumin may be helpful for predicting the prognosis. However, in those with oliguria, this conclusion is not valid.


Assuntos
Injúria Renal Aguda/terapia , Estado Terminal/terapia , Terapia de Substituição Renal , Albumina Sérica/deficiência , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Idoso , Análise de Variância , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Albumina Sérica/análise
14.
ACS Appl Mater Interfaces ; 13(39): 46738-46748, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34546702

RESUMO

Micropiezoelectric devices have become one of the most competitive candidates for use in self-powered flexible and portable electronic products because of their instant response and mechanic-electric conversion ability. However, achievement of high output performance of micropiezoelectric devices is still a significant and challenging task. In this study, a poly(vinylidene fluoride) (PVDF)/MXene piezoelectric microdevice was fabricated through a microinjection molding process. The synergistic effect of both an intense shear rate (>104 s-1) as well as numerous polar C-F functional groups in MXene flakes promoted the formation of ß-form crystals of PVDF in which the crystallinity of ß-form could reach as high as 59.9%. Moreover, the shear-induced shish-kebab crystal structure with a high orientation degree (fh = ∼0.9) and the stacked MXene acted as the driving force for the dipoles to regularly arrange and produce a self-polarizing effect. Without further polarization, the fabricated piezoelectric microdevices exhibited an open-circuit voltage of 15.2 V and a short-circuit current of 497.3 nA, under optimal conditions (400 mm s-1 and 1 wt % MXene). Impressively, such piezoelectric microdevices can be used for energy storage and for sensing body motion to monitor exercise, and this may have a positive impact on next-generation smart sports equipment.

15.
Gynecol Obstet Clin Med ; 1(2): 100-105, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38620602

RESUMO

At present, China is in the stage of the COVID-19 epidemic where regular prevention and control measures are required to contain the spread of disease. Reports of new sporadic cases are still widespread across China and medical personnel remain at high risk of exposure to infection. This is especially the case for medical staff working within emergency departments. Most gynecological emergency cases are complex and a high proportion require emergency surgical treatment. By referring to national regulations and requirements on COVID-19 prevention and control, and by summarizing our experiences in the battle against COVID-19 within Wuhan, this consensus report provides recommendations on the triage, reception, consultation, admission and surgical management of gynecological emergency patients. We also make suggestions for the environmental layout and disinfection and the medical waste management. This consensus aims to optimize the diagnosis and treatment process of gynecological emergency patients and reduce the exposure risk of medical staff within the current context of routine COVID-19 prevention and control.

16.
Chem Commun (Camb) ; 55(98): 14769-14772, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31754673

RESUMO

An unprecedented gold-catalyzed procedure for the synthesis of polysubstituted 4-quinolones from 1-(2'-azidoaryl) propynols is described. The reaction undergoes an intramolecular nucleophilic attack of the azide group to the Au-activated triple bonds in a 6-endo-dig manner and subsequent gold-assisted expulsion of N2 to furnish an α-imino gold carbene intermediate, which triggers a 1,2-carbon migration and finally is converted to 2,3-disubstituted 4-quinolone.

17.
Molecules ; 23(9)2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30200483

RESUMO

Ru-catalyzed tandem amine oxidative dehydrogenation/formal aza-Diels⁻Alder reaction for enantio- and diastereoselective synthesis of indoloquinolizidine-2-ones from tetrahydro-ß-carbolines and α,ß-unsaturated ketones is described. The reaction proceeds via tandem ruthenium-catalyzed amine dehydrogenation using tert-butyl hydroperoxide (TBHP) as the oxidant and a chiral thiourea-catalyzed formal aza-[4 + 2] cycloaddition, providing a step-economical strategy for the synthesis of these valuable heterocyclic products.


Assuntos
Carbolinas/química , Reação de Cicloadição , Cetonas/química , Quinolizidinas/síntese química , Alcaloides Indólicos/química , Oxirredução , Quinolizidinas/química
18.
Mol Med Rep ; 10(6): 3099-105, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25323477

RESUMO

Ceramide is a bioactive lipid which functions as a tumor suppressor, mediating processes such as apoptosis, growth arrest, senescence and differentiation. The effects of ceramide in ovarian cancers have not been well established. The objective of the present study was to investigate the effects of C2­ceramide treatment in A2780 ovarian cancer cells and its possible molecular mechanism. C2­ceramide-induced proliferation inhibition was analyzed using an MTT assay and Trypan blue test. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling were used to identify the induction of apoptosis. Transmission electron microscopy was used to confirm the formation of autophagosomes. Quantitative polymerase chain reaction was performed to analyze the messenger RNA expression of the autophagy and cell death associated genes and western blotting was used to analyze the protein expression of beclin 1, LC3, Akt, forkhead box O3 (FOXO3) and adenosine monophosphate-activated protein kinase in ovarian cancer cells. It was found that C2­ceramide inhibited A2780 cell proliferation in a time­ and dose­dependent manner and C2­ceremide induced A2780 cell apoptosis and autophagy. However, C2­ceramide­induced autophagy did not result in cell death, but instead protected ovarian cancer cells from apoptosis. Akt inhibition and FOXO3 activation were implicated in C2­ceramide­treated ovarian cancer cells. Furthermore, FOXO3 target genes, which were associated with autophagy (MAP1LC3, GABARAP and GABARAPL1) and cell death (BNIP3, BNIP3L, BIM and PUMA), were upregulated. The present study has shown that C2­ceramide induced apoptosis and autophagy in ovarian cancer cells. FOXO3 transcription was upregulated, which may contribute to C2­ceramide­induced apoptosis and autophagy.


Assuntos
Apoptose/genética , Autofagia/genética , Ceramidas/farmacologia , Fatores de Transcrição Forkhead/genética , Neoplasias Ovarianas/genética , Transcrição Gênica/genética , Regulação para Cima/genética , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Autofagia/efeitos dos fármacos , Proteína Beclina-1 , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Proteína Forkhead Box O3 , Humanos , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética , Regulação para Cima/efeitos dos fármacos
19.
Childs Nerv Syst ; 28(10): 1687-91, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22752120

RESUMO

OBJECTIVE: This study aims to evaluate effects and complications of the implantation of Ommaya reservoir in premature infants with posthemorrhagic hydrocephalus (PHH). METHODS: The effects and complications of the implantation of Ommaya reservoir in seven premature infants with PHH were retrospectively analyzed. Intracapsular puncture of the reservoir was performed for draining cerebrospinal fluid. RESULTS: Seven extremely low-weight premature infants with PHH (birthweight less than 1,000 g) were treated with the placement of an Ommaya reservoir. Ommaya reservoirs in five infants were removed, but were retained in two infants. Two premature infants had to undergo ventriculoperitoneal (VP) shunt. Postsurgical major complications (including skin dehiscence, cerebrospinal fluid (CSF) infection, ventricular hemorrhage, and CSF leak) occurred in 57% of all patients. Three infants of skin dehiscence and CSF leak occurred. Two infants of CSF infection occurred, as well as one clinically significant secondary hemorrhage. Six infants survived, and one died. CONCLUSION: The implantation of Ommaya reservoir is a cautious option of treating low-weight premature infants with PHH because of a relatively high complication rate. However, VP shunt surgery may be avoided in some infants.


Assuntos
Hemorragia Cerebral/complicações , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente Extremamente Prematuro , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/instrumentação , Hemorragia Cerebral/líquido cefalorraquidiano , Feminino , Humanos , Hidrocefalia/líquido cefalorraquidiano , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Surg Endosc ; 26(6): 1573-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22179461

RESUMO

OBJECTIVE: Minimally invasive esophagectomy (MIE) has been widely applied for esophageal carcinoma treatment. Thoracoscope-assisted transthoracic esophagectomy (TATTE) and mediastinoscope-assisted transhiatal esophagectomy (MATHE) are two kinds of MIE. The objective of this study is to compare these two methods with respect to surgical safety and survival. METHODS: Single-institution experience with MATHE and TATTE was analyzed to assess morbidity, adequacy of tumor clearance, and survival. A pair-matched case-control study was performed to compare 54 patients who underwent either MATHE or TATTE between July 2000 and December 2009. Patients were matched by age, sex, comorbidity, forced expiratory volume in 1 s (FEV1), tumor location, and stage. RESULTS: Statistically significant differences between the MATHE group and the TATTE group were: shorter operative time for MATHE (194.4 min) versus TATTE (228.1 min), less blood loss during operation in the TATTE group (142.6 ml) versus the MATHE group (214.6 ml), and more lymph nodes retrieved in the TATTE group (19.1 nodes) versus the MATHE group (11.4 nodes). There was no difference in survival between the groups. CONCLUSIONS: MATHE and TATTE are both technically feasible. TATTE can provide better visibility. TATTE has less blood loss compared with MATHE. More adequate tumor clearance in terms of lymph node dissection can be achieved with TATTE.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagoscopia/métodos , Mediastinoscopia/métodos , Toracoscopia/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Esofagoscopia/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Excisão de Linfonodo/mortalidade , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Masculino , Mediastinoscopia/mortalidade , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Toracoscopia/mortalidade , Resultado do Tratamento
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