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BACKGROUND: This study aimed to compare the efficacy and safety of TLTG with the overlap technique to LATG in patients with advanced Siewert III Esophagogastric Junction Cancer and upper and middle third gastric cancer. METHODS: This single-center RCT enrolled 292 patients with the mentioned cancers, randomly assigned to TLTG overlap (n=146) or LATG (n=146) groups. Data on demographics, pathology, intraoperative variables, postoperative complications, recovery parameters, and 3-year survival were collected. Main outcome: postoperative complications within 30 days. Secondary outcomes: 3-year disease-free and overall survival. RESULTS: TLTG versus LATG: TLTG had shorter incision, faster flatus/defecation, reduced analgesia, less opioid use, and shorter hospital stay. Similar operation time, anastomosis time, blood loss, and lymph node harvest. TLTG had lower overall post-op complication rate (P=0.047), no significant difference in serious complications (P=0.310). Variances in anastomotic stenosis occurrence at 3 months. No rehospitalization or mortality at 30 days. No significant differences in 3-month disease-free survival (P=0.058) or overall survival (P=0.236). CONCLUSION: Overlap method for anastomosis in TLTG is safe and feasible for advanced middle-upper-third gastric cancer, with positive short-term outcomes. This technique has potential as the preferred esophagojejunostomy approach in TLTG. TRIAL REGISTRATION: This trial has been registered at Chinese Clinical Trial Registry: XXXXXXXX (registration date: September 4, 2019).
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We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.
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Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Glicólise , Sirtuína 1 , Sirtuína 1/metabolismo , Sirtuína 1/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Humanos , Glicólise/efeitos dos fármacos , Animais , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Camundongos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Feminino , Masculino , Camundongos NusRESUMO
Primary cilia have versatile functions, such as receiving signals from the extracellular microenvironment, mediating signaling transduction, and transporting ciliary substances, in tissue and organ development and clinical disease pathogenesis. During early development (embryos within 10 weeks) in the oral and maxillofacial region, defects in the structure and function of primary cilia can result in severe craniofacial malformations. For example, mice with mutations in the cilia-related genes Kif3a and IFT88 exhibit midline expansion and cleft lip/palate, which occur due to abnormalities in the fusion of the single frontonasal prominence and maxillary prominences. In the subsequent development of the oral and maxillofacial region, we discussed the regulatory role of primary cilia in the development of the maxilla, mandible, Meckel cartilage, condylar cartilage, lip, tongue, and tooth, among others. Moreover, primary cilia are promising regulators in some oral and maxillofacial diseases, such as tumors and malocclusion. We also summarize the regulatory mechanisms of primary cilia in oral and maxillofacial development and related diseases, including their role in various signaling transduction pathways. For example, aplasia of submandibular glands in the Kif3a mutant mice is associated with a decrease in SHH signaling within the glands. This review summarizes the similarities and specificities of the role of primary cilia in tissue and organ development and disease progression in the oral and maxillofacial region, which is expected to contribute several ideas for the treatment of primary cilia-related diseases.
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Cílios , Cílios/metabolismo , Cílios/patologia , Animais , Humanos , Desenvolvimento Maxilofacial/genética , Camundongos , Transdução de Sinais , Cinesinas/metabolismo , Cinesinas/genéticaRESUMO
Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.
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Colangiografia , Drenagem , Nutrição Enteral , Icterícia Obstrutiva , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/terapia , Icterícia Obstrutiva/cirurgia , Masculino , Feminino , Drenagem/métodos , Nutrição Enteral/métodos , Pessoa de Meia-Idade , Idoso , Colangiografia/métodos , Stents , Resultado do Tratamento , Cateterismo/métodos , Complicações Pós-Operatórias/etiologia , Desnutrição/etiologia , Desnutrição/terapia , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: To investigate the prenatal imaging characteristics, genetic characteristics and pregnancy outcome of fetuses with cardiac rhabdomyoma. STUDY DESIGN: The prenatal ultrasound, cranial MRI imaging information and genetic test results of 35 fetuses prenatally diagnosed with cardiac rhabdomyoma were collected and retrospectively analyzed, and the pregnancy outcome was followed up. RESULT: Cardiac rhabdomyomas mainly occurred in left ventricular wall and ventricular septum; cranial MRI imaging was found abnormal in 38.1% (8/21) of the fetuses; genetic test was found abnormal in 58.82% (10/17) of the fetuses; the fetus was born in 12 cases and the pregnancy was terminated in 23 cases. CONCLUSION: TRIO whole exome sequencing (TrioWES) is recommended as the genetic test regime for cardiac rhabdomyoma. The comprehensive evaluation of prognosis of fetuses needs to consider the genetic results and whether the brain is involved; the prognosis of fetuses with simple cardiac rhabdomyoma is good.
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Doenças Fetais , Neoplasias Cardíacas , Rabdomioma , Esclerose Tuberosa , Feminino , Gravidez , Humanos , Resultado da Gravidez , Rabdomioma/diagnóstico por imagem , Rabdomioma/genética , Estudos Retrospectivos , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/genética , Diagnóstico Pré-Natal/métodos , Feto/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/genética , Ultrassonografia Pré-NatalRESUMO
Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1É expression to enhance the activities of VEGF and SDF-1É, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1É-VEGF/SDF-1É pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.
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Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Fatores de Diferenciação de Crescimento , Cicatrização , Animais , Humanos , Camundongos , Proteínas Morfogenéticas Ósseas/metabolismo , Quimiocina CXCL12/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Fatores de Diferenciação de Crescimento/uso terapêutico , Fatores de Diferenciação de Crescimento/metabolismo , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
Diabetic mellitus (DM) complicated with myocardial infarction (MI) is a serious clinical issue that remained poorly comprehended. The aim of the present study was to investigate the role of NAD+ in attenuating cardiac damage following MI in diabetic mice. The cardiac dysfunction in DM mice with MI was more severe compared with the non-diabetic mice and NAD+ administration could significantly improve the cardiac function in both non-diabetic and diabetic mice after MI for both 7 days and 28 days. Moreover, application of NAD+ could markedly reduce the cardiac injury area of DM complicated MI mice. Notably, the level of NAD+ was robustly decreased in the cardiac tissue of MI mice, which was further reduced in the DM complicated mice and NAD+ administration could significantly restore the NAD+ level. Furthermore, NAD+ was verified to facilitate the angiogenesis in the MI area of both diabetic mice and non-diabetic mice by microfil perfusion assay and immunofluorescence. Additionally, we demonstrated that NAD+ promoted cardiac angiogenesis after myocardial infarction in diabetic mice by promoting the M2 polarization of macrophages. At the molecular level, NAD+ promoted the secretion of VEGF in macrophages and therefore facilitating migration and tube formation of endothelial cells. Mechanistically, NAD+ was found to promote the generation of pro-angionesis VEGF165 and inhibit the generation of anti-angionesis VEGF165b via regulating the alternative splicing factors of VEGF (SRSF1 and SRSF6) in macrophages. The effects of NAD+ were readily reversible on deficiency of it. Collectively, our data showed that NAD+ could attenuate myocardial injury via regulating the alternative splicing of VEGF and promoting angiogenesis in diabetic mice after myocardial infarction. NAD+ administration may therefore be considered a potential new approach for the treatment of diabetic patients with myocardial infarction.
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Diabetes Mellitus , Infarto do Miocárdio , Animais , Camundongos , Processamento Alternativo , Células Endoteliais , Macrófagos , NAD/farmacologia , NAD/uso terapêutico , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The most devastating and catastrophic deterioration of myocardial ischemia-reperfusion injury (MIRI) is cardiomyocyte death. Here we aimed to evaluate the role of lncRNA-ZFAS1 in MIRI and delineate its mechanism of action. The level of lncRNA-ZFAS1 was elevated in MIRI hearts, and artificial knockdown of lncRNA-ZFAS1 in mice improved cardiac function. Notch1 is a potential target of lncRNA-ZFAS1, and lncRNA-ZFAS1 could bind to the promoter region of Notch1 and recruit DNMT3b to induce Notch1 methylation. Nicotinamide mononucleotide could promote the expression of Notch1 by competitively inhibiting the expression of DNMT3b and improving the apoptosis of cardiomyocytes and cardiac function.
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Low molecular weight heparin (LMWH), an anionic polysaccharide, has been widely used as a clinical anticoagulant. However, repeated subcutaneous injection is sometimes required due to its short half-life. To reduce the dosing frequency, the injectable polypseudorotaxane hydrogel was fabricated by inclusion complexation formation between Tween 80 and α-Cyclodextrin (αCD) for sustained release of LMWH. The physicochemical properties of such hydrogel were characterized by SEM, XRD, DSC, and FTIR. This hydrogel showed shear-thinning and thixotropic behavior and was easily injected through standard syringe needles. The gelation time, mechanical strength, shear viscosity, in vitro drug release rate, in vitro hydrogel dissolution rate, and in vivo hydrogel retention could be tuned by αCD concentration in the hydrogel. In vivo safety evaluation indicated that the polypseudorotaxane hydrogel was biocompatible. Most importantly, this polypseudorotaxane hydrogel could sustain release of LMWH after subcutaneous injection.
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alfa-Ciclodextrinas , Anticoagulantes/farmacologia , Ciclodextrinas , Preparações de Ação Retardada , Heparina de Baixo Peso Molecular , Hidrogéis/química , Poloxâmero , Polissorbatos , Rotaxanos , alfa-Ciclodextrinas/químicaRESUMO
OBJECTIVE: This study aimed to explore whether intraflagellar transport protein 88 (IFT88) was associated with polycystin 2 during mechanotransduction of mandibular condylar chondrocytes. METHODS: Rat mandibular condylar chondrocytes isolated from the condylar bone-cartilage junction were subjected to cyclic tensile strain (0.1 Hz, 10% elongation). Overexpression of IFT88 was achieved by lentiviral vector-mediated transfection. Knockdown of IFT88 and polycystin 2 was achieved by small interfering RNA (siRNA). The prevalence and length of cilia were reflected by immunofluorescence staining. The activities of hedgehog signaling were evaluated by western blot analysis. The interaction between polycystin 2 and IFT88 was evaluated by conducting a co-immunoprecipitation (co-IP) assay. RESULTS: Overexpression of IFT88 increased the length of cilia. Protein levels of polycystin 2, Indian hedgehog (Ihh), Patched 1 (Ptch1), Smoothened (Smo), and Glioma-associated oncogene homolog 1 (Gli1) were elevated in IFT88-overexpressing mandibular condylar chondrocytes under cyclic tensile strain. Knockdown of the protein level of IFT88 reduced the prevalence and length of cilia, and protein levels of polycystin 2, Ihh, Ptch1, Smo, and Gli1. A co-IP assay showed that IFT88 formed a complex with polycystin 2 under cyclic tensile strain. Knockdown of polycystin 2 decreased the protein levels of IFT88, Ihh, Ptch1, Smo, and Gli1 in mandibular condylar chondrocytes following cyclic tensile strain. CONCLUSION: These findings highlight the vital role of an interaction between IFT88 and polycystin 2 in mechanosensitive hedgehog signaling in mandibular condylar chondrocytes following cyclic tensile strain, which suggest that therapies regulating polycystin 2 may be considered for the disorders of temporomandibular joints.
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Condrócitos , Proteínas Hedgehog , Canais de Cátion TRPP , Animais , Condrócitos/metabolismo , Proteínas Hedgehog/metabolismo , Mecanotransdução Celular/fisiologia , RNA Interferente Pequeno/metabolismo , Ratos , Canais de Cátion TRPP/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
Diabetic cardiomyopathy (DCM) is initially characterized by early diastolic dysfunction, left ventricular remodeling, hypertrophy, and myocardial fibrosis, and it is eventually characterized by clinical heart failure. MicroRNAs (miRNAs), endogenous small noncoding RNAs, play significant roles in diabetes mellitus (DM). However, it is still largely unknown about the mechanism that links miRNAs and the development of DCM. Here, we aimed to elucidate the mechanism underlying the potential role of microRNA-340-5p in DCM in db/db mouse, which is a commonly used model of type 2 DM and diabetic complications that lead to heart failure. We first demonstrated that miR-340-5p expression was dramatically increased in heart tissues of mice and cardiomyocytes under diabetic conditions. Overexpression of miR-340-5p exacerbated DCM, which was reflected by extensive myocardial fibrosis and more serious dysfunction in db/db mice as represented by increased apoptotic cardiomyocytes, elevated ROS production, and impaired mitochondrial function. Inhibition of miR-340-5p by a tough decoy (TUD) vector was beneficial for preventing ROS production and apoptosis, thus rescuing diabetic cardiomyopathy. We identified myeloid cell leukemia 1 (Mcl-1) as a major target gene for miR-340-5p and showed that the inhibition of Mcl-1 was responsible for increased functional loss of mitochondria, oxidative stress, and cardiomyocyte apoptosis, thereby caused cardiac dysfunction in diabetic mice. In conclusion, our results showed that miR-340-5p plays a crucial role in the development of DCM and can be targeted for therapeutic intervention.
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MicroRNAs/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Estresse Oxidativo/genética , Animais , Antagomirs/metabolismo , Apoptose , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (Papp, 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUCAqueous humor, 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ-CD-based polypseudorotaxane hydrogels for ocular drug delivery.
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Ciclodextrinas/uso terapêutico , Flurbiprofeno/uso terapêutico , Hidrogéis/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Poloxâmero/uso terapêutico , Rotaxanos/uso terapêutico , Uveíte Anterior/tratamento farmacológico , gama-Ciclodextrinas/uso terapêutico , Administração Oftálmica , Animais , Ciclodextrinas/administração & dosagem , Ciclodextrinas/química , Sistemas de Liberação de Medicamentos , Flurbiprofeno/administração & dosagem , Flurbiprofeno/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/química , Poloxâmero/administração & dosagem , Poloxâmero/química , Coelhos , Rotaxanos/administração & dosagem , Rotaxanos/química , gama-Ciclodextrinas/administração & dosagem , gama-Ciclodextrinas/químicaRESUMO
Sagittal split ramus osteotomy (SSRO) is a versatile orthognathic procedure for correcting mandibular deformities. Various complications can possibly occur when performing SSRO, and it can even cause serious adverse consequences because of the complexity of anatomy and operative procedures. The types of complications and their accompanying clinical manifestations are closely related to the choice of diagnosis and treatment strategies and clinical outcomes. To discuss the causes, prevention, and treatment measures of various common complications of SSRO, domestic orthognathic surgery experts prepared this consensus to increase the awareness of SSRO complications, thereby ensuring safe surgical procedure and good results.
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Backgrounds: Our previous work revealed that AMP-activated protein kinase (AMPK) activation inhibits vascular smooth muscle cell migration in vitro by phosphorylating PDZ and LIM domain 5 (Pdlim5). As metformin is an AMPK activator, we used a mouse vascular smooth muscle cell (VSMC) line and a Myh11-cre-EGFP mice to investigate whether metformin could inhibit the migration of VSMCs in vitro and in a wire-injury model in vivo. It is recognized that VSMCs contribute to the major composition of atherosclerotic plaques. In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, we utilized ApoE-/- male mice to investigate whether metformin could suppress diabetes-accelerated atherosclerosis by inhibition of VSMC migration via the AMPK-Pdlim5 pathway. Methods: The mouse VSMC cell line was exogenously transfected wild type, phosphomimetic, or unphosphorylatable Pdlim5 mutant before metformin exposure. Myh11-cre-EGFP mice were treated with saline solution or metformin after these were subjected to wire injury in the carotid artery to study whether metformin could inhibit the migration of medial VSMCs into the neo-intima. In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, ApoE-/- male mice were divided randomly into control, streptozocin (STZ), and high-fat diet (HFD)-induced diabetes mellitus; STZ+HFD together with metformin or Pdlim5 mutant carried the adenovirus treatment groups. Results: It was found that metformin could induce the phosphorylation of Pdlim5 and inhibit cell migration as a result. The exogenous expression of phosphomimetic S177D-Pdlim5 inhibits lamellipodia formation and migration in VSMCs. It was also demonstrated that VSMCs contribute to the major composition of injury-induced neointimal lesions, while metformin could alleviate the occlusion of the carotid artery. The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin. Conclusions: The activation of the AMPK-Pdlim5 pathway by metformin could interrupt the migratory machine of VSMCs and inhibit cell migration in vitro and in vivo. The maintenance of AMPK activity by metformin is beneficial for suppressing diabetes-accelerated atherosclerosis.
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OBJECTIVE: To investigate the effect of tumor necrosis factor death receptor (DR) 4 demethylation to the proliferation and apoptosis of myeloid leukemia K562 cells. METHODS: The logarithmic phase of K562 cells were treated by desitabine (DCA) at 0, 0.8, 1.6 and 3.2 µmol/L, and the cells were divided into control group, DCA low dose group, DCA medium dose group and DCA high dose group respectively. The cells in control group were treated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) 0.5 µg/ml for 24 h, and the cells were divided into TRAIL group. The cells in DCA high dose group were treated by TRAIL 0.5 µg/ml for 24 h, and were divided into DCA high dose + TRAIL group. Methylation-specific polymerase chain reaction (MS-PCR) was used to measure the methylation status of the DR4 gene promoter in the control group and DCA low, medium and high dose groups. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to determine the relative expression of DR4 mRNA and protein in the control group and DCA low, medium and high dose groups. Dime- thylthiazole (MTT) method was used to determine the inhibition rate of cell proliferation of the cells in control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group. Flow cytometry was used to determine the apoptotic rate of the cells in control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group. RESULTS: The cells in the control group were methylation-positive, the brightness of the methylation bands of the cells in the DCA low, medium, and high dose groups was gradually decreased to disappear, and the DCA high dose group showed negative for methylation. The relative expression of DR4 mRNA and protein in the control group, DCA low, medium and high dose groups was increased sequentially (r=0.624, 0.704). The inhibition rate of cell proliferation of the cells in the control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group was increased sequentially (r=0.653, 0.754, 0.709, 0.725) at 24, 48 and 72 h. CONCLUSION: DCA can reverse the methylation level of DR4 gene promoter in ML K562 cells and up-regulate the expression of DR4, which may enhance the proliferation inhibition and apoptosis promotion effects of TRAIL on K562 cells.
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Leucemia Mieloide , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Desmetilação , Humanos , Células K562 , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismoRESUMO
Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide with poor survival. High expression of nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant transcript factor that protects malignant cells from death. Polygalacin D (PGD), a bioactive compound isolated from Platycodongrandiflorum (Jacq.), has recently been reported to be an anti-tumor agent. This study aimed to investigate the anti-cancer effects of PGD and its underlying molecular mechanisms in human ESCC. Here, we confirmed that Nrf2 was over-expressed in clinical ESCC tissues and cell lines. PGD treatments markedly reduced Nrf2 expression in a dose- and time-dependent manner in ESCC cell lines. Importantly, we found that PGD significantly reduced proliferation, and induced G2/M cell cycle arrest and apoptosis in ESCC cells. Also, PGD dramatically triggered autophagy in ESCC cells, and autophagy inhibitor bafilomycinA1 (BafA1) greatly abrogated the inhibitory role of PGD in cell viability and apoptosis. In addition, PGD evidently provoked reactive oxygen species (ROS) accumulation in ESCC cells, and pre-treatment of ROS scavenger N-acetyl-l-cysteine (NAC) markedly abolished PGD-triggered cell death. PGD also dramatically repressed migration and invasion in ESCC cells. Mechanistic investigation revealed that Nrf2 gene was directly targeted by miR-142-5p. MiR-142-5p negatively regulated Nrf2 expression in ESCC cells. We notably found that PGD-inhibited proliferation, migration and invasion in ESCC were considerably rescued by miR-142-5p knockdown; however, ROS production, apoptosis and autophagy induced by PGD were almost eliminated when miR-142-5p was silenced. On the contrast, over-expressing miR-142-5p could remarkably promote the anti-ESCC effects of PGD. Experiments in vivo by the tumor xenograft model confirmed that miR-142-5p effectively improved the activity of PGD to repress tumor growth and lung metastasis. Both in vitro and in vivo studies showed that PGD had few side effects on normal cells and major organs. Collectively, our findings provided the first evidence that PGD could be an effective therapeutic strategy for ESCC treatment by regulating miR-142-5p/Nrf2 axis with few adverse effects.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Saponinas/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/genéticaRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) have been confirmed to participate in the regulation of nasopharyngeal carcinoma. Here, we endeavored to explore the character of lncRNA ILF3-AS1 in the nasopharyngeal carcinoma and its function. METHODS: A total of 68 nasopharyngeal carcinoma tissues and adjacent normal nasopharyngeal tissues were collected. Expressions of lncRNA ILF3-AS1 in these tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between the expression level of lncRNA ILF3-AS1 and clinical pathological characteristics was analyzed. Inhibition of lncRNA ILF3-AS1 was done using small interference RNA. RESULTS: lncRNA ILF3-AS1 expression was significantly up-regulated in the 68 nasopharyngeal carcinoma tissue samples compared to their adjacent normal tissue samples. Increased lncRNA ILF3-AS1 level was related to the advanced tumor node metastasis stage and the metastasis of nasopharyngeal carcinoma. Also, increased lncRNA ILF3-AS1 indicated poor prognosis of nasopharyngeal carcinoma patients. Inhibition of lncRNA ILF3-AS1 reduced proliferation, invasion and migration of nasopharyngeal carcinoma cells. MicroRNA-320a (miR-320a) was determined as a direct target for lncRNA ILF3-AS1 in nasopharyngeal carcinoma. Furthermore, lncRNA ILF3-AS1 could sponge miR-320a to promote BMI1 expression. The expression of BMI1 was significantly inhibited by the down-regulation of lncRNA ILF3-AS1. CONCLUSIONS: For the first time, we demonstrated that lncRNA ILF3-AS1 was markedly over-expressed in nasopharyngeal carcinoma tissues and cells. Elevated lncRNA ILF3-AS1 expression was correlated with severe cancer stage and poor prognosis. lncRNA ILF3-AS1 could promote proliferation, invasion, and migration of cells, which might indicate a novel target site for the future diagnosis and therapy of nasopharyngeal carcinoma.
Assuntos
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas do Fator Nuclear 90/genética , RNA Longo não Codificante/metabolismo , Animais , Proliferação de Células/fisiologia , Feminino , Humanos , Masculino , Camundongos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Prognóstico , RNA Longo não Codificante/genética , Transfecção , Regulação para CimaRESUMO
BACKGROUND: The surgical approach of the zygomaticomaxillary complex fracture is usually performed with preauricular coronal incision assisted with intraoral maxillary sulcus incision. There will be preauricular scars postoperatively. METHODS: The authors introduce a postauricular hemicoronal incision to avoid the formation of scars in front of the ear. RESULTS AND DISCUSSION: The postauricular hemicoronal incision can avoid vascular damage caused by careless operation in the preauricular approach. It eliminates the possibility of dissection or ligation of the superficial arteries and veins when preauricular approach was used. It results in no scar in front of ear, while reducing suture time and complexity.
Assuntos
Fraturas Maxilares/cirurgia , Fraturas Zigomáticas/cirurgia , Adolescente , Cicatriz , Humanos , Masculino , Fraturas Maxilares/diagnóstico por imagem , Fraturas Zigomáticas/diagnóstico por imagemRESUMO
Increasing studies have demonstrated the important roles of circular RNAs (circRNAs) in human malignancies. Nevertheless, the molecular mechanisms and functions of circRNAs in hepatocellular carcinoma (HCC) are still not fully understood. In the present study, we evaluated circ_0021093 expression in 82 pairs of HCC tissues and 5 cell lines by qRT-PCR. The clinical implications of circ_0021093 were evaluated. In addition, the viability, apoptosis, migration and invasion capacities of different HCC cells were evaluated by gain-/loss-of-function experiments. Target prediction and dual-luciferase reporter experiments were performed to identify the molecular mechanisms of circ_0021093. Upregulation of circ_0021093 was found in HCC tumor samples and cells. Additionally, upregulated circ_0021093 was related to adverse clinical characteristics and an unfavorable prognosis. Furthermore, downregulated circ_0021093 attenuated cell growth, migration and invasion but increased cell apoptosis. By contrast, ectopically expressed circ_0021093 enhanced the abovementioned malignant biological behaviors. For mechanism exploration, circ_0021093 sponges of miR-766-3p were used in HCC cells. In addition, we found that metastasis-associated protein 3 (MTA3) was a direct target of miR-766-3p and that the oncogenic function of circ_0021093 was partly dependent on the miR-766-3p/MTA3 axis according to rescue assays. In conclusion, the circ_0021093/miR-766-3p/MTA3 regulatory axis may be an effective therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Circular , Regulação para Cima/genéticaRESUMO
To evaluate the value of intraperitoneal hyperthermic perfusion (IPHP) in the treatment of gastric cancer.Gastric cancer (GC) is a malignancy with poor prognosis, recent years have demonstrated advances in the use of IPHP for the treatment of advanced gastric cancer (AGC), but the outcome is controversial.Between January 2015 and January 2017, 134 patients with GC were treated with IPHP in our surgery department, 130 of them were advanced GC patients, and other 1439 cases were treated without IPHP for comparison. In this retrospective cohort study, demographic, perioperative data, and follow-up data were analyzed by univariant analysis, Kaplan-Meier and Cox regression survival analysis.We found the 1-year survival in IPHP group was significantly longer than it in non-IPHP group (85.5% vs 73.8%, Pâ=â.027). and IPHP decreased mortality 1.8 times in 2-year course (ORâ=â0.556, Pâ=â.004). The incidence rate of total complications in IPHP group was similar to that in the Non-IPHP group (6.67% vs 7.46%, respectively; Pâ=â.718). We classified all patients into four groups, operation alone, operationâ+âchemotherapy, operationâ+âIPHP, and operationâ+âIPHPâ+âchemotherapy. The 1-year survival in the groups was 70.2%, 77.5%, 83.1%, and 93.5%, respectively (Pâ=â.001), compared with the group of operation alone, the 2-year mortality risk was decreased 1.76 times (ORâ=â0.569, Pâ=â.030) and 2.59 times (ORâ=â0.385, Pâ=â.022) in operationâ+âIPHP group and operationâ+âIPHPâ+âchemotherapy group.Our results suggest that IPHP could contribute to improve survival of patients with gastric cancer. And the modality of operationâ+âIPHPâ+âchemotherapy is the optimal treatment modality for gastric cancer.