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1.
Soft Matter ; 19(17): 3222-3227, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37083022

RESUMO

Active particles without detailed balance can rectify their random motions to drive the directed movement or rotation of asymmetric passive obstacles. However, whether they can drive the directed movement of symmetric passive obstacles is still unclear. Here, we show that a rod-like passive particle which is fixed to move along the x-axis in an active bath can keep long-lived directed movement at nearly constant speed due to the spontaneous symmetry breaking of the neighboring active particle cluster. If the passive particle is further confined by a harmonic potential, it may undergo self-sustained periodic oscillation for an appropriate length of the passive particle and self-propelled velocity of active particles. The restoring force from the harmonic potential will trigger the velocity jump-off and thus lead to self-sustained periodic oscillation. Remarkably, the relationship between the velocity of the passive particle and the external force shows that the effective viscosity of the active bath may become negative in some regime. Finally, we develop a minimum 1D theoretical model to further probe the mechanism underlying the directed movement and self-sustained oscillation of the passive particle. Our findings reveal the effect of the moving boundary on the active bath and demonstrate a novel method to extract practical mechanical work from the active bath to propel microdevices.

2.
J Obstet Gynaecol Res ; 49(7): 1821-1826, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37186345

RESUMO

AIM: Complete perforation of the bladder caused by an intrauterine device (IUD) is rare. This study examined the characteristics of patients associated with IUD-related bladder perforation and evaluated the relationship between mislocated IUDs and their potential complications. METHODS: From October 2005 to December 2021, 13 reports regarding complete perforations to the bladder by IUDs were retrieved from the National Contraceptives Adverse Reaction Monitoring System of China. The clinical features of these cases were analyzed. RESULTS: The median patient age was 30 (range, 27-46) years. There were four cases (4/13, 30.8%) with IUDs placed during lactation, one case (1/13, 7.7%) with an IUD placed after medical abortion, and eight cases (8/13, 61.5%) placed after menstruation. Seven cases (7/13, 53.9%) were first-time IUD users. The median duration of IUD placement was 47 (range, 1-145) months. Unexpected pregnancy was reported in five cases (5/13, 38.5%). Six cases (6/13, 46.2%) reported bladder stones with varying degrees of abdominal pain or urinary tract infection. Removal methods included laparotomy (four cases), cystoscopy (four cases), laparoscopy (two cases), laparoscopy combined with cystoscopy (two cases), and laparotomy after cystoscopy (one case). All IUDs were successfully removed. CONCLUSIONS: Complete perforation to the bladder by IUDs is a rare adverse event. Regular follow-up is required after the placement of IUDs. The possibility of uterine perforation should be investigated if IUD users encounter persistent lower abdominal pain or urinary tract infection.


Assuntos
Dispositivos Intrauterinos , Laparoscopia , Bexiga Urinária , Perfuração Uterina , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Cistoscopia , Dispositivos Intrauterinos/efeitos adversos , Laparoscopia/efeitos adversos , Bexiga Urinária/lesões , Perfuração Uterina/epidemiologia , Perfuração Uterina/etiologia , Perfuração Uterina/cirurgia , Corpos Estranhos
3.
Arch Orthop Trauma Surg ; 143(6): 3163-3172, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35907003

RESUMO

INTRODUCTION: To date, there is no consensus on the optimal surgical strategy for the treatment of posterolateral tibial plateau fracture (PLF). This study introduced a novel, simple technique for treating PLF with a lateral locking plate plus antero-posterior lag screws (LPpLS). METHODS: We conducted a retrospective case series of 42 patients (Female/Male 19/23) with PLF treated with LPpLS between 1 July 2016 and 30 June 2019. Several pre- and postoperative outcomes were recorded, including operative time, intraoperative blood loss, CT findings, HSS, and ROM. For biomechanical studies, seventy synthetic tibiae with a simulated posterolateral split fracture were divided into seven groups. The biomechanical evaluation included displacement measurement at axial compression and fatigue testing. RESULTS: Forty-two eligible patients were followed up for an average of 18 months (range 14-21 months). Postoperative radiographs and CT showed good positioning of plates and screws, no fracture fragment loss, and normal articular surfaces in all 42 cases. The biomechanical study showed that the axial stiffness of LPpLS was in the same fashion as the posterior buttress plate and better than the other fixation methods (P < 0.05). Additionally, the LPpLS group had a smaller displacement of fracture fragments along the X-axis (medial to lateral direction) than the BP group (P < 0.01). CONCLUSIONS: The LPpLS technique could implement good reconstruction of the PLF, showing satisfactory therapeutic effect. The biomechanical evaluation demonstrated that the LPpLS had better stability in three-dimensional directions for PLF than other fixation strategies.


Assuntos
Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Masculino , Feminino , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Tíbia/cirurgia , Placas Ósseas , Fenômenos Biomecânicos
4.
Biophys J ; 121(9): 1610-1618, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35395246

RESUMO

Oscillations and waves are ubiquitous in living cellular systems. Generations of these spatiotemporal patterns are generally attributed to some mechanochemical feedbacks. Here, we treat cells as open systems, i.e., water and ions can pass through the cell membrane passively or actively, and reveal a new origin of wave generation. We show that osmotic shocks above a shock threshold will trigger self-sustained cell oscillations and result in long-range waves propagating without decrement, a phenomenon that is analogous to the excitable medium. The traveling wave propagates along the intercellular osmotic pressure gradient, and its wave speed scales with the magnitude of intercellular water flows. Furthermore, we also find that the traveling wave exhibits several hallmarks of solitary waves. Together, our findings predict a new mechanism of wave generation in living multicellular systems. The ubiquity of intercellular water exchanges implies that this mechanism may be relevant to a broad class of systems.


Assuntos
Água
5.
Biophys J ; 121(23): 4740-4747, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36116008

RESUMO

Touch allows us to gather abundant information in the world around us. However, how sensory cells embedded in the fingers convey texture information into their firing patterns is still poorly understood. Here, we develop an electromechanical model for roughness perception by incorporating main ingredients such as voltage-gated ion channels, active ion pumps, mechanosensitive channels, and cell deformation. The model reveals that sensory cells can convey texture wavelengths into the period of their firing patterns as the finger slides across object surfaces, but they can only convey a limited range of texture wavelengths. We also show that an increase in sliding speed broadens the decoding wavelength range at the cost of reduction of lower perception limits. Thus, a smaller sliding speed and a bigger contact force may be needed to successfully discern a smooth surface, consistent with previous psychophysical observations. Moreover, we show that cells with slowly adapting mechanosensitive channels can still fire action potentials under static loadings, indicating that slowly adapting mechanosensitive channels may contribute to the perception of coarse textures under static touch. Our work thus provides a new theoretical framework to study roughness perception and may have important implications for the design of electronic skin, artificial touch, and haptic interfaces.


Assuntos
Percepção
6.
Biophys J ; 120(11): 2306-2316, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33864788

RESUMO

Many studies have demonstrated that mitotic cells can round up against external impediments. However, how the stiffness of external confinement affects the dynamics of rounding force/pressure and cell volume remains largely unknown. Here, we develop a theoretical framework to study the rounding of adherent cells confined between a substrate and a cantilever. We show that the rounding force and pressure increase exclusively with the effective confinement on the cell, which is related to the cantilever stiffness and the separation between cantilever and substrate. Remarkably, an increase of cantilever stiffness from 0.001 to 1 N/m can lead to a 100-fold change in rounding force. This model also predicts an active role of confinement stiffness in regulating the dynamics of cell volume and hydrostatic pressure. We find that the dynamic changes of cellular volume and hydrostatic pressure after osmotic shocks are opposite if the cantilever is soft, whereas the dynamic changes of cellular volume and pressure are the same if the cantilever is stiff. Taken together, this work demonstrates that confinement stiffness appears as a critical regulator in regulating the dynamics of rounding force and pressure. Our findings also indicate that the difference in cantilever stiffness need to be considered when comparing the measured rounding force and pressure from various experiments.


Assuntos
Mitose , Forma Celular , Tamanho Celular , Células HeLa , Humanos , Pressão Hidrostática
7.
Biophys J ; 120(24): 5521-5529, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34838532

RESUMO

The ability of cells to regulate their shape and volume is critical for many cell functions. How endocytosis and exocytosis, as important ways of membrane trafficking, affect cellular volume regulation is still unclear. Here, we develop a theoretical framework to study the dynamics of cell volume, endocytosis, and exocytosis in response to osmotic shocks and mechanical loadings. This model can not only explain observed dynamics of endocytosis and exocytosis during osmotic shocks but also predict the dynamics of endocytosis and exocytosis during cell compressions. We find that a hypotonic shock stimulates exocytosis, while a hypertonic shock stimulates endocytosis; and exocytosis in turn allows cells to have a dramatic change in cell volume but a small change in membrane tension during hyposmotic swelling, protecting cells from rupture under high tension. In addition, we find that cell compressions with various loading speeds induce three distinct dynamic modes of endocytosis and exocytosis. Finally, we show that increasing endocytosis and exocytosis rates reduce the changes in cell volume and membrane tension under fast cell compression, whereas they enhance the changes in cell volume and membrane tension under slow cell compression. Together, our findings reveal critical roles of endocytosis and exocytosis in regulating cell volume and membrane tension.


Assuntos
Endocitose , Exocitose , Membrana Celular/metabolismo , Endocitose/fisiologia , Exocitose/fisiologia , Membranas , Pressão Osmótica
8.
FASEB J ; 34(7): 8876-8886, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32510740

RESUMO

Autophagy, a macromolecular degradation process, plays a pivotal role in cell differentiation and survival. This study was designed to investigate the role of autophagy in the osteogenic differentiation in ligamentum fibroblasts. Rat ligamentum fibroblasts were isolated from the posterior longitudinal ligament and cultured in osteogenic induction medium. Ultrastructural analysis, immunofluorescence assay, western blot, flow cytometry, and lysosomal activity assessment were performed to determine the presence and activity of autophagy in the cells. The mineralization deposit and osteogenic gene expressions were evaluated to classify the association between autophagy activity and the bone formation ability of the spinal ligament cells. The influence of leptin and endothelin-1 on the autophagy activity was also evaluated. Our study demonstrated that autophagy was present and increased in the ligament cells under osteogenic induction. Inhibition of autophagy with either pharmacologic inhibitors (Bafilomycin A and 3-methyladenine) or Belcin1 (BECN1) knocking down weakened the mineralization capacity, decreased the gene expressions of COL1A1, osteocalcin (Ocn), and runt-related transcription factor 2 (Runx2) in the ligamentum fibroblasts and increased cell apoptosis. The Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-BECN1 autophagic pathway was activated in the osteogenic differentiating ligamentum fibroblasts. Leptin significantly increased the autophagy activity in the ligament cells under osteogenic induction. These discoveries might improve our understanding for the mechanism of ossification of the posterior longitudinal ligament (OPLL) and provide new approaches on the prevention and treatment of this not uncommon disease.


Assuntos
Autofagia , Diferenciação Celular , Fibroblastos/citologia , Ligamentos Longitudinais/citologia , Ossificação do Ligamento Longitudinal Posterior/patologia , Osteogênese , Animais , Células Cultivadas , Fibroblastos/metabolismo , Ligamentos Longitudinais/metabolismo , Masculino , Ossificação do Ligamento Longitudinal Posterior/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
9.
BMC Musculoskelet Disord ; 22(1): 947, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781926

RESUMO

BACKGROUND: The aim of the present study was to investigate the efficacy and safety of mini-open oblique debridement and lumbar interbody fusion combined with lateral screw fixation for treating single-level pyogenic spondylodiscitis. METHODS: Twelve patients with single-level lumbar pyogenic spondylodiscitis underwent OLIF combined with lateral screw fixation were analyzed. Patients underwent follow-up for 12 to 24 months. The clinical characteristics, etiological examinations, operative time, intraoperative blood loss, Oswestry Disability Index (ODI), visual analog scale score (VAS), postoperative complications, and the bony fusion rate were recorded. RESULTS: The mean follow-up period of time was 14.8 months. The average operative time and intra-operative blood loss were 129.0 ± 19.76 min and 309.2 ± 92.96 mL, respectively. No severe intra-operative complications were observed during surgery, except in 1 case that develops abdominal pain and distension after surgery, 2 cases that develop left-sided transient thigh pain/numbness and 8 cases that complains of donor site (iliac crest) pain. All of these symptoms disappeared 8 weeks after surgery. Tissue sample cultures were obtained from all patients intraoperatively and four (33.3%) were positive, including 2 with Staphylococcus aureus, 1 with Staphylococcus epidermidis, and 1 with Escherichia coli. During an average of 22.5 ± 2.1 days (range, 14-29 days) after surgery, WBC, CPR, and ESR levels in all patients had returned to normal. All patients were pain free with no recurring infection. Solid bony fusions were observed in all cases within 6 months, including 10 with I grade fusion, 2 with II grade fusion according to the classification suggested by Burkus et al. No fixation failure was observed during follow up and solid bony fusions were observed in all 12 patients at finally follow-up. A significant postoperative increase was also observed in the mean segmental height and lordosis (P < 0.05), followed by a slight decrease of segmental height and lordosis at final follow-up. At the final follow up, the mean VAS (1.5 ± 0.6) and ODI (18.9 ± 7.6) were significantly lower than VAS (8.4 ± 2.7) and ODI (71.2 ± 16.5) before surgery (P < 0.01). CONCLUSION: Single-stage debridement with autogenous iliac bone graft through the OLIF corridor and lateral fixation was a feasible surgical approach in our consecutive 12 cases of pyogenic spondylitis.


Assuntos
Discite , Fusão Vertebral , Desbridamento , Discite/diagnóstico por imagem , Discite/cirurgia , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
10.
Biophys J ; 119(7): 1427-1438, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32898477

RESUMO

Cell durotaxis is an essential process in tissue development. Although the role of cytoskeleton in cell durotaxis has been widely studied, whether cell volume and membrane tension are implicated in cell durotaxis remains unclear. By quantifying the volume distribution during cell durotaxis, we show that the volume of 3T3 fibroblast cells decreases by almost 40% as cells migrate toward stiffer regions of gradient gels. Inhibiting ion transporters that can reduce the amplitude of cell volume decrease significantly suppresses cell durotaxis. However, from the correlation analysis, we find that durotaxis index does not correlate with the cell volume decrease. It scales with the membrane tension difference in the direction of stiffness gradient. Because of the tight coupling between cell volume and membrane tension, inhibition of Na+/K+ ATPase and Na+/H+ exchanger results in smaller volume decrease and membrane tension difference. Collectively, our findings indicate that the polarization of membrane tension is a central regulator of cell durotaxis, and Na+/K+ ATPase and Na+/H+ exchanger can help to maintain the membrane tension polarity.


Assuntos
Polaridade Celular , Fibroblastos , Células 3T3 , Animais , Movimento Celular , Citoesqueleto , Camundongos , ATPase Trocadora de Sódio-Potássio
11.
J Transl Med ; 18(1): 211, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32456662

RESUMO

BACKGROUND: Lipid abnormality and obesity have been proposed to be associated with lumbar disc degeneration, but little is known about the effect of 'lipid healthy but obese' (LH-O) and 'lipid abnormal but not obese' (LA-NO) phenotypes on lumbar disc degeneration in Chinese. The study aims to determine the impact and distinction of LH-O and LA-NO phenotypes on lumbar disc degeneration in Chinese, and to identify the association of related factors with risk of lumbar disc degeneration. METHODS: A total of 678 individuals were included with lumbar magnetic resonance imaging, serum lipid levels and anthropometric measurements. Obesity was defined on the basis of body mass index or waist to hip ratio (WHR). Pfirrmann score and Weishaupt's scale were utilized to assess the degree of disc degeneration and facet joint degeneration. RESULTS: The incidence of the LH-O and LA-NO phenotypes were 11.4% and 18.1%, respectively. LA-NO phenotype demonstrates a high incidence for disc degeneration (P < 0.05), while LH-O phenotype confers a severe disc degeneration grade (P < 0.05). No statistical difference in the percentage of severe facet joint degeneration grade in each group (P > 0.05). Elevated triglycerides and greater WHR may be the risk factors for lumbar disc degeneration in Chinese. CONCLUSION: LH-O and LA-NO phenotypes are common with different status of disc degeneration in Chinese. Elevated triglycerides and abdominal obesity appear to play crucial roles in the development of lumbar disc degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , China , Humanos , Lipídeos , Vértebras Lombares , Imageamento por Ressonância Magnética , Obesidade/complicações , Fenótipo
12.
Int Orthop ; 44(11): 2357-2363, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32529310

RESUMO

PURPOSE: Previous reports revealed a correlation between psychological problems and spinal surgery. There is a lack of knowledge on the effect of anxiety on the percutaneous transforaminal endoscopic discectomy (PTED) outcome at the two year follow-up. The purpose of this study is to investigate changes in anxiety after PTED among patients with lumbar disc herniation (LDH), to compare the effect of anxiety on the prognosis using propensity score matching analysis, and to identify the related parameters of anxiety. METHODS: A total of 145 patients with LDH requiring PTED surgery were included. Twenty-six LDH patients with anxiety were matched with 26 control patients utilizing propensity score matching analysis. The demographic and peri-operative data were collected and analyzed. A correlation analysis was utilized. RESULTS: Both groups achieved significant improvements in visual analogue scale (VAS) scores for pain, Japanese Orthopedic Association (JOA) scores for neurological deficit, and 36-item Short-Form Health Survey (SF-36) scores and Oswestry Disability Index (ODI) scores for quality of life. A statistical difference was detected between the pre-operative and the post-operative Zung Self-Rating Anxiety Scale scores in the anxiety cohort. However, the difference between the anxiety group and the control group was statistically significant in the aforementioned parameters. The VAS, JOA, ODI and the SF-36 scores, and the disease duration were associated with pre-operative anxiety. CONCLUSION: PTED may provide significant improvements in clinical outcomes and symptoms of anxiety. A negative impact on the patient's prognosis may be caused by the presence of anxiety. Pain severity, neurological deficit, disease duration, and quality of life were associated with anxiety.


Assuntos
Deslocamento do Disco Intervertebral , Qualidade de Vida , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Discotomia , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Medição da Dor , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
13.
Biophys J ; 114(3): 675-687, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29414713

RESUMO

The mechanical and physical properties of substrate play a crucial role in regulating many cell functions and behaviors. However, how these properties affect cell volume is still unclear. Here, we show that an increase in substrate stiffness, available spread area, or effective adhesion energy density results in a remarkable cell volume decrease (up to 50%), and the dynamic cell spreading process is also accompanied by dramatic cell volume decrease. Further, studies of ion channel inhibition and osmotic shock suggest that these volume decreases are due to the efflux of water and ions. We also show that disrupting cortex contractility leads to bigger cell volume. Collectively, these results reveal the "mechanism of adhesion-induced compression of cells," i.e., stronger interaction between cell and substrate leads to higher actomyosin contractility, expels water and ions, and thus decreases cell volume.


Assuntos
Actomiosina/fisiologia , Adesão Celular , Tamanho Celular , Citoesqueleto/metabolismo , Mecanotransdução Celular , Fenômenos Físicos , Tensoativos/metabolismo , Células 3T3 , Animais , Movimento Celular , Células HeLa , Humanos , Canais Iônicos/metabolismo , Transporte de Íons , Células MCF-7 , Camundongos , Especificidade por Substrato
14.
Clin Endocrinol (Oxf) ; 86(2): 263-269, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27581500

RESUMO

OBJECTIVE: The use of thyrotropin (TSH) in the initial assessment of thyroid nodules is inefficient and leads to unnecessary assessment costs. We compared the total costs of thyroid nodule assessment with or without the use of TSH in the initial assessment. METHODS: A total of 1808 patients with thyroid nodules received TSH, fine-needle aspiration (FNA) and thyroid scintigraphy (TS) assessment, including 83 autonomously functioning thyroid nodule (AFTN) cases and 1725 non-AFTN cases. The total costs of the TSH strategy and non-TSH strategies were compared. The ratio of single-use costs of FNA to TS (CFNA/TS ) was used as the main outcome measure. RESULTS: Only when 6·03 ≤ CFNA/TS ≤ 27·17, the lowest total costs were associated with using the conventional TSH strategy. When CFNA/TS <6·03 or CFNA/TS >27·17, the lowest costs were found with FNA and TS, respectively. CONCLUSION: From the perspective of cost economics, in iodine-sufficient areas, we recommend that the decision on the use of TSH for the initial assessment of thyroid nodules should be based on the testing costs of FNA and TS in that medical unit.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/economia , Tireotropina/administração & dosagem , Biópsia por Agulha Fina , Custos e Análise de Custo , Tomada de Decisões , Feminino , Humanos , Masculino , Curva ROC , Cintilografia/economia , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireotropina/economia
15.
Phys Rev Lett ; 118(20): 208102, 2017 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-28581769

RESUMO

Cell adhesion is an essential biological process. However, previous theoretical and experimental studies ignore a key variable, the changes of cellular volume and pressure, during the dynamic adhesion process. Here, we treat cells as open systems and propose a theoretical framework to investigate how the exchange of water and ions with the environment affects the shape and dynamics of cells adhered between two adhesive surfaces. We show that adherent cells can be either stable (convex or concave) or unstable (spontaneous rupture or collapse) depending on the adhesion energy density, the cell size, the separation of two adhesive surfaces, and the stiffness of the flexible surface. Strikingly, we find that the unstable states vanish when cellular volume and pressure are constant. We further show that the detachments of convex and concave cells are very different. The mechanical response of adherent cells is mainly determined by the competition between the loading rate and the regulation of the cellular volume and pressure. Finally, we show that as an open system the detachment of adherent cells is also significantly influenced by the loading history. Thus, our findings reveal a major difference between living cells and nonliving materials.


Assuntos
Adesão Celular , Água/química , Íons/química , Modelos Teóricos , Pressão
16.
Tumour Biol ; 37(4): 4679-88, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26511968

RESUMO

The growth of solid tumors requires angiogenesis to provide oxygen and nutrients and to support cell proliferation. The switch from an avascular to a vascular phenotype is typically related to acceleration of tumor growth. Anti-angiogenic therapy is becoming a very promising way for malignant tumors. Meanwhile, malignant tumor cells themselves were able to develop the formation of cell-lined vessels that contribute to tumor neovascularization and supply the nutrients and oxygen, which is called vasculogenic mimicry (VM). However, the molecular mechanism of VM remains unclear. The purpose of this study was to investigate the efficacy of the novel recombinant human endostatin (rh-Endo) protein combined with radiotherapy on human esophageal squamous cell carcinoma (ESCC) cell lines Eca-109 and TE13. Our results showed that rh-Endo combined with radiotherapy significantly inhibited the proliferation, migration, invasion, and VM of human esophageal cancer cells in a dose-dependent manner; however, it has no direct effect on apoptosis of carcinoma cells, which indicated that rh-Endo combined with radiotherapy significantly changed the microenvironment of esophageal carcinoma, and played an important role in preventing distant metastasis. Our findings suggested that rh-Endo inhibited the metastasis of esophageal cancer and the activation of AKT pathway, and the down-regulation of epithelial-mesenchymal transition (EMT) may be associated with such effect of rh-Endo. These results also supported the bright prospect of rh-Endo combined with radiotherapy for clinical applications in the future.


Assuntos
Carcinoma de Células Escamosas/terapia , Endostatinas/farmacologia , Neoplasias Esofágicas/terapia , Neovascularização Patológica/terapia , Radiossensibilizantes/farmacologia , Apoptose , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células , Quimiorradioterapia , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/patologia , Humanos , Concentração Inibidora 50 , Tolerância a Radiação/efeitos dos fármacos , Transdução de Sinais
17.
Tumour Biol ; 37(2): 1853-62, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26318432

RESUMO

Radiotherapy is a widespread treatment in human solid tumors. However, therapy resistance and poor prognosis are still problems. Gambogic acid (GA), extracted from the dried yellow resin of gamboges, has an anticancer effect against various types of cancer cells. To explore the radiosensitivity of GA on esophageal cancer cell line TE13, cell viability was tested by Cell Counting Kit-8 (CCK-8) assay, colony formation assay was used to assess the effects of GA on the radiosensitivity of TE13, and flow cytometry was performed to meter the percentage of apoptosis. The protein levels of microtubule-associated protein 1 light chain 3 (LC3), caspase3, caspase8, casepase9, pAkt, and p-mammalian target of rapamycin (p-mTOR) were tested using Western blot. The distribution of LC3 was detected by immunofluorescence. Additionally, we also examined reactive oxygen species (ROS) expression by laser scanning confocal microscope (LSCM). The cells were transfected with adenovial vector to monitor the autophagy through the expression of green fluorescent protein (GFP-red fluroscent protein (RFP)-LC3. The rates of apoptotic cells in combined-treated TE13 increased significantly compared with the control groups in accordance with the results of Western blot. The clonogenic survival assay showed that GA enhances radiosensitivity with a sensitizing enhancement ratio (SER) of 1.217 and 1.436 at different concentrations. The LC3-II protein level increased in the combined group indicating the increase of autophagy incidence, and the results of GFP-RFP-LC3 experiment showed that GA may block the process of autophagic flux in TE13 cells. Moreover, we successfully demonstrated that ROS is involved in the induction of autophagy. ROS-mediated autophagy depends on the inhibition of the Akt/mTOR pathway. Taken together, GA induced radiosensitivity involves autophagy and apoptosis which are regulated by ROS hypergeneration and Akt/mTOR inhibition.


Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Xantonas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspases/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/metabolismo , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
18.
Tumour Biol ; 36(6): 4079-87, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25946972

RESUMO

Autophagy differs from apoptosis and is independent of phagocytes by the appearance of autophagosomes, autolysosomes, and complete nuclei in the cell. This process significantly contributes to the antineoplastic effects of radiation. Radiation is an important strategy in cancer treatment; however, many types of cancer show radioresistance. The effects of radiotherapy are affected by factors, including the degree of tumor tissue hypoxia, the ability to repair DNA damage, and the presence of cancer stem cells. We review the relationships among autophagy, the three factors in cancer radiation, and the possible underlying molecular mechanisms. The therapeutic implications of these relationships and mechanisms in clinical settings are also discussed.


Assuntos
Autofagia/genética , Dano ao DNA/genética , Neoplasias/radioterapia , Tolerância a Radiação/genética , Apoptose/genética , Hipóxia Celular/genética , Humanos , Neoplasias/genética , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia
19.
Med Sci Monit ; 21: 2339-44, 2015 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-26258995

RESUMO

BACKGROUND: To investigate the in vitro inhibitory effects of PEI-RGD/125I-(αv)ASODN (PEI, polyethylenimine; RGD, Arg-Gly-Asp; ASODN, antisense oligodeoxynucleotide) on the growth and invasion of HepG2 cells. MATERIAL AND METHODS: ASODN of the integrin αv-subunit was marked with 125I and underwent complexation with PEI-RGD, a PEI derivative. Next, PEI-RGD/125I-(αv) ASODN was introduced into HepG2 cells via receptor-mediated transfection, and its inhibition rate on HepG2 cell growth was tested using the methyl thiazolyl tetrazolium (MTT) method. The effects of PEI-RGD/125I-(αv) ASODN on HepG2 cell invasion ability were evaluated using the Boyden chamber assay. RESULTS: 1) The 125I marking rate of (αv) ASODN was 73.78±4.09%, and the radiochemical purity was 96.68±1.38% (greater than 90% even after a 48-h incubation period at 37°C), indicating high stability. 2) The cytotoxicity assays showed that the cell inhibition rates did not differ significantly between the PEI-RGD/125I-(αv)ASODN group and the PEI-RGD/(αv) ASODN group, but they were both significantly higher than in the other groups and were positively correlated (r=0.879) with the dosage within a certain range. 3) The invasion assays showed that the inhibition rate was significantly greater in the PEI-RGD/125I-(αv) ASODN group compared to the other groups. CONCLUSIONS: PEI-RGD/125I-(αv) ASODN can efficiently inhibit the growth and proliferation of HepG2 cells and can also weaken their invasive ability.


Assuntos
Integrina alfaV/genética , Radioisótopos do Iodo/administração & dosagem , Oligodesoxirribonucleotídeos Antissenso/administração & dosagem , Oligodesoxirribonucleotídeos Antissenso/genética , Oligopeptídeos/administração & dosagem , Polietilenoimina/análogos & derivados , Sequência de Bases , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Células Hep G2 , Humanos , Invasividade Neoplásica , Polietilenoimina/administração & dosagem
20.
Eur J Orthop Surg Traumatol ; 25(1): 53-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24253957

RESUMO

PURPOSE: The optimal surgical procedure for displaced extra-articular distal tibia fractures remains debated at present. The objective of this systematic review is to compare the complications and functional outcomes of this type of fracture after plate fixation and intramedullary nailing . METHODS: A computer-aided search of PubMed, Embase and Cochrane was carried out on July, 2012. Two independent reviewers screened and assessed abstracts. Every study published in English about the comparison between plate fixation and intramedullary nailing for displaced extra-articular distal tibia fractures was included. The outcomes were pooled or summarized separately per study according to heterogeneity between studies. Pooled risk ratios (RR) with 95 % confidence intervals (95 % CIs) were calculated by Mantel-Haenszel method using either the fixed effects model or random effects model. RESULTS: Eight studies, with 270 patients in the intramedullary nailing and 217 patients in the plates fixation group, met the inclusion criteria. Functional outcome, days of hospital stay and time for bone union were comparable between intramedullary fixation and plate fixation. Total complication rate was significant higher for intramedullary nailing compared with plate fixation (44.5 vs. 25.8 %, P < 0.001). Similarly, the rate of minor complications was higher for intramedullary nailing than that for plate fixation (35.9 vs. 21.2 % P < 0.001). Major complication rate was 8.52 % for intramedullary nailing and 4.6 % for plate fixation, but the difference had no statistical significance (P = 0.06). Our pooled estimates showed a decreased risk of total complication in plate fixation (RR, 2.38; 95 % CI, 1.13-5.03; P = 0.02). Among these complications, malunion and anterior knee pain were more common in intramedullary nailing than in plate fixation (20.1 vs. 4.5 %, P < 0.001; 4.2 vs. 0.45 %, P = 0.02, respectively). Meanwhile, significantly less wound problems happened in intramedullary nailing than in plate fixation (2.9 vs. 7.5 %, P = 0.03). In addition, locking plate fixation with mini-invasive technique tended to have a lower complication rate than conventional plate fixation, although the difference was not significant (21 vs. 28.4 %, P = 0.26). CONCLUSIONS: The results of this systematic review suggested that plate fixation, especially minimally invasive percutaneous plating osteosynthesis technique would be preferred for extra-articular distal tibia fractures because of its low complication rate. Nevertheless, intramedullary fixation should be taken priority for distal tibia fractures with serious soft tissue injuries.


Assuntos
Placas Ósseas/efeitos adversos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas da Tíbia/cirurgia , Artralgia/etiologia , Fraturas Mal-Unidas/etiologia , Humanos , Articulação do Joelho , Tempo de Internação , Fatores de Tempo , Resultado do Tratamento , Cicatrização
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