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1.
J Reconstr Microsurg ; 39(7): 540-548, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36577496

RESUMO

BACKGROUND: One of the most challenging yet common areas in reconstructive surgery is the closure of defects in the lower leg. Surgeons can choose from several reconstructive options including local and free flaps. The aim of this study was to understand the reconstructive strategy for lower leg defects of different microsurgeons around the world by harnessing the power of social media and online questionnaires. METHODS: A case of a patient with an exposed plate over distal tibial fracture was presented via an online questionnaire distributed on various social media platforms. A total of 369 international microsurgeons replied with their preferred treatment choice. The data were analyzed according to geographic area, microsurgical training, seniority, and subspecialty. RESULTS: Among all the respondents (n = 369), 64% would have opted for a free flap reconstruction, while the remaining 36% would have opted for a local/pedicle flap. In the group that would have opted for a free flap, 63% would reconstruct the defect using a free fasciocutaneous flap, while the remaining 37% would have used a free muscle flap. In the local flap group, 60% would have used a local perforator while 30% would have chosen a conventional local flap. While North American and European microsurgeons had a clear preference toward free flaps, Asian, Middle Eastern, African, and South American surgeons were evenly divided between local and free flaps. CONCLUSION: In this study, we provide a current global overview of the reconstructive strategies for a lower limb with skin defect and bone or prosthesis exposure. We hope that this will be able to help global microsurgeons and patients worldwide.


Assuntos
Retalhos de Tecido Biológico , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Retalhos de Tecido Biológico/cirurgia , Tíbia/cirurgia , Perna (Membro)/cirurgia , Inquéritos e Questionários , Retalho Perfurante/cirurgia
2.
J Reconstr Microsurg ; 36(6): 412-419, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32110823

RESUMO

BACKGROUND: This study aimed to determine if International Microsurgery Club (IMC) is an effective online resource for microsurgeons worldwide, in providing an avenue for timely group discussions and advice regarding complicated cases, and an avenue for collaboration and information sharing. METHODS: All posts on the IMC Facebook group from member 1 to 8,000 were analyzed according to inclusion criteria and categorized into three categories-case discussion, question, and information sharing. Posts were retrospectively analyzed for number of responses, time of responses, number of "likes," number of treatment options, time of day, and demographics of authors and responders. RESULTS: A retrospective analysis of 531 cases showed an average response rate of 75.7% within 1 hour and as membership grew. The response rate stabilized averaging between 72.5 and 78% across all times of the day. An average of 11.8 microsurgeons was involved per case discussion, and 5.7 treatment options were provided per case. CONCLUSION: IMC is shown to be an effective resource to allow microsurgeons to access timely advice from other microsurgeons without time and distance limitation, and to have interactive group discussions on complicated cases.


Assuntos
Microcirurgia , Mídias Sociais , Humanos , Estudos Retrospectivos
3.
J Reconstr Microsurg ; 36(4): 301-310, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32023640

RESUMO

BACKGROUND: Replantation of a single digit at the distal phalanx level is not routinely performed since it is technically challenging with questionable cost-effectiveness. The purpose of this study was to analyze international microsurgeons' clinical decisions when faced with this common scenario. METHODS: A survey of a right-middle finger distal phalanx transverse complete amputation case was conducted via online and paper questionnaires. Microsurgeons around the world were invited to provide their treatment recommendations. In total, 383 microsurgeons replied, and their responses were stratified and analyzed by geographical areas, specialties, microsurgery fellowship training, and clinical experiences. RESULTS: Among 383 microsurgeons, 170 (44.3%) chose replantation as their preferred management option, 137 (35.8%) chose revision amputation, 62 (16.2%) chose local flap coverage, 8 (2.1%) chose composite graft, and 6 (1.6%) favored other choices as their reconstruction method for the case study. Microsurgeons from the Asia-Pacific, Middle East/South Asia, and Central/South America regions tend to perform replantation (70.7, 68.8, and 67.4%, respectively) whereas surgeons from North America and Europe showed a lower preference toward replantation (20.5 and 26.8%, respectively p < 0.001). Having completed a microsurgery fellowship increased the attempt rate of replantation by 15.3% (p = 0.004). Clinical experience and the surgeons' specialties did not show statistical significance in clinical decision making. CONCLUSION: From the present study, the geographic preferences and microsurgery fellowship experience influence the method of reconstruction for distal phalanx amputation. Multiple factors are taken into consideration in selecting the most suitable reconstructive method for each case scenario. In addition to the technical challenges of the proposed surgery, the cost of the procedure and the type of facility needed are important variables in the decision making process.


Assuntos
Amputação Traumática/cirurgia , Traumatismos dos Dedos/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Reimplante/métodos , Tomada de Decisões , Humanos , Microcirurgia , Retalhos Cirúrgicos , Inquéritos e Questionários
4.
J Reconstr Microsurg ; 35(6): 452-461, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30759488

RESUMO

BACKGROUND: Medical conferences are forums for research, continuing medical education, and networking. Social media is increasingly used for communication and networking due to its low cost and ability to overcome large distances. This study investigates the impact that social media brings to the current conference system. METHODS: There are three parts of this study: (1) comparing two similar brachial plexus injuries (BPIs) courses without (2009) and with (2017) social media support, and the participants' feedback; (2) sharing our experiences in the management of the 2018 International Course on SuperMicrosurgery (ICSM) conference; and (3) evaluating the studies from the social media platform International Microsurgery Club (IMC), for the consensus pertaining to social media and conference system. RESULTS: With the help of social media, international attendance increased during the 2017 BPI conference compared with the 2009 BPI course (25 nationalities in 2009 vs. 35 in 2017). At least 23% obtained their meeting information through social media. Live surgery was the overall main attraction (79%). The 2018 ICSM meeting revealed that video posts increased attendance; videos that were the most effective in attracting (viewership) were either short or pertained to surgical procedures. Facebook, Messenger, and WeChat smartphone applications were effective for immediate communication and troubleshooting among the participants. From the IMC polls, 78% believe that the social media and the conference complemented each other. 97% attended the conference to update their skills and knowledge. CONCLUSION: Social media is a quick and economic tool in promoting medical conferences and instant messenger systems offer immediate communication amongst associates. Despite the popularity of social media, the conference still has its irreplaceable role. The combination of the conference and the social media enhances the training and education of microsurgeons.


Assuntos
Congressos como Assunto , Microcirurgia , Mídias Sociais , Humanos
5.
J Reconstr Microsurg ; 34(6): 413-419, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29396982

RESUMO

BACKGROUND: The best reconstructive strategy for upper lip defects is still in debate. The purpose of this study was to analyze the decisions made by international microsurgeons, who were participated through online questionnaire, distributed by email and social media network. MATERIALS AND METHODS: A case of a two-thirds upper lip oncologic defect was presented via an online questionnaire and 402 microsurgeons replied their treatment options. The data were then analyzed according to the geographic area, microsurgical fellowship, seniority, and subspecialty. All the data were analyzed using SPSS 22. RESULTS: A total of 27.7% of microsurgeons chose a free flap, while 72.3% chose a local/pedicle flap as their preferred method for reconstruction. The most common choice of free and local/pedicle flaps was radial forearm (73.6%) and Abbé (36.2%), respectively. The microsurgeons in Europe preferred local/pedicle flaps than free flap when compared with Middle/South America, Asia-Pacific, Africa and South Asia/Middle East (11.6% versus 50%, 43.4%, 29.3% and 27.3%, respectively, multivariant p < 0.05). The microsurgeons with microsurgical fellowships preferred to use free flaps (32.9% versus 17.5%, multivariant p = 0.021). There was no difference for the seniority and specialty of the microsurgeons. CONCLUSIONS: The online questionnaire is valuable and feasible for obtaining experts' opinions. This study provides a current global overview of surgical preferences for this common complicated clinical scenario.


Assuntos
Neoplasias Labiais/cirurgia , Microcirurgia/métodos , Procedimentos de Cirurgia Plástica/métodos , Mídias Sociais/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Retalhos Cirúrgicos , Atitude do Pessoal de Saúde , Antebraço , Pesquisas sobre Atenção à Saúde , Humanos , Neoplasias Labiais/fisiopatologia , Reprodutibilidade dos Testes , Retalhos Cirúrgicos/transplante
6.
Ann Plast Surg ; 78(3 Suppl 2): S37-S40, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28166136

RESUMO

Compared with upper extremity injuries, toe amputations and their replantations are rare because of the difficulty of their relatively thinner soft tissue envelope. Consequently, fewer reconstructive options are available for toes and they are rarely reported in the literature. In this study, we reported a case of right third to fifth toe amputations and their subsequent reconstruction with iliac bone grafts and a free anterolateral thigh flap. After serial debulking and division procedures, 3 toes were divided successfully. Ten months after the initial operation, the patient regained pain-free functional ambulation despite some bone resorption noted on follow-up radiographs. The patient showed high satisfaction on her new toes in terms of aesthetical and functional outcomes. She was able to stand for over 30 minutes without pain. At the 2-year follow-up, the Foot Function Index was 18.3%. Although toe reconstruction is frequently considered unnecessary because of its relative high demand of surgical techniques and little gain on gait; nonetheless, in selected cases, toe reconstruction may still be beneficial if the metatarsophalangeal joints were intact and there is a strong individual desire for aesthetical restoration.


Assuntos
Retalhos de Tecido Biológico , Ílio/transplante , Procedimentos de Cirurgia Plástica/métodos , Dedos do Pé/lesões , Dedos do Pé/cirurgia , Adulto , Feminino , Humanos , Coxa da Perna/cirurgia
9.
Plast Reconstr Surg ; 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37257149

RESUMO

BACKGROUND: The present study evaluated the three-dimensional changes of the pharyngeal airway after orthognathic surgery (OGS) in patients with unilateral and bilateral clefts, and in unilateral cleft patients with and without pharyngeal flap (PF). METHODS: Forty-five patients with unilateral or bilateral clefts receiving OGS were enrolled. Cone-beam computed tomography images were obtained before (T0) and after (T1) OGS. We measured the pharyngeal airway volumes, minimal cross-sectional area, and the horizontal displacement of facial landmarks. RESULTS: The patients with bilateral cleft exhibited smaller initial velopharyngeal volume (unilateral: 8623 mm 3; bilateral: 7781 mm 3; p = 0.211), while the velopharyngeal volume increased significantly with median of 744 mm 3 after OGS (p = 0.031). The median horizontal displacement of A point was 2.9 and 2.6 mm among the patients with unilateral and bilateral clefts, respectively (p = 0.276), and the median horizontal displacement of B point was -2.9 and -3.3 mm among patients with unilateral and bilateral clefts, respectively (p = 0.618). The unilateral cleft patients with PF exhibited lower initial velopharyngeal volume (PF+: 7582 mm 3; PF-: 8756 mm 3; p = 0.129) and a lower increase in velopharyngeal volume (PF+: 437 mm 3; PF-: 627 mm 3; p = 0.739) after OGS. CONCLUSIONS: Midface hypoplasia and the decrease in the velopharyngeal volume were more prominent among the bilateral cleft patients and the unilateral cleft patients with PF. After OGS, the velopharyngeal volume considerably increased among the bilateral cleft patients, but no considerable differences were noted among the unilateral cleft patients with PF.

10.
Arch Plast Surg ; 48(6): 660-669, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34818714

RESUMO

BACKGROUND: The demand for aesthetic procedures continues to grow globally, particularly in East Asian countries. The popularity of specific aesthetic procedures varies, however, depending on the particular East Asian geographical region being studied. This study aimed to evaluate the experiences of and attitudes toward aesthetic procedures in five East Asian countries/regions, including China, Japan, South Korea, Hong Kong, and Taiwan. METHODS: To recruit participants, an online questionnaire was designed and distributed on social media networks between May 2015 and March 2016. The statistical analysis was conducted using SPSS software, version 22.0. RESULTS: A total of 3,088 people responded (approximately 600 in each country/region). Of these, 940 participants (47.8%) responded that they had experienced at least one aesthetic procedure in the past. Taiwan had the highest number of participants who had experienced at least one procedure (264/940, 41%), with primarily non-surgical experiences. Only in South Korea did surgical cosmetic experiences exceed non-surgical cosmetic experiences (55.9% vs. 44.1%). The popularity of particular procedures and the motivation for undergoing aesthetic procedures varied by country. CONCLUSIONS: The popularity of aesthetic procedures continues to evolve. Similar trends were observed across the East Asian regions; however, each country had its unique demands and preferences. The information provided by this study can help aesthetic plastic surgeons further understand the patients in their corresponding region, customize their practice, and develop the requisite skills.

11.
Plast Reconstr Surg ; 143(1): 221e-233e, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30286043

RESUMO

The presence of online learning resources has grown tremendously in recent years. They provide powerful and yet easily accessible means of learning and sharing knowledge. Online learning resources now encompass all aspects of medicine, and microsurgery is no exception. International Microsurgery Club is a closed, invitation-only group based on the Facebook social media platform. It was initiated on May 6, 2016, with the primary objectives of providing a convenient forum for discussing challenging cases, sharing valuable resources, and providing opportunities for research collaboration. The membership of International Microsurgery Club has grown to over 8700 at 2 years' existence, and continues to expand. International Microsurgery Club has become one of the largest online platforms for global microsurgeons. Here, the authors share their experience on how to establish a successful online platform for medical education.


Assuntos
Competência Clínica , Educação a Distância/organização & administração , Educação Médica/métodos , Microcirurgia/educação , Feminino , Humanos , Internacionalidade , Masculino , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Mídias Sociais , Sociedades Médicas
12.
Artigo em Inglês | WPRIM | ID: wpr-939145

RESUMO

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

13.
PLoS One ; 12(2): e0171570, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28182639

RESUMO

INTRODUCTION: Oncological resection of the tongue can be reconstructed using a multitude of free flaps. The medial sural artery perforator (MSAP) flap has been well described in the literature in terms of its anatomy and harvest. However, functional outcome studies of post-reconstruction tongue defects using the MSAP flap have not been reported. This study represents the largest outcome study of patients with tongue reconstructions using MSAP flaps and a comprehensive review of its use. MATERIALS AND METHODS: From December of 2010 to October of 2015, 579 patients with subtotal glossectomy and free flap reconstructions in Chang Gung Memorial Hospital were retrospectively reviewed. 27 patients were reconstructed with MSAP flap. The pre- and intra-operative factors, as well as flap-related factors were analyzed. Post-operative complications and functional outcomes were evaluated. Donor site assessment were also conducted. RESULTS: A 96.3% flap survival rate was found with an average total operating time of 6 hours and 18 minutes. 84.6% of patients had primary closure of the donor site with and the remaining either had skin grafts or delayed closure. Donor site closure can be achieved primarily with no functional deficit. Speech intelligibility remained for most patients. 100% of patients resumed normal oral feeding. CONCLUSION: The MSAP flap is a small to medium sized flap most suited for subtotal glossectomy defects where optimal outcomes can be achieved in terms of speech clarity and restoration of oral intake.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Glossectomia/efeitos adversos , Retalho Perfurante/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias , Neoplasias da Língua/cirurgia , Adulto , Artérias/cirurgia , Feminino , Glossectomia/instrumentação , Glossectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos , Língua/irrigação sanguínea , Língua/cirurgia
14.
Artigo em Inglês | WPRIM | ID: wpr-919432

RESUMO

BACKGROUND@#Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells.@*METHODS@#Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM.@*RESULTS@#BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family.@*CONCLUSION@#BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

15.
Artigo em Inglês | WPRIM | ID: wpr-742449

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.


Assuntos
Animais , Humanos , Camundongos , Apoptose , Bisbenzimidazol , Bleomicina , Pontos de Checagem do Ciclo Celular , Ciclo Celular , Linhagem Celular , Sobrevivência Celular , Citocinas , Ensaio de Imunoadsorção Enzimática , Células Epiteliais , Expressão Gênica , Genes vif , Fibrose Pulmonar Idiopática , Interleucina-6 , Pulmão , Propídio , RNA Mensageiro , Fatores de Crescimento Transformadores , Fator de Necrose Tumoral alfa
16.
Artigo em Inglês | WPRIM | ID: wpr-785832

RESUMO

BACKGROUND AND OBJECTIVES: Perivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated.METHODS AND RESULTS: In this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1β in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation.CONCLUSIONS: Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.


Assuntos
Animais , Humanos , Camundongos , Fatores Biológicos , Medula Óssea , Estresse do Retículo Endoplasmático , Inflamassomos , Inflamação , Macrófagos , Macrófagos Peritoneais , Células-Tronco Mesenquimais , Peritonite , Inibidor 1 de Ativador de Plasminogênio , Espécies Reativas de Oxigênio , Células-Tronco
17.
Artigo em Inglês | WPRIM | ID: wpr-764060

RESUMO

BACKGROUND AND OBJECTIVES: Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet well understood. METHODS: BM cells were harvested from femurs of mice and analyzed using flow cytometry. Human PVCs were cultured in serum-free α-MEM. After 24hrs, PVC-CM was collected and filtered through a 0.22 μm filter. RESULTS: In this study, we showed that hyperglycemia alters hematopoietic composition in the BM, which can partially be restored via paracrine mechanisms, including perivascular cells (PVCs) and NADPH oxidase (NOX) inhibition in mice with streptozotocin-induced diabetes. Prolonged hyperglycemic conditions resulted in an increase in the frequency and number of long-term hematopoietic stem cells as well as the number of total BM cells. The altered hematopoiesis in the BM was partially recovered by treatment with PVC-derived conditioned medium (CM). Long-term diabetes also increased the number of myeloid-derived suppressor cells in the BM, which was partially restored by the administration of PVC-CM and diphenyleneiodonium (DPI), a NOX inhibitor. We further showed the downregulation of ERK and p38 phosphorylation in BM cells of diabetic mice treated with PVC-CM and DPI. This may be associated with dysfunction of hematopoietic cells and promotion of subsequent diabetic complications. CONCLUSIONS: Our data suggested that alterations in BM hematopoietic composition due to prolonged hyperglycemic conditions might be restored by improvement of the hematopoietic microenvironment and modulation of NOX activity.


Assuntos
Animais , Humanos , Camundongos , Medula Óssea , Meios de Cultivo Condicionados , Complicações do Diabetes , Regulação para Baixo , Fêmur , Citometria de Fluxo , Hematopoese , Células-Tronco Hematopoéticas , Hiperglicemia , NADP , NADPH Oxidases , Fosforilação
18.
Artigo em Inglês | WPRIM | ID: wpr-763034

RESUMO

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.


Assuntos
Animais , Humanos , Camundongos , Actinas , Permeabilidade Capilar , Corioide , Neovascularização de Coroide , Claudina-5 , Células Endoteliais , Endotélio , Degeneração Macular , Óxido Nítrico Sintase Tipo III , Permeabilidade , Fosforilação , Receptores de Fatores de Crescimento do Endotélio Vascular , Retinaldeído , Fator A de Crescimento do Endotélio Vascular
19.
Artigo em Inglês | WPRIM | ID: wpr-649837

RESUMO

Pluripotent stem cells (PSCs) are a useful source of cells for exploring the role of genes related with early developmental processes and specific diseases due to their ability to differentiate into all somatic cell types. Recently, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein 9 system has proven to be a robust tool for targeted genetic modification. Here, we generated miR-451-deficient PSCs using the CRISPR/Cas9 system with PCR-based homologous recombination donor and investigated the impact of its deletion on self-renewal and hematopoietic development. CRISPR/Cas9-mediated miR-451 knockout did not alter the gene expressions of pluripotency, cellular morphology, and cell cycle, but led to impaired erythrocyte development. These findings propose that a combination of PSCs and CRISPR/Cas9 system could be useful to promote biomedical applications of PSCs by elucidating the function and manipulating of specific miRNAs during lineage specification and commitment.


Assuntos
Animais , Humanos , Camundongos , Ciclo Celular , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Eritrócitos , Expressão Gênica , Hematopoese , Recombinação Homóloga , MicroRNAs , Células-Tronco Embrionárias Murinas , Células-Tronco Pluripotentes , Doadores de Tecidos
20.
Artigo em Inglês | WPRIM | ID: wpr-727974

RESUMO

We investigated the inhibitory effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K⁺ (Kv) channels in freshly separated from rabbit coronary arterial smooth muscle cells. The application of escitalopram rapidly inhibited vascular Kv channels. Kv currents were progressively inhibited by an increase in the concentrations of escitalopram, suggesting that escitalopram inhibited vascular Kv currents in a concentration-dependent manner. The IC₅₀ value and Hill coefficient for escitalopram-induced inhibition of Kv channels were 9.54±1.33 µM and 0.75±0.10, respectively. Addition of escitalopram did not alter the steady-state activation and inactivation curves, suggesting that the voltage sensors of the channels were not affected. Pretreatment with inhibitors of Kv1.5 and/or Kv2.1 did not affect the inhibitory action of escitalopram on vascular Kv channels. From these results, we concluded that escitalopram decreased the vascular Kv current in a concentration-dependent manner, independent of serotonin reuptake inhibition.


Assuntos
Citalopram , Vasos Coronários , Músculo Liso , Miócitos de Músculo Liso , Serotonina
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