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1.
Front Mol Neurosci ; 17: 1384764, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742227

RESUMO

Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the SLC26A4 gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in Slc26a4-deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38749719

RESUMO

An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.


Assuntos
Carcinoma de Células Escamosas , Achados Incidentais , Neoplasias Pulmonares , Pericárdio , Pneumonectomia , Humanos , Masculino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pneumonectomia/efeitos adversos , Pericárdio/transplante , Idoso de 80 Anos ou mais , Resultado do Tratamento , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Toracotomia , Tomografia Computadorizada por Raios X , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/diagnóstico por imagem , Estadiamento de Neoplasias
3.
J Cardiol ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38490639

RESUMO

BACKGROUND: The ratio of early diastolic mitral inflow velocity to mitral annular velocity (E/e') is a prognostic factor in patients with ST-segment elevation myocardial infarction (STEMI). However, data are lacking on long-term outcomes and longitudinal changes in E/e' in patients with preserved left ventricular ejection fraction (LVEF) in the reperfusion era. METHODS: This is a pre-specified echocardiographic substudy of a randomized controlled trial evaluating the efficacy of beta-blockers in STEMI patients with LVEF ≥40 % after primary percutaneous coronary intervention (PCI). Patients were divided into 2 groups according to E/e' at discharge: ≤14 (normal E/e' group) or > 14 (high E/e' group). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, acute coronary syndrome, and heart failure hospitalization. We also assessed longitudinal changes in E/e' and conducted a landmark analysis using E/e' at 1 year after STEMI. RESULTS: There were 173 and 38 patients in the normal and high E/e' groups, respectively. During a median follow-up of 3.9 years, the primary outcome occurred in 19 patients (11.0 %) and 10 patients (26.3 %) in the normal and high E/e' groups, respectively. The cumulative incidence of the primary outcome was higher in the high E/e' group than in the normal E/e' group (21.9 % vs. 7.1 % at 3 years; log-rank p = 0.013). E/e' in the high E/e' group decreased over time (p < 0.001), but remained higher than in the normal E/e' group at 1 year after STEMI (13.7 ±â€¯5.3 vs. 8.6 ±â€¯2.3, p < 0.001). E/e' > 14 at 1 year was also associated with poor outcomes (log-rank p = 0.008). A sensitivity analysis using multivariate Cox proportional hazards regression models yielded consistent results. CONCLUSION: High E/e' at discharge is associated with poor long-term outcomes in STEMI patients with preserved LVEF after primary PCI, which may be explained by persistent high E/e' late after STEMI.

4.
Surg Today ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546862

RESUMO

PURPOSE: To investigate the clinical characteristics of lung cancer that develops after kidney transplantation. METHODS: The clinical data of patients with lung cancer diagnosed after kidney transplantation were collected retrospectively. The medical records were extracted from our database. All patients underwent routine chest examination after kidney transplantation. RESULTS: In total, 17 lung tumors were detected in 15 (0.6%) of 2593 patients who underwent kidney transplantation at our institution. Eleven lung tumors were completely resected from a collective 10 patients (surgical group). The remaining five patients did not receive surgical treatment (nonsurgical group). The surgical group underwent wedge resection (n = 5), segmentectomy (n = 1), lobectomy (n = 3), and bilobectomy (n = 1). The pathological stages were 0 (n = 1), IA1 (n = 2), IA2 (n = 4), IA3 (n = 2), and IB (n = 1). The surgical group had a significantly better prognosis than the nonsurgical group. There were no perioperative complications related to kidney transplantation in either group. CONCLUSIONS: Routine chest examination would be useful for the early diagnosis and treatment of lung cancer after kidney transplantation. Moreover, surgical resection for early-stage lung cancer was associated with a better prognosis for kidney transplantation patients.

5.
Nano Lett ; 24(9): 2805-2811, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38408433

RESUMO

High-speed atomic force microscopy (HS-AFM) is an indispensable technique in the field of biology owing to its imaging capability with high spatiotemporal resolution. Furthermore, recent developments established tip-scan stand-alone HS-AFM combined with an optical microscope, drastically improving its versatility. It has considerable potential to contribute to not only biology but also various research fields. A great candidate is a photoactive material, such as an azo-polymer, which is important for optical applications because of its unique nanoscale motion under light irradiation. Here, we demonstrate the in situ observation of nanoscale azo-polymer motion by combining tip-scan HS-AFM with an optical system, allowing HS-AFM observations precisely aligned with a focused laser position. We observed the dynamic evolution of unique morphologies in azo-polymer films. Moreover, real-time topographic line profile analyses facilitated precise investigations of the morphological changes. This important demonstration would pave the way for the application of HS-AFM in a wide range of research fields.

6.
Geriatrics (Basel) ; 9(1)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38392108

RESUMO

BACKGROUND: The second demonstration experiment of supporting elderly people going out with the Choisoko system was conducted. The first study showed that for women, friends, shopping, convenience, and events are factors that have the potential to be effective motivational factors for encouraging these women to go out. On the other hand, these factors did not lead to any behavioral change in men. Since there are approximately 15 million men over the age of 65 in Japan, behavioral changes in the entire elderly population will not occur without guidance for elderly men to go out. METHODS: Sixteen elderly men and forty-seven elderly women participated. Interestingly, men are far more passionate about games than women. Therefore, we hypothesized that a preference for games could be a hint as to how we might encourage older men to go out. Then, a second demonstration experiment was conducted, and we analyzed the relationship between six game preferences and the frequency of going out. RESULTS: Among gaming preferences, men with gaming preferences such as Philanthropists, Achievers, and Free Spirits showed a tendency to go out. CONCLUSIONS: These stimuli may have the potential to be factors that may encourage elderly men to go out.

7.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396947

RESUMO

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.


Assuntos
Amianto , Mesotelioma Maligno , Humanos , Amianto/toxicidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/genética , Análise de Sobrevida
8.
Artigo em Inglês | MEDLINE | ID: mdl-38296520

RESUMO

We encountered a rare case of low-grade fibromyxoid sarcoma, which is generally known as Evans tumor, with massive calcification originating from the lung. The patient was a 22-year-old man with Duchenne muscular dystrophy who was referred for a detailed investigation of an intrathoracic tumor with massive calcification. Although our preoperative diagnosis was a solitary fibrous tumor originating from the mediastinum or diaphragm, intraoperative thoracoscopy revealed the tumor arising from the left lower lobe without adhesion to the other organs. Considering his medical history, we aimed to preserve lung function and chose wedge resection, which completely removed the tumor. Based on the pathological findings, the tumor was diagnosed as low-grade fibromyxoid sarcoma with massive calcification originating from the lung. Although extremely rare, this tumor should be considered as a differential diagnosis for a solitary lung mass with massive calcification in young adults.


Assuntos
Fibrossarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Adulto Jovem , Diagnóstico Diferencial , Fibrossarcoma/diagnóstico por imagem , Fibrossarcoma/cirurgia , Pulmão , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Resultado do Tratamento
9.
Respir Investig ; 62(1): 77-84, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37976917

RESUMO

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.


Assuntos
Broncoscópios , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Biópsia , Broncoscopia/métodos , Endossonografia , Biópsia por Agulha Fina , Neoplasias Pulmonares/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia
10.
Biol Pharm Bull ; 47(1): 334-338, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38143078

RESUMO

This study employed high-speed atomic force microscopy to quantitatively analyze the interactions between therapeutic antibodies and Fcγ receptors (FcγRs). Antibodies are essential components of the immune system and are integral to biopharmaceuticals. The focus of this study was on immunoglobulin G molecules, which are crucial for antigen binding via the Fab segments and cytotoxic functions through their Fc portions. We conducted real-time, label-free observations of the interactions of rituximab and mogamulizumab with the recombinant FcγRIIIa and FcγRIIa. The dwell times of FcγR binding were measured at the single-molecule level, which revealed an extended interaction duration of mogamulizumab with FcγRIIIa compared with that of rituximab. This is linked to enhanced antibody-dependent cellular cytotoxicity that is attributed to the absence of the core fucosylation of Fc-linked N-glycan. This study also emphasizes the crucial role of the Fab segments in the interaction with FcγRIIa as well as that with FcγRIIIa. This approach provided quantitative insight into therapeutic antibody interactions and exemplified kinetic proofreading, where cellular discrimination relies on ligand residence times. Observing the dwell times of antibodies on the effector molecules has emerged as a robust indicator of therapeutic antibody efficacy. Ultimately, these findings pave the way for the development of refined therapeutic antibodies with tailored interactions with specific FcγRs. This research contributes to the advancement of biopharmaceutical antibody design and optimizing antibody-based treatments for enhanced efficacy and precision.


Assuntos
Imunoglobulina G , Receptores de IgG , Receptores de IgG/química , Receptores de IgG/metabolismo , Rituximab/farmacologia , Microscopia de Força Atômica , Ligação Proteica , Fatores Imunológicos , Proteínas de Transporte/metabolismo
12.
Mediastinum ; 7: 40, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090033

RESUMO

Background: Taste disorders in patients with thymoma accompanied by myasthenia gravis (MG) is rare. Case Description: The first case was a male in his 50s who underwent surgery for Masaoka stage III type B3 thymoma. He experienced a loss of taste before surgery, which showed no improvement after surgery. Due to a MG crisis 44 days after surgery, the patient underwent intensive treatment with mechanical ventilation, steroid pulse therapy, and intravenous immunoglobulin (IVIG) therapy. The patient recovered taste when he started oral food intake after the treatment for the MG crisis (about 3 months after surgery). Despite the recovery of taste after steroid pulse therapy and IVIG therapy, taste disorder gradually worsened about 1 year and 9 months after surgery, resulting in an almost complete loss of sweet taste 2 years after surgery. The second case was a male in his 60s who underwent surgery for Masaoka stage II type B1 thymoma. He experienced loss of taste before surgery, which showed no improvement after surgery. Five years and two months after surgery, the patient was diagnosed with a MG crisis and underwent steroid pulse therapy. Along with improvements in MG symptoms, taste disorders gradually improved. After 6 years and 10 months of surgery, the patient is still alive without MG symptoms (only pyridostigmine, 180 mg/body/day), taste disorder, and thymoma recurrence. Conclusions: The autoimmune mechanism may contribute to taste disorders in patients with thymoma, which can be recovered by immunosuppressive treatment in our cases.

13.
Cancers (Basel) ; 15(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38136420

RESUMO

Accurate identification of the intersegmental plane is essential in segmentectomy, and Indocyanine Green (ICG) assists in visualizing lung segments. Various factors, including patient-related, intraoperative, and technical issues, can influence boundary delineation. This study aims to assess the rate of unsuccessful intersegmental identification and identify the contributing factors. We analyzed cases of lung segmentectomy from April 2020 to March 2023, where intraoperative ICG was intravenously administered during robot-assisted or video-assisted thoracoscopic surgery. Cases where fluorescence extended beyond expected boundaries within 30 s were classified as the "unclear boundary group". This group was then compared to the "clear boundary group". The study encompassed 111 cases, 104 (94%) of which were classified under the "clear boundary group" and 7 (6%) under the "unclear boundary group". The "unclear boundary group" had a significantly lower DLCO (15.7 vs. 11.8, p = 0.03) and DLCO/VA (4.3 vs. 3.0, p = 0.01) compared to the "clear boundary group". All cases in the "unclear boundary group" underwent lower lobe segmentectomy. ICG administration effectively outlines pulmonary segments. Challenges in segment demarcation may occur in cases with low DLCO and DLCO/VA values, particularly during lower lobe segmentectomy.

14.
Front Neurol ; 14: 1255620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020664

RESUMO

Introduction: The wearable cyborg Hybrid Assistive Limb (HAL) is the world's first cyborg-type wearable robotic device, and it assists the user's voluntary movements and facilitates muscle activities. However, since the minimum height required for using the HAL is 150 cm, a smaller HAL (2S size) has been newly developed for pediatric use. This study aimed to (1) examine the feasibility and safety of a protocol for treatments with HAL (2S size) in pediatric patients and (2) explore the optimal method for assessing the efficacy of HAL. Methods: This clinical study included seven pediatric patients with postural and motor function disorders, who received 8-12 sessions of smaller HAL (2S size) treatment. The primary outcome was the Gross Motor Function Measure-88 (GMFM-88). The secondary outcomes were GMFM-66, 10-m walk test, 2- and 6-min walking distances, Canadian Occupational Performance Measure (COPM), a post-treatment questionnaire, adverse events, and device failures. Statistical analyses were performed using the paired samples t-test or Wilcoxon signed-rank test. Results: All participants completed the study protocol with no serious adverse events. GMFM-88 improved from 65.51 ± 21.97 to 66.72 ± 22.28 (p = 0.07). The improvements in the secondary outcomes were as follows: GMFM-66, 53.63 ± 11.94 to 54.96 ± 12.31, p = 0.04; step length, 0.32 ± 0.16 to 0.34 ± 0.16, p = 0.25; 2-MWD, 59.1 ± 57.0 to 62.8 ± 63.3, p = 0.54; COPM performance score, 3.7 ± 2.0 to 5.3 ± 1.9, p = 0.06; COPM satisfaction score, 3.3 ± 2.1 to 5.1 ± 2.1, p = 0.04. Discussion: In this exploratory study, we applied a new size of wearable cyborg HAL (2S size), to children with central nervous system disorders. We evaluated its safety, feasibility, and identified an optimal assessment method for multiple treatments. All participants completed the protocol with no serious adverse events. This study suggested that the GMFM would be an optimal assessment tool for validation trials of HAL (2S size) treatment in pediatric patients with posture and motor function disorders.

15.
Am J Case Rep ; 24: e941808, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37933098

RESUMO

BACKGROUND Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disease of the central nervous system that includes the triad of transverse myelitis, optic neuritis, and area postrema syndrome (APS), characterized by intractable nausea and vomiting. NMOSD can be part of a paraneoplastic syndrome and is associated with seropositivity to aquaporin-4 (AQP-4). We present a patient with uncontrollable nausea and vomiting who developed herpes zoster and acute myelitis and was finally diagnosed with paraneoplastic NMOSD due to breast cancer. CASE REPORT A 51-year-old woman was hospitalized due to 2 weeks of intractable nausea and vomiting. Although contrast-enhanced thoracoabdominal computed tomography (CT) on day 4 suggested breast cancer in her left breast, the etiology of her symptoms remained unknown. On day 13, she developed herpes zoster, followed by acute myelitis on day 25. Magnetic resonance imaging (MRI) showing longitudinal extensive transverse myelitis and an elevated serum AQP-4 antibody level led to the diagnosis of NMOSD. Brain MRI detected a small lesion in the dorsal medulla oblongata, which explained the preceding APS. After starting intravenous methylprednisolone pulse therapy, her nausea and vomiting rapidly subsided. Breast cancer was resected on day 63, and immunohistochemical staining revealed overexpression of AQP-4 in the tumor cells, suggesting paraneoplastic NMOSD. CONCLUSIONS This report has highlighted the presentation and diagnosis of NMOSD and supports the possibility that this can present as part of a paraneoplastic syndrome. In addition, diagnosis of NMOSD preceded by APS requires meticulous history taking and careful interpretation of MRI in the dorsal medulla oblongata.


Assuntos
Neoplasias da Mama , Herpes Zoster , Mielite Transversa , Neuromielite Óptica , Feminino , Humanos , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Neoplasias da Mama/complicações , Aquaporina 4 , Náusea/etiologia , Vômito/etiologia , Autoanticorpos
17.
Am J Cardiol ; 205: 431-441, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37660669

RESUMO

BACKGROUND: The optimal revascularization strategy in patients with multivessel disease and intermediate SYNTAX score (SS) has not been fully elucidated. This study aimed to investigate the clinical outcomes of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) stratified by SS. METHODS: This was a substudy of the OPTIVUS-Complex PCI study Multivessel Cohort, which aimed to meet the prespecified criteria for optimal stent expansion after IVUS-guided PCI. A total of 1,005 patients were divided into 3 groups according to SS: low, ≤22; intermediate, 23 to 32; and high, ≥33. The primary end points were major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of death, myocardial infarction, stroke, or coronary revascularization. RESULTS: The cumulative 1-year incidence of the primary end point was significantly higher in patients with high SS than in those with intermediate or low SS (25.0%, 10.9%, and 9.5%, respectively; p = 0.003). This difference was mainly caused by the incidence of coronary revascularization. In the multivariable Cox proportional hazards models, the excess risk of patients with high versus low SS remained significant for the primary end point (hazard ratio 3.19, 95% confidence interval 1.65 to 6.16, p <0.001), whereas the excess risk of patients with intermediate versus low SS was no longer significant (hazard ratio 1.20, 95% confidence interval 0.72 to 2.01, p = 0.46). CONCLUSIONS: After IVUS-guided multivessel PCI, patients with intermediate SS had a similar 1-year risk of MACCE to that of patients with low SS, whereas patients with high SS had a higher 1-year risk of MACCE than those with low SS.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Infarto do Miocárdio/epidemiologia , Stents , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
18.
Int J Mol Sci ; 24(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37629048

RESUMO

Multidomain proteins can exhibit sophisticated functions based on cooperative interactions and allosteric regulation through spatial rearrangements of the multiple domains. This study explored the potential of using multidomain proteins as a basis for Förster resonance energy transfer (FRET) biosensors, focusing on protein disulfide isomerase (PDI) as a representative example. PDI, a well-studied multidomain protein, undergoes redox-dependent conformational changes, enabling the exposure of a hydrophobic surface extending across the b' and a' domains that serves as the primary binding site for substrates. Taking advantage of the dynamic domain rearrangements of PDI, we developed FRET-based biosensors by fusing the b' and a' domains of thermophilic fungal PDI with fluorescent proteins as the FRET acceptor and donor, respectively. Both experimental and computational approaches were used to characterize FRET efficiency in different redox states. In vitro and in vivo evaluations demonstrated higher FRET efficiency of this biosensor in the oxidized form, reflecting the domain rearrangement and its responsiveness to intracellular redox environments. This novel approach of exploiting redox-dependent domain dynamics in multidomain proteins offers promising opportunities for designing innovative FRET-based biosensors with potential applications in studying cellular redox regulation and beyond.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Isomerases de Dissulfetos de Proteínas , Isomerases de Dissulfetos de Proteínas/genética , Regulação Alostérica , Sítios de Ligação , Oxirredução
19.
Laryngoscope Investig Otolaryngol ; 8(4): 1036-1043, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37621296

RESUMO

Objective: We aimed to elucidate the ossification process of the otic capsule in postnatal C57BL/6 mice and depict the three-dimensional (3D) process of otoconial mineralization in vivo. Methods: The otic capsules of C57BL/6 mice were stained with alizarin red and imaged/compared using micro-computed tomography on postnatal day (P) between P0 and P8, P10, P15, and P30 and 3-4 months old (P3-4Mo). We reconstructed 3D images of the otic capsule and otoconia and measured the bone mineral density using x-ray absorptiometry on each age. Results: The 3D reconstructed otic capsule images revealed two ossification centers of the otic capsule at P0. One was observed around the ampulla of the superior semicircular canal and utricle, and the other was observed around the ampulla of the posterior semicircular canal. The cross-sectional views demonstrated that modiolar ossification developed from the base to the apex from P4 to P8. The inter-scalar septum ossified bidirectionally from the modiolus and bony otic capsule from P8 to P15. The mineralized otoconia were first detected in the utricle at P3 and saccular otoconia at P6. The density of the utricle and saccular otoconia showed different growth trends. Conclusion: To the best of our knowledge, this is the first study to demonstrate the 3D appearance of the otic capsule and otoconia in different developmental stages of mice. We also revealed that modiolar and inter-scalar septal calcification is the final event in the cochlea and that it can be susceptible to pathological conditions (cochlear congenital malformations and hereditary vestibular diseases). The unique features of the ossification process and duration may explain these pathological conditions observed in humans. Level of Evidence: 3.

20.
JACC Asia ; 3(4): 649-661, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614540

RESUMO

Background: There are no studies comparing single-session vs staged multivessel intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) or non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Objectives: The authors aimed to compare single-session vs staged multivessel IVUS-guided PCI in patients with CCS or NSTE-ACS. Methods: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1,021 patients with CCS or NSTE-ACS undergoing multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared single-session vs staged multivessel PCI. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. Results: There were 246 patients (24.1%) undergoing single-session multivessel PCI, and 775 patients (75.9%) undergoing staged multivessel PCI. There was a wide variation in the prevalence of single-session multivessel PCI across the participating centers. The staged multivessel PCI group more often had complex coronary anatomy such as 3-vessel disease, chronic total occlusion, and calcified lesions requiring an atherectomy device compared with the single-session multivessel PCI group. The rates of PCI success, procedural complications, and meeting OPTIVUS criteria were not different between groups. The cumulative 1-year incidence of the primary endpoint was not different between single-session and staged multivessel PCI groups (9.0% vs 10.8%, log-rank P = 0.42). After adjusting confounders, the effect of single-session multivessel PCI relative to staged multivessel PCI was not significant for the primary endpoint (HR: 0.95; 95% CI: 0.58-1.55; P = 0.84). Conclusions: Single-session and staged multivessel IVUS-guided PCI had similar 1-year outcomes.

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