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1.
J Arthroplasty ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735551

RESUMO

BACKGROUND: Prediction of the risk of developing surgical site infection (SSI) in patients following total knee arthroplasty (TKA) is of clinical importance. Genetic susceptibility is involved in developing TKA-related SSI. Previously reported models for predicting SSI were constructed using non-genetic risk factors without incorporating genetic risk factors. To address this issue, we performed a genome-wide association study (GWAS) using the UK Biobank database. METHODS: Adult patients who underwent primary TKA (n = 19,767) were analyzed and divided into SSI (n = 269) and non-SSI (n = 19,498) cohorts. Non-genetic covariates, including demographic data and preoperative comorbidities, were recorded. Genetic variants associated with SSI were identified by GWAS and included to obtain standardized polygenic risk scores (zPRS, an estimate of genetic risk). Prediction models were established through analyses of multivariable logistic regression and the receiver operating characteristic (ROC) curve. RESULTS: There were four variants (rs117896641, rs111686424, rs8101598, and rs74648298) achieving genome-wide significance that were identified. The logistic regression analysis revealed seven significant risk factors: increasing zPRS, decreasing age, men, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, and peripheral vascular disease. The areas under the ROC curve (AUC) were 0.628 and 0.708 when zPRS (model 1) and non-genetic covariates (model 2) were used as predictors, respectively. The AUC increased to 0.76 when both zPRS and non-genetic covariates (model 3) were used as predictors. A risk-prediction nomogram was constructed based on model 3 to visualize the relative effect of statistically significant covariates on the risk of SSI and predict the probability of developing SSI. Age and zPRS were the top two covariates that contributed to the risk, with younger age and higher zPRS associated with higher risks. CONCLUSION: Our GWAS identified four novel variants that were significantly associated with susceptibility to SSI following TKA. Integrating genome-wide zPRS with non-genetic risk factors improved the performance of the model in predicting SSI.

2.
Tzu Chi Med J ; 36(1): 46-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406567

RESUMO

Achilles tendon rupture is a common and primary cause of lower limb tendon injury suffered during sports-related activities. The causes of Achilles tendon rupture include the calf muscle and tendon overuse, poor tendon quality, and various medical conditions. Historically, acute Achilles tendon rupture was treated conservatively. However, historical techniques are now associated with an increased risk of rerupture. To address this problem, open repair has been proposed. Open repair is associated with a reduced risk of rerupture; however, it is also closely associated with wound complications, like wound infection, whose treatment is time-consuming and costly. Therefore, minimally invasive Achilles tendon repair has been proposed as a promising option with acceptable functional outcomes. Nevertheless, despite its benefits, minimally invasive Achilles tendon repair is associated with increased risks of sural nerve injury and rerupture. In this review, we evaluate the currently used treatment strategies for acute Achilles tendon rupture and their historical evolution to provide evidence-based recommendations for physicians.

3.
Orthop J Sports Med ; 12(1): 23259671231218649, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38274016

RESUMO

Background: The arthroscopic Broström technique with or without Gould modification has been used to treat patients with anterior talofibular ligament injury who failed nonoperative management and progressed to chronic lateral ankle instability. However, some patients develop limited range of motion over the ankle joint postoperatively. Purpose/Hypothesis: To compare the clinical outcomes and midterm functional performance of knot-tying techniques between using a knot pusher and a semiconstrained freehand tie during arthroscopic Broström-Gould procedure with inferior extensor retinaculum (IER) augmentation. It was hypothesized that the semiconstrained freehand tie would provide better plantarflexion of the ankle joint compared with the knot pusher. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 135 consecutive patients with mild-to-moderate lateral ankle instability (mean age, 42.7 years; range, 16-78 years) who underwent an arthroscopic Broström-Gould procedure from March 1, 2016, to April 30, 2022. The patients were divided into 2 groups according to the tying technique used in the Gould modification: surgical tie using a knot pusher (KP group; n = 30) or a semiconstrained freehand tie (FT group; n = 105). Radiographic parameters and ultrasound dynamic testing were examined during the preoperative assessment. Preoperative and 2-year postoperative assessments comprised American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, visual analog scale for pain, and 12-Item Short Form Survey (SF-12) scores. Results: The 2 groups had no differences in age, sex, or severity distribution in the preoperative assessment. American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, visual analog scale pain, and SF-12 scores were significantly better at the postoperative evaluation (all P < .05) in both groups. No significant difference was noted between groups in outcome scores. In the KP group, however, 7 out of 30 patients (23.3%) developed ankle stiffness with tightness when performing plantarflexion movement. No patients in the FT group reported similar symptoms. Conclusion: For mild-to-moderate chronic lateral ankle instability, we propose an arthroscopic Broström procedure with the addition of IER augmentation using a semiconstrained freehand tie to avoid overtightening the IER. This ensures favorable patient satisfaction and clinical outcomes without limitation of plantarflexion of the ankle joint and avoids the possible complication of stiffness with plantarflexion.

4.
Biomater Adv ; 156: 213722, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101076

RESUMO

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. ß-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.


Assuntos
Lipossomos , Poloxâmero , Camundongos , Animais , Poloxâmero/química , Hidrogéis , Mucinas , Distribuição Tecidual , Polímeros , Pulmão
5.
Artigo em Inglês | MEDLINE | ID: mdl-38161195

RESUMO

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells. Subsequently, PGK1 was encapsulated in a liposomal system to evaluate its therapeutic efficiency in SCA3. The optimized liposomes exhibited a significantly enhanced positive charge, facilitating efficient intracellular protein delivery to the cells. The proteins were encapsulated within the liposomes using an optimized method involving a combination of heat shock and sonication. The liposomal system was further demonstrated to be deliverable to the brain via intranasal administration. PGK1/liposomes were intranasally delivered to SCA3 mice, which subsequently exhibited an amelioration of motor impairment, as assessed via the accelerated rotarod test. Additionally, fewer shrunken morphology Purkinje cells and a reduction in polyQ expression were observed in SCA3 mice that received PGK1/liposomes but not in the untreated, liposome-only, or PGK1-only groups. This study provides a non-invasive route for protein delivery and greater delivery efficiency via the liposomal system for treating neurodegenerative diseases.

6.
Eur J Pharm Sci ; 191: 106608, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37832855

RESUMO

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.


Assuntos
Exossomos , Doença de Machado-Joseph , MicroRNAs , Humanos , Camundongos , Animais , Doença de Machado-Joseph/tratamento farmacológico , Doença de Machado-Joseph/metabolismo , Exossomos/metabolismo , Células HEK293 , MicroRNAs/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-37669211

RESUMO

High-resolution ultrasound shear wave elastography has been used to determine the mechanical properties of hand tendons. However, because of fiber orientation, tendons have anisotropic properties; this results in differences in shear wave velocity (SWV) between ultrasound scanning cross sections. Rotating transducers can be used to achieve full-angle scanning. However, this technique is inconvenient to implement in clinical settings. Therefore, in this study, high-frequency ultrasound (HFUS) dual-direction shear wave imaging (DDSWI) based on two external vibrators was used to create both transverse and longitudinal shear waves in the human flexor carpi radialis tendon. SWV maps from two directions were obtained using 40-MHz ultrafast imaging at the same scanning cross section. The anisotropic map was calculated pixel by pixel, and 3-D information was obtained using mechanical scanning. A standard phantom experiment was then conducted to verify the performance of the proposed HFUS DDSWI technique. Human studies were also conducted where volunteers assumed three hand postures: relaxed (Rel), full fist (FF), and tabletop (TT). The experimental results indicated that both the transverse and longitudinal SWVs increased due to tendon flexion. The transverse SWV surpassed the longitudinal SWV in all cases. The average anisotropic ratios for the Rel, FF, and TT hand postures were 1.78, 2.01, and 2.21, respectively. Both the transverse and the longitudinal SWVs were higher at the central region of the tendon than at the surrounding region. In conclusion, the proposed HFUS DDSWI technique is a high-resolution imaging technique capable of characterizing the anisotropic properties of tendons in clinical applications.


Assuntos
Técnicas de Imagem por Elasticidade , Tendões , Humanos , Anisotropia , Tendões/diagnóstico por imagem , Ultrassonografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Imagens de Fantasmas
8.
Front Med (Lausanne) ; 10: 1160013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547611

RESUMO

Background: Predicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan. Methods: Data was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression. Results: In total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission. Conclusion: The results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs.

9.
J Exp Clin Cancer Res ; 42(1): 160, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415190

RESUMO

BACKGROUND: Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). METHODS: Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. RESULTS: CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. CONCLUSION: Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.


Assuntos
Fibroblastos Associados a Câncer , Células Endoteliais , Feminino , Humanos , Movimento Celular/genética , Células Endoteliais/metabolismo , Metástase Linfática , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Microambiente Tumoral
10.
Front Mol Biosci ; 10: 1113061, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325472

RESUMO

Transforming growth factor beta (TGFß) is named for the function it was originally discovered to perform-transformation of normal cells into aggressively growing malignant cells. It became apparent after more than 30 years of research, however, that TGFß is a multifaceted molecule with a myriad of different activities. TGFßs are widely expressed with almost every cell in the human body producing one or another TGFß family member and expressing its receptors. Importantly, specific effects of this growth factor family differ in different cell types and under different physiologic and pathologic conditions. One of the more important and critical TGFß activities is the regulation of cell fate, especially in the vasculature, that will be the focus of this review.

11.
Nanoscale ; 15(21): 9432-9439, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37158269

RESUMO

Wide band gap (WBG) alkaline-earth stannate transparent oxide semiconductors (TOSs) have attracted increasing attention in recent years for their high carrier mobility and outstanding optoelectronic properties, and have been applied widely in various devices, such as flat-panel displays. Most alkaline-earth stannates are grown by molecular beam epitaxy (MBE); there are some intractable issues with the tin source including the volatility with SnO and Sn sources and the decomposition of the SnO2 source. In contrast, atomic layer deposition (ALD) serves as an ideal technique for the growth of complex stannate perovskites with precise stoichiometry control and tunable thickness at the atomic scale. Herein, we report the La-SrSnO3/BaTiO3 perovskite heterostructure heterogeneously integrated on Si (001), which uses ALD-grown La-doped SrSnO3 (LSSO) as a channel material and MBE-grown BaTiO3 (BTO) as a dielectric material. The reflective high-energy electron diffraction and X-ray diffraction results indicate the crystallinity of each epitaxial layer with a full width at half maximum (FWHM) of 0.62°. In situ X-ray photoelectron spectroscopy results confirm that there was no Sn0 state in ALD-deposited LSSO. Besides, we report a strategy for the post-treatment of LSSO/BTO perovskite heterostructures by controlling the oxygen annealing temperature and time, with a maximum oxide capacitance Cox of 0.31 µF cm-2 and a minimum low-frequency dispersion for the devices with 7 h oxygen annealing at 400 °C. The enhancement of capacitance properties is primarily attributed to a decrease of oxygen vacancies in the films and interface defects in the heterostructure interfaces during an additional ex situ excess oxygen annealing. This work expands current optimization methods for reducing defects in epitaxial LSSO/BTO perovskite heterostructures and shows that excess oxygen annealing is a powerful tool for enhancing the capacitance properties of LSSO/BTO heterostructures.

12.
In Vivo ; 37(1): 242-246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593027

RESUMO

BACKGROUND/AIM: Surface biomarkers, such as CD44 and CD133, have been demonstrated to be expressed in prostate cancer cells, and our previous study has shown that prostate cancer cell lines could be divided into three groups according to the single and combined expression pattern of CD44 and 133. In order to refine prognostication in prostate cancer cells, we further investigated genetic biomarkers, prostate cancer antigen 3 (PCA3), kallikrein 4 (KLK4), and KLK9 in different prostate cancer cell lines. MATERIALS AND METHODS: CWR22Rv1, PC3, and DU145 cell lines were cultured until 95% confluence. The single expression of CD44 or CD133 and their combined expression were analyzed by flow cytometry, and gene expression of b-actin, PCA3, KLK4, and KLK9 was analyzed by real-time polymerase chain reaction. RESULTS: The single expression of CD133 was less than 4% in all cell lines examined. PC3 and DU145 cells displayed a high expression of CD44 (>91%), whereas CWR22Rv1 was the only cell line that demonstrated a high co-expression of both CD44 and CD133 (>91%). In addition, PC3 and DU145 displayed low expression of PCA3, KLK4, and KLK9 when compared with their own b-actin expression. In contrast, CWR22Rva showed high expression of PCA3 and KLK4 although KLK9 expression was also low. CONCLUSION: Both surface and genetic biomarkers should be validated for a more accurate prognosis in prostate cancer.


Assuntos
Actinas , Neoplasias da Próstata , Masculino , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Linhagem Celular , Próstata
13.
Polymers (Basel) ; 14(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36559720

RESUMO

Poloxamers are negatively temperature-sensitive hydrogels and their hydrophilic groups interact with water molecules at lower temperatures (liquid phase) while their hydrophobic groups interact more strongly with increases in temperature causing gelation. To investigate the factors affecting the rheological properties of poloxamers, various parameters including different poloxamer P407 concentrations, poloxamers P407/P188 blending ratios and additives were examined. The results presented a clear trend of decreasing gelling temperature/time when P407 was at higher concentrations. Moreover, the addition of P188 enhanced the gelling temperature regardless of poloxamer concentration. Polysaccharides and their derivatives have been widely used as components of hydrogel and we found that alginic acid (AA) or carboxymethyl cellulose (CMC) reduced the gelling temperature of poloxamers. In addition, AA-containing poloxamer promoted cell proliferation and both AA -and CMC-containing poloxamer hydrogels reduced cell migration. This study investigated the intriguing characteristics of poloxamer-based hydrogel, providing useful information to compounding an ideal and desired thermo-sensitive hydrogel for further potential clinical applications such as development of sprayable anti-adhesive barrier, wound-healing dressings or injectable drug-delivery system for cartilage repair.

14.
J Vis Exp ; (189)2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36440832

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, there is no cure for PAH. It is important to discover new compounds that can be used to treat PAH. The mouse hypoxia-induced PAH model is a widely used model for PAH research. This model recapitulates human clinical manifestations of PAH Group 3 disease and is an important research tool to evaluate the effectiveness of new experimental therapies for PAH. Research using this model often requires the administration of compounds in mice. For a compound that needs to be given directly into the bloodstream, optimizing intravenous (IV) administration is a key part of the experimental procedures. Ideally, the IV injection system should permit multiple injections over a set time course. Although the mouse hypoxia-induced PAH model is very popular in many laboratories, it is technically challenging to perform multiple IV bolus dosing and invasive hemodynamic assessment in this model. In this protocol, we present step-by-step instructions on how to carry out multiple IV bolus dosing via mouse jugular vein and perform arterial and right ventricle catheterization for hemodynamic assessment in mouse hypoxia-induced PAH model.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Camundongos , Animais , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Artéria Pulmonar , Hemodinâmica , Hipóxia , Modelos Animais de Doenças
15.
Oncogene ; 41(46): 4983-4993, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36220978

RESUMO

Enhancer of Zeste Homolog 2 (EZH2) is the catalytic component of the Polycomb Repressive Complex 2, a chromatin modifying complex, which mediates methylation of lysine 27 on histone 3 (H3K27me3), a repressive chromatin mark. Genetic alterations in EZH2 in melanoma include amplifications and activating point mutations at tyrosine 641 (Y641) whose underlying oncogenic mechanisms remain largely unknown. Here, we found that expression of Ezh2Y641F causes upregulation of a subset of interferon-regulated genes in melanoma cells. Upregulation of these genes was not a direct effect of changes in H3K27me3, but via a non-canonical interaction between Ezh2 and Signal Transducer and Activator of Transcription 3 (Stat3). Ezh2 and Stat3 together function as transcriptional activators to mediate gene activation of numerous genes, including MHC Class 1b antigen processing genes. Furthermore, expression of Stat3 is required to maintain an anti-tumor immune response in Ezh2Y641F melanomas and to prevent melanoma progression and recurrence.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Melanoma , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Histonas/genética , Histonas/metabolismo , Apresentação de Antígeno , Mutação , Melanoma/genética , Cromatina/genética
16.
Orthop J Sports Med ; 10(10): 23259671221126693, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36250031

RESUMO

Background: Roughly 30% of patients with chronic lateral ankle instability (CLAI) have long-lasting painful instability requiring surgical intervention. Ligament reconstruction with the traditional open method and using tendon allografts can provide sufficient mechanical stability for severe CLAI. Arthroscopic ligament reconstruction with tendon allograft has recently been introduced to treat CLAI. Purpose: In this study, we describe an arthroscopic ligament reconstruction procedure involving the use of the tendon allograft for patients with CLAI, and we compare the efficacy of this procedure with open ligament reconstruction with tendon allograft. Study Design: Cohort study; Level of evidence, 3. Methods: We enrolled 10 patients (4 men and 6 women) with CLAI (mean age, 37.3 years; range, 16-57 years) who underwent arthroscopic ligament reconstruction with tendon allografting between November 2017 and June 2019. The control group consisted of 10 patients who received open tendon allograft reconstruction. Preoperative and 2-year postoperative functional outcomes were evaluated using the American Orthopaedic Foot & Ankle Society ankle-hindfoot scale (AOFAS), Karlsson Ankle Functional Score (KAFS), pain visual analog scale (VAS), 12-Item Short Form Health Survey (SF-12), and Tegner activity score (TAS). Results: The mean operative time was 118 and 110 minutes in the arthroscopic and open groups, respectively. At 2-year follow-up, scores on the AOFAS improved significantly compared with preoperatively, from 71.3 to 96.4 (P = .006) in the arthroscopic group, and from 68.6 to 96.7 (P = .005) in the open group. The postoperative AOFAS, VAS, KAFS, and SF-12 scores did not differ significantly between the 2 groups; however, the TAS score was significantly higher in the arthroscopic reconstruction group compared with in the open group (7 vs 6.1, respectively; P = .01). Conclusion: Arthroscopic ligament reconstruction with tendon allografting resulted in sufficient ankle stability and no donor-site morbidity. This procedure can yield similar functional outcomes to open reconstruction technique and may be an option for the management of CLAI.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35954677

RESUMO

Depression is the most common mental problem among the elderly, especially in long-term care facilities. The purpose of the present study was to examine the effects of group music intervention on depression for elderly people in nursing homes. Methods: A randomized control trial consisting of sixty-three elderly participants randomly and blindly assigned to a music group or control group was utilized. The music group received 20 sessions of group music intervention (two 30-min sessions per week for 10 weeks), and the control group received usual care with no music intervention. The Geriatric Depression Scale-Short Form (GDS-SF) and salivary cortisol at baseline, 5 weeks, and 10 weeks were collected for analysis. Results of the GEEs (generalized estimating equations) analysis indicated that after 20 sessions for 10 weeks of group music intervention, the groups showed a statistically significant difference in depression at 5 weeks and 10 weeks. There was no significant difference in the salivary cortisol concentration between the two groups. The results show that the group music intervention may effectively reduce the depression scores for elderly people in nursing homes. Conclusion: The group music intervention has positive effects on depression.


Assuntos
Depressão , Musicoterapia , Idoso , Depressão/terapia , Humanos , Hidrocortisona , Musicoterapia/métodos , Casas de Saúde
18.
J Vis Exp ; (183)2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35575528

RESUMO

Apolipoprotein E (Apoe)- or low density lipoprotein receptor (Ldlr)-deficient hyperlipidemic mice are the two most commonly used models for atherosclerosis research. They are used to study the impact of a various genetic factors and different cell types on atherosclerotic lesion formation and as well as test the development of new therapies. Isolation, excision of the whole aorta, and quantification of Oil Red O-stained atherosclerotic lesions are basic morphometric methods used to evaluate atherosclerotic burden. The goal of this protocol is to describe an optimized, step-by-step surgical method to dissect, perfuse-fix, isolate, stain, image and analyze atherosclerotic lesions in mouse aortas with Oil Red O. Because atherosclerotic lesions can form anywhere in the entire aortic tree, this whole aorta Oil Red O staining method has the advantage of evaluating lipid-laden plaques in the entire aorta and all branches in a single mouse. In addition to Oil Red O staining, fresh isolated whole aortas can be used for variety of in vitro and in vivo experiments and cell isolations.


Assuntos
Aterosclerose , Hiperlipidemias , Placa Aterosclerótica , Aneurisma , Animais , Aorta/patologia , Apolipoproteínas E , Aterosclerose/metabolismo , Aterosclerose/patologia , Compostos Azo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência/métodos , Placa Aterosclerótica/patologia , Coloração e Rotulagem/métodos
19.
J Clin Med ; 11(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35456242

RESUMO

The plastic heel cup has been adopted to treat plantar heel problems for years. However, its mechanisms and biomechanical effects are yet to be fully understood. The purpose of this study was to investigate the effects of the plastic heel cup on the microchamber and macrochamber layers of the heel pad by comparing the stiffness (in terms of the shear wave speed) and thickness of these two layers with and without a plastic heel cup during static standing. Fifteen patients with unilateral plantar fasciitis were recruited. The shear wave speed and thickness of the microchamber and microchamber layers of each symptomatic heel pad during standing measured by ultrasound shear wave elastography were compared between conditions with and without a plastic heel cup. It was found that a plastic heel cup reduced the shear wave speed of the microchamber layer to 55.5% and increased its thickness to 137.5% compared with the condition without a plastic heel cup. For the microchamber layer, the shear wave speed was reduced to 89.7%, and thickness was increased to 113.6% compared with the condition without a plastic heel cup. The findings demonstrate that a plastic heel cup can help to reduce the stiffness and increase the thickness for both layers of the heel pad during standing, suggesting that the mechanism of a plastic heel cup, and its resulting biomechanical effect, is to reduce the internal stress of the heel pad by increasing its thickness through confinement.

20.
IEEE Trans Biomed Eng ; 69(9): 2745-2754, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35192460

RESUMO

OBJECTIVE: Ultrasound (US) shear wave elasticity imaging (SWEI) is a mature technique for diagnosing the elasticity of isotropic tissues. However, the elasticity of anisotropic tissues, such as muscle and tendon, cannot be diagnosed correctly using SWEI because the shear wave velocity (SWV) varies with tissue fiber orientations. Recently, SWEI has been studied for measuring the anisotropic properties of muscles by rotating the transducer; however, this is difficult for clinical practice. METHODS: In this study, a novel dual-direction shear wave imaging (DDSWI) technique was proposed for visualizing the mechanical anisotropy of muscles without rotation. Longitudinal and transverse shear waves were created by a specially designed external vibrator and supersonic pushing beam, respectively; the SWVs were then tracked using ultrafast US imaging. Subsequently, the SWV maps of two directions were obtained at the same scanning cross section, and the mechanical anisotropy was represented as the ratio between them at each pixel. RESULTS: The performance of DDSWI was verified using a standard phantom, and human experiments were performed on the gastrocnemius and biceps brachii. Experimental results of phantom revealed DDSWI exhibited a high precision of <0.81% and a low bias of <3.88% in SWV measurements. The distribution of anisotropic properties in muscle was visualized with the anisotropic ratios of 1.54 and 2.27 for the gastrocnemius and biceps brachii, respectively. CONCLUSION: The results highlight the potential of this novel anisotropic imaging in clinical applications because the conditions of musculoskeletal fiber orientation can be easily and accurately evaluated in real time by DDSWI.


Assuntos
Técnicas de Imagem por Elasticidade , Anisotropia , Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Humanos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Imagens de Fantasmas
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