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Importance: Meticulous postoperative flap monitoring is essential for preventing flap failure and achieving optimal results in free flap operations, for which physical examination has remained the criterion standard. Despite the high reliability of physical examination, the requirement of excessive use of clinician time has been considered a main drawback. Objective: To develop an automated free flap monitoring system using artificial intelligence (AI), minimizing human involvement while maintaining efficiency. Design, Setting, and Participants: In this prognostic study, the designed system involves a smartphone camera installed in a location with optimal flap visibility to capture photographs at regular intervals. The automated program identifies the flap area, checks for notable abnormalities in its appearance, and notifies medical staff if abnormalities are detected. Implementation requires 2 AI-based models: a segmentation model for automatic flap recognition in photographs and a grading model for evaluating the perfusion status of the identified flap. To develop this system, flap photographs captured for monitoring were collected from patients who underwent free flap-based reconstruction from March 1, 2020, to August 31, 2023. After the 2 models were developed, they were integrated to construct the system, which was applied in a clinical setting in November 2023. Exposure: Conducting the developed automated AI-based flap monitoring system. Main Outcomes and Measures: Accuracy of the developed models and feasibility of clinical application of the system. Results: Photographs were obtained from 305 patients (median age, 62 years [range, 8-86 years]; 178 [58.4%] were male). Based on 2068 photographs, the FS-net program (a customized model) was developed for flap segmentation, demonstrating a mean (SD) Dice similarity coefficient of 0.970 (0.001) with 5-fold cross-validation. For the flap grading system, 11â¯112 photographs from the 305 patients were used, encompassing 10â¯115 photographs with normal features and 997 with abnormal features. Tested on 5506 photographs, the DenseNet121 model demonstrated the highest performance with an area under the receiver operating characteristic curve of 0.960 (95% CI, 0.951-0.969). The sensitivity for detecting venous insufficiency was 97.5% and for arterial insufficiency was 92.8%. When applied to 10 patients, the system successfully conducted 143 automated monitoring sessions without significant issues. Conclusions and Relevance: The findings of this study suggest that a novel automated system may enable efficient flap monitoring with minimal use of clinician time. It may be anticipated to serve as an effective surveillance tool for postoperative free flap monitoring. Further studies are required to verify its reliability.
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Inteligencia Artificial , Colgajos Tisulares Libres , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Fotograbar/métodos , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentación , Adulto Joven , Adolescente , Procedimientos de Cirugía Plástica/métodos , Reproducibilidad de los ResultadosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD). AIM OF THE STUDY: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA). MATERIALS AND METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured. RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited ß-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-ß-apiofuranosyl (1 â 6)-ß-glucopyranoside. CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.
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Dermatitis Atópica , Dinitroclorobenceno , Modelos Animales de Enfermedad , Etanol , Inmunoglobulina E , Extractos Vegetales , Wikstroemia , Animales , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inducido químicamente , Wikstroemia/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Etanol/química , Inmunoglobulina E/sangre , Ratones Pelados , Antiinflamatorios/farmacología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Femenino , Antialérgicos/farmacología , Línea Celular Tumoral , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo , Masculino , Interleucina-4/metabolismoRESUMEN
Background: Hemiarthroplasty is frequently used to treat displaced femoral neck fractures in elderly patients, but it has a higher risk of postoperative dislocation. We introduced the posterior approach and inferior capsulotomy (PAICO) to enhance joint stability after bipolar hemiarthroplasty for femoral neck fracture. We evaluated whether the PAICO would have a lower dislocation rate than the conventional posterior approach with superior capsulotomy. Methods: From January 2021 to December 2021, we prospectively recruited 25 patients (25 hips) aged 50 years or older who underwent bipolar hemiarthroplasty for femoral neck fractures due to low-energy trauma as the PAICO group. We compared the PAICO group with a historical control group who had undergone hemiarthroplasty in 7 institutes between 2010 and 2020. The primary endpoint was dislocation within 1 year after the surgery. We compared data from the PAICO group with the data from the historical control group from the Korean Hip Fracture Registry which was carried out in South Korea. Results: A total of 25 patients (25 hips) were enrolled in the present study; 3,477 patients (3,571 hips) who underwent bipolar hemiarthroplasty were reviewed as the historical control group. In the PAICO group, we observed no dislocation, whereas the dislocation rate in the control group was 1.3%. Conclusions: In patients with displaced femoral neck fractures, the PAICO approach demonstrated comparable results in operation time and complication rates when compared to bipolar hemiarthroplasty using superior capsulotomy. Notably, there were no observed cases of dislocation among patients who underwent the PAICO approach. We recommend this PAICO approach to surgeons using the posterior approach, hoping to prevent dislocation in bipolar hemiarthroplasty.
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Fracturas del Cuello Femoral , Hemiartroplastia , Humanos , Fracturas del Cuello Femoral/cirugía , Hemiartroplastia/métodos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Cápsula Articular/cirugíaRESUMEN
Introduction: Basicervical femoral neck fracture (FNF) is an uncommon type of femoral neck fracture and is associated with an increased risk of fixation failure due to its inherent instability. The purpose of this study was to compare the surgical parameters and reoperation rate between the use of a multiple cannulated screw (MCS) and fixed angle device (FAD) in treating basicervical FNFs. Methods: We retrospectively reviewed the records of 885 patients who underwent internal fixation between May 2004 and August 2019 to determine basicervical FNF with at least 12 months of follow-up. Among the identified 77 patients with basicervical FNF, 17 patients who underwent multiple cannulated screw (MCS) fixation and 36 patients who underwent fixed angle device (FAD) fixation were included. We compared the rates of fracture-site collapse and reoperations according to the fixation device. Results: Among the 53 patients with basicervical FNF, 13 patients (24.5%) sustained surgical complications (8 collapses of fracture site and 5 reoperations). The reoperation rate in the MCS group was significantly higher than that in the FAD group (23.5% vs. 2.8%, p = 0.016), without any significant difference in the collapse of the fracture site (11.8% vs. 16.7%, p = 0.642). Conclusions: Although basicervical FNF was rare among hip fractures, fracture site collapse was prevalent and prone to fixation failure. Surgeons should keep this in mind, and consider FAD for basicervical FNF.
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Tornillos Óseos , Fracturas del Cuello Femoral , Fijación Interna de Fracturas , Humanos , Fracturas del Cuello Femoral/cirugía , Femenino , Masculino , Estudios Retrospectivos , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Reoperación/estadística & datos numéricos , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Predicting cellular responses to perturbations requires interpretable insights into molecular regulatory dynamics to perform reliable cell fate control, despite the confounding non-linearity of the underlying interactions. There is a growing interest in developing machine learning-based perturbation response prediction models to handle the non-linearity of perturbation data, but their interpretation in terms of molecular regulatory dynamics remains a challenge. Alternatively, for meaningful biological interpretation, logical network models such as Boolean networks are widely used in systems biology to represent intracellular molecular regulation. However, determining the appropriate regulatory logic of large-scale networks remains an obstacle due to the high-dimensional and discontinuous search space. To tackle these challenges, we present a scalable derivative-free optimizer trained by meta-reinforcement learning for Boolean network models. The logical network model optimized by the trained optimizer successfully predicts anti-cancer drug responses of cancer cell lines, while simultaneously providing insight into their underlying molecular regulatory mechanisms.
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Aprendizaje Automático , Humanos , Algoritmos , Línea Celular Tumoral , Modelos Biológicos , Simulación por Computador , Biología de SistemasRESUMEN
Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development.
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Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores , Diente , Animales , Ratones , Regulación del Desarrollo de la Expresión Génica , Morfogénesis , Odontogénesis , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Transducción de Señal , Diente/metabolismoRESUMEN
BACKGROUND: Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multicenter randomized controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts. METHODS: Twenty-three participants were enrolled for autologous fat transfer in the face, and assigned randomly to the experimental ( n = 11) or control ( n = 12) group. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded. RESULTS: The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks, 74.5% ± 9.99% versus 66.55% ± 13.77%, P < 0.025; 24 weeks, 71.27% ± 10.43% versus 61.98% ± 13.46%, P < 0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks ( P < 0.023). Furthermore, graft survival in the forehead ( P < 0.021) and cheeks ( P < 0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group ( P < 0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted. CONCLUSION: SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
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Tejido Adiposo , Supervivencia de Injerto , Humanos , Tejido Adiposo/trasplante , Fracción Vascular Estromal , Trasplante Autólogo , Complicaciones Posoperatorias , Células del Estroma/trasplanteRESUMEN
With rapid industrialization, urbanization, and climate change, the impact of environmental factors on human health is becoming increasingly evident and understanding the complex mechanisms involved is vital from a healthcare perspective. Nevertheless, the relationship between physiological stress resulting from environmental stressors and environmental disease is complex and not well understood. Chronic exposure to environmental stressors, such as air and water contaminants, pesticides, and toxic metals, has been recognized as a potent elicitor of physiological responses ranging from systemic inflammation to immune system dysregulation causing or progressing environmental diseases. Conversely, physiological stress can exacerbate susceptibility to environmental diseases. Stress-induced alterations in immune function and hormonal balance may impair the ability to detoxify harmful substances and combat pathogens. Additionally, prolonged stress can impact lifestyle choices, leading to harmful behaviors. Understanding the link between physiological stress and environmental disease requires a systematic, multidisciplinary approach. Addressing this complex relationship necessitates the establishment of a global research network. This perspective discusses the intricate interplay between physiological stress and environmental disease, focusing on common environmental diseases, cancer, diabetes, and cognitive degeneration. Furthermore, we highlight the intricate and reciprocal nature of the connection between physiological stress and these environmental diseases giving a perspective on the current state of knowledge as well as identifying where further information is necessary. Recognizing the role of physiological stress in environmental health outcomes will aid in the development of comprehensive strategies to safeguard public health and promote ecological balance.
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Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids- and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided.
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In this study, iron/iron-magnesium (Fe/Fe-Mg) additives were prepared through the impregnation of granular activated carbon (GAC) with iron and iron-magnesium (GFM) to enhance biohydrogen production. The microscope observation and chemical analysis revealed that the GAC matrixes were well infused with Fe/Fe-Mg, while the X-ray diffraction analysis revealed the species of metal formed on the GAC as Fe3+ and MgH2. The synergistic effect of Fe and Mg in GFM allowed it for a shorter delay time and higher hydrogen production rate than other additives, indicating their possible use in stimulating the fast release of hydrogen in anaerobic digestion. The co-metabolites analysis revealed that additives ensured biohydrogen production through the different pathways. The plausible mechanisms were through hydrogenases ensured by Fe3+ and hydrolysis by MgH2. GFM gave the best organic matter and nutrient removal efficiency to outperform other additives, suggesting its ability for biohydrogen synthesis and simultaneous wastewater treatment.
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Hierro , Aguas Residuales , Magnesio , Carbón Orgánico , HidrógenoRESUMEN
BACKGROUND: The purpose of the Korean Hip Fracture Registry (KHFR) Study is to establish a nationwide, hospital-based prospective cohort study of adults with hip fracture to explore the incidence and risk factors of second osteoporotic fractures for a Fracture Liaison Service (FLS) model. METHODS: The KHFR, a prospective multicenter longitudinal study, was launched in 2014. Sixteen centers recruited participants who were treated for hip fracture. The inclusion criteria were patients, who were treated for proximal femur fracture due to low-energy trauma and aged 50 or more at the time of injury. Until 2018, 5,841 patients were enrolled in this study. Follow-up surveys were conducted annually to determine occurrence of second osteoporotic fracture, and 4,803 participants completed at least one follow-up survey. DISCUSSION: KHFR is a unique resource of individual level on osteoporotic hip fracture with radiological, medical, and laboratory information including DXA (dual energy x-ray absorptiometry), bone turnover marker, body composition, and hand grip strength for future analyses for FLS model. Modifiable factors for mortality after hip surgery is planned to be identified with nutritional assessment and multi-disciplinary interventions from hospitalization to follow-ups. The proportions of femoral neck, intertrochanteric, and subtrochanteric fractures were 517 (42.0%), 730 (53.6%), and 60 (4.4%), respectively, from 2014 to 2016, which was similar in other studies. Radiologic definition of atypical subtrochanteric fracture was adopted and 17 (1.2%) fractures among 1,361 proximal femoral fractures were identified. Internal fixation showed higher reoperation rate compared to arthroplasty in unstable intertrochanteric fractures (6.1% vs. 2.4%, p = 0.046) with no significant difference in mortality. The KHFR plans to identify outcomes and risk factors associated with second fracture by conducting a 10-year cohort study, with a follow-up every year, using 5,841 baseline participants. TRIAL REGISTRATION: Present study was registered on Internet-based Clinical Research and Trial management system (iCReaT) as multicenter prospective observational cohort study (Project number: C160022, Date of registration: 22th, Apr, 2016).
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Fracturas de Cadera , Fracturas Osteoporóticas , Adulto , Humanos , Estudios Prospectivos , Estudios de Cohortes , Fuerza de la Mano , Estudios Longitudinales , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/epidemiología , Fracturas de Cadera/cirugía , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/cirugía , Sistema de Registros , República de Corea/epidemiologíaRESUMEN
Anaerobic co-digestion of food waste and algae was assessed to offset the drawbacks of anaerobic mono-digestion of each substrate. Batch test results indicated that a food waste and algae mixture ratio of 8:2 facilitated the highest CH4 yield (334 mL CH4/g CODInput). This ratio was applied to the anaerobic co-digestion reactor, resulting in a CH4 yield that was twice that of the anaerobic mono-digestion reactors, thereby facilitating high operational stability. In contrast to the anaerobic mono-digestion, anaerobic co-digestion resulted in stable CH4 production by overcoming volatile fatty acid accumulation and a decreased pH, even under a high organic loading rate (3 kg COD/m3âd). Furthermore, a comparative metagenomic analysis revealed that the abundance of volatile fatty acid-oxidizing bacteria and hydrogenotrophic and methylotrophic methanogens was significantly increased in the anaerobic co-digestion reactor. These findings indicate that the anaerobic co-digestion of food waste and algae significantly improves CH4 production and process stability.
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Alimentos , Eliminación de Residuos , Anaerobiosis , Biocombustibles/análisis , Eliminación de Residuos/métodos , Aguas del Alcantarillado/microbiología , Reactores Biológicos/microbiología , Metano , Ácidos Grasos VolátilesRESUMEN
Nymphoides peltata is widely used pharmacologically in Traditional Chinese Medicine and Ayurvedic medicine as a diuretic, antipyretic, or choleretic and to treat ulcers, snakebites, and edema. Previous studies have shown that phytochemicals from N. peltata have physiological activities such as anti-inflammatory, anti-tumor, and anti-wrinkle properties. Nevertheless, research on the anti-atopic dermatitis (AD) effect of N. peltata extract is limited. This study was undertaken to assess the in vitro and in vivo anti-atopic and antioxidant activities of a 95% EtOH extract of N. peltata roots (NPR). PI-induced RBL-2H3 cells and two typical hapten mice (oxazolone-induced BALB/c mice and 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice) were used to investigate the effect of NPR extract on AD. The expressions of AD-related inflammatory cytokines, skin-related genes, and antioxidant enzymes were analyzed by ELISA, immunoblotting, and immunofluorescence, and skin hydration was measured using Aquaflux AF103 and SKIN-O-MAT instruments. The chemical composition of NPR extract was analyzed using an HPLC-PDA system. In this study, NPR extracts were shown to most efficiently inhibit IL-4 in PI-induced RBL-2H3 cells and AD-like skin symptoms in oxazolone-BALB/c mice compared to its whole and aerial extracts. NPR extract markedly reduced DNCB-induced increases in mast cells, epidermal thickness, IL-4 and IgE expressions, and atopic-like symptoms in SKH-1 hairless mice. In addition, NPR extract suppressed DNCB-induced changes in the expressions of skin-related genes and skin hydration and activated the Nrf2/HO-1 pathway. Three phenolic acids (chlorogenic acid, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid) were identified by HPLC-PDA in NPR extract. The study shows that NPR extract exhibits anti-atopic activities by inhibiting inflammatory and oxidative stress and improving skin barrier functions, and indicates that NPR extract has potential therapeutic use for the prevention and treatment of AD.
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The epithelial-to-mesenchymal transition (EMT) of primary cancer contributes to the acquisition of lethal properties, including metastasis and drug resistance. Blocking or reversing EMT could be an effective strategy to improve cancer treatment. However, it is still unclear how to achieve complete EMT reversal (rEMT), as cancer cells often transition to hybrid EMT states with high metastatic potential. To tackle this problem, we employed a systems biology approach and identified a core-regulatory circuit that plays the primary role in driving rEMT without hybrid properties. Perturbation of any single node was not sufficient to completely revert EMT. Inhibition of both SMAD4 and ERK signaling along with p53 activation could induce rEMT in cancer cells even with TGFß stimulation, a primary inducer of EMT. Induction of rEMT in lung cancer cells with the triple combination approach restored chemosensitivity. This cell-fate reprogramming strategy based on attractor landscapes revealed potential therapeutic targets that can eradicate metastatic potential by subverting EMT while avoiding hybrid states. SIGNIFICANCE: Network modeling unravels the highly complex and plastic process regulating epithelial and mesenchymal states in cancer cells and discovers therapeutic interventions for reversing epithelial-to-mesenchymal transition and enhancing chemosensitivity.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Transición Epitelial-Mesenquimal , Diferenciación Celular , Transducción de Señal , Factor de Crecimiento Transformador beta/farmacología , Línea Celular TumoralRESUMEN
Snail is a key regulator of the epithelial-mesenchymal transition (EMT), the key step in the tumorigenesis and metastasis of tumors. Although induction of Snail transcription precedes the induction of EMT, the post-translational regulation of Snail is also important in determining Snail protein levels, stability, and its ability to induce EMT. Several kinases are known to enhance the stability of the Snail protein by preventing its ubiquitination; however, the precise molecular mechanisms by which these kinases prevent Snail ubiquitination remain unclear. Here, we identified ERK3 as a novel kinase that interacts with Snail and enhances its protein stability. Although ERK3 could not directly phosphorylate Snail, Erk3 increased Snail protein stability by inhibiting the binding of FBXO11, an E3 ubiquitin ligase that can induce Snail ubiquitination and degradation, to Snail. Importantly, functional studies and analysis of clinical samples indicated the crucial role of ERK3 in the regulation of Snail protein stability in pancreatic cancer. Therefore, we conclude that ERK3 is a key regulator for enhancing Snail protein stability in pancreatic cancer cells by inhibiting the interaction between Snail and FBXO11.
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Data on the coincidence site lattice (CSL) boundary relationship between Goss and matrix grains in Fe-3%Si grain-oriented electrical steel are reported herein. First, the matrix grains of the Fe-3%Si grain-oriented electrical steel after primary recrystallization were investigated to examine the CSL boundary relationship between major orientations namely, Goss (90°, 45°, 90°), Cube (0°, 0°, 0°), Brass (35°, 45°, 0°), and Copper (90°, 35°, 45°). Then, the abnormal growth morphology of the Goss grains was observed ex-situ using electron backscatter diffraction. During its abnormal growth, the Goss grain grew while consuming the matrix grains. However, matrix grains with a CSL boundary relationship with Goss grains did not disappear but remained. The matrix grains that either remained or disappeared when the Goss grains grew abnormally were investigated, and the fraction of matrix grains that had a CSL boundary relationship with the Goss grains was 27.9% among the 523 remaining grains and 12.8% among the 2813 disappearing grains.
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Oral cancer is a malignant neoplasm of oral cavity. It accounts for approximately 5% of all malignant tumors. Approximately 97% of all oral cancers are squamous cell carcinomas, followed by adenocarcinomas, and rarely malignant melanomas. It occurs particularly in males (twice as common in males than in females) of middle age (above 40 years). Agrimonia pilosa Ledeb. has traditionally been known for its effective antitumor activity and is currently used in China for cancer therapy. A. pilosa Ledeb. has been traditionally used for the treatment of abdominal pain, sore throat, headache, blood discharge, parasitic infections, and eczema in Korea and other Asian countries. Most studies on A. pilosa Ledeb. are related to the leaves and a few investigated the roots of the plant. However, detailed mechanisms of antitumor activity of A. pilosa Ledeb. have not been fully elucidated. Furthermore, to date, there have been no reports on the antitumor effect of A. pilosa Ledeb. in oral squamous cells. In this study, we used proteomic technology to observe changes in proteins related to anticancer activity of A. pilosa Ledeb. and identified target proteins among altered proteins to reveal the underlying mechanism of action.
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ABSTRACT: Breakage of the intramedullary nail is a rare complication after proximal femoral nail antirotation (PFNA) in intertrochanteric fracture treatment. The purpose of this study was (1) to investigate the frequency of nail breakage among the patients who were treated for mechanical failure after PFNA for intertrochanteric/pertrochanteric fracture, and (2) to determine the risk factors for nail breakage in PFNA treatment of intertrochanteric fracture.To identify mechanical failure after internal fixation using PFNA, we retrospectively reviewed the data of 35 patients (35 hips) who required reoperation after PFNA with a helical blade for intertrochanteric/pertrochanteric fracture between June 2005 and June 2018.We evaluated the frequency of breakage of PFNA and compared the demographic and radiologic parameters between the breakage and control (non-breakage) groups. We also compared the lever arm for the load of stress from the fulcrum according to the centrum-collum-diaphyseal (CCD) angle of blade by using reverse design technique.Among the 25 patients with mechanical failure after PFNA except 10 patients with peri-implant infection and osteonecrosis, 7 (28.0%) showed breakage of PFNA at average of 8 months (range, 5-13 months) after index surgery. A larger horizontal offset (the horizontal distance from the lateral surface of the IM nail and the medial tip of helical blade) was associated with an increased risk of nail breakage. A CCD angle of 130° has a shorter lever arm for the load of stress from the fulcrum, meaning a higher stress for nail breakage, although there was no association between CCD angle and breakage of the nail.Our study suggested that higher horizontal offset and a higher CCD angle can increase the risk of breakage of the PFNA nail at the aperture for the helical blade.
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Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas de Cadera , Clavos Ortopédicos/efectos adversos , Fracturas del Fémur/etiología , Fémur , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Fracturas de Cadera/etiología , Fracturas de Cadera/cirugía , Humanos , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia developing in post-operative patients. Limited data are available regarding pre-operative risk factors and prognostic impact of post-operative AF (POAF) following hip fracture surgery (HFS) in Korean population. AIM: We aimed to investigate the incidence, predictors, and hospital prognosis of POAF in HFS patients. METHODS: This study included 245 patients without history of AF who underwent HFS between August 2014 and November 2016. POAF was defined as new-onset AF that occurred during hospitalization after HFS. RESULTS: Twenty patients (8.2%) experienced POAF after HFS. POAF developed on median post-operative day 2 (interquartile range, 1-3). Multivariable logistic regression analysis showed that age [odds ratio (OR), 1.111; 95% confidence interval (CI), 1.022-1.209], chronic obstructive pulmonary disease (COPD) (OR, 6.352; 95%CI, 1.561-25.841) and E/e' ratio (OR, 1.174; 95%CI, 1.002-1.376) were significant predictors of POAF. Patients with POAF had a significantly higher intensive care unit admission rate (55.0% vs 14.7%, P < 0.001) and incidence of congestive heart failure (45.0% vs 10.7%, P < 0.001). In multivariable logistic regression analysis, POAF was significantly associated with increased incidence of congestive heart failure (OR, 4.856; 95%CI, 1.437-16.411) and intensive care unit admission (OR, 6.615; 95%CI, 2.112-20.718). CONCLUSION: POAF was frequently developed in elderly patients following HFS. Age, COPD and elevated E/e' ratio were found as significant predictors of POAF in HFS patients. Patients with POAF significantly experienced intensive care unit admission and incident congestive heart failure during hospitalization.
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BACKGROUND: Skeletal muscle atrophy is caused by aging, disuse, malnutrition, and several diseases. However, there are still no effective drugs or treatments for muscle atrophy. Codonopsis lanceolata (CL), a traditional medicinal plant and food, has been reported to have anti-oxidative, anti-inflammatory, anti-tumor, and anti-obesity effects. PURPOSE: This study aimed to investigate the efficacy and active component of CL on muscle atrophy in vitro and to confirm the effect of CL and its active component on muscle atrophy and the underlying molecular mechanisms in vivo. STUDY: design/Methods This study used the dexamethasone (Dex)-induced muscle atrophy C2C12 myotube model and immobilization (IM)-induced muscle atrophy C57BL/6 mice model. In vitro study, the myotube diameter was measured. In vivo study, the grip strength, muscle mass (quadriceps, gastrocnemius, and soleus) and muscle fiber cross-sectional area (CSA) was measured. Western blot analysis and qRT-PCR were performed to confirm the underlying molecular mechanisms Results:In vitro study, CL and its main component, Tangshenoside I (TSI), effectively restored C2C12 myotube diameters decreased by Dex. Surprisingly, TSI was identified as the active component responsible for the overall efficacy of CL on muscle atrophy. In vivo study, CL and TSI, dose-dependently increased grip strength, mass muscle, and muscle fiber CSA reduced by IM. In the molecular mechanism studies, CL and TSI increased muscle protein synthesis via activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin complex 1 (mTORC1) pathway and decreased muscle protein degradation via inhibiting the muscle ring finger-1 (MuRF1) and muscle atrophy F-box protein (Atrogin-1) expressions. It also upregulated mitochondrial biogenesis via the silent information regulator 1 (SIRT1)/ peroxisome proliferator-activated receptor gamma and coactivator-1 alpha (PGC-1α) pathway. CONCLUSION: This study suggests that CL and its active component, TSI, can be potential drug candidates for the prevention and treatment of muscle atrophy.