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1.
J Orthop Surg Res ; 19(1): 635, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39380108

RESUMEN

BACKGROUND: Sarcopenia and osteoarthritis are prevalent age-related diseases that mutually exacerbate each other, creating a vicious cycle that worsens both conditions. Exercise is key to breaking this detrimental cycle. Facing increasing demand for rehabilitation services within this patient demographic, ChatGPT-4 and wearable device may increase the availability, efficiency and personalization of such health care. AIM: To evaluate the clinical efficacy and cost-effectiveness of a rehabilitation system implemented on mobile platforms, utilizing the integration of ChatGPT-4 and wearable devices. METHODS: The study design is a prospective randomized open blinded end-point (PROBE) non-inferiority trial. 278 patients diagnosed with osteoarthritis and sarcopenia will be recruited and randomly assigned to the intervention group and the control group. In the intervention group patients receive mobile phone-based rehabilitation service where ChatGPT-4 generates personalized exercise therapy, and wearable device guides and monitor the patient to implement the exercise therapy. Traditional clinic based face-to-face exercise therapy will be prescribed and implemented in the control group. All patients will receive three-months exercise therapies following the frequency, intensity, type, time, volume and progression (FITT-VP) principle. The patients will be assessed at baseline, one month, three months, and six months after initiation. Outcome measures will include ROM, gait patterns, Visual Analogue Scale (VAS) for pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) for functional assessment, Short-Form Health Survey 12 (SF-12) for quality of life, Minimal Clinically Important Difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) for clinically significant measures. DISCUSSION: A rehabilitation system combining the capabilities of ChatGPT-4 and wearable devices potentially enhance the availability and efficiency of professional rehabilitation services, thus enhancing the therapeutic outcomes for a substantial population concurrently afflicted with sarcopenia and osteoarthritis.


Asunto(s)
Terapia por Ejercicio , Estudios de Factibilidad , Osteoartritis , Sarcopenia , Dispositivos Electrónicos Vestibles , Humanos , Terapia por Ejercicio/métodos , Terapia por Ejercicio/instrumentación , Sarcopenia/rehabilitación , Osteoartritis/rehabilitación , Osteoartritis/terapia , Estudios Prospectivos , Resultado del Tratamiento , Masculino , Anciano , Femenino , Teléfono Celular , Calidad de Vida , Persona de Mediana Edad
2.
BMC Oral Health ; 24(1): 1205, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39390416

RESUMEN

OBJECTIVE: A hybrid manufacturing technique that combines selective laser melting (SLM) and computer numerical control (CNC) has been developed for the fabrication of implant-platform/framework interfaces (PFIs) for mandibular and maxillary full-arch implant-supported titanium frameworks. The aim of this study was to compare the discrepancies in specimens fabricated using the hybrid technique (termed SLM/m hereafter) with those in specimens fabricated by conventional CNC milling. MATERIALS AND METHODS: Based on a mandibular four-PFI CAD model and a maxillary six-PFI CAD model, four groups of titanium frameworks (eight per group, totaling 32) were fabricated according to the fabrication technique (SLM/m or milling) and number of PFIs (four or six). The frameworks were scanned by a structured light scanner and aligned with the CAD model in Geomagic Control X. Discrepancy was defined as the difference between the PFIs of the scanned framework and those of the CAD model. Discrepancies were measured and evaluated by multilevel analysis using a mixed-effects model (α = 0.05), followed by independent samples t-tests (α = 0.0125). Furthermore, the manufacturing times and raw-material costs were recorded and compared. RESULTS: The maximum discrepancy values for the four-PFI and six-PFI hybrid frameworks were 52.2 and 64.3 µm, respectively. Multilevel analysis revealed that the fabrication technique and the number of PFIs had no significant effect on the discrepancy value. However, a significant interaction between the two factors was observed (P = 0.020). The discrepancies for the four-PFI hybrid frameworks were significantly lower than those for the four-PFI milled frameworks (P = 0.001). No significant difference in discrepancies between the six-PFI hybrid frameworks and six-PFI milled frameworks was observed (P = 0.697). Furthermore, the hybrid frameworks required only 11% of the raw materials and 25% of the milling time required for the conventionally milled frameworks. CONCLUSION: SLM/m hybrid frameworks are viable, accurate alternatives to CNC-milled frameworks, with the added benefit of substantial cost reduction.


Asunto(s)
Diseño Asistido por Computadora , Prótesis Dental de Soporte Implantado , Titanio , Titanio/química , Humanos , Rayos Láser , Mandíbula , Diseño de Prótesis Dental/métodos
3.
Front Immunol ; 15: 1457612, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39399490

RESUMEN

Esophageal cancer (EC) is among the most aggressive malignancies, ranking as the seventh most prevalent malignant tumor worldwide. Lymph node metastasis (LNM) indicates localized spread of cancer and often correlates with a poorer prognosis, emphasizing the necessity for neoadjuvant systemic therapy before surgery. However, accurate identification of LNM in EC presents challenges due to the lack of satisfactory diagnostic techniques. Imaging techniques, including ultrasound and computerized tomography scans, have low sensitivity and accuracy in assessing LNM. Additionally, the existing serological detection lacks precise biomarkers. The intricate and not fully understood molecular processes involved in LNM of EC contribute to current detective limitations. Recent research has shown potential in using various molecules, circulating tumor cells (CTCs), and changes in the microbiota to identify LNM in individuals with EC. Through summarizing potential biomarkers associated with LNM in EC and organizing the underlying mechanisms involved, this review aims to provide insights that facilitate biomarker development, enhance our understanding of the underlying mechanisms, and ultimately address the diagnostic challenges of LNM in clinical practice.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Esofágicas , Metástasis Linfática , Células Neoplásicas Circulantes , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/diagnóstico , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Ganglios Linfáticos/patología , Animales , Pronóstico
4.
Molecules ; 29(19)2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39407702

RESUMEN

Dissipative particle dynamics (DPD) simulations is used to study the effect of Am/2BmAm/2 and H-shaped (Am/4)2Bm(Am/4)2 block copolymers on the interfacial properties of ternary blends. Our simulations show the following: (i) The capacity of block copolymers to diminish interfacial tension is closely linked to their compositions. With identical molecular weights and concentrations, H-shaped block copolymers outperform triblock copolymers in mitigating interfacial tension. (ii) The interfacial tension within the blends correlates positively with the escalation in H-shaped block copolymer molecular weight. This correlation suggests that H-shaped block copolymers featuring a low molecular weight demonstrate superior efficacy as compatibilizers when contrasted with those possessing a high molecular weight. (iii) Enhancing the concentration of H-shaped block copolymers fosters their accumulation at the interface, leading to a reduction in correlations between immiscible homopolymers and a consequent decrease in interfacial tension. (iv) As the length of the homopolymer chains increases, there is a concurrent elevation in interfacial tension, suggesting that H-shaped block copolymers perform more effectively as compatibilizers in blends characterized by shorter homopolymer chain lengths. These findings elucidate the associations between the efficacy of H-shaped block copolymer compatibilizers and their specific molecular characteristics.

5.
J Surg Orthop Adv ; 33(3): 184-188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39475806

RESUMEN

This study compares radiographic osteoarthritis severity prior with total knee arthroplasty (TKA) by payer type. Five hundred and three primary TKAs were included. Preoperative radiographs were scored by Ahlback, Kellgren-Lawrence (KL), and International Knee Documentation Committee (IKDC) classifications. Osteoarthritis severity by age and insurance type (private, Medicare, and Medicaid) were compared using Mann Whitney U and Kruskal-Wallis testing. Three hundred and two (60%) subjects were under 65 years old, and 201 (40%) were 65 years and older. Younger subjects had no differences in radiographic severity in KL (p = 0.268), Ahlback (p = 1), or IKDC (p = 0.948) classification by insurance. Older subjects also had no differences in osteoarthritis severity for KL (p = 0.282), Ahlback (p = 0.354), or IKDC (p = 0.735) classifications by insurance. Three osteoarthritis classification systems found no difference in preoperative radiographic changes by payor type, suggesting that, in the study's population, there is no delay in appropriate surgical treatment by payer. Future studies should compare preoperative clinical symptoms. (Journal of Surgical Orthopaedic Advances 33(3):184-188, 2024).


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Medicare , Osteoartritis de la Rodilla , Índice de Severidad de la Enfermedad , Humanos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Anciano , Masculino , Femenino , Persona de Mediana Edad , Estados Unidos , Medicaid , Radiografía , Estudios Retrospectivos , Seguro de Salud/estadística & datos numéricos , Factores de Edad
6.
Front Public Health ; 12: 1408316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39319291

RESUMEN

Objectives: To provide valuable insights for targeted interventions and resource allocation, our analysis delved into the multifaceted burden, trends, risks, and projections of multi drug resistant tuberculosis (MDR-TB). Methods: This research employed data from the Global Burden of Disease (GBD) 2019 dataset, which used a comparative risk assessment to quantify the disease burden resulting from risk factors. Initially, this database was utilized to extract details concerning the disability-adjusted life years (DALYs), mortality, incidence, and the number of individuals afflicted by MDR-TB. Subsequently, regression analyses were conducted using the Joinpoint program to figure average annual percent change (AAPC) to ascertain the trend. Thirdly, the age-period-cohort model (APCM) was adopted to analyze evolutions in incidence and mortality. Finally, utilizing the Nordpred model within R software, we projected the incidence and mortality of MDR-TB from 2020 to 2030. Results: MDR-TB remained a pressing global health concern in regions with lower socio-demographic indexes (SDI), where the AAPC in DALYs topped 7% from 1990 to 2019. In 2019, the cumulative DALYs attributed to MDR-TB tallied up to 4.2 million, with India, the Russian Federation, and China bearing the brunt. Notably, the incidence rates have shown a steadfast presence over the past decade, and a troubling forecast predicts an uptick in these areas from 2020 to 2030. Additionally, the risk of contracting MDR-TB grew with advancing age, manifesting most acutely among men aged 40+ in lower SDI regions. Strikingly, alcohol consumption had been identified as a significant contributor, surpassing the impacts of smoking and high fasting plasma glucose, leading to 0.7 million DALYs in 2019. Conclusions: A robust strategy is needed to end tuberculosis (TB) by 2030, especially in lower SDI areas.


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Masculino , Incidencia , Femenino , Adulto , Persona de Mediana Edad , Carga Global de Enfermedades , Salud Global/estadística & datos numéricos , Años de Vida Ajustados por Discapacidad , Factores de Riesgo , Adolescente , Anciano , Adulto Joven , Medición de Riesgo
7.
Front Cell Infect Microbiol ; 14: 1452124, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39328360

RESUMEN

Introduction: Microbial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection. Methods: DPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed. Results: DPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a. Conclusions: Our study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.


Asunto(s)
Candida albicans , Pulpa Dental , Especies Reactivas de Oxígeno , Células Madre , Streptococcus mutans , Humanos , Pulpa Dental/microbiología , Pulpa Dental/citología , Pulpa Dental/inmunología , Células Madre/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Streptococcus mutans/genética , FN-kappa B/metabolismo , Adulto Joven , Análisis de la Célula Individual , Transducción de Señal , Células Cultivadas , Citocinas/metabolismo
8.
J Dent ; 150: 105329, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39243803

RESUMEN

OBJECTIVES: To compare the accuracy of robotic and dynamic navigation systems in assisting zygomatic implant (ZI) using an in vitro model experiment. METHODS: Preoperative cone-beam computed tomography (CBCT) images of patients who underwent ZI treatment between 2011 and 2023 were collected from local databases. Corresponding three-dimensional resin models were printed and assigned to two groups: the robotic and dynamic navigation system groups. Following preoperative plans, ZIs were placed in the models with the assistance of either a robotic or dynamic navigation system. Deviations in the in vitro navigation surgery were measured and compared between the groups. RESULTS: A total of 110 ZIs were placed in 56 models, with 55 ZIs in each group. No significant differences were observed in entry and angle deviations between the groups (p>0.05). However, the exit deviation in the robotic system group (2.39±1.24 mm) was larger than that in the dynamic navigation group (1.83±1.25 mm) (p<0.05). On the exit side, the Z-axis deviation in the robotic group (left: -0.28±1.43 mm, right: -0.21±1.30 mm) was smaller than that in the dynamic navigation group (left: 0.76±1.11 mm, right: 0.85±1.52 mm) (p<0.05), while no significant differences were found in X- and Y-axis deviations (p>0.05). CONCLUSIONS: Compared with the dynamic navigation system, the robotic system can effectively prevent ZI overextension. However, its accuracy on the exit side is slightly lower than that of the dynamic navigation system. CLINICAL SIGNIFICANCE: This preliminary in vitro study showed that the accuracy of the robotic system was slightly inferior to that of the dynamic navigation system in terms of exit deviation when used in ZI placement. Further clinical studies are required to confirm these findings.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Implantación Dental Endoósea , Procedimientos Quirúrgicos Robotizados , Cirugía Asistida por Computador , Cigoma , Humanos , Cirugía Asistida por Computador/métodos , Cigoma/cirugía , Cigoma/diagnóstico por imagen , Procedimientos Quirúrgicos Robotizados/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Implantación Dental Endoósea/métodos , Implantación Dental Endoósea/instrumentación , Implantes Dentales , Impresión Tridimensional , Modelos Anatómicos , Imagenología Tridimensional/métodos , Robótica , Técnicas In Vitro , Femenino
9.
BMC Oral Health ; 24(1): 1139, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334018

RESUMEN

BACKGROUND: Amelogenesis imperfecta (AI) is a group of genetic disorders characterized by tooth discoloration and enamel defects. Patients with AI always exhibit generalized attrition and defective tooth structure, leading to the loss of occlusal vertical dimension (OVD). Appropriate rehabilitation is challenging and essential to improve patients' aesthetics and function. CASE PRESENTATION: This case report presents a comprehensive management of a 30-year-old woman with hypoplastic AI. A 52-month follow-up revealed satisfactory full-mouth rehabilitation performances of lithium disilicate ceramic crowns after clinical crown lengthening, with increased vertical dimension. CONCLUSIONS: Patients with severe hypoplastic AI require proper full-mouth rehabilitation. Using full-crown lithium disilicate restorations to increase the OVD by 2‒4 mm is a safe and predictable recommendation for such cases. In addition, patients with AI require complex and comprehensive management. The long-term effects of full-mouth rehabilitation with lithium disilicate ceramic crowns still necessitate further follow-ups.


Asunto(s)
Amelogénesis Imperfecta , Coronas , Porcelana Dental , Humanos , Amelogénesis Imperfecta/rehabilitación , Femenino , Adulto , Rehabilitación Bucal/métodos , Alargamiento de Corona/métodos , Cerámica , Dimensión Vertical
10.
Sci Rep ; 14(1): 22495, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39341858

RESUMEN

The synthesis of facial sketch-photo has important applications in practical life, such as crime investigation. Many convolutional neural networks (CNNs) based methods have been proposed to address this issue. However, due to the substantial modal differences between sketch and photo, the CNN's insensitivity to global information, and insufficient utilization of hierarchical features, synthesized photos struggle to balance both identity preservation and image quality. Recently, State Space Sequence Models (SSMs) have achieved exciting results in computer vision (CV) tasks. Inspired by SSMs, we design a hybrid CNN-SSM model called FaceMamba for the Face Sketch-Photo Synthesis (FSPS) task. It includes an original Face Vision Mamba Attention for modeling in latent space using SSM. Additionally, it incorporates a general auxiliary method called Attention Feature Injection that combines encoding features, decoding features, and external auxiliary features using attention mechanisms. FaceMamba combines Mamba's modeling ability for long-range dependencies with CNN's powerful local feature extraction ability, and utilizes hierarchical features at the appropriate position. Adequate experimental and evaluation results reveal that FaceMamba has strong competitiveness in FSPS task, achieving the best balance between identity preservation and image quality.

11.
J Cell Mol Med ; 28(19): e18590, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39347925

RESUMEN

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are two typical types of non-coding RNAs that interact and play important regulatory roles in many animal organisms. Exploring the unknown interactions between lncRNAs and miRNAs contributes to a better understanding of their functional involvement. Currently, studying the interactions between lncRNAs and miRNAs heavily relies on laborious biological experiments. Therefore, it is necessary to design a computational method for predicting lncRNA-miRNA interactions. In this work, we propose a method called MPGK-LMI, which utilizes a graph attention network (GAT) to predict lncRNA-miRNA interactions in animals. First, we construct a meta-path similarity matrix based on known lncRNA-miRNA interaction information. Then, we use GAT to aggregate the constructed meta-path similarity matrix and the computed Gaussian kernel similarity matrix to update the feature matrix with neighbourhood information. Finally, a scoring module is used for prediction. By comparing with three state-of-the-art algorithms, MPGK-LMI achieves the best results in terms of performance, with AUC value of 0.9077, AUPR of 0.9327, ACC of 0.9080, F1-score of 0.9143 and precision of 0.8739. These results validate the effectiveness and reliability of MPGK-LMI. Additionally, we conduct detailed case studies to demonstrate the effectiveness and feasibility of our approach in practical applications. Through these empirical results, we gain deeper insights into the functional roles and mechanisms of lncRNA-miRNA interactions, providing significant breakthroughs and advancements in this field of research. In summary, our method not only outperforms others in terms of performance but also establishes its practicality and reliability in biological research through real-case analysis, offering strong support and guidance for future studies and applications.


Asunto(s)
Algoritmos , Biología Computacional , MicroARNs , ARN Largo no Codificante , ARN Largo no Codificante/genética , MicroARNs/genética , Biología Computacional/métodos , Animales , Humanos , Redes Reguladoras de Genes , Distribución Normal
12.
J Cell Mol Med ; 28(19): e18591, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39347936

RESUMEN

The unique non-coding RNA molecule known as circular RNA (circRNA) is distinguished from conventional linear RNA by having a longer half-life, greater degree of conservation and inherent solidity. Extensive research has demonstrated the profound impact of circRNA expression on cellular drug sensitivity and therapeutic efficacy. There is an immediate need for the creation of efficient computational techniques to anticipate the potential correlations between circRNA and drug sensitivity, as classical biological research approaches are time-consuming and costly. In this work, we introduce a novel deep learning model called SNMGCDA, which aims to forecast the relationships between circRNA and drug sensitivity. SNMGCDA incorporates a diverse range of similarity networks, enabling the derivation of feature vectors for circRNAs and drugs using three distinct calculation methods. First, we utilize a sparse autoencoder for the extraction of drug characteristics. Subsequently, the application of non-negative matrix factorization (NMF) enables the identification of relationships between circRNAs and drugs based on their shared features. Additionally, the multi-head graph attention network is employed to capture the characteristics of circRNAs. After acquiring the characteristics from these three separate components, we combine them to form a unified and inclusive feature vector for each cluster of circRNA and drug. Finally, the relevant feature vectors and labels are inputted into a multilayer perceptron (MLP) to make predictions. The outcomes of the experiment, obtained through 5-fold cross-validation (5-fold CV) and 10-fold cross-validation (10-fold CV), demonstrate SNMGCDA outperforms five other state-of-art methods in terms of performance. Additionally, the majority of case studies have predominantly confirmed newly discovered correlations by SNMGCDA, thereby emphasizing its reliability in predicting potential relationships between circRNAs and drugs.


Asunto(s)
ARN Circular , ARN Circular/genética , ARN Circular/metabolismo , Humanos , Biología Computacional/métodos , Aprendizaje Profundo , Algoritmos , Antineoplásicos/farmacología , Resistencia a Antineoplásicos/genética
13.
J Transl Med ; 22(1): 867, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334157

RESUMEN

BACKGROUND: Acute myeloid leukaemia (AML) comprises a group of heterogeneous and aggressive haematological malignancies with unsatisfactory prognoses and limited treatment options. Treatments targeting B-cell lymphoma-2 (BCL-2) with venetoclax have been approved for patients with AML, and venetoclax-based drug combinations are becoming the standard of care for older patients unfit for intensive chemotherapy. However, the therapeutic duration of either single or combination strategies is limited, and the development of resistance seems inevitable. Therefore, more effective combination regimens are urgently needed. METHODS: The efficacy of combination therapy with NL101, a SAHA-bendamustine hybrid, and venetoclax was evaluated in preclinical models of AML including established cell lines, primary blasts from patients, and animal models. RNA-sequencing and immunoblotting were used to explore the underlying mechanism. RESULTS: NL101 significantly potentiated the activity of venetoclax in AML cell lines, as evidenced by the enhanced decrease in viability and induction of apoptosis. Mechanistically, the addition of NL101 to venetoclax decreased the stability of the antiapoptotic protein myeloid cell leukaemia-1 (MCL-1) by inhibiting ERK, thereby facilitating the release of BIM and triggering mitochondrial apoptosis. Moreover, the strong synergy between NL101 and venetoclax also relied on the downregulation of c-Myc via PI3K/Akt/GSK3ß signalling. The combination of NL101 and venetoclax synergistically eliminated primary blasts from 10 AML patients and reduced the leukaemia burden in an MV4-11 cell-derived xenograft model. CONCLUSIONS: Our results encourage the pursuit of clinical trials of combined treatment with NL101 and venetoclax and provide a novel venetoclax-incorporating therapeutic strategy for AML.


Asunto(s)
Apoptosis , Compuestos Bicíclicos Heterocíclicos con Puentes , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-myc , Sulfonamidas , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Línea Celular Tumoral , Animales , Proteínas Proto-Oncogénicas c-myc/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Apoptosis/efectos de los fármacos , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/efectos de los fármacos , Femenino
14.
Int Immunopharmacol ; 142(Pt B): 113096, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39288625

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is characterized by high invasiveness and poor prognosis. The role of Sorbin and SH3 domain-containing protein 2 (SORBS2) in ESCC remains largely unexplored. METHODS: The expression levels of SORBS2 in ESCC were detected using RNA-seq and proteomics data. The biological functions of SORBS2 in ESCC were investigated through in vivo and in vitro experiments. The mechanism of SORBS2 was explored using RIP-seq technology, which identified the key downstream molecule metalloproteinase-3 (TIMP3). The interaction between SORBS2 and TIMP3, including specific binding sites, was validated through RIP-qPCR and RNA pull-down assays. The impact of altered SORBS2 expression in ESCC on HUVECs was assessed using endothelial tube formation assays. RESULTS: SORBS2 expression was significantly downregulated in ESCC tissues, and its decreased expression was associated with poor prognosis. Overexpression of SORBS2 in ESCC cell lines inhibited cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SORBS2 bound to the 3' UTR of TIMP3 mRNA, enhancing its stability and thereby regulating TIMP3 expression. Rescue experiments demonstrated that increased TIMP3 expression could reverse the promotive effects of SORBS2 knockdown on ESCC, confirming TIMP3 as a critical downstream molecule of SORBS2. Furthermore, downregulation of SORBS2 in ESCC cells was associated with activation of HUVEC functions, whereas upregulation of TIMP3 could reverse this effect. The SORBS2/TIMP3 axis may exert tumor suppressive effects by influencing extracellular matrix degradation. CONCLUSION: This study confirms that SORBS2 inhibits ESCC tumor progression by regulating extracellular matrix degradation through TIMP3, providing a potential therapeutic target for future treatment interventions.


Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Inhibidor Tisular de Metaloproteinasa-3 , Humanos , Inhibidor Tisular de Metaloproteinasa-3/genética , Inhibidor Tisular de Metaloproteinasa-3/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Animales , Línea Celular Tumoral , Masculino , Ratones Desnudos , Femenino , Ratones , Células Endoteliales de la Vena Umbilical Humana , Ratones Endogámicos BALB C , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Inhibidores de Serinpeptidasas Tipo Kazal
15.
Toxicol Appl Pharmacol ; 492: 117103, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278550

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) is among the most aggressive hematological malignancies and patients are commonly treated with combinatorial immunochemotherapies such as R-CHOP. Till now, the prognoses are still variable and unsatisfactory, depending on the molecular subtype and the treatment response. Developing effective and tolerable new agents is always urgently needed, and compounds from a natural source have gained increasing attentions. Wogonin is an active flavonoid extracted from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi and has shown extensive antitumor potentials. However, the therapeutic effect of wogonin on DLBCL remains unknown. Here, we found that treatment with wogonin dose- and time-dependently reduced the viability in a panel of established DLBCL cell lines. The cytotoxicity of wogonin was mediated through apoptosis induction, along with the loss of mitochondrial membrane potential and the downregulation of BCL-2, MCL-1, and BCL-xL. In terms of the mechanism, wogonin inhibited the PI3K and MAPK pathways, as evidenced by the clear decline in the phosphorylation of AKT, GSK3ß, S6, ERK, and P38. Furthermore, the combination of wogonin and the BCL-2 inhibitor venetoclax elicited synergistically enhanced killing effect on DLBCL cells regardless of their molecular subtypes. Finally, administration of wogonin significantly impeded the progression of the DLBCL tumor in a xenograft animal model without obvious side effects. Taken together, the present study suggests a promising potential of wogonin in the treatment of DLBCL patients either as monotherapy or an adjuvant for venetoclax-based combinations.

16.
Ital J Pediatr ; 50(1): 189, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300569

RESUMEN

BACKGROUND: Neurocognitive disorders frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities induced by preoperative cardiac structural changes. We aimed to evaluate subcortical nuclei volume changes and cognition in postoperative tetralogy of Fallot (TOF) children, and analyze their relationship with preoperative cardiac structural changes. METHODS: This case-control study involved thirty-six children with repaired TOF and twenty-nine healthy controls (HCs). We utilized three-dimensional (3D) T1-weighted high-resolution structural images alongside the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) to evaluate the cognitive differences between the TOF and HC group. RESULTS: We observed notable differences in subcortical nuclei volume between the TOF and HC group, specifically in the left amygdala nucleus (LAM, TOF: 1292.60 ± 155.57; HC: 1436.27 ± 140.62, p < 0.001), left thalamus proper nucleus (LTHA, TOF: 6771.54 ± 666.03; HC: 7435.36 ± 532.84, p < 0.001), and right thalamus proper nucleus (RTHA, TOF: 6514.61 ± 715.23; HC: 7162.94 ± 554.60, p < 0.001). Furthermore, a diminished integrity of LAM ( ß:-19.828, 95% CI: -36.462, -3.193), which showed an inverse relationship with the size of the preoperative ventricular septal defect (VSD), correlated with lower working memory indices in children with TOF. CONCLUSIONS: Our findings indicate that subcortical nuclei structural injuries possibly potentially stemming from cardiac anatomical abnormalities, are associated with impaired working memory in preschool-aged children with TOF. The LAM in particular may serve as a potential biomarker for neurocognitive deficits in TOF, offering predictive value for future neurodevelopmental outcomes, and shedding light on the neurophysiological mechanisms of these cognitive impairments.


Asunto(s)
Tetralogía de Fallot , Humanos , Tetralogía de Fallot/cirugía , Preescolar , Femenino , Masculino , Estudios Transversales , Estudios de Casos y Controles , Imagen por Resonancia Magnética , Cognición/fisiología , Procedimientos Quirúrgicos Cardíacos , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/patología
17.
JMIR Mhealth Uhealth ; 12: e56580, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240210

RESUMEN

Background: Physical therapy has demonstrated efficacy in managing nonspecific low back pain (NLBP) among patients. Nevertheless, the prevalence of NLBP poses a challenge, as the existing medical infrastructure may be insufficient to care for the large patient population, particularly in geographically remote regions. Telerehabilitation emerges as a promising method to address this concern by offering a method to deliver superior medical care to a greater number of patients with NLBP. Objective: The purpose of this study is to demonstrate the physical and psychological effectiveness of a user-centered telerehabilitation program, consisting of a smartphone app and integrated sensors, for patients with NLBP. Methods: This was a single-center, prospective, randomized controlled trial for individuals with NLBP for a duration exceeding 3 months. All participants were assigned randomly to either the telerehabilitation-based exercise group (TBEG) or the outpatient-based exercise group (OBEG). All participants completed a 30-minute regimen of strength and stretching exercises 3 times per week, for a total of 8 weeks, and were required to complete assessment questionnaires at 0, 2, 4, and 8 weeks. The TBEG completed home-based exercises and questionnaires using a telerehabilitation program, while the OBEG completed them in outpatient rehabilitation. The Oswestry Disability Index (ODI) served as the primary outcome measure, assessing physical disability. Secondary outcomes included the Numeric Pain Rating Scale, Fear-Avoidance Beliefs Questionnaire, and 36-item Short-Form Health Survey. Results: In total, 54 of 129 eligible patients were enrolled and randomly assigned to the study. The completion of all the interventions and assessments in the TBEG and OBEG was 89% (24/27) and 81% (22/27). The findings indicate that no statistical significance was found in the difference of ODI scores between the TBEG and the OBEG at 2 weeks (mean difference -0.91; odds ratio [OR] 0.78, 95% CI -5.96 to 4.14; P=.72), 4 weeks (mean difference -3.80; OR 1.33, 95% CI -9.86 to -2.25; P=.21), and 8 weeks (mean difference -3.24; OR 0.92, 95% CI -8.65 to 2.17; P=.24). The improvement of the ODI in the TBEG (mean -16.42, SD 7.30) and OBEG (mean -13.18, SD 8.48) was higher than 10 after an 8-week intervention. No statistically significant differences were observed between the 2 groups at the 8-week mark regarding the Fear-Avoidance Beliefs Questionnaire (mean difference 8.88; OR 1.04, 95% CI -2.29 to 20.06; P=.12) and Numeric Pain Rating Scale (mean difference -0.39; OR 0.44, 95% CI -2.10 to 1.31; P=.64). In the subgroup analysis, there was no statistically significant difference in outcomes between the 2 groups. Conclusions: Telerehabilitation interventions demonstrate comparable therapeutic efficacy for individuals with NLBP when compared to conventional outpatient-based physical therapy, yielding comparable outcomes in pain reduction and improvement in functional limitations.


Asunto(s)
Terapia por Ejercicio , Dolor de la Región Lumbar , Telerrehabilitación , Humanos , Dolor de la Región Lumbar/psicología , Dolor de la Región Lumbar/rehabilitación , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Terapia por Ejercicio/métodos , Terapia por Ejercicio/psicología , Encuestas y Cuestionarios , Resultado del Tratamiento , Dimensión del Dolor/métodos
19.
Clin Oral Investig ; 28(10): 543, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316184

RESUMEN

OBJECTIVES: To compare the occlusal contact regions (OCRs) obtained through an intraoral scanning system and conventional impression procedures via an innovative evaluation method. MATERIALS AND METHODS: Fifteen participants with complete dentitions and stable centric occlusion were included. Three groups were created based on the technique used to obtain the OCRs of quadrant posterior teeth at the maximal intercuspal position: 100 µm articulating paper (Control), an intraoral scanner (Test 1, T1) and conventional impression procedure (Test 2, T2). OCRs of control group were digitized by the intraoral scanner, while all conventional impressions were cast and digitized by an extraoral scanner. The virtual occlusal records of the 2 test groups were obtained by buccal bite registration. The OCRs within 100 µm in the 3 groups were three-dimensionally superimposed based on the tooth surfaces and the area of OCRs (SC, ST1, ST2) was calculated. The area of overlapping OCRs (SO) between the test groups and the control group was calculated. In the two test groups, the consistency rate of OCRs (SO/SC) and the positive rate of OCRs (SO/ST) were calculated and compared. For occlusal tightness evaluation, the mean occlusal clearances (OC) as well as minimum OC between the upper and lower models were calculated and compared. RESULTS: The consistency rate of OCRs was 0.73 ± 0.17 for T1 group and 0.23 ± 0.13 for T2 group (p < 0.001). The positive rate of OCRs was 0.67 ± 0.15 for T1 group and 0.56 ± 0.23 for T2 group (p = 0.143). The mean OC was 51.32 ± 16.04 µm for T1 group and 68.20 ± 18.15 µm for T2 group (p = 0.024). The minimum OC was - 61.74 ± 35.38 µm for T1 group and 4.09 ± 27.15 µm for T2 group (p < 0.001). CONCLUSIONS: For obtaining occlusal records in the quadrant posterior region, the tested intraoral scanning system was more reliable for recording occlusal contact regions and showed higher occlusal tightness compared with conventional impression procedures. CLINICAL RELEVANCE: (1) The evaluation method can assist clinicians in making more objective analysis and comparisons among different sources of virtual occlusal records. (2) Occlusal tightness is a key and indispensable indicator in the evaluation of virtual occlusal records, and it can be quantified by measuring the occlusal clearance utilizing the current evaluation method.


Asunto(s)
Técnica de Impresión Dental , Oclusión Dental , Humanos , Masculino , Femenino , Adulto , Registro de la Relación Maxilomandibular/métodos , Imagenología Tridimensional/métodos , Modelos Dentales
20.
Commun Biol ; 7(1): 1121, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261625

RESUMEN

Neurodevelopmental disorders are currently one of the major complications faced by patients with congenital heart disease (CHD). Chronic hypoxia in the prenatal and postnatal preoperative brain may be associated with neurological damage and impaired long-term cognitive function, but the exact mechanisms are unknown. In this study, we find that delayed neuronal migration and impaired synaptic development are attributed to altered Atoh1 under chronic hypoxia. This is due to the fact that excessive Atoh1 facilitates expression of Kif21b, which causes excess in free-state α-tubulin, leading to disrupted microtubule dynamic stability. Furthermore, the delay in neonatal brain maturation induces cognitive disabilities in adult mice. Then, by down-regulating Atoh1 we alleviate the impairment of cell migration and synaptic development, improving the cognitive behavior of mice to some extent. Taken together, our work unveil that Atoh1 may be one of the targets to ameliorate hypoxia-induced neurodevelopmental disabilities and cognitive impairment in CHD.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Disfunción Cognitiva , Neuronas , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Ratones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Neuronas/metabolismo , Hipoxia/metabolismo , Femenino , Neurogénesis , Animales Recién Nacidos , Ratones Endogámicos C57BL , Masculino , Movimiento Celular
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