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1.
ACS Nano ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975706

RESUMO

Electrolytic ablation (EA) is a burgeoning treatment for solid tumors, in which electrical energy catalyzes a chemical reaction to generate reactive species that can eradicate cancer cells. However, the application of this technique has been constrained owing to the limited spatial effectiveness and complexity of the electrode designs. Therefore, the incorporation of nanotechnology into EA is anticipated to be a significant improvement. Herein, we present a therapeutic approach based on difructose dianhydride IV-conjugated polyethylenimine-polyethylene glycol-modified gold nanorods as electric nanoantennas and nanoelectrocatalysts for EA. We demonstrate that square-wave direct current (DC) fields trigger a reaction between water molecules and chloride ions on the gold nanorod surface, generating electrolytic products including hydrogen, oxygen, and chlorine gases near the electrodes, changing the pH, and inducing cell death. These electric nanoantennas showed significant efficacy in treating colorectal cancer both in vitro and in vivo after DC treatment. These findings clearly indicate that gold nanoantennas enhance the effectiveness of EA by creating a localized electric field and catalyzing electrolytic reactions for the induction of locoregional pH changes within the tumor. By overcoming the limitations of traditional EA and offering an enhanced level of tumor specificity and control, this nanotechnology-integrated approach advances further innovations in cancer therapies.

2.
Cancer Lett ; 598: 217090, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945201

RESUMO

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.

3.
Sci Signal ; 17(840): eadc9142, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861615

RESUMO

Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms by which ADT induces neuroendocrine differentiation in advanced PCa. We found that transmembrane protein 1 (MCTP1), which has putative Ca2+ sensing function and multiple Ca2+-binding C2 domains, was abundant in samples from patients with advanced PCa. MCTP1 was associated with the expression of the EMT-associated transcription factors ZBTB46, FOXA2, and HIF1A. The increased abundance of MCTP1 promoted PC3 prostate cancer cell migration and neuroendocrine differentiation and was associated with SNAI1-dependent EMT in C4-2 PCa cells after ADT. ZBTB46 interacted with FOXA2 and HIF1A and increased the abundance of MCTP1 in a hypoxia-dependent manner. MCTP1 stimulated Ca2+ signaling and AKT activation to promote EMT and neuroendocrine differentiation by increasing the SNAI1-dependent expression of EMT and neuroendocrine markers, effects that were blocked by knockdown of MCTP1. These data suggest an oncogenic role for MCTP1 in the maintenance of a rare and aggressive prostate cancer subtype through its response to Ca2+ and suggest its potential as a therapeutic target.


Assuntos
Diferenciação Celular , Transição Epitelial-Mesenquimal , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Androgênios/metabolismo , Androgênios/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Fator 3-beta Nuclear de Hepatócito/metabolismo , Fator 3-beta Nuclear de Hepatócito/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Células Neuroendócrinas/metabolismo , Células Neuroendócrinas/patologia , Células PC-3 , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
4.
Chem Asian J ; 19(12): e202400166, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38664856

RESUMO

In this study, we demonstrate the influence of crystallinity and morphology on the analytical performance of various Cu2MoS4 (CMS) nanocatalysts-based electrochemical sensors for the high-efficiency detection of Ofloxacin (OFX) antibiotic. The electrochemical kinetics parameters including peak current response (ΔIp), peak-to-peak separation (ΔEp), electrochemically active surface area (ECSA), electron-transfer resistance (Rct), were obtained through the electrochemical analyses, which indicate the single-crystalline nature of CMS nanomaterials (NMs) is beneficial for enhanced electron-transfer kinetics. The morphological features and the electrochemical results for OFX detection substantiate that by tuning the tube-like to plate-like structures of the CMS NMs, it might noticeably enhance multiple adsorption sites and more intrinsic active catalytic sites due to the diffusion of analytes into the interstitial spaces between CMS nanoplates. As results, highly single-crystalline and plate-shaped morphology structures of CMS NMs would significantly enhance the electrocatalytic OFX oxidation in terms of onset potential (Eonset), Tafel slope, catalytic rate constant (kcat), and adsorption capacity (Γ). The CMS NMs-based electrochemical sensing platform showed excellent analytical performance toward the OFX detection with two ultra-wide linear detection concentration ranges from 0.25-100 and 100-1000 µM, a low detection limit of 0.058 µM, and an excellent electrochemical sensitivity (0.743 µA µM-1 cm-2).

5.
Lab Chip ; 24(9): 2485-2496, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38587207

RESUMO

The COVID-19 pandemic greatly impacted the in vitro diagnostic market, leading to the development of new technologies such as point-of-care testing (POCT), multiplex testing, and digital health platforms. In this study, we present a self-contained microfluidic chip integrated with an internet-of-things (IoT)-based point-of-care (POC) device for rapid and sensitive diagnosis of respiratory viruses. Our platform enables sample-to-answer diagnostics within 70 min by automating RNA extraction, reverse transcription-loop-mediated isothermal amplification (RT-LAMP), and fluorescence detection. The microfluidic chip is designed to store all the necessary reagents for the entire diagnostic assay, including a lysis buffer, a washing buffer, an elution buffer, and a lyophilized RT-LAMP cocktail. It can perform nucleic acid extraction, aliquoting, and gene amplification in multiple reaction chambers without cross-contamination. The IoT-based POC device consists of a Raspberry Pi 4 for device control and data processing, a CMOS sensor for measuring fluorescence signals, a resistive heater panel for temperature control, and solenoid valves for controlling the movement of on-chip reagent solutions. The proposed device is portable and features a touchscreen for user control and result display. We evaluated the performance of the platform using 11 clinical respiratory virus samples, including 5 SARS-CoV-2 samples, 2 influenza A samples, and 4 influenza B samples. All tested clinical samples were accurately identified with high specificity and fidelity, demonstrating the ability to simultaneously detect multiple respiratory viruses. The combination of the integrated microfluidic chip with the POC device offers a simple, cost-effective, and scalable solution for rapid molecular diagnosis of respiratory viruses in resource-limited settings.


Assuntos
COVID-19 , Internet das Coisas , Dispositivos Lab-On-A-Chip , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Técnicas de Diagnóstico Molecular/instrumentação , Desenho de Equipamento , Testes Imediatos , RNA Viral/análise , RNA Viral/isolamento & purificação , RNA Viral/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia
6.
IEEE J Biomed Health Inform ; 28(6): 3411-3421, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381640

RESUMO

OBJECTIVE: Exercise monitoring with low-cost wearables could improve the efficacy of remote physical-therapy prescriptions by tracking compliance and informing the delivery of tailored feedback. While a multitude of commercial wearables can detect activities of daily life, such as walking and running, they cannot accurately detect physical-therapy exercises. The goal of this study was to build open-source classifiers for remote physical-therapy monitoring and provide insight on how data collection choices may impact classifier performance. METHODS: We trained and evaluated multi-class classifiers using data from 19 healthy adults who performed 37 exercises while wearing 10 inertial measurement units (IMUs) on the chest, pelvis, wrists, thighs, shanks, and feet. We investigated the effect of sensor density, location, type, sampling frequency, output granularity, feature engineering, and training-data size on exercise-classification performance. RESULTS: Exercise groups (n = 10) could be classified with 96% accuracy using a set of 10 IMUs and with 89% accuracy using a single pelvis-worn IMU. Multiple sensor modalities (i.e., accelerometers and gyroscopes), high sampling frequencies, and more data from the same population did not improve model performance, but in the future data from diverse populations and better feature engineering could. CONCLUSIONS: Given the growing demand for exercise monitoring systems, our sensitivity analyses, along with open-source tools and data, should reduce barriers for product developers, who are balancing accuracy with product formfactor, and increase transparency and trust in clinicians and patients.


Assuntos
Acelerometria , Exercício Físico , Dispositivos Eletrônicos Vestíveis , Humanos , Adulto , Masculino , Feminino , Exercício Físico/fisiologia , Acelerometria/métodos , Adulto Jovem , Monitorização Ambulatorial/métodos , Monitorização Ambulatorial/instrumentação , Processamento de Sinais Assistido por Computador
8.
Gait Posture ; 107: 233-239, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37852884

RESUMO

BACKGROUND: While several studies have explored the impacts of smartphone usage on postural balance, their tasks are limited to texting or calling, and the studies were performed on rigid ground. RESEARCH QUESTIONS: METHODS: Sixteen healthy young adults were recruited to perform two smartphone tasks: taking selfies and posting statuses on social media; participants were standing on four different grounds: rigid, foam-based compliant, robot-simulated compliant, and robot-simulated oscillatory grounds. The center-of-pressure (CoP) under each foot was recorded via force plates and the net CoP was calculated. Temporal, spatial, and control aspects of postural balance were analyzed by virtual time-to-contact (VTC), CoP path length (PL) and sway area (SA), and switching rate (SR), respectively. Two-way repeated measures analysis of variance (ANOVA) tests were performed for each dependent variable to compare the mean differences between smartphone tasks and ground conditions and their interaction effect. Paired t-tests with Bonferroni correction were used to determine significant differences in post-hoc analyses. RESULTS: VTC decreased significantly whereas CoP PL and SA increased significantly during smartphone usage (all p-values <0.001). Interaction effects between task and ground condition (all p-values <0.001) were observed in all measures but SR, implying that the effect of smartphone usage on postural balance can significantly change depending on the ground condition. SIGNIFICANCE: These results highlight the potential fall risks due to the impact of modern smartphone usage on standing balance. Understanding the effect of smartphone usage on standing balance and the interaction effect with various ground conditions opens the door for potential balance assistive devices and mobile phone applications to minimize falls.


Assuntos
Smartphone , Envio de Mensagens de Texto , Adulto Jovem , Humanos , Posição Ortostática , , Equilíbrio Postural
9.
Int J Mol Sci ; 24(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37569304

RESUMO

Prostate cancer (PCa) is one of the most prevalent cancers in men, yet its pathogenic pathways remain poorly understood. Transcriptomics and high-throughput sequencing can help uncover cancer diagnostic targets and understand biological circuits. Using prostate adenocarcinoma (PRAD) datasets of various web-based applications (GEPIA, UALCAN, cBioPortal, SR Plot, hTFtarget, Genome Browser, and MetaCore), we found that upregulated dysbindin domain-containing 1 (DBNDD1) expression in primary prostate tumors was strongly correlated with pathways involving the cell cycle, mitotic in KEGG, WIKI, and REACTOME database, and transcription factor-binding sites with the DBNDD1 gene in prostate samples. DBNDD1 gene expression was influenced by sample type, cancer stage, and promoter methylation levels of different cancers, such as PRAD, liver hepatocellular carcinoma (LIHC), and lung adenocarcinoma (LUAD). Regulation of glycogen synthase kinase (GSK)-3ß in bipolar disorder and ATP/ITP/GTP/XTP/TTP/CTP/UTP metabolic pathways was closely correlated with the DBNDD1 gene and its co-expressed genes in PCa. DBNDD1 gene expression was positively associated with immune infiltration of B cells, Myeloid-derived suppressor cell (MDSC), M2 macrophages, andneutrophil, whereas negatively correlated with CD8+ T cells, T follicular helper cells, M1 macrophages, and NK cells in PCa. These findings suggest that DBNDD1 may serve as a viable prognostic marker not only for early-stage PCa but also for immunotherapies.

10.
Hum Mov Sci ; 91: 103134, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37531739

RESUMO

BACKGROUND: This study aimed to (1) investigate postural balance control on 2-Dimensional (2D) compliant surfaces using directional virtual time-to-contact (d-VTC), a novel method for VTC calculation; and (2) compare d-VTC with conventional balance measures in this context. METHODS: A dual-axis robotic platform was used to simulate 2D surfaces/grounds with varying compliance levels. Twenty healthy young adults stood on the platform with either open or closed eyes. Balance was evaluated using d-VTC in multiple aspects, including temporal (VTC mean), spatial (boundary contact - BC), and control aspects (switching rate - SR). Additionally, conventional balance measures, namely center-of-pressure (COP) area and COP root-mean-square (RMS), were employed for further comparisons with d-VTC measures. Normality checks were performed using Shapiro-Wilk tests. Two-way repeated measures ANOVA tests were used to examine the effects of surface compliance and vision on postural balance, followed by post-hoc pairwise comparisons across conditions with Bonferroni correction. RESULTS: The results showed that increasing surface compliance and/or absence of vision caused a significant decrease in VTC mean (all p-values <0.001; all ηp2 > 0.816). Interaction effects between surface compliance and vision on 2D and ML VTC mean were also significant (all p-values <0.019; all ηp2 > 0.355). The AP and ML BC values indicated a converging trend to 50%. No vision effect was observed (p = 0.458), but both surface compliance (p = 0.001; ηp2 = 0.522) and interaction (p = 0.002; ηp2 = 0.492) effects were significant. Decreases in SR were significant due to the compliance of the standing surface (p = 0.01; ηp2 = 0.401) but not vision (p = 0.109). COP area increased due to both surface and vision conditions (all p-values <0.001; all ηp2 > 0.872). AP and ML RMS were altered by vision (all p-values <0.001; all ηp2 > 0.741), but not by surface condition (all p-values >0.06). No interaction effect was observed in the conventional measures (all p-values >0.07). CONCLUSION: Balance control is compromised by 2D compliant surfaces, which is exacerbated when vision is absent. Among all balance measures, VTC mean measures demonstrated particularly high sensitivity in identifying decreased balance capabilities, while BC and SR provided new insights into fall risks and balance control mechanisms. These insights may facilitate the development of rehabilitation training or assistive devices for fall prevention.


Assuntos
Postura , Posição Ortostática , Adulto Jovem , Humanos , Visão Ocular , Fatores de Tempo , Equilíbrio Postural
11.
IEEE J Transl Eng Health Med ; 11: 282-290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275470

RESUMO

This paper presents a twin dual-axis robotic platform system which is designed for the characterization of postural balance under various environmental conditions and quantification of bilateral ankle mechanics in 2 degrees-of-freedom (DOF) during standing and walking. Methods: Validation experiments were conducted to evaluate performance of the system: 1) to apply accurate position perturbations under different loading conditions; 2) to simulate a range of stiffness-defined mechanical environments; and 3) to reliably quantify the joint impedance of mechanical systems. In addition, several human experiments were performed to demonstrate the system's applicability for various lower limb biomechanics studies. The first two experiments quantified postural balance on a compliance-controlled surface (passive perturbations) and under oscillatory perturbations with various frequencies and amplitudes (active perturbations). The second two experiments quantified bilateral ankle mechanics, specifically, ankle impedance in 2-DOF during standing and walking. The validation experiments showed high accuracy of the platform system to apply position perturbations, simulate a range of mechanical environments, and quantify the joint impedance. Results of the human experiments further demonstrated that the platform system is sensitive enough to detect differences in postural balance control under challenging environmental conditions as well as bilateral differences in 2-DOF ankle mechanics. This robotic platform system will allow us to better understand lower limb biomechanics during functional tasks, while also providing invaluable knowledge for the design and control of many robotic systems including robotic exoskeletons, prostheses and robot-assisted balance training programs. Clinical and Translational Impact Statement- Our robotic platform system serves as a tool to better understand the biomechanics of both healthy and neurologically impaired individuals and to develop assistive robotics and rehabilitation training programs using this information.


Assuntos
Robótica , Humanos , Robótica/métodos , Fenômenos Biomecânicos , Tornozelo , Articulação do Tornozelo , Caminhada
12.
Anal Chim Acta ; 1270: 341475, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37311615

RESUMO

Owing to the effective combination between MoS2 sheets with CuInS2 nanoparticles (NPs), a direct Z-scheme heterojunction was successfully constructed and proved as a promising structure to modify the working electrode surface with the aim of enhancing overall sensing performance towards CAP detection. Herein, MoS2 was employed as a high mobility carrier transport channel with a strong photo-response, large specific surface area, and high in-plane electron mobility, while CuInS2 acted as an efficient light absorber. This not only offered a stable nanocomposite structure but also created impressive synergistic effects of high electron conductivity, large surface area, highlight exposure interface, as well as favorable electron transfer process. Moreover, the possible mechanism and hypothesis of the transfer pathway of photo-induced electron-hole pairs on the CuInS2-MoS2/SPE as well as their impacts on the redox reaction of K3/K4 probes and CAP were proposed and investigated in detail via a series of calculated kinetic parameters, demonstrating the high practical applicability of light-assisted electrodes. Indeed, the detection concentration range of the proposed electrode was widened from 0.1 to 50 µM, compared with that of 1-50 µM without irradiation. Also, the LOD and sensitivity values were calculated to be approximately 0.06 µM and 0.4623 µA µM-1, which is better than that of 0.3 µM and 0.095 µA µM-1 without irradiation.

13.
Cell Death Dis ; 14(5): 304, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142586

RESUMO

Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer. Here, we demonstrated the tumor-suppressive role of the AR and found that activated AR could directly bind to the regulatory sequence of muscarinic acetylcholine receptor 4 (CHRM4) and downregulate its expression. CHRM4 was highly expressed in prostate cancer cells after androgen-deprivation therapy (ADT). CHRM4 overexpression may drive neuroendocrine differentiation of prostate cancer cells and is associated with immunosuppressive cytokine responses in the tumor microenvironment (TME) of prostate cancer. Mechanistically, CHRM4-driven AKT/MYCN signaling upregulated the interferon alpha 17 (IFNA17) cytokine in the prostate cancer TME after ADT. IFNA17 mediates a feedback mechanism in the TME by activating the CHRM4/AKT/MYCN signaling-driven immune checkpoint pathway and neuroendocrine differentiation of prostate cancer cells. We explored the therapeutic efficacy of targeting CHRM4 as a potential treatment for NEPC and evaluated IFNA17 secretion in the TME as a possible predictive prognostic biomarker for NEPC.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteínas Proto-Oncogênicas c-akt , Antagonistas de Androgênios/uso terapêutico , Interferon-alfa/uso terapêutico , Microambiente Tumoral , Linhagem Celular Tumoral , Diferenciação Celular , Receptores Androgênicos/metabolismo , Receptor Muscarínico M4/uso terapêutico
14.
RSC Adv ; 13(13): 8753-8764, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36936823

RESUMO

In this study, bio-Ag/ZnO NCs were synthesized via a microwave-assisted biogenic electrochemical method using mangosteen (Garcinia mangostana) peel extract as a biogenic reducing agent for the reduction of Zn2+ and Ag+ ions to form hybrid nanoparticles. The as-synthesized NC samples at three different microwave irradiation temperatures (Z 70, Z 80, Z 90) exhibited a remarkable difference in size and crystallinity that directly impacted their electrocatalytic behaviors as well as electrochemical sensing performance. The obtained results indicate that the Z 90 sample showed the highest electrochemical performance among the investigated samples, which is attributed to the improved particle size distribution and crystal microstructure that enhanced charge transfer and the electroactive surface area. Under the optimal conditions for carbaryl pesticide detection, the proposed nanosensor exhibited a high electrochemical sensitivity of up to 0.303 µA µM-1 cm-2 with a detection limit of LOD ∼0.27 µM for carbaryl pesticide detection in a linear range of 0.25-100 µM. Overall, the present work suggests that bio-Ag/ZnO NCs are a potential candidate for the development of a high-performance electrochemical-based non-enzymatic nanosensor with rapid monitoring, cost-effectiveness, and eco-friendly to detect carbaryl pesticide residues in agricultural products.

15.
Redox Biol ; 62: 102686, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36963289

RESUMO

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However, the metabolic pathways that regulate NE differentiation (NED) in PCa remain unclear. Herein, we show a regulatory mechanism in NED-associated metabolism dysfunction induced by ADT, whereby overexpression of pyruvate kinase L/R (PKLR) mediates oxidative stress through upregulation of reactive oxygen species modulator 1 (ROMO1), thereby promoting NED and aggressiveness. ADT mediates the nuclear translocation of PKLR, which binds to the MYCN/MAX complex to upregulate ROMO1 and NE-related genes, leading to altered mitochondrial function and NED of PCa. Targeting nuclear PKLR/MYCN using bromodomain and extra-terminal motif (BET) inhibitors has the potential to reduce PKLR/MYCN-driven NED. Abundant ROMO1 in serum samples may provide prognostic information in patients with ADT. Our results suggest that ADT resistance leads to upregulation of PKLR/MYCN/ROMO1 signaling, which may drive metabolic reprogramming and NED in PCa. We further show that increased abundance of serum ROMO1 may be associated with the development of NE-like PCa.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/farmacologia , Linhagem Celular Tumoral , Proteínas de Membrana , Proteínas Mitocondriais/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Piruvato Quinase/metabolismo , Transdução de Sinais
16.
Radiol Case Rep ; 18(4): 1605-1609, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36852290

RESUMO

Traumatic rupture of the thoracic aorta is a rare condition, with a high mortality rate. Over the last 2 decades, strategies for managing aortic injury caused by blunt chest trauma have changed substantially, resulting in significantly improved outcomes. The recent development of endovascular repair offers a less invasive alternative to conventional open repair, particularly in patients with multiple injuries. Here, we report the case of a 31-year-old man who was referred to our emergency department with blunt chest trauma following a motorcycle-truck collision. Computed tomography confirmed acute traumatic rupture of the thoracic aorta, and the patient was successfully treated with endovascular repair.

17.
ACS Sens ; 8(2): 515-521, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36722714

RESUMO

We proposed a portable sample pretreatment microsystem, which can be automatically operated through speech recognition in a smartphone app. The proposed sample pretreatment microsystem consists of a microfluidic chip, an air router, pressure and vacuum lines with air pump motors, six 3-way solenoid valves, and a microcontroller with a Bluetooth module. The command of a human voice conducted the whole process of DNA extraction from pathogenic bacterial samples. Thus, manual interference during the DNA extraction is eliminated, preventing any potential infection from human touch. The palm-sized sample pretreatment microsystem can be run by a portable battery or a conventional smartphone charger. Genomic DNA ofSalmonella typhimuriumwas purified on a chip in less than 1 min with an extraction efficiency of 70 ± 5%.


Assuntos
Aplicativos Móveis , Percepção da Fala , Humanos , Microfluídica , Smartphone , DNA/genética
18.
Sens Actuators B Chem ; 380: 133331, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36644652

RESUMO

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has threatened public health globally, and the emergence of viral variants has exacerbated an already precarious situation. To prevent further spread of the virus and determine government action required for virus control, accurate and rapid immunoassays for SARS-CoV-2 diagnosis are urgently needed. In this study, we generated monoclonal antibodies (mAbs) against the SARS-CoV-2 nucleocapsid protein (NP), compared their reactivity using an enzyme-linked immunosorbent assay (ELISA), and selected four mAbs designated 1G6, 3E10, 3F10, and 5B6 which have higher reactivity to NP and viral lysates of SARS-CoV-2 than other mAbs. Using an epitope mapping assay, we identified that 1G6 detected the C-terminal domain of SARS-CoV-2 NP (residues 248-364), while 3E10 and 3F10 bound to the N-terminal domain (residues 47-174) and 3F10 detected the N-arm region (residues 1-46) of SARS-CoV-2 NP. Based on the epitope study and sandwich ELISA, we selected the 1G6 and 3E10 Abs as an optimal Ab pair and applied them for a microfluidics-based point-of-care (POC) ELISA assay to detect the NPs of SARS-CoV-2 and its variants. The integrated and automatic microfluidic system could operate the serial injection of the sample, the washing solution, the HRP-conjugate antibody, and the TMB substrate solution simply by controlling air purge via a single syringe. The proposed Ab pair-equipped microsystem effectively detected the NPs of SARS-CoV-2 variants as well as in clinical samples. Collectively, our proposed platform provides an advanced protein-based diagnostic tool for detecting SARS-CoV-2.

19.
J Biomech ; 146: 111428, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36610387

RESUMO

Virtual time-to-contact (VTC) is a promising approach for investigating postural balance control. However, current VTC calculation approaches are limited as they (1) cannot be used to evaluate directional components of balance, and (2) only assess a single, temporal aspect of balance control. This study introduces a new approach for VTC calculation, namely directional VTC, expanding VTC to assess temporal, spatial, and control aspects of balance. Three case studies were conducted across varying populations and conditions as a proof-of-concept of the presented method. The first study examined quiet stance on a firm surface in people with Parkinson's disease (PD; n = 10) in comparison to their healthy peers (n = 10). The second and third studies assessed balance control of healthy individuals under challenging environments. Ten healthy individuals participated in standing tasks on compliant ground surfaces, while another ten on oscillatory ground surfaces, all simulated by a dual-axis robotic platform. Preliminary results not only provided a closer look at balance control with multiple aspects, including temporal, spatial, and control aspects, but also showed how different aspects of balance changed due to neurological diseases (Case Study I) or challenging standing grounds (Case Studies II and III). This study advances our understanding of posture biomechanics and its clinical applications.


Assuntos
Doença de Parkinson , Postura , Humanos , Posição Ortostática , Fatores de Tempo , Equilíbrio Postural
20.
Medicina (Kaunas) ; 58(9)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36143901

RESUMO

Background and Objectives: The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a pandemic even in 2022. As the initial symptoms of COVID-19 overlap with those of infections from other respiratory viruses, an accurate and rapid diagnosis of COVID-19 is essential for administering appropriate treatment to patients. Currently, the most widely used method for detecting respiratory viruses is based on real-time polymerase chain reaction (PCR) and includes reverse-transcription real-time quantitative PCR (RT-qPCR). However, RT-qPCR assays require sophisticated facilities and are time-consuming. This study aimed to develop a real-time quantitative loop-mediated isothermal amplification (RT-qLAMP) assay and compare its analytical performance with RT-qPCR. Materials and Methods: A total of 315 nasopharyngeal swabs from patients with symptoms of respiratory infections were included in this study. A primary screening of the specimens was performed using RT-qPCR. RNA/DNA from standard strains for respiratory viruses and heat-inactivated preparations of standard strains for SARS-CoV-2 were used to evaluate the accuracy and target specificity of the RT-qLAMP assay. Results: We successfully developed an RT-qLAMP assay for seven respiratory viruses: respiratory syncytial virus (RSV) A, RSV B, adenovirus, influenza (Flu) A (H1N1 and H3N2), Flu B, and SARS-CoV-2. RT-qLAMP was performed in a final reaction volume of 9.6 µL. No cross-reactivity was observed. Compared with the RT-PCR results, the sensitivity and specificity of the RT-qLAMP assay were 95.1% and 100%, respectively. The agreement between the two methods was 97.1%. The median amplification time to RT-qLAMP positivity was 22:34 min (range: 6:80-47:98 min). Conclusions: The RT-qLAMP assay requires a small number of reagents and samples and is performed with an isothermal reaction. This study established a fast, simple, and sensitive test that can be applied to point-of-care testing devices to facilitate the detection of respiratory viruses, including SARS-CoV-2.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , COVID-19/diagnóstico , Humanos , Vírus da Influenza A Subtipo H3N2 , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , RNA , SARS-CoV-2/genética , Sensibilidade e Especificidade
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