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BACKGROUND: Avascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis. METHODS: EVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS. RESULTS: Our results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN. CONCLUSIONS: These findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes.
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Researchers are increasingly interested in cell therapy using mesenchymal stem cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. Thus, we isolated and characterized extracellular vesicles (EVs) from human adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on RANKL-induced osteoclast differentiation. Purified EVs were collected from the supernatant of hMSCs by tangential flow filtration. Characterization of EVs included typical evaluation of the size and concentration of EVs by nanoparticle tracking analysis and morphology analysis using transmission electron microscopy. hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by EV treatment of osteoclasts. In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that has-miR122-5p was present at significantly high read counts. Overexpression of miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast differentiation and induced defects in F-actin ring formation and bone resorption. Our results also revealed that RANKL-induced phosphorylation of p38 and JNK and osteoclast-specific gene expression was decreased by miR122-5p transfection, which was consistent with the results of hMSC-EVs. These findings suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and could be a preventive candidate for destructive bone diseases.
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The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.
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Antineoplásicos , Neoplasias Ováricas , Femenino , Humanos , Animales , Ratones , Cisplatino/farmacología , Cisplatino/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/genética , Proteína X Asociada a bcl-2/genética , Línea Celular Tumoral , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proliferación Celular , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Proteínas de Homeodominio/farmacologíaRESUMEN
In this study, we propose high similarity and multiple angular segment display-based encoded microparticle fabrication using omni- and unidirectional data unit photolithography systems. Uniform high-correlation values are obtained regardless of the decoding direction when an omnidirectional data unit is used. In addition, multiple display angles are analyzed based on unidirectional data units with varying slit widths. Finally, encoded microparticles for multiple angular segment displays are fabricated and selective information recognition is demonstrated.
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BACKGROUND: Cervical spondylotic myelopathy (CSM) is a critical condition that results in significant neurologic deterioration. An accurate diagnosis is essential for determining its outcome and prognosis. The pathology is strongly associated with dynamic factors; therefore, dynamic magnetic resonance (MR) image could be crucial to accurately detect CSM. However, very few studies have evaluated the reliability and accuracy of dynamic MR in CSM. In this study, we aimed to compare intra- and interobserver reliabilities and accuracy of dynamic MR in detecting CSM using sagittal MR scans of the neck in the flexed, neutral, and extended position. METHODS: Out of 131 patients who underwent surgical treatments for CSM, 107 were enrolled in this study. The patient underwent three-types of sagittal MR scans that were obtained separately in different neck positions (neutral, flexion, and extension postures). The MR scans of the cervical spine were evaluated independently by three spine professionals, on the basis of tabled questionnaires. For accuracy, we performed a receiver operator characteristic analysis, and the overall discriminating ability of each method was measured by calculating the area under the ROC curve. The Cohen's kappa coefficient and the Fleiss-generalized kappa coefficient was used to the inter- and intra-observer reliabilities. RESULTS: The intraobserver reliability (using the Cohen's kappa coefficient) and interobserver reliability (using the Fless kappa coefficient) were respectively 0.64 and 0.52 for the neutral sagittal MR. The accuracy of neutral sagittal MR in detecting CSM was 0.735 (95% CI, 0.720 to 0.741) while that of extension sagittal MRI was 0.932 (96% CI, 0.921 to 0.948). CONCLUSIONS: Dynamic MR significantly showed better diagnostic reliability and accuracy in detecting CSM compared to conventional MR. In particular, extension MR scans could provide a more accurate diagnosis than other images.
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Enfermedades de la Médula Espinal , Espondilosis , Humanos , Reproducibilidad de los Resultados , Espondilosis/cirugía , Enfermedades de la Médula Espinal/cirugía , Imagen por Resonancia Magnética/métodos , Vértebras Cervicales/cirugíaRESUMEN
Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.
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Apoptosis/efectos de los fármacos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Eflornitina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo , Carcinoma Epitelial de Ovario/metabolismo , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Ornitina Descarboxilasa/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Human bone marrow (BM) is a kind of source of mesenchymal stem cells (MSCs) as well as growth factors and cytokines that may aid anti-inflammation and regeneration for various tissues, including cartilage and bone. However, since MSCs in BM usually occupy only a small fraction (0.001%) of nucleated cells, bone marrow aspirate concentrate (BMAC) for cartilage pathologies, such as cartilage degeneration, defect, and osteoarthritis, have gained considerable recognition in the last few years due to its potential benefits including disease modifying and regenerative capacity. Although further research with well-designed, randomized, controlled clinical trials is needed to elucidate the exact mechanism of BMAC, this may have the most noteworthy effect in patients with osteoarthritis. The purpose of this article is to review the general characteristics of BMAC, including its constituent, action mechanisms, and related issues. Moreover, this article aims to summarize the clinical outcomes of BMAC reported to date.
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Células de la Médula Ósea/metabolismo , Trasplante de Médula Ósea/métodos , Médula Ósea/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteoartritis/terapia , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Oligonol, a low molecular weight polyphenol derived from lychee fruit, not only has anti-inflammatory effects in various disease conditions but also has antitumor-promoting effects. We evaluate the nuclear factor-kappa B (NF-κB)-related anticancer effect of oligonol in ovarian cancer using SKOV-3 cells. METHODS: Cell viability was examined after oligonol treatment using MTT assay and reactive oxygen species (ROS) production measurement. Subsequently, apoptotic cell death was visualized by the TdT-mediated dUTP nick-end labeling (TUNEL) method. The effect of oligonol on the NF-κB signaling pathway was evaluated using western blot analysis and luciferase activity measurement of p65, an NF-κB subunit. RESULTS: Cell viability significantly decreased after oligonol treatment of 72 h. Apoptosis-related markers were highly expressed in oligonol-treated cells, and increased apoptosis after oligonol treatment was also confirmed using the TUNEL assay. Western blotting results showed the expression of NF-κB signaling pathway factors, p-ERK, TRAF2, and p-IκBα, increased following treatment with oligonol, whereas p65 and COX-2 expression decreased. Immunofluorescence imaging results showed p65 luciferase activity in the nucleus as well as a shift to cytoplasmic expression. CONCLUSION: Oligonol treatment significantly enhances apoptotic cell death in SKOV-3 cells, with the suppression of NF-κB activation, which plays an essential role in this anticancer effect.
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Apoptosis/efectos de los fármacos , Catequina/análogos & derivados , FN-kappa B/antagonistas & inhibidores , Neoplasias Ováricas/tratamiento farmacológico , Fenoles/farmacología , Catequina/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , FN-kappa B/fisiología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
PURPOSE: Treatment of a tibial plateau fracture (TPF) remains controversial and is generally challenging. Many authors report good results after conventional open reduction and internal fixation in TPF, but complications still occur. This study analyzed causes and outcomes of revision surgery for TPF. The usefulness of a flow chart for revision surgery in TPF was also evaluated. METHODS: We reviewed all patients who underwent more than two operations for a TPF between 2008 and 2015. Finally, 24 cases were selected and retrospectively investigated. The medial tibial plateau angle and proximal posterior tibial angle were radiologically evaluated. The American Knee Society Score (AKSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM), and bone union time were investigated after surgery. RESULTS: Revision surgery for infection was performed in eight cases, for nonunion in six cases, for posttraumatic arthritis (with total knee arthroplasty) in six cases, and for other reasons in four cases. The mean clinical AKSS at final follow-up was 87.3 ± 5.3 (range, 75-95), the functional AKSS was 81.9 ± 5.5 (range, 70-90), the WOMAC score was 9.9 ± 3.1 (range, 5-16), the flexion ROM was 119.8 ± 16.5° (range, 100-150°), and the extension ROM was 2.5 ± 3.3° (range, 0-10°). CONCLUSIONS: Although complications cannot be avoided in some cases, good clinical outcomes are possible when patients are divided according to the presence or absence of infection, with selection of appropriate revision surgery as shown in the flow chart. If an infection is present, treatment should be based on the presence or absence of bone union. If there is no infection, treatment should be based on the presence or absence of nonunion, post-traumatic arthritis, malunion, or immediate post-operative malreduction.
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Fijación Interna de Fracturas/efectos adversos , Traumatismos de la Rodilla/cirugía , Reducción Abierta/efectos adversos , Tibia/cirugía , Fracturas de la Tibia/cirugía , Adulto , Anciano , Femenino , Humanos , Traumatismos de la Rodilla/complicaciones , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Tibia/lesiones , Fracturas de la Tibia/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Pen-based devices have emerged as useful tools for measuring pH and glucose, and for fabricating microchannels and microarrays. Pen-based devices take advantage of flexible patterning, inexpensive costs, and small volumes, thereby saving time and increasing efficiency. We have developed a gradient nib marker pen device that generated simultaneously different antibiotic concentrations in bacteria antibiotic susceptibility testing (AST). METHODS: The device can deposit on the target surface with the antibiotic gradient. The designed polyester fiber nibs are a highly uniform porosity with unidirectional orientation and produce a visible gradient pattern. RESULTS: We have demonstrated and quantitatively analyzed bacterial growth after antibiotic marking. The antibiotic marking produces an inhibition zone of bacterial growth. The inhibition zones of bacterial growth are captured and converted to 8-bit grayscale images, and then quantified by gray values using the Image J program. A profile of the inhibition zone showed different gray values in response to bacterial viability. CONCLUSION: The gradient nib marker pen device can be used to determine the quantitative antibiotic concentration based on the relationship between gray values and bacterial density conveniently without requiring a series of dilution tubes, including nutrient medium, and diversely diluted antibiotics.
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Antibacterianos/farmacología , Bacterias , Pruebas de Sensibilidad MicrobianaRESUMEN
The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.
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Núcleo Celular/genética , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica/genética , Mitocondrias/genética , Proteínas Mitocondriales/genética , Factor 1 Relacionado con NF-E2/genética , Proteínas Represoras/genética , Factores de Transcripción/genética , Activación Transcripcional/genética , Línea Celular , HumanosRESUMEN
This article presents free-floating three-dimensional (3D) microstructure fabrication in a microfluidic channel using direct fine-tuned grayscale image lithography. The image is designed as a freeform shape and is composed of gray shades as light-absorbing features. Gray shade levels are modulated through multiple reflections of light in a digital micromirror device (DMD) to produce different height formations. Whereas conventional photolithography has several limitations in producing grayscale colors on photomask features, our method focuses on a maskless, single-shot process for fabrication of freeform 3D micro-scale shapes. The fine-tuned gray image is designed using an 8-bit grayscale color; thus, each pixel is capable of displaying 256 gray shades. The pattern of the UV light reflecting on the DMD is transferred to a photocurable resin flowing through a microfluidic channel. Here, we demonstrate diverse free-floating 3D microstructure fabrication using fine-tuned grayscale image lithography. Additionally, we produce polymeric microstructures with locally embedded gray encoding patterns, such as grayscale-encoded microtags. This functional microstructure can be applied to a biophysical detection system combined with 3D microstructures. This method would be suitable for fabricating 3D microstructures that have a specific morphology to be used for particular biological or medical applications.
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OBJECTIVES: The relationship between volar fragment size and postoperative volar tilt loss in complete articular distal radius fracture is not well known. In this study, we measured precise radiological parameters to help identify other factors that might contribute to volar tilt loss. MATERIAL AND METHODS: We retrospectively reviewed the radiological examinations and charts of 256 patients with distal radial fracture who underwent volar locking plate fixation between March 2014 and July 2022. Radiological parameters were measured based on preoperative CT and immediate postoperative radiographs. Univariate and multivariate linear regression analysis was performed to identify relevant factors associated with volar tilt loss following volar locking plate fixation. The receiver operating characteristic curve was used to identify the cutoff value of the independent parameters. RESULTS: On univariate analysis, 2 radiologic parameters on preoperative CT (volar fragment length at the lunate fossa, and teardrop angle) and 4 on immediate postoperative X-ray (radial inclination, radial length, capitate shift, and volar tilt) were significantly associated with postoperative volar tilt loss. On multivariate linear regression analysis, the risk of volar tilt loss increased as the capitate moved toward the back of the radial shaft. The cut-off for anteroposterior length in the lunate fossa was 6.5 mm. CONCLUSIONS: AO/OTA type-C distal radius fractures with <6.5 mm anteroposterior length in the lunate fossa had significantly higher rates of malunion with dorsal deformity. In addition, preoperative teardrop angle <37.2 ° and immediate postoperative volar tilt <3.7º are also predictors of postoperative volar tilt loss.
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Placas Óseas , Fijación Interna de Fracturas , Fracturas del Radio , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hueso Semilunar/diagnóstico por imagen , Hueso Semilunar/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Fracturas del Radio/cirugía , Fracturas del Radio/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Deep learning is an advanced machine-learning approach that is used in several medical fields. Here, we developed a deep learning model using an object detection algorithm to identify the L5 vertebra on anteroposterior lumbar spine radiographs, and assessed its detection accuracy. METHODS: We retrospectively recruited 150 participants for whom both anteroposterior whole-spine and lumbar spine radiographs were available. The anteroposterior lumbar spine radiographs of these patients were used as the input data. Of the 150 images, 105 (70%) were randomly selected as the training set, and the remaining 45 (30%) were assigned to the validation set. YOLOv5x, of the YOLOv5 family model, was used to detect the L5 vertebra area. RESULTS: The mean average precisions 0.5 and 0.75 of the trained L5 detection model were 99.2% and 96.9%, respectively. The model's precision was 95.7% and its recall was 97.8%. Furthermore, 93.3% of the validation data were correctly detected. CONCLUSION: Our deep learning model showed an outstanding ability to identify L5 vertebrae.
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Aprendizaje Profundo , Humanos , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Región Lumbosacra , RadiografíaRESUMEN
Physical unclonable functions (PUFs) have attracted interest in demonstrating authentication and cryptographic processes for Internet of Things (IoT) devices. We demonstrated four-dimensional PUFs (4D PUFs) to realize time-varying chaotic phosphorescent randomness on MoS2 atomic seeds. By forming hybrid states involving more than one emitter with distinct lifetimes in 4D PUFs, irregular lifetime distribution throughout patterns functions as a time-varying disorder that is impossible to replicate. Moreover, we established a bit extraction process incorporating multiple 64 bit-stream challenges and experimentally obtained physical features of 4D PUFs, producing countless random 896 bit-stream responses. Furthermore, the weak and strong PUF models were conceptualized and demonstrated based on 4D PUFs, exhibiting superior cryptological performances, including randomness, uniqueness, degree of freedom, and independent bit ratio. Finally, the data encryption and decryption in pictures were performed by a single 4D PUF. Therefore, 4D PUFs could enhance the counterfeiting deterrent of existing optical PUFs and be used as an anticounterfeiting security strategy for advanced authentication and cryptographic processes of IoT devices.
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This study presents an innovative solution for the enhanced tracking and security of pharmaceuticals through the development of microstructures incorporating environmentally responsive, coded microparticles. Utilizing maskless photolithography, we engineered these microparticles with a degradable masking layer with 30 µm thickness that undergoes controlled dissolution. Quantitative analysis revealed that the protective layer's degradation, monitored by red fluorescence intensity, diminishes predictably over 144 h in phosphate-buffered saline under physiological conditions. This degradation not only confirms the microparticles' integrity but also allows the extraction of encoded information, which can serve as a robust indicator of medicinal shelf life and a deterrent to tampering. These findings indicate the potential for applying this technology in real-time monitoring of pharmaceuticals, ensuring quality and authenticity in the supply chain.
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A noncontact sensor field is an innovative device that can detect, measure, or monitor physical properties or conditions without direct physical contact with the subject or object under examination. These sensors use a variety of methods, including electromagnetic, optical, and acoustic technique, to collect information about the target without physical interaction. Noncontact sensors find wide-ranging applications in various fields such as manufacturing, robotics, automobiles, security, environmental monitoring, space industry, agriculture, and entertainment. In particular, they are used in the medical field, where they provide continuous monitoring of patient conditions and offer opportunities in rehabilitation medicine. This article introduces the potential of noncontact sensors in the field of rehabilitation medicine.
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Efforts have been made to develop bromodomain inhibitors as cancer treatments. Sub-pathways, particularly in ovarian cancer, affected by bromodomain-containing protein (BRD) remain unclear. This study verified the antitumor effects of a new drug that can overcome OPT-0139-chemoresistance to treat ovarian cancer. A mouse xenograft model of human ovarian cancer cells, SKOV3 and OVCAR3, was used in this study. Cell viability and proliferation were assessed using MTT and ATP assays. Cell cycle arrest and apoptosis were determined using flow cytometry. BRD4 and c-Myc expression and apoptosis-related molecules were detected using RT-PCR and real-time PCR and Western blot. We confirmed the OPT-0139 effect and mechanism of action in epithelial ovarian cancer. OPT-0139 significantly reduced cell viability and proliferation and induced apoptosis and cell cycle arrest. In the mouse xenograft model, significant changes in tumor growth, volume, weight, and BRD4-related gene expression were observed, suggesting the antitumor effects of BRD4 inhibitors. Combination therapy with cisplatin promoted apoptosis and suppressed tumor growth in vitro and in vivo. Our results suggest OPT-0139, a BRD4 inhibitor, as a promising anticancer drug for the treatment of ovarian cancer by inhibiting cell proliferation, decreasing cell viability, arresting cell cycle, and inducing apoptosis.
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The ELISA is the most worldwide method for immunoassay. However, the ELISA is losing ground due to low reproducibility of manual experimental processes in both R&D and IVD areas. An automated platform is a good solution, but there are still limitations owning to extremely high cost and requiring large space to set up especially for a small size laboratory. Here, we present a novel all-in-one platform called "VEUS" settable on the laboratory table that offers comprehensive automation of the entire multiplex immunoassay process by exploiting antibody conjugated magnetic particles, quality control and then immunoanalytical reaction, thereby enhancing detection sensitivity and high reproducibility. As a proof of concept, the system exhibits a sensitive LOD of 0.6 and 3.1 pg mL-1 within 1 h run, comparable precision that of molecular diagnostic systems based on PCR method, enabling rapid multiplex diagnosis of Influenza A, Influenza B, and COVID-19 viruses with similar symptoms. Through automation by the all-in-one system, it can be used by novice users, something innovative for immunoassays, relying heavily on user experience. Furthermore, it can contribute to streamline entire immunoassay processes of diverse biomarkers with high reproducibility and convenience in laboratories.
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SARS-CoV-2 , Humanos , Inmunoensayo/métodos , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/química , Reproducibilidad de los Resultados , COVID-19/diagnóstico , COVID-19/virología , Ensayo de Inmunoadsorción Enzimática/métodos , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Automatización de Laboratorios/métodos , Límite de DetecciónRESUMEN
Sarcopenia is a condition in which muscle mass and strength are decreased and muscle function is impaired. It is an indicator of frailty and loss of independence in older adults. It is also associated with increased physical disability, which increases the risk of falls. As a multifactorial disease, sarcopenia is caused by a combination of factors including aging, hormonal changes, nutritional deficiencies, and physical inactivity. Understanding the underlying pathophysiology of sarcopenia and identifying its different causes is critical to developing effective prevention and treatment strategies. This review summarizes the pathophysiology, consequences, diagnostic methods, and multidisciplinary approaches to sarcopenia.