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1.
Materials (Basel) ; 17(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38730851

RESUMEN

AIM: This in vitro study aimed to compare the light-transmission properties of two chairside CAD/CAM lithium disilicate (LD) ceramics (a novel fully crystallized and a traditional pre-crystallized) across varying thicknesses. MATERIALS AND METHODS: One hundred flat specimens were obtained from precrystallized (e.max CAD, Ivoclar Vivadent, Schaan, Liechtenstein) and fully crystallized (LiSi GC Block; GC, Tokyo, Japan) LD at five different thicknesses (0.5, 0.75, 1.0, 1.50 and 2.0 mm). All specimens were polished with a polishing system for lithium disilicate restorations following recommendations from the manufacturer. Light transmission was evaluated with a radiometer. The statistical analysis between e.max CAD and LiSi GC Block was performed using a Mann-Whitney test for each thickness at a significance level of 0.05 (p < 0.05), followed by a Kruskal-Wallis test to compare the light transmission between the thicknesses of e.max CAD and LiSi GC Block. RESULTS: Light transmittance was significantly affected by ceramic thickness. The 0.5 mm thick specimens exhibited the highest transmittance values compared to all other groups, while a light transmittance of 0.00 was observed in the 2.0 mm thick specimens for both e.max CAD and LiSi GC Block. In the comparison between e.max CAD and LiSi GC Block according to thickness, there was a statistically significant difference exclusively between groups with a thickness of 1.50 mm (p = 0.002). CONCLUSIONS: Light transmission for pre- and fully crystallized CAD/CAM lithium disilicate ceramics only showed a statistical difference at the thickness of 1.50 mm (p = 0.002). E.max CAD demonstrated acceptable light transmission up to a thickness of 1.5 mm. CLINICAL SIGNIFICANCE: A thickness of 2 mm for chairside CAD/CAM lithium disilicate ceramics, whether pre-crystallized or fully crystallized, necessitates the use of dual-cure resin luting cement due to reduced light transmission.

2.
J Prosthodont ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38706398

RESUMEN

PURPOSE: This study evaluated the fracture resistance of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate crown, onlay, and non-anatomical occlusal veneer (A-OV) with and without margin fabricated. MATERIALS AND METHODS: Sixty-four CAD-CAM lithium disilicate restorations were designed as (1) complete coverage crown (CCC); (2) A-OV with margin; (3) non-A-OV with margin (NA-OV-M); and (4) non-A-OV without margin (NA-OV-NM), 16 of each. Restorations were crystallized and adhesively luted to resin dies using resin cement. Specimens were then subjected to 400,000 cycles of chewing in a mastication simulator. A universal testing machine was used to apply a compressive load at a crosshead speed of 1 mm/min to the long axis of the tooth with a stainless-steel sphere until fracture occurred. One-way ANOVA followed by post hoc tests were used to assess the impact of preparation design on the fracture load of CAD-CAM lithium disilicate restorations. RESULTS: The highest fracture load was recorded for CAD-CAM lithium disilicate indirect restorations for non-A-OVs preparation with margin (2549 ± 428 N) and onlay (2549 ± 293 N) and the lowest fracture load was recorded for CCCs (2389 ± 428 N); however, there was no significant (p = 0.640) between groups. CONCLUSIONS: CAD-CAM lithium disilicate restorations fabricated for anatomical and non-A-OV preparation display a fracture resistance similar to CCCs. Conservative partial coverage restorations may be considered an acceptable approach for posterior teeth.

3.
J Nanobiotechnology ; 22(1): 169, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609998

RESUMEN

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. MATERIALS AND METHODS: In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. RESULTS: Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. CONCLUSIONS: We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.


Asunto(s)
COVID-19 , Nanopartículas , Humanos , Enzima Convertidora de Angiotensina 2 , Quercetina/farmacología , Quercetina/uso terapéutico , SARS-CoV-2
4.
Opt Express ; 32(7): 12228-12242, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571052

RESUMEN

Highly collimated and directional backlights are essential for realizing advanced display technologies such as autostereoscopic 3D displays. Previously reported collimated backlights, either edge-lit or direct-lit, in general still suffer unsatisfactory form factors, directivity, uniformity, or crosstalk etc. In this work, we report a simple stacking architecture for the highly collimated and uniform backlights, by combining linear light source arrays and carefully designed cylindrical lens arrays. Experiments were conducted to validate the design and simulation, using the conventional edge-lit backlight or the direct-lit mini-LED (mLED) arrays as light sources, the NiFe (stainless steel) barrier sheets, and cylindrical lens arrays fabricated by molding. Highly collimated backlights with small angular divergence of ±1.45°âˆ¼±2.61°, decent uniformity of 93-96%, and minimal larger-angle sidelobes in emission patterns were achieved with controlled divergence of the light source and optimization of lens designs. The architecture reported here provides a convenient way to convert available backlight sources into a highly collimated backlight, and the use of optically reflective barrier also helps recycle light energy and enhance the luminance. The results of this work are believed to provide a facile approach for display technologies requiring highly collimated backlights.

5.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167099, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428686

RESUMEN

The abnormal proliferation, migration, and inflammation of vascular smooth muscle cells (VSMCs) play crucial roles in the development of neointimal hyperplasia and restenosis. Exposure to inflammatory cytokines such as platelet-derived growth factor (PDGF)-BB and tumour necrosis factor-alpha (TNF-α) induces the transformation of contractile VSMCs into abnormal synthetic VSMCs. Isoxanthohumol (IXN) has significant anti-inflammatory, antiproliferative, and antimigratory effects. This study aimed to explore the therapeutic impact and regulatory mechanism of IXN in treating neointimal hyperplasia. The present findings indicate that IXN effectively hinders the abnormal proliferation, migration, and inflammation of VSMCs triggered by PDGF or TNF-α. This inhibition is primarily achieved through the modulation of the apelin/AKT or AKT pathway, respectively. In an in vivo model, IXN effectively reduced neointimal hyperplasia in denuded femoral arteries. These results suggest that IXN holds promise as a potential and innovative therapeutic candidate for the treatment of restenosis.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Factor de Necrosis Tumoral alfa , Xantonas , Humanos , Hiperplasia/tratamiento farmacológico , Proliferación Celular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Apelina , Movimiento Celular , Becaplermina/farmacología , Neointima/tratamiento farmacológico , Neointima/metabolismo , Inflamación
6.
Sensors (Basel) ; 24(6)2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38544198

RESUMEN

Lower extremity exercises are considered a standard and necessary treatment for rehabilitation and a well-rounded fitness routine, which builds strength, flexibility, and balance. The efficacy of rehabilitation programs hinges on meticulous monitoring of both adherence to home exercise routines and the quality of performance. However, in a home environment, patients often tend to inaccurately report the number of exercises performed and overlook the correctness of their rehabilitation motions, lacking quantifiable and systematic standards, thus impeding the recovery process. To address these challenges, there is a crucial need for a lightweight, unbiased, cost-effective, and objective wearable motion capture (Mocap) system designed for monitoring and evaluating home-based rehabilitation/fitness programs. This paper focuses on the development of such a system to gather exercise data into usable metrics. Five radio frequency (RF) inertial measurement unit (IMU) devices (RF-IMUs) were developed and strategically placed on calves, thighs, and abdomens. A two-layer long short-term memory (LSTM) model was used for fitness activity recognition (FAR) with an average accuracy of 97.4%. An intelligent smartphone algorithm was developed to track motion, recognize activity, and calculate key exercise variables in real time for squat, high knees, and lunge exercises. Additionally, a 3D avatar on the smartphone App allows users to observe and track their progress in real time or by replaying their exercise motions. A dynamic time warping (DTW) algorithm was also integrated into the system for scoring the similarity in two motions. The system's adaptability shows promise for applications in medical rehabilitation and sports.


Asunto(s)
Ejercicio Físico , Dispositivos Electrónicos Vestibles , Humanos , Terapia por Ejercicio , Pierna , Muslo
7.
Materials (Basel) ; 17(5)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38473568

RESUMEN

BACKGROUND: Determination of the eligibility of several tooth analog materials for use in crown fracture testing. METHODS: A standardized premolar crown preparation was replicated into three types of resin dies (C&B, low modulus 3D printed resin; OnX, high modulus 3D printed resin composite; and highest modulus milled resin composite). 0.8 mm zirconia crowns were bonded to the dies and the maximum fracture load of the crowns was tested. Twelve extracted human premolars were prepared to a standardized crown preparation, and duplicate dies of the prepared teeth were 3D printed out of C&B. Zirconia crowns were bonded to both the dies and natural teeth, and their fracture load was tested. RESULTS: There was no statistical difference between the fracture load of zirconia crowns bonded to standardized dies of C&B (1084.5 ± 134.2 N), OnX (1112.7 ± 109.8 N) or Lava Ultimate (1137.5 ± 88.7 N) (p = 0.580). There was no statistical difference between the fracture load of crowns bonded to dentin dies (1313 ± 240 N) and a 3D-printed resin die (C&B, 1156 ± 163 N) (p = 0.618). CONCLUSIONS: There was no difference in the static fracture load of zirconia crowns bonded to standardized resin dies with different moduli or between a low modulus resin die and natural dentin die.

8.
Medicina (Kaunas) ; 60(2)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38399547

RESUMEN

With the life expectancy increasing, there is a growing need for prosthetic dental treatments to restore the oral health, function, and quality of life of edentulous patients. Presently, only a few articles are available describing the oral rehabilitation of patients with severely resorbed ridges with milled complete dentures. This clinical case report provides a straightforward protocol consisting of a combination of analog and digital techniques for the rehabilitation of edentulous patients with severely resorbed ridges with milled fixed and removable complete dentures. This technique permits the minimization of the number of appointments, improves patient comfort, allows for the digital archiving of important clinical data, and permits the manufacture of prostheses with improved mechanical properties. These favorable outcomes were achieved by using the patient's existing PMMA complete denture as a custom tray for a final impression with light-bodied Polyvinylsiloxane. Subsequently, the resulting models were digitized, and a digital complete denture was designed and manufactured in an expedited manner using CAD-CAM techniques. Therefore, this case report highlights the potential of CAD/CAM technology to predictably restabilize oral functions and improve patients' quality of life.


Asunto(s)
Boca Edéntula , Calidad de Vida , Humanos , Dentadura Completa , Boca Edéntula/rehabilitación , Diseño Asistido por Computadora
9.
Curr Res Toxicol ; 6: 100155, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38379848

RESUMEN

Paraquat (PQ), a toxic and nonselective bipyridyl herbicide, is one of the most extensively used pesticides in agricultural countries. In addition to pneumotoxicity, the liver is an important target organ for PQ poisoning in humans. However, the mechanism of PQ in hepatotoxicity remains unclear. In this study, we found that exposure of rat hepatic H4IIE cells to PQ (0.1-2 mM) induced significant cytotoxicity and apoptosis, which was accompanied by mitochondria-dependent apoptotic signals, including loss of mitochondrial membrane potential (MMP), cytosolic cytochrome c release, and changes in the Bcl-2/Bax mRNA ratio. Moreover, PQ (0.5 mM) exposure markedly induced JNK and ERK1/2 activation, but not p38-MAPK. Blockade of JNK and ERK1/2 signaling by pretreatment with the specific pharmacological inhibitors SP600125 and PD98059, respectively, effectively prevented PQ-induced cytotoxicity, mitochondrial dysfunction, and apoptotic events. Additionally, PQ exposure stimulated significant oxidative stress-related signals, including reactive oxygen species (ROS) generation and intracellular glutathione (GSH) depletion, which could be reversed by the antioxidant N-Acetylcysteine (NAC). Buffering the oxidative stress response with NAC also effectively abrogated PQ-induced hepatotoxicity, MMP loss, apoptosis, and phosphorylation of JNK and ERK1/2 protein, however, the JNK or ERK inhibitors did not suppress ROS generation in PQ-treated cells. Collectively, these results demonstrate that PQ exposure induces hepatic cell toxicity and death via an oxidative stress-dependent JNK/ERK activation-mediated downstream mitochondria-regulated apoptotic pathway.

10.
Materials (Basel) ; 17(2)2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38255531

RESUMEN

BACKGROUND: To determine what thickness of 5 mol% yttria zirconia (5Y-Z) translucent crowns cemented with different cements and surface treatments would have equivalent fracture resistance as 3 mol% yttria (3Y-Z) crowns. METHODS: The study included 0.8 mm, 1.0 mm, and 1.2 mm thickness 5Y-Z (Katana UTML) crowns and 0.5 and 1.0 mm thickness 3Y-Z (Katana HT) crowns as controls. The 5Y-Z crowns were divided among three treatment subgroups (n = 10/subgroup): (1) cemented using RMGIC (Rely X Luting Cement), (2) alumina particle-abraded then luted with the same cement, (3) alumina particle-abraded and cemented using a resin cement (Panavia SA Cement Universal). The 3Y-Z controls were alumina particle-abraded then cemented with RMGIC. The specimens were then loaded in compression at 30° until failure. RESULTS: All 5Y-Z crowns (regardless of thickness or surface treatment) had a similar to or higher fracture force than the 0.5 mm 3Y-Z crowns. Only the 1.2 mm 5Y-Z crowns with resin cement showed significantly similar fracture force to the 1 mm 3Y-Z crowns. CONCLUSION: In order to achieve a similar fracture resistance to 0.5 mm 3Y-Z crowns cemented with RMGIC, 5Y-Z crowns may be as thin as 0.8 mm. To achieve a similar fracture resistance to 1.0 mm 3Y-Z crowns cemented with RMGIC, 5Y-Z crowns must be 1.2 mm and bonded with resin cement.

11.
Phytomedicine ; 123: 155210, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38006807

RESUMEN

BACKGROUND: Oncogenic multidrug resistance (MDR) is a tough question in cancer therapy. However, no effective medications targeting oncogenic MDR are currently available. Studies have demonstrated that mosloflavone exerts anti-inflammatory effects, yet, its potential to ameliorate MDR remains unclear. PURPOSE: This study aimed to access the capability and elucidate molecular mechanisms of mosloflavone as a MDR resensitizing candidate. METHODS: We investigated the ability of mosloflavone to reverse oncogenic MDR and investigated its underlying mechanisms through cytotoxicity assay, cell cycle assay, apoptosis assay, and zebrafish xenograft model. The modulatory interplay between mosloflavone and P-gp was investigated through analysis of calcein-AM uptake, substrate efflux, ATPase assays, and molecular docking simulation. RESULTS: Mosloflavone inhibited P-gp efflux function in an uncompetitive manner without altering ABCB1 gene expression. In addition, it stimulated P-gp ATPase activity by binding to an active site distinct from that of verapamil. Regarding MDR reversal potential, mosloflavone resensitized MDR cancer cells to chemotherapies by arresting cell cycle and triggering apoptosis, possibly by enhancing reactive oxygen species accumulation and reducing phospho-STAT3. Moreover, in the zebrafish xenograft model, mosloflavone significantly potentiated the antitumor effect of paclitaxel. CONCLUSION: Our findings underscore the potential of mosloflavone as a novel dual modulator of STAT3 and P-gp, indicating it is a promising candidate for overcoming MDR in cancer treatment.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Antineoplásicos , Flavonoides , Animales , Humanos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Pez Cebra/metabolismo , Simulación del Acoplamiento Molecular , Resistencia a Antineoplásicos , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Resistencia a Múltiples Medicamentos , Adenosina Trifosfatasas/metabolismo , Línea Celular Tumoral , Doxorrubicina/farmacología , Antineoplásicos/farmacología , Factor de Transcripción STAT3/metabolismo
12.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38069259

RESUMEN

Liver fibrosis is reversible when treated in its early stages and when liver inflammatory factors are inhibited. Limited studies have investigated the therapeutic effects of corylin, a flavonoid extracted from Psoralea corylifolia L. (Fabaceae), on liver fibrosis. Therefore, we evaluated the anti-inflammatory activity of corylin and investigated its efficacy and mechanism of action in ameliorating liver fibrosis. Corylin significantly inhibited inflammatory responses by inhibiting the activation of mitogen-activated protein kinase signaling pathways and the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha in human THP-1 and mouse RAW264.7 macrophages. Furthermore, corylin inhibited the expression of growth arrest-specific gene 6 in human hepatic stellate cells (HSCs) and the activation of the downstream phosphoinositide 3-kinase/protein kinase B pathway. This inhibited the activation of HSCs and the expression of extracellular matrix proteins, including α-smooth muscle actin and type I collagen. Additionally, corylin induced caspase 9 and caspase 3 activation, which promoted apoptosis in HSCs. Moreover, in vivo experiments confirmed the regulatory effects of corylin on these proteins, and corylin alleviated the symptoms of carbon tetrachloride-induced liver fibrosis in mice. These findings revealed that corylin has anti-inflammatory activity and inhibits HSC activation; thus, it presents as a potential adjuvant in the treatment of liver fibrosis.


Asunto(s)
Células Estrelladas Hepáticas , Fosfatidilinositol 3-Quinasas , Animales , Humanos , Ratones , Antiinflamatorios/efectos adversos , Tetracloruro de Carbono , Flavonoides/farmacología , Flavonoides/uso terapéutico , Células Estrelladas Hepáticas/metabolismo , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal
13.
Nutrients ; 15(22)2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-38004158

RESUMEN

(1) Background: Many studies have revealed a relationship between serum 25-hydroxy vitamin D and physical activity. This study aimed to investigate the relationship between self-reported sitting time and serum 25-hydroxy vitamin D levels in middle-aged and elderly adults in Taiwan. (2) Methods: A total of 396 people were enrolled in our study during a community health examination in Taiwan in 2019. We grouped participants from low to high according to their tertile of serum 25-hydroxy vitamin D levels, using the following categories: deficiency, insufficiency, and sufficiency. Parameters including self-reported sitting time were analyzed between each group. Pearson correlation coefficients were calculated to explore the relationships of serum 25-hydroxy vitamin D levels with age-adjusted risk factors. A scatter plot demonstrated the relationship between serum 25-hydroxy vitamin D levels and self-reported sitting time. The association between serum 25-hydroxy vitamin D levels and self-reported sitting time was assessed by multivariate linear regression with adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (3) Results: We analyzed the data from 396 participants. A total of 41.4% of participants were male, and the average age of all participants was 64.91 (±8.80) years. The participants in the high serum 25-hydroxy vitamin D group were more likely to have shorter self-reported sitting time. Serum 25-hydroxy vitamin D was negatively correlated (Pearson's r) with self-reported sitting time, even after adjustment for age. According to the results of multivariate linear regression, vitamin D levels showed a negative association with self-reported sitting time (ß = -0.131, p = 0.006) after adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (4) Conclusions: According to our research, self-reported sitting time was inversely correlated with serum 25-hydroxy vitamin D in middle-aged and elderly people in Taiwan. Meanwhile, longer self-reported sitting time can be an independent risk factor for lower serum 25-hydroxy vitamin D levels.


Asunto(s)
Sedestación , Deficiencia de Vitamina D , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calcifediol , Estudios Transversales , Lipoproteínas LDL , Autoinforme , Triglicéridos , Vitamina D , Vitaminas
14.
BMC Endocr Disord ; 23(1): 234, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37872536

RESUMEN

BACKGROUND: Hyperglycemic crises are associated with high morbidity and mortality. Previous studies have proposed methods to predict adverse outcomes of patients in hyperglycemic crises; however, artificial intelligence (AI) has never been used to predict adverse outcomes. We implemented an AI model integrated with the hospital information system (HIS) to clarify whether AI could predict adverse outcomes. METHODS: We included 2,666 patients with hyperglycemic crises from emergency departments (ED) between 2009 and 2018. The patients were randomized into a 70%/30% split for AI model training and testing. Twenty-two feature variables from the electronic medical records were collected. The performance of the multilayer perceptron (MLP), logistic regression, random forest, Light Gradient Boosting Machine (LightGBM), support vector machine (SVM), and K-nearest neighbor (KNN) algorithms was compared. We selected the best algorithm to construct an AI model to predict sepsis or septic shock, intensive care unit (ICU) admission, and all-cause mortality within 1 month. The outcomes between the non-AI and AI groups were compared after implementing the HIS and predicting the hyperglycemic crisis death (PHD) score. RESULTS: The MLP had the best performance in predicting the three adverse outcomes, compared with the random forest, logistic regression, SVM, KNN, and LightGBM models. The areas under the curves (AUCs) using the MLP model were 0.852 for sepsis or septic shock, 0.743 for ICU admission, and 0.796 for all-cause mortality. Furthermore, we integrated the AI predictive model with the HIS to assist decision making in real time. No significant differences in ICU admission or all-cause mortality were detected between the non-AI and AI groups. The AI model performed better than the PHD score for predicting all-cause mortality (AUC 0.796 vs. 0.693). CONCLUSIONS: A real-time AI predictive model is a promising method for predicting adverse outcomes in ED patients with hyperglycemic crises. Further studies recruiting more patients are warranted.


Asunto(s)
Sepsis , Choque Séptico , Humanos , Inteligencia Artificial , Redes Neurales de la Computación , Servicio de Urgencia en Hospital
16.
Eur J Pharmacol ; 960: 176146, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37884184

RESUMEN

Multidrug resistance (MDR) is considered one of the significant chemotherapy failures of cancer patients and resulting in tumor recurrence and refractory cancer. The collateral sensitivity phenomenon is suggested as a potential alternative therapy for coring multidrug resistance in cancer. To achieve better effects and reduce toxicity, a polypharmacology strategy was applied. Arctigenin has been reported as a signal transducer and activator of transcription 3 (STAT3) inhibitor as an anticancer drug with low toxicity. However, the effective dosage of arctigenin was too high for re-sensitization in MDR cell lines. Therefore, we have designed and synthesized arctigenin derivatives and have evaluated their chemoreversal effects in KBvin and KB cells. The results conveyed that compounds 9, 10, and 12 displayed significant collateral sensitivity effects on MDR cancer cells, and the corresponding calculated RF values were 32, 174, and 133, respectively. In addition, compounds 9, 10, and 12 were identified to influence the activation of STAT3 and the function of P-glycoprotein in KBvin cells. Combining the active compounds (9, 10, and 12) with paclitaxel significantly inhibits MDR tumor growth in a zebrafish xenograft tumor model without toxicity. Thus, this study provided novel effective arctigenin derivatives and is considered a potential co-treatment with paclitaxel for treating MDR tumors.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Fosforilación , Factor de Transcripción STAT3/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra/metabolismo , Animales
17.
Int J Mol Sci ; 24(18)2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37762057

RESUMEN

In this study, we established a novel capillary electrophoresis method for monitoring the concentration of doripenem in human plasma. As a time-dependent antibiotic, doripenem maximizes its antibacterial effects and minimizes the potential for antibiotic resistance through careful therapeutic drug monitoring. Two online preconcentration techniques, field-enhanced sample stacking (FESS) and sweeping, were coupled to enhance the detection sensitivity. Briefly, an uncoated fused silica capillary (40 cm × 50 µm i.d) was rinsed with a high conductivity buffer (HCB) composed of 150 mM phosphate buffer (NaH2PO4, pH 2.5) and 20% methanol. A large sample plug prepared in a low-conductivity phosphate buffer (50 mM NaH2PO4, pH 2.5) was then hydrodynamically injected (5 psi, 80 s) into the capillary. Under an applied voltage of -30 kV, the analyte was accumulated at the FESS boundary and swept by the negatively charged micelles toward the UV detector. Plasma samples were pretreated by solid-phase extraction (SPE) to eliminate endogenous interferences. The validation results demonstrated a high coefficient of determination (r2 > 0.9995) for the regression curve with impressive precision and accuracy: relative standard deviation (RSD) <5.86% and relative error <4.63%. The limit of detection (LOD, S/N = 3) for doripenem was determined to be 0.4 µg/mL. Compared to the conventional micellar electrokinetic chromatography method, our developed method achieved a sensitivity enhancement of up to 488-fold for doripenem. Furthermore, the newly developed method successfully quantified doripenem concentrations in plasma samples obtained from patients accepting doripenem regimens, proving its application potential in the clinical realm.

18.
Molecules ; 28(16)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37630190

RESUMEN

Two types of angiotensin-converting enzyme (ACE) inhibitors, lisinopril and benazepril HCl, were tested in neuroblastoma cells and found to upregulate low-density lipoprotein-receptor-related protein 1B (LRP1B) and 14-3-3 protein zeta/delta. Additionally, benazepril HCl was found to increase the expression of calreticulin. The upregulation of these proteins by ACE inhibitors may contribute to the amelioration of cognitive deficits in Alzheimer's disease/dementia, as well as the clinically observed deceleration of functional decline in Alzheimer's patients. This discovery suggests that the supplementation of ACE inhibitors may promote neuronal cell survival independently of their antihypertensive effect. Overall, these findings indicate that ACE inhibitors may be a promising avenue for developing effective treatments for Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Fármacos Neuroprotectores , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Proteómica , Antihipertensivos
19.
Sensors (Basel) ; 23(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37420555

RESUMEN

This paper presents a healthcare information and medical resource management platform utilizing wearable devices, physiological sensors, and an indoor positioning system (IPS). This platform provides medical healthcare information management based on the physiological information collected by wearable devices and Bluetooth data collectors. The Internet of Things (IoT) is constructed for this medical care purpose. The collected data are classified and used to monitor the status of patients in real time with a Secure MQTT mechanism. The measured physiological signals are also used for developing an IPS. When the patient is out of the safety zone, the IPS will send an alert message instantly by pushing the server to remind the caretaker, easing the caretaker's burden and offering extra protection for the patient. The presented system also provides medical resource management with the help of IPS. The medical equipment and devices can be tracked by IPS to tackle some equipment rental problems, such as lost and found. A platform for the medical staff work coordination information exchange and transmission is also developed to expedite the maintenance of medical equipment, providing the shared medical information to healthcare and management staff in a timely and transparent manner. The presented system in this paper will finally reduce the loading of medical staff during the COVID-19 pandemic period.


Asunto(s)
COVID-19 , Internet de las Cosas , Dispositivos Electrónicos Vestibles , Humanos , Pandemias , Atención a la Salud
20.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-37259354

RESUMEN

Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells.

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