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1.
Mol Pharm ; 21(6): 2813-2827, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38752564

RESUMEN

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.


Asunto(s)
Administración Cutánea , Calcitriol , Sistemas de Liberación de Medicamentos , Agujas , Psoriasis , Ratas Sprague-Dawley , Psoriasis/tratamiento farmacológico , Animales , Calcitriol/análogos & derivados , Calcitriol/administración & dosificación , Ratas , Sistemas de Liberación de Medicamentos/métodos , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Piel/patología , Tamaño de la Partícula , Masculino , Nanopartículas/química , Imiquimod/administración & dosificación , Suspensiones , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/farmacocinética , Parche Transdérmico
2.
J Gastroenterol Hepatol ; 39(9): 1827-1836, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38744680

RESUMEN

BACKGROUND AND AIM: Risk assessment is of paramount importance for the detection and treatment of colorectal cancer. We developed and validated a feature interpretability screening framework to identify high-risk populations and recommend colonoscopy for them. METHODS: We utilized a training cohort consisting of 1 252 605 participants who underwent colonoscopies in Shanghai from 2013 to 2015 to develop the screening framework. We incorporated Shapley additive explanation values into feature selection to provide interpretability for the framework. Two sampling methods were separately employed to mitigate potential model bias caused by class imbalance. Furthermore, we employed various machine learning algorithms to construct risk assessment models and compared their performance. We tested the screening models on an external validation cohort of 359 462 samples and conducted comprehensive evaluation and statistical analysis of the validation results. RESULTS: The external validation results demonstrated that the models in the proposed framework achieved sensitivity over 0.734, specificity over 0.790, and area under the receiver operating characteristic curve ranging from 0.808 to 0.859. In the predictions of the best-performing model, the prevalence rates of colorectal cancer were 0.059% and 1.056% in the low- and high-risk groups, respectively. If colonoscopies were performed only on the high-risk group predicted by the model, only 14.36% of total colonoscopies would be needed to detect 74.86% of colorectal cancer cases. CONCLUSIONS: We developed and validated a novel framework to identify populations at high risk for colorectal cancer. Those classified as high risk should undergo colonoscopy for further diagnosis.


Asunto(s)
Colonoscopía , Neoplasias Colorrectales , Detección Precoz del Cáncer , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Medición de Riesgo , Detección Precoz del Cáncer/métodos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Aprendizaje Automático , Estudios de Cohortes , Tamizaje Masivo/métodos , Sensibilidad y Especificidad , China/epidemiología , Algoritmos , Curva ROC
3.
Eur Radiol ; 33(5): 3354-3365, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36547676

RESUMEN

OBJECTIVE: In this study, based on PET/CT radiomics features, we developed and validated a nomogram to predict progression-free survival (PFS) for cases with diffuse large B cell lymphoma (DLBCL) treated with immunochemotherapy. METHODS: This study retrospectively recruited 129 cases with DLBCL. Among them, PET/CT scans were conducted and baseline images were collected for radiomics features along with their clinicopathological features. Radiomics features related to recurrence were screened for survival analysis using univariate Cox regression analysis with p < 0.05. Next, a weighted Radiomics-score (Rad-score) was generated and independent risk factors were obtained from univariate and multivariate Cox regressions to build the nomogram. Furthermore, the nomogram was tested for their ability to predict PFS using time-dependent receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Blood platelet, Rad-score, and gender were included in the nomogram as independent DLBCL risk factors for PFS. We found that the training cohort areas under the curve (AUCs) were 0.79, 0.84, and 0.88, and validation cohort AUCs were 0.67, 0.83, and 0.72, respectively. Further, the DCA and calibration curves confirmed the predictive nomogram's clinical relevance. CONCLUSION: Using Rad-score, blood platelet, and gender of the DLBCL patients, a PET/CT radiomics-based nomogram was developed to guide cases' recurrence risk assessment prior to treatment. The developed nomogram can help provide more appropriate treatment plans to the cases. KEY POINTS: • DLBCL cases can be classified into low- and high-risk groups using PET/CT radiomics based Rad-score. • When combined with other clinical characteristics (gender and blood platelet count), Rad-score can be used to predict the outcome of the pretreatment of DLBCL cases with a certain degree of accuracy. • A prognostic nomogram was established in this study in order to aid in assessing prognostic risk and providing more accurate treatment plans for DLBCL cases.


Asunto(s)
Linfoma de Células B Grandes Difuso , Nomogramas , Humanos , Pronóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18/farmacología , Estudios Retrospectivos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen
4.
Sensors (Basel) ; 24(1)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38203043

RESUMEN

In the field of edge computing, quantizing convolutional neural networks (CNNs) using extremely low bit widths can significantly alleviate the associated storage and computational burdens in embedded hardware, thereby improving computational efficiency. However, such quantization also presents a challenge related to substantial decreases in detection accuracy. This paper proposes an innovative method, called Adaptive Global Power-of-Two Ternary Quantization Based on Unfixed Boundary Thresholds (APTQ). APTQ achieves adaptive quantization by quantizing each filter into two binary subfilters represented as power-of-two values, thereby addressing the accuracy degradation caused by a lack of expression ability of low-bit-width weight values and the contradiction between fixed quantization boundaries and the uneven actual weight distribution. It effectively reduces the accuracy loss while at the same time presenting strong hardware-friendly characteristics because of the power-of-two quantization. This paper extends the APTQ algorithm to propose the APQ quantization algorithm, which can adapt to arbitrary quantization bit widths. Furthermore, this paper designs dedicated edge deployment convolutional computation modules for the obtained quantized models. Through quantization comparison experiments with multiple commonly used CNN models utilized on the CIFAR10, CIFAR100, and Mini-ImageNet data sets, it is verified that the APTQ and APQ algorithms possess better accuracy performance than most state-of-the-art quantization algorithms and can achieve results with very low accuracy loss in certain CNNs (e.g., the accuracy loss of the APTQ ternary ResNet-56 model on CIFAR10 is 0.13%). The dedicated convolutional computation modules enable the corresponding quantized models to occupy fewer on-chip hardware resources in edge chips, thereby effectively improving computational efficiency. This adaptive CNN quantization method, combined with the power-of-two quantization results, strikes a balance between the quantization accuracy performance and deployment efficiency in embedded hardware. As such, valuable insights for the industrial edge computing domain can be gained.

5.
Int J Mol Sci ; 24(6)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36982200

RESUMEN

Drug and gene delivery systems mediated by nanoparticles have been widely studied for life science in the past decade. The application of nano-delivery systems can dramatically improve the stability and delivery efficiency of carried ingredients, overcoming the defects of administration routes in cancer therapy, and possibly maintaining the sustainability of agricultural systems. However, delivery of a drug or gene alone sometimes cannot achieve a satisfactory effect. The nanoparticle-mediated co-delivery system can load multiple drugs and genes simultaneously, and improve the effectiveness of each component, thus amplifying efficacy and exhibiting synergistic effects in cancer therapy and pest management. The co-delivery system has been widely reported in the medical field, and studies on its application in the agricultural field have recently begun to emerge. In this progress report, we summarize recent progress in the preparation and application of drug and gene co-delivery systems and discuss the remaining challenges and future perspectives in the design and fabrication.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Vehículos Farmacéuticos , Neoplasias/tratamiento farmacológico
6.
Pol J Pathol ; 73(1): 21-26, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35848477

RESUMEN

In this study, the immunohistochemical EnVision method was applied to detect CD3, CD4 and CD8 in synovial tissues of 40 patients with rheumatoid arthritis (RA) and 10 patients with osteoarthritis (OA). In 92.5% (37/40) RA cases, lymphocytes were focally aggregated, and even germinal centers appeared, forming lymphoid follicle-like structures. The expression of CD3, CD4, and CD8 were high in synovial tissue of RA group, but low in OA group. The number of CD3, CD4+, and CD8+ lymphocytes in OA group were significantly lower than that in RA group (p < 0.05); CD4+lymphocytes in RA accounted for the majority, and mostly were focally distributed. The number of CD8+lymphocytes in the synovial tissue were small, and were mostly scattered. The number of CD4+lymphocytes were significantly higher than CD8+lymphocytes (p<0.05). Compared with the OA group, the number of CD4+T and CD8+T lymphocytes in RA group were higher, and the ratio of CD4/CD8 was higher in RA group (p < 0.05). In conclusion, the CD3, CD4 and CD8 with high level may promote the occurrence and development of RA. The ratio of CD4+/CD8+ may be used as a reference index for the diagnosis and prognosis of RA.


Asunto(s)
Artritis Reumatoide , Artritis Reumatoide/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Humanos , Membrana Sinovial/química , Membrana Sinovial/metabolismo
7.
Int J Mol Sci ; 23(16)2022 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-36012653

RESUMEN

Sublethal doses of insecticides have many impacts on pest control and agroecosystems. Insects that survive a sublethal dose of insecticide could adapt their physiological and behavioral functions and resist this environmental stress, which contributes to the challenge of pest management. In this study, the sublethal effects of thiamethoxam on gene expression were measured through RNA sequencing in the melon aphid Aphis gossypii. Genes regulating energy production were downregulated, while genes related to neural function were upregulated. To further address the function of genes related to neurotransmission, RNA interference (RNAi) was implemented by transdermal delivery of dsRNA targeting synapsin (syn), a gene regulating presynaptic vesicle clustering. The gene expression of synapsin was knocked down and the mortality of aphids was increased significantly over the duration of the assay. Co-delivery of syn-dsRNA and thiamethoxam reversed the upregulation of synapsin caused by low-dose thiamethoxam and resulted in lethality to melon aphids, suggesting that the decreased presynaptic function may contribute to this synergistic lethal effect. In addition, the nanocarrier star polycation, which could bind both dsRNA and thiamethoxam, greatly improved the efficacy of lethality. These results increase our knowledge of the gene regulation induced by sublethal exposure to neonicotinoids and indicated that synapsin could be a potential RNAi target for resistance management of the melon aphid.


Asunto(s)
Áfidos , Insecticidas , Animales , Áfidos/genética , Insecticidas/farmacología , Nitrocompuestos/farmacología , ARN Bicatenario/genética , ARN Bicatenario/farmacología , Sinapsinas/genética , Transmisión Sináptica , Tiametoxam/farmacología
8.
Opt Lett ; 44(8): 1956-1959, 2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-30985784

RESUMEN

An active Q-switching light-emitting diode (LED)-pumped laser is demonstrated by Nd:YLF crystal with acousto-optic modulation for the first time. The spectrum-band pump characteristic is grasped to describe the essential difference between an LED pump and single-absorption-peak matching of laser-diode pump or no matching of lamp pump. An effective absorption spectrum concept is proposed to characterize the absorption features of the gain material with LED-band pumping. According to this new theory, a flat-top beam profile is designed for pumping Nd:YLF crystal with only a 14 W/cm2 peak power, resulting in 165 µJ output energy at 1047 nm. More importantly, by using the acousto-optic Q-switching technique, this LED-pumped Nd:YLF laser has successfully realized a TEM00 mode output with a pulse energy of 10.6 µJ and a pulse width of 452 ns.

9.
Opt Express ; 26(6): 6560-6571, 2018 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-29609344

RESUMEN

We present a high-repetition-rate, high-pulse-energy, high-beam-quality, and high-average-power laser system using an ultraclean closed-type stimulated-Brillouin-scattering phase-conjugate mirror (SBS-PCM). By controlling microparticles of SBS-PCM down to 40 nm, thermal load capacity of such closed-type SBS-PCM was greatly improved, which presented the best reported cleanliness. The closed-type SBS-PCM, lacking scanning wedge plates, achieved reflectivity as high as 92% and showed no optical breakdown phenomena or obvious thermal effects at a 500 Hz pulse-repetition frequency (PRF). Operation at 550 W output power, approximately 1.1 J pulse energy, and beam quality M2 of approximately 2 represents, to our knowledge, the best reported performance. Thermal phase distortion was compensated, and the maximum-output-power pulse-width compression improved from 30 ns to approximately 10 ns.

10.
Proc Natl Acad Sci U S A ; 111(45): 15940-5, 2014 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-25349385

RESUMEN

Bacterial chemotaxis is mediated by signaling complexes that sense chemical gradients and direct bacteria to favorable environments by controlling a histidine kinase as a function of chemoreceptor ligand occupancy. Core signaling complexes contain two trimers of transmembrane chemoreceptor dimers, each trimer binding a coupling protein CheW and a protomer of the kinase dimer. Core complexes assemble into hexagons, and these form hexagonal arrays. The notable cooperativity and amplification in bacterial chemotaxis is thought to reflect allosteric interactions in cores, hexagons, and arrays, but little is known about this presumed allostery. We investigated allostery in core complexes assembled with two chemoreceptor species, each recognizing a different ligand. Chemoreceptors were inserted in Nanodiscs, which rendered them water soluble and allowed isolation of individual complexes. Neighboring dimers in receptor trimers influenced one another's operational ligand affinity, indicating allosteric coupling. However, this coupling did not include the key function of kinase inhibition. Our data indicated that only one receptor dimer could inhibit kinase as a function of ligand occupancy. This selective allosteric coupling corresponded with previously identified structural asymmetry: only one dimer in a trimer contacts kinase and only one CheW. We suggest one of these dimers couples ligand occupancy to kinase inhibition. Additionally, we found that kinase protomers are allosterically coupled, conveying inhibition across the dimer interface. Because kinase dimers connect core complex hexagons, allosteric communication across dimer interfaces provides a pathway for receptor-generated kinase inhibition in one hexagon to spread to another, providing a crucial step for the extensive amplification characteristic of chemotactic signaling.


Asunto(s)
Quimiotaxis/fisiología , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Multimerización de Proteína/fisiología , Transducción de Señal/fisiología , Regulación Alostérica/fisiología , Escherichia coli/genética , Proteínas de Escherichia coli/genética
11.
Opt Express ; 23(17): 22532-43, 2015 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-26368220

RESUMEN

This paper demonstrates the fabrication and measurements of flexible photonic lightwave circuits in glass substrates. Using temporally and spatially shaped ultrafast laser pulses, highly symmetrical and low-loss optical waveguides were written in flexible glass substrates with thicknesses ranging from 25 µm to 100 µm. The waveguide propagation loss, measured by optical frequency domain reflectometry, was 0.11 dB/cm at 1550 nm telecommunication wavelength. The bend loss of the waveguide is negligible at a radius of curvature of 1.5 cm or greater. Additionally, the waveguides are thermally stable up to 400°C. This paper presents alternatives to fabricating flexible photonics in traditionally used polymeric materials.

12.
Opt Lett ; 39(3): 693-6, 2014 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-24487901

RESUMEN

This Letter reports a nonlinear directional waveguide coupler written by ultrafast laser in gallium lanthanum sulfide chalcogenide glass. The nonlinear waveguide device is tested with laser pulses input in two orthogonal polarizations, and all optical switching at 1040 nm between the two coupled waveguides is observed at a peak fluence of 16 GW/cm2. The spectra and autocorrelation measurement from the waveguide outputs show dominant nonlinear effects and negligible dispersion for light propagation in both channels.

13.
Opt Lett ; 39(12): 3579-82, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24978541

RESUMEN

Bragg waveguides are fundamental components in photonic integrated circuits and are particularly interesting for mid-IR applications in high index, highly nonlinear materials. In this work, we present Bragg waveguides fabricated in bulk chalcogenide glass using an ultrafast laser. Waveguides with near circularly symmetric cross sections and low propagation loss are obtained through spatial and temporal beam shaping. Using a single-pass technique, the waveguide and Bragg structure are formed at the same time. First through sixth order gratings with strengths of up to 25 dB are realized, and performance is evaluated based on the modulation duty cycle of the writing beam.

14.
Proc Natl Acad Sci U S A ; 108(23): 9390-5, 2011 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-21606342

RESUMEN

Bacterial chemoreceptors, histidine kinase CheA, and coupling protein CheW form clusters of chemotaxis signaling complexes. In signaling complexes kinase activity is enhanced several hundredfold and placed under receptor control. Activation is necessary to poise enzyme activity such that receptor control has physiologically relevant effects. Thus kinase activation can be considered the underlying core activity of signaling complexes. We defined the minimal physical unit that generates this activity using chemoreceptor Tar from Escherichia coli rendered water soluble by insertion into nanodiscs to (i) measure saturable binding of CheA and CheW to the smallest kinase-activating groups of receptor dimers and (ii) purify and characterize core units of signaling complexes. Purified complexes activated kinase almost as well as signaling complexes formed on arrays of receptors in isolated native membrane. Purified complexes contained two receptor trimers of dimers and two CheW for each CheA dimer, consistent with the approximately 1:1 CheACheW ratio determined by binding measurements. The 2:2:1 stoichiometry implied that CheA dimers, the enzymatically active form, connect two chemoreceptor trimers of dimers by interaction of one CheA protomer and a CheW with each trimer, an organization for which specific molecular interactions have previously been identified. The core unit associates six receptor dimers with a CheA dimer, providing sufficient capacity to account for much of the cooperativity and interdimer influence observed experimentally. We conclude that the 221 organization is the core structural and functional unit of chemotaxis signaling complexes and postulate that hexagonal arrays characteristic of signaling complexes are built from this unit.


Asunto(s)
Proteínas Bacterianas/metabolismo , Quimiotaxis/fisiología , Proteínas de Escherichia coli/metabolismo , Proteínas de la Membrana/metabolismo , Transducción de Señal/fisiología , Proteínas Bacterianas/química , Unión Competitiva , Células Quimiorreceptoras/química , Células Quimiorreceptoras/metabolismo , Electroforesis en Gel de Poliacrilamida , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Histidina Quinasa , Cinética , Proteínas de la Membrana/química , Proteínas Quimiotácticas Aceptoras de Metilo , Modelos Biológicos , Modelos Moleculares , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Nanoestructuras/química , Nanotecnología/métodos , Unión Proteica , Multimerización de Proteína , Receptores de Superficie Celular
15.
Ann Clin Lab Sci ; 54(4): 446-451, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39293832

RESUMEN

OBJECTIVE: Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease. The pathogenesis of RA is complex, and RA lacks effective therapeutic drugs. Heme oxygenase 1 (HO-1) is found to be reduced in RA. However, the role of HO-1 in RA and related mechanisms have not been elucidated. METHODS: RA rat model was established. The expression of HO-1 was upregulated by hemin. The increase weight rate, the degree of toe swelling, and the arthritis index were analyzed to evaluate the therapeutic effect of HO-1 on RA. In vitro RAW264.7 inflammatory cell model was established using 5 ng/mL IL-1. SnPP or hemin were used to inhibit or upregulate HO-1 expression. Tetrazolium salt colorimetric assay (MTT) was selected to test cell proliferation. ELISA was used to determine the concentrations of cellular inflammatory factors IL-1 and IL-6. Reactive oxygen species (ROS) activity was assessed. Western blot was performed to analyze NF-[Formula: see text]B and MMP-3 expressions. RESULTS: The expression of HO-1 was decreased in RA rats, and hemin increased HO-1 level in arthritic rats, which elevated the increase weight rate and decreased toe swelling degree and arthritis index (P<0.05). Hemin significantly upregulated HO-1 expression, inhibited inflammatory cell proliferation, decreased IL-1 and IL-6 expressions, declined ROS level, restrained NF-[Formula: see text]B expression, and enhanced MMP-3 expression in Raw264.7 cells induced by LPS (P<0.05). SnPP obviously inhibited the expression of HO-1, promoted cell proliferation, elevated IL-1 and IL-6 secretions, increased ROS level, promoted NF-[Formula: see text]B expression, and decreased MMP-3 level compared with LPS group (P<0.05). CONCLUSION: Upregulation of HO-1 can improve arthritis symptoms by reducing ROS expression, inhibiting NF-[Formula: see text]B signaling pathway, elevating MMP-3 expression, attenuating inflammatory factor secretion, and suppressing inflammatory cell proliferation.


Asunto(s)
Artritis Reumatoide , Hemo-Oxigenasa 1 , Hemina , Especies Reactivas de Oxígeno , Animales , Ratones , Ratas , Artritis Reumatoide/patología , Artritis Reumatoide/metabolismo , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Hemo Oxigenasa (Desciclizante) , Hemo-Oxigenasa 1/metabolismo , Hemina/farmacología , Inflamación/patología , Inflamación/metabolismo , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , FN-kappa B/metabolismo , Protoporfirinas/farmacología , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo
16.
J Funct Biomater ; 15(8)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39194658

RESUMEN

Diabetes mellitus, characterized by enduring hyperglycemia, precipitates oxidative stress, engendering a spectrum of complications, notably increased bone vulnerability. The genesis of reactive oxygen species (ROS), a byproduct of oxygen metabolism, instigates oxidative detriment and impairs bone metabolism in diabetic conditions. This review delves into the mechanisms of ROS generation and its impact on bone homeostasis within the context of diabetes. Furthermore, the review summarizes the cutting-edge progress in the development of ROS-neutralizing biomaterials tailored for the amelioration of diabetic osteopathy. These biomaterials are engineered to modulate ROS dynamics, thereby mitigating inflammatory responses and facilitating bone repair. Additionally, the challenges and therapeutic prospects of ROS-targeted biomaterials in clinical application of diabetic bone disease treatment is addressed.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38727689

RESUMEN

BACKGROUND: The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. MATERIALS AND METHODS: In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). RESULTS: The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). CONCLUSIONS: The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.

18.
Cell Signal ; 119: 111154, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38565412

RESUMEN

BACKGROUND: Circular RNAs (circRNAs), which are covalently closed non-coding RNAs, are frequently dysregulated in cancer. However, their precise role in bladder cancer (BCa) remains largely unknown. METHODS: Expression of hsa_circ_0005320 in tissues and cell lines was detected using quantitative real-time PCR. Proliferation and colony forming capacity of BCa cells were assessed using Cell Counting Kit-8, ethynyl-labeled deoxyuridine, and colony formation assays. The cell cycle was analyzed using flow cytometry. Protein expression of insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3) and cyclin dependent kinase 2 (CDK2) was examined using western blots. The binding of RNA and protein was validated using RNA immunoprecipitation. Additionally, xenograft tumor models were established to validate the function of hsa_circ_0005320 in vivo. RESULTS: We screened hsa_circ_0005320 from previous high-throughput sequencing and found that it was highly expressed in BCa tissues and associated with tumor differentiation and depth of invasion in BCa patients. Through functional experiments, we demonstrated that hsa_circ_0005320 promoted cell proliferation and regulated the cell cycle. Mechanistically, hsa_circ_0005320 interacted with and upregulated the expression of IGF2BP3, which binds to and enhances the stability of CDK2 mRNA. Furthermore, knockdown of hsa_circ_0005320 resulted in a reduction in tumor burden in vivo. CONCLUSIONS: Collectively, these findings highlight the pro-oncogenic role of hsa_circ_0005320 in BCa through the IGF2BP3/CDK2 axis, providing valuable insights into the mechanism of circRNAs in tumor progression.


Asunto(s)
Ciclo Celular , Proliferación Celular , Quinasa 2 Dependiente de la Ciclina , ARN Circular , Proteínas de Unión al ARN , Neoplasias de la Vejiga Urinaria , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Quinasa 2 Dependiente de la Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Circular/metabolismo , ARN Circular/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética
19.
Biomater Adv ; 161: 213889, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38781739

RESUMEN

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.


Asunto(s)
Administración Cutánea , Antiinflamatorios no Esteroideos , Diclofenaco , Sistemas de Liberación de Medicamentos , Agujas , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Animales , Ratas , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Nanopartículas/administración & dosificación , Masculino , Piel/metabolismo , Absorción Cutánea/efectos de los fármacos , Parche Transdérmico , Ratas Sprague-Dawley
20.
Psychiatry Res Neuroimaging ; 345: 111906, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39342873

RESUMEN

The hypothalamus is an important component of the hypothalamic-pituitary-adrenal axis and an important brain region of the limbic system. Twenty-four first depressive episode(FDE) patients and 25 healthy controls were recruited for this study. The hypothalamus was used as a seed to observe the characteristics of resting state and dynamic functional connectivity (FC) changes in FDE patients, and further observed the correlation between the different brain regions and clinical symptoms. The results found that compared with the HC group, the FDE group showed sFC was increased of the left hypothalamus with right superior parietal gyrus and right middle temporal gyrus, and dFC was increased of the left hypothalamus with left inferior occipital gyrus. And sFC was increased of the right hypothalamus with right orbital part of inferior frontal gyrus, right supplementary motor area, and right middle temporal gyrus, and the dFC was also increased of right hypothalamus with right superior parietal gyrus and left middle temporal gyrus. In addition,there was a negative correlation between dFC values of the right hypothalamus with the right superior parietal gyrus and clinical symptoms in the FDE group. This study provides new insights into understanding the altered neuropathological mechanisms of the hypothalamic circuit in FDE.

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