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1.
J Cosmet Dermatol ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38938219

RESUMEN

BACKGROUND: With growing interest in hair health, researchers are exploring aspects beyond the surface qualities of hair, such as its porous inner structure. While previous studies have focused on the effects of treatments such as perming and hair dying on hair porosity, less emphasis has been paid to the effects of harmful environmental factors such as ultraviolet (UV) rays and particulate matter on the porous nature of hair. AIMS: The aim of this study was to bridge this gap by investigating how UV rays and particulate matter affect hair porosity in different ways. Our study could help elucidate how these external factors influence hair health and shed light on previously unknown aspects of hair porosity. METHODS: Hair tresses were bleached, cut into 1 cm-long sections, and stained with methylene blue. The sections were then irradiated with UV light or exposed to particulate matter. RESULTS: Bleached hair absorbed more methylene blue than normal hair. UV radiation-induced hair porosity occurred at 3 h after irradiation and increased with time. Particulate matter alone did not affect the porosity of the damaged hair; however, in combination with UV irradiation, it substantially increased hair porosity. CONCLUSION: Environmental challenges such as a depleted ozone layer and increasing pollution may increase hair porosity, which can be prevented by maintaining healthy hair.

2.
ACS Nano ; 18(22): 14327-14338, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38767980

RESUMEN

In this study, we investigate the coexistence of short- and long-term memory effects owing to the programmable retention characteristics of a two-dimensional Au/MoS2/Au atomristor device and determine the impact of these effects on synaptic properties. This device is constructed using bilayer MoS2 in a crossbar structure. The presence of both short- and long-term memory characteristics is proposed by using a filament model within the bilayer transition-metal dichalcogenide. Short- and long-term properties are validated based on programmable multilevel retention tests. Moreover, we confirm various synaptic characteristics of the device, demonstrating its potential use as a synaptic device in a neuromorphic system. Excitatory postsynaptic current, paired-pulse facilitation, spike-rate-dependent plasticity, and spike-number-dependent plasticity synaptic applications are implemented by operating the device at a low-conductance level. Furthermore, long-term potentiation and depression exhibit symmetrical properties at high-conductance levels. Synaptic learning and forgetting characteristics are emulated using programmable retention properties and composite synaptic plasticity. The learning process of artificial neural networks is used to achieve high pattern recognition accuracy, thereby demonstrating the suitability of the use of the device in a neuromorphic system. Finally, the device is used as a physical reservoir with time-dependent inputs to realize reservoir computing by using short-term memory properties. Our study reveals that the proposed device can be applied in artificial intelligence-based computing applications by utilizing its programmable retention properties.

3.
Oncol Lett ; 27(5): 211, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38572064

RESUMEN

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

4.
Biosensors (Basel) ; 14(3)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38534236

RESUMEN

Vancomycin (VAN) is an effective antibiotic against Gram-positive bacteria and the first-line therapy to prevent and treat methicillin-resistant Staphylococcus aureus (MRSA) and severe infections. However, low concentrations of VAN can result in resistant strains. High doses of VAN can cause nephrotoxicity and ototoxicity; thus, VAN is a representative drug for which drug monitoring is recommended. Several methods have been proposed to detect VAN. Among them, lateral flow immunoassays (LFIAs) have advantages, such as simple and user-friendly operation, low sample volume requirement, and cost effectiveness. In this study, we developed an LFIA capable of rapid on-site detection such that the VAN concentration in plasma could be monitored within 20 min by a one-step detection process using whole blood without plasma separation. VAN can be detected in whole blood over a wide range of concentrations (20-10,000 ng/mL), and the LFIA reported here has a detection limit of 18 ng/mL. The applicability of the developed LFIA compared to the results of measuring VAN with a commercial enzyme-linked immunosorbent assay kit showed a satisfactory correlation (Spearman's rho, ρ = 0.891). Therefore, the developed LFIA enables rapid and wide-range VAN detection in whole blood and can aid in drug monitoring to evaluate patients' responses to treatment.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Vancomicina , Humanos , Vancomicina/farmacología , Antibacterianos/farmacología , Inmunoensayo/métodos , Ensayo de Inmunoadsorción Enzimática
5.
J Microbiol ; 62(1): 11-19, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38319586

RESUMEN

Two novel Gram-stain-negative, strictly-aerobic, rod-shaped (1.2 ± 3.4 µm × 0.3 ± 0.7 µm), and non-motile marine bacterial species, designated MEBiC05379T and MEBiC07777T, were isolated from a marine sponge Pseudaxinella sp. in Gangneung City and deep-sea sediments of the Ulleung basin in the East Sea of Korea, respectively. The 16S rRNA gene sequence analysis revealed high levels of similarities between these strains and members of the genus Flavivirga (97.0-98.4% sequence identities). Both novel strains revealed as mesophilic, neutrophilic in pH and slightly halophilic. Similar to those of other Flavivirga members, the primary cellular fatty acids of both strains were iso-C15:0, iso-C15:1 G, iso-C15:03-OH, and iso-C17:0 3-OH, with MEBiC05379T and MEBiC07777T containing relatively higher proportions of C12:0 and summed feature 3 (C16:1ω7c and/or C16:1ω6c). In both taxa, the major isoprenoid quinone was MK-6. The DNA G + C contents of MEBiC05379T and MEBiC07777T genomes were 32.62 and 32.46 mol%, respectively. Compared to other members of Flavivirga, both strains exhibited similar DNA G + C ratio and fatty acids pattern, yet enzyme expression and carbon sources utilization pattern were different. Genomes of the genus Flavivirga showed enzyme preferences to fucoidan and sulfated galactans. Considering the monophyly rule, AAI values delineate the genus Flavivirga from adjacent genera calculated to be 76.0-78.7%. Based on the phenotypic, genomic and biochemical data, strains for MEBiC05379T and MEBiC07777T thus represent two novel species in the genus Flavivirga, for which the names Flavivirga spongiicola sp. nov. (MEBiC05379T [= KCTC 92527 T = JCM 16662 T]), and Flavivirga abyssicola sp. nov. (MEBiC07777T [= KCTC 92563 T = JCM 36477 T]) are proposed.


Asunto(s)
Flavobacteriaceae , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , ADN Bacteriano/química , Análisis de Secuencia de ADN , Ácidos Grasos/análisis , Filogenia , Técnicas de Tipificación Bacteriana , Vitamina K 2/análisis
6.
ACS Nano ; 18(4): 3313-3322, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38226861

RESUMEN

Recently, we demonstrated the nonvolatile resistive switching effects of metal-insulator-metal (MIM) atomristor structures based on two-dimensional (2D) monolayers. However, there are many remaining combinations between 2D monolayers and metal electrodes; hence, there is a need to further explore 2D resistance switching devices from material selections to future perspectives. This study investigated the volatile and nonvolatile switching coexistence of monolayer hexagonal boron nitride (h-BN) atomristors using top and bottom silver (Ag) metal electrodes. Utilizing an h-BN monolayer and Ag electrodes, we found that the transition between volatile and nonvolatile switching is attributed to the thickness/stiffness of chain-like conductive bridges between h-BN and Ag surfaces based on the current compliance and atomristor area. Computations indicate a "weak" bridge is responsible for volatile switching, while a "strong" bridge is formed for nonvolatile switching. The current compliance determines the number of Ag atoms that undergo dissociation at the electrode, while the atomristor area determines the degree of electric field localization that forms more stable conductive bridges. The findings of this study suggest that the h-BN atomristor using Ag electrodes shows promise as a potential solution to integrate both volatile neurons and nonvolatile synapses in a single neuromorphic crossbar array structure through electrical and dimensional designs.

7.
Diabetes ; 73(4): 592-603, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38241027

RESUMEN

The fundamental mechanisms by which a diet affects susceptibility to or modifies autoimmune diseases are poorly understood. Excess dietary salt intake acts as a risk factor for autoimmune diseases; however, little information exists on the impact of salt intake on type 1 diabetes. To elucidate the potential effect of high salt intake on autoimmune diabetes, nonobese diabetic (NOD) mice were fed a high-salt diet (HSD) or a normal-salt diet (NSD) from 6 to 12 weeks of age and monitored for diabetes development. Our results revealed that the HSD accelerated diabetes progression with more severe insulitis in NOD mice in a CD4+ T-cell-autonomous manner when compared with the NSD group. Moreover, expression of IL-21 and SPAK in splenic CD4+ T cells from HSD-fed mice was significantly upregulated. Accordingly, we generated T-cell-specific SPAK knockout (CKO) NOD mice and demonstrated that SPAK deficiency in T cells significantly attenuated diabetes development in NOD mice by downregulating IL-21 expression in CD4+ T cells. Furthermore, HSD-triggered diabetes acceleration was abolished in HSD-fed SPAK CKO mice when compared with HSD-fed NOD mice, suggesting an essential role of SPAK in salt-exacerbated T-cell pathogenicity. Finally, pharmacological inhibition of SPAK activity using a specific SPAK inhibitor (closantel) in NOD mice ameliorated diabetogenesis, further illuminating the potential of a SPAK-targeting immunotherapeutic approach for autoimmune diabetes. Here, we illustrate that a substantial association between salt sensitivity and the functional impact of SPAK on T-cell pathogenicity is a central player linking high-salt-intake influences to immunopathophysiology of diabetogenesis in NOD mice.


Asunto(s)
Diabetes Mellitus Tipo 1 , Interleucinas , Cloruro de Sodio Dietético , Ratones , Animales , Diabetes Mellitus Tipo 1/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Ratones Endogámicos NOD , Linfocitos T CD4-Positivos/metabolismo
8.
Neuropsychopharmacology ; 49(7): 1091-1103, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38110609

RESUMEN

Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While current evidence implicates TAAR1-mediated regulation of dopaminergic tone as the primary circuit mechanism, little is known about the effects of TAAR1 agonists on the glutamatergic system and excitation-inhibition balance. Here we assessed the impact of ulotaront (SEP-363856), a TAAR1 agonist in Phase III clinical development for schizophrenia, on glutamate function in the mouse striatum and hippocampus. Ulotaront reduced spontaneous glutamatergic synaptic transmission and neuronal firing in striatal and hippocampal brain slices, respectively. Interestingly, ulotaront potentiated electrically-evoked excitatory synaptic transmission in both brain regions, suggesting the ability to modulate glutamatergic signaling in a state-dependent manner. Similar striatal effects were also observed with the TAAR1 agonist, RO5166017. Furthermore, we show that ulotaront regulates excitation-inhibition balance in the striatum by specifically modulating glutamatergic, but not GABAergic, spontaneous synaptic events. These findings expand the mechanistic circuit hypothesis of ulotaront and TAAR1 agonists, which may be uniquely positioned to normalize both the excessive dopaminergic tone and regulate abnormal glutamatergic function associated with schizophrenia.


Asunto(s)
Cuerpo Estriado , Ácido Glutámico , Hipocampo , Ratones Endogámicos C57BL , Receptores Acoplados a Proteínas G , Animales , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Ratones , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología
9.
Clin Med Insights Oncol ; 17: 11795549231218082, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38090634

RESUMEN

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

10.
Medicina (Kaunas) ; 59(10)2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37893469

RESUMEN

Introduction: Distal tibial fractures make up approximately 3% to 10% of all tibial fractures or about 1% of lower extremity fractures. MIPO is an appropriate procedure and method to achieve stable metal plate fixation and osseointegration by minimizing soft tissue damage and vascular integrity at the fracture site. MIPO to the medial tibia during distal tibial fractures induces skin irritation due to the thickness of the metal plate, which causes discomfort and pain on the medial side of the distal leg, and if severe, complications such as infection and skin defect may occur. The reverse sural flap is a well-researched approach for covering defects in the lower third of the leg, ankle, and foot. Materials and Methods: Among 151 patients with distal tibia fractures who underwent minimally invasive metal plate fixation, soft tissue was injured due to postoperative complications. We treated 13 cases with necrosis and exposed metal plates by retrograde nasogastric artery flap surgery. For these patients, we collected obligatory patient records, radiological data, and wound photographs of the treatment results and complications of reconstructive surgery. Results: In all the cases, flap survival was confirmed at the final outpatient follow-up. The exposed area of the metal plate was well coated, and there was no plate failure due to complete necrosis. Three out of four women complained of aesthetic dissatisfaction because the volume of the tunnel through which the skin mirror passed and the skin plate itself were thick. In two cases, defatting was performed to reduce the thickness of the plate while removing the metal plate. Conclusions: Metal plate exposure after distal tibial fractures have been treated with minimally invasive metal plate fusion and can be successfully treated with retrograde nasogastric artery flaps, and several surgical techniques are used during flap surgery.


Asunto(s)
Tibia , Fracturas de la Tibia , Humanos , Femenino , Tibia/cirugía , Fijación Interna de Fracturas/efectos adversos , Fracturas de la Tibia/cirugía , Colgajos Quirúrgicos , Resultado del Tratamiento , Placas Óseas , Necrosis
11.
Nano Lett ; 23(18): 8664-8673, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37669541

RESUMEN

Glucose oxidase-loaded ZIF-90 metal-organic framework nanoparticles conjugated to hemin-G-quadruplexes act as functional bioreactor hybrids operating transient dissipative biocatalytic cascaded transformations consisting of the glucose-driven H2O2-mediated oxidation of Amplex-Red to resorufin or the glucose-driven generation of chemiluminescence by the H2O2-mediated oxidation of luminol. One system involves the fueled activation of a reaction module leading to the temporal formation and depletion of the bioreactor conjugate operating the nickase-guided transient biocatalytic cascades. The second system demonstrates the fueled activation of a reaction module yielding a bioreactor conjugate operating the exonuclease III-dictated transient operation of the two biocatalytic cascades. The temporal operations of the bioreactor circuits are accompanied by kinetic models and computational simulations enabling us to predict the dynamic behavior of the systems subjected to different auxiliary conditions.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , G-Cuádruplex , Estructuras Metalorgánicas , Nanopartículas , Glucosa Oxidasa/metabolismo , Peróxido de Hidrógeno , Glucosa , Reactores Biológicos , Hemina
12.
Biochemistry ; 62(17): 2669-2676, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37531216

RESUMEN

Glycocin F (GccF), a ribosomally synthesized, post-translationally modified peptide secreted by Lactobacillus plantarum KW30, rapidly inhibits the growth of susceptible bacteria at nanomolar concentrations. Previous studies have highlighted structural features important for its activity and have shown the absolute requirement for the Ser18 O-linked GlcNAc on the eight-residue loop linking the two short helices of the (C-X6-C)2 structure. Here, we show that an ostensibly very small chemical modification to Ser18, the substitution of the Cα proton with a methyl group, reduces the antimicrobial activity of GccF 1000-fold (IC50 1.5 µM cf. 1.5 nM). A comparison of the GccFα-methylSer18 NMR structure (PDB 8DFZ) with that of the native protein (PDB 2KUY) showed a marked difference in the orientation and mobility of the loop, as well as a markedly different positioning of the GlcNAc, suggesting that loop conformation, dynamics, and glycan presentation play an important role in the interaction of GccF with as yet unknown but essential physiological target molecules.


Asunto(s)
Antiinfecciosos , Péptidos , Péptidos/química , Espectroscopía de Resonancia Magnética , Imagen por Resonancia Magnética , Estructura Secundaria de Proteína , Antiinfecciosos/farmacología
13.
J Hazard Mater ; 459: 132295, 2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37597397

RESUMEN

Expanded polystyrene (EPS), also known as Styrofoam, is a widespread global pollutant, and its lightweight floating property increases its chances of weathering by abrasion and ultraviolet (UV) irradiation, resulting in microplastics. Herein, we investigated the effects of particle size ((1 µm versus 10 µm), UV irradiation (pristine versus UV oxidation), and origin (secondary versus primary) on the toxicity of Styrofoam microplastics. The target cells used in this study were selected based on human exposure-relevant cell lines: differentiated THP-1 cells for macrophages, Caco-2 for enterocytes, HepG2 for hepatocytes, and A549 for alveolar epithelial cells. In the differentiated THP-1 cells, the levels of cytotoxicity and inflammatory cytokines showed size- (1 µm > 10 µm), UV oxidation- (UV > pristine), and origin- (secondary > primary) dependency. Furthermore, the intrinsic oxidative potential of the test particles was positively correlated with cellular oxidative levels and toxicity endpoints, suggesting that the toxicity of Styrofoam microplastics also follows the oxidative stress paradigm. Additionally, all microplastics induced the activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome and the release of interleukin-1ß (IL-1ß). These results imply that weathering process can aggravate the toxicity of Styrofoam microplastics due to the increased oxidative potential and decreased particle size.


Asunto(s)
Microplásticos , Poliestirenos , Humanos , Poliestirenos/toxicidad , Microplásticos/toxicidad , Plásticos , Células CACO-2 , Macrófagos
14.
Healthcare (Basel) ; 11(16)2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37628562

RESUMEN

BACKGROUND: Cardiovascular disease (CVD) is the primary cause of mortality worldwide and imposes a significant social burden on many countries. METHODS: This study assessed the health and economic benefits of omega-3 associated with CVD. The meta-analysis estimated the risk ratio (RR) and absolute risk reduction (ARR), and the economic impact was calculated using direct and indirect costs related to CVD treatments in Korean adults. RESULTS: A total of 33 studies were included in the meta-analysis on CVD outcomes, with 80,426 participants in the intervention group and 80,251 participants in the control group. The meta-analysis determined a significant reduction in omega-3 in CVD (RR = 0.92, 95% CI: 0.86~0.97) and ARR (1.48%). Additionally, the subgroup analysis indicated that higher doses and the long-term consumption of omega-3 could further enhance these effects. After applying ARR from meta-analysis to the target population of about 1,167,370 in 2021, the Republic of Korea, it was estimated that omega-3 consumption could result in an economic benefit of KRW 300 billion by subtracting the purchase expenses of omega-3 supplements from the total social cost savings. CONCLUSION: Omega-3 supplements can help to reduce the risk of CVD and subsequent economic benefits in the Republic of Korea.

15.
RSC Chem Biol ; 4(8): 533-547, 2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37547456

RESUMEN

Viral infections are one of the leading causes of acute morbidity in humans and much endeavour has been made by the synthetic community for the development of drugs to treat associated diseases. Peptide-based enzyme inhibitors, usually short sequences of three or four residues, are one of the classes of compounds currently under development for enhancement of their activity and pharmaceutical properties. This review reports the advances made in the design of inhibitors targeting the family of highly conserved viral proteases 3C/3CLpro, which play a key role in viral replication and present minimal homology with mammalian proteases. Particular focus is put on the reported development of P1 glutamine isosteres to generate potent inhibitors mimicking the natural substrate sequence at the site of recognition.'

16.
Chemosphere ; 338: 139596, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37480950

RESUMEN

Although several epidemiological studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) may induce brain atrophy, no longitudinal study has investigated the effect of PAH exposure on brain structural changes. This study examined the longitudinal associations between urinary PAH metabolites and brain cortical thickness. We obtained urinary concentrations of PAH metabolites and brain magnetic resonance images from 327 adults (≥50 years of age) without dementia at baseline and 3-year follow-up. We obtained whole-brain and regional cortical thicknesses, as well as an Alzheimer's disease (AD)-specific marker for cortical atrophy (a higher score indicated a greater similarity to patients with AD) at baseline and follow-up. We built a linear mixed-effect model including each of urinary PAH metabolites as the time-varying exposure variable of interest. We found that increases in urinary concentrations of 1-hydroxypyrene (ß = -0.004; 95% CI, -0.008 to -0.001) and 2-hydroxyfluorene (ß = -0.011; 95% CI, -0.015 to -0.006) were significantly associated with a reduced whole-brain cortical thickness. A urinary concentration of 2-hydroxyfluorene was significantly associated with an increased AD-specific cortical atrophy score (ß = 2.031; 95% CI, 0.512 to 3.550). The specific brain regions showing the association of urinary concentrations of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, or 2-hydroxyfluorene with cortical thinning were the frontal, parietal, temporal, and cingulate lobes. These findings suggested that exposure to PAHs may reduce brain cortical thickness and increase the similarity to AD-specific cortical atrophy patterns in adults.


Asunto(s)
Enfermedad de Alzheimer , Hidrocarburos Policíclicos Aromáticos , Humanos , Adulto , Hidrocarburos Policíclicos Aromáticos/metabolismo , Grosor de la Corteza Cerebral , Neuroimagen , Atrofia , Biomarcadores/orina
17.
J Phys Chem Lett ; 14(28): 6349-6354, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37418426

RESUMEN

Passive permeation of small molecules into vesicles with multiple compartments is a critical event in many chemical and biological processes. We consider the translocation of the peptide NAF-144-67 labeled with a fluorescent fluorescein dye across membranes of rhodamine-labeled 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) into liposomes with internal vesicles. Time-resolved microscopy revealed a sequential absorbance of the peptide in both the outer and inner micrometer vesicles that developed over a time period of minutes to hours, illustrating the spatial and temporal progress of the permeation. There is minimal perturbation of the membrane structure and no evidence for pore formation. On the basis of molecular dynamics simulations of NAF-144-67, we extended a local defect model to migration processes that include multiple compartments. The model captures the long residence time of the peptide within the membrane and the rate of permeation through the liposome and its internal compartments. Imaging experiments confirm the semi-quantitative description of the permeation of the model by activated diffusion and open the way for studies of more complex systems.


Asunto(s)
Liposomas , Fosfolípidos , Fosfolípidos/química , Liposomas/química , Fenómenos Químicos , Colorantes Fluorescentes/química , Péptidos , Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química
18.
Hum Mol Genet ; 32(18): 2773-2786, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37384417

RESUMEN

De novo heterozygous loss-of-function mutations in phosphatase and tensin homolog (PTEN) are strongly associated with autism spectrum disorders; however, it is unclear how heterozygous mutations in this gene affect different cell types during human brain development and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type specific developmental events that are affected by heterozygous mutations in PTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep-layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes of PTEN heterozygosity that later converge on disrupted neuronal activity.


Asunto(s)
Trastorno del Espectro Autista , Neuronas , Humanos , Neuronas/metabolismo , Diferenciación Celular , Organoides/metabolismo , Trastorno del Espectro Autista/genética , Mutación , Fosfohidrolasa PTEN/genética
19.
Front Med (Lausanne) ; 10: 1189243, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37283622

RESUMEN

Background: Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination. Methods: This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined. Results: Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5-49.5) weeks, six patients progressed to end-stage kidney disease (ESKD). Conclusion: Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.

20.
Bioengineering (Basel) ; 10(6)2023 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-37370563

RESUMEN

(1) Background: The purpose of this study was to investigate whether the loosening of total knee arthroplasty (TKA) implants could be detected accurately on plain radiographs using a deep convolution neural network (CNN). (2) Methods: We analyzed data for 100 patients who underwent revision TKA due to prosthetic loosening at a single institution from 2012 to 2020. We extracted 100 patients who underwent primary TKA without loosening through a propensity score, matching for age, gender, body mass index, operation side, and American Society of Anesthesiologists class. Transfer learning was used to prepare a detection model using a pre-trained Visual Geometry Group (VGG) 19. For transfer learning, two methods were used. First, the fully connected layer was removed, and a new fully connected layer was added to construct a new model. The convolutional layer was frozen without training, and only the fully connected layer was trained (transfer learning model 1). Second, a new model was constructed by adding a fully connected layer and varying the range of freezing for the convolutional layer (transfer learning model 2). (3) Results: The transfer learning model 1 gradually increased in accuracy and ultimately reached 87.5%. After processing through the confusion matrix, the sensitivity was 90% and the specificity was 100%. Transfer learning model 2, which was trained on the convolutional layer, gradually increased in accuracy and ultimately reached 97.5%, which represented a better improvement than for model 1. Processing through the confusion matrix affirmed that the sensitivity was 100% and the specificity was 97.5%. (4) Conclusions: The CNN algorithm, through transfer learning, shows high accuracy for detecting the loosening of TKA implants on plain radiographs.

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