Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.017
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
Mol Cell ; 80(3): 485-500.e7, 2020 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-33027691

RESUMEN

Peptide drugs targeting class B1 G-protein-coupled receptors (GPCRs) can treat multiple diseases; however, there remains substantial interest in the development of orally delivered non-peptide drugs. Here, we reveal unexpected overlap between signaling and regulation of the glucagon-like peptide-1 (GLP-1) receptor by the non-peptide agonist PF 06882961 and GLP-1 that was not observed for another compound, CHU-128. Compounds from these patent series, including PF 06882961, are currently in clinical trials for treatment of type 2 diabetes. High-resolution cryoelectron microscopy (cryo-EM) structures reveal that the binding sites for PF 06882961 and GLP-1 substantially overlap, whereas CHU-128 adopts a unique binding mode with a more open receptor conformation at the extracellular face. Structural differences involving extensive water-mediated hydrogen bond networks could be correlated to functional data to understand how PF 06882961, but not CHU-128, can closely mimic the pharmacological properties of GLP-1. These findings will facilitate rational structure-based discovery of non-peptide agonists targeting class B GPCRs.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Animales , Sitios de Unión/fisiología , Microscopía por Crioelectrón/métodos , Péptido 1 Similar al Glucagón/química , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/química , Humanos , Péptidos/química , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Relación Estructura-Actividad
2.
Brief Bioinform ; 24(4)2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37279476

RESUMEN

Identifying topologically associating domains (TADs), which are considered as the basic units of chromosome structure and function, can facilitate the exploration of the 3D-structure of chromosomes. Methods have been proposed to identify TADs by detecting the boundaries of TADs or identifying the closely interacted regions as TADs, while the possible inner structure of TADs is seldom investigated. In this study, we assume that a TAD is composed of a core and its surrounding attachments, and propose a method, named CATAD, to identify TADs based on the core-attachment structure model. In CATAD, the cores of TADs are identified based on the local density and cosine similarity, and the surrounding attachments are determined based on boundary insulation. CATAD was applied to the Hi-C data of two human cell lines and two mouse cell lines, and the results show that the boundaries of TADs identified by CATAD are significantly enriched by structural proteins, histone modifications, transcription start sites and enzymes. Furthermore, CATAD outperforms other methods in many cases, in terms of the average peak, boundary tagged ratio and fold change. In addition, CATAD is robust and rarely affected by the different resolutions of Hi-C matrices. Conclusively, identifying TADs based on the core-attachment structure is useful, which may inspire researchers to explore TADs from the angles of possible spatial structures and formation process.


Asunto(s)
Cromosomas , Código de Histonas , Animales , Ratones , Humanos
3.
Plant Cell ; 34(7): 2638-2651, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35445713

RESUMEN

In eukaryotes, three-dimensional (3D) chromatin architecture maintains genome stability and is important in regulating gene transcription. However, little is known about the mechanisms by which diverse ATP-dependent chromatin remodeling complexes regulate the 3D chromatin structure in plants. We examined the 3D chromatin structure within the ATPase subunit of the SWI/SNF, ISWI, INO80, and CHD remodeling complexes in wild-type (WT) and mutant Arabidopsis thaliana plants by combining high-throughput sequencing with in situ Hi-C, the enrichment of histone marks, nucleosome density, and gene expression. We found that compartment regions switched and compartmental strength was significantly weakened in all four enzyme mutants. Chromatin remodeling complexes differentially regulated the nucleosome distribution pattern and density within the switching compartments. Alterations of nucleosome distribution pattern and density were associated with a reduction in H3K27me3 levels in the chromatin remodeling enzyme mutants and led to compartment switching. Our data show that chromatin remodeling complexes regulate the linear nucleosome distribution pattern and density to promote H3K27me3 deposition, which in turn regulates 3D chromatin structure.


Asunto(s)
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Cromatina/genética , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina/genética , Histonas/metabolismo , Nucleosomas/genética , Nucleosomas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
4.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-35064078

RESUMEN

Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMA-specific probes incorporating glutamate-ureido-lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC); however, GUL-based PSMA tracers are still reported to have the potential to identify NEPC metastatic tumors. These probes may bind unknown proteins associated with PSMA-suppressed cancers. We have identified the up-regulation of PSMA-like aminopeptidase NAALADaseL and the metabotropic glutamate receptors (mGluRs) in PSMA-suppressed prostate cancers and find that their expression levels inversely correlate with PSMA expression and are associated with GUL-based radiotracer uptake. Furthermore, we identify that NAALADaseL and mGluR expression correlates with a unique cell cycle signature. This provides an opportunity for the future study of the biology of NEPC and potential therapeutic directions. Computationally predicting that GUL-based probes bind well to these targets, we designed and synthesized a fluorescent PSMA tracer to investigate these proteins in vitro, where it shows excellent affinity for PSMA, NAALADaseL, and specific mGluRs associated with poor prognosis.


Asunto(s)
Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Glutamatos , Lisina , Sondas Moleculares , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Urea , Animales , Antígenos de Superficie/química , Sitios de Unión , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Expresión Génica , Glutamato Carboxipeptidasa II/química , Glutamatos/química , Humanos , Inmunohistoquímica , Lisina/química , Masculino , Ratones , Modelos Moleculares , Conformación Molecular , Imagen Molecular/métodos , Sondas Moleculares/química , Neoplasias de la Próstata/genética , Unión Proteica , Receptores de Ácido Kaínico/genética , Receptores de Ácido Kaínico/metabolismo , Relación Estructura-Actividad , Urea/análogos & derivados , Urea/química
5.
Am J Physiol Gastrointest Liver Physiol ; 327(2): G284-G294, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38953837

RESUMEN

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).


Asunto(s)
Neoplasias Colorrectales , Proteína Forkhead Box M1 , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Células HT29 , Células HCT116 , Glucólisis , Regulación Neoplásica de la Expresión Génica , Efecto Warburg en Oncología , Transducción de Señal , Proliferación Celular , Reprogramación Celular/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reprogramación Metabólica
6.
Small ; 20(5): e2306646, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37759391

RESUMEN

Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid crystal elastomers (CLCEs) into complex structural color patterns with variable resolution and enhanced expansibility is reported. A volatile solvent is introduced into the synthesized CLC oligomers, modifying its rheological properties and allowing direct-ink-writing (DIW) under mild conditions. The combination of printing shear flow and anisotropic deswelling of ink drives the CLC molecules into an ordered cholesteric arrangement. The authors meticulously investigate the influence of printing parameters to achieve resolution control over a wide range, allowing for the printing of multi-sized 1D or 2D patterns with constant quality. Furthermore, such solvent-cast direct-ink-writing (DIW) strategy is highly expandable and can be integrated easily into the DIW of bionic robots. Multi-responsive bionic butterfly and flower are printed with biomimetic in both locomotion and coloration. Such designs dramatically reduced the processing difficulty of precise full-color printing and expanded the capability of structural color materials to collaborate with other systems.

7.
Brief Bioinform ; 23(3)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35262669

RESUMEN

Drug resistance is a major threat to the global health and a significant concern throughout the clinical treatment of diseases and drug development. The mutation in proteins that is related to drug binding is a common cause for adaptive drug resistance. Therefore, quantitative estimations of how mutations would affect the interaction between a drug and the target protein would be of vital significance for the drug development and the clinical practice. Computational methods that rely on molecular dynamics simulations, Rosetta protocols, as well as machine learning methods have been proven to be capable of predicting ligand affinity changes upon protein mutation. However, the severely limited sample size and heavy noise induced overfitting and generalization issues have impeded wide adoption of machine learning for studying drug resistance. In this paper, we propose a robust machine learning method, termed SPLDExtraTrees, which can accurately predict ligand binding affinity changes upon protein mutation and identify resistance-causing mutations. Especially, the proposed method ranks training data following a specific scheme that starts with easy-to-learn samples and gradually incorporates harder and diverse samples into the training, and then iterates between sample weight recalculations and model updates. In addition, we calculate additional physics-based structural features to provide the machine learning model with the valuable domain knowledge on proteins for these data-limited predictive tasks. The experiments substantiate the capability of the proposed method for predicting kinase inhibitor resistance under three scenarios and achieve predictive accuracy comparable with that of molecular dynamics and Rosetta methods with much less computational costs.


Asunto(s)
Aprendizaje Automático , Proteínas , Ligandos , Simulación de Dinámica Molecular , Mutación , Proteínas/química
8.
J Med Virol ; 96(7): e29793, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39023111

RESUMEN

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody-dependent-cellular-phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca-vaccinated individuals. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.


Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Vacunas de Subunidad , Vacunas de ARNm , Humanos , Inmunoglobulina G/sangre , Femenino , Anticuerpos Antivirales/sangre , Masculino , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Adulto , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/genética , Vacunas de Subunidad/administración & dosificación , Glicosilación , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Anciano , ARN Mensajero/genética , Adulto Joven , Vacunas de Subunidades Proteicas
9.
Microb Pathog ; 190: 106614, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38492825

RESUMEN

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.


Asunto(s)
Aeromonas hydrophila , Antioxidantes , Carpas , Eleutherococcus , Fermentación , Enfermedades de los Peces , Lacticaseibacillus rhamnosus , Probióticos , Animales , Lacticaseibacillus rhamnosus/metabolismo , Carpas/microbiología , Probióticos/farmacología , Probióticos/administración & dosificación , Antioxidantes/metabolismo , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/inmunología , Alimentación Animal , Inflamación/prevención & control , Citocinas/metabolismo , Acuicultura
10.
Langmuir ; 40(32): 17081-17089, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39078642

RESUMEN

Typically, gel-like materials consist of a polymer network structure in a solvent. In this work, a gel-like material is developed in a deep eutectic solvent (DES) without the presence of a polymer network, achieved simply by adding microgels. The DES is composed of choline chloride and citric acid and remains stably in a supercooled state at room temperature, exhibiting Newtonian fluid behavior with high viscosity. When the microgel (Carbopol) concentration exceeds 2 wt %, the DES undergoes a transition from a liquid to a soft gel state, characterized as a granular eutectogel. The soft gel characteristics of eutectogels exhibit a yield stress, and their storage moduli exceed the loss moduli. The yield stress and storage moduli are observed to increase with increasing microgel concentration. In contrast, the ion conductivity decreases with increasing microgel concentration but eventually levels off. Because the eutectogel can dissolve completely in excess water, it is a physical gel-like material, attributed to the densely packed structure of microgels in the supercooled DES. Due to the absence of networks, the granular eutectogel has the capability to self-heal simply by being pushed together after being cut into two pieces.

11.
Mol Cell Biochem ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138750

RESUMEN

Postoperative cognitive dysfunction (POCD) impacts a significant number of patients annually, frequently impairing their cognitive abilities and resulting in unfavorable clinical outcomes. Aimed at addressing cognitive impairment, vagus nerve stimulation (VNS) is a therapeutic approach, which was used in many mental disordered diseases, through the modulation of vagus nerve activity. In POCD model, the enhancement of cognition function provided by VNS was shown, demonstrating VNS effect on cognition in POCD. In the present study, we primarily concentrates on elucidating the role of the VNS improving the cognitive function in POCD, via two potential mechanisms: the inflammatory microenvironment and epigenetics. This study provided a theoretical support for the feasibility that VNS can be a potential method to enhance cognition function in POCD.

12.
Nicotine Tob Res ; 26(4): 474-483, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-37535700

RESUMEN

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Ratones , Animales , Masculino , Humanos , Nicotina/efectos adversos , Nicotina/metabolismo , Ratones Endogámicos C57BL , Pulmón , Aerosoles/farmacología
13.
Future Oncol ; 20(5): 245-256, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38018460

RESUMEN

Low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type has a favorable outcome with radiation therapy alone, and the addition of chemotherapy shows no survival benefit. Nonetheless, a proportion of patients will relapse or progress, with a dismal outcome, highlighting the need for a novel therapeutic strategy. Promising preliminary findings indicate the efficacy of PD-1/PD-L1 inhibitors in extranodal natural killer/T-cell lymphoma, nasal type, with good toxicity profiles. Here we describe the design of a phase II study (CLCG-NKT-2101), which is evaluating the safety and efficacy of adding anti-PD-1 antibody to the current radiation therapy regimen in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type patients. Tislelizumab will be added in an inductive and concurrent way to radiation therapy. The primary end point will be the complete response rate after induction immunotherapy. Clinical trial registration: ClinicalTrials.gov (NCT05149170).


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células T , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estadificación de Neoplasias , Linfoma de Células T/etiología , Células Asesinas Naturales , Ensayos Clínicos Fase II como Asunto
14.
Future Oncol ; 20(2): 71-81, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38179936

RESUMEN

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov).


Asunto(s)
Linfoma no Hodgkin , Humanos , Estudios Prospectivos , Linfoma no Hodgkin/tratamiento farmacológico , Resultado del Tratamiento , Ensayos Clínicos Fase II como Asunto , Estudios Multicéntricos como Asunto
15.
Neurol Sci ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39090356

RESUMEN

BACKGROUND: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. METHODS: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. RESULTS: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. CONCLUSIONS: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra.

16.
BMC Geriatr ; 24(1): 694, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164655

RESUMEN

BACKGROUND: This study conducted in-depth interviews to explore the factors that influence the adoption of fall detection technology among older adults and their families, providing a valuable evaluation framework for healthcare providers in the field of fall detection, with the ultimate goal of assisting older adults immediately and effectively when falls occur. METHODS: The method employed a qualitative approach, utilizing semi-structured interviews with 30 older adults and 29 families, focusing on their perspectives and expectations of fall detection technology. Purposive sampling ensured representation from older adults with conditions such as Parkinson's, dementia, and stroke. RESULTS: The results reveal key considerations influencing the adoption of fall-detection devices, including health factors, reliance on human care, personal comfort, awareness of market alternatives, attitude towards technology, financial concerns, and expectations for fall detection technology. CONCLUSIONS: This study identifies seven key factors influencing the adoption of fall detection technology among older adults and their families. The conclusion highlights the need to address these factors to encourage adoption, advocating for user-centered, safe, and affordable technology. This research provides valuable insights for the development of fall detection technology, aiming to enhance the safety of older adults and reduce the caregiving burden.


Asunto(s)
Accidentes por Caídas , Humanos , Accidentes por Caídas/prevención & control , Anciano , Masculino , Femenino , Anciano de 80 o más Años , Familia/psicología , Persona de Mediana Edad , Investigación Cualitativa , Aceptación de la Atención de Salud/psicología , Cuidadores/psicología
17.
Aging Clin Exp Res ; 36(1): 34, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38345702

RESUMEN

BACKGROUND: Sensory impairment significantly reduces speech discrimination and perception ability, presenting a challenge to effective communication. It can lead to social withdrawal and a reduced social network which can lead to cognitive impairment, seriously affecting the quality of life of older people. However, it is unclear which intervention components are effective to improving social network in older people with sensory impairment. OBJECTIVE: The aim of this systematic review was to summarize interventions designed to improve social network in older people with sensory impairment. METHODS: We searched seven databases from inception to December 1, 2023. Eligible studies included randomized clinical trials (RCT) and quasi-experimental studies of interventions for older people with sensory impairment aimed at improving social networks. Two reviewers searched databases, extracted data, and assessed the quality of the included studies independently. RESULTS: Nine studies including five RCTs and four quasi-experimental studies were selected, enrolling 721 older people with sensory impairment. Methodological quality of the studies was modest. Eight studies demonstrated a positive impact of the interventions used in older people with sensory impairment. The detailed effective intervention components may include communication strategies, resources for older people and their significant others, exercise or tech-back of communication, sensory device fitting, and use and maintenance of sensory devices. CONCLUSION: There are few interventions available for improving social network in older people with sensory impairment. Most interventions mainly focus on communication education and care, and sensory device fitting and education. To improve the social network in older people with sensory impairment, it is necessary to develop more effective, multidisciplinary collaborative effective interventions and conduct more high-quality original studies.


Asunto(s)
Red Social , Humanos , Anciano , Trastornos de la Sensación/terapia , Calidad de Vida , Apoyo Social
18.
BMC Musculoskelet Disord ; 25(1): 522, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970051

RESUMEN

BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.


Asunto(s)
Placas Óseas , Articulación del Codo , Fijación Interna de Fracturas , Fracturas Conminutas , Rango del Movimiento Articular , Fracturas del Cúbito , Humanos , Masculino , Femenino , Fracturas del Cúbito/cirugía , Fracturas del Cúbito/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Persona de Mediana Edad , Adulto , Fracturas Conminutas/cirugía , Fracturas Conminutas/diagnóstico por imagen , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/fisiopatología , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Curación de Fractura , Anciano , Medición de Resultados Informados por el Paciente , Adulto Joven
19.
BMC Musculoskelet Disord ; 25(1): 656, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169286

RESUMEN

OBJECTIVE: To investigate the clinical significance of using 3D printing guides in modified unilateral puncture percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fractures (OVCF), and to explore a new method for preventing paravertebral vein leakage during PVP in conjunction with a previous study of the optimal puncture-side bone cement/vertebral volume ratio(PSBCV/VV%). METHODS: This retrospective study analyzed 99 patients who underwent unilateral puncture PVP between January 2023 and December 2023. Patients were divided into a guide plate group (46 patients) and a conventional group (53 patients). The guide plate group underwent modified unilateral puncture PVP with the guidance of 3D printing guides, while the conventional group underwent unilateral puncture PVP using the conventional pedicle approach. The distribution of bone cement, surgical outcomes, and the occurrence of cement leakage into paravertebral veins were observed in both groups. RESULTS: The guide plate group had significantly shorter operating time and required fewer fluoroscopies compared to the conventional group. The amount of bone cement volume (BCV) used in the guide plate group was higher, but the amount of bone cement volume on the puncture side(PSBCV), the PSBCV/VV%, and the rate of paravertebral vein leakage were lower in the guide plate group compared to the conventional group (P < 0.05). Within each group, significant improvements in anterior vertebral margin height, Cobb angle, visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were observed at 1 day and 1 month postoperatively compared to preoperative values (P < 0.05). CONCLUSION: Using 3D printing guides in modified unilateral puncture PVP is a safe and effective method for treating OVCF. And it has the advantages of short operation time, less fluoroscopy, even distribution of bone cement, and a low rate of paravertebral vein leakage.


Asunto(s)
Cementos para Huesos , Fracturas por Compresión , Fracturas Osteoporóticas , Impresión Tridimensional , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Estudios Retrospectivos , Fracturas por Compresión/cirugía , Fracturas por Compresión/diagnóstico por imagen , Femenino , Vertebroplastia/métodos , Masculino , Anciano , Fracturas Osteoporóticas/cirugía , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/diagnóstico por imagen , Persona de Mediana Edad , Anciano de 80 o más Años , Cementos para Huesos/uso terapéutico , Resultado del Tratamiento , Punciones/métodos , Relevancia Clínica
20.
Molecules ; 29(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38893416

RESUMEN

Being a bio-sourced and biodegradable polymer, polylactic acid (PLA) has been considered as one of the most promising substitutes for petroleum-based plastics. However, its wide application is greatly limited by its very poor ductility, which has driven PLA-toughening modifications to be a topic of increasing research interest in the past decade. Toughening enhancement is achieved often at the cost of a large sacrifice in strength, with the toughness-strength trade-off having remained as one of the main bottlenecks of PLA modification. In the present study, a bio-elastomeric material of epoxidized soybean oil (ESO) crosslinked with sebacic acid (SA) and enhanced by graphene oxide (GO) nanoparticles (NPs) was employed to toughen PLA with the purpose of simultaneously preserving strength and achieving additional functions. The even dispersion of GO NPs in ESO was aided by ultrasonication and guaranteed during the following ESO-SA crosslinking with GO participating in the carboxyl-epoxy reaction with both ESO and SA, resulting in a nanoparticle-enhanced and dynamically crosslinked elastomer (GESO) via a ß-hydroxy ester. GESO was then melt-blended with PLA, with the interfacial reaction between ESO and PLA offering good compatibility. The blend morphology, and thermal and mechanical properties, etc., were evaluated and GESO was found to significantly toughen PLA while preserving its strength, with the GO loading optimized at ~0.67 wt%, which gave an elongation at break of ~274.5% and impact strength of ~10.2 kJ/m2, being 31 times and 2.5 times higher than pure PLA, respectively. Moreover, thanks to the presence of dynamic crosslinks and GO NPs, the PLA-GESO blends exhibited excellent shape memory effect and antistatic properties.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA