Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.157
Filtrar
1.
Oncol Lett ; 28(6): 573, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39397807

RESUMEN

The aim of the present study was to develop a prediction model for set-up error distribution in breast cancer image-guided radiotherapy (IGRT) using a Gaussian mixture model (GMM). To achieve this, the image-guided set-up errors data of 80 patients with breast cancer were selected, and the GMM was used to develop the set-up errors distribution prediction model. The predicted error center points, covariance and probability were calculated and compared with the planning target volume (PTV) margin formula. A total of 1,200 sets of set-up errors in IGRT for breast cancer were collected. The results of the Gaussian model parameters showed that the set-up errors were mainly in the direction of µ1-µ4 center points. All the raw errors in the lateral, longitudinal and vertical directions were -6.30-4.60, -5.40-1.47 and -2.70-1.70 mm, respectively. According to the probability of each center, the set-up error was most likely to shift in the µ1 direction, reaching 0.53. The set-up errors of the other three centers, µ2, µ3 and µ4, were 0.11, 0.34 and 0.12, respectively. According to the covariance parameters of the GMM, the maximum statistical standard deviation of the set-up errors reached 29.06. In conclusion, the results of the present study demonstrated that the GMM can be used to quantitatively describe and predict the distribution of set-up errors in IGRT for breast cancer, and these findings could be useful as a reference for set-up error control and tumor PTV expansion in breast cancer radiotherapy without routine, daily IGRT.

2.
Small ; : e2405321, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39402782

RESUMEN

Limited by the insufficient catalytic substrates such as H2O2 and O2 in the tumor microenvironment (TME), the continual propelling of nanozymes catalysis therapy of cancer remains a challenge. Here, an all-in-one MnO2@PtAuRu nanoreactor is constructed for self-propelled and cascade catalytic therapy of tumors. The MnO2@PtAuRu is constructed by using hollow MnO2 (≈150 nm) as the core-carrier and ultrasmall PtAuRu nanoclusters (≈2 nm) anchoring on the surface MnO2. According to the glucose oxidase (GOD)/catalase (CAT)/peroxidase (POD) mimic multienzyme activity of PtAuRu nanoclusters, cascaded nanocatalytic reactions can be self-replenishing to persistently produce •OH for superior chemodynamic therapy (CDT). Additionally, the MnO2 carrier can protect the ultrasmall PtAuRu nanoclusters during the circulation and the overexpressed glutathione (GSH) in the tumor can also be degraded by the MnO2 to synergy the CDT. The MnO2@PtAuRu displays obvious photothermal properties which further enhance the cascade catalytic ability and synergistic therapeutic effect. Therefore, this all-in-one nanozyme provides a promising strategy for the rational design of self-replenishment and self-replenishing cascade catalytic therapy of cancer.

3.
J Ethnopharmacol ; 337(Pt 2): 118891, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39362326

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The dried succulent stems of Cistanche tubulosa (Schenk) Wight are utilized in traditional medicine for tonifying kidney yang, which have shown to be effective in alleviating depression-like behaviors or male sexual dysfunction, respectively. However, the pharmacological effects and mechanisms of C. tubulosa and its combinations in the treatment of depression in comorbid with sexual dysfunction remain unclear. AIM OF THE STUDY: This study aims to elucidate the pharmacological effects and mechanisms of C. tubulosa aqueous extract (CTE) and its combination with fluoxetine (FLX) on depression in comorbid with sexual dysfunction. MATERIALS AND METHODS: A mouse model of depression in comorbid with sexual dysfunction was created using the chronic unpredictable mild stress (CUMS) procedure. The therapeutic effects of CTE and its combination with FLX were assessed using depressive-like and mating behavior experiments, histopathological analysis, and hypothalamic-pituitary-gonadal (HPG) axis function evaluation. The mechanisms were explored by integrated serum and testicular metabolomics combined with network correlation analysis. RESULTS: CTE was confirmed to significantly improve depressive-like behaviors, reduce mating abilities, testicular histopathological damage, and HPG axis hormone secretion disorders in CUMS mice. Subsequently, mechanism exploration findings indicated that CTE might exert its effect by regulating potential efficacy-related biomarkers (isobutyrylglycine, citric acid, D-galactose) to improve certain metabolic pathways centered around steroid hormone biosynthesis and tricarboxylic acid (TCA) cycle. Furthermore, the combination of CTE and FLX exhibited stronger antidepressant effects than FLX alone, and ameliorated the exacerbated sexual dysfunction induced by FLX. These effects were achieved through the regulation of potential efficacy-related biomarkers (17α-hydroxypregnenolone, tetrahydrodeoxy-corticosterone, sphingosine, cortol, thymine, and L-histidine), thereby improving disorders in glycerophospholipid and histidine metabolism. CONCLUSION: In conclusion, the amelioration effects of CTE and its combination with FLX on depression in comorbid with sexual dysfunction were confirmed for the first time. This key mechanism may be achieved by modulating the levels of potential efficacy-related biomarkers, and then emphatically intervene in steroid hormone biosynthesis, TCA cycle, glycerophospholipid and histidine metabolism. The study offers a new perspective for the development and utilization of C. tubulosa.

4.
Materials (Basel) ; 17(19)2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39410321

RESUMEN

This study, based on the analysis of existing experimental data, presents a third generation Calphad description of lithium, covering all temperature ranges, using nonlinear least squares in Matlab. We have expanded the SGTE database's description of lithium phases (face-centered cube, body-centered cube, liquid) down to 0 K with reasonable accuracy, taking into account the significant effort required to reconstruct the database for each element. During the evaluation process, it was determined that the low-temperature phase of lithium is fcc. The heat capacity of crystalline Li was accurately described using the extended Debye model. The third generation Calphad description of lithium utilized the two-state model and the extended Einstein model, leading to improved agreement with experimental data compared to previous assessments.

5.
J Sep Sci ; 47(19): e202400407, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39340368

RESUMEN

Sijunzi decoction (SJZD) has been widely used to treat splenic deficiency syndrome. Previous studies confirmed that polysaccharides and non-polysaccharides (NPS) are the main active components of SJZD. This study aimed to investigate the composition and activity of oligosaccharides in NPS. In this study, the oligosaccharide component (named SJZD-OGS), consisting of several different oligosaccharides, was separated and purified from non-polysaccharides of SJZD (SJZD_NPS). Ultra-high-performance liquid chromatography-ion mobility spectrometry-quadrupole time-of-flight mass spectrometry (UHPLC-IMS-QTOF/MS), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) were used to analyze SJZD-OGS. SJZD-OGS, with a molecular weight of 2178 Da, was composed of glucose and fructose, and its chemical composition mainly included fructo-oligosaccharides (FOS) with a degree of polymerization of 3-14 (DP 3-14). The results of oligosaccharide source exploration demonstrated that the chemical composition of SJZD-OGS was different from that of the oligosaccharides of each herb in SJZD. In addition, SJZD-OGS showed good anti-inflammatory activity on macrophage cells and intestinal epithelial cell protective activity. The present work provides experimental evidence for elucidating the pharmaceutical components of SJZD and presents an effective strategy for the research of oligosaccharides in traditional Chinese medicine (TCM).


Asunto(s)
Medicamentos Herbarios Chinos , Oligosacáridos , Oligosacáridos/química , Oligosacáridos/aislamiento & purificación , Oligosacáridos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Animales , Ratones , Células RAW 264.7 , Cromatografía Líquida de Alta Presión , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos
6.
Chem Sci ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39282650

RESUMEN

The controlled aggregation of organic chromophores into supramolecular structures offers a way to control and tune photocatalytic activity. However, the underlying mechanisms of charge transfer and accumulation are still unclear. Time-resolved vibrational spectroscopy is a powerful structural probe for studying photogenerated intermediates. Here, we employ time-resolved infrared (TRIR) spectroscopy to study CNP (2,6-bis(4-cyanophenyl)-4-(9-phenyl-9H-carbazol-3-yl)pyridine-3,5-dicarbonitrile) and its supramolecular aggregates. We show that excitation of the charge transfer (CT) band of semi-crystalline nanofibers (CNP-f) gives rise to long-lived delocalised polarons, which form within the instrument response timescale. By contrast the CNP nanospheres (CNP-s) give rise to a shorter lived polaron that appears to have a greater degree of localization. CNP-f and CNP-s are known to show markedly different levels of photocatalytic activity for hydrogen and hydrogen peroxide formation which are rationalised owing to these differences in photodynamics immediately following photon absorption.

7.
Bioinformatics ; 40(10)2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39316736

RESUMEN

MOTIVATION: Drug recommendation aims to allocate safe and effective drug combinations based on the patient's health status from electronic health records, which is crucial to assist clinical physicians in making decisions. However, the existing drug recommendation works face two key challenges: (i) difficulty in fully representing the patient's health status leads to biased drug representation; (ii) only focusing on diagnostic representations of multiple visits, neglecting the modeling of patient drug history. RESULTS: To address the above limitations, we propose a multi-view gating retrieval network (MGRN) for robust drug recommendation. We design visit-, sequence-, and token-level views to provide different perspectives on the interaction between patients and drugs, obtaining a more comprehensive representation of drugs. Moreover, we develop a gating drug retrieval module to capture critical drug information from multiple visits, which can assist in recommending more reasonable drug combinations for the current visit. When evaluated on publicly real-world MIMIC-III and MIMIC-IV datasets, the proposed MGRN establishes a new benchmark performance, particularly achieving improvements of 1.36%, 1.71%, 1.21% and 2.12%, 2.36%, 1.81% in Jaccard, PRAUC, and F1-score, respectively, compared to state-of-the-art models. AVAILABILITY AND IMPLEMENTATION: The code is available at: https://github.com/kyosen258/MGRN.git.


Asunto(s)
Registros Electrónicos de Salud , Humanos , Algoritmos , Almacenamiento y Recuperación de la Información/métodos
8.
Front Immunol ; 15: 1440911, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39229273

RESUMEN

Introduction: The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. Methods: In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptide-binding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. Results: The class I HED for recipient (R_HEDclass I) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease. The patients with high class II HED for donor-recipient (D/R_HEDclass II) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HEDclass II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HEDclass II was an independent risk factor for the development of severe aGVHD (P = 0.007), and a high R_HEDclass I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease-free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. Discussion: While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD. In haploidentical setting, class II HED for donor-recipient pair (D/R_HEDclass II) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts.


Asunto(s)
Selección de Donante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Masculino , Femenino , Adulto , Adolescente , Persona de Mediana Edad , Niño , Estudios Retrospectivos , Factores de Riesgo , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/genética , Adulto Joven , Antígenos HLA/genética , Antígenos HLA/inmunología , Preescolar , Trasplante Haploidéntico , Donantes de Tejidos , Evolución Molecular
9.
Artículo en Inglés | MEDLINE | ID: mdl-39279349

RESUMEN

Invertebrates and microorganisms are important but climate-dependent agents of wood decomposition globally. In this meta-analysis, we investigated what drives the invertebrate effect on wood decomposition worldwide. Globally, we found wood decomposition rates were on average approximately 40% higher when invertebrates were present compared to when they were excluded. This effect was most pronounced in the tropics, owing mainly to the activities of termites. The invertebrate effect was stronger for woody debris without bark as well as for that of larger diameter, possibly reflecting bark- and diameter-mediated differences in fungal colonisation or activity rates relative to those of invertebrates. Our meta-analysis shows similar overall invertebrate effect sizes on decomposition of woody debris derived from angiosperms and gymnosperms globally. Our results suggest the existence of critical interactions between microorganism colonisation and the invertebrate contribution to wood decomposition. To improve biogeochemical models, a better quantification of invertebrate contributions to wood decomposition is needed.

10.
BJR Open ; 6(1): tzae023, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39220325

RESUMEN

Objectives: Accurate beam modelling is essential for dose calculation in stereotactic radiation therapy (SRT), such as CyberKnife treatment. However, the present deep learning methods only involve patient anatomical images and delineated masks for training. These studies generally focus on traditional intensity-modulated radiation therapy (RT) plans. Nevertheless, this paper aims to develop a deep CNN-based method for CyberKnife plan dose prediction about brain cancer patients. It utilized modelled beam information, target delineation, and patient anatomical information. Methods: This study proposes a method that adds beam information to predict the dose distribution of CyberKnife in brain cases. A retrospective dataset of 88 brain and abdominal cancer patients treated with the Ray-tracing algorithm was performed. The datasets include patients' anatomical information (planning CT), binary masks for organs at risk (OARs) and targets, and clinical plans (containing beam information). The datasets were randomly split into 68, 6, and 14 brain cases for training, validation, and testing, respectively. Results: Our proposed method performs well in SRT dose prediction. First, for the gamma passing rates in brain cancer cases, with the 2 mm/2% criteria, we got 96.7% ± 2.9% for the body, 98.3% ± 3.0% for the planning target volume, and 100.0% ± 0.0% for the OARs with small volumes referring to the clinical plan dose. Secondly, the model predictions matched the clinical plan's dose-volume histograms reasonably well for those cases. The differences in key metrics at the target area were generally below 1.0 Gy (approximately a 3% difference relative to the prescription dose). Conclusions: The preliminary results for selected 14 brain cancer cases suggest that accurate 3-dimensional dose prediction for brain cancer in CyberKnife can be accomplished based on accurate beam modelling for homogeneous tumour tissue. More patients and other cancer sites are needed in a further study to validate the proposed method fully. Advances in knowledge: With accurate beam modelling, the deep learning model can quickly generate the dose distribution for CyberKnife cases. This method accelerates the RT planning process, significantly improves its operational efficiency, and optimizes it.

11.
J Neurosci Res ; 102(9): e25379, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39235282

RESUMEN

We reported that infiltrated Ly6C+ macrophages express brain-derived neurotrophic factor (BDNF) only at the cerebral cortex infarct in a rat dMCAO model. However, the changein neuron-expressed BDNF, the niche components that induce the Ly6C+ cells to express BDNF, and the cellular sources of these components, remain unclear. In this study, immunofluorescence double staining was performed to label BDNF and Ly6C on brain sections at 3, 24, and 48 h following distal middle cerebral artery occlusion (dMCAO) of male rats, and to stain BDNF with Ly6C, IL-4R, and IL-10R. A neutralizing anti-IL-4 antibody was injected into the infarct, and the IL-4 and BDNF concentrations in the subareas of the infarct were determined using enzyme-linked immunosorbent assay. To find out the cellular sources of IL-4, the markers for microglia, T cells, and neurons were co-stained with IL-4 separately. In certain infarct subareas, the main BDNF-expressing cells shifted quickly from NeuN+ neurons to Ly6C+ cells during 24-48 h post-stroke, and the Ly6C+/BDNF+ cells mostly expressed IL-4 receptor. Following IL-4 neutralizing antibody injection, the BDNF, IL-4 protein levels, and BDNF+/Ly6C+ cells decreased significantly. The main IL-4-expressing cell type in this infarct subarea is not neuron either, but immune cells, including microglia, monocyte, macrophages, and T cells. The neurons, maintained BDNF and IL-4 expression in the peri-infarct area. In conclusion, in a specific cerebral subarea of the rat dMCAO model, IL-4 secreted by immune cells is one of the main inducers for Ly6C+ cells to express BDNF.


Asunto(s)
Isquemia Encefálica , Factor Neurotrófico Derivado del Encéfalo , Interleucina-4 , Macrófagos , Animales , Masculino , Ratas , Isquemia Encefálica/metabolismo , Isquemia Encefálica/inmunología , Isquemia Encefálica/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Interleucina-4/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Neuronas/metabolismo , Neuronas/patología , Ratas Sprague-Dawley
12.
Front Plant Sci ; 15: 1404589, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39315377

RESUMEN

Interplanting crops is the best method to grow crops synergistically for better utilization of land and agro-resources. Grape (Vitis vinifera) and potato (Solanum tuberosum L.) have highly efficient agricultural planting systems in China, however, how soil physicochemical properties and soil microbial communities and metabolites affect the output of grape-potato interplanting remained unknown. In this study, we employed three planting patterns (CK: grape monocropping; YY: grape interplanted with potato (variety 'Favorita'); LS: grape interplanted with potato (variety 'Longshu7')) at two experimental sites i.e., the Huizhou (2022) site and the Qingyuan site (2023). The grape variety for all planting patterns was 'Sunshine Rose'. Soil samples (top 0-20 cm) at both sites were collected to observe the diversity of bacterial communities and soil metabolites. Our findings revealed that, compared with monocropping, the interplanted systems resulted in higher concentrations of total nitrogen, available phosphorus, and available potassium and enhanced the activities of acid phosphatase, urease, and protease. The potato root exudates also altered the relative abundance of Bacillus, Kaistobacter, and Streptomyces in the rhizosphere. Among the soil metabolites, lipids and organic acids showed the most significant changes. Notably, 13-L-hydroperoxylinoleic acid is the key differentially abundant metabolite involved in the regulation of linoleic acid metabolism pathways. The association analyses of the metabolome, microbiome, and soil physicochemical properties revealed that the interactions of microbes and metabolites resulted in differences in the soil nutrient content, whereas the interactions of 13-L-hydroperoxylinoleic acid and Firmicutes improved the soil nutrient levels and bacterial composition in the interplanting systems. In summary, our findings demonstrated that intercropping grapes with potato 'Favorita' was better with respect to improving soil nutrients, soil enzyme activity, the diversity of soil bacteria, and soil metabolites without causing adverse impacts on grape yield. Overall, this study explained the physiological mechanisms by which soil microorganisms and metabolites promote potato growth in grape interplanting and provided new perspectives for the utilization of soil resources in vineyards.

13.
J Hazard Mater ; 480: 135808, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39288524

RESUMEN

There is a correlation between long-term manganese (Mn) exposure and the Parkinson's-like disease (PD), with depression as an early symptom of PD. However, the direct relationship between Mn exposure and depression, and the mechanisms involved, remain unclear. We found that Mn exposure led to depressive-like behavior and mild cognitive impairment in mice, with Mn primarily accumulating in the cornu ammonis 3 (CA3) area of the hippocampus. Mice displayed a reduction in neuronal dendritic spines and damage to astrocytes specifically in the CA3 area. Spatial metabolomics revealed that Mn downregulated glutamic acid decarboxylase 1 (GAD1) expression in astrocytes, disrupting the Glutamine-Glutamate-γ-aminobutyric acid (GlnGluGABA) metabolic cycle in the hippocampus, leading to neurotoxicity. We established an in vitro astrocyte Gad1 overexpression (OEX) model and found that the cultured medium from Gad1 OEX astrocytes reversed neuronal synaptic damage and the expression of gamma-aminobutyric acid (GABA) related receptors. Using the astrocyte Gad1 OEX mouse model, results showed that OEX of Gad1 ameliorated depressive-like behavior and cognitive dysfunction in mice. These findings provide new insight into the important role of GAD1 mediated GlnGluGABA metabolism disorder in Mn exposure induced depressive-like behavior. This study offers a novel sight to understanding abnormal emotional states following central nervous system damage induced by Mn exposure.

14.
Nanoscale Horiz ; 9(10): 1703-1724, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39087682

RESUMEN

MXene-based architectures have paved the way in various fields, particularly in healthcare area, owing to their remarkable physiochemical and electromagnetic characteristics. Moreover, the modification of MXene structures and their combination with polymeric networks have gained considerable prominence to further develop their features. The combination of electrospun fibers with MXenes would be promising in this regard since electrospinning is a well-established technique that is now being directed toward commercial biomedical applications. The introduction of MXenes into electrospun fibrous frameworks has highlighted outcomes in various biomedical applications, including cancer therapy, controlled drug delivery, antimicrobial targets, sensors, and tissue engineering. Correspondingly, this review describes the employed strategies for the preparation of electrospun configurations in tandem with MXene nanostructures with remarkable characteristics. Next, the advantages of MXene-decorated electrospun fibers for use in biomedical applications are comprehensively discussed. According to the investigations, rich surface functional groups, hydrophilicity, large surface area, photothermal features, and antimicrobial and antibacterial activities of MXenes could synergize the performance of electrospun layers to engineer versatile biomedical targets. Moreover, the future of this path is clarified to combat the challenges related to the electrospun fibers decorated with MXene nanosheets.


Asunto(s)
Nanoestructuras , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Humanos , Ingeniería Biomédica/métodos , Ingeniería de Tejidos/métodos , Sistemas de Liberación de Medicamentos/métodos , Polímeros/química
15.
CNS Neurosci Ther ; 30(8): e14877, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39097914

RESUMEN

AIMS: The objective of this study was to evaluate the effectiveness of batroxobin in improving functional outcomes and reducing stroke recurrence among patients with acute ischemic stroke beyond the therapeutic time window for thrombolytic therapy. METHODS: This multicenter, retrospective study enrolled 492 patients with acute moderate-to-severe ischemic stroke within 24 h. 238 patients were given standard (basic) therapy. On the basis of standard treatment, 254 patients received an initial intravenous infusion of batroxobin 10 U on day 1, followed by subsequent infusions of batroxobin 5 U on the 3rd and 5th days, respectively. RESULTS: In the batroxobin group, 8.3% of patients experienced recurrence stroke, compared to 17.2% in the control group (HR, 0.433; 95% CI, 0.248 to 0.757; p = 0.003). Furthermore, intravenous batroxobin significantly improved the distribution of 90-120 day disability. Moderate-to-severe bleeding events were reported in three patients (1.2%) in the batroxobin group and one patient (0.4%) in the control group (p = 0.369). CONCLUSIONS: Among patients with acute moderate-to-severe ischemic stroke beyond the time window for thrombolytic therapy, treatment with intravenous batroxobin had a lower risk of stroke recurrence and a better recovery of function outcome without increasing bleeding events. Prospective studies are needed to further confirm.


Asunto(s)
Batroxobina , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Batroxobina/uso terapéutico , Batroxobina/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años
16.
bioRxiv ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39211173

RESUMEN

Lupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that affects kidney function. Here, we investigated the role of CD11b, a protein encoded by the ITGAM gene, in the development of LN and its functional activation as a therapeutic strategy. Genetic coding variants of ITGAM significantly increase the risk for SLE and LN by producing a less active CD11b and leading to elevated levels of type I interferon (IFN I). However, a molecular mechanism for how these variants increase LN risk has been unclear. Here, we determined that these variants also significantly associate with elevations in soluble urokinase plasminogen activator receptor (suPAR), a known biomarker linked to kidney disease, suggesting a novel molecular connection. Pharmacologic activation of CD11b with a novel, clinical-stage agonist ONT01 significantly suppressed suPAR production in myeloid cells and reduced systemic inflammation and kidney damage in multiple experimental models of LN. Importantly, delaying treatment with ONT01 until after disease onset also significantly reduced serum suPAR and inflammatory cytokines, and decreased immune complex deposition in the glomerulus, glomerulonephritis and albuminuria, suggesting that CD11b activation is therapeutic for LN. Genetic activation of CD11b via a gain-of-function CD11b mutation also showed complete protection from LN, whereas genetic deletion of CD11b worsened the disease in mice, providing further evidence of the role of CD11b activation in regulating LN. Finally, transfer of human LN PBMCs generated human LN like disease in mice that was significantly reduced by ONT01. Together, these data provide strong evidence that ONT01 mediated CD11b activation can therapeutically modulate TLR7-driven inflammation and protect against LN. These findings support clinical development of CD11b agonists as novel therapeutics for treating lupus nephritis in human patients.

17.
Neurobiol Dis ; 200: 106635, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39128813

RESUMEN

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.


Asunto(s)
Diferenciación Celular , Movimiento Celular , Epilepsia , Proteínas HSP90 de Choque Térmico , Accidente Cerebrovascular Isquémico , Células-Madre Neurales , Animales , Masculino , Ratones , Diferenciación Celular/fisiología , Movimiento Celular/fisiología , Progresión de la Enfermedad , Epilepsia/metabolismo , Epilepsia/genética , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/genética , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Ratones Endogámicos C57BL , Células-Madre Neurales/metabolismo , Proteínas Proto-Oncogénicas c-jun
18.
Food Chem ; 460(Pt 2): 140382, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39126741

RESUMEN

Herein, a stable and ultra-sensitive rutin electrochemical sensor was successfully developed. This sensor based on glassy carbon electrode (GCE) modified with C-GCS@ZIF-F/PL nanocomposite, which was made of thermally carbonized glucose (GCS) doped with flower-like ZIF (ZIF-F) and pencil lead (PL). The electrochemical response of rutin was considerably significant at C-GCS@ZIF-F/PL/GCE, demonstrating favorable conductivity and electrocatalytic properties for detection of rutin. Under optimal conditions, the linear range is 0.1-100 µM, with a low detection limit (LOD) of 0.0054 µM. It also exhibits excellent stability, reproducibility, as well as selectivity over common interfering ions such as Na+, uric acid, quercetin and riboflavin, etc. Meanwhile, the practical utility of developed sensor was evaluated in food samples including honey, orange, and buckwheat tea, achieving satisfactory recovery rates ranging from 98.2% to 101.7%. This paper introduces a novel technique for the detection of rutin in foods.


Asunto(s)
Técnicas Electroquímicas , Límite de Detección , Rutina , Rutina/análisis , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Miel/análisis , Fagopyrum/química , Contaminación de Alimentos/análisis , Electrodos , Carbono/química , Glucosa/análisis , Reproducibilidad de los Resultados , Nanocompuestos/química , Té/química , Análisis de los Alimentos/instrumentación
19.
Cortex ; 179: 1-13, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39089096

RESUMEN

Attention-deficit/hyperactivity disorder (ADHD) is among the most prevalent, inheritable, and heterogeneous childhood-onset neurodevelopmental disorders. Children with a hereditary background of ADHD have heightened risk of having ADHD and persistent impairment symptoms into adulthood. These facts suggest distinct familial-specific neuropathological substrates in ADHD that may exist in anatomical components subserving attention and cognitive control processing pathways during development. The objective of this study is to investigate the topological properties of the gray matter (GM) structural brain networks in children with familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), as well as matched controls. A total of 452 participants were involved, including 132, 165 and 155 in groups of ADHD-F, ADHD-NF and typically developed children, respectively. The GM structural brain network was constructed for each group using graph theoretical techniques with cortical and subcortical structures as nodes and correlations between volume of each pair of the nodes within each group as edges, while controlled for confounding factors using regression analysis. Relative to controls, children in both ADHD-F and ADHD-NF groups showed significantly higher nodal global and nodal local efficiencies in the left caudal middle frontal gyrus. Compared to controls and ADHD-NF, children with ADHD-F showed distinct structural network topological patterns associated with right precuneus (significantly higher nodal global efficiency and significantly higher nodal strength), left paracentral gyrus (significantly higher nodal strength and trend toward significantly higher nodal local efficiency) and left putamen (significantly higher nodal global efficiency and trend toward significantly higher nodal local efficiency). Our results for the first time in the field provide evidence of familial-specific structural brain network alterations in ADHD, that may contribute to distinct clinical/behavioral symptomology and developmental trajectories in children with ADHD-F.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Encéfalo , Sustancia Gris , Imagen por Resonancia Magnética , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/patología , Niño , Masculino , Femenino , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/patología , Adolescente , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Mapeo Encefálico/métodos
20.
Talanta ; 280: 126700, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39180872

RESUMEN

Epidemiology and public health concerns have primarily relied on the accurate control of gas pollutants, requiring highly efficient gas sensor devices for detecting hazardous gases. Despite the dedication of many efforts in this era, the precise, continuous scrutiny of gases remains elusive for appropriate gas selectivity, prompt response and recovery time, proper repeatability, as well as low cost. Accordingly, nanostructured architectural sensing cues have received enormous attention toward versatile detection and sensing procedures. As a representational nanostructure, the MXene family has been widely introduced to tailor and augment sensor patterns by providing large surface area, tunable surface chemistry, superior electrical conductivity, chemical stability, compatibility with flexible substrates, and potential for multifunctionality. Additionally, they could be synthesized in various formations of film and layered designs, fibrous membranes, and gel-like structures, creating synergetic effects that can provide superior gas-sensing performance. Herein, the synthesis and benefits of MXene nanosheets as gas-sensitive materials, in tandem with the past-to-present progress of MXene-based gas sensors in the formation of films, fibrous, and gel-like configurations, are comprehensively reviewed. As an in-depth reference, the present overview could shed light on further advancing gas sensor architectures developed based on MXene structures.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA