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1.
Alzheimers Res Ther ; 16(1): 103, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38725083

RESUMEN

BACKGROUND: The role of α-synuclein in dementia has been recognized, yet its exact influence on cognitive decline in non-demented older adults is still not fully understood. METHODS: A total of 331 non-demented individuals were included in the study from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were divided into two distinct groups based on their α-synuclein levels: one with lower levels (α-synuclein-L) and another with higher levels (α-synuclein-H). Measurements included neuropsychiatric scales, cerebrospinal fluid (CSF) biomarkers, and blood transcriptomics. The linear mixed-effects model investigated the longitudinal changes in cognition. Kaplan-Meier survival analysis and the Cox proportional hazards model were utilized to evaluate the effects of different levels of α-synuclein on dementia. Gene set enrichment analysis (GSEA) was utilized to investigate the biological pathways related to cognitive impairment. Pearson correlation, multiple linear regression models, and mediation analysis were employed to investigate the relationship between α-synuclein and neurodegenerative biomarkers, and their potential mechanisms affecting cognition. RESULTS: Higher CSF α-synuclein levels were associated with increased risk of cognitive decline and progression to dementia. Enrichment analysis highlighted the activation of tau-associated and immune response pathways in the α-synuclein-H group. Further correlation and regression analysis indicated that the CSF α-synuclein levels were positively correlated with CSF total tau (t-tau), phosphorylated tau (p-tau) 181, tumor necrosis factor receptor 1 (TNFR1) and intercellular cell adhesion molecule-1 (ICAM-1). Mediation analysis further elucidated that the detrimental effects of CSF α-synuclein on cognition were primarily mediated through CSF t-tau and p-tau. Additionally, it was observed that CSF α-synuclein influenced CSF t-tau and p-tau181 levels via inflammatory pathways involving CSF TNFR1 and ICAM-1. CONCLUSIONS: These findings elucidate a significant connection between elevated levels of CSF α-synuclein and the progression of cognitive decline, highlighting the critical roles of activated inflammatory pathways and tau pathology in this association. They underscore the importance of monitoring CSF α-synuclein levels as a promising biomarker for identifying individuals at increased risk of cognitive deterioration and developing dementia.


Asunto(s)
Biomarcadores , Disfunción Cognitiva , alfa-Sinucleína , Proteínas tau , Humanos , Femenino , Masculino , Disfunción Cognitiva/líquido cefalorraquídeo , alfa-Sinucleína/líquido cefalorraquídeo , Anciano , Proteínas tau/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Anciano de 80 o más Años , Pruebas Neuropsicológicas
2.
Food Chem ; 451: 139449, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38678654

RESUMEN

The addition of corn starch (CS) enhances the interfacial adhesion of the film-forming liquids (FFLs), weakening the internal relative molecular motion. As a result, the rheological properties and zeta potential values of the FFLs were affected. A tight spatial network structure between capsicum leaf protein (CLP), lignocellulose nanocrystals (LNCs) and CS can be formed through intermolecular entanglement and hydrogen bonding interactions. The crystallinity, thermal degradation temperature, tensile strength and water contact angle of the protein-based bionanocomposite films (PBBFs) increased with increasing CS addition. This is due to the transformation of the secondary space structure of the CLP inside the PBBFs and the increase in cohesion. However, the excessive addition of CS forms aggregated clusters on the surface of PBBFs, which increases the surface roughness of PBBFs and causes more light scattering. Therefore, the brightness and yellowness values of the PBBFs increase, and the transmittance decreases.

3.
Int J Biol Macromol ; 266(Pt 2): 131366, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580020

RESUMEN

A functional starch (TPS-E) was designed and constructed by incorporating epoxy soybean oil (ESO) and an antibacterial agent polyhexamethylene guanidine hydrochloride (PHMG), then the film was prepared by reaction extrusion and blow molding using TPS-E and poly(butylene adipate-co-terephthalate) (PBAT). The micro-crosslinking structure, forming through ring-opening reaction between the epoxy active site of TPS-E and the end group of PBAT, improved the compatibility of starch/PBAT blend and reduce the dispersed starch phase size, leading to significantly increase the tensile strength. Compared to starch/PBAT films, the tensile strength of TPS-E/PBAT in the longitudinal direction increase by 112% with the same starch content of 30%. Furthermore, these TPS-E/PBAT films demonstrated long-lasting antibacterial performance with a 98% inhibition ratio even after 10 cycles, without any observed leaching of the antibacterial agent, highlighting the high coupling efficiency of PHMG. TPS-E with the degradable ESO also promotes the degradation of PBAT. Thus, an important method of synergistic improving the mechanical, degradable and antibacterial properties of blown films through the design of reactive micro-crosslinked starch structures was established.


Asunto(s)
Antibacterianos , Almidón , Resistencia a la Tracción , Almidón/química , Antibacterianos/química , Antibacterianos/farmacología , Poliésteres/química , Escherichia coli/efectos de los fármacos , Fenómenos Mecánicos , Reactivos de Enlaces Cruzados/química , Staphylococcus aureus/efectos de los fármacos
4.
Huan Jing Ke Xue ; 45(3): 1803-1811, 2024 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-38471891

RESUMEN

To investigate the effect of chelating agents on plant uptake of heavy metals, castor (Ricinus communis L.) was used as the test plant. Soil culture and pot experiments were conducted to study the effects of different concentrations of ethylenediamine disuccinic acid (EDDS) on the forms of Cu and Cd in soil and their absorption and transport by castor. The results showed that the application of EDDS significantly increased the content of available Cu and Cd. After 15 days of cultivation, the available Cu and Cd concentrations in the soil increased by 43.01%-103.55% and 51.78%-69.43%, respectively. EDDS promoted the conversion of reducible Cu to weak acid extractable and increased the mobility of Cu. Meanwhile, the application of EDDS promoted the absorption, transport, and enrichment of Cu in castor. Under the application of 2.5 mmol·kg-1 EDDS and 5.0 mmol·kg-1 EDDS, the Cu concentrations in the shoots were 4.88 times and 16.65 times higher than that of the control (P< 0.05), and the Cu concentrations in the roots were 2.89 times and 3.60 times higher than that of the control (P< 0.05), respectively. The Cu transport coefficient significantly increased by 72.73% and 381.82% when treated with EDDS 2.5 and EDDS 5.0. Simultaneously, the phytoextraction of Cu in shoots, roots, and their sum were 14.08, 2.16, and 4.70 times higher than that of the control (P<0.05), respectively, when treated with EDDS 5.0. Furthermore, EDDS significantly increased the Cd concentrations in castor. When treated with EDDS 2.5 the shoots and roots increased by 15.15% and 57.42%, respectively, and the phytoextraction of total Cd significantly increased by 13.44%. Generally, the EDDS treatment could increase the available Cu and Cd in soil, promote the uptake of Cu and Cd, and improve the phytoremediation efficiency of castor. Among them, the addition of 5.0 mmol·kg-1 EDDS had the best effect for Cu, whereas the addition of 2.5 mmol kg-1 EDDS had a higher increase in the phytoextraction of Cd.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , Suelo , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Etilenodiaminas , Quelantes/farmacología , Biodegradación Ambiental , Succinatos/farmacología
5.
Front Oncol ; 14: 1304478, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38313798

RESUMEN

Infantile hemangioma (IH) is the most common benign vascular tumor characterized by three phases - proliferation, early involution and late involution. Mast cells (MCs) play an important role in allergic reactions and numerous diseases, including tumors. While the mechanisms underlying MCs migration, activation and function in the life cycle of IH remain unclear, previous studies suggested that MCs circulate through the vasculature and migrate into IH, and subsequently mature and get activated. Estradiol (E2) emerges as a potential attractant for MC migration into IH and their subsequent activation. In various stages of IH, activated MCs secrete both proangiogenic and anti-angiogenic modulators, absorbed by various cells adjacent to them. Imbalances in these modulators may contribute to IH proliferation and involution.

6.
Food Funct ; 15(3): 1720, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38226873

RESUMEN

Correction for 'Wheat peptides inhibit the activation of MAPK and NF-κB inflammatory pathways and maintain epithelial barrier integrity in NSAID-induced intestinal epithelial injury' by Zhiyuan Feng et al., Food Funct., 2024, https://doi.org/10.1039/D3FO03954D.

7.
J Food Sci Technol ; 61(2): 340-352, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38196720

RESUMEN

In order to utilize salmon skin for high value, and investigate the structural identification and combination mechanism of iron (II)-chelating peptides systemically, Atlantic salmon (Salmo salar L.) skin, a by-product of Atlantic salmon processing, was treated by two-step enzymatic hydrolysis to obtain salmon skin active peptides (SSAP). Then they reacted with iron (II) to obtain iron (II)-chelating salmon skin active peptides (SSAP-Fe) with a high iron (II) chelating ability of 98.84%. The results of Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) spectroscopy, 8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate (ANS) combined fluorescence measurement, isothermal titration calorimetry (ITC) and full wavelength ultraviolet (UV) scanning showed that the structural characteristics of SSAP changed before and after chelating iron (II). Reverse phase high performance liquid chromatography (RP-HPLC) and mass spectrometry were used to identify and quantify the peptides in SSAP-Fe. Four peptide sequences (STEGGG, GIIKYGDDFMH, PGQPGIGYDGPAGPPGPPGPPGAP and QNQRESWTTCRSQSSLPDG) were identified. The content of PGQPGIGYDGPAGPPGPPGPPGAP was the highest, at 25.17 µg/mg. The pharmacokinetic and pharmacodynamic properties of these four peptides were also investigated, and the results indicated that they have satisfactory predicted ADMET properties. Molecular docking technology was used to analyze the binding sites between iron (II) and SSAP, and it was found that PGQPGIGYDGPAGPPGPPGPPGAP had the lowest predicted binding energy with iron (II) and the most stable predicted binding energy with iron (II). This results showed that the stability of SSAP-Fe were closely related to the number of covalent bonds and the types of amino acids. This study revealed the structure and combination mechanism of SSAP-Fe, and indicated that SSAP-Fe prepared by chelation may be used as a Fe supplement that can be applied in functional foods or ingredients.

8.
Int J Biol Macromol ; 257(Pt 1): 127944, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37951448

RESUMEN

This paper investigates the effect of five different types of nanocellulose on the properties of protein-based bionanocomposite films (PBBFs) and the mechanism of action. The results show that TEMPO-oxidized nanocellulose (TNC) PBBFs have the smoothest surface structure. This is because some hydroxyl groups in TNC are converted to carboxyl groups, increasing hydrogen bonding and cross-linking with proteins. Bacterial nanocellulose (BNC) PBBFs have the highest crystallinity. Filamentous BNC can form an interlocking network with protein, promoting effective stress transfer in the PBBFs with maximum tensile strength. The PBBFs of lignin nanocellulose (LNC) have superior elasticity due to the presence of lignin, which gives them the greatest creep properties. The PBBFs of cellulose nanocrystals (CNCs) have the largest water contact angle. This is because the small particle size of CNC can be uniformly distributed in the protein matrix. The different types of nanocellulose differ in their microscopic morphology and the number of hydroxyl groups and hydrogen bonding sites on their surfaces. Therefore, there are differences in the spatial distribution and the degree of intermolecular cross-linking of different types of nanocellulose in the protein matrix. This is the main reason for the differences in the material properties of PBBFs.


Asunto(s)
Nanocompuestos , Nanopartículas , Lignina , Nanocompuestos/química , Agua/química , Celulosa/química , Nanopartículas/química
9.
Int Arch Allergy Immunol ; 185(2): 190-195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37952519

RESUMEN

INTRODUCTION: Chronic spontaneous urticaria (CSU) with autoreactivity is often resistant to antihistamines. Autologous whole blood injection (AWBI) has shown potential efficacy in the treatment of this disease, but it is controversial. It is necessary to screen patients who are suitable for this therapy in advance. This study aimed to identify biomarkers that predict the efficacy of AWBI treatment in CSU patients with autoreactivity. METHODS: A total of 30 patients with autologous serum skin test-positive CSU treated with AWBI were included in this study; urticaria activity score (UAS7) was recorded and the treatment response was judged based on it. Levels of total serum IgE, anti-high-affinity IgE receptor (FcεRI) IgG, and basophils CD63 and FcεRI expressions, and D-dimer of all patients were determined and analyzed. RESULTS: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed good correlations with UAS7 variations. D-dimer, basophil FcεRI and CD63 expressions changed significantly before and after AWBI treatment in AWBI responders, and the basophil FcεRI and CD63 expressions consistently and dynamically decreased in AWBI responders during the treatment. Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed certain predictive values for AWBI response. CONCLUSIONS: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions could be biomarkers of predicting AWBI efficacy in patients with CSU with autoreactivity.


Asunto(s)
Urticaria Crónica , Urticaria , Humanos , Inmunoglobulina E , Receptores de IgE/metabolismo , Urticaria/terapia , Urticaria/metabolismo , Basófilos/metabolismo , Biomarcadores/metabolismo , Enfermedad Crónica
10.
Int J Biol Macromol ; 256(Pt 1): 128383, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38000617

RESUMEN

Soluble pea protein isolate-curcumin nanoparticles were successfully prepared at a novel pH combination, with encapsulation efficiency and drug loading amount of 95.69 ± 1.63 % and 32.73 ± 0.56 µg/mg, respectively, resulting in >4000-fold increase in the water solubility of curcumin. The encapsulation propensity and interaction mechanism of pea protein isolates with curcumin and colchicine were comparatively evaluated by structural characterization, molecular dynamics simulations and molecular docking. The results showed that the nanoparticles formed by curcumin and colchicine with pea protein isolates were mainly driven by hydrogen bonding and hydrophobic interactions, and the binding process did not alter the secondary structure of pea protein. In contrast, pea protein isolate-curcumin nanoparticles exhibited smaller particle size, lower RMSD value, lower binding Gibbs free energy and greater structural stability. Therefore, pea protein isolate is a suitable encapsulation material for hydrophobic compounds. Furthermore, the pea protein isolate-curcumin nanoparticles showed remarkably enhanced antitumor activity, as evidenced by a significant reduction in IC50, and the anti-tumor mechanism of it involved the ROS-induced mitochondria-mediated caspase cascade apoptosis pathway. These findings provide insights into the development of pea protein-based delivery systems and the possibility of a broader application of curcumin in antitumor activity.


Asunto(s)
Curcumina , Nanopartículas , Proteínas de Guisantes , Curcumina/química , Simulación del Acoplamiento Molecular , Nanopartículas/química , Concentración de Iones de Hidrógeno , Colchicina , Tamaño de la Partícula , Portadores de Fármacos/química
11.
Food Funct ; 15(2): 823-837, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38131381

RESUMEN

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has negative effects on the gastrointestinal tract, but the proton pump inhibitors currently in use only protect against gastrointestinal disease and may even make NSAID-induced enteropathy worse. Therefore, new approaches to treating enteropathy are required. This study aimed to investigate the protective effect of wheat peptides (WPs) against NSAID-induced intestinal damage in mice and their mechanism. Here, an in vivo mouse model was built to investigate the protective and reparative effects of different concentrations of WPs on NSAID-induced intestinal injury. WPs ameliorated NSAID-induced weight loss and small intestinal tissue damage in mice. WP treatment inhibited NSAID-induced injury leading to increased levels of oxidative stress and expression levels of inflammatory factors. WPs protected and repaired the integrity and permeability injury of the intestinal tight junction induced by NSAIDs. An in vitro Caco-2 cell model was built with lipopolysaccharide (LPS). WP pretreatment inhibited LPS-induced changes in the Caco-2 cell permeability and elevated the levels of oxidative stress. WPs inhibited LPS-induced phosphorylation of NF-κB p65 and mitogen-activated protein kinase (MAPK) signaling pathways and reduced the expression of inflammatory factors. In addition, WPs increased tight junction protein expression, which contributed to improved intestinal epithelial dysfunction. Our results suggest that WPs can ameliorate NSAID-induced impairment of intestinal barrier functional integrity by improving intestinal oxidative stress levels and reducing inflammatory factor expression through inhibition of NF-κB p65 and MAPK signaling pathway activation. WPs can therefore be used as potential dietary supplements to reduce NSAID-induced injury of the intestine.


Asunto(s)
Enfermedades Gastrointestinales , Enfermedades Intestinales , Humanos , Ratones , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Triticum/metabolismo , Células CACO-2 , Antiinflamatorios no Esteroideos/farmacología , Lipopolisacáridos/farmacología , Enfermedades Intestinales/metabolismo , Péptidos/farmacología , Péptidos/metabolismo , Mucosa Intestinal/metabolismo
12.
Prog Neurobiol ; 231: 102534, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37783430

RESUMEN

N-Methyl-D-aspartate glutamate receptors (NMDARs) are involved in multiple physiopathological processes, including synaptic plasticity, neuronal network activities, excitotoxic events, and cognitive impairment. Abnormalities in NMDARs can initiate a cascade of pathological events, notably in Alzheimer's disease (AD) and even other neuropsychiatric disorders. The subunit composition of NMDARs is plastic, giving rise to a diverse array of receptor subtypes. While they are primarily found in neurons, NMDAR complexes, comprising both traditional and atypical subunits, are also present in non-neuronal cells, influencing the functions of various peripheral tissues. Furthermore, protein-protein interactions within NMDAR complexes has been linked with Aß accumulation, tau phosphorylation, neuroinflammation, and mitochondrial dysfunction, all of which potentially served as an obligatory relay of cognitive impairment. Nonetheless, the precise mechanistic link remains to be fully elucidated. In this review, we provided an in-depth analysis of the structure and function of NMDAR, investigated their interactions with various pathogenic proteins, discussed the current landscape of NMDAR-based therapeutics, and highlighted the remaining challenges during drug development.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/metabolismo , N-Metilaspartato/uso terapéutico , Ácido Glutámico , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
13.
Materials (Basel) ; 16(17)2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37687639

RESUMEN

To improve heat dissipation capability and enhance mechanical properties, a series of silica aerogel (SA) and modified glass fiber (GF)-filled SBR composites were prepared. It was found that the addition of SA successfully reduced the thermal conductivity of SBR by 35%, owing to the heat shield of the nanoscale porous structure of SA. Moreover, the addition of modified glass fiber (MGF) yielded a significant increase in the tensile and tear strength of SBR/SA composite rubber of 37% and 15%, respectively. This enhancement was more pronounced than the improvement observed with unmodified GF, and was attributed to the improved dispersion of fillers and crosslinking density of the SBR matrix. Rheological analysis revealed that the addition of SA and MGF weakened the ω dependence. This was due to the partial relaxation of immobilized rubber chains and limited relaxation of rubber chains adsorbed on the MGF. Furthermore, the strain amplification effect of MGF was stronger than that of GF, leading to a more pronounced reinforcing effect.

14.
Inflamm Res ; 72(9): 1877-1894, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37725104

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) shares similar immune characteristics with autoimmune diseases like systemic lupus erythematosus (SLE). However, such associations have not yet been investigated at the single-cell level. METHODS: We integrated and analyzed RNA sequencing results from different patients and normal controls from the GEO database and identified subsets of immune cells that might involve in the pathogenesis of SLE and COVID- 19. We also disentangled the characteristic alterations in cell and molecular subset proportions as well as gene expression patterns in SLE patients compared with COVID-19 patients. RESULTS: Key immune characteristic genes (such as CXCL10 and RACK1) and multiple immune-related pathways (such as the coronavirus disease-COVID-19, T-cell receptor signaling, and MIF-related signaling pathways) were identified. We also highlighted the differences in peripheral blood mononuclear cells (PBMCs) between SLE and COVID-19 patients. Moreover, we provided an opportunity to comprehensively probe underlying B-cell‒cell communication with multiple ligand-receptor pairs (MIF-CD74+CXCR4, MIF-CD74+CD44) and the differentiation trajectory of B-cell clusters that is deemed to promote cell state transitions in COVID-19 and SLE. CONCLUSIONS: Our results demonstrate the immune response differences and immune characteristic similarities, such as the cytokine storm, between COVID-19 and SLE, which might pivotally function in the pathogenesis of the two diseases and provide potential intervention targets for both diseases.

15.
ESC Heart Fail ; 10(6): 3340-3351, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37697922

RESUMEN

AIMS: Left ventricular reverse remodelling (LVRR) is an important objective of optimal medical management for dilated cardiomyopathy (DCM) patients, as it is associated with favourable long-term outcomes. Cardiac magnetic resonance (CMR) can comprehensively assess cardiac structure and function. We aimed to assess the CMR parameters at baseline and investigate independent variables to predict LVRR in DCM patients. METHODS AND RESULTS: Nighty-eight initially diagnosed DCM patients who underwent CMR and echocardiography examinations at baseline were included. CMR parameters and feature tracking (FT) based left ventricular (LV) global strain (nStrain) and nStrain indexed to LV cardiac mass index (rStrain) were measured. The predictors of LVRR were determined by multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of CMR parameters and were compared by the DeLong test. At a median follow-up time of 9 [interquartile range, 7-12] months, 35 DCM patients (36%) achieved LVRR. The patients with LVRR had lower LV volume, mass, LGE extent and stroke volume index (LVSVi) and higher left ventricular remodelling index (LVRI), nStrains, rStrains, and peak systolic strain rate (PSSR) in the longitudinal direction and rStrains in the circumferential direction at baseline (all P < 0.05). In the multivariate logistic regression analyses, LVRI [per SD, odds ratio (OR) 1.79; 95% confidence interval (CI) 1.08-2.98; P = 0.024] and the ratio of global longitudinal peak strain (rGLPS) (per SD, OR 1.88; 95% CI 1.18-3.01; P = 0.008) were independent predictors of LVRR. The combination of LVSVi, LVRI, and rGLPS had a greater area under the curve (AUC) than the combination of LVSVi and LVRI (0.75 vs. 0.68), but not significantly (P = 0.09). CONCLUSIONS: Patients with LVRR had a lower LV volume index, lower LVSV index, lower LGE extent, higher LVRI, and preserved myocardial deformation in the longitudinal direction at baseline. LVRI and rGLPS at baseline were independent determinants of LVRR.


Asunto(s)
Cardiomiopatía Dilatada , Humanos , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/complicaciones , Remodelación Ventricular , Corazón , Miocardio/patología , Volumen Sistólico
16.
Int Arch Allergy Immunol ; 184(11): 1126-1134, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37604140

RESUMEN

INTRODUCTION: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. METHODS: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. RESULTS: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. CONCLUSION: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity.


Asunto(s)
Urticaria Crónica , Urticaria , Humanos , Animales , Basófilos , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo , Urticaria Crónica/patología , Inmunoglobulina E , Alérgenos/metabolismo , Pyroglyphidae , Urticaria/metabolismo
17.
Sci Rep ; 13(1): 12299, 2023 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-37516800

RESUMEN

Pharyngeal muscle activity and responsiveness are key pathophysiological traits in human obstructive sleep apnea (OSA) and strong contributors to improvements with pharmacotherapy. The thyrotropin-releasing hormone (TRH) analog taltirelin is of high pre-clinical interest given its neuronal-stimulant properties, minimal endocrine activity, tongue muscle activation following microperfusion into the hypoglossal motor nucleus (HMN) or systemic delivery, and high TRH receptor expression at the HMN compared to rest of the brain. Here we test the hypothesis that taltirelin increases HMN activity and/or responsivity to excitatory stimuli applied across sleep-wake states in-vivo. To target hypoglossal motoneurons with simultaneous pharmacological and optical stimuli we used customized "opto-dialysis" probes and chronically implanted them in mice expressing a light sensitive cation channel exclusively on cholinergic neurons (ChAT-ChR2, n = 12) and wild-type mice lacking the opsin (n = 10). Both optical stimuli applied across a range of powers (P < 0.001) and microperfusion of taltirelin into the HMN (P < 0.020) increased tongue motor activity in sleeping ChAT-ChR2 mice. Notably, taltirelin increased tonic background tongue motor activity (P < 0.001) but not responsivity to excitatory optical stimuli across sleep-wake states (P > 0.098). This differential effect on tonic motor activity versus responsivity informs human studies of the potential beneficial effects of taltirelin on pharyngeal motor control and OSA pharmacotherapy.


Asunto(s)
Diálisis Renal , Apnea Obstructiva del Sueño , Humanos , Animales , Ratones , Neuronas Motoras , Sueño , Cafeína , Colina O-Acetiltransferasa , Niacinamida , Actividad Motora
18.
Neural Plast ; 2023: 1863686, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37274448

RESUMEN

Methods: A pilot double-blind and randomized clinical trial. Ninety-one subjects with subacute stroke were treated with cathodal/sham stimulation tDCS based on CGR (physiotherapy 40 min/d and occupational therapy 20 min/d) once daily for 20 consecutive working days. Computer-based stratified randomization (1 : 1) was employed by considering age and sex, with concealed assignments in opaque envelopes to ensure no allocation errors after disclosure at the study's end. Patients were evaluated at T0 before treatment, T1 immediately after the posttreatment assessment, and T2 assessment one month after the end of the treatment. The primary outcome index was assessed: lower limb Fugl-Meyer motor score (FMA-LE); secondary endpoints were other gait assessment and relevant stroke scale assessment. Results: Patients in the trial group performed significantly better than the control group in all primary outcome indicators assessed posttreatment T1 and at follow-up T2: FMA-LE outcome indicators between the two groups in T1 (P = 0.032; effect size 1.00, 95% CI: 0.00 to 2.00) and FMA-LE outcome indicators between the two groups in T2 (P = 0.010; effect size 2.00, 95% CI: 1.00 to 3.00). Conclusion: In the current pilot study, ctDCS plus CGR was an effective treatment modality to improve lower limb motor function with subacute stroke. The effectiveness of cathodal tDCS in poststroke lower limb motor dysfunction is inconclusive. Therefore, a large randomized controlled trial is needed to verify its effectiveness.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación Transcraneal de Corriente Directa , Humanos , Proyectos Piloto , Recuperación de la Función , Accidente Cerebrovascular/terapia , Extremidad Inferior , Resultado del Tratamiento , Extremidad Superior
19.
Food Funct ; 14(13): 6049-6061, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37313959

RESUMEN

Iron deficiency (ID) is the biggest cause of anemia. This pilot study aimed to investigate the effects of food-derived oligopeptide iron chelates on ameliorating liver injury and restoring gut microbiota homeostasis in iron-deficiency anemia (IDA) female rats. Female Sprague-Dawley rats at 21 days old were selected and randomly divided into a control group (N = 4) and an ID model group (N = 16). The ID model group was fed an iron-deficient diet containing 4 mg kg-1 iron for 28 days to generate the IDA rat model and then randomly subdivided into four groups (N = 4 for each group): ID group, ferrous sulfate group, marine fish oligopeptide iron chelate (MCOP-Fe) group, and whey protein oligopeptide iron chelate (WPP-Fe) group. Iron supplements were given to rats in the three intervention groups once per day via intragastric administration for three weeks. After iron supplementation, the hemoglobin levels in the three intervention groups were significantly improved, with the MCOP-Fe and WPP-Fe groups returning to normal. The ALT and AST levels in the ID group increased significantly, while levels in all intervention groups decreased to normal levels. Liver glutathione in the WPP-Fe group was increased, while the activity of superoxide dismutase also tended to be higher. In addition, 16S rRNA gene sequencing showed that IDA resulted in changes to intestinal microbiota. After intervention, the WPP-Fe group showed increased alpha diversity of intestinal microbes. Therefore, MCOP-Fe and WPP-Fe may improve the iron status of IDA female rats as well as ameliorate liver damage, with WPP-Fe showing a greater potential in improving gut microbiota imbalance.


Asunto(s)
Anemia Ferropénica , Microbioma Gastrointestinal , Deficiencias de Hierro , Ratas , Femenino , Animales , Hierro/metabolismo , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/metabolismo , Proyectos Piloto , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Ratas Sprague-Dawley , Oligopéptidos/metabolismo , Hígado/metabolismo , Quelantes del Hierro/metabolismo
20.
Food Sci Nutr ; 11(6): 2925-2941, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37324839

RESUMEN

Fermentation technology was used to prepare the acaí (Euterpe oleracea) fermentation liquid. The optimal fermentation parameters included a strain ratio of Lactobacillus paracasei: Leuconostoc mesenteroides: Lactobacillus plantarum = 0.5:1:1.5, a fermentation time of 6 days, and a nitrogen source supplemental level of 2.5%. In optimal conditions, the ORAC value of the fermentation liquid reached the highest value of 273.28 ± 6.55 µmol/L Trolox, which was 55.85% higher than the raw liquid. In addition, the FRAP value of the acaí, as well as its scavenging ability of DPPH, hydroxyl, and ABTS free radicals, increased after fermentation. Furthermore, after fermentation treatment, the microstructure, basic physicochemical composition, amino acid composition, γ-aminobutyric acid, a variety of volatile components, and so on have changed. Therefore, fermentation treatment can significantly improve the nutritional value and flavor of the acaí. This provides a theoretical basis for the comprehensive utilization of acaí.

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