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1.
Immunity ; 53(5): 1108-1122.e5, 2020 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-33128875

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis. However, little is known about the pathogenesis and biomarkers of COVID-19. Here, we profiled host responses to COVID-19 by performing plasma proteomics of a cohort of COVID-19 patients, including non-survivors and survivors recovered from mild or severe symptoms, and uncovered numerous COVID-19-associated alterations of plasma proteins. We developed a machine-learning-based pipeline to identify 11 proteins as biomarkers and a set of biomarker combinations, which were validated by an independent cohort and accurately distinguished and predicted COVID-19 outcomes. Some of the biomarkers were further validated by enzyme-linked immunosorbent assay (ELISA) using a larger cohort. These markedly altered proteins, including the biomarkers, mediate pathophysiological pathways, such as immune or inflammatory responses, platelet degranulation and coagulation, and metabolism, that likely contribute to the pathogenesis. Our findings provide valuable knowledge about COVID-19 biomarkers and shed light on the pathogenesis and potential therapeutic targets of COVID-19.


Asunto(s)
Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/patología , Plasma/metabolismo , Neumonía Viral/sangre , Neumonía Viral/patología , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , Biomarcadores/sangre , Proteínas Sanguíneas/metabolismo , COVID-19 , Infecciones por Coronavirus/clasificación , Infecciones por Coronavirus/metabolismo , Femenino , Humanos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Pandemias/clasificación , Neumonía Viral/clasificación , Neumonía Viral/metabolismo , Proteómica , Reproducibilidad de los Resultados , SARS-CoV-2
2.
Proc Natl Acad Sci U S A ; 121(22): e2310677121, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38753503

RESUMEN

Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry-based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC50 cellular antiviral activity against several influenza A group 1 strains. X-ray structures of six of these compounds with HA indicate that the appended moieties occupy additional pockets on the HA surface and increase the binding interaction, where the accumulation of several polar interactions also contributes to the improved affinity. The compounds here represent the most potent HA small-molecule inhibitors to date. Our divergent HTMC platform is therefore a powerful, rapid, and cost-effective approach to develop bioactive chemical probes and drug-like candidates against viral targets.


Asunto(s)
Antivirales , Glicoproteínas Hemaglutininas del Virus de la Influenza , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Humanos , Antivirales/farmacología , Antivirales/química , Química Farmacéutica/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Cristalografía por Rayos X/métodos , Química Clic/métodos , Animales , Virus de la Influenza A/efectos de los fármacos , Células de Riñón Canino Madin Darby , Inhibidores de Proteínas Virales de Fusión/farmacología , Inhibidores de Proteínas Virales de Fusión/química , Perros
3.
Plant Physiol ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917205

RESUMEN

Plant virus-derived vectors are rapid and cost-effective for protein expression and gene functional studies in plants, particularly for species that are difficult to genetically transform. However, few efficient viral vectors are available for functional studies in Asteraceae plants. Here, we identified a potyvirus named zinnia mild mottle virus (ZiMMV) from common zinnia (Zinnia elegans Jacq.) through next-generation sequencing. Using a yeast homologous recombination strategy, we established a full-length infectious cDNA clone of ZiMMV under the control of the cauliflower mosaic virus 35S promoter. Furthermore, we developed an efficient expression vector based on ZiMMV for the persistent and abundant expression of foreign proteins in the leaf, stem, root, and flower tissues with mild symptoms during viral infection in common zinnia. We showed that the ZiMMV-based vector can express ZeMYB9, which encodes a transcript factor inducing dark red speckles in leaves and flowers. Additionally, the expression of a gibberellic acid (GA) biosynthesis gene from the ZiMMV vector substantially accelerated plant height growth, offering a rapid and cost-effective method. In summary, our work provides a powerful tool for gene expression, functional studies, and genetic improvement of horticultural traits in Asteraceae plant hosts.

4.
Proc Natl Acad Sci U S A ; 119(34): e2117089119, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35943976

RESUMEN

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Convalecencia , Citocinas , Dipéptidos , Inhibidores de la Dipeptidil-Peptidasa IV , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , COVID-19/sangre , COVID-19/inmunología , Citocinas/sangre , Dipéptidos/sangre , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Aprendizaje Automático , Metaboloma , Ratones , SARS-CoV-2 , Vacunación
5.
Proc Natl Acad Sci U S A ; 119(46): e2210562119, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36343224

RESUMEN

The development of chimeric antigen receptor (CAR) T cell therapy has become a critical milestone in modern oncotherapy. Despite the remarkable in vitro effectiveness, the problem of safety and efficacy of CAR T cell therapy against solid tumors is challenged by the lack of tumor-specific antigens required to avoid on-target off-tumor effects. Spatially separating the cytotoxic function of CAR T cells from tumor antigen recognition provided by protein mediators allows for the precise control of CAR T cell cytotoxicity. Here, the high affinity and capability of the bacterial toxin-antitoxin barnase-barstar system were adopted to guide CAR T cells to solid tumors. The complementary modules based on (1) ankyrin repeat (DARPin)-barnase proteins and (2) barstar-based CAR (BsCAR) were designed to provide switchable targeting to tumor cells. The alteration of the DARPin-barnase switches enabled the targeting of different tumor antigens with a single BsCAR. A gradual increase in cytokine release and tunable BsCAR T cell cytotoxicity was achieved by varying DARPin-barnase loads. Switchable BsCAR T cell therapy was able to eradicate the HER2+ ductal carcinoma in vivo. Guiding BsCAR T cells by DARPin-barnase switches provides a universal approach for a controlled multitargeted adoptive immunotherapy.


Asunto(s)
Neoplasias , Linfocitos T , Humanos , Receptores de Antígenos de Linfocitos T , Inmunoterapia Adoptiva , Neoplasias/metabolismo , Antígenos de Neoplasias
6.
Nano Lett ; 24(1): 511-518, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38147442

RESUMEN

Inversion symmetry breaking has played an important role in recent discoveries of nonreciprocal charge transport. Niobium diselenide, for example, lacks an inversion center in the monolayer form and can host prominent nonreciprocal transport property. Here, however, we observe a nonreciprocal transport signal in the second-harmonic channel of bulk-like NbSe2, in which inversion symmetry of the lattice seems preserved. The second-harmonic signal occurs along different in-plane current orientations and appears not only in the vortex-liquid regime but also even in the superconducting fluctuation regime without an applied magnetic field. By adding a direct current (DC) bias, we quantify the symmetry breaking effect in the vortex-liquid regime. The DC bias also suggests that the rectification effect at the contacts may account for the seemingly nonreciprocal transport at zero magnetic field. Our results demonstrate that DC biasing is a useful knob for addressing nonreciprocal charge transport in a wide range of materials.

7.
Nano Lett ; 24(7): 2181-2187, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38340079

RESUMEN

Recently discovered as an intrinsic antiferromagnetic topological insulator, MnBi2Te4 has attracted tremendous research interest, as it provides an ideal platform to explore the interplay between topological and magnetic orders. MnBi2Te4 displays distinct exotic topological phases that are inextricably linked to the different magnetic structures of the material. In this study, we conducted electrical transport measurements and systematically investigated the anomalous Hall response of epitaxial MnBi2Te4 films when subjected to an external magnetic field sweep, revealing the different magnetic structures stemming from the interplay of applied fields and the material's intrinsic antiferromagnetic (AFM) ordering. Our results demonstrate that the nonsquare anomalous Hall loop is a consequence of the distinct reversal processes within individual septuple layers. These findings shed light on the intricate magnetic structures in MnBi2Te4 and related materials, offering insights into understanding their transport properties and facilitating the implementation of AFM topological electronics.

8.
Small ; : e2310469, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38282141

RESUMEN

Water splitting (or, water electrolysis) is considered as a promising approach to produce green hydrogen and relieve the ever-increasing energy consumption as well as the accompanied environmental impact. Development of high-efficiency, low-cost practical water-splitting systems demands elegant design and fabrication of catalyst-loaded electrodes with both high activity and long-life time. To this end, dimensional engineering strategies, which effectively tune the microstructure and activity of electrodes as well as the electrochemical kinetics, play an important role and have been extensively reported over the past years. Here, a type of most investigated electrode configurations is reviewed, combining particulate catalysts with 3D porous substrates (aerogels, metal foams, hydrogels, etc.), which offer special advantages in the field of water splitting. It is analyzed the design principles, structural and interfacial characteristics, and performance of particle-3D substrate electrode systems including overpotential, cycle life, and the underlying mechanism toward improved catalytic properties. In particular, it is also categorized the catalysts as different dimensional particles, and show the importance of building hybrid composite electrodes by dimensional control and engineering. Finally, present challenges and possible research directions toward low-cost high-efficiency water splitting and hydrogen production is discussed.

9.
J Synchrotron Radiat ; 31(Pt 3): 635-645, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38656774

RESUMEN

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

10.
Ann Neurol ; 93(6): 1069-1081, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36843248

RESUMEN

OBJECTIVE: To investigate aquaporin-4 antibody (AQP4-IgG) dynamics and relapse risk in patients with seropositive neuromyelitis optica spectrum disorder treated with immunosuppressants. METHODS: This observational cohort study with prospectively collected data included 400 neuromyelitis optica spectrum disorder patients seropositive for AQP4-IgG and treated with immunosuppressants. Serum AQP4-IgG was detected by fixed cell-based assay every 6 months. RESULTS: After treatment with immunosuppressants, 128 patients became AQP4-IgG seronegative. The median time to become seronegative for 400 patients was 76.4 months (61.4 months, NA). Among those patients with negative change of AQP4-IgG, the mean annualized relapse rate significantly decreased after patients became seronegative (0.20 vs 0.77, p < 0.001), and a positive correlation was observed between time to become seronegative and relapse (OR 1.018, 95% CI 1.001-1.035, p < 0.05). Independent risk factors for AQP4-IgG becoming seronegative were older age at onset, initiation of immunosuppressants at onset, and shorter disease duration before maintenance therapy. Independent risk factors for relapse included younger age (≤46.4 years) at onset, poly-system involvement in the first attack, and unchanged or increased AQP4-IgG titer. The relapse risk was not associated with sex, combination with connective tissue disease, seropositivity for systemic autoimmune antibodies, or incomplete recovery from the first attack. INTERPRETATION: Patients with younger age at onset, poly-system involvement in the first attack, and unchanged or increased titer of AQP4-IgG are most likely to experience relapse under treatment with immunosuppressants. Time to AQP4-IgG becoming seronegative and change of AQP4-IgG titer may become the surrogate efficacy biomarkers in clinical trials. ANN NEUROL 2023;93:1069-1081.


Asunto(s)
Neuromielitis Óptica , Humanos , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Acuaporina 4 , Autoanticuerpos , Enfermedad Crónica , Biomarcadores , Recurrencia , Inmunoglobulina G
11.
Langmuir ; 40(23): 12216-12225, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38805563

RESUMEN

This article reports the synthesis of a novel sulfonated fluorocarbon surfactant (SFDC) containing double C6 perfluorinated branched short chains and compares its surface properties with a similar structured compound (SFDC-L) in solutions. The critical micelle concentration (CMC) and the corresponding surface tension (γCMC) of SFDC aqueous solution are 9.77 × 10-3 mmol/L and 22.15 mN/m, respectively, indicating that SFDC has excellent surface properties. Besides, the addition of n-hexyltrimethylammonium bromide (HTAB) could further enhance the surface properties of SFDC. Meanwhile, the micellization, aggregation behavior, wettability, and adsorption at the air-water interface of SFDC and SFDC/HTAB mixture aqueous solutions are systematically investigated. Both SFDC and SFDC/HTAB show excellent wettability at low concentrations. The aggregation of SFDC and SFDC/HTAB mixtures in aqueous solution could be clearly seen as vesicles and rod-like micelles on TEM micrographs.

12.
Anticancer Drugs ; 35(6): 569-575, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38527281

RESUMEN

For critically ill patients with non-small cell lung cancer (NSCLC) in need of life-saving treatment, there is currently no reported evidence regarding the use of medication specifically targeting epidermal growth factor receptor ( EGFR ) p.C797S mutation, which is known to cause resistance to third-generation tyrosine kinase inhibitors (TKIs). Our report aims to investigate and explore treatment strategies to overcome resistance associated with EGFR p.C797S mutation in order to provide potential therapeutic options for these patients. Here, we reported two cases with NSCLC who initially harbored an EGFR -sensitive mutation and were both treated with osimertinib, a third-generation TKI. Next-generation sequencing tests conducted prior to the initiation of fifth-line therapy in critically ill patients revealed the presence of EGFR p.C797S mutations in both patients, suggesting acquired resistance. In the course of fifth-line therapy, the administration of a combination of brigatinib and cetuximab proved vital in saving critically ill patients, moderately extending their overall survival period. Our findings suggested that a combined regimen of brigatinib and cetuximab could serve as a potentially life-saving therapeutic strategy for critically ill patients with NSCLC, particularly those demonstrating EGFR p.C797S-mediated resistance. Further studies, however, are required to validate and expand upon these promising findings.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Cetuximab , Receptores ErbB , Neoplasias Pulmonares , Mutación , Compuestos Organofosforados , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Cetuximab/administración & dosificación , Cetuximab/uso terapéutico , Masculino , Compuestos Organofosforados/uso terapéutico , Compuestos Organofosforados/administración & dosificación , Persona de Mediana Edad , Femenino , Enfermedad Crítica , Anciano , Resistencia a Antineoplásicos , Acrilamidas/uso terapéutico , Compuestos de Anilina , Indoles
13.
J Bone Miner Metab ; 42(2): 242-252, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38498197

RESUMEN

INTRODUCTION: This study was to investigate the correlations between pyrethroid exposure and bone mineral density (BMD) and osteopenia. MATERIALS AND METHODS: This cross-sectional study included 1389 participants over 50 years of age drawn from the 2007-2010 and 2013-2014 National Health and Nutrition Examination Survey (NHANES). Three pyrethroid metabolites, 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid (trans-DCCA), and 4-fluoro-3-phenoxybenzoic acid (4-F-3PBA) were used as indicators of pyrethroid exposure. Low BMD was defined as T-score < - 1.0, including osteopenia. Weighted multivariable linear regression analysis or logistic regression analysis was utilized to evaluate the correlation between pyrethroid exposure and BMD and low BMD. Bayesian kernel machine regression (BKMR) model was utilized to analyze the correlation between pyrethroids mixed exposure and low BMD. RESULTS: There were 648 (48.41%) patients with low BMD. In individual pyrethroid metabolite analysis, both tertile 2 and tertile 3 of trans-DCCA were negatively related to total femur, femur neck, and total spine BMD [coefficient (ß) = - 0.041 to - 0.028; all P < 0.05]. Both tertile 2 and tertile 3 of 4-F-3PBA were negatively related to total femur BMD (P < 0.05). Only tertile 2 [odds ratio (OR) = 1.63; 95% CI = 1.07, 2.48] and tertile 3 (OR = 1.65; 95% CI = 1.10, 2.50) of trans-DCCA was correlated with an increased risk of low BMD. The BKMR analysis indicated that there was a positive tendency between mixed pyrethroids exposure and low BMD. CONCLUSION: In conclusion, pyrethroids exposure was negatively correlated with BMD levels, and the associations of pyrethroids with BMD and low BMD varied by specific pyrethroids, pyrethroid concentrations, and bone sites.


Asunto(s)
Benzoatos , Enfermedades Óseas Metabólicas , Insecticidas , Éteres Fenílicos , Piretrinas , Adulto , Humanos , Persona de Mediana Edad , Piretrinas/efectos adversos , Piretrinas/análisis , Piretrinas/metabolismo , Insecticidas/efectos adversos , Insecticidas/análisis , Insecticidas/metabolismo , Encuestas Nutricionales , Estudios Transversales , Densidad Ósea , Teorema de Bayes , Exposición a Riesgos Ambientales/efectos adversos , Enfermedades Óseas Metabólicas/inducido químicamente , Enfermedades Óseas Metabólicas/epidemiología
14.
Drug Resist Updat ; 71: 101003, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37866104

RESUMEN

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Transportador de Glucosa de Tipo 1 , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Inhibidores mTOR , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico
15.
Biochem Genet ; 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310198

RESUMEN

The pivotal role of lysosomal function in preserving neuronal homeostasis is recognized, with its dysfunction being implicated in neurodegenerative processes, notably in Parkinson's disease (PD). Yet, the molecular underpinnings of lysosome-related genes (LRGs) in the context of PD remain partially elucidated. We collected RNA-seq data from the brain substantia nigra of 30 PD patients and 20 normal subjects from the GEO database. We obtained molecular classification clusters from the screened lysosomal expression patterns. The lysosome-related diagnostic model of Parkinson's disease was constructed by XGBoost and Random Forest. And we validated the expression patterns of signature LRGs in the diagnostic model by constructing a PD rat model. Finally, the linkage between PD and cancer through signature genes was explored. The expression patterns of the 33 LRGs screened can be divided into two groups of PD samples, enabling exploration of the variance in biological processes and immune elements. Cluster A had a higher disease severity. Subsequently, critical genes were sieved through the application of machine learning methodologies culminating in the identification of two intersecting feature genes (ACP2 and LRP2). A PD risk prediction model was constructed grounded on these signature genes. The model's validity was assessed through nomogram evaluation, which demonstrated robust confidence validity. Then we analyzed the correlation analysis, immune in-filtration, biological function, and rat expression validation of the two genes with common pathogenic genes in Parkinson's disease, indicating that these two genes play an important role in the pathogenesis of PD. We then selected ACP2, which had a significant immune infiltration correlation, as the entry gene for the pan-cancer analysis. The pan-cancer analysis revealed that ACP2 has profound associations with prognostic indicators, immune infiltration, and tumor-related regulatory processes across various neoplasms, suggesting its potential as a therapeutic target in a range of human diseases, including PD and cancers. Our study comprehensively analyzed the molecular grouping of LRGs expression patterns in Parkinson's disease, and the disease progression was more severe in cluster A. And the PD diagnosis model related to LRGs is constructed. Finally, ACP2 is a potential target for the relationship between Parkinson's disease and tumor.

16.
Phytother Res ; 38(7): 3782-3800, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38839050

RESUMEN

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.


Asunto(s)
Enfermedades Intestinales , Polifenoles , Humanos , Polifenoles/farmacología , Niño , Enfermedades Intestinales/tratamiento farmacológico , Enfermedades Intestinales/dietoterapia , Enfermedades Intestinales/prevención & control , Antioxidantes/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Antiinflamatorios/farmacología , Dieta
17.
Nano Lett ; 23(23): 11272-11279, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38038230

RESUMEN

Thermogalvanic hydrogels have been quickly developed and are widely used in thermal energy harvesting. However, the freezing behaviors of thermogalvanic hydrogels at subzero temperatures greatly limit their practical applications. Herein, we design an antifreezing thermogalvanic hydrogel based on [Fe(CN)6]3-/4- ions for thermoelectric power generation in ultralow temperature environments. The antifreezing thermogalvanic hydrogels show excellent flexibility at -80 °C owing to the hydrogen bonding between ethylene glycol and water molecules. Even after 500 cyclic tensile strains, the thermogalvanic hydrogels can still maintain excellent mechanical stability, and the Seebeck coefficient is as high as 1.43 mV/K, corresponding to a large retention rate of ∼95%. Moreover, we demonstrate a wearable thermoelectric shoe based on antifreezing thermogalvanic hydrogels for harvesting human thermal energy in a simulated winter environment of -30 °C, and the electricity can drive a green LED. This work provides important guidance for the design and optimization of antifreezing thermogalvanic hydrogels.

18.
Rev Esp Enferm Dig ; 116(3): 177-178, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37350663

RESUMEN

A 65-year-old woman was admitted to our hospital with complaints of lower abdominal pain. Her physical examination was unremarkable. The results of routine laboratory testing were within the normal limits. In addition, abdominal CT was normal. Colonoscopy showed a cecum submucosal tumor with a pale yellow surface. Endoscopic ultrasound revealed homogeneous hypoechoic lesions originated from submucosal layer. ESD was subsequently performed to remove the submucosal lesion. During the ESD procedure, fecal outflowed from appendix opening . Yellow fecal-like material was visible after submucosal incision. The trap electrocut surface uplift showed more fecal attachment on the lamina propria surface, and myolayer integrity after clean the fecal (Fig1c), The final pathology of the surface bulge suggested hyperplasia (Fig1d). Patients were discharged with relieved lower abdominal pain. The final diagnosis was submucosal fecalith mimicking a submucosal tumor, eventually leads to chronic appendicitis. Common causes of cecal submucosal tumor include neuroendocrine tumors, lipomas, etc. There was few report about fecalith mimicking a submucosal tumor. ERTA is currently an effective endoscopic method for treating appendicitis combined with fecalith blockage. To our knowledge, this is the first report on a case of cecum submucosal fecalith mimicking a submucosal tumor and was successfully removed using endoscopy.


Asunto(s)
Apendicitis , Neoplasias del Ciego , Impactación Fecal , Humanos , Femenino , Anciano , Colonoscopía/métodos , Neoplasias del Ciego/diagnóstico por imagen , Neoplasias del Ciego/cirugía , Colon/patología , Dolor Abdominal/etiología
19.
Rev Esp Enferm Dig ; 116(1): 55-56, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37073689

RESUMEN

Brunner's gland adenoma (BGA), also known as Brunneroma or polypoid hamartoma, is a rare benign duodenal tumor that proliferates from Brunner's glands of the duodenum. They are usually asymptomatic and discovered by chance during endoscopy. Some giant lesions can sometimes present with chronic abdominal pain, nausea, vomiting, and anemia, including gastrointestinal bleeding and obstructive symptoms, and need to be resected by surgery or endoscopy. Here we report a giant BGA that was easily and safely removed by Endoloop pre-ligation assisted resection.


Asunto(s)
Adenoma , Glándulas Duodenales , Neoplasias Duodenales , Humanos , Neoplasias Duodenales/diagnóstico por imagen , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/patología , Glándulas Duodenales/diagnóstico por imagen , Glándulas Duodenales/cirugía , Glándulas Duodenales/patología , Duodeno/patología , Endoscopía , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Adenoma/patología
20.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2699-2709, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812170

RESUMEN

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 µg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.


Asunto(s)
Dispepsia , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Dispepsia/tratamiento farmacológico , Dispepsia/fisiopatología , Dispepsia/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Flavonoides/química , Flavonoides/farmacología , Motilina , Péptido Intestinal Vasoactivo/metabolismo , Ghrelina , Somatostatina
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