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1.
Sleep Med ; 119: 342-351, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38754344

RESUMEN

OBJECTIVE: The executive function profile in patients with narcolepsy type 1 (NT1) has been mentioned; however, limited research exists on children and adolescent patients with NT1.This study aims to assess executive function in children and adolescent patients with NT1 in China, examine potential influencing factors and evaluate the short-term treatment effect on executive function. METHODS: 53 NT1 patients (36 males, age 12.2 ± 3.4 years) and 37 healthy controls (23 males, age 12.2 ± 2.5 years) underwent self-reported measures assessing subjective sleepiness, depression, anxiety and sleep quality. A comprehensive neuropsychological test was administered to assess executive function domains, including processing speed, inhibitory control, cognitive flexibility and working memory. These assessments were repeated in NT1 patients after three-day regular drug treatment. RESULTS: NT1 patients exhibited higher levels of excessive daytime sleepiness, depression, anxiety, and poor sleep quality compared to healthy controls. Patients showed impaired processing speed, inhibitory control and cognitive flexibility (p < 0.05), whereas working memory was unaffected (p > 0.05). Regression analysis revealed that parameters from sleep monitoring, such as sleep efficiency and sleep latency, were correlated with executive function performance after controlling for age, gender, and education years. The short-term treatment led to improvements in inhibitory control, cognitive flexibility, and working memory. CONCLUSION: The findings showed that executive function was impaired among children and adolescent patients with NT1, which was associated with objective sleep parameters. Furthermore, this study emphasizes the necessity of neuropsychological assessments and early interventions among children and adolescent NT1 patients.

2.
BMC Genomics ; 25(1): 485, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755540

RESUMEN

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.


Asunto(s)
Pollos , Domesticación , Homocigoto , Animales , Pollos/genética , Selección Genética , Sitios de Carácter Cuantitativo , Genoma , Genómica/métodos , Polimorfismo de Nucleótido Simple
3.
Sci Rep ; 14(1): 10700, 2024 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730232

RESUMEN

This cross-sectional study, conducted between January 2020 and July 2023, aimed to assess the knowledge, attitude, and post-traumatic stress symptoms (PTSS) among parents with children undergoing extracorporeal membrane oxygenation (ECMO) treatment. Out of 201 valid questionnaires collected, the median knowledge score was 3.00, the mean attitude score was 27.00 ± 3.20, and the mean PTSS score was 3.50 ± 1.54. Logistic regression identified associations between PTSS and parents with lower education levels, particularly junior high school and high school/technical secondary school education, as well as those occupied as housewives. Structural equation modeling highlighted direct effects, such as the impact of residence on education, education on employment status, and associations between knowledge, attitude, PTSS, employment status, monthly income, and parental demographics. The findings indicated inadequate knowledge and suboptimal attitudes among parents, especially those with lower education levels, emphasizing the need for educational resources. Furthermore, addressing parental PTSS through psychosocial support and screening was deemed essential, providing valuable insights for tailored interventions in this context.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Conocimientos, Actitudes y Práctica en Salud , Padres , Trastornos por Estrés Postraumático , Humanos , Femenino , Masculino , Padres/psicología , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/psicología , Adulto , Estudios Transversales , Encuestas y Cuestionarios , Persona de Mediana Edad , Niño , Escolaridad
4.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1154-1163, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621962

RESUMEN

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Medicina Tradicional China , Sistema Hipotálamo-Hipofisario/patología , Sistema Hipófiso-Suprarrenal/patología , Sistema Nervioso Central , Isquemia Encefálica/terapia , Sistema Inmunológico , Inflamación
5.
J Chromatogr A ; 1724: 464893, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38643615

RESUMEN

Simultaneous monitoring of plasma concentration levels of multiple antiepileptic drugs (AEDs) is essential for dose adjustment in comprehensive epilepsy treatment, necessitating a sensitive technique for accurate extraction and determination of AEDs. Herein, a magnetic solid-phase extraction (MSPE) technique on the basis of modified biochar (BC) is investigated to extract four AEDs from plasma, in conjunction with high performance liquid chromatography. BC derived from Zizyphus jujuba seed shells was activated by phosphoric acid (PBC) and magnetized via coprecipitation to produce MPBC. The MPBCCD obtained after modification with ß-cyclodextrin (CD) was characterized and evaluated for adsorption. It exhibited fast adsorption kinetics based on second-order kinetics and satisfactory adsorption capacity for AEDs. Then it was employed as the MSPE adsorbent and the influencing parameters were optimized. The enrichment factor was 18.75. The validation analysis revealed a favorable linearity that ranged from 0.04 to 20 µg·mL-1 along with a low limit of detection of 6.85 to 10.19 ng·mL-1. The recovery of the AEDs ranged from 78.7 to 109.2 %, with relative standard deviations below 6.7 %. Using quantum chemistry theory calculations and experimental results analysis, the adsorption mechanism was investigated. It disclosed that the suggested strategy built upon MPBCCD was appropriate for the assessment of AEDs in plasma and expanded the usage of BC as the environmentally favorable matrix for the analysis of biological samples.


Asunto(s)
Anticonvulsivantes , Carbón Orgánico , Límite de Detección , Extracción en Fase Sólida , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Anticonvulsivantes/sangre , Anticonvulsivantes/aislamiento & purificación , Anticonvulsivantes/química , Carbón Orgánico/química , Extracción en Fase Sólida/métodos , Adsorción , Cromatografía Líquida de Alta Presión/métodos , Humanos , Ziziphus/química , Reproducibilidad de los Resultados
6.
J Cancer ; 15(9): 2810-2828, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577599

RESUMEN

Background: Previous studies have shown that cellular senescence is strongly associated with tumorigenesis and the tumor microenvironment. Accordingly, we developed a novel prognostic signature for intrahepatic cholangiocarcinoma (ICCA) based on senescence-associated long non-coding RNAs (SR-lncRNAs) and identified a lncRNA-miRNA-mRNA axis involving in ICCA. Methods: Based on the 197 senescence-associated genes (SRGs) from Genacards and their expression in Fu-ICCA cohort, we identified 20 lncRNAs as senescence-associated lncRNAs (SR-lncRNAs) through co-expression and cox-regression analysis. According to 20 SR-lncRNAs, patients with ICCA were classified into 2 molecular subtypes using unsupervised clustering machine learning approach and to explore the prognostic and functional heterogeneity between these two subtypes. Subsequently, we integrated 113 machine learning algorithms to develop senescence-related lncRNA signature, ultimately identifying 11 lncRNAs and constructing prognostic models and risk stratification. The correlation between the signature and the immune landscape, immunotherapy response as well as drug sensitivity are explored too. Results: We developed a novel senescence related signature. The predictive model and risk score calculated by the signature exhibited favorable prognostic predictive performance, which is a suitable independent risk factor for the prognosis of patients with ICCA based on Kaplan-Meier plotter, nomogram and receiving operating characteristic (ROC) curves. The results were validated using external datasets. Estimate, ssGSEA (single sample gene set enrichment analysis), IPS (immunophenotype score) and TIDE (tumor immune dysfunction and exclusion) algorithms revealed higher immune infiltration, higher immune scores, lower immune escape potential and better response to immunotherapy in the high-risk group. In addition, signature identifies eight chemotherapeutic agents, including cisplatin for patients with different risk levels, providing guidance for clinical treatment. Finally, we identified a set of lncRNA-miRNA-mRNA axes involved in ICCA through regulation of senescence. Conclusion: SR-lncRNAs signature can favorably predict the prognosis, risk stratification, immune landscape and immunotherapy response of patients with ICCA and consequently guide individualized treatment.

7.
Planta ; 259(6): 127, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637411

RESUMEN

MAIN CONCLUSION: Overexpression of OsNRT1.1A promotes early heading and increases the tolerance in wheat under nitrogen deficiency conditions. The application of inorganic nitrogen (N) fertilizers is a major driving force for crop yield improvement. However, the overuse of fertilizers significantly raises production costs and leads to environmental problems, making it critical to enhance crop nitrogen use efficiency (NUE) for the sake of sustainable agriculture. In this study, we created a series of transgenic wheat lines carrying the rice OsNRT1.1A gene, which encodes a nitrate transporter, to investigate its possible application in improving NUE in wheat. The transgenic wheat exhibited traits such as early maturation that were highly consistent with the overexpression of OsNRT1.1A in Arabidopsis and rice. However, we also observed that overexpression of the OsNRT1.1A gene in wheat can facilitate the growth of roots under low N conditions but has no effect on other aspects of growth and development under normal N conditions. Thus, it may lead to the improvement of wheat low N tolerance,which is different from the effects reported in other plants. A field trial analysis showed that transgenic wheat exhibited increased grain yield per plant under low N conditions. Moreover, transcriptome analysis indicated that OsNRT1.1A increased the expression levels of N uptake and utilization genes in wheat, thereby promoting plant growth under low N conditions. Taken together, our results indicated that OsNRT1.1A plays an important role in improving NUE in wheat with low N availability.


Asunto(s)
Arabidopsis , Oryza , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/genética , Oryza/metabolismo , Triticum , Nitrógeno/metabolismo , Fertilizantes , Arabidopsis/metabolismo
8.
Int J Biol Macromol ; 266(Pt 1): 130941, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38521305

RESUMEN

Recent studies revealed that insect chemosensory proteins (CSPs) both play essential roles in insect olfaction and insect resistance. However, functional evidence supporting the crosslink between CSP and insecticide resistance remains unexplored. In the present study, 22 SfruCSP transcripts were identified from the fall armyworm (FAW) and SfruCSP1 and SfruCSP2 are enriched in the larval cuticle and could be induced by multiple insecticides. Both SfruCSP1 and SfruCSP2 are highly expressed in the larval inner endocuticle and outer epicuticle, and these two proteins exhibited high binding affinities with three insecticides (chlorfenapyr, chlorpyrifos and indoxacarb). The knockdown of SfruCSP1 and SfruCSP2 increased the susceptibility of FAW larvae to the above three insecticides, and significantly increased the penetration ratios of these insecticides. Our in vitro and in vivo evidence suggests that SfruCSP1 and SfruCSP2 are insecticide binding proteins and confer FAW larval resistance to chlorfenapyr, chlorpyrifos and indoxacarb by an insecticide sequestration mechanism. The study should aid in the exploration of larval cuticle-enriched CSPs for insect resistance management.


Asunto(s)
Proteínas de Insectos , Resistencia a los Insecticidas , Insecticidas , Larva , Oxazinas , Spodoptera , Animales , Spodoptera/efectos de los fármacos , Spodoptera/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Larva/efectos de los fármacos , Cloropirifos/farmacología
9.
Curr Med Sci ; 44(2): 281-290, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38453792

RESUMEN

Recent studies have shown that cellular levels of polyamines (PAs) are significantly altered in neurodegenerative diseases. Evidence from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress, mitochondrial metabolism, cellular immunity, and ion channel functions. Dysfunction of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative diseases. Therefore, in the current work, evidence was collected to determine the possible associations between cellular levels of PAs, and related enzymes and the development of several neurodegenerative diseases, which could provide a new idea for the treatment of neurodegenerative diseases in the future.


Asunto(s)
Enfermedades Neurodegenerativas , Poliaminas , Animales , Poliaminas/metabolismo , Estrés Oxidativo , Mitocondrias/metabolismo , Apoptosis , Enfermedades Neurodegenerativas/metabolismo
10.
Materials (Basel) ; 17(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38541404

RESUMEN

Austenitic stainless steel has high toughness and plasticity; however, it tends to exhibit low yield strength, which severely limits the widespread application of this steel. It can be strengthened by cold working; however, this will cause many defects in the structure. Therefore, annealing treatment must be carried out before use. In this paper, the effects of annealing treatment at different temperatures and times on the microstructure and mechanical properties of cold-rolled 305 stainless steel sheet were studied and the theoretical mechanism was further analyzed to provide better theoretical guidance for production and application. It was found that the microstructure grains obtained by annealing at 850 °C for 30 s were finer and more uniform, and the mechanical properties were also the best, which met the requirements of strong plasticity. Therefore, the rolling and annealing experiments could be carried out again under this annealing condition, and the requirements of the finished product could be finally obtained. At this time, the thickness of the plate was about 0.15 mm, the yield strength was 1238 MPa, and the permeability was below 1.02, which met the production requirements of the metal mask plate.

11.
Sci Rep ; 14(1): 6866, 2024 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-38514755

RESUMEN

Myocardial infarction (MI) induces neuroinflammation indirectly, chronic neuroinflammation may cause neurodegenerative diseases. Changes in the proteomics of heart and brain tissue after MI may shed new light on the mechanisms involved in neuroinflammation. This study explored brain and heart protein changes after MI with a data-independent acquisition (DIA) mode proteomics approach. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in the heart of rats, and the immunofluorescence of microglia in the brain cortex was performed at 1d, 3d, 5d, and 7d after MI to detect the neuroinflammation. Then proteomics was accomplished to obtain the vital proteins in the heart and brain post-MI. The results show that the number of microglia was significantly increased in the Model-1d group, the Model-3d group, the Model-5d group, and the Model-7d group compared to the Sham group. Various proteins were obtained through DIA proteomics. Linking to key targets of brain disease, 14 proteins were obtained in the brain cortex. Among them, elongation of very long chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) were verified through western blotting (WB). The results of WB were consistent with the proteomics results. Therefore, these proteins may be related to the pathogenesis of neuroinflammation after MI.


Asunto(s)
Ventrículos Cardíacos , Infarto del Miocardio , Ratas , Animales , Ventrículos Cardíacos/patología , Enfermedades Neuroinflamatorias , Proteómica , Infarto del Miocardio/patología , Corazón
12.
Front Chem ; 12: 1359946, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38449477

RESUMEN

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions. Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous "cryo-shocked" neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen "cryo-shock" strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety. Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice. Discussion: The results of this study demonstrate the potential of autologous "cryo-shocked" neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 213-218, 2024 Feb 15.
Artículo en Chino | MEDLINE | ID: mdl-38436322

RESUMEN

The patient was a male infant, born full-term, admitted to the hospital at 28 days of age due to jaundice for 20 days and abdominal distension for 15 days. The patient developed symptoms of jaundice, hepatosplenomegaly, massive ascites, and progressively worsening liver function leading to liver failure, severe coagulation disorders, and thrombocytopenia one week after birth. Various treatments were administered, including anti-infection therapy, fluid restriction, use of diuretics, use of hepatoprotective and choleretic agents, intermittent paracentesis, blood exchange, and intravenous immunoglobulin, albumin, and plasma transfusions. However, the patient's condition did not improve, and on the 24th day of hospitalization, the family decided to discontinue treatment and provide palliative care. Sequencing of the patient's liver tissue and parental blood samples using whole-exome sequencing did not identify any pathogenic variants that could explain the liver failure. However, postmortem liver tissue pathology suggested congenital hepatic fibrosis (CHF). Given the rarity of CHF causing neonatal liver failure, further studies on the prognosis and pathogenic genes of CHF cases are needed in the future. This article provides a comprehensive description of the differential diagnosis of neonatal liver failure and introduces a multidisciplinary diagnostic and therapeutic approach to neonatal liver failure.


Asunto(s)
Enfermedades Genéticas Congénitas , Ictericia , Fallo Hepático , Lactante , Recién Nacido , Humanos , Masculino , Cirrosis Hepática , Fallo Hepático/etiología
14.
Microbiol Spectr ; 12(3): e0232723, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38329365

RESUMEN

Staphylococcus aureus (S. aureus) causes many infections with significant morbidity and mortality. S. aureus can form biofilms, which can cause biofilm-associated diseases and increase resistance to many conventional antibiotics, resulting in chronic infection. It is critical to develop novel antibiotics against staphylococcal infections, particularly those that can kill cells embedded in biofilms. This study aimed to investigate the bacteriocidal and anti-biofilm activities of thiazolidinone derivative (TD-H2-A) against S. aureus. A total of 40 non-duplicate strains were collected, and the minimum inhibitory concentrations (MICs) of TD-H2-A were determined. The effect of TD-H2-A on established S. aureus mature biofilms was examined using a confocal laser scanning microscope (CLSM). The antibacterial effects of the compound on planktonic bacteria and bacteria in mature biofilms were investigated. Other characteristics, such as cytotoxicity and hemolytic activity, were researched. A mouse skin infection model was used, and a routine hematoxylin and eosin (H&E) staining was used for histological examination. The MIC values of TD-H2-A against the different S. aureus strains were 6.3-25.0 µg/mL. The 5 × MIC TD-H2-A killed almost all planktonic S. aureus USA300. The derivative was found to have strong bacteriocidal activity against cells in mature biofilms meanwhile having low cytotoxicity and hemolytic activity against Vero cells and human erythrocytes. TD-H2-A had a good bacteriocidal effect on S. aureus SA113-infected mice. In conclusion, TD-H2-A demonstrated good bacteriocidal and anti-biofilm activities against S. aureus, paving the way for the development of novel agents to combat biofilm infections and multidrug-resistant staphylococcal infections.IMPORTANCEStaphylococcus aureus, a notorious pathogen, can form a stubborn biofilm and develop drug resistance. It is crucial to develop new anti-infective therapies against biofilm-associated infections. The manuscript describes the new antibiotic to effectively combat multidrug-resistant and biofilm-associated diseases.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Chlorocebus aethiops , Humanos , Animales , Ratones , Staphylococcus aureus , Células Vero , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Biopelículas , Pruebas de Sensibilidad Microbiana
15.
Nat Nanotechnol ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383890

RESUMEN

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M. tuberculosis simultaneously. In a mouse model of TB, intravenously injected nanoparticles image individual granulomas in situ in the lungs via signal emission in the near-infrared region IIb, with an imaging resolution much higher than that of clinical computed tomography. With 1,064 nm laser irradiation from outside the thoracic cavity, the photothermal effect generated by these nanoparticles eradicates the targeted M. tuberculosis and alleviates pathological damage and excessive inflammation in the lungs, resulting in a better therapeutic efficacy compared with a combination of first-line antibiotics. This precise photothermal modality that uses dual-targeted imaging in the near-infrared region IIb demonstrates a theranostic strategy for TB management.

16.
Cell Rep ; 43(2): 113721, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38310514

RESUMEN

Inflammation is closely associated with many neurodegenerative disorders. Yet, whether inflammation causes, exacerbates, or responds to neurodegeneration has been challenging to define because the two processes are so closely linked. Here, we disentangle inflammation from the axon damage it causes by individually blocking cytotoxic T cell function and axon degeneration. We model inflammatory damage in mouse skin, a barrier tissue that, despite frequent inflammation, must maintain proper functioning of a dense array of axon terminals. We show that sympathetic axons modulate skin inflammation through release of norepinephrine, which suppresses activation of γδ T cells via the ß2 adrenergic receptor. Strong inflammatory stimulation-modeled by application of the Toll-like receptor 7 agonist imiquimod-causes progressive γδ T cell-mediated, Sarm1-dependent loss of these immunosuppressive sympathetic axons. This removes a physiological brake on T cells, initiating a positive feedback loop of enhanced inflammation and further axon damage.


Asunto(s)
Dermatitis , Inflamación , Animales , Ratones , Retroalimentación , Axones , Terminales Presinápticos
17.
Chem Biol Interact ; 392: 110923, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38382706

RESUMEN

Aflatoxin B1 (AFB1) is the most toxic mycotoxin and a proven human carcinogen that requires metabolic activation, known by cytochrome P450 (CYP) 1A2 and 3A4. Previous evidence showed that AFB1 is activated by human recombinant CYP1A1 expressed in budding yeast. Yet, the toxicity, in particular the genotoxicity of the reactive metabolites formed from AFB1 remains unclear. Humans could be exposed to both AFB1 and benzo(a)pyrene (BaP) simultaneously, thus we were interested in their combined genotoxic effects subsequent to metabolic activation by CYP1A1. In this study, molecular docking of AFB1 to human CYP1A1 indicated that AFB1 is valid as a substrate. In the incubations with AFB1 in human CYP1A1-expressed microsomes, AFM1 as a marking metabolite of AFB1 was detected. Moreover, AFB1 induced micronucleus formation in a Chinese hamster V79-derived cell line and in a human lung epithelial BEAS-2B cell line, both expressing recombinant human CYP1A1, V79-hCYP1A1 and 2B-hCYP1A1 cells, respectively. Immunofluorescence of centromere protein B stained micronuclei was dominant in AFB1-treated BEAS-2B cells exposed to AFB1, suggesting an aneugenic effect. Moreover, AFB1 elevated the levels of ROS, 8-OHdG, AFB1-DNA adduct, and DNA breaks in 2B-hCYP1A1 cells, compared with those in the parental BEAS-2B cells. Meanwhile, AFB1 increased CYP1A1, RAD51, and γ-H2AX protein levels in 2B-hCYP1A1 cells, which were attenuated by the CYP1A1 inhibitor bergamottin. Co-exposure of AFB1 with BaP increased 8-OHdG, RAD51, and γ-H2AX levels (indicating DNA damage). In conclusion, AFB1 could be activated by human CYP1A1 for potent aneugenicity, which may be further enhanced by co-exposure to BaP.


Asunto(s)
Citocromo P-450 CYP1A1 , Sistema Enzimático del Citocromo P-450 , Animales , Humanos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Benzo(a)pireno/toxicidad , Aneugénicos , Simulación del Acoplamiento Molecular , Mamíferos/metabolismo
18.
Phytochemistry ; 220: 114032, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38369172

RESUMEN

Penicillium citrinum GZWMJZ-836 is an endophytic fungus from Drynaria roosii Nakaike. Five previously undescribed citrinin derivatives (1-5) and six intermediates related to their biosynthesis (6-11) were obtained from the extract of this strain's solid fermentation using multiple column chromatography separations, including high-performance liquid chromatography. The structures of these compounds were determined through comprehensive spectroscopic analyses, primarily using NMR and HRESIMS data. The stereochemistry was mainly confirmed by ECD calculations, and the configurations of C-7' in compounds 4 and 5 were determined using 13C NMR calculations. Compounds 4-5 and 8 showed antibacterial activity against five strains, with minimum inhibitory concentration values ranging from 7.8 to 125 µM. Compounds 4 and 7 exhibited inhibitions against three plant pathogenic fungi, with IC50 values ranging from 66.6 to 152.1 µM. Additionally, a putative biosynthetic pathway for compounds 1-5 derived from citrinin was proposed.


Asunto(s)
Citrinina , Penicillium , Citrinina/farmacología , Citrinina/química , Estructura Molecular , Penicillium/química , Hongos , Espectroscopía de Resonancia Magnética
19.
Sci Data ; 11(1): 169, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316816

RESUMEN

Compared to commercial chickens, local breeds exhibit better in meat quality and flavour, but the productivity (e.g., growth rate, body weight) of local chicken breeds is rather low. Genetic analysis based on whole-genome sequencing contributes to elucidating the genetic markers or putative candidate genes related to some economic traits, facilitating the improvement of production performance, the acceleration of breeding progress, and the conservation of genetic resources. Here, a total of 209 local chickens from 13 breeds were investigated, and the observation of approximately 91.4% high-quality sequences (Q30 > 90%) and a mapping rate over 99% for each individual indicated good results of this study, as confirmed by a genome coverage of 97.6%. Over 19 million single nucleotide polymorphisms (SNPs) and 1.98 million insertion-deletions (InDels) were identified using the reference genome (GRCg7b), further contributing to the public database. This dataset provides valuable resources for studying genetic diversity and adaptation and for the cultivation of new chicken breeds/lines.


Asunto(s)
Pollos , Genoma , Animales , Pollos/genética , China , Marcadores Genéticos , Variación Genética , Fenotipo , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma
20.
Reprod Sci ; 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38379071

RESUMEN

Male fertility and metabolic disorders, including obesity and diabetes, are closely connected. Since hyperuricemia and metabolic syndrome are strongly related, male fertility and hyperuricemia may, to some degree, be associated. According to recent studies, hyperuricemia imposes various effects on sex hormones, semen quality, and male erectile dysfunction. Some researchers claim that uric acid worsens male semen and raises the risk of erectile dysfunction (ED), while others state that it safeguards both penile erection and male semen. Additionally, it has been shown that gout and metabolic syndrome also raise the risk of ED. To clarify this controversy, the influence and potential mechanisms of hyperuricemia on ED, semen quality, sex hormone levels, and the effects of hyperuricemia-related disorders on ED will be comprehensively summarized.

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