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1.
J Nanobiotechnology ; 22(1): 275, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778401

RESUMO

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.


Assuntos
Gota , Indóis , Polímeros , Espécies Reativas de Oxigênio , Ácido Úrico , Gota/tratamento farmacológico , Gota/metabolismo , Gota/terapia , Espécies Reativas de Oxigênio/metabolismo , Animais , Camundongos , Polímeros/química , Indóis/química , Indóis/farmacologia , Nanopartículas/química , Platina/química , Platina/farmacologia , Platina/uso terapêutico , Humanos , Peróxido de Hidrogênio/metabolismo , Hipertermia Induzida/métodos , Células RAW 264.7 , Terapia Fototérmica/métodos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Masculino
2.
Vaccine ; 42(15): 3522-3528, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38704251

RESUMO

BACKGROUND: The Recombinant Omicron BA.4/5-Delta COVID-19 Vaccine (ZF2202-A) is primarily designed for the Delta and Omicron BA.4/5 variants. Our objective was to assess the safety and immunogenicity of ZF2202-A in Chinese adults. METHODS: A total of 450 participants aged ≥ 18 years, who had completed primary or booster vaccination with a COVID-19 vaccine more than 6 months prior, were enrolled in this randomized, double-blind, active-controlled trial. Participants in the study and control groups were administered one dose of ZF2202-A and ZF2001, respectively. Immunogenicity subgroups were established in each group. RESULTS: At 14 days after vaccination, the seroconversion rates of Omicron BA.4/5, BF.7, and XBB.1 in the ZF2022-A group were 67.7 %, 58.6 %, and 62.6 %, with geometric mean titers (GMTs) of neutralizing antibodies at 350.2, 491.8, and 49.5, respectively. The main adverse reactions (ARs) were vaccination site pain, pruritus, fatigue, and asthenia in both the ZF2022-A group and ZF2001 group. CONCLUSIONS: The novel bivalent vaccine ZF2202-A demonstrated satisfactory immunogenicity and safety against Omicron variants as booster dose in adults with prior vaccination of COVID-19 vaccines.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , SARS-CoV-2 , Vacinas Sintéticas , Humanos , Masculino , Adulto , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Método Duplo-Cego , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/administração & dosagem , China , Adulto Jovem , Imunização Secundária/métodos , Vacinação/métodos , Idoso , População do Leste Asiático
3.
Mol Med Rep ; 30(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38695247

RESUMO

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole­exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis­like but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG, STS, KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS: c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosis­associated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.


Assuntos
Sequenciamento do Exoma , Proteínas Filagrinas , Ictiose , Ceratodermia Palmar e Plantar , Linhagem , Esteril-Sulfatase , Humanos , Feminino , Masculino , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/patologia , Criança , Ictiose/genética , Ictiose/diagnóstico , Adulto , Testes Genéticos , Serpinas/genética , Queratina-10/genética , Adolescente , Pré-Escolar , Mutação de Sentido Incorreto , Mutação , Adulto Jovem , Predisposição Genética para Doença
4.
BMC Med Genomics ; 17(1): 116, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684994

RESUMO

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.


Assuntos
Histona-Lisina N-Metiltransferase , Síndrome de Sotos , Humanos , Histona-Lisina N-Metiltransferase/genética , Síndrome de Sotos/genética , Masculino , Feminino , Pré-Escolar , Criança , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sequenciamento do Exoma , Mutação , Cariotipagem , Histona Metiltransferases/genética , Proteínas Nucleares/genética
5.
Med ; 5(5): 401-413.e4, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38574739

RESUMO

BACKGROUND: The recently circulating Omicron variants BA.2.86 and JN.1 were identified with more than 30 amino acid changes on the spike protein compared to BA.2 or XBB.1.5. This study aimed to comprehensively assess the immune escape potential of BA.2.86, JN.1, EG.5, and EG.5.1. METHODS: We collected human and murine sera to evaluate serological neutralization activities. The participants received three doses of coronavirus disease 2019 (COVID-19) vaccines or a booster dose of the ZF2022-A vaccine (Delta-BA.5 receptor-binding domain [RBD]-heterodimer immunogen) or experienced a breakthrough infection (BTI). The ZF2202-A vaccine is under clinical trial study (ClinicalTrials.gov: NCT05850507). BALB/c mice were vaccinated with a panel of severe acute respiratory syndrome coronavirus 2 RBD-dimer proteins. The antibody evasion properties of these variants were analyzed with 41 representative human monoclonal antibodies targeting the eight RBD epitopes. FINDINGS: We found that BA.2.86 had less neutralization evasion than EG.5 and EG.5.1 in humans. The ZF2202-A booster induced significantly higher neutralizing titers than BTI. Furthermore, BA.2.86 and JN.1 exhibited stronger antibody evasion than EG.5 and EG.5.1 on RBD-4 and RBD-5 epitopes. Compared to BA.2.86, JN.1 further lost the ability to bind to several RBD-1 monoclonal antibodies and displayed further immune escape. CONCLUSIONS: Our data showed that the currently dominating sub-variant, JN.1, showed increased immune evasion compared to BA.2.86 and EG.5.1, which is highly concerning. This study provides a timely risk assessment of the interested sub-variants and the basis for updating COVID-19 vaccines. FUNDING: This work was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, the Beijing Life Science Academy, the Bill & Melinda Gates Foundation, and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (CPSF).


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Vacinas contra COVID-19 , COVID-19 , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas de Subunidades Antigênicas , Humanos , Animais , Anticorpos Monoclonais/imunologia , SARS-CoV-2/imunologia , Camundongos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , COVID-19/prevenção & controle , COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Masculino , Soros Imunes/imunologia , Adulto , Evasão da Resposta Imune , Testes de Neutralização , Epitopos/imunologia
6.
Heliyon ; 10(6): e27590, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509940

RESUMO

Based on the usual Wigner-Weyl transformation theory we find that the Wigner hyperbolic rotation in phase space will map onto fractional squeezing operator in Hilbert space. The merit of Weyl ordering and the coherent state representation of Fresnel operator is used in our derivation.

7.
Mol Genet Genomic Med ; 12(3): e2401, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444278

RESUMO

BACKGROUND: The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported. MATERIALS AND METHODS: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. RESULTS: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts. CONCLUSIONS: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.


Assuntos
Artrogripose , Túnica Conjuntiva , Contratura , Pterígio , Humanos , Masculino , Artrogripose/genética , Túnica Conjuntiva/anormalidades , Contratura/genética , Família
8.
Sci Rep ; 14(1): 2861, 2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311615

RESUMO

Accurately predicting prognosis subcutaneous leiomyosarcoma (LMS) is crucial for guiding treatment decisions in patients. The objective of this study was to develop prediction models for cancer-specific survival (CSS) in patients with subcutaneous LMS. The collected cases of diagnosed subcutaneous LMS were randomly divided into a training cohort and a validation cohort at a 6:4 ratio based on tumor location and histological code. The X-tile program was utilized to determine the optimal cutoff points for age index. Univariate and Cox multivariate regression analyses were conducted to identify independent risk factors for subcutaneous LMS patients. Nomograms were constructed to predict CSS, and their performance was assessed using C-index and calibration plots. Additionally, a decision tree model was established using recursive partitioning analysis to determine the total score for CSS prediction in subcutaneous LMS patients based on the nomogram model. A total of 1793 patients with subcutaneous LMS were found. X-tile software divides all patients into ≤ 61 years old, 61-82 years old, and ≥ 82 years old. The most important anatomical sites were the limbs (including the upper and lower limbs, 48.0%). Only 6.2% of patients received chemotherapy, while 44% had a history of radiotherapy and 92.9% underwent surgery. The independent risk factors for patients with subcutaneous LMS were age, summary stage, grade, and surgery. CSS was significantly decreased in patients with distant metastases, which showed the highest independent risk predictor (HR 4.325, 95% CI 3.010-6.214, p < 0.001). The nomogram prediction model of LMS was constructed based on four risk factors. The C-index for this model was 0.802 [95% CI 0.781-0.823] and 0.798 [95% CI 0.768-0.829]. The training cohort's 3-, 5-, and 10-year AUCs for CSS in patients with subcutaneous LMS were 0.833, 0.830, and 0.859, and the validation cohort's AUC for predicting CSS rate were 0.849, 0.830, and 0.803, respectively. Recursive segmentation analysis divided patients into 4 risk subgroups according to the total score in the nomogram, including low-risk group < 145, intermediate-low-risk group ≥ 145 < 176, intermediate-high-risk group ≥ 176 < 196, and high-risk group ≥ 196; The probability of the four risk subgroups is 9.1%, 34%, 49%, and 79% respectively. In this retrospective study, a novel nomogram or corresponding risk classification system for patients with subcutaneous LMS were developed, which may assist clinicians in identifying high-risk patients and in guiding the clinical decision.


Assuntos
Compostos de Anilina , Leiomiossarcoma , Nomogramas , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Extremidade Inferior , Programa de SEER , Prognóstico
9.
J Affect Disord ; 352: 509-516, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38412929

RESUMO

BACKGROUND: Psychological resilience is a protective factor of depression. However, the neuroimaging characteristics of the relationship between psychological resilience and brain imaging in depression are not very clear. Our objectives were to explore the brain functional imaging characteristics of different levels of resilience in female patients with depression. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 58 female depressed patients. According to the resilience score, participants were divided into three groups: Low resilience (Low-res), Medium resilience (Med-res) and High resilience (High-res). We compared the differences in the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) among the three groups and correlated psychological resilience with ALFF and FC. RESULTS: According to ALFF, there was a higher activation in RI and RPG in the High-res compared with Med-res and Low-res, but no significant differences between Med-res and Low-res. The FC between the RPG and supramarginal gyrus (SG) in the High-res was significantly stronger than that in the Med-res and the Low-res, and the FC of the Med-res is stronger than that of the Low-res. Both ALFF and FC were positively correlated with the score of resilience. LIMITATIONS: The sample size of this study was relatively small and it lacked healthy controls. The results of this study could be considered preliminary. CONCLUSIONS: Among female patients with depression, patients with higher psychological resilience had higher resting state activation in the RI and RPG and had a stronger interaction between the RPG and the SG.


Assuntos
Resiliência Psicológica , Humanos , Feminino , Córtex Somatossensorial , Imageamento por Ressonância Magnética/métodos , Encéfalo , Mapeamento Encefálico/métodos
10.
BMC Genomics ; 25(1): 175, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38350848

RESUMO

BACKGROUND: Brain diseases pose a significant threat to human health, and various network-based methods have been proposed for identifying gene biomarkers associated with these diseases. However, the brain is a complex system, and extracting topological semantics from different brain networks is necessary yet challenging to identify pathogenic genes for brain diseases. RESULTS: In this study, we present a multi-network representation learning framework called M-GBBD for the identification of gene biomarker in brain diseases. Specifically, we collected multi-omics data to construct eleven networks from different perspectives. M-GBBD extracts the spatial distributions of features from these networks and iteratively optimizes them using Kullback-Leibler divergence to fuse the networks into a common semantic space that represents the gene network for the brain. Subsequently, a graph consisting of both gene and large-scale disease proximity networks learns representations through graph convolution techniques and predicts whether a gene is associated which brain diseases while providing associated scores. Experimental results demonstrate that M-GBBD outperforms several baseline methods. Furthermore, our analysis supported by bioinformatics revealed CAMP as a significantly associated gene with Alzheimer's disease identified by M-GBBD. CONCLUSION: Collectively, M-GBBD provides valuable insights into identifying gene biomarkers for brain diseases and serves as a promising framework for brain networks representation learning.


Assuntos
Doença de Alzheimer , Semântica , Humanos , Encéfalo/diagnóstico por imagem , Doença de Alzheimer/genética , Marcadores Genéticos , Aprendizagem
11.
Clin Interv Aging ; 19: 93-107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250174

RESUMO

Objective: To investigate the correlation between specific fiber tracts and grip strength and cognitive function in patients with Alzheimer's disease (AD) by fixel-based analysis (FBA). Methods: AD patients were divided into AD with low grip strength (AD-LGS, n=29) and AD without low grip strength (AD-nLGS, n=25), along with 31 normal controls (NC). General data, neuropsychological tests, grip strength and cranial magnetic resonance imaging (MRI) scans were collected. FBA evaluated white matter (WM) fiber metrics, including fiber density (FD), fiber cross-sectional (FC), and fiber density and cross-sectional area (FDC). The mean fiber indicators of the fiber tracts of interest (TOI) were extracted in cerebral region of significant statistical differences in FBA to further compare the differences between groups and analyze the correlation between fiber properties and neuropsychological test scores. Results: Compared to AD-nLGS group, AD-LGS group showed significant reductions in FDC in several cerebral regions. In AD patients, FDC values of bilateral uncinate fasciculus and left superior longitudinal fasciculus were positively correlated with Clock Drawing Test scores, while FDC of splenium of corpus callosum, bilateral anterior cingulate tracts, forceps major, and bilateral inferior longitudinal fasciculus were positively correlated with the Executive Factor Score of Memory and Executive Screening scale scores. Conclusion: Reduced grip strength in AD patients is associated with extensive impairment of WM structural integrity. Changes in FDC of specific WM fiber tracts related to executive function play a significant mediating role in the reduction of grip strength in AD patients.


Assuntos
Doença de Alzheimer , Galactosilceramidas , Substância Branca , Humanos , Função Executiva , Doença de Alzheimer/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Força da Mão
12.
Water Sci Technol ; 89(1): 20-37, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38214984

RESUMO

Chlorophyll-a (Chl-a) is an important parameter in water bodies. Due to the complexity of optics in water bodies, it is difficult to accurately predict Chl-a concentrations in water bodies by current traditional methods. In this paper, using Sentinel-2 remote sensing images as the data source combined with measured data, taking Wuliangsu Lake as the study area, a new intelligent algorithm is proposed for prediction of Chl-a concentration, which uses the adaptive ant colony exhaustive optimization algorithm (A-ACEO) for feature selection and the gray wolf optimization algorithm (GWO) to optimize support vector regression (SVR) to achieve Chl-a concentration prediction. The ant colony optimization algorithm is improved to select remote sensing feature bands for Chl-a concentration by introducing relevant optimization strategies. The GWO-SVR model is built by optimizing SVR using GWO with the selected feature bands as input and comparing it with the traditional SVR model. The results show that the usage of feature bands selected by the presented A-ACEO algorithm as inputs can effectively reduce complexity and improve the prediction performance of the model, under the condition of the same model, which can provide valuable references for monitoring the Chl-a concentration in Wuliangsu Lake.


Assuntos
Monitoramento Ambiental , Lagos , Clorofila A/análise , Monitoramento Ambiental/métodos , Clorofila , Algoritmos , Água
13.
Magn Reson Imaging ; 106: 24-30, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37541457

RESUMO

This study aimed to determine the pattern of fractional dimension (FD) in Alzheimer's disease (AD) patients, and investigate the relationship between FD and the locus coeruleus (LC) signal intensity.A total of 27 patients with AD and 25 healthy controls (HC) were collected to estimate the pattern of fractional dimension (FD) and cortical thickness (CT) using the Computational Anatomy Toolbox (CAT12), and statistically analyze between groups on a vertex level using statistical parametric mapping 12. In addition, they were examined by neuromelanin sensitive MRI(NM-MRI) technique to calculate the locus coeruleus signal contrast ratios (LC-CRs). Additionally, correlations between the pattern of FD and LC-CRs were further examined.Compared to HC, AD patients showed widespread lower CT and FD Furthermore, significant positive correlation was found between local fractional dimension (LFD) of the left rostral middle frontal cortex and LC-CRs. Results suggest lower cortical LFD is associated with LCCRs that may reflect a reduction due to broader neurodegenerative processes. This finding may highlight the potential utility for advanced measures of cortical complexity in assessing brain health and early identification of neurodegenerative processes.


Assuntos
Doença de Alzheimer , Locus Cerúleo , Humanos , Locus Cerúleo/diagnóstico por imagem , Locus Cerúleo/anatomia & histologia , Doença de Alzheimer/diagnóstico por imagem , Encéfalo , Imageamento por Ressonância Magnética/métodos , Lobo Frontal
14.
Int Forum Allergy Rhinol ; 14(3): 711-715, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37466463

RESUMO

KEY POINTS: Hydrocortisone 21-hemisuccinate (HCHS) influenced the growth and metabolism of Staphylococcus aureus S. aureus metabolic activity was high and antibiotic susceptibility low at 1.4 mg/mL HCHS S. aureus metabolized HCHS to cortisol and reduced poly(I:C)-induced IL-6 secretion.


Assuntos
Anti-Infecciosos , Staphylococcus aureus , Humanos , Staphylococcus , Hidrocortisona , Biofilmes , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
15.
Cell Death Discov ; 9(1): 404, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907480

RESUMO

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

16.
Aging Clin Exp Res ; 35(12): 2987-2996, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37910289

RESUMO

BACKGROUND: Accurately diagnosing depressive symptoms in Alzheimer's disease (AD) patients is often challenging. Eye movement parameters have been demonstrated as biomarkers for assessing cognition and psychological conditions. AIM: To investigate the differences in eye movement between AD patients with and without depressive symptoms. METHODS: Eye movement data of 65 AD patients were compared between the depressed AD (D-AD) and non-depressed AD (nD-AD) groups. Logistic regression analysis was employed to identify diagnostic biomarkers and the ROC curve was plotted. The correlation between eye movement and HAMD-17 scores was assessed by partial correlation analysis. RESULTS: The D-AD patients showed longer saccade latency and faster average/peak saccade velocities in the overlap prosaccade test, longer average reaction time and faster average saccade velocity in the gap prosaccade test, longer start-up durations, slower pursuit velocity, more offsets, and larger total offset degrees in the smooth pursuit test, and poorer fixation stability in both the central and lateral fixation tests compared to nD-AD patients. The start-up duration in the smooth pursuit test and the number of offsets in the central fixation test were identified as the diagnostic eye movement parameters for D-AD patients with the area under the ROC curves of 0.8011. Partial correlation analysis revealed that the start-up duration and pursuit velocity in the smooth pursuit test and the total offset degrees in the lateral fixation test were correlated with HAMD-17 scores in D-AD patients. DISCUSSION AND CONCLUSIONS: Eye movement differences may help to differentiate D-AD patients from nD-AD patients in a non-invasive and cost-effective manner.


Assuntos
Doença de Alzheimer , Movimentos Oculares , Humanos , Doença de Alzheimer/diagnóstico , Depressão , Movimentos Sacádicos , Biomarcadores
17.
Arch Microbiol ; 206(1): 3, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37991548

RESUMO

Psoriasis is one of the common chronic inflammatory skin diseases worldwide. The skin microbiota plays a role in psoriasis through regulating skin homeostasis. However, the studies on the interactions between symbiotic microbial strains and psoriasis are limited. In this study, Staphylococcus strain XSB102 was isolated from the skin of human, which was identified as Staphylococcus warneri using VITEK2 Compact. To reveal the roles of Staphylococcus warneri on psoriasis, XSB102 were applied on the back of imiquimod-induced psoriasis-like dermatitis mice. The results indicated that it exacerbated the psoriasis and significantly increased the thickening of the epidermis. Furthermore, in vitro experiments confirmed that inactivated strain XSB102 could promote the proliferation of human epidermal keratinocytes (HaCaT) cell. However, real-time quantitative PCR and immunofluorescence results suggested that the expression of inflammatory factors such as IL-17a, IL-6, and so on were not significantly increased, while extracellular matrix related factors such as Col6a3 and TGIF2 were significantly increased after XSB102 administration. This study indicates that Staphylococcus warneri XSB102 can exacerbate psoriasis and promote keratinocyte proliferation independently of inflammatory factors, which paves the way for further exploration of the relationship between skin microbiota and psoriasis.


Assuntos
Dermatite , Psoríase , Camundongos , Humanos , Animais , Imiquimode/efeitos adversos , Imiquimode/metabolismo , Psoríase/induzido quimicamente , Psoríase/metabolismo , Pele , Queratinócitos/metabolismo , Staphylococcus/genética , Proliferação de Células , Dermatite/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Proteínas Repressoras/metabolismo , Proteínas de Homeodomínio/efeitos adversos , Proteínas de Homeodomínio/metabolismo
18.
J Am Chem Soc ; 145(41): 22720-22727, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37791919

RESUMO

Construction of gold-based metal-organic frameworks (Au-MOFs) would bring the merits of gold chemistry into MOFs. However, it still remains challenging because gold cations are easily reduced to metallic gold under solvothermal conditions. Herein, we present the first example of Au-MOFs prepared from the networking of cyclic trinuclear gold(I) complexes by formal transimination reaction in a rapid (<15 min) and scalable (up to 1 g) fashion under ambient condition. The Au-MOFs feature uniform porosity, high crystallinity, and superior chemical stability toward base (i.e., 20 M NaOH). With open Au(I) sites in the skeleton, the Au-MOFs as heterogeneous catalysts delivered good performance and substrate tolerance for the carboxylation reactions of alkynes with CO2. This work demonstrates a facile approach to reticularly synthesize Au-MOFs by combining the coordination and dynamic covalent chemistry.

19.
Clin Psychopharmacol Neurosci ; 21(4): 617-633, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37859436

RESUMO

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], -1.61; 95% confidence interval [95% CI], -2.44 to -0.79; p < 0.001), attention deficit hyperactivity disorders (SMD, -0.39; 95% CI, -0.78 to -0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, -0.86; 95% CI, -1.48 to -0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, -0.06; 95% CI, -0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63-0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69-0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

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