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1.
J Cancer Res Clin Oncol ; 150(5): 232, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703186

RESUMO

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.


Assuntos
Quimiorradioterapia , Metástase Linfática , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas Recombinantes , Humanos , Masculino , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Feminino , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Adulto , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Endostatinas/administração & dosagem , Idoso , Adulto Jovem
2.
AME Case Rep ; 8: 37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711886

RESUMO

Background: Breast cancer accounts for 5% of the population who develop central nervous system metastasis, which is only second to the lung cancer. Breast cancer metastasis to the brain including parenchymal brain metastasis (BM) and leptomeningeal metastasis (LM). Compared with BM, LM is a more rare but aggressive metastatic diagnosis with poor outcome. Case Description: We reported a 38-year-old woman presented to the neurology department due to progressive headache for 1 month, accompanied with dizziness, nausea, vomiting and neck pain. During hospitalization, she experienced paroxysmal loss of consciousness twice. Five months prior to this visit, her first visit was diagnosed with breast cancer on the right side which was of triple-negative subtype and with homolateral axillary lymph node involvement by biopsy. After the clinician assessment she had received six cycles of TCb (docetaxel/carboplatin) neo-adjuvant chemotherapy. During the period of neo-adjuvant chemotherapy, she did not report the presence of severe neurological symptoms. Twenty days ago, she underwent right breast-conserving surgery and the postoperative evaluation was ypT1N3M0 stage and Miller-Payne grade 2. Head computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging (MRI) didn't find typical brain imaging changes. No other signs of metastasis were seen in the CT examinations of the patient's chest and abdomen. Finally, lumbar puncture with cerebrospinal fluid (CSF) analysis showed the presence of malignant cells. Given the patient's clinical history and new neurologic symptoms, the diagnosis was LM from breast cancer. Various treatment modalities including intrathecal thiotepa, oral temozolomide (TMZ) and whole-brain radiation therapy (WBRT) had been used, but none of them showed significant benefit for survival. Conclusions: Breast cancer metastasis to the brain, especially LM, should be given sufficient vigilance and attention at the beginning of the diagnosis and treatment, particularly in triple-negative breast cancer patients who are at high risk. Symptoms of LM may be masked by the chemotherapy adverse effects. The results of MRI and CT may show negative results, thus lumbar puncture with CSF should be done promptly if LM is highly suspected in clinical practice. Early prevention, early detection and timely treatment are crucial according to the poor prognosis.

3.
Mikrochim Acta ; 191(6): 310, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38714566

RESUMO

A ratiometric fluorescence sensor has been established based on dual-excitation carbon dots (D-CDs) for the detection of flavonoids (morin is chosen as the typical detecting model for flavonoids). D-CDs were prepared using microwave radiation with o-phenylenediamine and melamine and exhibit controllable dual-excitation behavior through the regulation of their concentration. Remarkably, the short-wavelength excitation of D-CDs can be quenched by morin owing to the inner filter effect, while the long-wavelength excitation remains insensitive, serving as the reference signal. This contributes to the successful design of an excitation-based ratiometric sensor. Based on the distinct and differentiated variation of excitation intensity, morin can be determined from 0.156 to 110 µM with a low detection limit of 0.156 µM. In addition, an intelligent and visually lateral flow sensing device is developed for the determination  of morin content in real samples with satisfying recoveries, which indicates the potential application for human health monitoring.


Assuntos
Carbono , Flavonoides , Limite de Detecção , Nitrogênio , Impressão Tridimensional , Pontos Quânticos , Espectrometria de Fluorescência , Flavonoides/análise , Flavonoides/química , Carbono/química , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Nitrogênio/química , Corantes Fluorescentes/química , Humanos , Flavonas
4.
Infect Dis Model ; 9(3): 816-827, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38725432

RESUMO

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

5.
Food Res Int ; 186: 114305, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729687

RESUMO

Kefir is a traditional dairy beverage, usually made from cow or goat milk fermented with kefir grains, and has many health benefits. To elucidate the fermentation patterns of animal milk kefirs during the fermentation process and find the optimal milk types, cow, camel, goat, and donkey milk were fermented with kefir grains for 0, 1, 3, 5, and 7 days. Volatile and non-volatile metabolites and microbial changes were dynamically monitored. The results showed that volatile flavor substances were massively elevated in four kefirs on days 1-3. Lipids and carbohydrates gradually decreased, while amino acids, small peptides, and tryptophan derivatives accumulated during fermentation in four kefirs. Besides, four kefirs had similar alterations in Lactobacillus and Acetobacter, while some distinctions existed in low-abundance bacteria. Association analysis of microorganisms and volatile and non-volatile metabolites also revealed the underlying fermentation mechanism. This study found that appropriately extending the fermentation time contributed to the accumulation of some functional nutrients. Furthermore, goat and donkey milk could be the better matrices for kefir fermentation.


Assuntos
Equidae , Fermentação , Cabras , Kefir , Leite , Animais , Kefir/microbiologia , Bovinos , Leite/microbiologia , Leite/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Paladar , Camelus , Microbiologia de Alimentos , Lactobacillus/metabolismo , Microbiota , Acetobacter/metabolismo , Aminoácidos/metabolismo , Aminoácidos/análise
6.
Sci Bull (Beijing) ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38729803

RESUMO

The mitigation of environmental and energy crises could be advanced by reclaiming platinum group precious metals (PGMs) from decommissioned air purification catalysts. However, the complexity of catalyst composition and the high chemical inertness of PGMs significantly impede this process. Consequently, recovering PGMs from used industrial catalysts is crucial and challenging. This study delves into an environmentally friendly approach to selectively recover PGMs from commercial air purifiers using photocatalytic redox technology. Our investigation focuses on devising a comprehensive strategy for treating three-way catalysts employed in automotive exhaust treatment. By meticulously pretreating and modifying reaction conditions, we achieved noteworthy results, completely dissolving and separating rhodium (Rh), palladium (Pd), and platinum (Pt) within a 12-h time frame. Importantly, the solubility selectivity persists despite the remarkably similar physicochemical properties of Rh, Pd, and Pt. To bolster the environmental sustainability of our method, we harness sunlight as the energy source to activate the photocatalysts, facilitating the complete dissolution of precious metals under natural light irradiation. This eco-friendly recovery approach demonstrated on commercial air purifiers, exhibits promise for broader application to a diverse range of deactivated air purification catalysts, potentially enabling implementation on a large scale.

7.
Front Cell Infect Microbiol ; 14: 1350181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803569

RESUMO

Objectives: This study aimed to explore the effects of removable aligners and fixed appliances on the supragingival bacterial communities in adult female patients undergoing orthodontic treatment. Methods: Supragingival plaque samples from 48 female individuals underwent microbiome analysis (16S rRNA gene sequencing) using PacBio Sequel sequencing. The study included 13 adults without orthodontic treatment needs as the control group (Group C), and 35 patients with comparable initial orthodontic conditions who received treatment at a university clinic in Beijing, China. The treatment involved either traditional fixed brackets (Group B, n = 17) or Invisalign® aligners (Group AT, n = 18). Bioinformatics methods were used for data analysis. Results: From the 48 plaque samples, a total of 334,961 valid reads were obtained, averaging 6,978 sequences per sample. The 16S rDNA sequences were classified into 25,727 amplicon sequence variants (ASVs). Significant variances in alpha and beta diversity among the groups were noted. Group B microbiome exhibited an increased presence of Gram-negative bacteria. At the phylum level, Actinobacteriota was significantly more prevalent in Group C samples, while Bacteroidota was enriched in Group B samples. Family-level relative abundance analysis showed a notable increase in Saccharibacteria (formerly TM7) and Prevotellaceae in Group B. Genus-level analysis revealed a significant rise in Lautropia in Group AT. Fixed orthodontic appliances were linked to oral microbiome changes, notably an enhanced relative abundance of anaerobes, including periodontal pathogens. Conclusion: The observation points to the impact of orthodontic appliance on the oral microbial community, highlighting the difference between traditional braces (Group B) and clear aligners (Group AT)in terms of the predominance of anaerobic and gram negative bacteria. This emphasizes the importance of considering the microbiological effects when choosing orthodontic appliance and underscores the need for tailored oral hygiene practices for individuals undergoing these treatments. This research might provide insights that could assist in the development of innovative cleaning techniques and antibacterial materials.


Assuntos
Bactérias , Placa Dentária , Má Oclusão , Microbiota , Aparelhos Ortodônticos Fixos , RNA Ribossômico 16S , Humanos , Feminino , Estudos Transversais , Adulto , Placa Dentária/microbiologia , RNA Ribossômico 16S/genética , Adulto Jovem , Má Oclusão/terapia , Má Oclusão/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , China , Aparelhos Ortodônticos Removíveis/microbiologia
8.
Plant Physiol Biochem ; 212: 108767, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38797009

RESUMO

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.

9.
Front Genet ; 15: 1395315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808332

RESUMO

Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA. Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings. Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023-1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013-1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18-1.49, p-value <0.001). Conclusion: Our findings underscore the clinical importance of screening for ILD in RA patients and suggest that effective management of RA could significantly benefit ILD patients. The potential applicability of novel RA treatments to ILD warrants further exploration. Additionally, racial disparities in the manifestation of these diseases should not be overlooked, as they may offer new perspectives for targeted therapies in diverse populations.

10.
Med Ultrason ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808493

RESUMO

AIM: To evaluate the contrast-enhanced ultrasound (CEUS) versus conventional ultrasound (US) in guided liver puncture biopsy through a systematic review and meta-analysis. MATERIAL AND METHODS: Comparative studies on CEUS and US in liver puncture biopsy were systematically searched from PubMed, Embase, Cochrane library, Chinese Biomedical Literature Database. Two researchers independently screened and extracted data, and RevMan 5.3 software was used for data analysis. RESULTS: The area under the curve (AUC) for CEUS and US in diagnosing liver biopsy was 0.98 (95%CI 0.99-0.97) and 0.95 (95%CI 0.97-0.93), respectively. CEUS demonstrated significantly higher single puncture success rate (38.0% vs 36.4%) [OR=2.67; 95% CI 1.38-5 .17; p=0 .003] and pathological diagnosis rate (95.6% vs 90.5%) [OR =4.35; 95%CI 2.25 -8.39; p<0 .001] compared to the US group. The diagnostic accuracy of the CEUS group was 95.6 % (1964/2054), while that of the US group was 90.5% (1729/1909). The combined analysis indicated significant advantages for CEUS over US [(OR = 2.36). 95 %CI 1.81-3.09, p<0.001]. CONCLUSIONS: CEUS is superior to US in the diagnostic performance, single puncture success rate, pathological diagnosis rate and diagnostic accuracy of liver biopsy in patients with liver lesions.

11.
Front Pediatr ; 12: 1369823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783921

RESUMO

Background and purpose: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders that is characterized by core features in social communication impairment and restricted, repetitive sensory-motor behaviors. This study aimed to further investigate the utilization of fecal microbiota transplantation (FMT) in children with ASD, both with and without gastrointestinal (GI) symptoms, evaluate the effect of FMT and analyze the alterations in bacterial and fungal composition within the gut microbiota. Methods: A total of 38 children diagnosed with ASD participated in the study and underwent oral lyophilized FMT treatment. The dosage of the FMT treatment was determined based on a ratio of 1 g of donor stool per 1 kg of recipient body weight, with a frequency of once every 4 weeks for a total of 12 weeks. In addition, 30 healthy controls (HC) were included in the analysis. The clinical efficacy of FMT was evaluated, while the composition of fecal bacteria and fungi was determined using 16S rRNA and ITS gene sequencing methods. Results: Median age of the 38 children with ASD was 7 years. Among these children, 84.2% (32 of 38) were boys and 81.6% (31 of 38) exhibited GI symptoms, with indigestion, constipation and diarrhea being the most common symptoms. Sample collections and assessments were conducted at baseline (week 0), post-treatment (week 12) and follow-up (week 20). At the end of the follow-up phase after FMT treatment, the autism behavior checklist (ABC) scores decreased by 23% from baseline, and there was a 10% reduction in scores on the childhood autism rating scale (CARS), a 6% reduction in scores on the social responsiveness scale (SRS) and a 10% reduction in scores on the sleep disturbance scale for children (SDSC). In addition, short-term adverse events observed included vomiting and fever in 2 participants, which were self-limiting and resolved within 24 h, and no long-term adverse events were observed. Although there was no significant difference in alpha and beta diversity in children with ASD before and after FMT therapy, the FMT treatment resulted in alterations in the relative abundances of various bacterial and fungal genera in the samples of ASD patients. Comparisons between children with ASD and healthy controls (HC) revealed statistically significant differences in microbial abundance before and after FMT. Blautia, Sellimonas, Saccharomycopsis and Cystobasidium were more abundant in children with ASD than in HC, while Dorea were less abundant. After FMT treatment, levels of Blautia, Sellimonas, Saccharomycopsis and Cystobasidium decreased, while levels of Dorea increased. Moreover, the increased abundances of Fusicatenibacter, Erysipelotrichaceae_UCG-003, Saccharomyces, Rhodotorula, Cutaneotrichosporon and Zygosaccharomyces were negatively correlated with the scores of ASD core symptoms. Conclusions: Oral lyophilized FMT could improve GI and ASD related symptoms, as well as sleep disturbances, and alter the gut bacterial and fungal microbiota composition in children with ASD. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200055943. Registered 28 January 2022, www.chictr.org.cn.

12.
Anal Chim Acta ; 1309: 342687, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772659

RESUMO

BACKGROUND: Cysteine (Cys), glutathione (GSH), and homocysteine (Hcy), as three major biothiols are involved in a variety of physiological processes and play a crucial role in plant growth. Abnormal levels of Cys can cause plants to fail to grow properly. To date, although a very large number of fluorescent probes have been reported for the detection of biothiols, very few of them can be used for the selective discrimination of Cys from GSH and Hcy due to their structural similarity, and only a few of them can be used for plant imaging. RESULTS: Here, three fluorescent probes (o-/m-/p-TMA) based on TMN fluorophore and the ortho-/meta-/para-substituted maleimide recognition groups were constructed to investigate the selective response effect of Cys. Compared to the o-/m-TMA, p-TMA can selectively detect Cys over GSH and Hcy with a rapid response time (10 min) and a low detection limit (0.26 µM). The theoretical calculation confirmed that the intermediate p-TMA-Cys-int has shorter interatomic reaction distances (3.827 Å) compared to o-/m-TMA-Cys (5.533/5.287 Å), making it more suitable for further transcyclization reactions. Additionally, p-TMA has been employed for selective tracking of exogenous and endogenous Cys in Arabidopsis thaliana using both single-/two-photon fluorescence imaging. Furthermore, single cell walls produced obvious two-photon fluorescence signals, indicating that p-TMA can be used for high-concentration Cys analysis in single cells. Surprisingly, p-TMA can be used as a fluorescent dye for protein staining in SDS-PAGE with higher sensitivity (7.49 µg/mL) than classical Coomassie brilliant blue (14.11 µg/mL). SIGNIFICANCE: The outstanding properties of p-TMA make it a promising multifunctional molecular tool for the highly selective detection of Cys over GSH and Hcy in various complex environments, including water solutions, zebrafish, and plants. Additionally, it has the potential to be developed as a fluorescent dye for a simple and fast SDS-PAGE fluorescence staining method.


Assuntos
Cisteína , Eletroforese em Gel de Poliacrilamida , Corantes Fluorescentes , Glutationa , Homocisteína , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Cisteína/análise , Cisteína/química , Glutationa/análise , Glutationa/química , Homocisteína/análise , Homocisteína/química , Animais , Fótons , Imagem Óptica , Arabidopsis/química , Humanos , Ciclização , Peixe-Zebra
13.
J Mol Neurosci ; 74(2): 55, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776015

RESUMO

The dysregulation of lipid metabolism has been strongly associated with Alzheimer's disease (AD) and has intricate connections with various aspects of disease progression, such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Here, a comprehensive bioinformatic assessment was conducted on lipid metabolism genes in the brains and peripheral blood of AD-derived transcriptome datasets, characterizing the correlation between differentially expressed genes (DEGs) of lipid metabolism and disease pathologies, as well as immune cell preferences. Through the application of weighted gene co-expression network analysis (WGCNA), modules eigengenes related to lipid metabolism were pinpointed, and the examination of their molecular functions within biological processes, molecular pathways, and their associations with pathological phenotypes and molecular networks has been characterized. Analysis of biological networks indicates notable discrepancies in the expression patterns of the DEGs between neuronal and immune cells, as well as variations in cell type enrichments within both brain tissue and peripheral blood. Additionally, drugs targeting the DEGs from central and peripheral and a diagnostic model for hub genes from the blood were retrieved and assessed, some of which were shown to be useful for therapeutic and diagnostic. These results revealed the distinctive pattern of transcriptionally abnormal lipid metabolism in central, peripheral, and immune cell activation, providing valuable insight into lipid metabolism for diagnosing and guiding more effective treatment for AD.


Assuntos
Doença de Alzheimer , Metabolismo dos Lipídeos , Transcriptoma , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Encéfalo/metabolismo , Redes Reguladoras de Genes
14.
J Vis Exp ; (207)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38767370

RESUMO

Preclinical gene therapy research, particularly in rodent and large animal models, necessitates the production of AAV vectors with high yield and purity. Traditional approaches in research laboratories often involve extensive use of cell culture dishes to cultivate HEK293T cells, a process that can be both laborious and problematic. Here, a unique in-house method is presented, which simplifies this process with a specific cell factory (or cell stacks, CF10) platform. An integration of polyethylene glycol/aqueous two-phase partitioning with iodixanol gradient ultracentrifugation improves both the yield and purity of the generated AAV vectors. The purity of the AAV vectors is verified through SDS-PAGE and silver staining, while the ratio of full to empty particles is determined using transmission electron microscopy (TEM). This approach offers an efficient cell factory platform for the production of AAV vectors at high yields, coupled with an improved purification method to meet the quality demands for in vivo studies.


Assuntos
Dependovirus , Vetores Genéticos , Dependovirus/genética , Humanos , Vetores Genéticos/química , Células HEK293 , Ácidos Tri-Iodobenzoicos/química , Polietilenoglicóis/química , Microscopia Eletrônica de Transmissão
15.
J Agric Food Chem ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776233

RESUMO

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.

16.
Biosens Bioelectron ; 259: 116400, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38776799

RESUMO

CRISPR based nucleic acid detection technology provides a deployable approach to point of care testing. While, there remain challenges limiting its practical applications, such as the need for pre-amplification and the long turnaround time. Here, we present a self-cascade signal amplification method with LwaCas13a and an artificially designed "U" rich RNA of stem-loop structure (URH) for pre-amplification-free ultra-fast and ultra-sensitive point-of-care testing (PASSPORT). The PASSPORT system contains: URH, crRNA targeted the URH, crRNA targeted the interesting RNA, fluorescent RNA reporter and LwaCas13a. The assay realized the detection of 100 copies/mL, within 5 min. The PASSPORT platform was further adopted for the detection of marker gene from SASR-CoV-2 and Severe fever with thrombocytopenia syndrome virus (SFTSV), respectively, and 100% accuracy for the analysis of clinical specimens (100 SASR-CoV-2 specimens and 16 SFTSV specimens) was obtained. Integrated with a lateral flow assay device, this assay could provide an alternative platform for the development of point of care testing (POCT) biosensors. PASSPORT has the potential to enable sensitive, specific, user-friendly, rapid, affordable, equipment-free and point-of-care testing for the purpose of large-scale screening and in case of epidemic outbreak.

17.
Front Oncol ; 14: 1369027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690163

RESUMO

Objective: Metabolic risks (MRs) are the primary determinants of breast cancer (BC) mortality among women. This study aimed to examine the changing trends in BC mortality associated with MRs and explore how they related to age, time period, and birth cohorts in Chinese women aged 25 and above. Methods: Data were sourced from the Global Burden of Disease Study 2019 (GBD2019). The BC mortality trajectories and patterns attributable to MRs were assessed using Joinpoint regression. The age-period-cohort (APC) model was employed to evaluate cohort and time period effects. Results: The age-standardized mortality rate (ASMR) of BC mortality linked to MRs displayed an escalating trend from 1990 to 2019, demonstrating an average annual percentage change (AAPC) of 1.79% (95% CI: 1.69~1.87). AAPCs attributable to high fasting plasma glucose (HFPG) and high body mass index (HBMI) were 0.41% (95% CI: 0.32~0.53) and 2.75% (95% CI: 2.68~2.82), respectively. APC analysis revealed that BC mortality due to HBMI in women aged 50 and above showed a rise with age and mortality associated with HFPG consistently demonstrated a positive correlation with age. The impact of HBMI on BC mortality significantly outweighed that of HFPG. The risk of BC mortality linked to HBMI has steadily increased since 2005, while HFPG demonstrated a trend of initial increase followed by a decrease in the period effect. Regarding the cohort effect, the relative risk of mortality was greater in the birth cohort of women after the 1960s of MRs on BC mortality, whereas those born after 1980 displayed a slight decline in the relative risk (RR) associated with BC mortality due to HBMI. Conclusion: This study suggests that middle-aged and elderly women should be considered as a priority population, and control of HBMI and HFPG should be used as a primary tool to control metabolic risk factors and effectively reduce BC mortality.

18.
J Electrocardiol ; 84: 137-144, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38696980

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is associated with increased rates of cardiovascular disease and mortality and is linked to abnormal electrocardiogram (ECG) parameters. We aimed to explore the relationships and interactions among MetS and its components, abnormal P-wave axis (aPWA), and mortality rates. METHODS: We analyzed data from 7526 adult participants with sinus rhythm recruited from the National Health and Nutrition Examination Survey III. MetS was classified based on the NCEP ATP III-2005 definition. aPWA included all P-wave axis outside 0-75°. The National Death Index was utilized to identify survival status. Hazard ratios (HRs) and 95% confidence intervals (CIs) categorized by aPWA, MetS, and their components were analyzed using Cox proportional hazards models to investigate all-cause and cardiovascular mortalities. RESULTS: Within a median follow-up period of 20.76 years, 4686 deaths were recorded, of which 1414 were attributable to cardiovascular disease. Participants with both MetS and aPWA had higher all-cause (HR: 1.45, 95% CI: 1.29-1.64, interaction P = 0.043) and cardiovascular (HR: 1.36, 95% CI: 1.02-1.79, interaction P-value = 0.058) mortality rates than participants without MetS and with a normal P-wave axis. Participants with the greatest number of MetS components and aPWA had a higher risk of all-cause mortality (HR: 1.70, 95% CI: 1.13-2.55, P = 0.011). CONCLUSIONS: Individuals with both aPWA and MetS have a higher risk of mortality, and those with a greater number of MetS components and aPWA have a higher risk of all-cause mortality. These findings highlight the significance of integrating ECG characteristics with metabolic health status in clinical assessment.

19.
Mil Med Res ; 11(1): 29, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741175

RESUMO

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.


Assuntos
Materiais Biocompatíveis , Implantes Dentários , Peri-Implantite , Peri-Implantite/terapia , Peri-Implantite/prevenção & controle , Peri-Implantite/tratamento farmacológico , Humanos , Implantes Dentários/normas , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Propriedades de Superfície , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia
20.
Int J Environ Health Res ; : 1-9, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753525

RESUMO

Circadian rhythm (24-hour period of physiological and behavioral changes) is the basis of the overall health, including mood and health. This study aimed to explore the influence of circadian rhythm and sleep schedules on depressive symptoms in Chinese adolescents. In this cross-sectional study, 841 middle school students were recruited and divided into two groups (depressive group, DG, n = 210, and control group, n = 631) depending on the total score of The Center for Epidemiological Studies Depression Scale for Children (CES-DC). The circadian rhythm and sleep quality among adolescents were evaluated by using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Self-rating scale of Sleep (SRSS) scales. Furthermore, correlation analysis and logistic regression analysis were used to determine the effects of demographic factors, sleeping arrangement, sleep quality, and circadian rhythm on depressive symptoms. The DG group's CES-DC, BRIAN and SRSS scores were significantly higher than the control group's. Higher scores of BRIAN and SRSS were risk factors for depressive symptoms in Chinese adolescents. Attending a day school and waking up later on weekends may be weak protective factors. Our results suggest that circadian rhythm disturbance, sleep quality, and sleeping arrangement have a significant influence on depressive symptoms among adolescents in China.

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