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1.
Trials ; 25(1): 538, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143596

RESUMO

BACKGROUND: Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients' limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients' physical function and the burden of caregivers. METHODS/DESIGN: A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training. DISCUSSION: Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden. TRIAL REGISTRATION: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.


Assuntos
Cuidadores , AVC Isquêmico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Cuidadores/educação , AVC Isquêmico/reabilitação , AVC Isquêmico/enfermagem , AVC Isquêmico/fisiopatologia , Feminino , Pessoa de Meia-Idade , Masculino , Sobrecarga do Cuidador , Fatores de Tempo , Resultado do Tratamento , China , Adulto , Atividades Cotidianas , Idoso , Atividade Motora , Qualidade de Vida , Estado Funcional
2.
Crit Rev Oncol Hematol ; 202: 104461, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39103129

RESUMO

The treatment of thoracic tumors with ionizing radiation can cause radiation-induced lung injury (RILI), which includes radiation pneumonitis and radiation-induced pulmonary fibrosis. Preventing RILI is crucial for controlling tumor growth and improving quality of life. However, the serious adverse effects of traditional RILI treatment methods remain a major obstacle, necessitating the development of novel treatment options that are both safe and effective. This review summarizes the molecular mechanisms of RILI and explores novel treatment options, including natural compounds, gene therapy, nanomaterials, and mesenchymal stem cells. These recent experimental approaches show potential as effective prevention and treatment options for RILI in clinical practice.

3.
Front Nutr ; 11: 1433544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39101009

RESUMO

Background: Sepsis triggers a strong inflammatory response, often leading to organ failure and high mortality. The role of serum albumin levels in sepsis is critical but not fully understood, particularly regarding the significance of albumin level changes over time. This study utilized Group-based Trajectory Modeling (GBTM) to investigate the patterns of serum albumin changes and their impact on sepsis outcomes. Methods: We conducted a retrospective analysis on ICU patients from West China Hospital (2015-2022), employing GBTM to study serum albumin fluctuations within the first week of ICU admission. The study factored in demographics, clinical parameters, and comorbidities, handling missing data through multiple imputation. Outcomes assessed included 28-day mortality, overall hospital mortality, and secondary complications such as AKI and the need for mechanical ventilation. Results: Data from 1,950 patients revealed four serum albumin trajectories, showing distinct patterns of consistently low, increasing, moderate, and consistently high levels. These groups differed significantly in mortality, with the consistently low level group experiencing the highest mortality. No significant difference in 28-day mortality was observed among the other groups. Subgroup analysis did not alter these findings. Conclusion: The study identified four albumin trajectory groups in sepsis patients, highlighting that those with persistently low levels had the worst outcomes, while those with increasing levels had the best. Stable high levels above 30 g/L did not change outcomes significantly. These findings can inform clinical decisions, helping to identify high-risk patients early and tailor treatment approaches.

4.
Clin Lung Cancer ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39095235

RESUMO

OBJECTIVES: Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring. MATERIALS AND METHODS: We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms. RESULTS: High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (MYC, TEK, FANCA, FAM123B, and MET) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in TEK, MYC, FGF19, RET, and MET were associated with high-grade irAEs; while for the squamous subtype, ERBB2 mutations were associated with high-grade irAEs. CONCLUSION: This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.

6.
Brief Bioinform ; 25(5)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39120644

RESUMO

Recent advancements in spatial imaging technologies have revolutionized the acquisition of high-resolution multichannel images, gene expressions, and spatial locations at the single-cell level. Our study introduces xSiGra, an interpretable graph-based AI model, designed to elucidate interpretable features of identified spatial cell types, by harnessing multimodal features from spatial imaging technologies. By constructing a spatial cellular graph with immunohistology images and gene expression as node attributes, xSiGra employs hybrid graph transformer models to delineate spatial cell types. Additionally, xSiGra integrates a novel variant of gradient-weighted class activation mapping component to uncover interpretable features, including pivotal genes and cells for various cell types, thereby facilitating deeper biological insights from spatial data. Through rigorous benchmarking against existing methods, xSiGra demonstrates superior performance across diverse spatial imaging datasets. Application of xSiGra on a lung tumor slice unveils the importance score of cells, illustrating that cellular activity is not solely determined by itself but also impacted by neighboring cells. Moreover, leveraging the identified interpretable genes, xSiGra reveals endothelial cell subset interacting with tumor cells, indicating its heterogeneous underlying mechanisms within complex cellular interactions.


Assuntos
Análise de Célula Única , Análise de Célula Única/métodos , Humanos , Algoritmos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Biologia Computacional/métodos
7.
Autophagy ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177202

RESUMO

Starvation- or stress-induced phosphatidylinositol 3-phosphate (PtdIns3P/PI3P) production at the endoplasmic reticulum (ER) subdomains organizes phagophore assembly and autophagosome formation. Coat protein complex II (COPII) vesicles budding from ER exit site (ERES) also contribute to autophagosome formation. Whether any PtdIns3P phosphatase functions at ERES to inhibit macroautophagy/autophagy is unknown. Here we report Myotubularin 2 (MTM2) of Arabidopsis as a PtdIns3P phosphatase that localizes to ERES and negatively regulates autophagy. MTM2 binds PtdIns3P with its PH-GRAM domain in vitro and acts toward PtdIns3P in vivo. Transiently expressed MTM2 colocalizes with ATG14b, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex, and overexpression of MTM2 blocks autophagic flux and causes over-accumulation of ATG18a, ATG5, and ATG8a. The mtm2 mutant has higher levels of autophagy and is more tolerant to starvation, whereas MTM2 overexpression leads to reduced autophagy and sensitivity to starvation. The phenotypes of mtm2 are suppressed by ATG2 mutation, suggesting that MTM2 acts upstream of ATG2. Importantly, MTM2 does not affect the endosomal functions of PtdIns3P. Instead, MTM2 specifically colocalizes with COPII coat proteins and is cradled by the ERES-defining protein SEC16. MTM2 interacts with SEC23A with its phosphatase domain and inhibits COPII-mediated protein secretion. Finally, a role for MTM2 in salt stress response is uncovered. mtm2 resembles the halophyte Thellungiella salsuginea in its efficient vacuolar compartmentation of Na+, maintenance of chloroplast integrity, and timely regulation of autophagy-related genes. Our findings reveal a balance between PtdIns3P synthesis and turnover in autophagosome formation, and provide a new link between autophagy and COPII function.

8.
J Med Internet Res ; 26: e49403, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39110493

RESUMO

BACKGROUND: The use of wearable monitoring devices (WMDs), such as smartwatches, is advancing support and care for community-dwelling older adults across the globe. Despite existing evidence of the importance of WMDs in preventing problems and promoting health, significant concerns remain about the decline in use after a period of time, which warrant an understanding of how older adults experience the devices. OBJECTIVE: This study aims to explore and describe the experiences of community-dwelling older adults after receiving our interventional program, which included the use of a smartwatch with support from a community health workers, nurses, and social workers, including the challenges that they experienced while using the device, the perceived benefits, and strategies to promote their sustained use of the device. METHODS: We used a qualitative descriptive approach in this study. Older adults who had taken part in an interventional study involving the use of smartwatches and who were receiving regular health and social support were invited to participate in focus group discussions at the end of the trial. Purposive sampling was used to recruit potential participants. Older adults who agreed to participate were assigned to focus groups based on their community. The focus group discussions were facilitated and moderated by 2 members of the research team. All discussions were recorded and transcribed verbatim. We used the constant comparison analytical approach to analyze the focus group data. RESULTS: A total of 22 participants assigned to 6 focus groups participated in the study. The experiences of community-dwelling older adults emerged as (1) challenges associated with the use of WMDs, (2) the perceived benefits of using the WMDs, and (3) strategies to promote the use of WMDs. In addition, the findings also demonstrate a hierarchical pattern of health-seeking behaviors by older adults: seeking assistance first from older adult volunteers, then from social workers, and finally from nurses. CONCLUSIONS: Ongoing use of the WMDs is potentially possible, but it is important to ensure the availability of technical support, maintain active professional follow-ups by nurses and social workers, and include older adult volunteers to support other older adults in such programs.


Assuntos
Agentes Comunitários de Saúde , Grupos Focais , Vida Independente , Pesquisa Qualitativa , Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Masculino , Feminino , Assistentes Sociais/psicologia , Enfermeiras e Enfermeiros/psicologia , Enfermeiras e Enfermeiros/estatística & dados numéricos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
9.
Int J Biol Macromol ; : 134929, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39179078

RESUMO

Laccases with highly catalytic properties have been widely used in developing green applications for water remediation. However, the poor stability and low reutilization rate of free laccase make it difficult to be applied practically. Hence, in this study, an immobilized laccase was prepared using dopamine (DA) functionalized sodium alginate (SA)/polyethylene glycol (PEG) composite hydrogels to realize the recyclability of the laccase. The SA/PEG composite hydrogels, as the protective carrier for laccase, exhibited excellent catalytic stability in various interfering environments. After 30 days, Lac@SA-PDA/PEG beads could remain 70.23 % of the initial activity, as the residual activity of free laccase was only 12.35 %. When free laccase and Lac@SA-PDA/PEG beads were used for decolorization of Reactive Blue 19 (RB-19,100 mg/L), the degradation rate of Lac@SA-PDA/PEG is 6.88 times higher than free laccase. More importantly, the SA-PDA/PEG composite hydrogel exhibited a high reutilization rate, which after six cycles, Lac@SA-PDA/PEG beads retained 90.23 % of its initial activity. Besides, the degradation effect of Lac@SA-PDA/PEG on different dyes was analyzed. In addition, the conjectured degradation pathways of RB-19 by laccase were analyzed. The work showed that immobilized laccase has tremendous potential for the treatment of dyestuff wastewater.

10.
Eur J Dermatol ; 34(4): 371-377, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39193673

RESUMO

Conventional histopathological features of psoriasis and atopic dermatitis often overlap. We aimed to investigate Galectin-3 (Gal-3) expression in psoriatic skin lesions and its potential as an immunohistochemical marker for distinguishing between psoriasis and atopic dermatitis on a pathological basis. Based on immunohistochemical analysis, we assessed Gal-3 expression in formalin-fixed, paraffin-embedded tissue sections from 21 patients with psoriasis and 15 patients with atopic dermatitis. Quantitative analysis of expression intensity was performed using the average density (average optical density) method. We analysed the relationship between Gal-3 expression and clinical characteristics, as well as conventional histopathological features. Patients with psoriasis exhibited significantly decreased Gal-3 expression in the epidermis (0.11±0.05) compared to the atopic dermatitis group (0.36±0.15) and healthy controls (0.49±0.13) (p<0.0001). Reduction in Gal-3 expression in the psoriatic epidermis around areas of neutrophil aggregation was more pronounced than around areas of non-neutrophil aggregation (0.07±0.02 vs 0.16±0.05, p<0.01). In both psoriasis (r=-0.48, p<0.05) and atopic dermatitis groups (r=-0.70, p<0.01), Gal-3 expression negatively correlated with epidermal thickness. When epidermal thickness was matched between the two groups, the decrease in epidermal Gal-3 expression remained significant in the psoriasis group compared to the atopic dermatitis group (0.14±0.05 Vs 0.30±0.07, p<0.01). Patients with psoriasis show specific downregulation of epidermal Gal-3, correlating with epidermal thickness and neutrophil-related factors. Gal-3 may serve as an auxiliary discriminative marker between psoriasis and atopic dermatitis, potentially associated with keratinocyte proliferation and neutrophil function.


Assuntos
Dermatite Atópica , Epiderme , Galectina 3 , Psoríase , Humanos , Psoríase/metabolismo , Psoríase/patologia , Epiderme/metabolismo , Epiderme/patologia , Galectina 3/metabolismo , Galectina 3/análise , Feminino , Masculino , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Adulto , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Biomarcadores/análise , Imuno-Histoquímica , Estudos de Casos e Controles , Adulto Jovem , Idoso , Diagnóstico Diferencial
11.
Sci Rep ; 14(1): 17965, 2024 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095375

RESUMO

Postoperative acute kidney injury (AKI) is a common complication that is associated with chronic kidney disease, early postsurgical mortality, and prolonged hospital stays. Preterm neonates who undergo surgery are at risk factors for AKI due to underdeveloped kidneys. To date, little is known about the incidence and perioperative risk factors for AKI in preterm neonates undergoing noncardiac surgery. Preterm neonates who underwent noncardiac surgery between January May 1, 2020, and February 28, 2023, were enrolled in the trial according to the inclusion criteria. Both multivariable and logistic regression analyses were used to analyze the associations between characteristic data and AKI. In total, 106 preterm neonates met the inclusion criteria, and 25 preterm neonates (23.6%) developed postoperative AKI. Multivariate analysis revealed that the factors associated with AKI were gestational age < 32 weeks [OR: 4.88; 95% CI (1.23-19.42)], preoperative sepsis [OR: 3.98; 95% CI (1.29-12.28)], and intraoperative hypotension [OR: 3.75; 95% CI (1.26-11.15)]. Preterm neonates who developed AKI were more likely to have longer hospital length of stays (38 [18,69] days vs. 21[12,46]) and higher medical costs (93,181.6 [620450.0,173,219.0] ï¿¥ vs. 58,134.6 [31015.1,97,224,1) ï¿¥ than neonates who did not develop AKI. Preterm neonates who underwent noncardiac surgery had a high incidence of AKI. Independent risk factors for AKI in preterm neonates who underwent noncardiac surgery were low gestational age, preoperative sepsis, and intraoperative hypotension. Preterm neonates who developed AKI were more likely to have longer hospital stays and higher medical costs.


Assuntos
Injúria Renal Aguda , Recém-Nascido Prematuro , Tempo de Internação , Complicações Pós-Operatórias , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Recém-Nascido , Fatores de Risco , Masculino , Feminino , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Idade Gestacional , Incidência , Sepse/epidemiologia , Sepse/etiologia , Sepse/complicações , Procedimentos Cirúrgicos Operatórios/efeitos adversos
12.
J Clin Pathol ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168612

RESUMO

AIMS: The International Association for the Study of Lung Cancer (IASLC) has proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, the efficacy of this grading system in predicting distant metastases in patients with LUAD remains unexplored. This study aims to assess the potential of the IASLC grading system in predicting the occurrence of brain and bone metastases in patients with resectable LUAD, thereby identifying individuals at high risk of post-surgery distant metastasis. METHODS: We retrospectively analysed clinical data and pathological reports of 174 patients with early-stage LUAD who underwent surgical resection between 2008 and 2015 at our cancer center. Patients were monitored for 5 years, and their bone and brain metastasis-free survival rates were determined. RESULTS: 28 out of 174 patients developed distant metastases in 5 years with a median overall survival of 60 months for metastasis-free patients and 38.3 months for patients with distant metastasis. Tumour grading of all samples was evaluated by both IASLC grading and predominant pattern-based grading systems. Receiver operating characteristic (ROC) curves were used to evaluate the predictive capabilities of the IASLC grading system and tumour stage for distant metastasis. Compared with the predominant pattern-based grading system, the IASLC grading system showed a better correlation with the incidence of distant metastasis and lymphovascular invasion. ROC analyses revealed that the IASLC grading system outperformed tumour stage in predicting distant metastasis. CONCLUSIONS: Our study indicates that the IASLC grading system is capable of predicting the incidence of distant metastasis among patients with early-stage invasive LUAD.

13.
Int J Palliat Nurs ; 30(7): 370-378, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39028315

RESUMO

BACKGROUND: Caring for patients with advanced cancer is complex and challenging, requiring varied expertise, including symptom management, communication skills, care coordination and emotional resilience. Within existing literature, the lived experiences of oncology nurses are poorly articulated in countries with a lower income where formal palliative care (PC) is absent. AIM: To explore the lived experiences of Gazan oncology nurses who provide care to patients with advanced cancer in healthcare systems, without formal palliative care infrastructure. METHODS: A phenomenological approach was adopted. Semi-structured interviews were conducted between January and April 2022, in the Turkish Palestinian Friendship Hospital. Thematic analysis used the themes (corporeality, relationality, spatiality and temporality) to facilitate reflection on the meaning of participants' lived experiences. RESULTS: Interviews were undertaken with 16 oncology nurses. The experience of the 'erosion of nurses' work when coping with anxious attachments to patients and families' was the overarching theme in nurses' views, characterised by five sub-themes: (1) inadequacy of PC training and resources, (2) serving humanity, (3) pride in their profession, (4) existential distress and the coping strategies used by nurses, and (5) reported stress and anxiety when caring for seriously ill patients and their families. CONCLUSIONS: The study sheds light on the challenges and powerful emotions experienced by oncology nurses who care for patients with advanced cancer, yet lack the necessary PC training and institutional resources. The findings indicate an urgent need for PC training for nurses within the Gazan healthcare system and other lower-income settings. Assessing nurses' emotions and relationships with patients and family caregivers is imperative to enable optimum care for patients with cancer and to foster resilience among their nurses.


Assuntos
Neoplasias , Enfermagem Oncológica , Humanos , Neoplasias/enfermagem , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Pesquisa Qualitativa , Adaptação Psicológica , Turquia , Entrevistas como Assunto
14.
Artigo em Inglês | MEDLINE | ID: mdl-38995188

RESUMO

A Gram-negative, ellipsoidal to short-rod-shaped, motile bacterium was isolated from Beijing's urban air. The isolate exhibited the closest kinship with Noviherbaspirillum aerium 122213-3T, exhibiting 98.4 % 16S rRNA gene sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that it clustered closely with N. aerium 122213-3T, thus forming a distinct phylogenetic lineage within the genus Noviherbaspirillum. The average nucleotide identity and digital DNA-DNA hybridization values between strain I16B-00201T and N. aerium 122213-3T were 84.6 and 29.4 %, respectively. The respiratory ubiquinone was ubiquinone 8. The major fatty acids (>10 %) were summed feature 3 (C16:1ω6c/C16:1ω7c, 43.3 %), summed feature 8 (C18:1ω7c/C18:1ω6c, 15.9 %) and C12:0 (11.0 %). The polyamine profile showed putrescine as the predominant compound. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, unknown lipids and unknown phosphatidylaminolipids. The phenotypic, phylogenetic and chemotaxonomic results consistently supported that strain I16B-00201T represented a novel species of the genus Noviherbaspirillum, for which the name Noviherbaspirillum album sp. nov. is proposed, with I16B-00201T (=CPCC 100848T=KCTC 52095T) designated as the type strain. Its DNA G+C content is 59.4 mol%. Pan-genome analysis indicated that some Noviherbaspirillum species possess diverse nitrogen and aromatic compound metabolism pathways, suggesting their potential value in pollutant treatment.


Assuntos
Microbiologia do Ar , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Hibridização de Ácido Nucleico , Fosfolipídeos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Ubiquinona , RNA Ribossômico 16S/genética , Pequim , DNA Bacteriano/genética , Ácidos Graxos/análise , Fosfolipídeos/análise
15.
Acta Pharmacol Sin ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956416

RESUMO

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

16.
Alcohol Clin Exp Res (Hoboken) ; 48(8): 1519-1528, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38951043

RESUMO

BACKGROUND: Excessive alcohol consumption has a multifaceted impact on the body's metabolic pathways and organ systems. The objectives of this study were to characterize global metabolomic changes and identify specific pathways that are altered in individuals with excessive alcohol use. METHODS: This exploratory study included 22 healthy controls with no known history of excessive alcohol use and 38 patients identified as using alcohol excessively. A Fibrosis-4 score was used to determine the risk of underlying alcohol-associated liver disease among the excessive drinkers. RESULTS: We found significantly altered urinary and serum metabolites among excessive drinkers, affecting various metabolic pathways including the metabolism of lipids, amino acids and peptides, cofactors and vitamins, carbohydrates, and nucleotides. Levels of two steroid hormones-5alpha-androstan-3beta,17beta-diol disulfate and androstenediol (3beta,17beta) disulfate-were significantly higher in both the serum and urine samples of excessive drinkers. These elevated levels may be associated with a higher risk of liver fibrosis in individuals with excessive alcohol use. CONCLUSION: Alcohol consumption leads to marked alterations in multiple metabolic pathways, highlighting the systemic impact of alcohol on various tissues and organ systems. These findings provide a foundation for future mechanistic studies aimed at elucidating alcohol-induced changes in these metabolic pathways and their implications.

17.
Biosens Bioelectron ; 263: 116577, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39033656

RESUMO

Implementation of cost-effective, reliable, and efficient technologies for the sensitive, rapid, and accurate detection of pesticide residues in agriproducts presents a promising solution to the escalating food safety concerns. Herein, a high-performance surface-enhanced Raman scattering (SERS) aptasensor based on nanotag (AuNS@4-MBN@Ag-aptamer) was introduced for ultrasensitive, reliable, and interference-free detection of chlorpyrifos (CPF). This aptasensor featured star-shaped bimetallic nanotag as the principal Raman signal enhancement material and 4-mercaptobenzonitrile (4-MBN) as "biological-silent"-window reporter (at 2228 cm-1). Moreover, cDNA-linked Fe3O4@AuNPs (FA-cDNA) served as magnetic substrates to simplify the separation process of FA-cDNA-combined nanotags. In the aptasensor, the formation of FA-cDNA-aptamer-AuNS@4-MBN@Ag hybrids was hindered by CPF, and its Raman intensity decreased with increasing CPF concentration. Under optimal SERS conditions, the aptasensor exhibited a broad linear detection range from 2.5 × 102 to 5.0 × 104 pg⋅mL-1, with an impressively low limit of detection of 220.35 pg⋅mL-1 (signal-to-noise ratio = 3). The selectivity and reproducibility assessments highlighted its exceptional sensitivity and interference-free capabilities. Furthermore, practical applications on wheat and apples demonstrated satisfactory spiked recovery rates, ranging from 89.61% to 107.33% (relative standard deviation ≤ 14.55%). Consequently, the high-performance "biological-silent"-window nanotag-based aptasensor is a promising tool for monitoring trace CPF in complex matrices.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Clorpirifos , Contaminação de Alimentos , Ouro , Limite de Detecção , Nanopartículas Metálicas , Prata , Análise Espectral Raman , Clorpirifos/análise , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Ouro/química , Prata/química , Nanopartículas Metálicas/química , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Inseticidas/análise , Inseticidas/isolamento & purificação
18.
Cardiooncology ; 10(1): 46, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080734

RESUMO

BACKGROUND: Participation in cardio-oncological rehabilitation is low, and the effects incline to decrease after the initial rehabilitation term. Home-based exercise has the potential to enhance involvement in cardio-oncology rehabilitation and was demonstrated to be feasible, safe, and helpful in increasing short-term cardiorespiratory fitness. The lasting effects on cardiorespiratory fitness and physical activity are uncertain. Hence, a novel approach via telehealth management based on objectively measured exercise at home was proposed. OBJECTIVES: To improve self-monitoring, such as self-confidence, behavioral change, and goal setting for individual exercise, and afterward, increase long-term effects concerning cardiorespiratory fitness. DESIGN: This randomized controlled trial compares a 12-week guided home exercise telehealth intervention with a center-based exercise intervention of the same duration and intensity of exercise in lymphoma cancer survivors entering cardio-oncology rehabilitation after treatment. Participants will be instructed to exercise gradually at 60-85% of their maximum heart rate for 30-50 min 3 times a week. Participants will receive individual remote guidance (feedback about frequency, duration, and exercise intensity) by preferred contact (phone call, text message) once a week based on shared exercise data through the web platform. The primary outcome is a change in cardiorespiratory fitness expressed as maximal oxygen uptake assessed through cardiopulmonary exercise test at baseline, 12 weeks, and 1 year. Secondary objectives are quality of life, muscle strength, body composition, incidence of adverse events, and exercise adherence. This study will determine whether a telehealth model is effective and safe compared to a center-based model in cancer survivors and whether exercise prescriptions are followed by participants. Additionally, an overview of the long-term effectiveness of telehealth cardio-oncology rehabilitation will be provided. This approach aligns with the trend of moving non-complex healthcare services into the patients' home environment. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05779605.

19.
BMC Oral Health ; 24(1): 758, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956625

RESUMO

BACKGROUND: The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. METHODS: Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. RESULTS: For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. CONCLUSIONS: The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Implantes Dentários , Análise de Elementos Finitos , Incisivo , Maxila , Procedimentos de Ancoragem Ortodôntica , Ligamento Periodontal , Técnicas de Movimentação Dentária , Humanos , Técnicas de Movimentação Dentária/métodos , Técnicas de Movimentação Dentária/instrumentação , Procedimentos de Ancoragem Ortodôntica/instrumentação , Procedimentos de Ancoragem Ortodôntica/métodos , Ligamento Periodontal/diagnóstico por imagem , Imageamento Tridimensional/métodos , Dente Canino/diagnóstico por imagem , Desenho de Aparelho Ortodôntico , Análise do Estresse Dentário , Fenômenos Biomecânicos , Aparelhos Ortodônticos Removíveis
20.
Front Oncol ; 14: 1336106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962268

RESUMO

Objective: The escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal heterogeneity in leukemia progenitor cells and explore molecular or signaling pathways associated with AML immune escape. Methods: Single-cell RNA sequencing (scRNA-seq) was performed to identified AML-related cellular subsets, and intercellular communication was analyzed to investigate molecular mechanisms associated with AML immune escape. Bulk RNA sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs) related to hematopoietic stem cell progenitors (HSC-Prog) in AML, and critical ore signaling pathways and hub genes were found by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA level of the hub gene was verified using quantitative real-time PCR (qRT-PCR) and the protein level of human leukocyte antigen A (HLA-A) using enzyme-linked immuno sorbent assay (ELISA). Results: scRNA-seq analysis revealed a large heterogeneity of HSC-Prog across samples, and the intercellular communication analysis indicated a strong association between HSC-Prog and CD8+-T cells, and HSC-Prog also had an association with HLA-A. Transcriptome analysis identified 1748 DEGs, enrichment analysis results showed that non-classical wnt signaling pathway was associated with AML, and 4 pathway-related genes (RHOA, RYK, CSNK1D, NLK) were obtained. After qRT-PCR and ELISA validation, hub genes and HLA-A were found to be down-regulated in AML and up-regulated after activation of the non-classical Wnt signaling pathway. Conclusion: In this study, clonal heterogeneity of HSC-Prog cells in AML was identified, non-classical wnt signaling pathways associated with AML were identified, and it was verified that HLA-A could be upregulated by activation of non-classical wnt signaling, thereby increasing antigen presentation.

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