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1.
Exp Physiol ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643470

RESUMO

Traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. We unveiled the diagnostic value of serum NLRP3, metalloproteinase-9 (MMP-9) and interferon-γ (IFN-γ) levels in post-craniotomy intracranial infections and hydrocephalus in patients with severe craniocerebral trauma to investigate the high risk factors for these in patients with TBI, and the serological factors predicting prognosis, which had a certain clinical predictive value. Study subjects underwent bone flap resection surgery and were categorized into the intracranial infection/hydrocephalus/control (without postoperative hydrocephalus or intracranial infection) groups, with their clinical data documented. Serum levels of NLRP3, MMP-9 and IFN-γ were determined using ELISA kits, with their diagnostic efficacy on intracranial infections and hydrocephalus evaluated by receiver operating characteristic curve analysis. The independent risk factors affecting postoperative intracranial infections and hydrocephalus were analysed by logistic multifactorial regression. The remission after postoperative symptomatic treatment was counted. The intracranial infection/control groups had significant differences in Glasgow Coma Scale (GCS) scores, opened injury, surgical time and cerebrospinal fluid leakage, whereas the hydrocephalus and control groups had marked differences in GCS scores, cerebrospinal fluid leakage and subdural effusion. Serum NLRP3, MMP-9 and IFN-γ levels were elevated in patients with post-craniotomy intracranial infections/hydrocephalus. The area under the curve values of independent serum NLRP3, MMP-9, IFN-γ and their combination for diagnosing postoperative intracranial infection were 0.822, 0.722, 0.734 and 0.925, respectively, and for diagnosing hydrocephalus were 0.865, 0.828, 0.782 and 0.957, respectively. Serum NLRP3, MMP-9 and IFN-γ levels and serum NLRP3 and MMP-9 levels were independent risk factors influencing postoperative intracranial infection and postoperative hydrocephalus, respectively. Patients with hydrocephalus had a high remission rate after postoperative symptomatic treatment. Serum NLRP3, MMP-9 and IFN-γ levels had high diagnostic efficacy in patients with postoperative intracranial infection and hydrocephalus, among which serum NLRP3 level played a major role.

2.
IEEE Trans Biomed Eng ; PP2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470574

RESUMO

Some classification studies of brain-computer interface (BCI) based on speech imagery show potential for improving communication skills in patients with amyotrophic lateral sclerosis (ALS). However, current research on speech imagery is limited in scope and primarily focuses on vowels or a few selected words. In this paper, we propose a complete research scheme for multi-character classification based on EEG signals derived from speech imagery. Firstly, we record 31 speech imagery contents, including 26 alphabets and 5 commonly used punctuation marks, from seven subjects using a 32-channel electroencephalogram (EEG) device. Secondly, we introduce the wavelet scattering transform (WST), which shares a structural resemblance to Convolutional Neural Networks (CNNs), for feature extraction. The WST is a knowledge-driven technique that preserves high-frequency information and maintains the deformation stability of EEG signals. To reduce the dimensionality of wavelet scattering coefficient features, we employ Kernel Principal Component Analysis (KPCA). Finally, the reduced features are fed into an Extreme Gradient Boosting (XGBoost) classifier within a multi-classification framework. The XGBoost classifier is optimized through hyperparameter tuning using grid search and 10-fold cross-validation, resulting in an average accuracy of 78.73% for the multi-character classification task. We utilize t-Distributed Stochastic Neighbor Embedding (t-SNE) technology to visualize the low-dimensional representation of multi-character speech imagery. This visualization effectively enables us to observe the clustering of similar characters. The experimental results demonstrate the effectiveness of our proposed multi-character classification scheme. Furthermore, our classification categories and accuracy exceed those reported in existing research.

3.
J Am Chem Soc ; 146(9): 5952-5963, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38408428

RESUMO

The ability of alkylamines to spontaneously liberate hydride ions is typically restrained, except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular hydride transfer reactions of alkylamines under mild conditions. Besides transformations of small molecules, these reactions enable unique late-stage modification of complex peptides. Mechanistic investigations uncover that the key to these intermolecular hydride transfer processes lies in the accommodating conformation of solvent-mediated macrocyclic transition states, where the aggregates of HFIP molecules act as dexterous proton shuttles. Importantly, negative hyperconjugation between the lone electron pair of nitrogen and the antibonding orbital of amine's α C-H bond plays a critical role in the C-H activation, promoting its hydride liberation.

4.
Signal Transduct Target Ther ; 9(1): 37, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38360862

RESUMO

The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.


Assuntos
Doenças Neurodegenerativas , Probióticos , Humanos , Encéfalo/metabolismo , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/metabolismo , Eixo Encéfalo-Intestino , Probióticos/uso terapêutico , Prebióticos
5.
Angew Chem Int Ed Engl ; 63(16): e202318893, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38376389

RESUMO

α-Ketoaldehydes play versatile roles in the ubiquitous natural processes of protein glycation. However, leveraging the reactivity of α-ketoaldehydes for biomedical applications has been challenging. Previously, the reactivity of α-ketoaldehydes with guanidine has been harnessed to design probes for labeling Arg residues on proteins in an aqueous medium. Herein, a highly effective, broadly applicable, and operationally simple protocol for stapling native peptides by crosslinking two amino groups through diverse imidazolium linkers with various α-ketoaldehyde reagents is described. The use of hexafluoroisopropanol as a solvent facilitates rapid and clean reactions under mild conditions and enables unique selectivity for Lys over Arg. The naturally occurring GOLD/MOLD linkers have been expanded to encompass a wide range of modified glyoxal-lysine dimer (OLD) linkers. In a proof-of-concept trial, these modular stapling reactions enabled a convenient two-round strategy to streamline the structure-activity relationship (SAR) study of the wasp venom peptide anoplin, leading to enhanced biological activities.


Assuntos
Glioxal , Lisina , Glioxal/química , Lisina/química , Aminas , Aldeídos , Peptídeos , Reagentes de Ligações Cruzadas/química
6.
Int J Med Sci ; 21(2): 277-283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169716

RESUMO

Objective: This study aimed to investigate the association between serum potassium variability and 60-day mortality and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients following the coronavirus disease 2019 (COVID-19) infection. Methods: We conducted a retrospective study on MHD patients treated at the affiliated hospital of Qingdao University hemodialysis center who were infected with the novel coronavirus between December 1, 2022, and January 31, 2023. Baseline characteristics of patients were collected from electronic medical records. Kaplan-Meier survival analysis was used to obtain patient survival probabilities, and multivariate Cox hazard regression models and binary Logistic regression models were used to obtain hazard ratios (HR), odds ratios (OR), and 95% confidence intervals (95% CI) between exposure and outcomes. Results: A total of 296 patients were included in this study, with a mean age of 57.2±16.3 years, and 59.8% were male. The 60-day mortality rate was 10.8%, and the incidence of CVD was 32.8%. Kaplan-Meier curves showed that a higher potassium variability coefficient was associated with higher all-cause mortality (P = 0.024). After adjusting for potential confounders, multivariate Cox regression analysis showed that the HR for 60-day mortality in the Q4 group compared to the Q1 group was 2.06 (95% CI = 1.03-4.09, P = 0.040), and binary Logistic regression analysis showed that the OR for 60-day CVD in the Q4 group compared to the Q1 group was 4.09 (95% CI = 1.52-10.97, P = 0.005). Conclusion: Increased serum potassium variability in MHD patients after COVID-19 infection significantly increased the likelihood of 60-day mortality and CVD.


Assuntos
COVID-19 , Doenças Cardiovasculares , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , COVID-19/complicações , Diálise Renal/efeitos adversos , Potássio
7.
Mol Neurobiol ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296899

RESUMO

Heat stroke (HS) is a severe medical condition characterized by a systemic inflammatory response that may precipitate multi-organ dysfunction, with a particular predilection for inducing profound central nervous system impairments. We aim to employ bioinformatics techniques for the retrieval and analysis of genes associated with heat stroke-induced neurological damage. We performed a comprehensive analysis of the GSE64778 dataset from the Sequence Read Archive, resulting in the identification of 1178 significantly differentially expressed genes (DEGs). We retrieved 2914 genes associated with heat stroke from the GeneCards database and 2377 genes associated with heat stroke from the Comparative Toxicogenomics Database (CTD). The intersection of the top 300 DEGs in the GSE64778 dataset intersected with the search results of GeneCards and CTD, yielding 25 final candidates for DEGs associated with heat stroke. Gene Ontology functional annotation results indicated that the target genes were mainly involved in apoptosis, stress response, and negative regulation of cellular processes and function in processes such as protein dimerization and protein binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed a predominant enrichment of candidate target genes within the PI3K-AKT signaling pathway. Subsequent protein-protein interaction network analysis highlighted HSP90aa1 as a central gene, indicating its pivotal role by possessing the highest number of edges among the genes enriched in the PI3K-AKT signaling pathway. Quantitative reverse transcription-polymerase chain reaction analysis performed on blood samples from patients validated the expression of Hsp90aa1 in individuals exhibiting early neurological damage in HS, consistent with the findings from the mRNA bioinformatics analysis. Additionally, the bioinformatics analysis of the upstream microRNAs (miRNAs) regulating HSP90aa1 and the target miRNAs associated with candidate long non-coding RNAs (lncRNAs) identified three lncRNAs, eight miRNAs, and one mRNA in the regulatory network. The DIANA Tools database and algorithms were employed for pathway enrichment and correlation analysis, revealing a significant association between LOC102547734 and MIR-206-3p, with the latter being identified as a target binding site Moreover, the analysis unveiled a correlation between MIR-206-3p and HSP90aa1, implicating the latter as a potential target binding site within the regulatory network.

8.
Adv Mater ; 36(6): e2305384, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37672674

RESUMO

Adoptive cell therapy has emerged as a promising approach for cancer treatment. However, the transfer of macrophages exhibits limited efficacy against solid tumors due to the dynamic cellular phenotypic shift from antitumor to protumor states within the immunosuppressive tumor microenvironment. In this study, a strategy of attaching bacteria to macrophages (Mø@bac) is reported that endows adoptively infused macrophages with durable stimulation by leveraging the intrinsic immunogenicity of bacteria. These attached bacteria, referred to as backpacks, are encapsulated with adhesive nanocoatings and can sustainably control the cellular phenotypes in vivo. Moreover, Mø@bac can repolarize endogenous tumor-associated macrophages, leading to a more robust immune response and thus reducing the tumor progression in a murine 4T1 cancer model without any side effects. This study utilizing bacteria as cellular backpacks opens a new avenue for the development of cell therapies.


Assuntos
Neoplasias , Camundongos , Animais , Neoplasias/patologia , Macrófagos , Transferência Adotiva , Bactérias , Microambiente Tumoral , Imunoterapia
9.
J Pediatr Nurs ; 75: 31-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38101309

RESUMO

PROBLEM: Most rare diseases occur in childhood and are difficult to diagnose and treat. The caregivers are faced with the challenge of providing care to the children afflicted with these rare diseases, resulting in a significant burden of care and an altered family dynamic. ELIGIBILITY CRITERIA: A meta-synthesis review was conducted to explore the caregivers' experience of children with rare diseases using eight electronic databases PubMed, Web of Science, the Cochrane Library, EMBASE, VIP database, Wan Fang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure from each database's inception to October 5, 2023. SAMPLE: 4207 records were identified and 20 eligible studies were included. RESULTS: Three themes emerged: (1) Life is changed by "rare"; (2) many unmet needs; (3) Strive to adapt and grow. CONCLUSIONS: Caregivers of children with rare diseases are full of stress and challenges in the process of caring for them, and their lives have changed greatly due to "rare". Appropriate measures need to be taken to reduce the burden on caregivers. IMPLICATIONS: According to the findings, both the medical and health systems, as well as society, should pay attention to the care load and unmet requirements of carers of children with rare diseases, and offer them with practical supportive services. Finally, it can improve the quality of life for caregivers and families of children with rare diseases, as well as stimulate the development of rare diseases.


Assuntos
Cuidadores , Qualidade de Vida , Criança , Humanos , Pesquisa Qualitativa , Doenças Raras
10.
World J Clin Cases ; 11(32): 7770-7777, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38073695

RESUMO

BACKGROUND: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort. AIM: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD. METHODS: Eighty AECOPD patients were included in the study. The patients were in the intensive care department of our hospital from October 2019 to October 2021. The patients were divided into the control and treatment groups according to the different treatment methods with 40 patients in each group. Differences in patient comfort, blood gas analysis and infection indices were analyzed between the two groups. RESULTS: After treatment, symptoms including nasal, throat and chest discomfort were significantly lower in the treatment group compared to the control group on the 3rd and 5th days (P < 0.05). Before treatment, the PaO2, PaO2/FiO2, PaCO2, and SaO2 in the two groups of patients were not significantly different (P > 0.05). After treatment, the same indicators were significantly improved in both patient groups but had improved more in the treatment group compared to the control group (P < 0.05). After treatment, the white blood cell count, and the levels of C-reactive protein and calcitonin in patients in the treatment group were significantly higher compared to patients in the control group (P < 0.05). CONCLUSION: HFNC treatment can improve the ventilation of AECOPD patients whilst also improving patient comfort, and reducing complications. HFNC is a clinically valuable technique for the treatment of AECOPD.

11.
ACS Nano ; 17(24): 24947-24960, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38055727

RESUMO

Cancer vaccines have been considered to be an alternative therapeutic strategy for tumor therapy in the past decade. However, the popularity and efficacy of cancer vaccines were hampered by tumor antigen heterogeneity and the impaired function of cross-presentation in the tumor-infiltrating dendritic cells (TIDCs). To overcome these challenges, we engineered an in situ nanovaccine (named as TPOP) based on lipid metabolism-regulating and innate immune-stimulated nanoparticles. TPOP could capture tumor antigens and induce specific recognition by TIDCs to be taken up. Meanwhile, TPOP could manipulate TIDC lipid metabolism and inhibit de novo synthesis of fatty acids, thus improving the ability of TIDCs to cross-present by reducing their lipid accumulation. Significantly, intratumoral injection of TPOP combined with pretreatment with doxorubicin showed a considerable therapeutic effect in the subcutaneous mouse colorectal cancer model and melanoma model. Moreover, in combination with immune checkpoint inhibitors, such TPOP could markedly inhibit the growth of distant tumors by systemic antitumor immune responses. This work provides a safe and promising strategy for improving the function of immune cells by manipulating their metabolism and activating the immune system effectively for in situ cancer vaccines.


Assuntos
Vacinas Anticâncer , Melanoma , Nanopartículas , Neoplasias , Camundongos , Animais , Nanovacinas , Células Dendríticas , Metabolismo dos Lipídeos , Imunoterapia , Neoplasias/tratamento farmacológico , Melanoma/tratamento farmacológico , Antígenos de Neoplasias/metabolismo , Modelos Animais de Doenças
12.
Heliyon ; 9(9): e20296, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809651

RESUMO

We investigate the effect of the adoption of electric vehicles (EVs) on CO2 emissions using spatial econometric models and have three findings. First, there are spatial spillover effects of EV adoption on CO2 emissions, implying that the CO2 mitigation of a city depends on local sales of EVs and sales of EVs in neighboring cities. A 1% increase in the sale of EVs in a city can reduce CO2 emissions locally by 0.096% and by 0.087% in a nearby city. Second, EVs indirectly impact CO2 emissions through the substitution effect, energy consumption effect, and technological effect. The overall impact of EV adoption on CO2 emissions is negative. Finally, we demonstrate the moderating effect of urban energy structure on EVs' CO2 emissions mitigation. A 1% increase in the proportion of renewable energy generation increases the decarbonization of EVs by 0.036%. These findings provide policy implications for the coordinated development of EV market and energy system.

13.
Planta ; 258(3): 58, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37528331

RESUMO

Extensive spaceflight life investigations (SLIs) have revealed observable space effects on plants, particularly their growth, nutrition yield, and secondary metabolite production. Knowledge of these effects not only facilitates space agricultural and biopharmaceutical technology development but also provides unique perspectives to ground-based investigations. SLIs are specialized experimental protocols and notable biological phenomena. These require specialized databases, leading to the development of the NASA Science Data Archive, Erasmus Experiment Archive, and NASA GeneLab. The increasing interests of SLIs across diverse fields demand resources with comprehensive content, convenient search facilities, and friendly information presentation. A new database SpaceLID (Space Life Investigation Database http://bidd.group/spacelid/ ) was developed with detailed menu search tools and categorized contents about the phenomena, protocols, and outcomes of 459 SLIs (including 106 plant investigations) of 92 species, where 236 SLIs and 57 plant investigations are uncovered by the existing databases. The usefulness of SpaceLID as an SLI information source is illustrated by the literature-reported analysis of metabolite, nutrition, and symbiosis variations of spaceflight plants. In conclusion, this study extensively investigated the impact of the space environment on plant biology, utilizing SpaceLID as an information source and examining various plant species, including Arabidopsis thaliana, Brassica rapa L., and Glycyrrhiza uralensis Fisch. The findings provide valuable insights into the effects of space conditions on plant physiology and metabolism.


Assuntos
Arabidopsis , Brassica rapa , Voo Espacial , Ausência de Peso , Plantas , Biologia
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 999-1004, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37551468

RESUMO

OBJECTIVE: To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients. METHODS: A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed. RESULTS: The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients. CONCLUSION: In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.


Assuntos
Cadeias Leves Substitutas da Imunoglobulina , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Criança , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Relevância Clínica , Intervalo Livre de Doença , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Prednisona/uso terapêutico , Prognóstico , Recidiva , Cadeias Leves Substitutas da Imunoglobulina/genética
15.
NMR Biomed ; 36(10): e4991, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37392139

RESUMO

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.


Assuntos
Concussão Encefálica , Substância Branca , Humanos , Concussão Encefálica/diagnóstico por imagem , Estudos Transversais , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Biomarcadores , Encéfalo/diagnóstico por imagem
16.
J Med Chem ; 66(14): 9363-9375, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37424079

RESUMO

The farnesoid X receptor (FXR) is a ligand-activated nuclear receptor. Activation of FXR significantly impacts the expressions of the pivotal genes involved in bile acid metabolism, inflammation, fibrosis, and homeostasis of lipid and glucose, leading to considerable interests in developing FXR agonists for the treatment of nonalcoholic steatohepatitis (NASH) or other FXR-relevant diseases. Herein, we describe the design, optimization, and characterization of a series of N-methylene-piperazinyl derivatives as the nonbile acid FXR agonists. Particularly, compound 23 (HPG1860), a potent full FXR agonist, shows high selectivity, favorable ADME and pharmacokinetics profile, along with favorable in vivo activities demonstrated in both rodent PD model and HFD-CCl4 model and is currently in clinical development in patients with NASH in phase II.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Citoplasmáticos e Nucleares , Ácidos e Sais Biliares , Inflamação , Relação Estrutura-Atividade
17.
BMC Genomics ; 24(1): 426, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516822

RESUMO

Comprehensive analysis of multiple data sets can identify potential driver genes for various cancers. In recent years, driver gene discovery based on massive mutation data and gene interaction networks has attracted increasing attention, but there is still a need to explore combining functional and structural information of genes in protein interaction networks to identify driver genes. Therefore, we propose a network embedding framework combining functional and structural information to identify driver genes. Firstly, we combine the mutation data and gene interaction networks to construct mutation integration network using network propagation algorithm. Secondly, the struc2vec model is used for extracting gene features from the mutation integration network, which contains both gene's functional and structural information. Finally, machine learning algorithms are utilized to identify the driver genes. Compared with the previous four excellent methods, our method can find gene pairs that are distant from each other through structural similarities and has better performance in identifying driver genes for 12 cancers in the cancer genome atlas. At the same time, we also conduct a comparative analysis of three gene interaction networks, three gene standard sets, and five machine learning algorithms. Our framework provides a new perspective for feature selection to identify novel driver genes.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Estudos de Associação Genética , Aprendizado de Máquina , Mapeamento de Interação de Proteínas
18.
Int Urol Nephrol ; 55(10): 2421-2429, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37368087

RESUMO

INTRODUCTION: Sanjin Paishi Decoction (SJPSD) has positive effects on stone prevention; however, there is a lack of convincing evidence in the prevention of calcium oxalate stones. This study aimed investigates the effect of SJPSD on calcium oxalate stones and to explore its mechanism. METHODS: The rat model of calcium oxalate stones was established and rats were treated with different doses of SJPSD. The pathological damage of kidney tissues was observed by HE staining, the deposition of calcium oxalate crystals in kidney tissues was examined by Von Kossa staining, and the levels of creatinine (CREA), urea (UREA), calcium (Ca), phosphorus (P), and magnesium (Mg) in serum were analyzed biochemically, the levels of IL-1ß, IL-6, and TNF-α in serum were measured by ELISA, and the protein expression of Raf1, MEK1, p-MEK1, ERK1/2, p-ERK1/2, and Cleaved caspase-3 in kidney tissues was analyzed by Western blot. Moreover, the changes in gut microbiota were analyzed by 16S rRNA sequencing. RESULTS: SJPSD attenuated the pathological damage of renal tissues, reduced the levels of CREA, UREA, Ca, P, and Mg, and inhibited the expression of Raf1, p-MEK1, p-ERK1/2, and Cleaved caspase-3 in renal tissues (P < 0.05). SJPSD treatment affected the composition of intestinal microbiota in rats with calcium oxalate stones. CONCLUSION: The mechanism of SJPSD inhibition of calcium oxalate stone injury in rats may be related to the inhibition of the MAPK signaling pathway and regulation of gut microbiota imbalance.


Assuntos
Microbioma Gastrointestinal , Cálculos Renais , Ratos , Animais , Oxalato de Cálcio/metabolismo , Cálculos Renais/tratamento farmacológico , Cálculos Renais/prevenção & controle , Cálculos Renais/metabolismo , Caspase 3/metabolismo , Sistema de Sinalização das MAP Quinases , RNA Ribossômico 16S , Cálcio , Transdução de Sinais , Ureia
19.
J Nurs Meas ; 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353318

RESUMO

Background and Purpose: Compassion is increasingly considered essential to quality nursing care and is a concept that is strongly embedded across cultures, including Chinese culture. The Patient Compassion Model (PCM) depicts the unique yet overlapping domains of compassion. The Sinclair Compassion Questionnaire (SCQ) was directly developed and validated from this empirical model. In this study, we sought to establish initial validation of a translated SCQ among Mandarin-speaking patients by assessing the transferability of the PCM and the clinical sensibility of the SCQ. Methods: Forward and back-translation of the PCM and SCQ were performed in accordance with World Health Organization guidelines. Qualitative interviews were used to assess the transferability of the PCM with conceptualizations of compassion within a Chinese context. Cognitive interviews were conducted to assess the clarity, readability, wording, questions, and response scales of the Mandarin translation of the SCQ. Qualitative data were analyzed using constant comparative analysis, and cognitive interviews were analyzed using framework analysis. Results: The original categories of the PCM were verified in this Mandarin-speaking patient population. Specifically, participants' understandings of compassion is described as consisting of healthcare provider virtues, emphasizing the importance of a virtuous response that sought to understand the individual and their unique needs, to relationally communicate from a place of shared humanity and to ameliorate suffering. Participants were able to answer, comprehend, and endorse all 15 Mandarin SCQ items, resulting in no modifications to the Mandarin SCQ. Conclusions: This study provides initial validation of the Mandarin SCQ and PCM. Future studies should consider further establishing the validity and reliability of the Mandarin SCQ among a larger Chinese patient population.

20.
Mol Neurobiol ; 60(8): 4450-4471, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37115405

RESUMO

Spinal cord injury (SCI) is a devastating neurological disorder characterized by high morbidity and disability. However, there is still a lack of effective treatments for it. The identification of drugs that promote autophagy and inhibit apoptosis in neurons is critical for improving patient outcomes following SCI. Previous studies have shown that increasing the activity of silent information regulator 1 (SIRT1) and downstream protein AMP-activated protein kinase (AMPK) in rat models of SCI is highly neuroprotective. Oxymatrine (OMT), a quinolizidine alkaloid, has exhibited neuroprotective effects in various central nervous system (CNS) diseases. However, its explicit effect and molecular mechanism in SCI are still unclear. Herein, we aimed to investigate the therapeutic effects of OMT and explore the potential role of autophagy regulation following SCI in rats. A modified compressive device (weight 35 g, time 5 min) was applied to induce moderate SCI in all groups except the sham group. After treatment with drugs or vehicle (saline), our results indicated that OMT treatment significantly reduced the lesion size, promoted survival of motor neurons, and subsequently attenuated motor dysfunction following SCI in rats. OMT significantly enhanced autophagy activity, inhibited apoptosis in neurons, and increased SIRT1 and p-AMPK expression levels. Interestingly, these effects of OMT on SCI were partially prevented by co-treatment with SIRT1 inhibitor EX527. Furthermore, combining OMT with the potent autophagy inhibitor chloroquine (CQ) could effectively abolish its promotion of autophagic flux. Taken together, these data revealed that OMT exerts a neuroprotective role in functional recovery against SCI in rats, and these effects are potentially associated with OMT-induced activation of autophagy via the SIRT1/AMPK signaling pathway.


Assuntos
Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Ratos , Animais , Ratos Sprague-Dawley , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 1/metabolismo , Traumatismos da Medula Espinal/patologia , Autofagia , Neurônios Motores/metabolismo , Apoptose , Medula Espinal/patologia , Recuperação de Função Fisiológica
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