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1.
J Nurs Adm ; 53(5): 271-276, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37098867

RESUMO

OBJECTIVE: This study aimed to describe the current situation and explore overwork predictors among ICU nurses in China. BACKGROUND: Overwork is a comprehensive condition of labor where employees work for extended periods with high intensity and high pressure, which can negatively affect their health. Limited literature exists regarding the prevalence, characteristics, professional identity, and environment of overwork among ICU nurses. METHODS: A cross-sectional design study was conducted. The Professional Identification Scale for Nurses, the Practice Environment Scale of the Nursing Work Index, and the Overwork Related Fatigue Scale (ORFS) were used. To explore relationships between variables, univariate analysis or bivariate correlations were used. Multiple regression was used to identify predictors of overwork. RESULTS: Almost 85% of nurses were categorized as overworked, of which, 30% were moderately to severely overworked. Gender, form of employment, stress related to ICU nursing technology and equipment updates, nurses' professional identity, and nurse working environment accounted for 36.6% in the ORFS. CONCLUSIONS: Overwork is common among ICU nurses. Nurse managers need to develop and implement strategies to better support nurses to prevent overwork.


Assuntos
Enfermeiros Administradores , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Humanos , Estudos Transversais , Fadiga , Fatores de Risco , Unidades de Terapia Intensiva , Inquéritos e Questionários , Satisfação no Emprego
2.
Eur J Neurosci ; 55(7): 1709-1723, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35239205

RESUMO

Microglia are the static resident cells possessing the phagocytic properties in the central nervous system (CNS). In many relevant studies, the immortalized murine microglial cell line BV2 has been used as a tool in primary microglia (PM) relevant studies. Microglia participate in neuroinflammation by converting into M1- and M2-like phenotypes. In this study, we established M1- and M2-like phenotype response models by exposing PM and BV2 cells to lipopolysaccharides (LPS) and interlukin-4 (IL-4), respectively, and discovered the proteomic differences between the two types of microglia. It turned out that the BV2 cell responses to LPS and IL-4 were narrower and weaker than that of PM. In addition, irradiation, which has been shown to activate microglia and induces neuroinflammation, was also used as a treatment in this study. The results showed that BV2 cells have stronger capacity of DNA damage repair. Besides, irradiation had a negative effect on the regulation of KEGG pathways such as proteasome, ribosome, oxidative phosphorylation and TCA cycle in both cells. Furthermore, the KEGG pathways including cell cycle and DNA replication (significantly downregulated), and antigen processing and presentation and FC γ R mediated phagocytosis (significantly up-regulated) were only found in irradiated PM. These data demonstrate that PM is more fragile to irradiation. Results in this study indicate that BV2 cells only partially model PM, and thus, using BV2 in microglia related studies should be carefully considered.


Assuntos
Lipopolissacarídeos , Microglia , Animais , Linhagem Celular , Interleucina-4/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Proteômica
3.
Cancer Sci ; 112(8): 3005-3017, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34028936

RESUMO

Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death-1/programmed cell death-ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non-small-cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes' signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti-programmed cell death-1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression-free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8+ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor-based immunotherapy.


Assuntos
Bactérias/classificação , Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Pulmonares/terapia , Análise de Sequência de DNA/métodos , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Quimiorradioterapia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/microbiologia , Masculino , Metástase Neoplásica , Filogenia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Streptococcus/isolamento & purificação , Análise de Sobrevida , Resultado do Tratamento
4.
Org Biomol Chem ; 19(39): 8607-8612, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34569587

RESUMO

The chiral keto-substituted propargylamines are an essential class of multifunctional compounds in the field of organic and pharmaceutical synthesis and have attracted considerable attention, but the related synthetic approaches remain limited. Therefore, a concise and efficient method for the enantioselective synthesis of ß-keto propargylamines via chiral phosphoric acid-catalyzed asymmetric Mannich reaction between ß-keto acids and C-alkynyl N-Boc N,O-acetals as easily available C-alkynyl imine precursors has been demonstrated here, affording a broad scope of ß-keto N-Boc-propargylamines in high yields (up to 97%) with generally high enantioselectivities (up to 97 : 3 er).

5.
J Nat Prod ; 83(11): 3471-3475, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33180498

RESUMO

Penisarins A (1) and B (2), sesquiterpene coumarins with an unusual tricyclic sesquiterpene system, were isolated from endophytic Penicillium sp. KMU18029. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 2 showed significant cytotoxicities against two human cancer cell lines, HL-60 and SMMC-7721, with IC50 values of 3.6 ± 0.2 and 3.7 ± 0.2 µM, respectively.


Assuntos
Cumarínicos/isolamento & purificação , Penicillium/química , Sesquiterpenos/isolamento & purificação , Linhagem Celular Tumoral , Dicroísmo Circular , Cumarínicos/química , Cristalografia por Raios X , Humanos , Estrutura Molecular , Sesquiterpenos/química
6.
Med Sci Monit ; 26: e926669, 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32948737

RESUMO

BACKGROUND The aim of this study was to analyze the risk factors of pressure injury (PI) in critically ill patients with cancer to build a risk prediction model for PI. MATERIAL AND METHODS Between January 2018 and December 2019, a total of 486 critically ill patients with cancer were enrolled in the study. Univariate analysis and binary logistic regression analysis were used to explore risk factors. Then, a risk prediction equation was constructed and a receiver operator characteristic (ROC) curve analysis model was used for prediction. RESULTS Of the 486 critically ill patients with cancer, 15 patients developed PI. Risk factors found to have a significant impact on PI in critically ill patients with cancer included the APACHE II score (P<0.001), semi-reclining position (P=0.006), humid environment/moist skin (P<0.001), and edema (P<0.001). These 4 independent risk factors were used in the regression equation, and the risk prediction equation was constructed as Z=0.112×APACHE II score +2.549×semi-reclining position +2.757×moist skin +1.795×edema-9.086. From the ROC curve analysis, the area under the curve (AUC) was 0.938, sensitivity was 100.00%, specificity was 83.40%, and Youden index was 0.834. CONCLUSIONS The PI risk prediction model developed in this study has a high predictive value and provides a basis for PI prevention and treatment measures for critically ill patients with cancer.


Assuntos
Modelos Biológicos , Neoplasias/epidemiologia , Úlcera por Pressão/epidemiologia , Idoso , China/epidemiologia , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
7.
J Stroke Cerebrovasc Dis ; 27(7): e138-e143, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29571757

RESUMO

BACKGROUND: Clinically infarction of the columns of the fornix is very rare. It is also easy to be overlooked during imaging examination due to the special anatomical localization and features of columns of the fornix. In the meantime, with memory disorder to be its most prominent manifestation, it is very easily false diagnosed as other diseases when the lesion focus is overlooked, causing unnecessary invasive examinations like cerebrospinal fluid tests. METHODS: Case report and Literature review. RESULTS: We presented a 66-year-old woman with memory impairment due to a small acute infarction of the columns of the fornix. Through her diagnosis and treatment, we believed that early diagnosis and treatment were important to these patients who were enduring the disease. In addition, literature review informed us that for those unwilling to undergo cerebral angiography or for small cerebrovascular lesions that cannot be detected by angiography, 7T magnetic resonance imaging (MRI) might be an ideal diagnostic method. CONCLUSION: This case illustrated the significance of MRI in diagnosis for patients with acute memory impairment. When reading MRI results, one needs to pay attention to identify small lesions at special locations. In addition, cerebral apoplexy is still the first consideration of diagnosis when acute memory impairment occurs in patients with cerebrovascular disease risk factors.


Assuntos
Infarto Encefálico/complicações , Fórnice/irrigação sanguínea , Transtornos da Memória/etiologia , Idoso , Encéfalo/diagnóstico por imagem , Infarto Encefálico/diagnóstico , Infarto Encefálico/psicologia , Infarto Encefálico/terapia , Feminino , Humanos , Transtornos da Memória/diagnóstico , Transtornos da Memória/terapia
8.
J Org Chem ; 81(18): 8296-305, 2016 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-27571411

RESUMO

α,ß-Unsaturated ynones have historically been used as Michael acceptors in conjugate addition reactions. Herein, we have demonstrated for the first time that ynones can be harnessed as Michael donors for use in catalytic asymmetric conjugate addition reactions by strategically introducing a CO2t-Bu group as a multitasking directing group. Furthermore, this concept has enabled designer ynones as versatile synthetic equivalents of both α' anions of ynones and γ monoanions of 1,3-diketones, which are synthetically valued but difficult to generate. The first catalytic enantioselective conjugate addition of ynones as Michael donors has been realized in good yields with high enantioselectivities. A unified approach to regiospecifically and chemo- and enantioselectively access hitherto elusive γ-Michael adducts of 1,3-diketones has been achieved in a divergent manner. The strategy described here by exploring new reactivity and creating new reagents holds great potential applications in other still unsolved transformations.

9.
Chemistry ; 20(20): 6112-9, 2014 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-24700723

RESUMO

We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition.


Assuntos
Alcaloides de Amaryllidaceae/síntese química , Indóis/química , Fenantridinas/síntese química , Alcaloides de Amaryllidaceae/química , Catálise , Indóis/síntese química , Fenantridinas/química , Estereoisomerismo
10.
Cent Eur J Immunol ; 39(2): 216-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26155127

RESUMO

Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 ±1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 ±1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p < 0.01). Moreover, there was a significant positive correlation between the concentrations of soluble CD28 in plasma and levels of FT3 (r = 0.663), FT4 (r = 0.624) and TRAb (r = 0.728) in serum, but a negative correlation was found between sCD28 levels and TSH (r = -0.726). Through in vitro experiments we observed that engagement of soluble CD28 protein and B7-1/B7-2 molecules expressed on dendritic cells could exert the secretion of cytokine IL-6, which may promote the production of autoantibody and aggravate Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis.

11.
Eur J Pharmacol ; 968: 176417, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38346470

RESUMO

Ten-eleven translocation protein 1 (Tet1) is associated with the regulation of depression-like behaviour in mice. However, the mechanism by which Tet1 affects neurogenesis in mice to regulate depression-like behaviours remains unclear. In this study, the chronic social defeat stress (CSDS) paradigm was constructed by overexpressing Tet1 protein in the mouse hippocampus, and 5-ethynyl-2'-deoxyuridine (EdU, 50 mg/kg) was injected on the seventh day to explore the mechanism of the regulation of the Tet1/Delta-like protein 3 (DLL3)/Notch1 protein pathway in mice hippocampal neurogenesis and its influence on depression-like behaviour. Following CSDS, the expression level of Tet1 decreased significantly. Moreover, due to the downregulation of Tet1 protein, the maintenance of the DNA methylation and demethylation balance was affected, resulting in a significant increase in the methylation levels of Notch1 and DLL3 and a significant decrease in the protein expression levels of DLL3, Notch1, and brain-derived neurotrophic factor (BDNF). At the same time, the proliferation and differentiation of neurones were affected, which was related to a significant decrease in the number of EdU+, doublecortin (DCX)+, and Ki67+ cells in the hippocampus of the CSDS model mice. When the Tet1 protein was overexpressed in the mouse hippocampus, DLL3 and Notch1 protein expression levels were upregulated, promoting hippocampal neurogenesis and alleviating depression-like behaviour in mice. These findings suggest that regulation of the hippocampal Tet1/DLL3/Notch1 protein pathway to influence neurogenesis may be a therapeutic strategy for depression.


Assuntos
Depressão , Receptor Notch1 , Camundongos , Animais , Receptor Notch1/metabolismo , Transdução de Sinais , Neurogênese/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL
12.
J Ethnopharmacol ; 327: 117973, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38403002

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: It has been found that pilose antler peptide has an antidepressant effect on depression. However, the exact molecular mechanism of its antidepressant effect is still unclear. AIM OF THE STUDY: The study sought to determine the impact of monomeric pilose antler peptide (PAP; sequence LVLVEAELRE) on depression as well as investigate potential molecular mechanisms. MATERIALS AND METHODS: Chronic unexpected mild stress (CUMS) was used to establish the model, and the effect of PAP on CUMS mice was detected by the behavioral test. The influence of PAP on neuronal cells and dendritic spine density was observed by immunofluorescence and Golgi staining. FGFR3 and the CaMKII-associated pathway were identified using quantitative real-time polymerase chain reaction, and Western blot analysis was utilized to measure their proteins and gene expression levels. Molecular docking and microscale thermophoresis were applied to detect the binding of PAP and FGFR3. Finally, the effect of FGFR3's overexpression on PAP treatment of depression was detected. RESULTS: PAP alleviated the changes in depressive behavior induced by CUMS, promoted the growth of nerve cells, and the density of dendritic spines was increased to its original state. PAP therapy successfully downregulated the expression of FGFR3 and ERK1/2 while upregulating the expression of CREB, BDNF, and CaMKII. CONCLUSION: Based on the current research, PAP has a therapeutic effect on depression brought on by CUMS by inhibiting FGFR3 expression and enhancing synaptic plasticity.


Assuntos
Depressão , Peptídeos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Camundongos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Simulação de Acoplamento Molecular , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Hipocampo/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças
13.
Fitoterapia ; 173: 105793, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38158161

RESUMO

Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Structurally, phometide A (1) represented the first example of C12 polyketide characterized by an unusual tetrahydrobenzofuran-3(2H)-one core with an α,ß-unsaturated ketone functionality, while phometide B (2) was an unprecedented molecule containing a 2-pentylcycloheptan-1-one scaffold. In an antimicrobial activity assay, phometide A (1) exhibited significant inhibitory activity against Staphylococcus aureus with MIC value of 4 µg/mL. Phometide B (2) showed moderate antifungal activity against Candida albicans with an MIC value of 16 µg/mL. Furthermore, compounds 1 and 2 were evaluated for their acetylcholinesterase inhibitory and cytotoxic activities.


Assuntos
Gastrodia , Policetídeos , Estrutura Molecular , Phoma , Acetilcolinesterase , Dicroísmo Circular
14.
BMC Neurol ; 13: 183, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24261578

RESUMO

BACKGROUND: A wealth of published studies have been published on association between Chlamydia pneumoniae (C.pneumoniae) infection and cerebrovascular (CV) disease, but the results were inconsistent. This meta-analysis provides a systematic review of the available evidence from all serological and pathological studies of CV disease and C.pneumoniae. METHODS: A comprehensive research was conducted of MEDLINE, EMBASE, CNKI, WanFang technological periodical database and reference lists of articles to identify eligible case-control and cohort studies. Odds radio (OR) was calculated for each study outcome. Random effect model was used as pooling method and publication bias was estimated for the results. RESULTS: Fifty-two published studies that met criteria were selected. In case control studies, an association between C.pneumoniae infection and CV disease was revealed by serum specific IgG (OR, 1.61; 95% CI: 1.34 to 1.94), serum IgA (OR, 2.33; 95% CI: 1.76 to 3.08) and PCR technique of C.pneumoniae in peripheral blood cells (OR, 1.90; 95% CI: 1.17 to 3.07). No significant association was found in serum anti-C.pneumonae IgM seropositivity or in-situ-detection of C.pneumoniae in arterial biopsies with CV disease. Subgroup analysis by available studies suggested that C.pneumoniae may paly a role in atherosclerotic stroke, but be less significant in stroke of cardioembolism or other etiologies. CONCLUSION: Association between C.pneumoniae infection and CV disease depends on the analytical method adopted, which seems stronger with stroke due to large artery atherosclerosis. Establishing a causal relationship between C.peumoniae infection and CV disease will require more prospective studies with combination of techniques and stratified by etiological subtypes.


Assuntos
Transtornos Cerebrovasculares/etiologia , Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae/patogenicidade , Transtornos Cerebrovasculares/microbiologia , Chlamydophila pneumoniae/genética , Bases de Dados Bibliográficas/estatística & dados numéricos , Humanos
15.
Lasers Med Sci ; 28(3): 725-34, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22714676

RESUMO

The aim of the present study was to determine the effects of low-level laser therapy (LLLT) on the homeostasis of reactive oxygen species (ROS) and expression of IGF-1 and TGF-ß1 in the gastrocnemius muscles of rats following contusion. Muscle regeneration involves cell proliferation, migration, and differentiation and is regulated by growth factors. A growing body of evidence suggests that LLLT promotes skeletal muscle regeneration and accelerates tissue repair. Adult male Sprague-Dawley rats (n=96) were randomly divided into three groups: control group (no lesion, untreated, n=6), contusion group (n=48), and contusion-plus-LLLT group (n=42). Gallium aluminum arsenide (GaAlAs) laser irradiation (635 nm; beam spot, 0.4 cm(2); output power, 7 mW; power density, 17.5 mW/cm(2); 20 min) was administered to the gastrocnemius contusion for 20 min daily for 10 days. Muscle remodeling was evaluated at 0 h and 1, 2, 3, 7, 14, 21, and 28 days after injury. Hematoxylin and eosin and Van Gieson staining were used to evaluate regeneration and fibrosis; muscle superoxide dismutase (SOD) and malondialdehyde (MDA) were detected via biochemical methods; expression of transforming growth factor beta-1 (TGF-ß1) and insulin-like growth factor-1 (IGF-1) were investigated via immunohistochemistry. The results showed that LLLT markedly promoted the regeneration of muscle and reduced scar formation. LLLT also significantly enhanced muscle SOD activity and significantly decreased muscle MDA levels 1, 2, and 3 days after injury. LLLT increased the expression of IGF-1 2, 3, and 7 days after injury and decreased the expression of IGF-1 21 and 28 days after injury. LLLT decreased the expression of TGF-ß1 3 and 28 days after injury but increased expression at 7 and 14 days after injury. Our study showed that LLLT could modulate the homeostasis of ROS and of the growth factors IGF-1 and TGF-ß1, which are known to play important roles in the repair process. This may constitute a new preventive approach to muscular fibrosis.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Terapia com Luz de Baixa Intensidade , Músculo Esquelético/lesões , Músculo Esquelético/efeitos da radiação , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização/efeitos da radiação , Animais , Fibrose , Homeostase/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Masculino , Malondialdeído/metabolismo , Músculo Esquelético/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Regeneração/fisiologia , Regeneração/efeitos da radiação , Superóxido Dismutase/metabolismo
16.
Neurol Res ; 45(4): 319-333, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36417294

RESUMO

OBJECTIVES: This study aims to explore the role of lncRNA TMPO-AS1 in ischemic stroke and corresponding mechanism. METHODS: Adult male C57BL/6 J mice were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, then TMPO-AS1 shRNA lentivirus were injected into ipsilateral striatum of mice. The neurological score and cerebral infarction volume were evaluatedHypoxia/glucose deprivation/reoxygenation (OGD/R)-induced BV2 cells were transfected with TMPO-AS1 shRNA (sh-TMPO-AS1) or together with pcDNA-INPP5D, as well as transfected with sh-PU.1 or together with pcDNA-INPP5D, then TMPO-AS1 level, the expression of PU.1 and INPP5D proteins, the secretion of inflammatory factors (TNF-α, IL-6 and IL-1ß), the levels of iNOS, CD68,Arg1 and CD206 mRNA were detected. RIP and PNA-pull down assays were used to detect the binding of TMPO-AS1 and PU.1, luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays were used to detect the binding activity of PU.1 and INPP5D. RESULTS: TMPO-AS1 level was increased in peripheral blood of ischemic stroke patients , brain tissues of MCAO/R model mice and OGD/R-induced BV2 cells. TMPO-AS1 interference inhibited the inflammation of OGD/R-induced BV2 cells. TMPO-AS1 also enhanced the nuclear accumulation of PU.1 by binding to the transcription factor PU.1, and promoted the transcriptional activation of INPP5D. The anti-inflammatory effects of TMPO-AS1 interference were reversed by INPP5D overexpression. In addition, TMPO-AS1 interference improved the infarct volume of MCAO mice, and improved sensorimotor and cognitive functions. CONCLUSION: INPP5D underexpression mediated by TMPO-AS1-PU.1 complex alleviated neuroinflammation after ischemic stroke.


Assuntos
AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Animais , Masculino , Camundongos , Infarto da Artéria Cerebral Média/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Doenças Neuroinflamatórias , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , RNA Interferente Pequeno , Acidente Vascular Cerebral/metabolismo
17.
Front Neurosci ; 17: 1177930, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250389

RESUMO

Background and purpose: The dynamic alterations in spontaneous neural activity of the brain during the acute phase of post-stroke aphasia (PSA) remain unclear. Therefore, in this study, dynamic amplitude of low-frequency fluctuation (dALFF) was applied to explore abnormal temporal variability in local functional activity of the brain during acute PSA. Materials and methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data from 26 patients with PSA and 25 healthy controls (HCs) were acquired. The sliding window method was used to assess dALFF, with the k-means clustering method used to identify dALFF states. The two-sample t-test was applied to compare differences in dALFF variability and state metrics between the PSA and HC groups. Results: (1) In the PSA group, greater variance of dALFF in the cerebellar network (CBN) and left fronto-temporo-parietal network (FTPN) was observed. (2) Three dALFF states were identified among all subjects. States 1 and 2 were identified in the PSA patients, and the two dALFF states shared a similar proportion. Moreover, the number of transitions between the two dALFF states was higher in the patients compared with that in HCs. Conclusion: The results of this study provide valuable insights into brain dysfunction that occurs during the acute phase (6.00 ± 3.52 days) of PSA. The observed increase in variability of local functional activities in CBN and left FTPN may be related to the spontaneous functional recovery of language during acute PSA, and it also suggests that cerebellum plays an important role in language.

18.
Eur J Med Res ; 28(1): 446, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37853442

RESUMO

BACKGROUND: To investigate the value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) within asymmetrical prominent veins sign (APVS) on susceptibility-weighted imaging predicting collateral circulation and prognosis in patients with acute anterior circulation ischemic stroke. METHOD: Patients with severe stenosis or occlusion of ICA or MCA M1, who underwent MRI within 72 h from stroke onset were reviewed. The Alberta Stroke Program Early CT Score was used to evaluate the volume of infarction on DWI, the degree of FVH and APVS. Spearman correlation analysis was used to evaluate the correlation between FVH and APVS. All patients were divided into the good prognosis group and the poor prognosis group according to the score of the modified ranking scale (mRS) 90 days after the stroke. Logistic regression analysis was used to explore the relationship between FVH and APVS and functional prognosis, while receiver operating characteristic (ROC) curves were plotted to assess the value of FVH and APVS in predicting prognosis. RESULTS: Spearman correlation analysis revealed moderate positive correlations between FVH and APVS (r = 0.586, P < 0.001). The poor prognosis group had a higher rate of a history of atrial fibrillation, a larger cerebral infarction volume, a higher NIHSS score at admission, and a higher FVH and APVS score compared with the good prognosis group (all P < 0.05). A further logistic regression indicated that the NIHSS score, cerebral infarction volume, FVH and APVS were independent risk factors for a poor functional prognosis. In terms of FVH, APVS, alone and their combination for the diagnosis of poor prognosis, the sensitivity, specificity, area under the ROC curve (AUC), and 95% confidence interval (CI) were 86.8%, 83.3%, 0.899 (95% CI 0.830-0.968); 60.5%, 93.7%, 0.818 (95% CI 0.723-0.912); 86.8%, 89.6%, 0.921 (95% CI 0.860-0.981), respectively. CONCLUSION: The presence of FVH and APVS can provide a comprehensive assessment of collateral circulation from the perspective of veins and arteries, and the correlation between the two is positively correlated. Both of them were independent risk factors for poor prognosis, their combination is complementary and can improve the predictive value.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico por imagem , Circulação Colateral , Acidente Vascular Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Infarto Cerebral , Estudos Retrospectivos
19.
Front Cell Infect Microbiol ; 13: 1123026, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816582

RESUMO

Vaginal microbiome is mutually beneficial to the host and has a significant impact on health and disease. Candida species, including Candida albicans, are part of the mucosal flora of most healthy women. Under suitable conditions, they can live in the vulvovaginal mucosa, resulting in symptomatic vulvovaginal candidiasis (VVC). Based on the analysis of 16S ribosomal RNA gene sequences, great progress has been made in exploring the composition and structure of vaginal bacterial community. Moreover, researchers have conducted several studies on whether vaginal microbiome will change during VVC infection. In addition, it has been reported that vaginal colonization of probiotics in vaginal microorganisms, especially Lactobacillus, can effectively reduce the risk of VVC and treat VVC. This review aims to summarize the changes of vaginal microflora during VVC infection, and further point out the possibility of using lactic acid bacteria as probiotics to treat VVC, so as to reduce the adverse consequences of VVC infection and reduce the expensive treatment cost.


Assuntos
Candidíase Vulvovaginal , Probióticos , Feminino , Humanos , Vagina/microbiologia , Candida albicans , Candida , Antifúngicos/uso terapêutico
20.
Org Lett ; 25(10): 1711-1716, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36892283

RESUMO

Herein, we described a highly regio- and enantioselective Friedel-Crafts alkylation of aniline derivatives with in situ generated ortho-quinone methides enabled by chiral phosphoric acid, furnishing a wide range of enantioenriched triarylmethanes bearing three similar benzene rings in high yields (up to 98%) with excellent stereoselectivities (up to 98% ee). Furthermore, the large-scale reactions and diversified transformations of product demonstrate the practicality of the protocol. Density functional theory calculations elucidate the origin of the enantioselectivity.

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