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1.
Sci Rep ; 14(1): 14376, 2024 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909094

RESUMO

Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 µM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819-60.761)) and mortality (HR 3.418, 95% CI (1.308-8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , Receptores Acoplados a Proteínas G , Ácido Succínico , Ácido Succínico/metabolismo , Ácido Succínico/sangue , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/mortalidade , Animais , Masculino , Camundongos , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Modelos Animais de Doenças , Biomarcadores/sangue , Fibroblastos/metabolismo , Ciclo do Ácido Cítrico
2.
Prev Med ; 185: 108026, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844051

RESUMO

INTRODUCTION: This study explored the association between psoriasis and the weight-adjusted waist index (WWI), a newly developed measure of adiposity. The research was conducted among adults in the United States. METHODS: Utilizing survey data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2014, the present study aimed to investigate the potential correlation between psoriasis and WWI within a sample of 15,920 adult participants. Employing multivariable logistic regression and nonlinear curve fitting techniques, we analyzed this plausible association. Additionally, a subgroup analysis was conducted to ascertain the consistency across diverse populations. RESULTS: A significant positive association was discovered between psoriasis and WWI in the investigated sample of 15,920 adults. After conducting a comprehensive adjustment of the model, it was observed that each incremental unit of WWI was significantly associated with an 14% elevated likelihood of developing psoriasis (OR = 1.16, 95% CI 1.01-1.36). Moreover, individuals belonging to the highest quartile of WWI exhibited a 47% higher risk of psoriasis compared to those in the lowest quartile (OR = 1.44, 95% CI 1.01-2.06). This positive correlation remained consistent across various subgroups. The study also compared WWI with BMI and waist circumference, finding that WWI is a more stable metric of obesity. CONCLUSIONS: Our study suggested that in US adults, there is a positive association between WWI and psoriasis. It also indicated that WWI showed potential as a valuable index of psoriasis among the general population.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124550, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38823240

RESUMO

Near-infrared organic fluorescent probes have great need in biological sciences and medicine but most of them are still largely unable to meet demand. In this work, a delicate multipurpose organic fluorescent probe (DPPM-TPA) with aggregation-induced emission performances is designed and prepared by facile method to reflect fluorescence labeling, two-photon imaging, and long-term fluorescent tracking. Specifically, DPPM-TPA NPs was constructed from 4-(diphenylamino)phenylboronic acid and DPPM-Br by classical Suzuki coupling reaction and then coated with F127. Such nanoprobe possessed high stability in diverse medium under ambient temperatures, low cytotoxicity, and brilliant fluorescence performance. More importantly, DPPM-TPA NPs showed excellent two-photon imaging and extraordinary long-term fluorescence tracing capacity to malignant tumor, and it can last up to 9 days. These results indicated that DPPM-TPA NPs is expected to serve as a fluorescent probe for photodiagnostic and providing a new idea for the development of long-term fluorescent tracker.


Assuntos
Corantes Fluorescentes , Corantes Fluorescentes/química , Humanos , Animais , Neoplasias , Camundongos , Espectrometria de Fluorescência , Nanopartículas/química , Linhagem Celular Tumoral , Ácidos Borônicos/química
4.
Arch Oral Biol ; 165: 106027, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38870610

RESUMO

OBJECTIVE: This study examined how range concentrations of Fibroblast Growth Factor-2 (FGF-2) influence the differentiation and activity of human-derived periodontal ligament (hPDLSCs) and alveolar bone-derived stem cells (haBMSCs). DESIGN: hPDLSCs and haBMSCs were cultured with varying concentrations of FGF-2 (0, 1, 2.5, 5, 10, 20 ng/mL) and monitored for osteogenic differentiation through alkaline phosphatase (ALP) activity and quantification of gene expression (qRT-PCR) for osteogenesis markers. Additionally, alizarin red staining and a hydroxyproline colorimetric assay evaluated and quantified osteogenic matrix mineralization and collagen deposition. Statistical analyses were performed using one-way ANOVA or two-way ANOVA for multiple comparisons between groups. RESULTS: At low FGF-2 concentrations, hPDLSCs differentiated toward an osteogenic lineage, whereas higher concentrations of FGF-2 inhibited osteogenesis and promoted fibroblastic differentiation. The effect of FGF-2 at the lowest concentration tested (1 ng/mL) led to significantly higher ALP activity than osteogenically induced positive controls at early time points and equivalent RUNX2 expression at early and later time points. FGF-2 supplementation of haBMSC cultures was sufficient, at all concentrations, to increase ALP activity at an earlier time point. Mineralization of haBMSC cultures increased significantly within 5-20 ng/mL FGF-2 concentrations under basal growth media conditions (α-minimal essential medium supplemented with 15 % fetal bovine serum and 1 % penicillin/streptomycin). CONCLUSIONS: FGF-2 has a dual capacity in promoting osteogenic and fibroblastic differentiation within hPDLSCs contingent upon the dosage and timing of administration, alongside supporting osteogenic differentiation in haBMSCs. These findings underscore the need for precision growth factors dosing when considering the design of biomaterials for periodontal regeneration.

5.
J AAPOS ; : 103938, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38796139

RESUMO

PURPOSE: To investigate the prevalence and body mass index (BMI) associations of congenital lower epiblepharon in children in China and the difference in the refractive errors between children with and without epiblepharon. METHODS: Children 6-12 years of age in Beichen District of Tianjin were screened for congenital epiblepharon from September to October 2017. All children underwent slit-lamp examination, strabismus screening, visual acuity examination and refraction. Weight and height were also recorded. The prevalence of lower epiblepharon in school-age children was evaluated, and its association with age, sex, BMI, and refractive error was analyzed. RESULTS: A total of 28,225 children were examined; 564 had epiblepharon. The prevalence of epiblepharon was found to be, for 6-year-olds, 2.50%; for 7-year-olds, 2.13%; for 8-year-olds, 2.10%; for 9-year-olds, 1.97%; for 10-year-olds, 1.85%; for 11-year-olds, 1.67%; and for 12-year-olds, 1.19% (P < 0.05). The prevalence of overweight and obesity in children with epiblepharon was found to be 16.7% and 47.2%, respectively. The prevalence and degree of astigmatism was higher than in nonepiblepharon children. We found a possible association between severity of astigmatism and severity of epiblepharon. CONCLUSIONS: In our study, the prevalence of epiblepharon decreased with advancing age, and the majority of children with epiblepharon were found to be overweight or obese. Epiblepharon was associated with astigmatism.

6.
Biomed Pharmacother ; 175: 116695, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713950

RESUMO

Kokusaginine is an active ingredient alkaloid that has been isolated and extracted from Ruta graveolens L. Some researches have indicated that alkaloids possess anti-inflammatory and antioxidant effects. Nevertheless, the potential nephroprotective effects of kokusaginine on renal fibrosis remain undetermined. This study was conducted to examine the protective effect of kokusaginine on renal fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. Renal fibrosis was induced in male C57BL/6 J mice by feeding with 0.2% adenine-containing food and UUO surgery. Kokusaginine was administered orally simultaneously after the establishment of renal fibrosis. Renal function was measured by serum levels of creatinine and urea nitrogen. Renal pathological changes were assessed by HE staining and Masson staining. Western blotting was employed to detect the expression levels of fibrosis-related proteins in mice and cells. Additionally, network pharmacology analysis and RNA-seq were utilized to predict the pathways through which kokusaginine could exert its anti-fibrotic effects. The treatment with kokusaginine enhanced renal function, alleviated renal histoarchitectural lesions, and mitigated renal fibrosis in the renal fibrosis models. The network pharmacology and RNA-seq enrichment analysis of the KEGG pathway demonstrated that kokusaginine could exert anti-renal fibrosis activity via the PI3K/AKT signaling pathway. And the results were verified in both in vitro and in vivo experiments. In conclusion, our data implied that kokusaginine inhibited the activation of the PI3K/AKT signaling pathway both in vitro and in vivo, and suppressed the formation of renal fibrosis. Thus, the kokusaginine-mediated PI3K/AKT signaling pathway may represent a novel approach for the treatment of renal fibrosis.


Assuntos
Fibrose , Nefropatias , Rim , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Nefropatias/prevenção & controle , Nefropatias/metabolismo , Modelos Animais de Doenças , Farmacologia em Rede , Humanos
7.
Aging (Albany NY) ; 16(8): 7293-7310, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38656879

RESUMO

BACKGROUND: CESC is the second most commonly diagnosed gynecological malignancy. Given the pivotal involvement of metabolism-related genes (MRGs) in the etiology of multiple tumors, our investigation aims to devise a prognostic risk signature rooted in cancer stemness and metabolism. METHODS: The stemness index based on mRNA expression (mRNAsi) of samples from the TCGA dataset was computed using the One-class logistic regression (OCLR) algorithm. Furthermore, potential metabolism-related genes related to mRNAsi were identified through weighted gene co-expression network analysis (WGCNA). We construct a stemness-related metabolic gene signature through shrinkage estimation and univariate analysis, thereby calculating the corresponding risk scores. Moreover, we selected corresponding DEGs between groups with high- and low-risk score and conducted routine bioinformatic analyses. Furthermore, we validated the expression of four hub genes at the protein level through immunohistochemistry (IHC) in samples obtained from our patient cohort. RESULTS: According to the findings, it was found that six genes-AKR1B10, GNA15, ALDH1B1, PLOD2, LPCAT1, and GPX8- were differentially expressed in both TCGA-CSEC and GEO datasets among 23 differentially expressed metabolism-related genes (DEMRGs). mRNAsi exhibited a notable association with the extent of key oncogene mutation. The results showed that the AUC values for forecasting survival at 1, 3, and 5 years are 0.715, 0.689, and 0.748, individually. We observed a notable association between the risk score and different immune cell populations, along with enrichment in crucial signaling pathways in CESC. Four genes differentially expressed between different risk score groups were validated by IHC to be highly expressed in the CESC samples at the protein level. CONCLUSION: The current investigation indicated that a 3-gene signature based on stemness-related metabolic and 4 hub genes with differential expression between high and low-risk score subgroups may serve as valuable prognostic markers and potential therapeutic targets in CESC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas , Neoplasias do Colo do Útero , Humanos , Feminino , Prognóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , Pessoa de Meia-Idade , Transcriptoma
8.
Front Plant Sci ; 15: 1342307, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638356

RESUMO

Introduction: Density management is a key silvicultural tool in management programs that enhances compositional and structural diversity and hence forest growth during the conversion of even-aged pure stands into mixed forests. Methods: To determine the optimum stand density, a model of maximum size-density relationships was employed to explore the relationship of the self-thinning trajectory with growth, species mixing, latitude, and site conditions during the transition of even-aged pure Chinese fir stands to Chinese fir-dominated mixed forests using stochastic frontier analysis. Data were obtained from a total of 591 permanent plots located in Fujian, Jiangxi, Zhejiang, and Anhui provinces in southern China. Results: The results showed that (1) the slope of the maximum size-density relationship of Chinese fir-dominated mixed forests increased and plateaued over time; (2) the slope of the maximum size-density relationship of Chinese fir-dominated mixed forests did not deviate from Reineke's assumed universal slope of -1.605; and (3) mixing proportion had a positive effect on maximum size-density relationships, and latitude and site conditions had the opposite effect on maximum size-density relationships. Conclusions: Our findings will provide valuable guidance for the forest management of areas in which even-aged pure stands are being converted to mixed forests (i.e., when broadleaved tree species are planted after thinning to improve overall stand density and promote stand growth).

9.
J Phys Chem Lett ; 15(17): 4694-4704, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38656198

RESUMO

Batteries with intercalation-conversion-type electrodes tend to achieve high-capacity storage, but the complicated reaction process often suffers from confusing electrochemical mechanisms. Here, we reinterpreted the essential issue about the potential of the conversion reaction and whether there is an intercalation reaction in a lithium/sodium-ion battery (LIB/SIB) with the FeP anode based on the evolution of the magnetic phase. Especially, the ever-present intercalation process in a large voltage range followed by the conversion reaction with extremely low potential was confirmed in FeP LIB, while it is mainly the conversion reaction for the sodium storage mechanism in FeP SIB. The insufficient conversion reaction profoundly limits the actual capacity to the expectedly respectable value. Accordingly, a graphene oxide modification strategy was proposed to increase the reversible capacity of FeP LIB/SIB by 99% and 132%, respectively. The results facilitate the development of anode materials with a high capacity and low operating potential.

10.
Genome Biol ; 25(1): 82, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566187

RESUMO

The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell-cell interactions, and spatial expression patterns, they are limited to the multicellular scale. We present Bento, a Python toolkit that takes advantage of single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests molecular coordinates and segmentation boundaries to perform three analyses: defining subcellular domains, annotating localization patterns, and quantifying gene-gene colocalization. We demonstrate MERFISH, seqFISH + , Molecular Cartography, and Xenium datasets. Bento is part of the open-source Scverse ecosystem, enabling integration with other single-cell analysis tools.


Assuntos
Ecossistema , Propanolaminas , Perfilação da Expressão Gênica , Comunicação Celular , Análise de Célula Única , Transcriptoma
11.
Behav Brain Res ; 466: 114974, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38554850

RESUMO

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.


Assuntos
Região CA1 Hipocampal , Dendritos , Diterpenos do Tipo Caurano , Potenciação de Longa Duração , Animais , Feminino , Masculino , Região CA1 Hipocampal/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Camundongos , Dendritos/efeitos dos fármacos , Memória/efeitos dos fármacos , Fatores Sexuais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia
12.
Hemoglobin ; 48(1): 4-14, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38419555

RESUMO

Long noncoding RNAs (lncRNAs) are important because they are involved in a variety of life activities and have many downstream targets. Moreover, there is also increasing evidence that some lncRNAs play important roles in the expression and regulation of γ-globin genes. In our previous study, we analyzed genetic material from nucleated red blood cells (NRBCs) extracted from premature and full-term umbilical cord blood samples. Through RNA sequencing (RNA-Seq) analysis, lncRNA H19 emerged as a differentially expressed transcript between the two blood types. While this discovery provided insight into H19, previous studies had not investigated its effect on the γ-globin gene. Therefore, the focus of our study was to explore the impact of H19 on the γ-globin gene. In this study, we discovered that overexpressing H19 led to a decrease in HBG mRNA levels during erythroid differentiation in K562 cells. Conversely, in CD34+ hematopoietic stem cells and human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, HBG expression increased. Additionally, we observed that H19 was primarily located in the nucleus of K562 cells, while in HUDEP-2 cells, H19 was present predominantly in the cytoplasm. These findings suggest a significant upregulation of HBG due to H19 overexpression. Notably, cytoplasmic localization in HUDEP-2 cells hints at its potential role as a competing endogenous RNA (ceRNA), regulating γ-globin expression by targeting microRNA/mRNA interactions.


Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , gama-Globinas/genética , gama-Globinas/metabolismo , Regulação para Cima , RNA Mensageiro/genética , Expressão Gênica
13.
RSC Adv ; 14(1): 83-89, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38173574

RESUMO

Carbon dots (C-dots) as promising fluorescent materials have attracted much attention because of their low toxicity and excellent optoelectronic properties. However, the aggregation-caused quenching (ACQ) of the solid-state C-dots has limited their potential applications in anti-counterfeiting and optoelectronic devices. In this work, C-dot powder was prepared by directly dispersing the as-prepared C-dots in a polymer matrix or in situ formation of the C-dot/Ca-complex by vacuum heating in the presence of boric acid. The as-prepared C-dots have high quantum yields (QYs) in the range of 40-67% with temperature-dependent photoluminescent (PL) properties. As a proof of concept, the as-synthesized C-dots were used to produce a flexible anti-counterfeiting code and showed high-level security. This highlights the potential of C-dots in solid-state information, anti-information encryption and anti-counterfeiting.

14.
Heliyon ; 10(1): e23683, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192798

RESUMO

The purpose of this work was to use integrated bioinformatics analysis to screen for pyroptosis-related genes (PRGs) and possible immunological phenotypes linked to the development and course of IPF. Transcriptome sequencing datasets GSE70866, GSE47460 and GSE150910 were obtained from GEO database. From the GSE70866 database, 34 PRGs with differential expression were found in IPF as compared to healthy controls. In addition, a diagnostic model containing 4 genes PRGs (CAMP, MKI67, TCEA3 and USP24) was constructed based on LASSO logistic regression. The diagnostic model showed good predictive ability to differentiate between IPF and healthy, with ROC-AUC ranging from 0.910 to 0.997 in GSE70866 and GSE150910 datasets. Moreover, based on a combined cohort of the Freiburg and the Siena cohorts from GSE70866 dataset, we identified ten PRGs that might predict prognosis for IPF. We constructed a prognostic model that included eight PRGs (CLEC5A, TREM2, MMP1, IRF2, SEZ6L2, ADORA3, NOS2, USP24) by LASSO Cox regression and validated it in the Leuven cohort. The risk model divided IPF patients from the combined cohort into high-risk and low-risk subgroups. There were significant differences between the two subgroups in terms of IPF survival and GAP stage. There is a close correlation between leukocyte migration, plasma membrane junction, and poor prognosis in a high-risk subgroup. Furthermore, a high-risk score was associated with more plasma cells, activated NK cells, monocytes, and activated mast cells. Additionally, we identified HDAC inhibitors in the cMAP database that might be therapeutic for IPF. To summarize, pyroptosis and its underlying immunological features are to blame for the onset and progression of IPF. PRG-based predictive models and drugs may offer new treatment options for IPF.

15.
Inflamm Res ; 73(1): 131-144, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38091015

RESUMO

OBJECTIVE: Proinflammatory necroptosis is the main pathological mechanism of ischemic stroke. Homer scaffolding protein 1 (Homer1) is a postsynaptic scaffolding protein that exerts anti-inflammatory effects in most central nervous system diseases. However, the relationship between Homer1 and proinflammatory necroptosis in ischemic stroke remains unclear. AIM: This study aimed to investigate the role of Homer1 in ischemia-induced necroptosis. METHODS: C57BL/6 mice were used to establish a model of permanent middle cerebral artery occlusion model (pMCAO). Homer1 knockdown mice were generated using adeno-associated virus (AAV) infection to explore the role of Homer1 and its impact on necroptosis in pMCAO. Finally, Homer1 protein was stereotaxically injected into the ischemic cortex of Homer1flox/flox/Nestin-Cre +/- mice, and the efficacy of Homer1 was investigated using behavioral assays and molecular biological assays to explore potential mechanisms. RESULTS: Homer1 expression peaked at 8 h in the ischemic penumbral cortex after pMCAO and colocalized with neurons. Homer1 knockdown promoted neuronal death by enhancing necroptotic signaling pathways and aggravating ischemic brain damage in mice. Furthermore, the knockdown of Homer1 enhanced the expression of proinflammatory cytokines. Moreover, injection of Homer1 protein reduced necroptosis-induced brain injury inhibited the expression of proinflammatory factors, and ameliorated the outcomes in the Homer1flox/flox/Nestin-Cre+/- mice after pMCAO. CONCLUSIONS: Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation. These data suggested that Homer1 is a novel regulator of neuronal death and neuroinflammation.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Camundongos , Animais , AVC Isquêmico/complicações , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Nestina/metabolismo , Nestina/farmacologia , Doenças Neuroinflamatórias , Necroptose , Camundongos Endogâmicos C57BL , Infarto da Artéria Cerebral Média/patologia , Neurônios/patologia , Isquemia Encefálica/metabolismo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Proteínas de Arcabouço Homer/genética , Proteínas de Arcabouço Homer/metabolismo , Proteínas de Arcabouço Homer/farmacologia
16.
Acta Biomater ; 173: 495-508, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37939819

RESUMO

Pulp capping is a necessary procedure for preserving the vitality and health of the dental pulp, playing a crucial role in preventing the need for root canal treatment or tooth extraction. Here, we developed an electrospun gelatin methacryloyl (GelMA) fibrous scaffold incorporating beta-tricalcium phosphate (TCP) particles for pulp capping. A comprehensive morphological, physical-chemical, and mechanical characterization of the engineered fibrous scaffolds was performed. In vitro bioactivity, cell compatibility, and odontogenic differentiation potential of the scaffolds in dental pulp stem cells (DPSCs) were also evaluated. A pre-clinical in vivo model was used to determine the therapeutic role of the GelMA/TCP scaffolds in promoting hard tissue formation. Morphological, chemical, and thermal analyses confirmed effective TCP incorporation in the GelMA nanofibers. The GelMA+20%TCP nanofibrous scaffold exhibited bead-free morphology and suitable mechanical and degradation properties. In vitro, GelMA+20%TCP scaffolds supported apatite-like formation, improved cell spreading, and increased deposition of mineralization nodules. Gene expression analysis revealed upregulation of ALPL, RUNX2, COL1A1, and DMP1 in the presence of TCP-laden scaffolds. In vivo, analyses showed mild inflammatory reaction upon scaffolds' contact while supporting mineralized tissue formation. Although the levels of Nestin and DMP1 proteins did not exceed those associated with the clinical reference treatment (i.e., mineral trioxide aggregate), the GelMA+20%TCP scaffold exhibited comparable levels, thus suggesting the emergence of differentiated odontoblast-like cells capable of dentin matrix secretion. Our innovative GelMA/TCP scaffold represents a simplified and efficient alternative to conventional pulp-capping biomaterials. STATEMENT OF SIGNIFICANCE: Vital pulp therapy (VPT) aims to preserve dental pulp vitality and avoid root canal treatment. Biomaterials that bolster mineralized tissue regeneration with ease of use are still lacking. We successfully engineered gelatin methacryloyl (GelMA) electrospun scaffolds incorporated with beta-tricalcium phosphate (TCP) for VPT. Notably, electrospun GelMA-based scaffolds containing 20% (w/v) of TCP exhibited favorable mechanical properties and degradation, cytocompatibility, and mineralization potential indicated by apatite-like structures in vitro and mineralized tissue deposition in vivo, although not surpassing those associated with the standard of care. Collectively, our innovative GelMA/TCP scaffold represents a simplified alternative to conventional pulp capping materials such as MTA and Biodentine™ since it is a ready-to-use biomaterial, requires no setting time, and is therapeutically effective.


Assuntos
Materiais Biocompatíveis , Alicerces Teciduais , Alicerces Teciduais/química , Células Cultivadas , Materiais Biocompatíveis/química , Diferenciação Celular , Apatitas/farmacologia , Polpa Dentária
17.
BMC Psychiatry ; 23(1): 914, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057778

RESUMO

BACKGROUND: Patients with Alzheimer's disease (AD) often exhibit neuropsychiatric symptoms (NPS), particularly delusions. Previous studies have shown an association between white matter hyperintensities (WMH) and specific NPS. This study aims to explore the relationship between WMH volume and delusions in AD patients by comparing the WMH volumes of delusional and non-delusional subgroups. METHODS: 80 AD patients were divided into a delusion group (n = 36) and a non-delusion group (n = 44) based on the Neuropsychiatric Inventory (NPI). The brain cortical volume and WMH volume were quantitatively calculated for all 80 patients, including total WMH volume, periventricular WMH (PVWMH) volume, deep WMH volume, as well as bilateral frontal lobe, temporal lobe, parietal lobe, and occipital lobe WMH volumes. Firstly, we compared the differences in WMH volumes between the delusion group and non-delusion group. Then, within the delusion group, we further categorized patients based on severity scores of their delusional symptoms into mild (1 point), moderate (2 points), or severe groups (3 points). We compared the WMH volumes among these three groups to investigate the role of WMH volume in delusional symptoms. RESULTS: There was a significant difference in left occipital lobe WMH volume between the delusion group and non-delusion group(P < 0.05). Within the delusion group itself, there were significant differences in overall WMH volume as well as PVWMH volume among patients with mild or severe levels of delusions(P < 0.05). CONCLUSION: Left occipital lobe WMH volume may be associated with the occurrence of delusional AD patients, and the total volume of whole-brain WMH and PVWMH volume may affect the degree of severity of delusional symptoms.


Assuntos
Doença de Alzheimer , Substância Branca , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Encéfalo , Lobo Parietal/diagnóstico por imagem , Imageamento por Ressonância Magnética
18.
Opt Lett ; 48(23): 6240-6243, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039236

RESUMO

A magnetic field (MF) sensor with a stable structure and high sensitivity has been proposed and experimentally verified. We used the water bath method to produce a layer of Fe2O3 nanorods on a tapered few mode fiber (FMF) surface to form a Mach-Zehnder interferometer (MZI). The experiment found that the nanostructure produced on the surface of FMF were particularly stable and firm. Under the action of an external MF, the magnetic permeability of a Fe2O3 nanorod will change, leading to a change in its refractive index, resulting in a linear shift in the resonance wavelength of MZI. The experimental results showed that the MF sensitivity of MZI reached -0.5348 nm/mT in 10 mT∼80 mT. In addition, MZI has a certain sensitivity to environmental humidity and temperature. A long-period fiber grating and a fiber Bragg grating are cascaded with MZI to achieve a simultaneous measurement of three quantities and eliminate their cross-sensitivity.

19.
Chem Commun (Camb) ; 60(2): 220-223, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38050964

RESUMO

A Si/Si-Co multilayer film, with Co confined doping in the silicon anode, was successfully fabricated by alternating magnetron sputtering, achieving both metal doping and surface coating. Operando magnetometry revealed the stability of the Si-Co layers during cycling. The symmetrical Si-Co layers can protect the overall structure of the Si anodes and facilitate electron conduction. Consequently, the resultant Si anode delivers an impressive initial coulombic efficiency of 93.4% with large capacity retention of 85.07% after 100 cycles.

20.
J Transl Med ; 21(1): 805, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951977

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. METHODS: A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. RESULTS: Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2-3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. CONCLUSIONS: In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.


Assuntos
Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Prognóstico , Capacidade Vital , Biomarcadores , Fibrose , Estudos Retrospectivos
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