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1.
J Mol Neurosci ; 74(2): 36, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568285

RESUMO

After ischemic stroke, microRNAs (miRNAs) participate in various processes, including immune responses, inflammation, and angiogenesis. Diabetes is a key factor increasing the risk of ischemic stroke; however, the regulatory pattern of miRNAs at different stages of diabetic stroke remains unclear. This study comprehensively analyzed the miRNA expression profiles in diabetic mice at 1, 3, and 7 days post-reperfusion following the middle cerebral artery occlusion (MCAO). We identified differentially expressed (DE) miRNAs in diabetic stroke and found significant dysregulation of some novel miRNAs (novel_mir310, novel_mir89, and novel_mir396) post-stroke. These DEmiRNAs were involved in apoptosis and the formation of tight junctions. Finally, we identified three groups of time-dependent DE miRNAs (miR-6240, miR-135b-3p, and miR-672-5p). These have the potential to serve as biomarkers of diabetic stroke. These findings provide a new perspective for future research, emphasizing the dynamic changes in miRNA expression after diabetic stroke and offering potential candidates as biomarkers for future clinical applications.


Assuntos
Diabetes Mellitus Experimental , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Animais , Camundongos , Diabetes Mellitus Experimental/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Plantas Geneticamente Modificadas , Acidente Vascular Cerebral/genética , Biomarcadores
2.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345992

RESUMO

BACKGROUND: This study was conducted to investigate the correlation between KCNQ1 rs2237895 A/C gene polymorphism and blood indexes and prognosis in non-small cell lung cancer (NSCLC). METHODS: A total of 260 NSCLC patients were selected and classified into stage I - II (n = 109) and stage III - IV (n = 151) according to by American Joint Committee on Cancer Staging Manual. A control group was established with another 92 healthy subjects. The genotype distribution of rs2237895 was analyzed in all subjects. 2 analysis or Fisher's test was employed to analyze the association between genotype and allele distribution frequencies with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen, and cytokeratin fragment 19 (CyfrA 21-1). Overall survival was compared by genotype stratification using Kaplan-Meier analysis. Univariate and multivariate Cox risk regression analyses were used to determine the prognostic value of allele C in NSCLC. RESULTS: AC/CC genotypes in NSCLC patients were associated with gender, hypertension, smoking, clinical TNM stage, lymph node metastasis, and distant metastasis. C allele was associated with higher risk levels of serum tumor markers. Patients with allele C (AC + CC) had lower overall survival than patients with genotype AA. Finally, clinical stage, lymph node metastasis, higher CEA and CyfrA 21-1 serum levels, and rs2237895 A/C gene poly-morphism were independent prognostic factors of NSCLC. CONCLUSIONS: rs2237895 A/C polymorphism of the KCNQ1 gene can be a prognostic predictor in patients with surgically treated NSCLC.


Assuntos
Antígenos de Neoplasias , Carcinoma Pulmonar de Células não Pequenas , Queratina-19 , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Antígeno Carcinoembrionário , Neoplasias Pulmonares/patologia , Metástase Linfática , Canal de Potássio KCNQ1/genética , Prognóstico , Biomarcadores Tumorais/genética , Polimorfismo Genético
3.
Circ Cardiovasc Imaging ; 16(9): e015340, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37725670

RESUMO

BACKGROUND: Rapid plaque progression (RPP) is associated with a higher risk of acute coronary syndromes compared with gradual plaque progression. We aimed to develop and validate a coronary computed tomography angiography (CCTA)-based radiomics signature (RS) of plaques for predicting RPP. METHODS: A total of 214 patients who underwent serial CCTA examinations from 2 tertiary hospitals (development group, 137 patients with 164 lesions; validation group, 77 patients with 101 lesions) were retrospectively enrolled. Conventional CCTA-defined morphological parameters (eg, high-risk plaque characteristics and plaque burden) and radiomics features of plaques were analyzed. RPP was defined as an annual progression of plaque burden ≥1.0% on lesion-level at follow-up CCTA. RS was built to predict RPP using XGBoost method. RESULTS: RS significantly outperformed morphological parameters for predicting RPP in both the development group (area under the receiver operating characteristic curve, 0.82 versus 0.74; P=0.04) and validation group (area under the receiver operating characteristic curve, 0.81 versus 0.69; P=0.04). Multivariable analysis identified RS (odds ratio, 2.35 [95% CI, 1.32-4.46]; P=0.005) as an independent predictor of subsequent RPP in the validation group after adjustment of morphological confounders. Unlike unchanged RS in the non-RPP group, RS increased significantly in the RPP group at follow-up in the whole dataset (P<0.001). CONCLUSIONS: The proposed CCTA-based RS had a better discriminative value to identify plaques at risk of rapid progression compared with conventional morphological plaque parameters. These data suggest the promising utility of radiomics for predicting RPP in a low-risk group on CCTA.


Assuntos
Angiografia por Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Angiografia , Coração
4.
Radiology ; 307(2): e221693, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36786701

RESUMO

Background A noninvasive coronary CT angiography (CCTA)-based radiomics technique may facilitate the identification of vulnerable plaques and patients at risk for future adverse events. Purpose To assess whether a CCTA-based radiomic signature (RS) of vulnerable plaques defined with intravascular US was associated with increased risk for future major adverse cardiac events (MACE). Materials and Methods In a retrospective study, an RS of vulnerable plaques was developed and validated using intravascular US as the reference standard. The RS development data set included patients first undergoing CCTA and then intravascular US within 3 months between June 2013 and December 2020 at one tertiary hospital. The development set was randomly assigned to training and validation sets at a 7:3 ratio. Diagnostic performance was assessed internally and externally from three tertiary hospitals using the area under the curve (AUC). The prognostic value of the RS for predicting MACE was evaluated in a prospective cohort with suspected coronary artery disease between April 2018 and March 2019. Multivariable Cox regression analysis was used to evaluate the RS and conventional anatomic plaque features (eg, segment involvement score) for predicting MACE. Results The RS development data set included 419 lesions from 225 patients (mean age, 64 years ± 10 [SD]; 68 men), while the prognostic cohort included 1020 lesions from 708 patients (mean age, 62 years ± 11; 498 men). Sixteen radiomic features, including two shape features and 14 textural features, were selected to build the RS. The RS yielded a moderate to good AUC in the training, validation, internal, and external test sets (AUC = 0.81, 0.75, 0.80, and 0.77, respectively). A high RS (≥1.07) was independently associated with MACE over a median 3-year follow-up (hazard ratio, 2.01; P = .005). Conclusion A coronary CT angiography-derived radiomic signature of coronary plaque enabled the detection of vulnerable plaques that were associated with increased risk for future adverse cardiac outcomes. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by De Cecco and van Assen in this issue.


Assuntos
Doença da Artéria Coronariana , Placa Aterosclerótica , Masculino , Humanos , Pessoa de Meia-Idade , Angiografia por Tomografia Computadorizada/métodos , Estudos Retrospectivos , Estudos Prospectivos , Doença da Artéria Coronariana/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/complicações , Angiografia Coronária/métodos , Prognóstico , Valor Preditivo dos Testes
5.
Front Genet ; 13: 1036402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353107

RESUMO

To investigate the potential relationship between Ikaros family genes and skin cutaneous melanoma (SKCM), we undertook a pan-cancer analysis of the transcriptional signature and clinical data of melanoma through multiple databases. First, 10,327 transcriptomic samples from different cancers were included to determine the overall characteristics and clinical prognoses associated with Ikaros gene expression across cancer types. Second, differentially expressed genes analysis, prognostic evaluation, and gene set enrichment analysis were employed to investigate the role of Ikaros (IKZF) genes in SKCM. Third, we evaluated the relationship between Ikaros family genes and SKCM immune infiltrates and verified the findings using the GEO single-cell sequencing dataset. The results show that Ikaros genes were widely expressed among different cancer types with independently similar patterns as follows: 1. IKZF1 and IKZF3, and 2. IKZF2 and IKZF4-5. IKZF2 and IKZF5 were downregulated in the primary tumor, and IKZF1-3 expression decreased significantly as the T-stage or metastasis increased in SKCM. Moreover, high IKZF1-3 expression was associated with better overall survival, disease-specific survival, and progression-free interval. IKZF3 is an independent prognostic factor of SKCM. Among Ikaros genes, the expression of IKZF1 and IKZF3 positively correlated with the infiltration level of CD4+ T cells and CD8+ T cells, B cells, and Tregs in SKCM and negatively correlated with the infiltration level of M0 and M1 macrophages. Moreover, single-cell sequencing data analysis revealed that IKZF1 and IKZF3 were mainly expressed by immune cells. Correlation analysis shows the immune factors and drug responses associated with IKZF3 expression. In conclusion, the present study is the first, to our knowledge, to identify a pan-cancer genomic signature of the Ikaros gene family among different cancers. Expression of these family members, particularly high levels of IKZF3, indicate positive immunological status and beneficial clinical outcomes of SKCM. IKZF3 may therefore serve as potential targets for immunotherapy of melanoma.

6.
Molecules ; 27(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35807297

RESUMO

Aconiti Lateralis Radix Praeparata (Fu Zi) is the processed lateral root of Aconitum carmichaelii Debx, which is widely used in emergency clinics. Poisoning incidents and adverse reactions occur with the improper intake of Fu Zi. Metabolic characteristics of aconitum alkaloids of Fu Zi may vary, and the effects of Fu Zi in healthy and Long QT syndrome (LQTS) patients is unknown. In this experiment, 24 Sprague Dawley rats were randomly divided into three groups: 2.0, 1.0, and 0.5 g/kg dose groups, and blood samples were collected after the oral administration of Fu Zi extract. We used an ultra-high performance liquid chromatography-tandem mass spectrometry system to detect the concentrations of six aconitum alkaloids. Cell toxicity, calcium imaging, and patch-clamp recordings of human induced pluripotent stem cells-cardiomyocytes (hiPSC-CMs) of aconitine in healthy and LQTS were observed. We found that the AUC(0-48h), Cmax, and t1/2 of the six compounds increased with the multiplicative dosages; those in the high group were significantly higher than those in the low group. Aconitine concentration-dependently decreased the amplitude, which has no significant effect on the cell index of normal hiPSC-CMs. Aconitine at 5.0 µM decreased the cell index between 5-30 min for LQTS hiPSC-CMs. Meanwhile, aconitine significantly increased the frequency of calcium transients in LQTS at 5 µM. Aconitine significantly shortened the action potential duration of human cardiomyocytes in both normal and LQTS groups. These results show metabolic behaviors of aconitum alkaloids in different concentrations of Fu Zi and effects of aconitine in healthy and LQTS patients.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Células-Tronco Pluripotentes Induzidas , Síndrome do QT Longo , Aconitina/farmacologia , Aconitum/química , Alcaloides/análise , Alcaloides/farmacologia , Animais , Cálcio , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Humanos , Síndrome do QT Longo/induzido quimicamente , Miócitos Cardíacos , Ratos , Ratos Sprague-Dawley
7.
J Colloid Interface Sci ; 622: 960-970, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561614

RESUMO

Realizing both high gravimetric and volumetric specific capacitances (noted as CW and CV, respectively) is an essential prerequisite for the next-generation, high performance supercapacitors. However, the need of electronic/ionic transport for electrochemical reactions causes a "trade-off" between compacted density and capacitance of electrode, thereby impairing gravimetric or volumetric specific capacitances. Herein, we report a high-performance, film-based supercapacitor via a thermal reduction of graphene oxide (GO) in air. The reduced, layer-structured graphene film ensures high electrode density and high electron conductivity, while the hierarchical channels generated from reduction-induced gas releasing process offer sufficient ion transport pathways. Note that the resultant graphene film is employed directly as electrodes without using any additives (binders and conductive agents). As expected, the as-prepared electrodes perform particularly well in both CW (420F g-1) and CV (360F cm-3) at a current density of 0.5 A g-1. Even at an ultrahigh current density of 50 A g-1, CW and CV maintain in 220F g-1 and 189F cm-3, respectively. Furthermore, the corresponding symmetric two-electrode supercapacitor achieves both high gravimetric energy density of 54 W h kg-1 and high gravimetric power density of 1080 W kg-1, corresponding to volumetric energy density of 46 W h L-1 and volumetric power density of 917 W L-1.

8.
Front Plant Sci ; 12: 720022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603350

RESUMO

Near-infrared spectroscopy (NIR) is a non-destructive, fast, and low-cost method to measure the grain quality of different cereals. However, the feasibility for determining the critical biochemicals, related to the classifications for food, feed, and fuel products are not adequately investigated. Fourier-transform (FT) NIR was applied in this study to determine the eight biochemicals in four types of sorghum samples: hulled grain flours, hull-less grain flours, whole grains, and grain flours. A total of 20 hybrids of sorghum grains were selected from the two locations in China. Followed by FT-NIR spectral and wet-chemically measured biochemical data, partial least squares regression (PLSR) was used to construct the prediction models. The results showed that sorghum grain morphology and sample format affected the prediction of biochemicals. Using NIR data of grain flours generally improved the prediction compared with the use of NIR data of whole grains. In addition, using the spectra of whole grains enabled comparable predictions, which are recommended when a non-destructive and rapid analysis is required. Compared with the hulled grain flours, hull-less grain flours allowed for improved predictions for tannin, cellulose, and hemicellulose using NIR data. This study aimed to provide a reference for the evaluation of sorghum grain biochemicals for food, feed, and fuel without destruction and complex chemical analysis.

9.
Chem Commun (Camb) ; 57(85): 11181-11184, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34618880

RESUMO

A small amount of the 3-(hexyldimethylammonio)propane-1-sulfonate zwitterionic side chain was integrated into a diketopyrrolopyrrole ambipolar polymer to modulate its field-effect carrier-transport characteristics. It was found that such a modification can strengthen the interchain interaction, promote crystallization, and thus improve the hole and electron mobilities by 3.9- and 8.2-fold, respectively.

10.
Onco Targets Ther ; 14: 3467-3480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079292

RESUMO

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80%-85% of all cases of lung cancer. Huntingtin interacting protein-1 interacting protein (HIPPI) is a transcription regulator and plays an important role in apoptotic cell death. However, the role of HIPPI in NSCLC remains unclear. METHODS: Immunohistochemistry (IHC) and qRT-PCR were performed for expression analysis. The roles of HIPPI were studied using cell counting kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell invasion assays and mouse xenograft model. Gene microarray analysis and bioinformatics analysis were used to identify differentially expressed genes after HIPPI silencing. RESULTS: HIPPI is highly expressed in NSCLC tissues relative to adjacent normal tissues. Targeting HIPPI by RNA interference inhibits NSCLC cell proliferation in vitro and tumor growth in vivo. HIPPI silencing also attenuates cell migration and invasion and enhances cisplatin sensitivity in NSCLC cells. Mechanistic investigation suggests that HIPPI can positively regulate the expression of MCM2, MCM6 and MCM8, which are key regulators of DNA replication. Furthermore, consistent with HIPPI, MCM2, MCM6 and MCM8 are also upregulated in NSCLC tissues. CONCLUSION: Our study highlights the importance of HIPPI for tumor biology in NSCLC and suggests that HIPPI may be a potential therapeutic target for NSCLC treatment.

11.
Stem Cell Res Ther ; 12(1): 220, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789742

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. METHOD: A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. RESULT: Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. CONCLUSIONS: The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.


Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Células Endoteliais , Ratos , Fator A de Crescimento do Endotélio Vascular , Cicatrização
12.
Photobiomodul Photomed Laser Surg ; 39(5): 311-320, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33872063

RESUMO

Objective: The effects of photobiomodulation therapy (PBMT) and carbon arc lamp therapy (CALT) on the repair of chronic soft tissue injury were compared. Background data: PBMT improves soft tissue repair of chronic injury. However, there has been no research on the effect of CALT. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated using PBMT and CALT at 2 J/cm2 to observe their effects on cell proliferation and migration. The effects of PBMT and CALT on soft tissue injury repair were assessed using a chronic gastrocnemius injury model of the posterior limb in rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) were examined by biochemical analyses. The degree of tissue damage repair was evaluated by the immunohistochemical method [CD45, CD34, vascular endothelial growth factor (VEGF), and actin] and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: Treatment by PBMT and CALT significantly accelerated the proliferation and migration of HUVECs. Moreover, significant decreases in the contents of MDA and PGE2 were observed in the PBMT and CALT groups, while SOD activity was increased. The histological assessment shows that the content of inflammatory cells and apoptotic cells significantly decreased in the CALT group. However, the microvascular density, VEGF content, and actin content were increased in the CALT group. Conclusions: The results demonstrate that CALT has a stronger effect on promoting chronic soft tissue injury repair in comparison with PBMT.


Assuntos
Terapia com Luz de Baixa Intensidade , Lesões dos Tecidos Moles , Animais , Carbono , Células Endoteliais , Ratos , Ratos Wistar , Lesões dos Tecidos Moles/radioterapia , Fator A de Crescimento do Endotélio Vascular
13.
Eur J Radiol ; 136: 109551, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33485126

RESUMO

PURPOSE: To explore whether CT texture analysis can identify thin-cap fibroatheroma (TCFA) determined by optical coherence tomography (OCT). METHODS: Thirty-three patients with 43 lesions who underwent both CCTA and OCT within 3 months were retrospectively included. 12 conventional CT-derived plaque features, fat attenuation index (FAI) and 1691 plaque radiomics features were extracted to discriminate TCFA lesions and non-TCFA lesions determined by OCT. Minimum redundancy and maximum relevance (mRMR) method was employed to select radiomics features. The top ranked features were used to construct a forward stepwise logistic radiomics model. The performance of radiomics model was compared with the conventional high-risk plaque (HRP) features model and FAI model for the detection of TCFA. RESULTS: Out of 1691 features, 35 features were significantly different between TCFA and non-TCFA lesions (all p<0.05) while only low attenuation plaque (LAP) was more frequent in TCFA group (p = 0.004). There was no significant difference in FAI between TCFA and non-TCFA lesions. Five features were ultimately integrated into the radiomics model after mRMR analysis, which demonstrated significantly higher AUC for the detection of TCFA (0.952; 95 % CI: 0.897-1.000) compared with the conventional HRP features model (0.621; 95 % CI: 0.469-0.773, p < 0.001) and FAI model (0.52; 95 % CI: 0.33-0.70, p < 0.001). CONCLUSION: CT texture analysis performs better at identifying TCFA determined by OCT compared with conventional CT-derived plaque parameters and FAI. Texture analysis may serve as a potential non-invasive method of evaluating vulnerable plaque.


Assuntos
Doença da Artéria Coronariana , Placa Aterosclerótica , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia de Coerência Óptica , Tomografia Computadorizada por Raios X
14.
Med Sci Monit ; 26: e922703, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32946432

RESUMO

BACKGROUND As we know, chemotherapy resistance is a critical factor leading to recurrence and metastasis of nonsmall-cell lung cancer (NSCLC). To clarify the key target and potential mechanism of resistance to gemcitabine (GEM) in NSCLC, we selected Gene Expression Omnibus Data Set and statistically analyzed a parent cell group and a GEM-resistant cell group. Results showed that the expression of troponin C1, slow skeletal and cardiac type (TNNC1) in GEM-resistant cells was higher than in parent cells, which implies that TNNC1 was associated with GEM resistance in lung cancer cells. MATERIAL AND METHODS TNNC1 expression level was detected by reverse transcription-quantitative polymerase chain reaction or western blot in GEM-resistant patient serum and cell lines. It could reduce or increase autophagy response and GEM resistance accordingly by inhibition of the short interfering ribonucleic acid or by forced overexpression of TNNC1 viruses in A549 cell line and GEM-resistant cell line (A549/GemR) respectively. Blocking autophagy with 3-methyladenine increased the sensitivity of chemotherapy confirmed by flow cytometry and microtubule-associated protein 1A/1B - light chain 3 punctate assay. What's more, in a loss-of-function model, silencing of forkhead box 03 (FOXO3) in A549/GemR cells could rescue the autophagy weakened by TNNC1. RESULTS TNNC1 promoted GEM chemoresistance of NSCLC by activating cytoprotective autophagy, regulated negatively by FOXO3. This research may provide a completely new strategy for NSCLC treatment. CONCLUSIONS Targeting the TNNC1/FOXO3 signaling pathway in NSCLC may be a novel strategy to combat GEM resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/biossíntese , Troponina C/biossíntese , Células A549 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/genética , Troponina C/genética , Gencitabina
15.
Brain Res ; 1726: 146518, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31647899

RESUMO

Chloroquine, a prototype anti-malaria drug, has been reported to possess anti-inflammatory effects. Moreover, chloroquine pretreatment could improve DNA damage repair. It is therefore reasonable to hypothesize that chloroquine pretreatment could attenuate ischemia/reperfusion injury in the brain. Considering the fact that chloroquine could also improve glucose metabolism, we speculated that the potential effects of chloroquine on ischemia/reperfusion injury might be particularly pronounced in diabetic mice. In this study, chloroquine pretreatment protected neurons from Oxygen Glucose Deprivation (OGD) induced cytotoxicity and apoptosis. In vivo, Ob/ob mice and wildtype (WT) mice were pretreated with chloroquine for 3 weeks. Then, ischemic stroke was induced by 60 min Middle Cerebral Artery Occlusion (MCAO). We found that chloroquine pretreatment normalized blood glucose in diabetic ob/ob mice, and reduced cerebral damage after ischemic stroke especially for diabetic mice. In addition, chloroquine pretreatment reduced High-mobility group box 1 (HMGB1) content in the cerebrospinal fluid (CSF) and serum and lowered myeloperoxidase (MPO) activity and inflammatory cytokines gene expression both in the ob/ob diabetic mice and WT mice. Moreover, harmful DNA damage-signaling responses, including PARP activation and p53 activation, were also attenuated by chloroquine pretreatment in these two kinds of mice. In conclusion, chloroquine pretreatment could reduce cerebral damage after ischemic stroke especially in diabetic mice through multiple mechanisms, which include reducing neural cell DNA injury, restoring euglycemia and anti-inflammatory effects. The findings may provide potential for the development of chloroquine in the prevention and treatment of stroke in diabetic high-risk patients.


Assuntos
Isquemia Encefálica/fisiopatologia , Encéfalo/efeitos dos fármacos , Cloroquina/administração & dosagem , Diabetes Mellitus/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Traumatismo por Reperfusão/fisiopatologia , Animais , Glicemia/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/prevenção & controle , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Proteína HMGB1/líquido cefalorraquidiano , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/fisiologia , Cultura Primária de Células , Traumatismo por Reperfusão/prevenção & controle
16.
Biomed Res Int ; 2020: 6406395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33415151

RESUMO

Adipose-derived stem cells (ADSCs) have been documented as possible candidates for skin rejuvenation. However, the effects of ADSC-derived exosomes on photoaged skin remain to be fully elucidated. This study was aimed at determining the antiaging effects of ADSC-derived exosomes on photoaged skin. Human ADSCs were isolated from the adipose tissue of healthy women and cultured in vitro. Then, exosomes were extracted from the cultured ADSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the identification of specific biomarkers. Meanwhile, the optimal exosome concentration and treatment time were selected. The photoaged skin model was created by subjecting Sprague-Dawley rats to ultraviolet B radiation. Exosomes were injected into the photoaged skin in a single therapeutic dose. The thickness of the epidermis and dermis was observed by HE staining. The relative mRNA expression of type I collagen, type III collagen, and matrix metalloproteinases (MMP-1 and MMP-3) was determined by real-time PCR. In the rat model of photoaged skin, the injected exosomes markedly decreased the epidermal thickness and increased the dermal thickness of the photoaged skin 7 days after treatment. Moreover, the proportion of the stratum corneum of the epidermis was decreased. Furthermore, real-time RT-PCR showed that the mRNA expression of type I collagen was increased and that of type III collagen, MMP-1, and MMP-3 was decreased. Our results demonstrate that ADSC-derived exosome treatment could significantly improve skin photodamage and that ADSC-derived exosomes may be a potential agent for photoaged skin treatment.


Assuntos
Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Envelhecimento da Pele/efeitos da radiação , Adulto , Animais , Núcleo Celular/metabolismo , Proliferação de Células , Forma Celular , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Derme/metabolismo , Exossomos/ultraestrutura , Feminino , Fibroblastos/metabolismo , Humanos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley
17.
Cell Mol Neurobiol ; 40(5): 785-799, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31845160

RESUMO

The ataxia-telangiectasia mutated (ATM) protein is regarded as the linchpin of cellular defenses to stress. Deletion of ATM results in strong oxidative stress and degenerative diseases in the nervous system. However, the role of ATM in neuronal ischemic preconditioning and lethal ischemic injury is still largely unknown. In this study, mice cortical neurons preconditioned with sublethal exposure to oxygen glucose deprivation (OGD) exhibited ATM/glucose-6-phosphate dehydrogenase pathway activation. Additionally, pharmacological inhibition of ATM prior to the preconditioning reversed neuroprotection provided by preconditioning in vitro and in vivo. Meanwhile, we found that ATM/P53 pro-apoptosis pathway was driven by lethal OGD injury, and pharmacological inhibition of ATM during fatal oxygen-glucose deprivation/reperfusion injury promoted neuronal survival. More importantly, inhibition of ATM activity after cerebral ischemia protected against cerebral ischemic-reperfusion damage in mice. In conclusion, our data show the dual role of ATM in neuronal ischemic preconditioning and lethal ischemic injury, involving in the protection of ischemic preconditioning, but promoting neuronal death in lethal ischemic injury. Thus, the present study provides new opportunity for the treatment of ischemic stroke.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Isquemia Encefálica/terapia , Córtex Cerebral/irrigação sanguínea , Precondicionamento Isquêmico , Animais , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Isquemia Encefálica/metabolismo , Sobrevivência Celular , Teste de Esforço , Glucose/deficiência , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle
18.
Photobiomodul Photomed Laser Surg ; 37(1): 17-24, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31050942

RESUMO

Objective: The objective of the present study was to investigate the application of a carbon arc lamp on wound healing in a rat cutaneous full-thickness wound model. Background data: In clinical practice, wound healing has been promoted by irradiation with a carbon arc lamp. However, the corresponding mechanism has not been clearly defined. Methods: A cutaneous full-thickness wound on the back of rats was irradiated using a carbon arc lamp at a wavelength peak range of 620-740 nm with 54 J/cm2. Injured sham-irradiated control rats were used as the control. The rats were euthanized after 7, 14, and 21 days, while wound reepithelialization and healing quality were examined by histological analyses with comparison between groups. Cell proliferation was observed by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining. Results: Irradiation by the carbon arc lamp significantly accelerated wound healing. The wound-healing rate in the treated group at day 21 was 98.42% ± 0.56%, compared with 93.58% ± 1.26% in the control group (p < 0.05). Significant increases in the length of epithelial edges, collagen content, and microvessel density were observed in the wound sites in the treated group at days 7, 14, and 21 (p < 0.05). Moreover, the number of BrdU-labeled cells increased in the wound edge at days 7 and 14 due to irradiation (p < 0.05). Conclusions: The results demonstrated that the carbon arc lamp can promote wound healing together with improvement in its quality by stimulating cell proliferation.


Assuntos
Terapia com Luz de Baixa Intensidade/instrumentação , Lesões dos Tecidos Moles/radioterapia , Cicatrização/efeitos da radiação , Animais , Carbono , Proliferação de Células , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
19.
Sheng Wu Gong Cheng Xue Bao ; 34(10): 1693-1705, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30394036

RESUMO

Organic waste is an important biomass resource. In this study the definition of coefficients for the calculation of all the secondary 10 forestry residue categories was improved and established according to literature reviewing of previous reports between 1982 and 2017. The rationality of value-taking for each coefficient in previous literature was examined by tracing to its citation sources. The irrational, or unstudied coefficients were assessed using the data in previous reports or questionnaire surveys. Lastly, values of the coefficient for the calculation of woody nursery residue, forest woody pruning residue, wood logging residue, firewood, wood bucking residue, wood handling residue, waste wood, banana and pineapple plant residue, bamboo processing residue and waste bamboo were reasonably assessed in this study.


Assuntos
Biomassa , Agricultura Florestal , Madeira
20.
Photomed Laser Surg ; 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30335572

RESUMO

OBJECTIVE: The objective of the present study was to investigate the application of a carbon arc lamp on wound healing in a rat cutaneous full-thickness wound model. BACKGROUND DATA: In clinical practice, wound healing has been promoted by irradiation with a carbon arc lamp. However, the corresponding mechanism has not been clearly defined. METHODS: A cutaneous full-thickness wound on the back of rats was irradiated using a carbon arc lamp at a wavelength peak range of 620-740 nm with 54 J/cm2. Injured sham-irradiated control rats were used as the control. The rats were euthanized after 7, 14, and 21 days, while wound reepithelialization and healing quality were examined by histological analyses with comparison between groups. Cell proliferation was observed by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining. RESULTS: Irradiation by the carbon arc lamp significantly accelerated wound healing. The wound-healing rate in the treated group at day 21 was 98.42% ± 0.56%, compared with 93.58% ± 1.26% in the control group (p < 0.05). Significant increases in the length of epithelial edges, collagen content, and microvessel density were observed in the wound sites in the treated group at days 7, 14, and 21 (p < 0.05). Moreover, the number of BrdU-labeled cells increased in the wound edge at days 7 and 14 due to irradiation (p < 0.05). CONCLUSIONS: The results demonstrated that the carbon arc lamp can promote wound healing together with improvement in its quality by stimulating cell proliferation.

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