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1.
PLoS Pathog ; 20(5): e1012266, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38787906

RESUMO

Mycoplasmas are minimal but notorious bacteria that infect humans and animals. These genome-reduced organisms have evolved strategies to overcome host apoptotic defense and establish persistent infection. Here, using Mycoplasma bovis as a model, we demonstrate that mycoplasma glycine cleavage system (GCS) H protein (GcvH) targets the endoplasmic reticulum (ER) to hijack host apoptosis facilitating bacterial infection. Mechanically, GcvH interacts with the ER-resident kinase Brsk2 and stabilizes it by blocking its autophagic degradation. Brsk2 subsequently disturbs unfolded protein response (UPR) signaling, thereby inhibiting the key apoptotic molecule CHOP expression and ER-mediated intrinsic apoptotic pathway. CHOP mediates a cross-talk between ER- and mitochondria-mediated intrinsic apoptosis. The GcvH N-terminal amino acid 31-35 region is necessary for GcvH interaction with Brsk2, as well as for GcvH to exert anti-apoptotic and potentially pro-infective functions. Notably, targeting Brsk2 to dampen apoptosis may be a conserved strategy for GCS-containing mycoplasmas. Our study reveals a novel role for the conserved metabolic route protein GcvH in Mycoplasma species. It also sheds light on how genome-reduced bacteria exploit a limited number of genomic proteins to resist host cell apoptosis thereby facilitating pathogenesis.


Assuntos
Apoptose , Proteínas de Bactérias , Retículo Endoplasmático , Humanos , Retículo Endoplasmático/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Animais , Infecções por Mycoplasma/metabolismo , Infecções por Mycoplasma/microbiologia , Mycoplasma bovis/metabolismo , Glicina/metabolismo , Resposta a Proteínas não Dobradas , Proteínas Serina-Treonina Quinases/metabolismo
2.
J Org Chem ; 89(7): 5049-5059, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38491018

RESUMO

A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.

3.
Appl Microbiol Biotechnol ; 108(1): 290, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587616

RESUMO

For the development of a competitive ELISA (cELISA) to detect serum antibodies against the Mycoplasma mycoides subsp. Mycoides (Mmm) (strain PG1), the causative agent of contagious bovine pleuropneumonia (CBPP), all the proteins of this pathogen were analyzed. Then, a specific extracellular region of a transmembrane protein with the potential for diagnosis was identified. After that, a monoclonal antibody (Mab) named 3A8 was obtained using this extracellular region as an immunogen. Finally, a cELISA was established with the extracellular domain of this transmembrane protein as the coating antigen, Mab 3A8 as the competitive antibody, and HRP-labeled goat anti-mouse IgG as the enzyme-labeled antibody. This established method was used to detect the antibody dynamic regularity of goats which are artificially immunized Mmm and was also compared with a commercial ELISA kit. Further, the sera of 1011 different cattle from border provinces of China were monitored using a candidate Mab 3A8 cELISA. The detection results of known background sera used in this study indicate that a candidate diagnostic marker was successfully identified by analyzing all the coding proteins of Mmm in this research, and the cELISA established based on the Mab 3A8 against this protein can detect CBPP-positive serum with specificity and has no cross-reaction with other related epidemic disease-positive sera. In addition, we tested the sera collected from the border areas of China using the established ELISA, and no positive sample was detected. The research protocol of the CBPP cELISA established in this study is different from the traditional method, which can greatly reduce the investment of manpower and capital and save development time. We believe that this study's protocol could serve as a reference for the development of detection methods for mycoplasma and other complex pathogens. KEY POINTS: • A Mmm-specific diagnostic marker was obtained based on protein characteristics. • A cELISA was established for CBPP serum antibody detection. • The serological investigation was conducted for CBPP in the border areas of China.


Assuntos
Anticorpos Monoclonais , Pleuropneumonia , Animais , Bovinos , Proteínas de Membrana , China , Ensaio de Imunoadsorção Enzimática , Cabras
4.
Mol Microbiol ; 118(3): 208-222, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35791781

RESUMO

The unfolded protein response (UPR) plays a crucial role in Mycoplasma hyopneumoniae (M. hyopneumoniae) pathogenesis. We previously demonstrated that M. hyopneumoniae interferes with the host UPR to foster bacterial adhesion and infection. However, the underlying molecular mechanism of this UPR modulation is unclear. Here, we report that M. hyopneumoniae membrane protein Mhp271 interacts with host GRP78, a master regulator of UPR localized to the porcine tracheal epithelial cells (PTECs) surface. The interaction of Mhp271 with GRP78 reduces the porcine beta-defensin 2 (PBD-2) production, thereby facilitating M. hyopneumoniae adherence and infection. Furthermore, the R1-2 repeat region of Mhp271 is crucial for GRP78 binding and the regulation of PBD-2 expression. Intriguingly, a coimmunoprecipitation (Co-IP) assay and molecular docking prediction indicated that the ATP, rather than the substrate-binding domain of GRP78, is targeted by Mhp271 R1-2. Overall, our findings identify host GRP78 as a target for M. hyopneumoniae Mhp271 modulating the host UPR to facilitate M. hyopneumoniae adherence and infection.


Assuntos
Mycoplasma hyopneumoniae , Adesinas Bacterianas/metabolismo , Animais , Chaperona BiP do Retículo Endoplasmático , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Mycoplasma hyopneumoniae/genética , Mycoplasma hyopneumoniae/metabolismo , Suínos , Resposta a Proteínas não Dobradas
5.
J Biomed Inform ; 142: 104371, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37149274

RESUMO

Accurate and efficient extraction of key information related to diseases from medical examination reports, such as X-ray and ultrasound images, CT scans, and others, is crucial for accurate diagnosis and treatment. These reports provide a detailed record of a patient's health condition and are an important part of the clinical examination process. By organizing this information in a structured way, doctors can more easily review and analyze the data, leading to better patient care. In this paper, we introduce a new technique for extracting useful information from unstructured clinical text examination reports, which we refer to as a medical event extraction (EE) task. Our approach is based on Machine Reading Comprehension (MRC) and involves two sub-tasks: Question Answerability Judgment (QAJ) and Span Selection (SS). We use BERT to build a question answerability discriminator (Judger) that determines whether a reading comprehension question can be answered or not, thereby avoiding the extraction of arguments from unanswerable questions. The SS sub-task first obtains the encoding of each word in the medical text from the final layer of BERT's Transformer, then utilizes the attention mechanism to identify important information related to the answer from these word encodings. This information is then input into a bidirectional LSTM (BiLSTM) module to obtain a global representation of the text, which is used, along with the softmax function, to predict the span of the answer (i.e., the start and end positions of the answer in the text report). We use interpretable methods to calculate the Jensen-Shannon Divergence (JSD) score between various layers of the network and confirm that our model has strong word representation capabilities, enabling it to effectively extract contextual information from medical reports. Our experiments demonstrate that our method outperforms existing medical event extraction methods, achieving state-of-the-art results with a notable F1 score.


Assuntos
Neoplasias , Relatório de Pesquisa , Humanos
6.
Clin Exp Pharmacol Physiol ; 50(12): 954-963, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37771072

RESUMO

Myocardial ischemia/reperfusion (I/R) injury is the primary cause of heart damage in the treatment of myocardial infarction, and the imbalance of the energy metabolism in the pathogenesis of myocardial I/R is one of the main triggers of cardiac dysfunction. Monocarboxylate transporter 4 (MCT4) is a key transporter of lactate, which plays a vital role in cellular metabolism. The present study investigated the role and underlying mechanism of MCT4 in myocardial I/R injury. The results of this study showed that MCT4 was upregulated during oxygen-glucose deprivation (OGD) and restored after reoxygenation in cardiomyocytes HL-1. Interestingly, the overexpression of MCT4 increased cell viability and decreased apoptosis of OGD/R-induced HL-1 cells. Furthermore, MCT4 boosted glucose uptake and lactate levels and promoted protein expression of glycolysis regulator LDHA, while also impeding oxidative phosphorylation (OXPHOS) regulators C-MYC and NDUFB8 in OGD/R-induced HL-1 cells. A reduction in reactive oxygen species and oxidative stress markers malonaldehyde and superoxide dismutase was also observed within the OGD/R stimulated HL-1 cells. Additionally, the in vivo exogenous application of MCT4 restored cardiac function, as demonstrated by the reduced infarct size and decreased myocardial apoptosis in I/R rats. OXPHOS and oxidative stress declined, while glycolysis was activated when the I/R mice were injected with AAV-MCT4. Our findings indicate that MCT4 could exert a cardioprotective effect after myocardial I/R injury by inducing OXPHOS/glycolysis interconversion and inhibiting oxidative stress.


Assuntos
Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Ratos , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Fosforilação Oxidativa , Estresse Oxidativo , Miócitos Cardíacos , Oxigênio/metabolismo , Glicólise , Lactatos/metabolismo , Lactatos/farmacologia , Apoptose , Traumatismo por Reperfusão/patologia , Glucose/metabolismo
7.
Eat Weight Disord ; 27(8): 3389-3398, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36071328

RESUMO

PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Comportamentos Relacionados com a Saúde , Humanos , Adolescente , Adulto Jovem , Adulto , Ortorexia Nervosa , Estudos Transversais , Reprodutibilidade dos Testes , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Estudantes , Inquéritos e Questionários , Psicometria/métodos
8.
Infect Immun ; 88(7)2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32312764

RESUMO

Mycoplasma hyopneumoniae causes the disease porcine enzootic pneumonia, a highly contagious and chronic disease affecting pigs. Understanding the molecular mechanisms of its pathogenicity is critical for developing effective interventions to control this swine respiratory disease. Here, we describe a novel virulence mechanism by which M. hyopneumoniae interferes with the host unfolded protein response (UPR) and eventually facilitates bacterial adhesion and infection. We observed that M. hyopneumoniae infection suppressed the UPR target molecules GRP78 and CHOP by reducing PKR-like endoplasmic reticulum kinase/eukaryotic initiation factor 2 alpha (PERK/eIF2α) phosphorylation, ATF6 cleavage, and X-box binding protein 1 (XBP1) splicing. Interestingly, further analyses revealed that host UPR inhibition subsequently suppressed the NF-κB pathway, leading to the reduced production of porcine beta-defensin 2 (PBD-2), thus facilitating M. hyopneumoniae adherence and infection. This study provides new insights into the molecular pathogenesis of M. hyopneumoniae and sheds light upon its interactions with the host.


Assuntos
Mycoplasma hyopneumoniae/fisiologia , Pneumonia Suína Micoplasmática/metabolismo , Pneumonia Suína Micoplasmática/microbiologia , Resposta a Proteínas não Dobradas , beta-Defensinas/biossíntese , Animais , Aderência Bacteriana , Biomarcadores , Interações Hospedeiro-Patógeno , NF-kappa B/metabolismo , Transdução de Sinais , Suínos
9.
Appl Opt ; 58(27): 7298-7304, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674373

RESUMO

The conical diffraction Offner hyperspectral imaging spectrometer (CDO-HIS) is a hyperspectral calibrator for monitoring the radiation stability of an ocean color sensor. The spectrometer adopts the structure of the conical diffraction Offner configuration (CDO-CF), containing a convex blazed grating to produce a nearly nondistortion and high spectral fidelity image. The theory analysis of the conical diffraction Offner is discussed and introduced to the instrument design. The optimization procedure and design results of CDO-HIS and the conical diffraction grating are provided based on the design ideas, which show benefits of the employment of CDO-CF. The results of laboratory characterization are presented, including the grating diffraction efficiency and the instrument performance.

10.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067654

RESUMO

As a gaseous biological signaling molecule, nitric oxide (NO) regulates many physiological processes in plants. Over the last decades, this low molecular weight compound has been identified as a key signaling molecule to regulate plant stress responses, and also plays an important role in plant development. However, elucidation of the molecular mechanisms for NO in leaf development has so far been limited due to a lack of mutant resources. Here, we employed the NO-deficient mutant nia1nia2 to examine the role of NO in leaf development. We have found that nia1nia2 mutant plants displayed very different leaf phenotypes as compared to wild type Col-0. Further studies have shown that reactive oxygen species (ROS) levels are higher in nia1nia2 mutant plants. Interestingly, ROS-related enzymes ascorbate peroxidase (APX), catalases (CAT), and peroxidases (POD) have shown decreases in their activities. Our transcriptome data have revealed that the ROS synthesis gene RBOHD was enhanced in nia1nia2 mutants and the photosynthesis-related pathway was impaired, which suggests that NO is required for chloroplast development and leaf development. Together, these results imply that NO plays a significant role in plant leaf development by regulating ROS homeostasis.


Assuntos
Arabidopsis/metabolismo , Homeostase , Óxido Nítrico/metabolismo , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Nitrato Redutase/genética , Nitrato Redutase/metabolismo , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento
11.
J Cell Biochem ; 116(11): 2465-75, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25650113

RESUMO

Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to be associated with carcinogenesis. However, the cellular function of TAZ in human hepatocellular carcinoma (HCC) remains elusive. In this study, an immunohistochemistry analysis revealed that the expression of TAZ in cancer tissue samples from 180 HCC patients was significantly higher than that in adjacent normal tissues. In addition, TAZ overexpression was significantly correlated with aggressive tumor characteristics such as tumor size, TNM stage, lymph node or distant metastasis, histological differentiation, and recurrent HCC (P < 0.05). The Kaplan-Meier test showed that TAZ-positive expression was related to a poor prognosis compared to TAZ-negative expression (P < 0.05). Furthermore, the expression level of TAZ was generally correlated with the invasiveness of cancer cells. The overexpression of TAZ in the Huh7 cell line, which endogenously expresses TAZ at low levels, significantly promoted cell proliferation, migration and invasion and inhibited apoptosis, whereas RNA interference-mediated knockdown of TAZ in the highly invasive cell line MHCC-97H significantly suppressed cell proliferation, migration and invasion in vitro and tumor formation in vivo.


Assuntos
Carcinoma Hepatocelular/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/patologia , Oncogenes , Idoso , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Prognóstico , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional
12.
Hepatobiliary Pancreat Dis Int ; 14(2): 186-93, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25865692

RESUMO

BACKGROUND: Cell therapy has been promising for various diseases. We investigated whether transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) has any therapeutic effects on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced fulminant hepatic failure in mice. METHODS: hUCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with GalN/LPS-induced fulminant hepatic failure. After transplantation, the localization and differentiation of hUCMSCs in the injured livers were investigated by immunohistochemical and genetic analyses. The recovery of the injured livers was evaluated histologically. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test. RESULTS: hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adipogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the formation of hUCMSCs-derived hepatocyte-like cells in vivo. CONCLUSIONS: hUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUCMSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.


Assuntos
Antígenos CD/análise , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Falência Hepática Aguda/terapia , Fígado/patologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/química , Albuminas/análise , Elementos Alu/genética , Animais , Diferenciação Celular , Galactosamina , Humanos , Queratina-18/análise , Lipopolissacarídeos , Lipase Lipoproteica/genética , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Masculino , Camundongos , Camundongos SCID , Necrose/etiologia , Necrose/terapia , Osteopontina/genética , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/sangue , alfa-Fetoproteínas/análise
13.
Cell Biol Int ; 38(5): 599-609, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24375611

RESUMO

Restenosis severely limits the overall efficacy of interventions. One of the reasons is the lack of reendothelialization related to inhibition of endothelial cell proliferation and migration since drug is delivered to the luminal surface. Statins can promote angiogenic processes by improving endothelial function, proliferation and migration in cardiac microvascular endothelial cells (CMECs). This study clarified the effect of simvastatin on Akt/mTOR/p70 S6K and FoxO3a signalling pathways in rat CMECs following pretreated with rapamycin. Rapamycin treatment for 24 h inhibited CMECs' proliferation, migration and NO (nitric oxide) secretion, but with increased cell apoptosis and reactive oxygen species (ROS) production. In contrast, simvastatin pretreatment significantly improved proliferation, migration and NO secretion, and inhibited CMECs' apoptosis and ROS production in rapamycin-induced CMECs. Western blot assay showed that, after treatment with simvastatin, the phosphorylation of Akt/mTOR/p70 S6K and FoxO3a were up-regulated in rapamycin-induced CMECs, which was significantly reversed by pretreatment with LY294002. The data suggest that simvastatin inhibits rapamycin-induced CMECs dysfunction and apoptosis, probably through activation of PI3K/Akt/mTOR/p70 S6K and mTOR/FoxO3a signalling pathway in a sequential manner and this pathway may be important in some of the pleiotropic effects of statins.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sinvastatina/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Endoteliais/efeitos dos fármacos , Proteína Forkhead Box O3 , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Masculino , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley
14.
Front Bioeng Biotechnol ; 11: 1150819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937764

RESUMO

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds.

15.
Oxid Med Cell Longev ; 2023: 2345279, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860732

RESUMO

As a critical member in wound healing, vascular endothelial cells (ECs) impaired under high levels of reactive oxygen species (ROS) would hamper neovascularization. Mitochondria transfer can reduce intracellular ROS damage under pathological condition. Meanwhile, platelets can release mitochondria and alleviate oxidative stress. However, the mechanism by which platelets promote cell survival and reduce oxidative stress damage has not been clarified. Here, first, we selected ultrasound as the best method for subsequent experiments by detecting the growth factors and mitochondria released from manipulation platelet concentrates (PCs), as well as the effect of manipulation PCs on the proliferation and migration of HUVECs. Then, we found that sonicate platelet concentrates (SPC) decreased the level of ROS in HUVECs treated with hydrogen peroxide in advance, increased mitochondrial membrane potential, and reduced apoptosis. By transmission electron microscope, we saw that two kinds of mitochondria, free or wrapped in vesicles, were released by activated platelets. In addition, we explored that platelet-derived mitochondria were transferred to HUVECs partly by means of dynamin-dependent clathrin-mediated endocytosis. Consistently, we determined that platelet-derived mitochondria reduced apoptosis of HUVECs caused by oxidative stress. What is more, we screened survivin as the target of platelet-derived mitochondria via high-throughput sequencing. Finally, we demonstrated that platelet-derived mitochondria promoted wound healing in vivo. Overall, these findings revealed that platelets are important donors of mitochondria, and platelet-derived mitochondria can promote wound healing by reducing apoptosis caused by oxidative stress in vascular endothelial cells. And survivin is a potential target. These results further expand the knowledge of the platelet function and provide new insights into the role of platelet-derived mitochondria in wound healing.


Assuntos
Células Endoteliais , Estresse Oxidativo , Espécies Reativas de Oxigênio , Survivina , Cicatrização , Mitocôndrias
16.
Front Oncol ; 13: 1110796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37265799

RESUMO

Objective: To explore the correlation between ultrasound images and molecular typing of invasive breast cancer, so as to analyze the predictive value of preoperative ultrasound for invasive breast cancer. Methods: 302 invasive breast cancer patients were enrolled in Heping Hospital affiliated to Changzhi Medical College in Shanxi, China during 2020 to 2022. All patients accepted ultrasonic and pathological examination, and all pathological tissues received molecular typing with immunohistochemical (IHC) staining. The relevance between different molecular typings and ultrasonic image, pathology were evaluated. Results: Univariate analysis: among the four molecular typings, there were significant differences in tumor size, shape, margin, lymph node and histological grade (P<0.05). 1. Size: Luminal A tumor was smaller (69.4%), Basal -like type tumors are mostly larger (60.9%); 2. Shape: Basal-like type is more likely to show regular shape (45.7%); 3. Margin: Luminal A and Luminal B mostly are not circumscribed (79.6%, 74.8%), Basal -like type shows circumscribed(52.2%); 4. Lymph nodes: Luminal A type tends to be normal (87.8%), Luminal B type,Her-2+ type and Basal-like type tend to be abnormal (35.6%,36.4% and 39.1%). There was no significant difference in mass orientation, echo pattern, rear echo and calcification (P>0.05). Multivariate analysis: Basal-like breast cancer mostly showed regular shape, circumscribed margin and abnormal lymph nodes (P<0.05). Conclusion: There are differences in the ultrasound manifestations of different molecular typings of breast cancer, and ultrasound features can be used as a potential imaging index to provide important information for the precise diagnosis and treatment of breast cancer.

17.
Zhong Yao Cai ; 35(10): 1679-83, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23627138

RESUMO

OBJECTIVE: To study the optimum extraction technology of total flavonoids and total triterpenoids from Tetrastigma planicaule and their antioxidant activity. METHODS: Optimized the extraction of total flavonoids and total triterpenoids using an L9 (3(4)) orthogonal array design, and the antioxidant activity was extimated by FRAP assay, salicylicl acid assay and ABTS assay. RESULTS: The best extraction conditions for total flavonoids from Tetrastigma planicaule were as follows: 70 degrees C of 70% ethanol ultrasound-assisted extracting for 1 h and extracting three times, and total triterpenoids was:70 degrees C of 60% ethanol microwave extracting for 5 min and extracting two times. Compared with the positive control samples VC and tea polyphenol, the activity of reducing Fe3+ antioxidant and scavenging ABTS + * of flavonoids from Tetrastigma planicaule was higher than that of tea polyphenol, but scavenging OH * was lower than theirs; CONCLUSION: The method of using ultrasound-assisted extraction to extract total flavonoids and microwave extraction to extract total triterpenoids is the best, the extracts of Tetrastigma planicaule also shows certain antioxidative activity.


Assuntos
Antioxidantes/farmacologia , Flavonoides/isolamento & purificação , Tecnologia Farmacêutica/métodos , Triterpenos/isolamento & purificação , Vitaceae/química , Antioxidantes/isolamento & purificação , Etanol/química , Flavonoides/farmacologia , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Micro-Ondas , Oxirredução/efeitos dos fármacos , Caules de Planta/química , Solventes , Triterpenos/farmacologia , Ultrassom
18.
J Biomed Nanotechnol ; 18(2): 535-545, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35484761

RESUMO

In this study we evaluated the impact of topical application of bioactive glass fibers loaded PRP on a deep seconddegree thermal wound and its healing process sub-streaming molecular pathway of re-epithelialization. Wistar rats were randomly divided into four groups: normal control group, model group (deep second-degree thermal wound), PRP group, and PRP+nanobioactive glass fiber group. After treatment, the changes of wounds were observed daily. H&E staining was used to evaluate the pathological changes and also, qRT-PCR was used to detect the mRNA expression of KGF, IL-1, IL-6, IL-10, TGF-ß, EGF, VEGF, HIF-1α, integrin α3 and integrin ß1 in wound tissues. In the current study, we observed that PRP group and the PRP group basically re-epithelized on the 21st day. The wound healing rates of the PRP+nanobioactive glass fiber group and PRP group at each time point were higher than those in the model group, while there was no significant difference in wound healing rate between the PRP+nanobioactive glass fiber group and PRP group at each time point. H&E staining showed that the pathological scores of skin wound repairing in the PRP+nanobioactive glass fiber group on the 7th, 14th and 21st day were higher than that of in the model group. The qPCR results suggested the mRNA expression of IL-1, IL-6 and IL-10 in the PRP+nanobioactive glass fiber group and the PRP group were lower than those in the untreated group on the 14th day; the expression of VEGF and EGF mRNA were higher on the 3rd day; the mRNA expression of TGF-ß, HIF-1α showed a tendency of increasing first and decreasing then; integrin ß1 mRNA expression increased significantly, which was highest; integrin α3 mRNA expression was higher on day 3rd and 21th, respectively. The PRP+nanobioactive glass fibers and PRP can shorten the wound healing time and improve the healing quality mainly by promoting the wound epithelization through increasing the expression of EGF, VEGF, TGF-ß, HIF-1α, Integrin α3, and meanwhile increasing the release of Integrin ß1 and other mechanisms.


Assuntos
Interleucina-10 , Plasma Rico em Plaquetas , Animais , Fator de Crescimento Epidérmico/metabolismo , Vidro , Integrina alfa3/metabolismo , Integrina beta1/metabolismo , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Plasma Rico em Plaquetas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização
19.
Front Bioeng Biotechnol ; 10: 908585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662842

RESUMO

Wound repair is accomplished by the interaction between the cells involved in the repair and the extracellular matrix (ECM). Collagen is the main component of ECM, which is involved in transduction of signal, transportation of growth factors and cytokines. Fibronectin (FN) is also an important ECM, which participates in the initiation of fibroblast cell (FC) and promotes adhesion, migration, proliferation and differentiation of target cells. Compared with natural protein, the recombinant protein prepared by artificial method has the advantages of poor immunogenicity, wide range of sources, low cost and high activity. In this study, we used recombinant human-like collagen (RHC) and recombinant human-like fibronectin (rhFN) to treat acute wounds in C57BL/6 mice individually or in combination, and explored their effects on wound healing. Our study confirmed that these two recombinant proteins could effectively promote the proliferation, migration and adhesion of FCs. Meanwhile, it could positively regulate the healing speed and quality of acute wounds, re-epithelialization, collagen deposition, inflammation and angiogenesis. Moreover, we proved that the combination of the two was better than the treatment alone. Consequently, it has a good prospect as a new tissue material in the field of skin repair.

20.
Sci Total Environ ; 843: 156925, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35753451

RESUMO

A novel molecularly imprinted electrochemiluminescence (MIECL) sensor based on the luminescence of molecularly imprinted polymer-perovskite (MIP-CsPbBr3) layer and Ru(bpy)32+ was fabricated for simazine detection. MIP-CsPbBr3 layers were immobilized onto the surface of glassy carbon electrode as the capture and signal amplification probe, and Ru(bpy)32+ and co-reactant tripropylamine exhibited stronger electrochemiluminescence (ECL) emission. Under optimal conditions, the ECL signal of the MIECL sensor was linearly quenched, with the logarithm of simazine concentration ranging from 0.1 µg/L to 500.0 µg/L, correlation coefficient of 0.9947, and limit of detection of 0.06 µg/L. The practicality of the developed MIECL sensor method for simazine determination in aquatic samples was validated. Excellent recoveries of 86.5 %-103.9 % with relative standard deviation below 1.6 % were obtained for fish and shrimp samples at three different spiked concentrations. The MIECL sensor exhibited excellent selectivity, sensitivity, reproducibility, accuracy, and precision for simazine determination in actual aquatic samples.


Assuntos
Técnicas Eletroquímicas , Medições Luminescentes , Animais , Compostos de Cálcio , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , Óxidos , Reprodutibilidade dos Testes , Simazina , Titânio
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