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1.
Clin Exp Pharmacol Physiol ; 51(8): e13872, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38886134

RESUMO

Atherosclerosis, a lipid-driven chronic inflammatory disorder, is a significant global health concern associated with high rates of morbidity and mortality, imposing a substantial societal burden. The purpose of this study is to investigate the possible molecular mechanisms of atherosclerosis and identify potential therapeutic targets. We conducted an integrated bioinformatics analysis using data from peripheral blood mononuclear cell and TISSUE databases obtained from the Gene Expression Omnibus, to identify key genes associated with the progression of atherosclerosis. Here, IRF8 was found to be a key gene in atherosclerosis patients. Silencing IRF8 with small interfering RNA reduced inflammation in endothelial cells. This suggests IRF8 is a crucial biomarker for immune infiltration in atherosclerosis advance.


Assuntos
Aterosclerose , Biomarcadores , Biologia Computacional , Fatores Reguladores de Interferon , Humanos , Aterosclerose/genética , Aterosclerose/imunologia , Biologia Computacional/métodos , Fatores Reguladores de Interferon/genética , Biomarcadores/metabolismo , Inflamação/genética , Inflamação/imunologia
2.
BMC Biotechnol ; 23(1): 16, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391752

RESUMO

BACKGROUND: Currently, broad industrial application of laccases is commonly restricted by the high-cost related production. Solid state fermentation (SSF) using agricultural waste is an attractively economic strategy for laccase production, yet its efficiency is low. Pretreatment of cellulosic substrate might be a vital breakpoint to solve the problem in solid state fermentation (SSF). In this study, sodium hydroxide pretreatment was involved to prepare solid substrates from rice straw. Fermentability of solid substrates in terms of carbon resource supply, accessibility and water retention value, and their influence on performance of SSF were analyzed. RESULTS: The results showed that sodium hydroxide pretreatment provided desirable solid substrates with higher enzymatic digestibility and optimal water retention value, which further facilitated the homogeneity of mycelium growth, laccase distribution and nutrition utilization during SSF. The pretreated rice straw (1 h) with diameter less than 0.085 cm gave the maximum laccase production of 2912.34 U/g, which was 7.72 times higher than the control. CONCLUSION: Hence, we proposed that enough balance between nutrition accessibility and structure support was a must for rational design and preparation of solid substrate. Additionally, sodium hydroxide pretreatment of lignocellulosic waste might be an ideal step to enhance the efficiency and lower the production cost in SSF.


Assuntos
Oryza , Estudos de Viabilidade , Fermentação , Lacase , Hidróxido de Sódio , Água
3.
Small ; 19(22): e2205511, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36871143

RESUMO

Noble metal nanozymes hold promise in cancer therapy due to adjustable enzyme-like activities, unique physicochemical properties, etc. But catalytic activities of monometallic nanozyme are confined. In this study, 2D titanium carbide (Ti3 C2 Tx )-supported RhRu alloy nanoclusters (RhRu/Ti3 C2 Tx ) are prepared by a hydrothermal method and utilized for synergistic therapy of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) on osteosarcoma. The nanoclusters are small in size (3.6 nm), uniform in distribution, and have excellent catalase (CAT) and peroxidase (POD)-like activities. Density functional theory calculations show that there is a significant electron transfer interaction between RhRu and Ti3 C2 Tx , which has strong adsorption to H2 O2 and is beneficial to enhance the enzyme-like activity. Furthermore, RhRu/Ti3 C2 Tx nanozyme acts as both PTT agent for converting light into heat, and photosensitizer for catalyzing O2 to 1 O2 . With the NIR-reinforced POD- and CAT-like activity, excellent photothermal and photodynamic performance, the synergistic CDT/PDT/PTT effect of RhRu/Ti3 C2 Tx on osteosarcoma is verified by in vitro and in vivo experiments. This study is expected to provide a new research direction for the treatment of osteosarcoma and other tumors.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Ligas , Osteossarcoma/tratamento farmacológico , Adsorção , Neoplasias Ósseas/tratamento farmacológico
4.
Bioprocess Biosyst Eng ; 46(10): 1427-1435, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37490146

RESUMO

The underlying interplay between physicochemical property and enzymatic hydrolysis of cellulose still remains unclear. The impacts of matrix glycan composition of sugar beet pulp (SBP) on physical structure and saccharification efficiency were emphasized. The results showed that aqueous ammonia (AA) pretreatment could remove the non-cellulosic polysaccharides and destroy the linkage between the pectin and lignin. The cellulose supramolecule was changed significantly after AA pretreatment, in terms of the decline in hardness, gumminess, springiness, thickness and degree of polymerization. Furthermore, vascular cell was exposed and degraded. The highest reducing sugar yield of 355.06 mg/g was obtained from the pretreated SBP (80 °C) with enzyme loading of 30 U/g, which was 1.01 times higher than that of the untreated SBP. This research also supported the idea that recognizing and precisely removing the primary epitopes in cell walls might be an ideal strategy to accomplish the improved enzymatic hydrolysis through mild pretreatment.


Assuntos
Beta vulgaris , Beta vulgaris/química , Amônia/química , Hidrólise , Açúcares , Celulose/química , Pectinas , Parede Celular , Lignina
5.
Chin J Traumatol ; 26(3): 139-146, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36344366

RESUMO

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION: The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.


Assuntos
Traumatismos por Explosões , Lesão Pulmonar , Animais , Lesão Pulmonar/etiologia , Cabras , Explosões , Pulmão/patologia
6.
Angew Chem Int Ed Engl ; 62(51): e202316257, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37941302

RESUMO

The electrocatalytic oxidation of glucose plays a vital role in biomass conversion, renewable energy, and biosensors, but significant challenges remain to achieve high selectivity and high activity simultaneously. In this study, we present a novel approach for achieving complete glucose electrooxidation utilizing Cu-based metal-hydroxide-organic framework (Cu-MHOF) featuring coordinatively unsaturated Cu active sites. In contrast to traditional Cu(OH)2 catalysts, the Cu-MHOF exhibits a remarkable 40-fold increase in electrocatalytic activity for glucose oxidation, enabling exclusive oxidation of glucose into formate and carbonate as the final products. The critical role of open metal sites in enhancing the adsorption affinity of glucose and key intermediates was confirmed by control experiments and density functional theory simulations. Subsequently, a miniaturized nonenzymatic glucose sensor was developed showing superior performance with a high sensitivity of 214.7 µA mM-1 cm-2 , a wide detection range from 0.1 µM to 22 mM, and a low detection limit of 0.086 µM. Our work provides a novel molecule-level strategy for designing catalytically active sites and could inspire the development of novel metal-organic framework for next-generation electrochemical devices.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Glucose/química , Estruturas Metalorgânicas/química , Cobre/química , Limite de Detecção , Técnicas Eletroquímicas
7.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 43-46, 2023 Jan 30.
Artigo em Zh | MEDLINE | ID: mdl-36752005

RESUMO

OBJECTIVE: To use the low-cost anesthesia monitor for realizing anesthesia depth monitoring, effectively assist anesthesiologists in diagnosis and reduce the cost of anesthesia operation. METHODS: Propose a monitoring method of anesthesia depth based on artificial intelligence. The monitoring method is designed based on convolutional neural network (CNN) and long and short-term memory (LSTM) network. The input data of the model include electrocardiogram (ECG) and pulse wave photoplethysmography (PPG) recorded in the anesthesia monitor, as well as heart rate variability (HRV) calculated from ECG, The output of the model is in three states of anesthesia induction, anesthesia maintenance and anesthesia awakening. RESULTS: The accuracy of anesthesia depth monitoring model under transfer learning is 94.1%, which is better than all comparison methods. CONCLUSIONS: The accuracy of this study meets the needs of perioperative anesthesia depth monitoring and the study reduces the operation cost.


Assuntos
Anestesia , Inteligência Artificial , Redes Neurais de Computação , Frequência Cardíaca , Eletrocardiografia , Fotopletismografia/métodos
8.
BMC Cancer ; 22(1): 760, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35831854

RESUMO

BACKGROUND: Breast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction. METHODS: To assess the potential of soluble POSTN as a circulating biomarker, 242 participants, including 173 patients with different stages of BCa and 69 healthy individuals, were enrolled in this study. Soluble POSTN, together with CA153 and CEA, were determined in serum by enzyme linked immunosorbent assay (ELISA) or electrochemiluminescence immunoassays. RESULTS: Serum POSTN levels in locoregional BCa patients were significantly higher than that in healthy controls. Receiver operating curve (ROC) analysis revealed that, to distinguish health controls from locoregional BCa, POSTN was observed with the highest AUC (area under curve) (AUCPOSTN = 0.72 [0.65 - 0.79], AUCCA153 = 0.57 [0.49 - 0.64], AUCCEA = 0.62 [0.55 - 0.69]), and both CA153 and CEA were observed with significantly improved AUCs by combination with POSTN (AUCPOSTN + CA153 = 0.74 [0.67 - 0.80], P < 0.001; AUCPOSTN + CEA = 0.77 [0.70 - 0.82], P < 0.001). Moreover, the performances of the POSTN were comparable with that of CA153 in predicting distant metastasis of BCa (AUCPOSTN = 0.78 [0.71 - 0.84], AUCCA153 = 0.82 [0.76 - 0.88]). Kaplan-Meier analysis indicated that elevated serum POSTN was associated with poor overall survival and progression-free survival. CONCLUSIONS: This study suggested that soluble POSTN is a promising potential biomarker for diagnosis and metastasis prediction of BCa.


Assuntos
Neoplasias da Mama , Antígeno Carcinoembrionário , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Moléculas de Adesão Celular , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Neoplásica , Prognóstico , Curva ROC
9.
Blood Purif ; 51(1): 31-37, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34107477

RESUMO

AIM: This study aimed to evaluate the efficacy of the resin hemoperfusion device (HA380 hemoperfusion cartridge) on inflammatory responses during adult cardiopulmonary bypass (CPB). METHODS: Sixty patients undergoing surgical valve replacement were randomized into the HP group (n = 30) with an HA380 hemoperfusion cartridge in the CPB circuit or the control group (n = 30) with the conventional CPB circuit. The results of routine blood tests, blood biochemical indexes, and inflammatory factors were analyzed at V0 (pre-CPB), V1 (CPB 30 min), V2 (ICU 0 h), V3 (ICU 6 h), and V4 (ICU 24 h). RESULTS: The HP group had significantly lower levels of IL-6, IL-8, and IL-10. Significant estimation of group differences in the generalized estimating equation (GEE) models was also observed in IL-6 and IL-10. The HP group had significantly lower levels of creatinine (Cr), aminotransferase (AST), and total bilirubin (TBil) compared to the control group. The estimation of differences of Cr, AST, and TBil all reached statistical significance in GEE results. The HP group had significantly less vasopressor requirement and shorter mechanical ventilation time and ICU stay time as compared to the control group. CONCLUSION: The HA380 hemoperfusion cartridge could effectively reduce the systemic inflammatory responses and improve postoperative recovery of patients during adult CPB.


Assuntos
Ponte Cardiopulmonar/instrumentação , Hemoperfusão/instrumentação , Inflamação/etiologia , Adulto , Feminino , Hemodinâmica , Humanos , Inflamação/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade
10.
BMC Anesthesiol ; 22(1): 16, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996374

RESUMO

BACKGROUND: Sepsis is a highly heterogeneous syndrome with stratified severity levels and immune states. Even in patients with similar clinical appearances, the underlying signal transduction pathways are significantly different. To identify the heterogeneities of sepsis from multiple angles, we aimed to establish a combined risk model including the molecular risk score for rapid mortality prediction, pathway risk score for the identification of biological pathway variations, and immunity risk score for guidance with immune-modulation therapy. METHODS: We systematically searched and screened the mRNA expression profiles of patients with sepsis in the Gene Expression Omnibus public database. The screened datasets were divided into a training cohort and a validation cohort. In the training cohort, authentic prognostic predictor characteristics (differentially expressed mRNAs, pathway activity variations and immune cells) were screened for model construction through bioinformatics analysis and univariate Cox regression, and a P value less than 0.05 of univariate Cox regression on 28-day mortality was set as the cut-off value. The combined risk model was finally established by the decision tree algorithm. In the validation cohort, the model performance was assessed and validated by C statistics and the area under the receiver operating characteristic curve (AUC). Additionally, the current models were further compared in clinical value with traditional indicators, including procalcitonin (PCT) and interleukin-8 (IL-8). RESULTS: Datasets from two sepsis cohort studies with a total of 585 consecutive sepsis patients admitted to two intensive care units were downloaded as the training cohort (n = 479) and external validation cohort (n = 106). In the training cohort, 15 molecules, 20 pathways and 4 immune cells were eventually enrolled in model construction. These prognostic factors mainly reflected hypoxia, cellular injury, metabolic disorders and immune dysregulation in sepsis patients. In the validation cohort, the AUCs of the molecular model, pathway model, immune model, and combined model were 0.81, 0.82, 0.62 and 0.873, respectively. The AUCs of the traditional biomarkers (PCT and IL-8) were 0.565 and 0.585, respectively. The survival analysis indicated that patients in the high-risk group identified by models in the current study had a poor prognosis (P < 0.05). The above results indicated that the models in this study are all superior to the traditional biomarkers for the predicting the prognosis of sepsis patients. Furthermore, the current study provides some therapeutic recommendations for patients with high risk scores identified by the three submodels. CONCLUSIONS: In summary, the present study provides opportunities for bedside tests that could quantitatively and rapidly measure heterogeneous prognosis, underlying biological pathway variations and immune dysfunction in sepsis patients. Further therapeutic recommendations for patients with high risk scores could improve the therapeutic system for sepsis.


Assuntos
Escores de Disfunção Orgânica , Sepse/imunologia , Sepse/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Sepse/diagnóstico , Adulto Jovem
11.
Microcirculation ; 28(7): e12722, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34242445

RESUMO

BACKGROUND: Pulsatile flow protects vital organ function and improves microcirculatory perfusion during extracorporeal membrane oxygenation (ECMO). Studies revealed that pulsatile shear stress plays a vital role in microcirculatory function and integrity. The objective of this study was to investigate how pulsatility affects wall shear stress and endothelial glycocalyx components during ECMO. METHODS: Using the i-Cor system, sixteen canine ECMO models were randomly allocated into the pulsatile or the non-pulsatile group (eight canines for each). Hemodynamic parameters, peak wall shear stress (PWSS), serum concentration of syndecan-1, and heparan sulfate were measured at different time points during ECMO. Pulsatile shear stress experiments were also performed in endothelial cells exposed to different magnitudes of pulsatility (five plates for each condition), with cell viability, the expressions of syndecan-1, and endothelial-to-mesenchymal transformation (EndMT) markers analyzed. RESULTS: The pulsatile flow generated more surplus hemodynamic energy and preserved higher PWSS during ECMO. Serum concentrations of both syndecan-1 and heparan sulfate were negatively correlated with PWSS, and significantly lower levels were observed in the pulsatile group. Besides, non-pulsatility triggered EndMT and endothelial cells exposed to low pulsatility had the lowest possibility of EndMT. CONCLUSION: The maintenance of the PWSS by pulsatility during ECMO possesses beneficial effects on glycocalyx integrity. Moreover, pulsatility prevents EndMT in endothelial cells, and low pulsatility exhibits the best protective effects. The augmentation of pulsatility may be a plausible future direction to improve the clinical outcome in ECMO.


Assuntos
Oxigenação por Membrana Extracorpórea , Animais , Cães , Células Endoteliais , Glicocálix/metabolismo , Microcirculação , Fluxo Pulsátil
12.
J Nanobiotechnology ; 19(1): 160, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051801

RESUMO

Photodynamic therapy (PDT) is a non-invasive or minimally-invasive treatment which applies photosensitizers (PSs) to create reactive oxygen species (ROS) exposed to light trigger to destroy cancer cells. PDT can activate host anti-tumor immune responses but not powerful enough to kill metastatic tumors. Because of its carrier advantage, imaging, and therapeutic function together with enhanced permeability and retention (EPR) effect, nano-materials have already been used in photo-immunotherapy. Herein, photodynamic immunotherapy (PDIT) based on nanotechnology seems to be a hopeful new form of cancer therapy. In this article, we firstly summarize the recent development in photodynamic immunotherapy based on nanotechnology.


Assuntos
Imunoterapia/métodos , Nanotecnologia , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Animais , Linhagem Celular Tumoral , Humanos , Nanopartículas/uso terapêutico , Neoplasias/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio
13.
Med Sci Monit ; 27: e928205, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33395402

RESUMO

BACKGROUND We aimed to explore the effect of parecoxib sodium on myocardial ischemia-reperfusion (I/R) injury rats and its mechanism. MATERIAL AND METHODS The coronary artery of Sprague-Dawley rats was occluded for 6 h of myocardial ischemia, followed by reperfusion for 30 min (I/R group). Before ischemia, parecoxib sodium (10 mg/kg) was intraperitoneally injected twice a day for 3 consecutive days, followed by reperfusion for 6 h (I/R+Pare group). The cardiac function and changes in the infarction area were evaluated via echocardiography in each group. The differences in the expressions of apoptosis-related proteins were determined via immunohistochemistry and western blotting. Then, the percentage of reactive oxygen species (ROS)⁺ cells and the content of lipid peroxide were detected, based on which the degree of oxidative stress was evaluated. Next, the expressions of nuclear factor-kappaB (NF-kappaB) and nuclear factor E2-related factor 2 (Nrf-2) signaling pathways and downstream target genes were determined using real-time quantitative polymerase chain reaction (PCR). RESULTS After treatment with parecoxib sodium, the cardiac function of I/R injury rats was restored, and the infarction area and apoptosis level were reduced (P<0.05). Parecoxib sodium reduced the levels of ROS and lipid peroxidation in myocardial I/R injury rats, thereby weakening oxidative stress. It also regulated the redox imbalance caused by I/R injury through regulating NF-kappaB and Nrf-2 (P<0.01). In addition, after treatment with parecoxib sodium, NF-kappaB was significantly downregulated, while Nrf-2 was upregulated, and the content of proinflammatory cytokines was obviously reduced (P<0.01). CONCLUSIONS Parecoxib sodium exerts a protective effect against myocardial I/R injury through regulating antioxidant and inflammatory mechanisms.


Assuntos
Isoxazóis/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Citocinas/metabolismo , Testes de Função Cardíaca , Mediadores da Inflamação/metabolismo , Isoxazóis/farmacologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Small ; 16(42): e2004677, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32939988

RESUMO

Due to the widespread antibiotic-resistant microbes and the slow development in antibiotics, innovative new antibacterial agents are eagerly desired to control infection in the resistance era. Here, it is demonstrated that the antibacterial ability against drug-resistant bacteria can be endowed to transition metal dichalcogenides (XS2 , X = Mo/W) quantum dots by sulfur vacancies, and their application in bacterial keratitis. The sulfur vacancies are generated by the ion irradiation with the controlled influences, which ensures the one-way electron transport from the external environment to XS2 leading to a strong reactive oxygen speciesindependent oxidative stress. With the concentration of 140 µg mL-1 of XS2-0.1 quantum dots, the sterilization efficiency of Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus more than 99.9% within 20 min at room temperature in the dark is realized. For biomedical application against bacterial keratitis, it is observed that the occurrence of severe clinical manifestation like ocular perforation can be prevented. This work demonstrates the vacancy as a novel, simple, and effective strategy to tune XS2 as the antibacterial agent with a fast response and no reliance on light that has significant potential therapeutic effects on clinical drug resistant bacterial keratitis.


Assuntos
Ceratite , Staphylococcus aureus Resistente à Meticilina , Preparações Farmacêuticas , Pontos Quânticos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Humanos , Ceratite/tratamento farmacológico , Testes de Sensibilidade Microbiana
16.
Artif Organs ; 44(6): 577-583, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31875973

RESUMO

With the acceleration of demographic aging, heart failure has become a global public health issue. Left ventricular assist device (LVAD) provides a therapeutic option serving as a bridge to transplantation or destination treatment for end-stage heart failure. However, neither the molecular mechanism nor the gene expression profile of LVAD pathophysiology is well understood. Microarray dataset (GSE21610) was retrieved from the online database of the gene expression omnibus (GEO). Differentially expressed genes (DEGs) between microarrays obtained before and after LVAD therapy were analyzed using GEO2R. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out, followed by protein-protein interaction (PPI) network construction, which was further visualized by the Cytoscape software. Finally, a target gene-microRNA (miRNA) network was built using the NetworkAnalyst to predict potential miRNA interactions. A total of 36 upregulated DEGs and 14 downregulated DEGs were screened out. Five hub genes with the highest degree of connectivity were identified, including CCL2, CX3CR1, CD163, TLR7, and SERPINE1. CCL2 was identified as the most outstanding hub gene which is specially regulated by miR-124, miR-141, and miR-495. Our study indicates that CCL2 is crucial to the LVAD pathophysiology. The identified hub genes may be involved in cardiac inflammatory responses, remodeling, and the chemokine signaling pathway. These DEGs, pathways, hub genes, miRNAs are valuable for further investigations. This study provides a better understanding of the gene expression profile in LVAD pathophysiology.


Assuntos
Redes Reguladoras de Genes , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Complicações Pós-Operatórias/genética , Mapas de Interação de Proteínas/genética , Quimiocina CCL2/genética , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Complicações Pós-Operatórias/prevenção & controle , Mapeamento de Interação de Proteínas
17.
Molecules ; 25(24)2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33419270

RESUMO

Five new cyclic diarylheptanoids (platycary A-E, compounds 1-5) and three previously identified analogues (i.e., phttyearynol (compound 6), myricatomentogenin (compound 7), and juglanin D (compound 8)) were isolated from the stem bark of Platycarya strobilacea. The structures of these compounds were determined using NMR, HRESIMS, and electronic circular dichroism (ECD) data. The cytotoxicity of compounds 1-5 and their ability to inhibit nitric oxide (NO) production, as well as protect against the corticosterone-induced apoptosis of Pheochromocytoma (PC12) cells, were evaluated in vitro using the appropriate bioassays. Compounds 1 and 2 significantly inhibited the corticosterone-induced apoptosis of PC12 cells at a concentration of 20 µΜ.


Assuntos
Diarileptanoides/farmacologia , Juglandaceae/química , Estrutura Molecular , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Diarileptanoides/isolamento & purificação , Humanos , Neoplasias/patologia , Óxido Nítrico/metabolismo , Ratos
18.
J Cell Physiol ; 234(10): 18879-18886, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30972742

RESUMO

The aim of this study was to identify the association polymorphism (rs11536889) in the 3'-untranslated region (3'-UTR) of Toll-like receptors 4 (TLR4) and the risk for ventilator-associated pneumonia (VAP). miRNA database online and luciferase assays were used to validate TLR4 as the target gene of miR-1236. Enzyme-linked immunosorbent assay analysis and western blot were used to analyze the level of TLR4 in different genotype groups. In the present study, miR-1236 was predicted to bind to the rs11536889 G allele rather than the rs11536889 C allele, which was further confirmed by the luciferase activity suppressed by a fragment of 3'-UTR containing the rs11536889 G allele induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6). Bronchial epithelial cells isolated from participants genotyped as GG, GC, and CC, with no remarkable difference in TLR4 messenger RNA (mRNA) levels were observed among these genotype groups. After stimulating by LPS, a TLR4 ligand, the CC-genotyped cells expressed higher levels of IL-8, IL-6, and tumor necrosis factor alpha (TNF-α) on their surfaces than cells with the other genotypes. Finally, the western blot analysis results showed that the expression level of IL-8, IL-6, and TNF-α protein was much higher in the CC group than the GC and GG groups subsequent to stimulation by LPS, and the IL-8, IL-6, and TNF-α protein levels in the GC were grouped much lower compared with the GG group. These findings indicated the regulatory association of miR-1236 with TLR4 and the abnormal expression of TLR4 caused by the presence of rs11536889 in the 3'-UTR of mRNA, which interfere with its interaction with the miR-1236, contributing to the risk of VAP.


Assuntos
Regiões 3' não Traduzidas/genética , MicroRNAs/genética , Pneumonia Associada à Ventilação Mecânica/genética , Pneumonia Associada à Ventilação Mecânica/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Receptor 4 Toll-Like/genética , Alelos , Células Epiteliais Alveolares/fisiologia , Células Cultivadas , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/genética , RNA Mensageiro/genética , Respiração Artificial/métodos , Fator de Necrose Tumoral alfa/metabolismo
19.
Biochem Biophys Res Commun ; 513(1): 147-153, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30948157

RESUMO

OBJECTIVE: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. METHODS: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. RESULTS: Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. CONCLUSION: Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.


Assuntos
Calpaína/metabolismo , Glucose/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , Transdução de Sinais , Animais , Apoptose , Sinalização do Cálcio , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
20.
Bioprocess Biosyst Eng ; 42(4): 567-574, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30652220

RESUMO

Chemical composition and physical structure of solid substrate have significantly impacts on fermentation performance. The aqueous ammonia was used to pretreat rice straw. Furthermore, the feasibility of pretreatment to improve laccase production was also evaluated in terms of the enzymatic digestibility, chemical structure, physical structure, and laccase production. The results showed that aqueous ammonia pretreatment could modify chemical compositions, destroy rigid structure of the lignocellulosic substrate, increase enzymatic digestibility and change water state, which were beneficial to facilitate the fungus growth and nutrition utilization. Pretreatment of lignocellulosic substrate with aqueous ammonia at 80 °C gave the best effect on laccase production, yielding 172.74 U/g laccase at 14 days, which was 3.4 times higher than that of the control. The aqueous ammonia pretreatment could alternate the physicochemical characteristics of lignocellulosic substrate, resulting in the improved laccase production, which was a promising method that might be explored in solid-state fermentation.


Assuntos
Basidiomycota/crescimento & desenvolvimento , Proteínas Fúngicas/biossíntese , Lacase/biossíntese , Lignina , Oryza/química , Fermentação , Hidrólise , Lignina/química , Lignina/metabolismo
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