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1.
Artigo em Inglês | MEDLINE | ID: mdl-38658189

RESUMO

Iron is a fundamental element for biological life, starting from bacteria till humans. Iron is essential for cell function and survival, energy production and metabolism, whereas increased levels cause oxidative stress. It is also a constituent of haemoglobin and thus it is necessary for oxygen transportation through the body. Given these multiple functions, the regulation of iron metabolism is complex and tight coupled with oxygen homeostasis at tissue and cellular levels, thanks to the interaction with the hypoxia inducible factor (HIF) system. In patients with chronic kidney disease (CKD), iron deficiency significantly contributes to anaemia development. This frequently overlaps with chronic inflammation, causing iron- restricted erythropoiesis. To add further complexity, metabolic hyperferritinemia may, on one side, increase the risk for CKD and, on the other, overlaps with functional iron deficiency. Excessive intracellular iron in certain cell types during CKD can also mediate cellular death (called ferroptosis), and contribute to the pathogenesis of kidney damage, atherosclerosis and vascular calcifications. This review is aimed at broadening the perspective of iron metabolism in the setting of CKD not just as a contributor to anaemia in CKD patients, but also as an important player with an impact on cell metabolism, renal fibrosis, and the cardiovascular system.

2.
Chem Biodivers ; 21(6): e202301509, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38594219

RESUMO

Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.


Assuntos
Janus Quinase 2 , Microalgas , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Oxidopamina , Fator de Transcrição STAT3 , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Microalgas/química , Microalgas/metabolismo , Oxidopamina/farmacologia , Oxidopamina/antagonistas & inibidores , Heme Oxigenase-1/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Transdução de Sinais/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos
3.
Molecules ; 29(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38338436

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile-Ile-Ala-Val-Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight. The structure and antioxidant activity of IIAVE were tested in a previous study and proved to have good antioxidant potential. In this study, the chemical properties of IIAVE were calculated using quantum chemical methods, including frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural population analysis (NPA), and global reactivity properties. The interaction of IIAVE with Bcl-2 and DJ-1 was investigated using the molecular docking method. The results showed that IIAVE promoted the activation of the Keap1/Nrf2 pathway and up-regulated the expression of the superoxide dismutase 1 (SOD-1) protein by inhibiting the level of reactive oxygen species (ROS) in cells. In addition, IIAVE inhibits ROS production and prevents 6-OHDA-induced oxidative damage by restoring mitochondrial membrane potential. Furthermore, IIAVE inhibited cell apoptosis by increasing the Bcl-2/Bax ratio and inhibiting the activation of Caspase-9 and Caspase-3. Thus, IIAVE may become a potential drug for the treatment and prevention of PD.


Assuntos
Haptófitas , Neuroblastoma , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Idoso , Neuroproteção , Espécies Reativas de Oxigênio/metabolismo , Oxidopamina/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Haptófitas/metabolismo , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Apoptose , Antioxidantes/farmacologia , Doença de Parkinson/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
4.
Mar Drugs ; 21(3)2023 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36976205

RESUMO

Epi-aszonalenin A (EAA) is an alkaloid that is isolated and purified from the secondary metabolites of coral symbiotic fungi and has been shown to have good atherosclerotic intervention activity and anti-angiogenic activity in our previous studies. In the present study, antiangiogenic activity was used as a basis of an intensive study of its mechanism of action against tumor metastasis and invasion. Invasive metastatic pairs are a hallmark of malignancy, and the dissemination of tumor cells is the most dangerous process in the development of tumors. The results of cell wound healing and the Transwell chamber assay showed that EAA interfered well with PMA-induced migration and invasion of HT1080 cells. Western blot and the ELISA assay showed that EAA decreased MMPs and vascular endothelial growth factor (VEGF) activity and inhibited the expression of N-cadherin and hypoxia-inducible factor-1α (HIF-1α) by regulating the phosphorylation of downstream mitogen-activated protein kinase (MAPK), PI3K/AKT, and NF-κB pathways. Simultaneous molecular docking results revealed that the mimic coupling between the EAA and MMP-2/-9 molecules formed a stable interaction. The results of this study provide a research basis for the inhibition of tumor metastasis by EAA, and together with previous studies, confirm the potential pharmacology and drug potential for this class of compound for application in angiogenesis-related diseases and further improve the availability of coral symbiotic fungi.


Assuntos
Fosfatidilinositol 3-Quinases , Fator A de Crescimento do Endotélio Vascular , Fator A de Crescimento do Endotélio Vascular/metabolismo , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Movimento Celular , Subunidade alfa do Fator 1 Induzível por Hipóxia
5.
PLoS Genet ; 16(10): e1009148, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33085664

RESUMO

[This corrects the article DOI: 10.1371/journal.pgen.1008456.].

6.
BMC Musculoskelet Disord ; 24(1): 295, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37060012

RESUMO

PURPOSE: This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF). METHODS: A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler's formula was employed to estimate the patient's blood volume (PBV), Gross's formula to estimate TBL, and Sehat's formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance. RESULTS: TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group. CONCLUSIONS: Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Resultado do Tratamento , Fusão Vertebral/efeitos adversos , Exsanguinação , Procedimentos Cirúrgicos Minimamente Invasivos
7.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674443

RESUMO

Alzheimer's disease (AD), a neurodegenerative disease, is the most common cause of dementia in humans worldwide. Although more in-depth research has been carried out on AD, the therapeutic effect of AD is not as expected, and natural active substances are increasingly sought after by scientists. In the present study, we evaluated two benzaldehydes from a coral-derived Aspergillus terreus strain C23-3, their anti-neuroinflammatory activity in microglia (BV-2), and their neuroprotective activity and mechanisms in hippocampal neuronal cells (HT-22). These include the protein expression of iNOS, COX-2, MAPKs pathways, Tau protein-related pathways, caspases family-related signaling pathways. They also include the levels of TNF-α, IL-6, IL-18 and ROS, as well as the level of mitochondrial oxidative stress and neuronal cell apoptosis. The results showed that both benzaldehydes were effective in reducing the secretion of various inflammatory mediators, as well as pro-inflammatory factors. Among these, benzaldehyde 2 inhibited mitochondrial oxidative stress and blocked neuronal cell apoptosis through Tau protein-related pathways and caspases family-related signaling pathways, thereby inhibiting ß-amyloid (Aß)-induced neurological damage. This study reveals that benzaldehyde 2 has potential as a therapeutic agent for Alzheimer's disease, and offers a new approach to the high-value use of marine natural products.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteínas tau/metabolismo , Benzaldeídos , Peptídeos beta-Amiloides/metabolismo , Caspases
8.
Environ Monit Assess ; 195(6): 634, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37133617

RESUMO

Mangroves are located at the intersection of land and sea and are also heavily affected by plastic wastes. Biofilms of plastic wastes in mangroves are reservoirs for antibiotic resistance genes (ARGs). In this study, plastic wastes and ARG pollution were investigated from three typical mangrove areas in Zhanjiang, South China. Transparent was the dominant colors of plastic wastes in three mangroves. Fragment and film shape accounted for 57.73-88.23% of plastic waste samples in mangroves. In addition, 39.50% of plastic wastes in protected area mangroves are PS. The metagenomic results shows that the 175 ARGs were found on plastic wastes of the three mangroves, the abundance accounting for 91.11% of the total ARGs. The abundance of Vibrio accounted for 2.31% of the total bacteria genera in aquaculture pond area mangrove. Correlation analysis shows that a microbe can carry multiple ARGs that may improve resistance to antibiotics. Microbes are the potential hosts of most ARGs, suggesting that ARGs can be transmitted by microbes. Because the mangroves are closely related to human activities and the high abundance of ARGs on plastic increases the ecological risks, people should improve plastic waste management and prevent the spread of ARGs by reducing plastic pollution.


Assuntos
Antibacterianos , Genes Bacterianos , Humanos , Antibacterianos/farmacologia , Plásticos , Monitoramento Ambiental , Resistência Microbiana a Medicamentos/genética
9.
J Gene Med ; 24(3): e3395, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34668273

RESUMO

BACKGROUND: This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)-129-5p/MAPK1. METHODS: Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (n = 14) and IVDD (n = 34). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)-induced NP cell model. After loss- and gain-of-function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR-129-5p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR-129-5p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR-129-5p agomir and/or oe-EZH2 in vivo. RESULTS: miR-129-5p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS-induced NP cells. miR-129-5p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR-129-5p through H3K27me3 modification in the miR-129-5p promoter. miR-129-5p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR-129-5p agomir in vivo. CONCLUSIONS: Taken together, EZH2 inhibits miR-129-5p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.


Assuntos
Degeneração do Disco Intervertebral , MicroRNAs , Animais , Apoptose/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas , Humanos , Degeneração do Disco Intervertebral/genética , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Ratos
10.
Biochem Biophys Res Commun ; 634: 10-19, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36228540

RESUMO

Extracellular vesicles (EVs) and their exosome subsets are vesicle-like nanoparticles (EVs) that are secreted by cells and contain various factors that treat various diseases. However, studies on extracting EVs from marine shellfish are still relatively lacking. In this study, EVs were isolated from Pinctada martensii mucus and the efficacy of EVs in modulating the inflammatory environment was demonstrated. A human skin inflammatory cell model was established to investigate the effect of Pinctada martensii mucus-derived EVs on inflammation. The results showed that EVs could restore the viability of inflammatory HaCaT cells and decrease the level of reactive oxygen species (ROS), as well as the mRNA expression of IL-6, IL-8 and TNF-α. The inflammation of HaCaT cells was treated by inhibiting the activation of the MAPK, NF-κB and NLRP3 inflammasome signaling pathways, which prevented the phosphorylation of related inflammatory proteins and the entry of P65 protein into the nucleus. This study provides novel EVs from marine shellfish-derived bioactive materials.


Assuntos
Dermatite , Vesículas Extracelulares , Pinctada , Animais , Humanos , Vesículas Extracelulares/metabolismo , Inflamassomos/metabolismo , Inflamação , Muco/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pinctada/metabolismo , Proteínas Quinases Ativadas por Mitógeno
11.
Int J Clin Pract ; 2022: 7770214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685568

RESUMO

Background: Percutaneous kyphoplasty (PKP) is an effective minimally invasive technique for the treatment of osteoporotic vertebral fracture (OVF) in recent years. This study focuses on the analysis of PKP surgery and anesthesia in osteoporotic vertebral facture patients over 90 years old with the concept of "enhanced recovery after surgery." Methods: This study reviewed 239 patients who were diagnosed with OVF retrospectively between October 2015 and June 2019. According to the method of anesthesia, these patients were divided into Group A (n = 125) and Group B (n = 114). According to the pedicle puncture approach, these patients were divided into Group C (n = 102) and Group D (n = 137). The anterior vertebral height (AVH) and local kyphosis angle (LKA) were used to evaluate the degree of vertebral damage and restoration. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) scores were used for assessing functional outcomes. Some parameters were used to assess the perioperative conditions such as operation time, amount of bone cement perfusion, intraoperative fluoroscopy times, anesthesia recovery time, time out of the bed, hospital stay, hospitalization cost, and complications. Results: The visual analogue scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height (AVH), and local kyphosis angle (LKA) 1 day, 1 year after surgery, and at the last follow-up all showed significant improvement (P < 0.05) in comparison with those before surgery both in Groups A and B and Groups C and D. The ODI 1 day after surgery was significantly better in Group B than Group A (P < 0.05). Compared with Group B, Group A required longer time of anesthesia, operation time, anesthesia recovery time, time to get out of bed, and length of hospital stay and more hospitalization costs (P < 0.05). Group D required longer operation time, longer time to get out of bed, more bone cement volume, fluoroscopy time, and more operation hospitalization costs compared with Group C (P < 0.05). Conclusion: We recommend unilateral puncture under local anesthesia for OVF in the patients aged over 90 from the perspective of rapid recovery.


Assuntos
Anestesia , Fraturas por Compressão , Cifoplastia , Cifose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos/uso terapêutico , Fraturas por Compressão/cirurgia , Humanos , Cifoplastia/métodos , Cifose/cirurgia , Fraturas por Osteoporose/cirurgia , Punções , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia
12.
Mol Cell Neurosci ; 111: 103589, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33422672

RESUMO

Iron has a key role in the activation of the autophagic pathway in rats with intracerebral hemorrhage (ICH), and hepcidin has the ability to reduce brain iron in ICH-rats. We therefore hypothesized that hepcidin might be able to inhibit autophagy by reducing iron in an ICH brain. Here, we investigated the effects of Ad-hepcidin and/or hepcidin peptide on autophagic activities in ICH models in vitro and in vivo. We demonstrated that ad-hepcidin and hepcidin peptide both inhibited hemin-induced increase in LC3-II/LC3-I conversion ratio and reversed the reduction in p62 content in cortical neurons in vitro. We also showed that ad-hepcidin inhibited ICH-induced increase in LC3-II/LC3-I conversion ratio and reversed ICH-induced reduction in p62 content in the brain cortex of rats in vivo. Based on these findings plus previous data on the effects of ad-hepcidin and/or hepcidin peptide on iron contents in ICH models, we suggested that hepcidin-induced inhibition of autophagy might be mediated via reducing iron in hemin-treated neurons in vitro and ICH-rat brain in vivo.


Assuntos
Autofagia , Hemorragia Cerebral/metabolismo , Hepcidinas/metabolismo , Adenoviridae/genética , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Vetores Genéticos/genética , Hepcidinas/genética , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteína Sequestossoma-1/metabolismo
13.
Hereditas ; 159(1): 7, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35063044

RESUMO

BACKGROUND: Breast cancer is the malignant tumor with the highest incidence in women. DNA methylation has an important effect on breast cancer, but the effect of abnormal DNA methylation on gene expression in breast cancer is still unclear. Therefore, it is very important to find therapeutic targets related to DNA methylation. RESULTS: In this work, we calculated the DNA methylation distribution and gene expression level in cancer and para-cancerous tissues for breast cancer samples. We found that DNA methylation in key regions is closely related to gene expression by analyzing the relationship between the distribution characteristics of DNA methylation in different regions and the change of gene expression level. Finally, the 18 key genes (17 tumor suppressor genes and 1 oncogene) related to prognosis were confirmed by the survival analysis of clinical data. Some important DNA methylation regions in these genes that result in breast cancer were found. CONCLUSIONS: We believe that 17 TSGs and 1 oncogene may be breast cancer biomarkers regulated by DNA methylation in key regions. These results will help to explore DNA methylation biomarkers as potential therapeutic targets for breast cancer.


Assuntos
Neoplasias da Mama , Metilação de DNA , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Regiões Promotoras Genéticas
14.
PLoS Genet ; 15(12): e1008456, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830036

RESUMO

How genomes are organized within cells and how the 3D architecture of a genome influences cellular functions are significant questions in biology. A bacterial genomic DNA resides inside cells in a highly condensed and functionally organized form called nucleoid (nucleus-like structure without a nuclear membrane). The Escherichia coli chromosome or nucleoid is composed of the genomic DNA, RNA, and protein. The nucleoid forms by condensation and functional arrangement of a single chromosomal DNA with the help of chromosomal architectural proteins and RNA molecules as well as DNA supercoiling. Although a high-resolution structure of a bacterial nucleoid is yet to come, five decades of research has established the following salient features of the E. coli nucleoid elaborated below: 1) The chromosomal DNA is on the average a negatively supercoiled molecule that is folded as plectonemic loops, which are confined into many independent topological domains due to supercoiling diffusion barriers; 2) The loops spatially organize into megabase size regions called macrodomains, which are defined by more frequent physical interactions among DNA sites within the same macrodomain than between different macrodomains; 3) The condensed and spatially organized DNA takes the form of a helical ellipsoid radially confined in the cell; and 4) The DNA in the chromosome appears to have a condition-dependent 3-D structure that is linked to gene expression so that the nucleoid architecture and gene transcription are tightly interdependent, influencing each other reciprocally. Current advents of high-resolution microscopy, single-molecule analysis and molecular structure determination of the components are expected to reveal the total structure and function of the bacterial nucleoid.


Assuntos
DNA Bacteriano/química , Proteínas de Ligação a DNA/química , Escherichia coli/crescimento & desenvolvimento , RNA Bacteriano/química , DNA Super-Helicoidal/química , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/química , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Conformação Molecular , Imagem Individual de Molécula
15.
Plant Foods Hum Nutr ; 77(2): 181-189, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35476173

RESUMO

In the early stage, oxidized low density lipoprotein (ox-LDL) caused atherosclerosis, followed by human umbilical vein endothelial cells (HUVEC) damage, leading to a variety of cardiovascular related diseases. This study investigated the mechanism of nonapeptide (EMFGTSSET, ETT) isolated from in vitro gastrointestinal digestion of Isochrysis zhanjiang on endothelial cell inflammation and apoptosis induced by ox-LDL in atherosclerosis. At the cellular level, the results shown that ETT inhibited the up-regulation of oxidized low-density lipoprotein receptor-1 (LOX-1) induced by ox-LDL. Furthermore, ETT inhibited the fluorescence intensity of ROS, inflammatory factors (interleukin-6, interleukin-1ß, and tumor necrosis factor-α) and the expression of cell adhesion molecules (vascular cell adhesion protein 1 and intercellular cell adhesion molecule-1). In addition, it also upregulates nuclear red blood cell 2 related factor 2 (Nrf2), heme oxygenase-1 (HO -1), p-Akt, and bcl-2 levels. But down-regulated the expression of p-p65, p-IκB-α, p-p38, p-ERK, p-JNK, bax, and cleaved caspase-9/-3 (c-c-9/-3), thereby inhibited ox-LDL induction inflammation and apoptosis of atherosclerosis. Through molecular docking, it was judged that the stable interaction between ETT and LOX-1 and VCAM-1 was maintained through hydrogen bonding. These results can provide a theoretical basis for ETT as a potential substance for the prevention and treatment of atherosclerosis, and further improve the value of Isochrysis zhanjiangensis.


Assuntos
Aterosclerose , Haptófitas , Microalgas , Apoptose , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Haptófitas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/tratamento farmacológico , Lipoproteínas LDL , Microalgas/metabolismo , Simulação de Acoplamento Molecular , Receptores Depuradores Classe E/metabolismo
16.
J Cell Mol Med ; 25(2): 925-936, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33277782

RESUMO

The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour-infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.


Assuntos
Neoplasias Encefálicas/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Glioma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/imunologia , Glioma/patologia , Humanos , Imunidade , Nomogramas , Prognóstico , Transdução de Sinais/genética , Análise de Sobrevida , Microambiente Tumoral/genética
17.
J Cell Physiol ; 236(6): 4515-4527, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33442879

RESUMO

Ischemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)-induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor-κB (NF-κB) in cell survival and adaption to oxidative stress, we hypothesized that NF-κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes. Here, we investigated the effects of IP neurons on NF-κB activation, cell viability, reactive oxygen species (ROS), expression of antioxidant enzymes, erythropoietin (EPO), and tumor necrosis factor α (TNF-α), in the presence or absence of BAY11-7082 (an NF-κB inhibitor), anti-EPO, and anti-TNF-α antibodies, in astrocytes treated with or without I/R. We found that IP neurons could keep NF-κB activation at a relatively higher but beneficial level, and in turn, upregulated the activity of antioxidant enzymes and hence enhanced cell viability and reduced ROS in I/R treated astrocytes. The results collectively indicated that IP neurons are able to significantly inhibit the I/R-induced NF-κB overactivation, probably via EPO and TNF-α, being essential for IP neuron-induced astroprotection under the conditions of I/R. We concluded that NF-κB-mediated antioxidative stress is one of the mechanisms by which IP neurons protect astrocytes against I/R injury.


Assuntos
Astrócitos/metabolismo , Córtex Cerebral/metabolismo , NF-kappa B/metabolismo , Neurônios/metabolismo , Comunicação Parácrina , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/metabolismo , Astrócitos/enzimologia , Astrócitos/patologia , Hipóxia Celular , Células Cultivadas , Córtex Cerebral/patologia , Meios de Cultivo Condicionados/metabolismo , Eritropoetina/metabolismo , Glucose/deficiência , Neurônios/patologia , Estresse Oxidativo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
18.
Opt Express ; 29(16): 24674-24683, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614818

RESUMO

We demonstrate a laser frequency stabilization method with large tuning range to stabilize a UV laser by installing piezoelectric ceramic actuators into a Fabry-Pérot cavity with an ultra-low expansion spacer. To suppress piezoelectric drift, a two-layer symmetrical structure is adopted for the piezoelectric actuator, and a 14.7 GHz tuning range is achieved. The short-term drift of the piezoelectric ceramics caused by temperature and creep is eliminated, and the long-term drift is 0.268 MHz/h when the Fabry-Pérot cavity is sealed in a chamber without a vacuum environment. The long-term frequency drift is mainly caused by stress release and is eliminated by compensating the cavity voltage with an open loop. Without the need for an external reference or a vacuum environment, the laser frequency stabilization system is greatly simplified, and it can be extended to wavelengths ranging from ultraviolet to infrared. Owing to its simplicity, stability, and large tuning range, it is applicable in cold atom and trapped ion experiments.

19.
Opt Express ; 29(23): 38488-38496, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808901

RESUMO

In research on hybrid quantum networks, visible or near-infrared frequency conversion has been realized. However, technical limitations mean that there have been few studies involving the ultraviolet band, and unfortunately the wavelengths of the rare-earth or alkaline-earth metal atoms or ions that are used widely in research on quantum information are often in the UV band. Therefore, frequency conversion of the ultraviolet band is very important. In this paper, we demonstrate a quantum frequency conversion between ultraviolet and visible wavelengths by fabricating waveguides in a period-poled MgO:LiTaO3 crystal with a laser writing system, which will be used to connect the wavelength of the dipole transition of 171Yb+ at 369.5 nm and the absorption wavelength of Eu3+ at 580 nm in a solid-state quantum memory system. An external conversion efficiency of 0.85% and a signal-to-noise ratio of greater than 500 are realized with a pumping power of 3.28 W at 1018 nm. Furthermore, we complete frequency conversion of the classical polarization state by means of a symmetric optical setup based on the fabricated waveguide, and the process fidelity of the conversion is (96.13 ± 0.021)%. This converter paves the way for constructing a hybrid quantum network and realizing a quantum router in the ultraviolet band in the future.

20.
Phys Rev Lett ; 127(26): 263603, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35029497

RESUMO

In cold atomic systems, fast and high-resolution microscopy of individual atoms is crucial, since it can provide direct information on the dynamics and correlations of the system. Here, we demonstrate nanosecond-scale two-dimensional stroboscopic pictures of a single trapped ion beyond the optical diffraction limit, by combining the main idea of ground-state depletion microscopy with quantum-state transition control in cold atoms. We achieve a spatial resolution up to 175 nm using a NA=0.1 objective in the experiment, which represents a more than tenfold improvement compared with direct fluorescence imaging. To show the potential of this method, we apply it to observe the secular motion of the trapped ion; we demonstrate a temporal resolution up to 50 ns with a displacement detection sensitivity of 10 nm. Our method provides a powerful tool for probing particle positions, momenta, and correlations, as well as their dynamics in cold atomic systems.

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