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1.
Biochem Biophys Res Commun ; 722: 150074, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38805785

RESUMO

Genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome enhances the extinction of contextual fear memory, which is attributed to its role in neuronal and synaptic dysregulation, concurrent with neurotransmitter function disturbances. This study aimed to determine whether NLRP3 plays a role in generalizing fear via the inflammatory axis. We established the NLRP3 KO mice model, followed by behavioral and biochemical analyses. The NLRP3 KO mice displayed impaired fear generalization, lower neuroinflammation levels, and dysregulated neurotransmitter function. Additionally, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not the inhibition of NMDA or 5-HT2C receptors, resulted in fear generalization in NLRP3 KO mice because TAT-GluA2 3Y, but not SB242084 and D-cycloserine, treated blocked NLRP3 deprivation effects on fear generalization. Thus, global knockout of NLRP3 is associated with aberrant fear generalization, possibly through AMPA receptor signaling.


Assuntos
Medo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptores de AMPA , Animais , Masculino , Camundongos , Medo/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Receptores de AMPA/metabolismo , Receptores de AMPA/genética
2.
Biochem Biophys Res Commun ; 701: 149550, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38310688

RESUMO

The beneficial effect of a beta-lactam antibiotic, Ceftriaxone (CEF), to improve depressive-like symptoms has been documented previously, attributed to its modulation of glutamate neurotransmission. Here, we aimed to determine whether CEF could improve LPS-altered glutamatergic signaling associated with neuroinflammation-allied depression. To assess our goals, we established a neuroinflammation-allied depression mice model by injecting lipopolysaccharides (LPS), followed by behavioral and biochemical analysis. LPS-treated mice displayed depressive symptoms, neuroinflammation, dysregulated glutamate and its transporter (GLT-1) expression, altered expression of astrocyte reactive markers (GFAP, cxcl10, steap4, GBP2, and SRGN), and dysregulated BDNF/TrkB signaling. However, these changes were rescued by CEF treatment, as we found decreased neuroinflammation, relief of depression symptoms, and improved GLT-1 and BDNF/TrkB signaling upon CEF treatment. Moreover, GLT-1 and BDNF/TrkB regulation role of CEF was validated by K252a and DHK treatment. In summary, the anti-depressive effects of glutamate modulators, like CEF, are closely related to their anti-inflammatory role.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Ceftriaxona , Camundongos , Animais , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lipopolissacarídeos , Doenças Neuroinflamatórias , Ácido Glutâmico/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo
3.
Med Sci Monit ; 30: e944662, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551033

RESUMO

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Wei Wei, Yanqin Wang, Xiaoming Yu, Lan Ye, Yuhua Jiang, Yufeng Cheng. Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its Biological Significance. Med Sci Monit, 2015; 21: 3016-3022. DOI: 10.12659/MSM.894640.

4.
PLoS Genet ; 17(3): e1009355, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33760820

RESUMO

Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.


Assuntos
Diferenciação Celular , Genômica , Neurogênese/genética , Neurônios/metabolismo , Lobo Temporal/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores , Diferenciação Celular/genética , Células Cultivadas , Córtex Cerebral/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Genes Reporter , Heterogeneidade Genética , Genômica/métodos , Histonas , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Neurônios/citologia , RNA Longo não Codificante/genética , Análise de Célula Única , Fatores de Transcrição , Sítio de Iniciação de Transcrição
5.
Biochem Biophys Res Commun ; 671: 292-300, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37320861

RESUMO

Aging adipose tissue exhibits elevated inflammation and oxidative stress that are major sources of age-related metabolic dysfunction. However, the exact metabolic changes associated with inflammation and oxidative stress are unclear. To address this topic, we assessed variation in metabolic phenotypes of adipose tissue from 18 months adult sedentary (ASED), 26 months old sedentary (OSED), and 8 months young sedentary (YSED). The results of metabolomic analysis showed that ASED and OSED group had higher palmitic acid, elaidic acid, 1-heptadecanol, and α-tocopherol levels than YSED, but lower sarcosine levels. Furthermore, stearic acid was specifically elevated in ASED compared with YSED. Cholesterol was upregulated specifically in the OSED group compared with YSED, whereas linoleic acid was downregulated. In addition, ASED and OSED had more inflammatory cytokines, lower antioxidant capacity, and higher expression of ferroptosis-related genes than YSED. Moreover, mitochondrial dysfunction associated with abnormal cardiolipin synthesis was more pronounced in the OSED group. In conclusion, both ASED and OSED can affect the FA metabolism and increase oxidative stress in adipose tissue, leading to inflammation. In particular, linoleic acid content specifically decreases in OSED, which associated with abnormal cardiolipin synthesis and mitochondrial dysfunction in adipose tissue.


Assuntos
Cardiolipinas , Ferroptose , Ratos , Feminino , Animais , Cardiolipinas/metabolismo , Ácido Linoleico/metabolismo , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Metabolômica
6.
Opt Express ; 31(6): 9750-9759, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157538

RESUMO

A mathematical model is derived to predict the maximum speed of a focused laser beam in the laser cutting of thin materials. This model contains only two material parameters and is used to obtain an explicit relationship between the cutting speed and laser parameters. The model shows that there exists an optimal focal spot radius with which cutting speed is maximized for a given laser power. We compare the modeling results with experiments and find a good agreement after correcting laser fluence. This work is useful for the practical application of lasers in processing thin materials such as sheets and panels.

7.
Cytokine ; 164: 156139, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36738525

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are an important source of seed cells for regenerative medicine and tissue engineering therapy. BMSCs have multiple differentiation potentials and can release paracrine factors to facilitate tissue repair. Although the role of the osteogenic differentiation of BMSCs has been fully confirmed, the function and mechanism of BMSC paracrine factors in bone repair are still largely unclear. This study aimed to determine the roles of transforming growth factor beta-1 (TGF-ß1) produced by BMSCs in bone tissue repair. METHODS: To confirm our hypothesis, we used a Transwell system to coculture hBMSCs and human osteoblast-like cells without contact, which could not only avoid the interference of the osteogenic differentiation of hBMSCs but also establish the cell-cell relationship between hBMSCs and human osteoblast-like cells and provide stable paracrine substances. In the transwell coculture system, alkaline phosphatase activity, mineralized nodule formation, cell migration and chemotaxis analysis assays were conducted. RESULTS: Osteogenesis, migration and chemotaxis of osteoblast-like cells were regulated by BMSCs in a paracrine manner via the upregulation of osteogenic and migration-associated genes. A TGF-ß receptor I inhibitor (LY3200882) significantly antagonized BMSC-induced biological activity and related gene expression in osteoblast-like cells. Interestingly, coculture with osteoblast-like cells significantly increased the production of TGF-ß1 by BMSCs, and there was potential intercellular communication between BMSCs and osteoblast-like cells. CONCLUSIONS: Our findings provide evidence that the biological mechanism of BMSC-produced TGF-ß1 promotes bone regeneration and repair, providing a theoretical basis and new directions for the application of BMSC transplantation in the treatment of osteonecrosis and bone injury.


Assuntos
Células-Tronco Mesenquimais , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , Osteogênese , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Células da Medula Óssea/metabolismo
8.
Biogerontology ; 24(5): 753-769, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37289374

RESUMO

We investigated the effects of lifelong aerobic exercise and 8 months of detraining after 10 months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8 months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26 months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.


Assuntos
Ferroptose , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Ratos Sprague-Dawley , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adiponectina , Fosfatidilinositol 3-Quinases , Músculo Esquelético/fisiologia , Envelhecimento , Atrofia Muscular/metabolismo , RNA Mensageiro/genética , Inflamação/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
9.
Scand J Med Sci Sports ; 33(6): 834-847, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36789636

RESUMO

Exercise-induced microRNA (miRNA) and HIPPO pathways participate in the regulation of skeletal muscle plasticity but their underlying mechanisms remain unclear. We aimed to investigate the effect of high-intensity interval training (HIIT) on miRNA expression and the HIPPO pathway in the skeletal muscle of aging rats to determine its role in the amelioration of muscle aging. Thirty-six 18-month-old female rats were randomly divided into sedentary control (SED, n = 12), moderate-intensity continuous training (MICT, n = 12), and HIIT (n = 12) groups, with continuous exercise for 8 months. Quantitative reverse transcription-polymerase chain reaction, immunoblotting, KEGG enrichment, and dual-luciferase assays were performed on the target skeletal muscle. Compared with the SED group, the MICT and HIIT groups showed a significant trend of improvement in Lee's index and grip strength and a marked increase in skeletal muscle mitochondrial function, apoptosis, antioxidant, and lipolysis-related protein expression. They also exhibited PI3K/AKT pathway activation and a decrease in expression of HIPPO pathway-related proteins; 20 miRNAs were differentially expressed and enriched in the exercise group compared with the SED group, including the HIPPO pathway and metabolic pathways. Further analysis of L6 cells confirmed that miR-182 may target PTEN, which indirectly regulates HIPPO signaling, but not Mob1. the combined application of HIIT and MICT increased the antioxidant and lipolytic capacities of skeletal muscle and improved atrophy of aging skeletal muscle; HIIT was more effective than MICT. This may be related to HIIT-mediated AKT pathway activation and HIPPO pathway inhibition by miRNAs (miR-486 and miR-182).


Assuntos
Treinamento Intervalado de Alta Intensidade , MicroRNAs , Condicionamento Físico Animal , Ratos , Feminino , Animais , Via de Sinalização Hippo , Antioxidantes/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Condicionamento Físico Animal/fisiologia , Músculo Esquelético/fisiologia , Envelhecimento
10.
BMC Pediatr ; 23(1): 389, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553563

RESUMO

BACKGROUND: LGI-1 antibody-associated encephalitis is a type of autoimmune encephalitis with a lower prevalence than NMDAR antibody-associated encephalitis. LGI-1 antibody-associated encephalitis is the second most prevalent of all autoimmune encephalitides. LGI-1 antibodies interfere with the interactions of inter-synaptic proteins to produce clinical manifestations (N Engl J Med 378:840-851, 2018). CASE PRESENTATION: Leucine-rich glioma-inactivated protein 1 (LGI-1) antibody-associated encephalitis is a subtype of autoimmune encephalitis with a low incidence. We report a case of a girl aged 22 months with convulsive seizures, psycho-behavioral abnormalities, sleep disorders, and limb tremors. This patient was diagnosed with LGI-1 antibody-associated encephalitis based on electroencephalography (EEG) examinations and autoimmune encephalitis antibody analyses. A combined therapy of anti-epileptic and immunosuppressant drugs was effective in controlling the patient's neurological symptoms. CONCLUSIONS: The incidence of LGI-1 antibody-associated encephalitis is low and it occurs mostly in middle-aged and elderly patients, although it occasionally occurs in pediatric patients. To the best of our knowledge, this report describes the youngest patient with LGI-1 antibody-associated encephalitis. Following timely diagnosis, administration of anti-epileptic and immunosuppressant therapy was remarkably effective.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Glioma , Feminino , Humanos , Lactente , Autoanticorpos , Doenças Autoimunes do Sistema Nervoso/complicações , Encefalite/diagnóstico , Encefalite/tratamento farmacológico , Glioma/complicações , Imunossupressores , Peptídeos e Proteínas de Sinalização Intracelular , Leucina
11.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36902412

RESUMO

Herein, we present a mussel-inspired supramolecular polymer coating to improve the an-ti-corrosion and self-healing properties of an AZ31B magnesium alloy. A self-assembled coating of polyethyleneimine (PEI) and polyacrylic acid (PAA) is a supramolecular aggregate that takes advantage of the weak interaction of non-covalent bonds between molecules. The cerium-based conversion layers overcome the corrosion problem between the coating and the substrate. Catechol mimics mussel proteins to form adherent polymer coatings. Chains of PEI and PAA interact electrostatically at high density, forming a dynamic binding that causes strand entanglement, enabling the rapid self-healing properties of a supramolecular polymer. The addition of graphene oxide (GO) as an anti-corrosive filler gives the supramolecular polymer coating a superior barrier and impermeability properties. The results of EIS revealed that a direct coating of PEI and PAA accelerates the corrosion of magnesium alloys; the impedance modulus of a PEI and PAA coating is only 7.4 × 103 Ω·cm2, and the corrosion current of a 72 h immersion in a 3.5 wt% NaCl solution is 1.401 × 10-6 Ω·cm2. The impedance modulus of the addition of a catechol and graphene oxide supramolecular polymer coating is up to 3.4 × 104 Ω·cm2, outperforming the substrate by a factor of two. After soaking in a 3.5 wt% NaCl solution for 72 h, the corrosion current is 0.942 × 10-6 A/cm2, which is superior to other coatings in this work. Furthermore, it was found that 10-micron scratches were completely healed in all coatings within 20 min, in the presence of water. The supramolecular polymer offers a new technique for the prevention of metal corrosion.


Assuntos
Magnésio , Cloreto de Sódio , Magnésio/química , Polímeros/química , Ligas/química
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(8): 1036-1040, 2023 Aug 10.
Artigo em Zh | MEDLINE | ID: mdl-37532508

RESUMO

OBJECTIVE: To explore the clinical characteristics and molecular genetic mechanism of a fetus with recombinant chromosome 8 (Rec8) syndrome. METHODS: A fetus who was diagnosed with Rec8 syndrome at the Provincial Hospital Affiliated to Shandong First Medical University on July 20, 2021 due to high risk for sex chromosomal aneuploidy indicated by non-invasive prenatal testing (NIPT) (at 21st gestational week) was selected as the study subject. Clinical data of the fetus was collected. G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out on the amniotic fluid sample. Peripheral blood samples of the couple were also subjected to G banded karyotyping analysis. RESULTS: Prenatal ultrasonography at 23rd gestational week revealed hypertelorism, thick lips, renal pelvis separation, intrahepatic echogenic foci, and ventricular septal defect. The karyotype of amniotic fluid was 46,XX,rec(8)(qter→q22.3::p23.1→qter), and CMA was arr[GRCh37]8p23.3p23.1(158049_6793322)×1, 8q22.3q24.3(101712402_146295771)×3. The karyotype of the pregnant woman was 46,XX,inv(8)(p23.1q22.3), whilst that of her husband was normal. CONCLUSION: The Rec8 syndrome in the fetus may be attributed to the pericentric inversion of chromosome 8 in its mother. Molecular testing revealed that the breakpoints of this Rec8 have differed from previously reported ones.


Assuntos
Cromossomos Humanos Par 8 , Feto , Humanos , Feto/anormalidades , Feminino , Gravidez , Cariotipagem
13.
Appl Intell (Dordr) ; 53(2): 2452-2470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35572052

RESUMO

In a complex and changeable stock market, it is very important to design a trading agent that can benefit investors. In this paper, we propose two stock trading decision-making methods. First, we propose a nested reinforcement learning (Nested RL) method based on three deep reinforcement learning models (the Advantage Actor Critic, Deep Deterministic Policy Gradient, and Soft Actor Critic models) that adopts an integration strategy by nesting reinforcement learning on the basic decision-maker. Thus, this strategy can dynamically select agents according to the current situation to generate trading decisions made under different market environments. Second, to inherit the advantages of three basic decision-makers, we consider confidence and propose a weight random selection with confidence (WRSC) strategy. In this way, investors can gain more profits by integrating the advantages of all agents. All the algorithms are validated for the U.S., Japanese and British stocks and evaluated by different performance indicators. The experimental results show that the annualized return, cumulative return, and Sharpe ratio values of our ensemble strategy are higher than those of the baselines, which indicates that our nested RL and WRSC methods can assist investors in their portfolio management with more profits under the same level of investment risk.

14.
Reprod Biomed Online ; 45(6): 1230-1236, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36274014

RESUMO

RESEARCH QUESTION: What are conception rates and pregnancy outcomes after laparoscopic treatment of subtle distal tubal abnormalities among infertile women, and which factors relate to natural conception? DESIGN: Prospective cohort study (n = 234) conducted in a single fertility referral centre between January 2017 and December 2018. Subtle abnormalities included fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis and accessory fallopian tube. Pregnancy outcomes were followed-up annually until 36 months. RESULTS: One hundred and nine patients conceived naturally (natural conception rate 46.6%), and 59 patients conceived after IVF. Term live birth rate of the natural conception group was significantly higher than the IVF conception group (86.2% versus 71.2%, chi-squared = 5.625, P = 0.018). Preterm birth (11.9% versus 0%, P = 0.001) and multiple pregnancy rates (27.1% versus 0%, P < 0.001) of the IVF conception group were significantly higher than the natural conception group. Patient age (hazard ratio = 0.917, 95% CI 0.870 to 0.967, P = 0.001), duration of infertility (hazard ratio = 0.846, 95% CI 0.740 to 0.966, P = 0.014) and concurrent types of subtle abnormalities (hazard ratio = 0.636, 95% CI 0.416 to 0.970, P = 0.036) were factors associated with natural conception. CONCLUSIONS: Laparoscopy is an effective treatment for infertile patients with subtle abnormalities, especially for young patients with a short infertile period and at most two types of subtle abnormalities. For older women, a long infertile period and more than two types of subtle abnormalities, IVF may be more suitable after laparoscopic diagnosis.


Assuntos
Doenças das Tubas Uterinas , Infertilidade Feminina , Laparoscopia , Nascimento Prematuro , Recém-Nascido , Masculino , Gravidez , Humanos , Feminino , Idoso , Infertilidade Feminina/complicações , Infertilidade Feminina/cirurgia , Resultado da Gravidez , Tubas Uterinas , Estudos Prospectivos , Doenças das Tubas Uterinas/complicações , Doenças das Tubas Uterinas/cirurgia , Taxa de Gravidez
15.
Chem Biodivers ; 19(10): e202200386, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36073658

RESUMO

Myocardial ischemia is a cardio-physiological condition due to a decrease in blood perfusion to the heart, leading to reduced oxygen supply and abnormal myocardial energy metabolism. Guizhi-Fuling (GZFL) is effective in treating Myocardial ischemia. However, its mechanism of action is unclear and requires further exploration. We attempt to decipher the mechanisms behind GZFL treating Myocardial ischemia by integrating metabolomics and network pharmacology. In this study, myocardial metabolomic analysis was performed using GC/MS to identify the potential mechanism of action of GZFL during myocardial ischemia. Then, network pharmacology was utilized to analyze key pathways and construct a pathway-core target network. Molecular docking was incorporated to validate core targets within network pharmacological signaling pathways. Finally, western blots were utilized to verify core targets of metabolomics, network pharmacology integrated pathways, and key signaling targets. Thus, 22 critical biomarkers of GZFL for treating myocardial ischemia were identified. Most of these metabolites were restored using modulation after GZFL treatment. Based on the network pharmacology, 297 targets of GZFL in treating myocardial ischemia were identified. The further comprehensive analysis focused on three key targets, such as Tyrosine hydroxylase (TH), myeloperoxidase (MPO), and phosphatidylinositol 3-kinases (PIK3CA), and their related metabolites and pathways. Compared with the model group, the protein expression levels of TH, MPO and PIK3CA were reduced in GZFL. Therefore, the mechanism of GZFL for treating myocardial ischemia could inhibit myocardial inflammatory factors, reduce myocardial inflammation, and restore endothelial function while controlling norepinephrine release and uric acid concentration.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Humanos , Peroxidase , Simulação de Acoplamento Molecular , Ácido Úrico/uso terapêutico , Tirosina 3-Mono-Oxigenase/uso terapêutico , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Isquemia Miocárdica/tratamento farmacológico , Biomarcadores , Norepinefrina/uso terapêutico , Fosfatidilinositol 3-Quinases , Classe I de Fosfatidilinositol 3-Quinases/uso terapêutico , Oxigênio
16.
J Biol Chem ; 295(47): 15974-15987, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-32913124

RESUMO

The molecular mechanisms behind infection and propagation of human restricted pathogens such as human norovirus (HuNoV) have defied interrogation because they were previously unculturable. However, human intestinal enteroids (HIEs) have emerged to offer unique ex vivo models for targeted studies of intestinal biology, including inflammatory and infectious diseases. Carbohydrate-dependent histo-blood group antigens (HBGAs) are known to be critical for clinical infection. To explore whether HBGAs of glycosphingolipids contribute to HuNoV infection, we obtained HIE cultures established from stem cells isolated from jejunal biopsies of six individuals with different ABO, Lewis, and secretor genotypes. We analyzed their glycerolipid and sphingolipid compositions and quantified interaction kinetics and the affinity of HuNoV virus-like particles (VLPs) to lipid vesicles produced from the individual HIE-lipid extracts. All HIEs had a similar lipid and glycerolipid composition. Sphingolipids included HBGA-related type 1 chain glycosphingolipids (GSLs), with HBGA epitopes corresponding to the geno- and phenotypes of the different HIEs. As revealed by single-particle interaction studies of Sydney GII.4 VLPs with glycosphingolipid-containing HIE membranes, both binding kinetics and affinities explain the patterns of susceptibility toward GII.4 infection for individual HIEs. This is the first time norovirus VLPs have been shown to interact specifically with secretor gene-dependent GSLs embedded in lipid membranes of HIEs that propagate GII.4 HuNoV ex vivo, highlighting the potential of HIEs for advanced future studies of intestinal glycobiology and host-pathogen interactions.


Assuntos
Antígenos de Grupos Sanguíneos/metabolismo , Infecções por Caliciviridae/metabolismo , Glicoesfingolipídeos/metabolismo , Mucosa Intestinal/metabolismo , Norovirus/metabolismo , Organoides/metabolismo , Ligação Viral , Infecções por Caliciviridae/patologia , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Organoides/patologia , Organoides/virologia
17.
Opt Express ; 29(4): 5635-5643, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33726097

RESUMO

Pursuing ever-smaller feature size in laser-based lithography is a research topic of vital importance to keep this technique competitive with other micro-/nano-fabrication methods. Features smaller than the diffraction-limited spot size can be obtained by "thresholding", which utilizes the deterministic nature of damage threshold with ultrashort laser pulses and is achieved by precisely tuning pulse energies so that only the central portion of the focal spot produces permanent modification. In this paper, we examine the formulation commonly used to describe thresholding and show that the relationship between feature size (r) and laser fluence (F) is invariant with respect to the nature of laser absorption. Verified by our experiments performed on metal, semiconductor, and dielectric samples, such invariance is used to predict the smallest feature size that can be achieved for different materials in a real-world system.

18.
Opt Express ; 29(13): 20673-20686, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34266151

RESUMO

We demonstrate an approach to double the optical efficiency of virtual reality (VR) systems based on a directional backlight and a diffractive deflection film (DDF). The directional backlight consists of a commercial collimated light-emitting diode (LED) array and a two-layer privacy film, while the DDF is a three-domain Pancharatnam-Berry (PB) phase lens. Such a PB phase lens was fabricated by the zone exposure and spin-coating method. The focal length of each domain is designed according to the imaging optics of the VR system. Our approach works well in both Fresnel and "pancake" VR systems. We also build the corresponding models in LightTools, and the simulation results are in good agreement with experiment. In experiment, we achieved a 2.25x optical efficiency enhancement for both systems, which agrees with the simulation results (2.48x for Fresnel and 2.44x for "pancake" systems) well. Potential application for high efficiency VR displays is foreseeable.

19.
Opt Express ; 29(10): 14201-14207, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985144

RESUMO

We demonstrate, for the first time, the direct writing of curved optical waveguides in monocrystalline silicon with curve radii from 2 mm to 6 cm. The bending loss of the curved waveguides is measured and a good agreement with theoretical values is found. Raman spectroscopy measurements suggest the formation of inhomogeneous amorphous and polycrystalline phases in the laser-modified region. This direct laser-writing method may advance fabrication capabilities for integrated 3D silicon photonic devices.

20.
Opt Express ; 29(10): 15023-15030, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985211

RESUMO

Multiple 11-fs infrared, few-cycle laser pulses were applied to a polycrystal ZnSe surface to study the evolution of surface damage morphologies. The polycrystalline grain boundaries seem to be the initiation site of surface damage and formation of ripples, which evolve as the result of many laser pulses at the same site. Scanning electron microscopy and atomic force microscopy (AFM) were applied to characterize the surface. The crystalline change and material phase transition were examined by confocal Raman spectroscopy. The thermal expansion coefficient increased slightly in the ablated zone compared to the non-ablated zone according to an AFM thermal tip test. The results show the growth and organization of surface ripples and the change of thermal properties as the number of irradiations at each site increases.

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