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1.
J Virol ; 98(5): e0029924, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38557225

RESUMO

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) Ac93 is highly conserved in all sequenced baculovirus genomes, and it plays important roles in both the nuclear egress of nucleocapsids and the formation of intranuclear microvesicles. In this study, we characterized a cellular CRM1-dependent nuclear export signal (NES) of AcMNPV Ac93. Bioinformatic analysis revealed that AcMNPV Ac93 may contain an NES at amino acids 115-125. Green fluorescent protein (GFP) fused to the NES (GFP:NES) of AcMNPV Ac93 is localized to the cytoplasm of transfected cells. Multiple point mutation analysis demonstrated that NES is important for the nuclear export of GFP:NES. Bimolecular fluorescence complementation experiments and co-immunoprecipitation assays confirmed that Ac93 interacts with Spodoptera frugiperda CRM1 (SfCRM1). However, AcMNPV Ac34 inhibits cellular CRM1-dependent nuclear export of GFP:NES. To determine whether the NES in AcMNPV Ac93 is important for the formation of intranuclear microvesicles, an ac93-null AcMNPV bacmid was constructed; the wild-type and NES-mutated Ac93 were reinserted into the ac93-null AcMNPV bacmid. Immunofluorescence analysis showed that Ac93 and SfCRM1 were predominantly colocalized at intranuclear microvesicles in infected cells, while the construct containing point mutations at residues 123 and 125 of Ac93 resulted in a defect in budded virus production and the abolishment of intranuclear microvesicles. Together, these data demonstrate that Ac93 contains a functional NES, which is required for the production of progeny viruses and the formation of intranuclear microvesicles.IMPORTANCEAutographa californica multiple nucleopolyhedrovirus (AcMNPV) Ac93 is important for the formation of intranuclear microvesicles. However, how the baculovirus manipulates Ac93 for the formation of intranuclear microvesicles is unclear. In this study, we identified a nuclear export signal (NES) at amino acids 115-125 of AcMNPV Ac93. Our results showed that the NES is required for the interaction between Ac93 and Spodoptera frugiperda CRM1 (SfCRM1). However, AcMNPV Ac34 inhibits the nuclear export of green fluorescent protein fused to the NES. Our analysis revealed that Ac93 and SfCRM1 were predominantly colocalized at intranuclear microvesicles in AcMNPV-infected cells. Together, our results indicate that Ac93 participates in the formation of intranuclear microvesicles via the Ac93 NES-mediated CRM1 pathway.


Assuntos
Transporte Ativo do Núcleo Celular , Sinais de Exportação Nuclear , Nucleopoliedrovírus , Proteínas Virais , Animais , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Proteína Exportina 1 , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Fluorescência Verde/genética , Carioferinas/metabolismo , Nucleopoliedrovírus/metabolismo , Nucleopoliedrovírus/fisiologia , Nucleopoliedrovírus/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Células Sf9 , Spodoptera/virologia , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
2.
Sensors (Basel) ; 24(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38339727

RESUMO

Magnetic position sensors have extensive applications in various industrial sectors and consumer products. However, measuring angles in the full range of 0-360° in a wide field range using a single magnetic sensor remains a challenge. Here, we propose a magnetic position sensor based on a single Wheatstone bridge structure made from a single ferromagnetic layer. By measuring the anisotropic magnetoresistance (AMR) signals from the bridge and two sets of anomalous Nernst effect (ANE) signals from the transverse ports on two perpendicular Wheatstone bridge arms concurrently, we show that it is possible to achieve 0-360° angle detection using a single bridge sensor. The combined use of AMR and ANE signals allows a mean angle error in the range of 0.51-1.05° within a field range of 100 Oe-10,000 Oe to be achieved.

3.
Nano Lett ; 23(22): 10274-10281, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37909311

RESUMO

Recently, orbital Hall current has attracted attention as an alternative method to switch the magnetization of ferromagnets. Here we present our findings on electrical switching of the antiferromagnetic state in Mn3Sn/Cr, where despite the much smaller spin Hall angle of Cr, the switching current density is comparable to heavy metal-based heterostructures. However, the inverse process, i.e., spin-to-charge conversion in Cr-based heterostructures, is much less efficient than the Pt-based equivalents, as manifested in the 1 order of magnitude smaller terahertz emission intensity and spin current-induced magnetoresistance. These results in combination with the slow decay of terahertz emission against Cr thickness (diffusion length of ∼11 nm) suggest that the observed magnetic switching can be attributed to orbital current generation in Cr, followed by efficient conversion to spin current. Our work demonstrates the potential of light metals like Cr as efficient orbital/spin current sources for antiferromagnetic spintronics.

4.
Analyst ; 148(7): 1437-1441, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36919562

RESUMO

Formaldehyde (FA) and viscosity play multiple roles in human health and diseases, and viscosity has great regional differences due to the diversity of subcellular organelles. However, it is challenging to achieve dual detection of viscosity and FA in subcellular organelles. Herein, we developed a near infrared (NIR) fluorescent probe FA-Cy, which can simultaneously monitor the viscosity and FA concentration of mitochondria in living cells. The probe could detect mitochondrial viscosity and exogenous and endogenous FA in living cells and zebrafish.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Humanos , Corantes Fluorescentes/toxicidade , Células HeLa , Viscosidade , Imagem Óptica/métodos , Mitocôndrias , Formaldeído
5.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446141

RESUMO

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-ß1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.


Assuntos
Injúria Renal Aguda , Iohexol , Humanos , Iohexol/efeitos adversos , Meios de Contraste/efeitos adversos , Apoptose , Injúria Renal Aguda/induzido quimicamente , Ciclo Celular , Fibrose
6.
J Clin Lab Anal ; 36(5): e24408, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35396749

RESUMO

BACKGROUND: Circular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non-small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC. METHODS: Circ_0011298, microRNA-486-3p (miR-486-3p), and CRABP2 mRNA expression were determined using qRT-PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual-luciferase reporter and RIP assays were performed to confirm the relationship between miR-486-3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo. RESULTS: Circ_0011298 was overexpressed in Taxol-resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol-resistant NSCLC cells. Circ_0011298 was a sponge of miR-486-3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR-486-3p inhibition. Moreover, miR-486-3p directly targeted CRABP2, and miR-486-3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR-486-3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo. CONCLUSION: Circ_0011298 elevated Taxol resistance of NSCLC by sponging miR-486-3p and upregulating CRABP2, providing a possible circRNA-targeted therapy for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Paclitaxel , RNA Circular , Receptores do Ácido Retinoico , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , MicroRNAs/genética , Paclitaxel/farmacologia , RNA Circular/genética , Receptores do Ácido Retinoico/genética
7.
Int J Mol Sci ; 23(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35563195

RESUMO

Berberine exerts therapeutic effects in inflammation-associated diseases. In a lipopolysaccharide (LPS)-induced endotoxemic acute lung injury (ALI) rat model, berberine alleviated lung injury through different anti-inflammatory mechanisms; however, treatment effects on CX3CL1 expression and shedding remain to be examined. As these processes play important roles in promoting the binding of leukocytes to the endothelium, the CX3CL1/CX3CR1 axis and its related pathways may serve as potential targets for the clinical treatment of ALI. The anti-inflammatory effects of berberine were investigated in LPS-stimulated rats, human umbilical cord vein endothelial cells (HUVECs), and THP-1 monocytic cells. Cx3cl1 expression in rat pulmonary tissues was examined using immunohistochemistry. CX3CL1, CX3CR1, RELA, STAT3, and ADAM10 levels were examined using Western blotting. CX3CL1 and ADAM10 mRNA levels were examined using quantitative real-time polymerase chain reaction. Soluble fractalkine levels in LPS-stimulated rats and HUVECs were examined using the enzyme-linked immunosorbent assay. Berberine significantly mitigated the LPS-induced upregulation of fractalkine and soluble fractalkine in rats and cultured HUVECs. Berberine mitigated the LPS-induced activation of the NF-κB and STAT3 signaling pathways. In THP-1 cells, berberine mitigated the LPS-induced upregulation of CX3CR1. Furthermore, the membrane expression of ADAM10 in LPS-stimulated HUVECs was suppressed by the berberine treatment. Berberine dose-dependently inhibited the LPS-induced activation of the CX3CL1/CX3CR1 axis and fractalkine shedding through ADAM10. These findings reveal a novel molecular mechanism underlying the inhibitory effect of berberine on monocyte adherence to the endothelium during inflammation.


Assuntos
Lesão Pulmonar Aguda , Berberina , Proteína ADAM10/genética , Animais , Anti-Inflamatórios , Berberina/farmacologia , Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Leucócitos/metabolismo , Lipopolissacarídeos/toxicidade , Ratos
8.
Int J Mol Sci ; 23(11)2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35682967

RESUMO

Chemotherapy-induced thrombocytopenia (CIT) is a common complication when treating malignancies with cytotoxic agents wherein carboplatin is one of the most typical agents causing CIT. Janus kinase 2 (JAK2) is one of the critical enzymes to megakaryocyte proliferation and differentiation. However, the role of the JAK2 in CIT remains unclear. In this study, we used both carboplatin-induced CIT mice and MEG-01 cell line to examine the expression of JAK2 and signal transducer and activator of transcription 3 (STAT3) pathway. Under CIT, the expression of JAK2 was significantly reduced in vivo and in vitro. More surprisingly, the JAK2/STAT3 pathway remained inactivated even when thrombopoietin (TPO) was administered. On the other hand, carboplatin could cause prominent S phase cell cycle arrest and markedly increased apoptosis in MEG-01 cells. These results showed that the thrombopoiesis might be interfered through the downregulation of JAK2/STAT3 pathway by carboplatin in CIT, and the fact that exogenous TPO supplement cannot reactivate this pathway.


Assuntos
Megacariócitos , Trombocitopenia , Animais , Apoptose , Carboplatina/efeitos adversos , Pontos de Checagem do Ciclo Celular , Regulação para Baixo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Megacariócitos/metabolismo , Camundongos , Fase S , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Trombocitopenia/induzido quimicamente , Trombocitopenia/metabolismo , Trombopoetina/metabolismo
9.
Int J Mol Sci ; 23(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36142591

RESUMO

Combined inhibition of vascular endothelial growth factor receptor (VEGFR) and the programmed cell death protein 1 (PD-1) pathways has shown efficacy in multiple cancers; however, the clinical outcomes show limited benefits and the unmet clinical needs still remain and require improvement in efficacy. Using murine colon carcinoma (CT26) allograft models, we examined the efficacy and elucidated novel tumor microenvironment (TME) remodeling mechanisms underlying the combination of chidamide (a benzamide-based class l histone deacetylase inhibitor; brand name in Taiwan, Kepida®) with VEGF receptor tyrosine kinase inhibitor (TKIs; cabozantinib/regorafenib, etc.) and immune checkpoint inhibitors (ICIs; anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies). The TME was assessed using flow cytometry and RNA-sequencing to determine the novel mechanisms and their correlation with therapeutic effects in mice with significant treatment response. Compared with ICI alone or cabozantinib/regorafenib + ICI, combination of chidamide + cabozantinib/regorafenib + ICI increased the tumor response and survival benefits. In particular, treatment of CT26-bearing mice with chidamide + regorafenib + anti-PD-1 antibody showed a better objective response rate (ORR) and overall survival (OS). Similar results were observed in anti-PD-1 treatment-resistant mice. After treatment with this optimal combination, in the TME, RNA-sequencing revealed that downregulated mRNAs were correlated with leukocyte migration, cell chemotaxis, and macrophage gene sets, and flow cytometry analysis showed that the cell numbers of myeloid-derived polymorphonuclear suppressor cells and tumor-associated macrophages were decreased. Accordingly, chidamide + regorafenib + anti-PD-1 antibody combination therapy could trigger a novel TME remodeling mechanism by attenuating immunosuppressive cells, and restoring T-cell activation to enhance ORR and OS. Our studies also showed that the addition of Chidamide to the regorafenib + anti-PD-1 Ab combination could induce a durable tumor-specific response by attenuating immune suppression in the TME. In addition, this result suggests that TME remodeling, mediated by epigenetic immunomodulator combined with TKI and ICI, would be more advantageous for achieving a high objective response rate, when compared to TKI plus ICI or ICI alone, and maintaining long-lasting antitumor activity.


Assuntos
Neoplasias do Colo , Microambiente Tumoral , Aminopiridinas , Anilidas , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Compostos de Fenilureia , Receptor de Morte Celular Programada 1 , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas , RNA , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular
10.
Microb Pathog ; 155: 104880, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33905870

RESUMO

The present study was aimed to evaluate the isoxanthanol against Staphylococcus aureus chronic obstructive pulmonary disease (COPD) in rat model. The isoxanthanol decreased the parasitic load by almost 99% in the Staphylococcus aureus infected rats. It significantly (P < 0.05) decreased mortality rate of the rats, prevented pulmonary tissue damage and aggregation of inflammatory cytokines. In Staphylococcus aureus infected rats, isoxanthanol treatment inhibited production of interleukin-18, interleukin-1ß and TNF-α significantly (P < 0.05) in the BALF and pulmonary tissues. Treatment of the Staphylococcus aureus-infected rats with isoxanthanol inhibited up-regulation of NLRP3, ASC and caspase-1 expression. In Staphylococcus aureus-infected rats the expression of miR-145-5p was remarkably increased on treatment with isoxanthanol. In summary, isoxanthanol prevents Staphylococcus aureus-induced COPD in rats through up-regulation of miR-145-5p and suppression of inflammatory cytokines. Therefore, isoxanthanol can be of therapeutic importance for the treatment of Staphylococcus aureus induced COPD.


Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Animais , Pulmão , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Staphylococcus aureus , Fator de Necrose Tumoral alfa
11.
Insect Mol Biol ; 30(4): 400-409, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33837597

RESUMO

Proteins containing nuclear localization signals (NLSs) are actively transported into the nucleus via the classic importin-α/ß-mediated pathway, and NLSs are recognized by members of the importin-α family. Most studies of insect importin-αs have focused on Drosophila to date, little is known about the importin-α proteins in Lepidoptera insects. In this study, we identified four putative importin-α homologues, Spodoptera frugiperda importin-α1 (SfIMA1), SfIMA2, SfIMA4 and SfIMA7, from Sf9 cells. Immunofluorescence analysis showed that SfIMA2, SfIMA4 and SfIMA7 localized to the nucleus, while SfIMA1 distributed in cytoplasm. Additionally, SfIMA4 and SfIMA7 were also detected in the nuclear membrane of Sf9 cells. SfIMA1, SfIMA4 and SfIMA7, but not SfIMA2, were found to associate with the C terminus of AcMNPV DNA polymerase (DNApol) that harbours a typical monopartite NLS and a classic bipartite NLS. Further analysis of protein-protein interactions revealed that SfIMA1 specifically recognizes the bipartite NLS, while SfIMA4 and SfIMA7 bind to both monopartite and bipartite NLSs. Together, our results suggested that SfIMA1, SfIMA4 and SfIMA7 play important roles in the nuclear import of AcMNPV DNApol C terminus in Sf9 cells.


Assuntos
DNA Polimerase Dirigida por DNA/metabolismo , Nucleopoliedrovírus , Spodoptera , alfa Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Proteínas de Insetos/metabolismo , Sinais de Localização Nuclear/metabolismo , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/metabolismo , Domínios e Motivos de Interação entre Proteínas , Células Sf9/metabolismo , Células Sf9/virologia , Spodoptera/metabolismo , Spodoptera/virologia , Proteínas Virais/metabolismo
12.
Gynecol Endocrinol ; 37(7): 591-599, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33501880

RESUMO

BACKGROUND: We aimed to summarize the available data regarding the levels of leptin and adiponectin and the key modulators of endometriosis compared to the controls. METHODS: The electronic databases such as MEDLINE, Embase, Scopus, Cochrane Library, and Web of Science were searched up to October 2020. The circulating and peritoneal levels of leptin and circulating levels of adiponectin were included. We used the Cochrane's Q test and the I2 statistic in this study. These tests' weighted mean difference (WMD) and 95% CIs were considered as the summary effect size. They were then pooled using a random-effects model with the DerSimonian-Laird method. RESULTS: Twenty eligible articles (or 25 studies) with 2645 participants (1362 women with endometriosis and 1283 controls) were included. Pooled results showed that women with endometriosis had significantly higher leptin levels (WMD = 4.45 mg/ml, 95%CI = 2.42-6.49, p < .01) and leptin/BMI ratio (WMD = 0.32 mg/ml, 95%CI = 0.23-0.42, p < .001) than the controls, whereas adiponectin levels (WMD = -0.24 mg/ml, 95%CI = -4.27 to -0.01, p = .038) were significantly lower. The pooled results also indicated significantly lower leptin levels in women with advanced-stage endometriosis (WMD = -8.07 mg/ml, 95%CI = -14.22 to -1.92, p = .01) than in the early stage. It was found, however, that there were no significant differences in adiponectin levels of women with advanced-stage endometriosis (WMD = -0.16 mg/ml, 95%CI = -0.64 to 0.32, p = .512) and the early-stage ones. CONCLUSION: We showed that leptin levels and leptin/BMI ratio were significantly higher in women with endometriosis than the controls. Nonetheless, patients with endometriosis had significantly lower levels of adiponectin than the controls.


Assuntos
Adiponectina/metabolismo , Endometriose/metabolismo , Leptina/metabolismo , Índice de Massa Corporal , Feminino , Humanos
13.
Cytokine ; 116: 48-60, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30685603

RESUMO

Quercetin is a flavonoid polyphenolic compound present in fruits and vegetables that has proven anti-inflammatory activity. The goal of the present investigation was to investigate the effects of quercetin on tumor necrosis factor-α (TNF-α)-induced inflammatory responses via the expression of ICAM-1 and MMP-9 in human retinal pigment epithelial cells (ARPE-19 cells). Real-time PCR, gelatin zymography, and Western blot analysis showed that TNF-α induced the expression of ICAM-1 and MMP-9 protein and mRNA in a time-dependent manner. These effects were attenuated by pretreatment of ARPE-19 cells with quercetin. Quercetin inhibited the TNF-α-induced phosphorylation of PKCδ, JNK1/2, ERK1/2. Quercetin, rottlerin, SP600125 and U0126 attenuated TNF-α-stimulated c-Jun phosphorylation and AP-1-Luc activity. Pretreatment with quercetin, rottlerin, SP600125, or Bay 11-7082 attenuated TNF-α-induced NF-κB (p65) phosphorylation, translocation and RelA/p65-Luc activity. TNF-α significantly increased MMP-9 promoter activity and THP-1 cell adherence, and these effects were attenuated by pretreatment with quercetin, rottlerin, SP600125, U0126, tanshinone IIA or Bay 11-7082. These results suggest that quercetin attenuates TNF-α-induced ICAM-1 and MMP-9 expression in ARPE-19 cells via the MEK1/2-ERK1/2 and PKCδ-JNK1/2-c-Jun or NF-κB pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Molécula 1 de Adesão Intercelular/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Quercetina/farmacologia , Epitélio Pigmentado da Retina/metabolismo , Linhagem Celular , Regulação para Baixo , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosforilação , Proteína Quinase C-delta/metabolismo , Epitélio Pigmentado da Retina/citologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Proc Natl Acad Sci U S A ; 113(47): 13283-13288, 2016 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-27830649

RESUMO

Estimating the number of unseen species is an important problem in many scientific endeavors. Its most popular formulation, introduced by Fisher et al. [Fisher RA, Corbet AS, Williams CB (1943) J Animal Ecol 12(1):42-58], uses n samples to predict the number U of hitherto unseen species that would be observed if [Formula: see text] new samples were collected. Of considerable interest is the largest ratio t between the number of new and existing samples for which U can be accurately predicted. In seminal works, Good and Toulmin [Good I, Toulmin G (1956) Biometrika 43(102):45-63] constructed an intriguing estimator that predicts U for all [Formula: see text] Subsequently, Efron and Thisted [Efron B, Thisted R (1976) Biometrika 63(3):435-447] proposed a modification that empirically predicts U even for some [Formula: see text], but without provable guarantees. We derive a class of estimators that provably predict U all of the way up to [Formula: see text] We also show that this range is the best possible and that the estimator's mean-square error is near optimal for any t Our approach yields a provable guarantee for the Efron-Thisted estimator and, in addition, a variant with stronger theoretical and experimental performance than existing methodologies on a variety of synthetic and real datasets. The estimators are simple, linear, computationally efficient, and scalable to massive datasets. Their performance guarantees hold uniformly for all distributions, and apply to all four standard sampling models commonly used across various scientific disciplines: multinomial, Poisson, hypergeometric, and Bernoulli product.


Assuntos
Biota , Previsões , Algoritmos , Animais , Ecossistema , Especiação Genética , Estatísticas não Paramétricas
15.
Int J Mol Sci ; 20(12)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31212975

RESUMO

Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1ß (IL-1ß)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1ß, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5-20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1ß-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/ß, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1ß-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.


Assuntos
Citocinas/biossíntese , Mediadores da Inflamação/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Biomarcadores , Linhagem Celular , Quimiocinas/metabolismo , Humanos , Interleucina-1beta/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo
16.
Sensors (Basel) ; 18(11)2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-30373281

RESUMO

3D scene reconstruction is an important topic in computer vision. A complete scene is reconstructed from views acquired along the camera trajectory, each view containing a small part of the scene. Tracking in textureless scenes is well known to be a Gordian knot of camera tracking, and how to obtain accurate 3D models quickly is a major challenge for existing systems. For the application of robotics, we propose a robust CPU-based approach to reconstruct indoor scenes efficiently with a consumer RGB-D camera. The proposed approach bridges feature-based camera tracking and volumetric-based data integration together and has a good reconstruction performance in terms of both robustness and efficiency. The key points in our approach include: (i) a robust and fast camera tracking method combining points and edges, which improves tracking stability in textureless scenes; (ii) an efficient data fusion strategy to select camera views and integrate RGB-D images on multiple scales, which enhances the efficiency of volumetric integration; (iii) a novel RGB-D scene reconstruction system, which can be quickly implemented on a standard CPU. Experimental results demonstrate that our approach reconstructs scenes with higher robustness and efficiency compared to state-of-the-art reconstruction systems.

17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(3): 834-40, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26117907

RESUMO

There are many valuable rare and unusual objects in spectra dataset of Sloan Digital Sky Survey (SDSS) Data Release eight (DR8), such as special white dwarfs (DZ, DQ, DC), carbon stars, white dwarf main-sequence binaries (WDMS), cataclysmic variable (CV) stars and so on, so it is extremely significant to search for rare and unusual celestial objects from massive spectra dataset. A novel algorithm based on Kernel dense estimation and K-nearest neighborhoods (KNN) has been presented, and applied to search for rare and unusual celestial objects from 546 383 stellar spectra of SDSS DR8. Their densities are estimated using Gaussian kernel density estimation, the top 5 000 spectra in descend order by their densities are selected as rare objects, and the top 300 000 spectra in ascend order by their densities are selected as normal objects. Then, KNN were used to classify the rest objects, and simultaneously K nearest neighbors of the 5 000 rare spectra are also selected as rare objects. As a result, there are totally 21 193 spectra selected as initial rare spectra, which include error spectra caused by deletion, redden, bad calibration, spectra consisting of different physically irrelevant components, planetary nebulas, QSOs, special white dwarfs (DZ, DQ, DC), carbon stars, white dwarf main-sequence binaries (WDMS), cataclysmic variable (CV) stars and so on. By cross identification with SIMBAD, NED, ADS and major literature, it is found that three DZ white dwarfs, one WDMS, two CVs with company of G-type star, three CVs candidates, six DC white dwarfs, one DC white dwarf candidate and one BL Lacertae (BL lac) candidate are our new findings. We also have found one special DA white dwarf with emission lines of Ca II triple and Mg I, and one unknown object whose spectrum looks like a late M star with emission lines and its image looks like a galaxy or nebula.

18.
Acta Otolaryngol ; 144(1): 23-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38461404

RESUMO

BACKGROUND: There is no comprehensive and up-to-date overview of audiovestibular approach to the posterior fossa tumors in the literature. OBJECTIVE: This paper reviewed the literature relating to tumors at the posterior cranial fossa to find red flags alerting a posterior fossa lesion from audiovestibular perspectives. METHODS: This review was developed from articles published in those journals listed on the journal citation reports. Through the PubMed database, Embase, Google Scholar, and Cochrane library, 60 articles were finally obtained based on the PRISMA guidelines for reporting reviews. RESULTS: The presence of one red flag indicates a positive predictive value of 33% for detecting a posterior fossa lesion. Clinical features, namely, 1) mid-frequency sudden sensorineural hearing loss (SNHL), 2) bilateral sudden SNHL, and 3) rebound nystagmus may indicate a posterior fossa lesion, representing one, two, and three red flags, respectively. CONCLUSION: Those with 1) mid-frequency sudden SNHL, 2) bilateral sudden SNHL, and 3) rebound nystagmus trigger one, two, and three red flags, respectively, alerting clinicians the possibility of a posterior fossa lesion, which warrant MR imaging to exclude life-threatening or treatable conditions. SIGNIFICANCE: Patients with posterior fossa tumors may have potential life-threatening outcome.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Neoplasias Infratentoriais , Nistagmo Patológico , Humanos , Perda Auditiva Neurossensorial/patologia , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/etiologia , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/diagnóstico , Neoplasias Infratentoriais/patologia , Fossa Craniana Posterior/diagnóstico por imagem , Fossa Craniana Posterior/patologia , Perda Auditiva Súbita/patologia
19.
RSC Adv ; 14(25): 17814-17823, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38832239

RESUMO

Polysaccharides are considered to be ideal green raw materials for enhancing biocompatibility and dispersion effects of nanoparticles. In this study, we coated and dispersed ZnO nanoparticles (NPs) using the denaturation-renaturation process of a triple helix glucan lentinan (LNT), induced by changes in pH value within the reaction system. Various ZnO/LNT composites with different particle sizes and crystal morphologies were prepared and characterized. The results demonstrated that renatured LNT (r-LNT) effectively encapsulated the {101̄0} crystal planes of ZnO, preventing crystal growth during the renaturation process and resulting in smaller, uniformly dispersed nanoparticles. Among the samples, ZnO/r-LNT-2 exhibited significantly higher antimicrobial activity, and it had a certain inhibitory effect on various plant pathogens. It also displayed the highest inhibitory effect against Candida albicans, with a minimum inhibitory concentration (MIC) of up to 8 µg mL-1. Consistently, ZnO/r-LNT-2 generated the highest amount of reactive oxygen species (ROS), thus exhibiting the most effective antimicrobial activity. However, excessive introduction of the dispersant LNT may reduce these activities. This study provides a foundation for further exploring the detailed mechanism of ROS generation catalyzed by ZnO and for harnessing the full potential of this type of antimicrobial agent.

20.
Heliyon ; 10(10): e30828, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38770333

RESUMO

Modified Jiawei Juanbi decoction (MJD) is used for the treatment of early-stage knee osteoarthritis (KOA). Here, modified Jiawei Juanbi decoction (MJD) was employed for the treatment of early-stage knee osteoarthritis (KOA) and its mechanisms were assessed via metabonomics and network pharmacology. A total of 24 male Sprague-Dawley rats were randomly allocated into a normal control group, a model group, and an MJD group (n = 8 rats per group). Each rat group was further equally divided into two subgroups for investigation for either 14 or 28 days. A rat model of early-stage KOA was constructed and rats were treated with MJD. Effects were evaluated based on changes in knee circumference, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). We also analyzed histopathological changes in articular cartilage. High-resolution mass spectrometry was used to analyze the chemical profile of MJD, identifying 228 components. Using an LC-Q-TOF-MS metabonomics approach, 33 differential metabolites were identified. The relevant pathways significantly associated with MJD include arginine and proline metabolism, vitamin B6 metabolism, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. The system pharmacology paradigm revealed that MJD contains 1027 components and associates with 1637 genes, of which 862 disease genes are related to osteoarthritis. The construction of the MJD composition-target-KOA network revealed a total of 140 intersection genes. A total of 39 hub genes were identified via integration of betweenness centrality values greater than 100 using CytoHubba. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed several significantly affected signaling pathways including the HIF-1, AGE-RAGE (in diabetic complications), IL-17, rheumatoid arthritis and TNF pathways. Integrated-omics and network pharmacology approaches revealed a necessity for further detailed investigation focusing on two major targets, namely NOS2 and NOS3, along with their essential metabolite (arginine) and associated pathways (HIF-1 signaling and arginine and proline metabolism). Real-time PCR validated significantly greater downregulation of NOS2 and HIF-1ɑ in the MJD as compared to the model group. Molecular docking analysis further confirmed the binding of active MJD with key active components. Our findings elucidate the impact of MJD on relevant pathophysiological and metabolic networks relevant to KOA and assess the drug efficacy of MJD and its underlying mechanisms of action.

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