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1.
Nano Lett ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954769

RESUMO

Cr2(NCN)3 is a potentially high-capacity and fast-charge Li-ion anode owing to its abundant and broad tunnels. However, high intrinsic chemical instability severely restricts its capacity output and electrochemical reversibility. Herein we report an effective crystalline engineering method for optimizing its phase and crystallinity. Systematic studies reveal the relevancy between electrochemical performance and crystalline structure; an optimal Cr2(NCN)3 with high phase purity and uniform crystallinity exhibits a high reversible capacity of 590 mAh g-1 and a stable cycling performance of 478 mAh g-1 after 500 cycles. In-operando heating XRD reveals its high thermodynamical stability over 600 °C, and in-operando electrochemical XRD proves its electrochemical Li storage mechanism, consisting of the primary Li-ion intercalation and subsequent conversion reactions. This study introduces a facile and low-cost method for fabricating high-purity Cr2(NCN)3, and it also confirms that the Li storage of Cr2(NCN)3 can be further improved by tuning its phase and crystallinity.

2.
J Nanobiotechnology ; 22(1): 333, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877492

RESUMO

In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.


Assuntos
Tecido Adiposo , Apoptose , Isquemia , MicroRNAs , Animais , Camundongos , Tecido Adiposo/citologia , MicroRNAs/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Estresse Oxidativo , Retalhos Cirúrgicos , Células Cultivadas , Camundongos Endogâmicos C57BL , Masculino , Sobrevivência Celular , Neovascularização Fisiológica , Técnicas de Cultura de Células em Três Dimensões/métodos
3.
J Invertebr Pathol ; 203: 108071, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286328

RESUMO

Entomopathogenic fungi, including Metarhizium species, represent promising environmentally friendly biopesticides. Understanding the molecular mechanisms governing their infection processes is vital for enhancing their effectiveness. Transcription factors (TFs) play critical roles in gene regulation, yet the functions of many TFs in M. robertsii remain unknown. Homeobox transcription factors, implicated in diverse cellular processes, have received limited attention in entomopathogenic fungi. Here, we identify and characterize, a homeobox TF, MrHOX7, in the model entomopathogenic fungus M. robertsii. Subcellular localization and transcriptional profiling revealed MrHOX7's nuclear localization and high expression during conidia and appressoria formation. Deletion of Mrhox7 (ΔMrhox7) enhanced conidial tolerance to heat and UV-B stress, accompanying with upregulated stress-related gene expression. Intriguingly, ΔMrhox7 exhibits inhibited virulence exclusively through topical inoculation. Further investigations unveiled reduced conidial adhesion and appressorium formation, with downregulation of the adhesion gene Mad1 and appressorium-related genes, as the underlying causes of the reduced fungal virulence. Our findings illuminate the role of MrHOX7 in stress tolerance and virulence, providing insights into the molecular basis of fungal biopesticides.


Assuntos
Metarhizium , Fatores de Transcrição , Animais , Virulência/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Genes Homeobox , Agentes de Controle Biológico , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Esporos Fúngicos/genética
4.
Psychiatry Clin Neurosci ; 78(2): 83-96, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37877617

RESUMO

Extracellular vesicles (EVs) are membrane-enclosed nanovesicles secreted by cells into the extracellular space and contain functional biomolecules, e.g. signaling receptors, bioactive lipids, nucleic acids, and proteins, which can serve as biomarkers. Neurons and glial cells secrete EVs, contributing to various physiological and pathological aspects of brain diseases. EVs confer their role in the bidirectional crosstalk between the central nervous system (CNS) and the periphery owing to their distinctive ability to cross the unique blood-brain barrier (BBB). Thus, EVs in the blood, cerebrospinal fluid (CSF), and urine can be intriguing biomarkers, enabling the minimally invasive diagnosis of CNS diseases. Although there has been an enormous interest in evaluating EVs as promising biomarkers, the lack of ultra-sensitive approaches for isolating and detecting brain-derived EVs (BDEVs) has hindered the development of efficient biomarkers. This review presents the recent salient findings of exosomal biomarkers, focusing on brain disorders. We summarize highly sensitive sensors for EV detection and state-of-the-art methods for single EV detection. Finally, the prospect of developing advanced EV analysis approaches for the non-invasive diagnosis of brain diseases is presented.


Assuntos
Encefalopatias , Doenças do Sistema Nervoso Central , Vesículas Extracelulares , Humanos , Encéfalo/metabolismo , Vesículas Extracelulares/metabolismo , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/metabolismo , Encefalopatias/diagnóstico , Biomarcadores
5.
Phytother Res ; 38(5): 2539-2559, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38459660

RESUMO

Avascular necrosis frequently occurs as a complication following surgery involving the distal perforator flap. Dihydrocapsaicin (DHC) can protect tissue from ischemia-reperfusion (I/R) injury, but its specific role in multizone perforator flaps remains unclear. In this study, the prospective target of DHC in the context of I/R injury was predicted using network pharmacology analysis. Flap viability was determined through survival area analysis, laser Doppler blood flow, angiograms, and histological examination. The expressions of angiogenesis, apoptosis, NLR family pyrin domain containing 3 (NLRP3) inflammasome, oxidative stress, and molecules related to cyclic guanosine monophosphate (GMP)-adenosine monophosphate synthase (cGAS)-interferon gene stimulant (STING) pathway were assessed using western blotting, immunofluorescence, TUNEL staining, and dihydroethidium (DHE) staining. Our finding revealed that DHC promoted the perforator flap survival, which involves the cGAS-STING pathway, oxidative stress, NLRP3 inflammasome, apoptosis, and angiogenesis. DHC induced oxidative stress resistance and suppressed the NLRP3 inflammasome, preventing apoptosis in vascular endothelial cells. Through regulation of STING pathway, DHC controlled oxidative stress in endothelial cells and NLRP3 levels in ischemic flaps. However, activation of the cGAS-STING pathway led to the accumulation of reactive oxygen species (ROS) and NLRP3 inflammasome, thereby diminishing the protective role of DHC. DHC enhanced the survival of multidomain perforator flaps by suppressing the cGAS-STING pathway, oxidative stress, and the formation of NLRP3 inflammasome. These findings unveil a potentially novel mechanism with clinical significance for promoting the survival of multidomain perforator flaps.


Assuntos
Apoptose , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Retalho Perfurante , Traumatismo por Reperfusão , Animais , Humanos , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Inflamassomos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
6.
Molecules ; 29(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38542893

RESUMO

A disposable electrochemical sensor based on silver nanoparticle-embedded cellulose hydrogel composites was developed for sensitive detection of sulfamethoxazole residues in meat samples. Scanning electron microscopy confirmed the porous structure of the cellulose matrix anchored with 20-50 nm silver nanoparticles (AgNPs). Fourier transform infrared spectroscopy and X-ray diffraction verified that the metallic AgNPs coordinated with the amorphous cellulose chains. At an optimum 0.5% loading, the nanocomposite sensor showed a peak-to-peak separation of 150 mV, diffusion-controlled charge transfer kinetics, and an electron transfer coefficient of 0.6 using a ferro/ferricyanide redox probe. Square-wave voltammetry was applied for sensing sulfamethoxazole based on its two-electron oxidation peak at 0.72 V vs. Ag/AgCl in Britton-Robinson buffer of pH 7.0. A linear detection range of 0.1-100 µM sulfamethoxazole was obtained with a sensitivity of 0.752 µA/µM and limit of detection of 0.04 µM. Successful recovery between 86 and 92% and less than 6% RSD was achieved from spiked meat samples. The key benefits of the proposed disposable sensor include facile fabrication, an antifouling surface, and a reliable quantification ability, meeting regulatory limits. This research demonstrates the potential of novel cellulose-silver nanocomposite materials towards developing rapid, low-cost electroanalytical devices for decentralized on-site screening of veterinary drug residues to ensure food safety.


Assuntos
Nanopartículas Metálicas , Prata , Prata/química , Sulfametoxazol , Nanopartículas Metálicas/química , Hidrogéis , Carne , Celulose , Técnicas Eletroquímicas/métodos
7.
Am J Physiol Cell Physiol ; 325(4): C833-C848, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37642235

RESUMO

Breast cancer has become the malignant disease with the highest morbidity and mortality among female cancer patients. The prognosis of metastatic breast cancer is very poor, and the therapeutic effects still need to be improved. The molecular mechanism of breast cancer has not been fully clarified. Bioinformatics analysis was used to find the differentially expressed gene that affects the occurrence and development of breast cancer. Furthermore, scratch assays, Transwell assays, immunofluorescence, and Western blotting were used to determine the biological behavior of breast cancer cells affected by DEP domain-containing protein 1B (DEPDC1B). The molecular mechanism was investigated by mass spectrometry analysis, coimmunoprecipitation, and ubiquitin assays. Here, we found that DEPDC1B was highly expressed in breast cancer cells and tissues and was associated with lower overall survival (OS) in patients. We found that DEPDC1B interference significantly inhibited tumor invasion and migration in vitro and tumor metastasis in vivo. Mechanistically, DEPDC1B was first shown to activate the wnt/ß-catenin signaling pathway as an oncogene in breast cancer cells. In addition, we also confirmed the interaction between DEPDC1B, ubiquitin-specific protease 5 (USP5), and ß-catenin. Then, we found that DEPDC1B mediates the deubiquitination of ß-catenin via USP5, which promotes cell invasion and migration. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be considered a potential therapeutic target for breast cancer.NEW & NOTEWORTHY By using bioinformatics analysis and the experimental techniques of cell biology and molecular biology, we found that DEP domain-containing protein 1B (DEPDC1B) can promote the invasion and migration of breast cancer cells and that DEPDC1B mediates the deubiquitination of ß-catenin by ubiquitin-specific protease 5 (USP5), thus activating the wnt/ß-catenin pathway. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be used as a potential therapeutic target for breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , beta Catenina/genética , Via de Sinalização Wnt , Proteases Específicas de Ubiquitina/genética , Proteínas Ativadoras de GTPase , Melanoma Maligno Cutâneo
8.
Environ Res ; 237(Pt 1): 116911, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37597825

RESUMO

Nitrate (NO3-) pollution of groundwater is a global concern in agricultural areas. To gain a comprehensive understanding of the sources and destiny of nitrate in soil and groundwater within intensive agricultural areas, this study employed a combination of chemical indicators, dual isotopes of nitrate (δ15N-NO3- and δ18O-NO3-), random forest model, and Bayesian stable isotope mixing model (MixSIAR). These approaches were utilized to examine the spatial distribution of NO3- in soil profiles and groundwater, identify key variables influencing groundwater nitrate concentration, and quantify the sources contribution at various depths of the vadose zone and groundwater with different nitrate concentrations. The results showed that the nitrate accumulation in the cropland and kiwifruit orchard at depths of 0-400 cm increased, leading to subsequent leaching of nitrate into deeper vadose zones and ultimately groundwater. The mean concentration of nitrate in groundwater was 91.89 mg/L, and 52.94% of the samples exceeded the recommended grade III value (88.57 mg/L) according to national standards. The results of the random forest model suggested that the main variables affecting the nitrate concentration in groundwater were well depth (16.6%), dissolved oxygen (11.6%), and soil nitrate (10.4%). The MixSIAR results revealed that nitrate sources vary at different soil depths, which was caused by the biogeochemical process of nitrate. In addition, the highest contribution of nitrate in groundwater, both with high and low concentrations, was found to be soil nitrogen (SN), accounting for 56.0% and 63.0%, respectively, followed by chemical fertilizer (CF) and manure and sewage (M&S). Through the identification of NO3- pollution sources, this study can take targeted measures to ensure the safety of groundwater in intensive agricultural areas.

9.
Opt Express ; 30(9): 15201-15210, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473247

RESUMO

Dispersive time stretch has made many ultrafast applications possible owing to its high frame rate, as compared to conventional spectroscopies. By further introducing a converging time lens, this spectroscopy can resolve arbitrary emission spectra within the aperture. However, a spectral resolution of tens of picometers hinders its high-precision application. There are two limitations: the temporal aperture of the acquired signal and the actual acquisition bandwidth. To overcome these restrictions, two approaches were developed. First, a large-aperture time lens, with higher-order dispersion compensation, is used to overcome the fundamental limit of the time-bandwidth product. Second, asynchronous optical sampling, based on two frequency combs, overcomes the technical limit of the acquisition bandwidth. As a result, in this study, time-stretch spectroscopy achieved a 1-pm spectral resolution, 24-nm observation bandwidth, and 1-kHz frame rate. Moreover, it was used to observe some spectral dynamics of the random lasing process and devices with narrow spectral widths. This scheme provides essential improvement for time-stretch spectroscopy to achieve high precision.

10.
Arch Virol ; 168(1): 11, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576583

RESUMO

MicroRNAs (miRNAs) are endogenous small and noncoding RNA molecules (18-25 nt) that can regulate expression of their target genes post-transcriptionally. Previously, using high-throughput sequencing data obtained on a Solexa platform, we found that Bos taurus bta-miR-2904 (miR-2904) was significantly upregulated in Madin-Darby bovine kidney (MDBK) cells infected with bovine viral diarrhea virus (BVDV) strain NADL at 2, 6, and 18 h postinfection (hpi) compared to uninfected MDBK cells. Moreover, miR-2904 overexpression significantly reduced BVDV replication. However, the mechanism by which miR-2904 inhibits viral replication remains unclear. In this study, we used electron microscopy, laser confocal microscopy, dual-luciferase reporter analysis, real-time PCR, and Western blot assays to investigate the effect of the miR-2904 expression on BVDV NADL replication and virus-infection-induced autophagy. The results indicate that miR-2904 inhibits autophagy of MDBK cells by targeting autophagy-related gene 13 (ATG13), and overexpression of miR-2904 inhibited the replication of BVDV NADL.


Assuntos
Vírus da Diarreia Viral Bovina Tipo 1 , Vírus da Diarreia Viral Bovina Tipo 2 , Vírus da Diarreia Viral Bovina , MicroRNAs , Viroses , Animais , Bovinos , Linhagem Celular , Vírus da Diarreia Viral Bovina/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Replicação Viral/genética , Fatores de Transcrição , Autofagia/genética , Vírus da Diarreia Viral Bovina Tipo 2/genética , Diarreia , Vírus da Diarreia Viral Bovina Tipo 1/genética
11.
Eur Spine J ; 31(9): 2311-2325, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35434775

RESUMO

PURPOSE: Genetic diagnosis is a promising approach because several single-nucleotide polymorphisms (SNPs) associated with adolescent idiopathic scoliosis (AIS) progression have been reported. We review the predictive value of SNPs in curve progression of adolescent idiopathic scoliosis. METHODS: We reviewed DNA-based prognostic testing to predict curve progression. Then, the multiple polymorphisms in loci related to AIS progression were also reviewed, and we elucidated the predictive value of SNPs from four functional perspectives, including endocrine metabolism, neuromuscular system, cartilage and extracellular matrix, enzymes, and cytokines. RESULTS: The ScoliScores were less successful predictors than expected, and the weak power of predictive SNPs might account for its failure. Susceptibility loci in ESR1, ESR2, GPER, and IGF1, which related to endocrine metabolism, have been reported to predict AIS progression. Neuromuscular imbalance might be a potential mechanism of scoliosis, and SNPs in LBX1, NTF3, and SOCS3 have been reported to predict the curve progression of AIS. Susceptibility loci in SOX9, MATN1, AJAP1, MMP9, and TIMP2, which are related to cartilage and extracellular matrix, are also potentially related to AIS progression. Enzymes and cytokines play essential roles in regulating bone metabolism and embryonic development. SNPs in BNC2, SLC39A8, TGFB1, IL-6, IL-17RC, and CHD7 were suggested as predictive loci for AIS curve progression. CONCLUSIONS: Many promising SNPs have been identified to predict the curve progression of AIS. However, conflicting results from replication studies and different ethnic groups hamper their reliability. Convincing SNPs from multiethnic populations and functional verification are needed.


Assuntos
Cifose , Escoliose , Adolescente , Humanos , Povo Asiático , Estudos de Casos e Controles , Citocinas/genética , Predisposição Genética para Doença/genética , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Escoliose/diagnóstico
12.
Molecules ; 27(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889471

RESUMO

As the largest group of structurally diverse metabolites, terpenoids are versatile natural compounds that act as metabolism mediators, plant volatiles, and ecological communicators. However, few terpenoid compounds have been identified in plant parts of sacred lotus (Nelumbo nucifera Gaertn.). To elucidate the molecular genetic basis of the terpene biosynthetic pathway, terpenes from different parts of the plant, including seeds (S), young leaves (YL), mature leaves (ML), white flowers (WF), yellow flowers (YF), and red flowers (RF), were identified by LC-MS/MS and the relative contents of the same terpenes in different parts were compared. The results indicate that all plant parts primarily consist of triterpenes, with only minor quantities of sesquiterpenes and diterpenes, and there were differences in the terpene content detected in different plant parts. To illustrate the biosynthesis of various terpenoids, RNA sequencing was performed to profile the transcriptomes of various plant parts, which generated a total of 126.95 GB clean data and assembled into 29,630 unigenes. Among these unigenes, 105 candidate unigenes are involved in the mevalonate (MVA) pathway, methyl-erythritol phosphate (MEP) pathway, terpenoid backbone biosynthesis pathway, and terpenoid synthases pathway. Moreover, the co-expression network between terpene synthase (TPS) and WRKY transcription factors provides new information for the terpene biosynthesis pathway.


Assuntos
Nelumbo , Cromatografia Líquida , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Nelumbo/genética , Espectrometria de Massas em Tandem , Terpenos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
13.
J Cell Physiol ; 236(1): 79-92, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33459380

RESUMO

Circular RNAs (circRNAs) have been associated with lung cancer (LC), one of the most common cancers, but the underlying molecular mechanisms of the specific correlation with LC carcinogenesis remain unveiled. Quantitative real-time polymerase chain reaction was applied to examine the level of circZNF609. LC cells were transfected with silenced circZNF609 by siRNAs, and cell proliferation, migration, and apoptosis were evaluated to reflect the influences of circZNF609 knockdown in LC. Biotin-coupled circRNA capture, FISH and luciferase reporter assays were performed to study the relationship between circZNF609 and miR-142-3p. In current work, it was discovered that circZNF609 functioned as an onco-circRNA, which exhibited high expression as well as facilitated the proliferation and migration in LC cells. Next, we discovered that FUS RNA-binding protein, which could bind to the ZNF609 pre-mRNA, induced circZNF609 formation, and increased circZNF609 expression in LC. Furthermore, circZNF609 was verified to sponge and sequester miR-142-3p; circZNF609 enhanced LC cell proliferative and migrative ability via targeting miR-142-3p. Finally, G protein subunit beta 2 (GNB2) was figured out to involve in circZNF609/miR-142-3p axis-induced LC development. Conclusively, the results indicated that FUS-induced circZNF609 exerts promotional effects on LC cell proliferation and migration through modulation of the miR-142-3p/GNB2 axis, which could offer new insight for understanding LC.


Assuntos
Carcinogênese/genética , Proliferação de Células/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA Circular/genética , Proteína FUS de Ligação a RNA/genética , Células A549 , Animais , Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transativadores/genética
14.
Opt Express ; 29(2): 2402-2410, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33726436

RESUMO

This work reports the real-time observation of the thermo-optical dynamics in silica microsphere resonators based on the dispersive time stretch technique. In general, the thermo-optical dynamics of silica microsphere resonators, including the thermal refraction and thermal expansion, can be characterized by the resonance wavelength shift, whose duration is at the millisecond timescale. However, this fast wavelength shift process cannot be directly captured by conventional spectroscopy, and only its transmission feature can be characterized by a fast-scanning laser and an intensity detector. With the advance of the time-stretch spectroscopy, whose temporal resolution is up to tens of nanoseconds, the thermo-optical dynamics can be observed in a more straight-forward way, by utilizing the pump-probe technology and mapping the resonance wavelength to the time domain. Here, the thermo-optical dynamics are explored as a function of the power and the scanning rate of the pump laser. Theoretical simulations reproduce the experimental results, revealing that the thermo-optical dynamics of silica microsphere resonators is dominated by the fast thermo-optical effect and the slow heat dissipation process to the surroundings, which leads to gradual regression of the resonance wavelength. This work provides an alternative solution for studying the thermo-optical dynamics in whispering gallery mode microresonators, which would be crucial for future applications of microresonator photonic systems.

15.
J Cell Physiol ; 235(10): 7541-7553, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32239719

RESUMO

Lung cancer ranks topmost among the most frequently diagnosed cancers. Despite increasing research, there are still unresolved mysteries in the molecular mechanism of lung cancer. Long noncoding RNA small nucleolar RNA host gene 11 (SNHG11) was found to be upregulated in lung cancer and facilitated lung cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression while suppressed cell apoptosis. Moreover, the high expression of SNHG11 was correlated with poor prognosis of lung cancer patients, TNM stage, and tumor size. Further assays demonstrated that SNHG11 functioned in lung cancer cells via Wnt/ß-catenin signaling pathway. Subsequently, Wnt/ß-catenin pathway was found to be activated through SNHG11/miR-4436a/CTNNB1 ceRNA axis. As inhibiting miR-4436 could only partly rescue the suppression of cell function induced by silencing SNHG11, it was suspected that ß-catenin might enter cell nucleus through other pathways. Mechanism investigation proved that SNHG11 would directly bind with ß-catenin to activate classic Wnt pathway. Subsequently, in vivo tumorigenesis was also demonstrated to be enhanced by SNHG11. Hence, SNHG11 was found to promote lung cancer progression by activating Wnt/ß-catenin pathway in two different patterns, implying that SNHG11 might contribute to lung cancer treatment by acting as a therapeutic target.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Células A549 , Animais , Apoptose/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética
16.
Immunology ; 160(2): 209-219, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32149403

RESUMO

CD100 is an immune semaphorin constitutively expressed on T-cells. Matrix metalloproteinase (MMP) is an important mediator of membrane-bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T-cell function in non-small cell lung cancer (NSCLC). sCD100 and MMP-14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung-resident CD8+ T-cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP-14 on mCD100 shedding for the regulation of non-cytolytic and cytolytic functions of CD8+ T-cells were also analysed in direct and indirect contact co-culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8+ T-cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8+ T-cells compared with the non-tumour site. Recombinant CD100 stimulation enhanced non-cytolytic and cytolytic functions of CD8+ T-cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8+ T-cell activity. NSCLC patients had lower MMP-14 in the serum and in BALF from the tumour site. Recombinant MMP-14 mediated mCD100 shedding from CD8+ T-cell membrane, and led to promotion of CD8+ T-cell response in NSCLC patients. Overall, decreased MMP-14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung-resident CD8+ T-cell activity in NSCLC.


Assuntos
Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Metaloproteinase 14 da Matriz/metabolismo , Semaforinas/metabolismo , Adulto , Idoso , Antígenos CD/sangue , Líquido da Lavagem Broncoalveolar/química , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Técnicas de Cocultura , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Ativação Linfocitária , Masculino , Metaloproteinase 14 da Matriz/sangue , Pessoa de Meia-Idade , Cultura Primária de Células , Proteínas Recombinantes/metabolismo , Semaforinas/sangue , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Evasão Tumoral , Microambiente Tumoral/imunologia
17.
Can J Microbiol ; 66(5): 351-358, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32040345

RESUMO

Iron is a fundamental element required by most organisms, including Brucella. Several researchers have suggested that the iron response regulator (irr) and rhizobial iron regulator (rirA) genes regulate iron acquisition by Brucella abortus, influencing heme synthesis by and virulence of this pathogen. However, little is known about another Brucella species, Brucella melitensis. In this research, we successfully constructed two mutants: M5-90Δirr and M5-90ΔrirA. The adhesion, invasion, and intracellular survivability of these two mutants were evaluated in RAW264.7 cells infected with 1 × 106 CFU of M5-90Δirr, M5-90ΔrirA, or M5-90. We also tested the sensitivity of cells to hydrogen peroxide and their ability to grow. In addition, the virulence of these two mutants was evaluated in BALB/c mice. The results showed that the ability of these two mutants to invade and adhere inside the murine macrophages RAW264.7 was attenuated but their ability to replicate intracellularly was strengthened, enhancing the resistance to hydrogen peroxide. The M5-90Δirr mutant showed stronger growth ability than the parental strain under iron-limiting conditions. No differences were observed in the number of bacteria in spleen between M5-90 and M5-90Δirr at 7 or 15 days postinfection. However, the number of M5-90ΔrirA in spleen reduced significantly at 15 days postinfection. The splenic index of the M5-90Δirr group is evidently lower than that of M5-90. This is the first report that irr and rirA genes of B. melitensis are associated not only with virulence but also with growth ability. Together, our data suggest that M5-90Δirr is a promising Brucella vaccine candidate.


Assuntos
Proteínas de Bactérias/genética , Brucella melitensis/genética , Brucella melitensis/patogenicidade , Regulação Bacteriana da Expressão Gênica/fisiologia , Ferro/metabolismo , Fatores de Transcrição/genética , Animais , Anti-Infecciosos Locais/toxicidade , Western Blotting , Vacina contra Brucelose/imunologia , Brucelose/prevenção & controle , Contagem de Colônia Microbiana , Feminino , Peróxido de Hidrogênio/toxicidade , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/microbiologia , Virulência/genética
18.
J Med Internet Res ; 22(3): e16233, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202507

RESUMO

BACKGROUND: Endoscopic examination is a popular and routine procedure for the diagnosis and treatment of gastrointestinal (GI) diseases. Skilled endoscopists are in great demand in clinical practice, but the training process for beginners to become endoscopy specialists is fairly long. Convenience and a self-paced, learner-centered approach make electronic learning (e-learning) an excellent instructional prospect. OBJECTIVE: This study aimed to develop and apply an e-learning system in gastroscopy teaching and learning and to evaluate its effectiveness and user satisfaction. METHODS: The e-learning software Gastroscope Roaming System was developed for primary learners. The system simulates the real structure of the upper gastrointestinal (UGI) tract to teach the main characteristics of gastroscopy under both normal conditions and conditions of common UGI tract diseases. A randomized controlled trial was conducted. Participants were randomly allocated to an e-learning group (EG)or a non-e-learning control group after a pretest. On completing the training, participants undertook a posttest and gastroscopy examination. In addition, the EG completed a satisfaction questionnaire. RESULTS: Of the 44 volunteers, 41 (93%) completed the gastroscopy learning and testing components. No significant pretest differences were found between the intervention and control groups (mean 50.86, SD 6.12 vs mean 50.76, SD 6.88; P=.96). After 1 month of learning, the EG's posttest scores were higher (mean 83.70, SD 5.99 vs mean 78.76, SD 7.58; P=.03) and improved more (P=.01) than those of the control group, with better performance in the gastroscopy examination (mean 91.05, SD 4.58 vs mean 84.38, SD 5.19; P<.001). Overall, 85% (17/20) of the participants were satisfied with the e-learning system, and 95% (19/20) of the participants considered it successful. CONCLUSIONS: E-learning is an effective educational strategy for primary learners to acquire skills in gastroscopy examination and endoscopic imaging of the GI tract. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17013091; http://www.chictr.org.cn/showproj.aspx?proj=22142.


Assuntos
Gastroscopia/métodos , Adulto , Feminino , Humanos , Aprendizagem , Masculino , Inquéritos e Questionários , Voluntários , Adulto Jovem
19.
Phytother Res ; 34(11): 3019-3028, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32468636

RESUMO

Ginsenoside Rd (GRd) is a biologically active component of ginseng that stimulates the proliferation of endogenous stem cells. The objective of our research was to evaluate the utility of GRd in gastrointestinal mucosal regeneration in a rat model of inflammatory bowel disease (IBD) and to clarify whether GRd exerts its pharmacological effects by modulating endogenous intestinal stem cells. The IBD rat model was established via subcutaneous injection of indomethacin, and 10, 20, or 40 mg/kg GRd or an equal volume of physiological saline was then administered orally to rats in different groups every day for seven consecutive days. We observed that GRd treatment, especially 20 mg/kg GRd, significantly reduced indomethacin-induced damage compared with that in the control group. By measuring the mRNA and protein levels of the intestinal stem cell markers Bmi and Msi-1 and the intestinal epithelial cell marker CDX-2 as well as by double-labelling these markers with 5-bromo-2-deoxyuridine (BrdU), we inferred that GRd could stimulate the proliferation and differentiation of endogenous intestinal stem cells in IBD model rats, leading to improved recovery of intestinal function.


Assuntos
Ginsenosídeos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ginsenosídeos/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley
20.
Gastroenterol Hepatol ; 43(5): 266-272, 2020 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32094046

RESUMO

Melanosis coli (MC) is a common condition characterized by a black or brown pigment deposited in the colorectal mucosa. It is a reversible condition that is influenced by many factors, such as living habits and bowel function. However, the epidemiology and etiology of MC are still unclear. Most studies show that there is a significant correlation between the use of anthraquinone laxatives and the occurrence of MC. At present, the mechanism of the apoptosis theory is widely recognized as regards the pathogenesis of MC. There is no specific clinical manifestation of MC, and its diagnosis is mainly based on a complimentary examination, such as endoscopic and histopathological tests. General treatment, such as changing living habits, is preferred, and medical or surgical treatment should not be considered in the absence of serious malignancy. The aim of this review is to systematically present and outline the concepts of the epidemiology, etiology, histopathology, pathogenesis, clinical manifestations, diagnosis and treatment of MC, in order to improve the understanding of this condition.


Assuntos
Doenças do Colo , Melanose , Antraquinonas/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Apoptose , Doenças do Colo/diagnóstico , Doenças do Colo/epidemiologia , Doenças do Colo/etiologia , Doenças do Colo/terapia , Terapia Combinada , Sistema Enzimático do Citocromo P-450/biossíntese , Sistema Enzimático do Citocromo P-450/genética , Dieta/efeitos adversos , Humanos , Incidência , Inflamação , Mucosa Intestinal/patologia , Laxantes/efeitos adversos , Macrófagos/química , Macrófagos/patologia , Mastócitos/patologia , Melanose/diagnóstico , Melanose/epidemiologia , Melanose/etiologia , Melanose/terapia , Estresse Oxidativo , Pigmentos Biológicos/análise
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