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1.
J Am Chem Soc ; 146(32): 22180-22192, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39087925

RESUMO

Metal nanoclusters (NCs) hold great promise for expressing multipeak emission based on their well-defined total structure with diverse luminescent centers. Herein, we report the surface motif-dictated triple phosphorescence of Au NCs with dynamic color turning. The deprotonation-triggered isomerization of terminal thiouracils can evolve into a mutual transformation among their hierarchical motifs, thus serving a multipeak-emission expression with good tailoring. More importantly, the underlying electron transfer is thoroughly identified by excluding the radiative and nonradiative energy transfer, where electrons flow from the first phosphorescent state to the last two ones. The findings shed light on finely tailing motifs at the molecular level to motivate studies on customizable luminescence characteristics of metal NCs.

2.
Int Arch Allergy Immunol ; 185(8): 775-785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38588656

RESUMO

INTRODUCTION: Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent allergic symptom of diseases of allergic rhinitis and asthma. However, the mechanism of CARAS remains unclear. The study aimed to investigate the impact of microRNA-21 (miR-21) on CARAS via targeting poly (ADP-ribose) polymerase-1 (PARP-1) and phosphoinositide 3-kinase (PI3K)/AKT pathways. METHODS: The levels of miR-21-5p and PARP-1 in CARAS patients were detected by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). An ovalbumin-sensitized mouse model of CARAS was established. And knock down of miR-21-5p was constructed by intranasally administering with miR-21-5p shRNA-encoding adeno-associated virus vector. Airway resistance and airway inflammatory response were detected. ELISA was used to evaluate IL-4/IL-5/IL-13 levels in bronchoalveolar lavage fluid (BALF). Expression levels of E-cadherin, fibronectin, and α-SMA were determined using Western blotting. The levels of PARP-1 and the activation of PI3K/AKT were assayed. RESULTS: Downregulation of miR-21-5p relieved pathophysiological symptoms of asthma including airway hyperreactivity and inflammatory cell infiltration. Downregulation of miR-21-5p significantly reduced the levels of IL4, IL-5, and IL-13 in BALF. Additionally, downregulation of miR-21-5p inhibited the epithelial-mesenchymal transition (EMT) process in CARAS mice. Furthermore, miR-21-5p regulated PARP-1 and was involved in PI3K/AKT activation in CARAS mice. CONCLUSION: Downregulation of miR-21-5p ameliorated CARAS-associated lung injury by alleviating airway inflammation, inhibiting the EMT process, and regulating PARP-1/PI3K/AKT in a mouse model of CARAS.


Assuntos
Asma , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , MicroRNAs , Poli(ADP-Ribose) Polimerase-1 , Proteínas Proto-Oncogênicas c-akt , Rinite Alérgica , Animais , MicroRNAs/genética , Asma/metabolismo , Asma/genética , Asma/imunologia , Transição Epitelial-Mesenquimal/genética , Camundongos , Rinite Alérgica/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Feminino , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Masculino
3.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 225-232, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38650129

RESUMO

Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.


Assuntos
Apoptose , Asma , Proliferação de Células , MicroRNAs , Rinite Alérgica , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Rinite Alérgica/genética , Rinite Alérgica/metabolismo , Asma/genética , Asma/patologia , Masculino , Feminino , Apoptose/genética , Adulto , Proliferação de Células/genética , Animais , Inflamação/genética , Inflamação/patologia , Movimento Celular/genética , Pyroglyphidae/imunologia , Citocinas/metabolismo , Citocinas/sangue , NF-kappa B/metabolismo , Estudos de Casos e Controles , Células Epiteliais/metabolismo , Síndrome , Relevância Clínica
4.
COPD ; 21(1): 2327352, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38573027

RESUMO

Accumulating evidence has highlighted the importance of immune cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the understanding of the causal association between immunity and COPD remains incomplete due to the existence of confounding variables. In this study, we employed a two-sample Mendelian randomization (MR) analysis, utilizing the genome-wide association study database, to investigate the causal association between 731 immune-cell signatures and the susceptibility to COPD from a host genetics perspective. To validate the consistency of our findings, we utilized MR analysis results of lung function data to assess directional concordance. Furthermore, we employed MR-Egger intercept tests, Cochrane's Q test, MR-PRESSO global test, and "leave-one-out" sensitivity analyses to evaluate the presence of horizontal pleiotropy, heterogeneity, and stability, respectively. Inverse variance weighting results showed that seven immune phenotypes were associated with the risk of COPD. Analyses of heterogeneity and pleiotropy analysis confirmed the reliability of MR results. These results highlight the interactions between the immune system and the lungs. Further investigations into their mechanisms are necessary and will contribute to inform targeted prevention strategies for COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Bases de Dados Factuais
5.
Angew Chem Int Ed Engl ; 63(14): e202319690, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38320965

RESUMO

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.


Assuntos
Infecções Bacterianas , Gálio , Porfirinas , Humanos , Ferro/metabolismo , Hemina/metabolismo , Bactérias/metabolismo , Antibacterianos/metabolismo , Biofilmes , Gálio/farmacologia , Porfirinas/farmacologia , Porfirinas/metabolismo , Infecções Bacterianas/tratamento farmacológico , Homeostase , Íons/metabolismo , Polímeros/metabolismo
6.
Clin Immunol ; 255: 109736, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37604355

RESUMO

OBJECTIVE: The abnormal expansion of Tfh cells plays a key role in chronic inflammation of RA joint. We speculated that STUB1 is an important regulatory factor in promoting the differentiation of Tfh cells in RA. CONTENT AND METHODS: The proportion of Tfh cells and the level of STUB1 in Tfh cells was measured. CD4+T cells were isolated from PBMCs of RA patients, and the percentage of Tfh cells was detected after up- or down-regulating the expression of STUB1. The levels of mTORC1 pathway activator p-mTOR and p-S6K were measured by Western blot. The ubiquitination of p62 by STUB1 and its ubiquitination type as well as the activation of mTORC1 was detected in vitro, and the activation of the mTORC1 and the differentiation of Tfh cells was detected in STUB1-upregulated CD4+ T cells with overexpressed p62. RESULTS: The level of STUB1 is elevated in Tfh cells of patients. Up-regulation of STUB1 can promote the differentiation of Tfh cells. STUB1 promotes the degradation of p62 via K48-linked ubiquitination and promotes the activation of mTORC1. Overexpression of p62 can reverse the promoting effect of STUB1 on the differentiation of Tfh cells and the activation of mTORC1. CONCLUSION: STUB1 can promote the differentiation of Tfh cells in RA by mediating the activation of mTORC1 pathway through ubiquitination of p62.


Assuntos
Artrite Reumatoide , Alvo Mecanístico do Complexo 1 de Rapamicina , Ubiquitina-Proteína Ligases , Humanos , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Diferenciação Celular , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Células T Auxiliares Foliculares/metabolismo , Linfócitos T Auxiliares-Indutores/fisiologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/genética
7.
Small ; 19(43): e2302547, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37376834

RESUMO

Porphyrin-based antibacterial photodynamic therapy (aPDT) has found widespread applications in treating periodontitis. However, its clinical use is limited by poor energy absorption, resulting in limited reactive oxygen species (ROS) generation. To overcome this challenge, a novel Z-scheme heterostructured nanocomposite of Bi2 S3 /Cu-TCPP is developed. This nanocomposite exhibits highly efficient light absorption and effective electron-hole separation, thanks to the presence of heterostructures. The enhanced photocatalytic properties of the nanocomposite facilitate effective biofilm removal. Theoretical calculations confirm that the interface of the Bi2 S3 /Cu-TCPP nanocomposite readily adsorbs oxygen molecules and hydroxyl radicals, thereby improving ROS production rates. Additionally, the photothermal treatment (PTT) using Bi2 S3 nanoparticles promotes the release of Cu2+ ions, enhancing the chemodynamic therapy (CDT) effect and facilitating the eradication of dense biofilms. Furthermore, the released Cu2+ ions deplete glutathione in bacterial cells, weakening their antioxidant defense mechanisms. The synergistic effect of aPDT/PTT/CDT demonstrates potent antibacterial activity against periodontal pathogens, particularly in animal models of periodontitis, resulting in significant therapeutic effects, including inflammation alleviation and bone preservation. Therefore, this design of semiconductor-sensitized energy transfer represents an important advancement in improving aPDT efficacy and the treatment of periodontal inflammation.


Assuntos
Nanocompostos , Periodontite , Fotoquimioterapia , Animais , Espécies Reativas de Oxigênio , Fotoquimioterapia/métodos , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Biofilmes , Inflamação/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Íons
8.
Ecotoxicol Environ Saf ; 262: 115175, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37379666

RESUMO

The occurrence of antibiotics in agricultural soils has raised concerns due to their potential risks to ecosystems and human health. However, a comprehensive understanding of antibiotic accumulation, distribution, and potential risks to terrestrial ecosystems on a global scale is still limited. Therefore, in this study, we evaluated the accumulation of antibiotics and their potential risks to soil microorganisms and plants, and highlighted the driving factors of antibiotic accumulation in agricultural soils based on 134 peer-reviewed studies (between 2000 and 2022). The results indicated that 56 types of antibiotics were detected at least once in agricultural soils with concentrations ranging from undetectable to over 7000 µg/kg. Doxycycline, tylosin, sulfamethoxazole, and enrofloxacin, belonging to the tetracyclines, macrolides, sulfonamides, and fluoroquinolones, respectively, were the most accumulated antibiotics in agricultural soil. The accumulation of TCs, SAs, and FQs was found to pose greater risks to soil microorganisms (average at 29.3%, 15.4%, and 21.8%) and plants (42.4%, 26.0%, and 38.7%) than other antibiotics. East China was identified as a hot spot for antibiotic contamination due to high levels of antibiotic concentration and ecological risk to soil microorganisms and plants. Antibiotic accumulation was found to be higher in vegetable fields (245.5 µg/kg) and orchards (212.4 µg/kg) compared to croplands (137.2 µg/kg). Furthermore, direct land application of manure resulted in a greater accumulation of TCs, SAs, and FQs accumulation in soils than compost fertilization. The level of antibiotics decreased with increasing soil pH and organic matter content, attributed to decreasing adsorption and enhancing degradation of antibiotics. In conclusion, this study highlights the need for further research on the impacts of antibiotics on soil ecological function in agricultural fields and their interaction mechanisms. Additionally, a whole-chain approach, consisting of antibiotic consumption reduction, manure management strategies, and remediation technology for soil contaminated with antibiotics, is needed to eliminate the potential environmental risks of antibiotics for sustainable and green agriculture.

9.
Sensors (Basel) ; 23(10)2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37430555

RESUMO

Polydopamine (PDA) is a multifunctional biomimetic material that is friendly to biological organisms and the environment, and surface-enhanced Raman scattering (SERS) sensors have the potential to be reused. Inspired by these two factors, this review summarizes examples of PDA-modified materials at the micron or nanoscale to provide suggestions for designing intelligent and sustainable SERS biosensors that can quickly and accurately monitor disease progression. Undoubtedly, PDA is a kind of double-sided adhesive, introducing various desired metals, Raman signal molecules, recognition components, and diverse sensing platforms to enhance the sensitivity, specificity, repeatability, and practicality of SERS sensors. Particularly, core-shell and chain-like structures could be constructed by PDA facilely, and then combined with microfluidic chips, microarrays, and lateral flow assays to provide excellent references. In addition, PDA membranes with special patterns, and hydrophobic and strong mechanical properties can be used as independent platforms to carry SERS substances. As an organic semiconductor material capable of facilitating charge transfer, PDA may possess the potential for chemical enhancement in SERS. In-depth research on the properties of PDA will be helpful for the development of multi-mode sensing and the integration of diagnosis and treatment.


Assuntos
Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Humanos , Animais , Pesquisa Biomédica
10.
Ecotoxicol Environ Saf ; 247: 114262, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36327786

RESUMO

Volatile chlorinated hydrocarbons (VCHs) contaminated groundwater has a low indigenous microorganism population, and lack of nutrient substrates involved in degradation reactions, resulting in a weak natural remediation ability of groundwater ecosystems. In this study, based on the principle of degradation of VCHs by indigenous microorganisms in groundwater, and combined with biostimulation and controlled-release technology, we developed a starch-based encapsulated targeted bionutrient (YH-1) with easy uptake, good stability, controllable slow-release migration, and long timeliness for the remediation of groundwater contaminated by VCHs by indigenous microorganisms. The results showed that YH-1 is easily absorbed by microorganisms and can rapidly initiate itself to stimulate the microbial degradation of VCHs, and the degradation rate of various VCH components within 7 days was 82.38-92.38 %. The release rate of nutrient components in YH-1 increases with increasing VCH concentrations in groundwater; this could effectively prolong the action time of nutrient components, while also improving the degradation efficiency of pollutants with a sustained effect of more than 15 days. Simultaneously, owing to the fluidity, water solubility, and biodegradability of YH-1 in lithologic media, YH-1 injection did not cause blockage of the lithologic media in the aquifer. Through YH-1 stimulation, indigenous microorganisms grew rapidly in the underground environment, the diversity of microbial communities and the total number of species increased, and the correlation between genera strengthened. Simultaneously, YH-1 improved the ability of microbial community to convert inorganic electron donors/acceptors, thereby strengthening the co-metabolic mechanism between microorganisms. Additionally, there was a significant increase in the percentage of many microorganisms (e.g., Sphingomonas, Janthinobacterium, Duganella, etc.) that mediated the reductive dechlorination process and were redox inorganic electron donors/acceptors. This was conducive to the reductive dechlorination process of VCHs and achieved the efficient degradation of VCHs.


Assuntos
Antineoplásicos , Água Subterrânea , Hidrocarbonetos Clorados , Microbiota , Amido , Preparações de Ação Retardada , Nutrientes , Oxidantes
11.
Ecotoxicol Environ Saf ; 246: 114139, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36193588

RESUMO

The resistance mechanism of microbial communities in contaminated groundwater under combined stresses of aromatic hydrocarbons (AHs), NH4+, and Fe-Mn exceeding standard levels was studied in an abandoned oil depot in Northeast China. The response of environmental parameters and microbial communities under different pollution levels in the study area was discussed, and microscopic experiments were conducted using background groundwater with different AHs concentrations. The results showed that indigenous microbial community were significantly affected by environmental factors, including pH, TH, CODMn, TFe, Cr (VI), NH4+, NO3-, and SO42-. AHs likely had a limited influence on microbial communities, mainly causing indirect changes in the microbial community structure by altering the electron donor/acceptor (mainly Fe, Mn, NO3-, NO2-, NH4+, and SO42-) content in groundwater, and there was no linear effect of AHs content on the microbial community. In low- and medium-AHs-contaminated groundwater, the microbial diversity increased, whereas high AHs contents decreased the diversity of the microbial community. The microbial community had the strongest ability to metabolize AHs in the medium-AHs-contaminated groundwater. In the high-AHs-contaminated groundwater, microbial communities mainly degraded AHs through a complex co-metabolic mechanism due to the inhibitory effect caused by the high concentration of AHs, whereas in low-AHs-contaminated groundwater, microbial communities mainly caused a mutual transformation of inorganic electron donors/acceptors (mainly including N, S), and the microbial community's ability to metabolize AHs was weak. In the high-AHs-contaminated groundwater, the microbial community resisted the inhibitory effect of AHs mainly via a series of resistance mechanisms, such as regulating their life processes, avoiding unfavorable environments, and enhancing their feedback to the external environment under high-AHs-contaminated conditions.


Assuntos
Água Subterrânea , Hidrocarbonetos Aromáticos , Microbiota , Poluentes Químicos da Água , Biodegradação Ambiental , Poluentes Químicos da Água/análise , Água Subterrânea/química
12.
Bull Environ Contam Toxicol ; 108(4): 629-634, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34613433

RESUMO

To develop high-performance biochar adsorbents, the adsorption ability and rate of untreated (BC-CK) and six modified biochars with amino (BC-NH), epoxy (BC-C2H2O), ethoxy (BC-C2H5O), hydrosulfuryl (BC-SH), selenium (BC-Se), and chitosan (BC-Chitosan) on Hg(II) and MeHg were investigated by simulated experiment. The results indicated that the some modified biochars (BC-NH, BC-C2H2O, BC-C2H5O and BC-Chitosan) showed lower adsorption capacity than the untreated, possibly due to the decreased specific surface area and pore volume. Whereas, BC-SH and BC-Se was improved immensely by forming stable -SH-Hg and Hg-Se with the adsorption capacity 1.26 and 1.51 times as much as BC-CK, respectively. In spite of that, Hg desorption capacities and rates of all biochars were extremely low, exhibiting great adsorption stability of biochars on Hg in another way. In addition, BC-Chitosan performed the highest adsorption speed. These provided insights on the adsorption effectiveness for Hg in the aqueous solution that was critical for evaluating the application of modified biochars.


Assuntos
Mercúrio , Adsorção , Carvão Vegetal
13.
Pharm Biol ; 60(1): 347-358, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35171066

RESUMO

CONTEXT: Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). OBJECTIVE: To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. MATERIALS AND METHODS: We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. RESULTS: SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (-72%), PIK3R1 (-40%), and COL3A1 (-65%) compared with OVA + LPS. CONCLUSIONS: Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA.


Assuntos
Asma/tratamento farmacológico , Extrato de Sementes de Uva/farmacologia , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proantocianidinas/farmacologia , Adulto , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/farmacologia , Asma/genética , Asma/fisiopatologia , Estudos de Casos e Controles , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica , Extrato de Sementes de Uva/administração & dosagem , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Ovalbumina , Proantocianidinas/administração & dosagem , Índice de Gravidade de Doença
14.
Anticancer Drugs ; 32(1): 11-21, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33290312

RESUMO

Lung cancer is one of the most common human cancers. Long noncoding RNA AFAP1-AS1 (LncRNA AFAP1-AS1) and microRNA-545-3p (miR-545-3p) were reported to play important roles in lung cancer development. This study aimed to elucidate the functional mechanisms of AFAP1-AS1 and miR-545-3p in lung cancer. Quantitative real time polymerase chain reaction was carried out to determine the levels of AFAP1-AS1, miR-545-3p and hepatoma-derived growth factor (HDGF). Cell proliferation, apoptosis, migration and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and transwell migration and invasion assays, respectively. Furthermore, the interaction between miR-545-3p and AFAP1-AS1 or HDGF was predicted by bioinformatics analysis software starbase and confirmed by the dual luciferase reporter assay. Western blot assay was used to detect the protein level of HDGF. Besides, murine xenograft model was conducted through injecting A549 cells transfected with sh-AFAP1-AS1. The expression levels of AFAP1-AS1 and HDGF were increased, while miR-545-3p was decreased in lung cancer tissues and cells. AFAP1-AS1 knockdown suppressed lung cancer cell proliferation, migration, and invasion and induced apoptosis. Furthermore, AFAP1-AS1 mediated cell progression through regulating miR-545-3p expression. In addition, miR-545-3p negatively regulated the expression level of HDGF via binding 3'-untranslated region of HDGF. As expected, AFAP1-AS1 knockdown inhibited lung cancer progression via affecting miR-545-3p/HDGF axis. Besides, AFAP1-AS1 knockdown suppressed lung cancer tumor growth in vivo. Collectively, our results suggested that AFAP1-AS1 promoted the development of lung cancer via regulating miR-545-3p/HDGF axis, providing a potential target for the treatment of lung cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Invasividade Neoplásica , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Cell Physiol Biochem ; 50(3): 1140-1153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355907

RESUMO

BACKGROUND/AIMS: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. This study aimed to identify overlapping or diverging dysregulated genes, lncRNAs, miRNAs and signaling pathways in smoking and non-smoking chronic obstructive pulmonary disease (COPD). METHODS: Compared to normal controls, we identified the shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in smoking and non-smoking COPD by RNA-sequencing and bioinformatics analysis. Functional annotation of DEmRNAs were performed. Both cis and trans-target DEmRNAs of DElncRNAs were identified. The target DEmRNAs of DEmiRNAs were identified as well. The DEmiRNA-DEmRNA-DElncRNA interaction network was constructed. QRT-PCR was performed to validat the selected DEmiRNAs, DEmRNA and DElncRNAs in COPD. RESULTS: Compared to normal control, 1234 DEmRNAs, 96 DElncRNAs and 151 DEmiRNAs were identified in non-smoking patients with COPD; 670 DEmRNAs, 44 DElncRNAs and 63 DEmiRNAs were identified in smoking patients with COPD. Leukocyte transendothelial migration and pathways in cancer were significantly enriched pathways in non-smoking and smoking COPD, respectively. MiR-122-5p-A2M-LINC00987/A2M-AS1/ linc0061 interactions might play key roles in COPD irrespective with the smoking status. Let-7-ADRB1-HLA-DQB1-AS1 might play a key role in the pathogenesis of smoking COPD while miR-218-5p/miR15a-RORA-LOC101928100/LINC00861 and miR-218-5p/miR15a-TGFß3-RORA-AS1 interactions might involve with non-smoking COPD. CONCLUSION: We identified the shared and diverging genes, lncRNAs, miRNAs and their interactions and pathways in smoking and non-smoking COPD which provided clues for understanding the mechanism and developing novel diagnostic and therapeutic strategies for COPD.


Assuntos
MicroRNAs/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Fumar , Adulto , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/metabolismo
16.
Heliyon ; 10(7): e28469, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560267

RESUMO

There is mounting evidence that coronavirus disease 2019 (COVID-19) can cause immune dysregulation. The consequence of this immune dysregulation may contribute to susceptibility to tuberculosis (TB). Thyroid gland involvement by TB is extremely uncommon and typically the result of disseminated infection. It can be hard to diagnose because there are no identifiable symptoms. We present the case of a Chinese patient who had a fever again after COVID-19 infection that was finally diagnosed as thyroid tuberculosis with a cold abscess. Clinicians should maintain a high index of suspicion for high-risk patients from endemic regions with medical comorbidities, such as immunocompromised disease and malnutrition.

17.
Sci Total Environ ; 947: 174480, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38972400

RESUMO

Reference evapotranspiration (ET0) estimation is crucial for efficient irrigation planning, optimized water management and ecosystem modeling, yet it presents significant challenges, particularly when meteorological data availability is limited. This study utilized remote sensing data of land surface temperature (LST), day of year, and latitude, and employed a machine learning approach (i.e., random forest) to develop an improved remote sensing ET0 model. The model performed excellently in 567 meteorological stations in China with an R2 of 0.97, RMSE of 0.40, MBE of 0.00, and MAPE of 0.11 compared to the FAO-PM ET0; it also performed well globally, yielding an average R2 of 0.97 and RMSE of 0.43 across 120 sites in mid-latitude (20°-50°) regions. This model demonstrates simplicity, accuracy, robust and generalization, holding great potential for widespread application, especially in the large-scale, high-resolution estimation of ET0. This study will contribute to advancements in water resources management, agricultural planning, and climate change studies.

18.
Int Immunopharmacol ; 130: 111739, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38442574

RESUMO

Persistent type (T) 2 airway inflammation plays an important role in the development of severe asthma. However, the molecular mechanisms leading to T2 severe asthma have yet to be fully clarified. Human normal lung epithelial cells (BEAS-2B cells) were transfected with LINC00158/BCL11B plasmid/small interfering RNA (siRNA). Levels of epithelial-mesenchymal transition (EMT)-related markers were measured using real-time qPCR (RT-qPCR) and western blot. A dual luciferase reporter assay was used to validate the targeting relationship between LINC00158 and BCL11B. The effects of LINC00158-lentivirus vector-mediated overexpression and dexamethasone on ovalbumin (OVA)/lipopolysaccharide (LPS)-induced severe asthma were investigated in mice in vivo. Our study showed that overexpression of LINC00158/BCL11B inhibited the levels of EMT-related proteins, apoptosis, and promoted the proliferation of BEAS-2B cells. BCL11B was a direct target of LINC00158. And LINC00158 targeted BCL11B to regulate EMT, apoptosis, and cell proliferation of BEAS-2B cells. Compared with severe asthma mice, LINC00158 overexpression alleviated OVA/LPS-induced airway hyperresponsiveness and airway inflammation, including reductions in T helper 2 cells factors in lung tissue and BALF, serum total- and OVA-specific IgE, inflammatory cell infiltration, and goblet cells hyperplasia. In addition, LINC00158 overexpression alleviated airway remodeling, including reduced plasma TGF-ß1 and collagen fiber deposition, as well as suppression of EMT. Additionally, overexpression of LINC00158 enhanced the therapeutic effect of dexamethasone in severe asthmatic mice models. LINC00158 regulates BEAS-2B cell biological function by targeting BCL11B. LINC00158 ameliorates T2 severe asthma in vivo and provides new insights into the clinical treatment of severe asthma.


Assuntos
Remodelação das Vias Aéreas , Asma , RNA Longo não Codificante , Proteínas Repressoras , Proteínas Supressoras de Tumor , Animais , Humanos , Camundongos , Asma/imunologia , Asma/terapia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Supressoras de Tumor/genética , RNA Longo não Codificante/administração & dosagem , RNA Longo não Codificante/genética , Transfecção
19.
Nat Prod Res ; : 1-9, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824431

RESUMO

A novel cytochalasin named diaporchalasin A (1) bearing a cinnamenyl and an epoxy-macrocycloketone, and a new benzenepropionic acid derivative (2), and two known compounds (3 and 4) were isolated from Conus marmoreus-derived fungus Diaporthe sp. XMA007. Their structures were elucidated through detailed spectroscopic analysis, and the absolute configuration of 1 was determined by conformational analysis and TDDFT-ECD calculation. Their activity evaluation on PDE4 inhibition and breast cancer cell cytotoxicity were conducted, and compound 1 showed moderate inhibition on PDE4.

20.
Front Microbiol ; 15: 1441476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39184027

RESUMO

Background: The Herpesviridae family contains several human-related viruses, which are able to establish colonizing and latency in the human body, posing a significant threat to the prognosis of patients. Pulmonary infections represent one of the predominant infectious diseases globally, characterized by diverse and multifaceted clinical manifestations that have consistently attracted clinician's concern. However, the relationship of herpesviruses on the prognosis of pulmonary infections and the respiratory microbiota remains poorly understood. Methods: Here, we retrospectively analyzed respiratory samples from 100 patients with pulmonary infection detected by metagenomic next-generation sequencing (mNGS). Results: Employing mNGS, five herpesvirus species were detected: Human alphaherpesvirus 1 (HSV-1), Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), Human betaherpesvirus 7 (HHV-7), and Human betaherpesvirus 6B (HHV-6B). Regression analysis showed that the age and positivity of herpesviruses in patients were independently correlated with ICU admission rates. In addition, positivity of herpesvirus was related with increased ICU days and total hospital stay. The herpesvirus-positive group demonstrated markedly higher incidences of co-infections and fungi-positive, predominantly involving Pneumocystis jirovecii and Aspergillus fumigatus. Analysis of respiratory microbiota revealed a substantially altered community composition within the herpesvirus-positive group, and herpesviruses were significantly positively correlated with the diverse respiratory opportunistic pathogens. Conclusion: Overall results substantiate that the active herpesviruses in patients with pulmonary infections were significantly associated with high ICU admission rate. Moreover, the herpesviruses promotes the dysbiosis of the respiratory microbiota and an increased proportion of co-infections. These insights could contribute to unraveling the underlying mechanisms connecting active herpesviruses to the progression of severe illnesses.

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