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1.
Proteomics ; : e2300383, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700048

RESUMO

Aeromonas hydrophila, a prevalent pathogen in the aquaculture industry, poses significant challenges due to its drug-resistant strains. Moreover, residues of antibiotics like streptomycin, extensively employed in aquaculture settings, drive selective bacterial evolution, leading to the progressive development of resistance to this agent. However, the underlying mechanism of its intrinsic adaptation to antibiotics remains elusive. Here, we employed a quantitative proteomics approach to investigate the differences in protein expression between A. hydrophila under streptomycin (SM) stress and nonstress conditions. Notably, bioinformatics analysis unveiled the potential involvement of metal pathways, including metal cluster binding, iron-sulfur cluster binding, and transition metal ion binding, in influencing A. hydrophila's resistance to SM. Furthermore, we evaluated the sensitivity of eight gene deletion strains related to streptomycin and observed the potential roles of petA and AHA_4705 in SM resistance. Collectively, our findings enhance the understanding of A. hydrophila's response behavior to streptomycin stress and shed light on its intrinsic adaptation mechanism.

2.
Mol Cell Proteomics ; 21(9): 100248, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35605723

RESUMO

Protein lysine acetylation (Kac) modification plays important roles in diverse physiological functions. However, there is little evidence on the role of Kac modification in bacterial antibiotic resistance. Here, we compared the differential expressions of whole-cell proteins and Kac peptides in oxytetracycline sensitive and oxytetracycline resistance (OXYR) strains of Aeromonas hydrophila using quantitative proteomics technologies. We observed a porin family protein Aha1 downregulated in the OXYR strain, which may have an important role in the OXY resistance. Interestingly, seven of eight Kac peptides of Aha1 decreased abundance in OXYR as well. Microbiologic assays showed that the K57R, K187R, and K197R Aha1 mutants significantly increased antibiotic resistance to OXY and reduced the intracellular OXY accumulation in OXY stress. Moreover, these Aha1 mutants displayed multidrug resistance features to tetracyclines and ß-lactam antibiotics. The 3D model prediction showed that the Kac states of K57, K187, and K197 sites located at the extracellular pore vestibule of Aha1 may be involved in the uptake of specific types of antibiotics. Overall, our results indicate a novel antibiotic resistance mechanism mediated by Kac modification, which may provide a clue for the development of antibiotic therapy strategies.


Assuntos
Aeromonas hydrophila , Oxitetraciclina , Acetilação , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Lisina/metabolismo , Oxitetraciclina/metabolismo , Porinas/metabolismo , beta-Lactamas/farmacologia
3.
J Environ Manage ; 358: 120882, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38663080

RESUMO

This study offers an insightful and detailed examination of microplastic pollution in the Huixian karst wetland's groundwater, providing novel insights into the complex interplay of microplastic characteristics and their seasonal dynamics. We meticulously quantified microplastic concentrations, observing significant seasonal variation with values ranging from 4.9 to 13.4 n·L-1 in the wet season and 0.53-49.4 n·L-1 in the dry season. Our analysis pinpoints human activities and atmospheric deposition as key contributors to this contamination. A critical finding of our research is the pronounced disparity in microplastic levels between open wells and covered artesian wells, highlighting the vulnerability of open wells to higher pollution levels. Through correlation analysis, we unearthed the crucial influence of the karst region's unique hydrogeological characteristics on microplastic migration, distinctively different from non-karst areas. The karst terrain, characterized by its caves and subterranean rivers, facilitates the downward movement of microplastics from surface to groundwater, exacerbating pollution levels. Our investigation identifies agricultural runoff and domestic wastewater as primary pollution sources. These findings not only underscore the urgent need for environmental stewardship in karst regions but also provide a crucial foundation for formulating effective strategies to mitigate microplastic pollution in karst groundwater. The implications of this study extend beyond the Huixian karst wetland, offering a template for addressing microplastic pollution in similar ecosystems globally.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Microplásticos , Estações do Ano , Poluentes Químicos da Água , Áreas Alagadas , Água Subterrânea/química , Água Subterrânea/análise , Poluentes Químicos da Água/análise , Microplásticos/análise , Ecossistema
4.
J Proteome Res ; 22(4): 1193-1200, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-36856436

RESUMO

Recently, the prevalence of Aeromonas hydrophila antibiotic-resistant strains has been reported in aquaculture, but its intrinsic antibiotic resistance mechanisms are largely unknown. In the present study, a label-free proteomics technology was used to compare the differential protein abundances in response to norfloxacin (NOR) stress in A. hydrophila. The results showed that there were 186 proteins decreasing and 220 proteins increasing abundances in response to NOR stress. Bioinformatics analysis showed that the differentially expressed proteins were enriched in several biological processes, such as sulfur metabolism and homologous recombination. Furthermore, the antibiotic sensitivity assays showed that the deletion of AHA_0904, cirA, and cysI significantly decreased the resistance against NOR, whereas ΔAHA_1239, ΔcysA, ΔcysD, and ΔcysN significantly increased the resistance against NOR. Our results provide insights into NOR resistance mechanisms and indicate that AHA_0904, cirA, AHA_1239, and sulfur metabolism may play important roles in NOR resistance in A. hydrophila.


Assuntos
Aeromonas hydrophila , Norfloxacino , Norfloxacino/farmacologia , Norfloxacino/metabolismo , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Proteínas de Bactérias/metabolismo , Proteômica/métodos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Enxofre/metabolismo
5.
Environ Microbiol ; 25(5): 977-989, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604972

RESUMO

The colicin I receptor (CirA) is a well-studied outer membrane protein that has been reported to play important roles in antibiotic resistance, virulence, and iron homeostasis, although its exact physiological roles require further investigation. In this study, differentially expressed proteins between the ΔahcirA and wild-type (WT) strains of Aeromonas hydrophila were compared using quantitative proteomics. Bioinformatics analysis revealed that the expression of peptide, histidine, and arginine ATP-binding cassette (ABC) transporter system-related proteins was significantly higher in the ΔahcirA strain. Subsequent growth assays revealed that ΔahcirA grew slower than the WT strain in nutrient-limited medium when supplemented with dipeptide, histidine, and arginine as the carbon source. Far-western blot analysis further confirmed that AhCirA can directly bind to histidine/arginine and dipeptide small-molecule substrates in addition to their periplasmic-binding proteins, AhDppA and AhHisJ, respectively. These results indicate that AhCirA may play an important role in the uptake of amino acids and peptides as a channel-forming porin while also directly interacting with ABC transporters to transport nutrient substances into the plasma membrane. Overall, this study demonstrates that AhCirA is a multifunctional protein in A. hydrophila and extends our understanding of known nutrient transport mechanisms among bacteria.


Assuntos
Proteínas de Bactérias , Colicinas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Colicinas/metabolismo , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Proteômica/métodos , Histidina/metabolismo , Nutrientes , Arginina/metabolismo
6.
Skeletal Radiol ; 52(7): 1305-1311, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36512027

RESUMO

OBJECTIVE: To investigate the value of high frequency ultrasound in diagnosis of neuralgic amyotrophy. MATERIALS AND METHODS: From January 2010 to December 2020, the ultrasonographic images of 117 patients with neuralgic amyotrophy diagnosed by the Department of Neurology and hand & foot surgery of Shandong Provincial Hospital Affiliated to Shandong First Medical University were retrospectively analyzed. The ultrasonographic features were summarized. RESULTS: High frequency ultrasound could clearly show the degree of the affected nerves: No ultrasonic findings were found in 12 cases (10%). The affected nerves were thickening and hypoechogenicity with loss of normal fascicular definition in 28 cases (24%). The affected nerves showed hourglass-like changes, including constriction and torsion in 77 cases (66%). In addition, ultrasound can determine the extent of the lesion, and microvascular imaging can display small blood flow signal within the nerve. There was a significant statistical difference between the diameter of the thickened nerve fascicle and the diameter of the nerve fascicle at the corresponding site of the contralateral normal limb. CONCLUSIONS: High frequency ultrasound is a valuable imaging method for diagnosis of neuralgic amyotrophy.


Assuntos
Neurite do Plexo Braquial , Humanos , Neurite do Plexo Braquial/diagnóstico por imagem , Neurite do Plexo Braquial/patologia , Estudos Retrospectivos , Ultrassonografia/métodos , Extremidade Superior/patologia , Constrição Patológica
7.
J Dtsch Dermatol Ges ; 21(3): 229-236, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36855837

RESUMO

Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and intense pruritus, is a major skin-related burden worldwide. The diagnosis and treatment of AD is often challenging due to the high heterogeneity of AD, and its exact etiology is unknown. Metabolomics offers the opportunity to follow continuous physiological and pathological changes in individuals, which allows accurate diagnosis and management as well as providing deep insights into the etiopathogenesis of AD. Several metabolomic studies of AD have been published over the past few years. The aim of this review is to summarize these findings and help researchers to understand the rapid development of metabolomics for AD. A comprehensive and systematic search was performed using the PubMed, Embase, Cochrane Library and Web of Science databases. Twenty-six papers were finally included in the review after quality assessment. Significant differences in metabolite profiles were found between patients with AD and healthy individuals. This study provides a comprehensive overview of metabolomic research in AD. A better understanding of the metabolomics of AD may offer novel diagnostic, prognostic, and therapeutic approaches.


Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Prurido , Pele/patologia , Doença Crônica
8.
J Proteome Res ; 21(7): 1707-1717, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35674493

RESUMO

In recent years, the intracellular mechanisms that contribute to antibiotic resistance have received increasing attention, and outer membrane vesicles (OMVs) have been reported to be related to antibiotic resistance in several Gram-negative bacterial species. However, the intrinsic molecular mechanisms and the form of such antibiotic resistance are still largely unknown. In this study, OMVs from an oxytetracycline (OXY) sensitive aquatic pathogen, Aeromonas hydrophila (OXY-S), were found with significantly increased OXY resistance. Interestingly, the OXY-resistant strain (OXY-R) had a more protective role in OXY resistance. Therefore, a DIA-based quantitative proteomics analysis was performed to compare the differential expression of OMV proteins between OXY-R (OMVsR) and OXY-S (OMVsS). The results showed that seven proteins increased and five proteins decreased in OMVsR vs OMVsS. A subsequent antibiotics susceptibility assay showed that the deletion of icd, rpsF, and iscS significantly increased OXY sensitivity. Moreover, the exogenous addition of the crude OMV fractions of overexpressed recombinant proteins in E. coli with rRpsF, rIcd, rIscS, rOmpA, rPepA, rFrdA, and rRplQ demonstrated that these proteins promoted the OXY resistance of A. hydrophila. Overall, our results indicate the important protective role of OMVs in antibiotic resistance in A. hydrophila and provide novel insights on bacterial antibiotic resistance mechanisms.


Assuntos
Aeromonas hydrophila , Oxitetraciclina , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana , Escherichia coli/metabolismo , Oxitetraciclina/metabolismo , Proteômica/métodos
9.
J Biol Chem ; 297(3): 101111, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34437900

RESUMO

Pulmonary endothelial barrier dysfunction is a major pathophysiology observed in acute respiratory distress syndrome (ARDS). Ghrelin, a key regulator of metabolism, has been shown to play protective roles in the respiratory system. However, its effects on lipopolysaccharide (LPS)-induced pulmonary endothelial barrier injury are unknown. In this study, the effects of ghrelin on LPS-induced ARDS and endothelial cell injury were evaluated in vivo and in vitro. In vivo, mice treated with LPS (3 mg/kg intranasal application) were used to establish the ARDS model. Annexin V/propidium iodide apoptosis assay, scratch-wound assay, tube formation assay, transwell permeability assay, and Western blotting experiment were performed to reveal in vitro effects and underlying mechanisms of ghrelin on endothelial barrier function. Our results showed that ghrelin had protective effects on LPS-induced ARDS and endothelial barrier disruption by inhibiting apoptosis, promoting cell migration and tube formation, and activating the PI3K/AKT signaling pathway. Furthermore, ghrelin stabilized LPS-induced endothelial barrier function by decreasing endothelial permeability and increasing the expression of the intercellular junction protein vascular endothelial cadherin. LY294002, a specific inhibitor of the PI3K pathway, reversed the protective effects of ghrelin on the endothelial cell barrier. In conclusion, our findings indicated that ghrelin protected against LPS-induced ARDS by impairing the pulmonary endothelial barrier partly through activating the PI3K/AKT pathway. Thus, ghrelin may be a valuable therapeutic strategy for the prevention or treatment of ARDS.


Assuntos
Grelina/metabolismo , Síndrome do Desconforto Respiratório/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Feminino , Grelina/genética , Grelina/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Junções Intercelulares/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Microb Pathog ; 162: 105356, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34915138

RESUMO

AhyI is homologous to the protein LuxI and is conserved throughout bacterial species including Aeromonas hydrophila. A. hydrophila causes opportunistic infections in fish and other aquatic organisms. Furthermore, this pathogennot only poses a great risk for the aquaculture industry, but also for human public health. AhyI (expressing acylhomoserine lactone) is responsible for the biosynthesis of autoinducer-1 (AI-1), commonly referred to as a quorum sensing (QS) signaling molecule, which plays an essential role in bacterial communication. Studying protein structure is essential for understanding molecular mechanisms of pathogenicity in microbes. Here, we have deduced a predicted structure of AhyI protein and characterized its function using in silico methods to aid the development of new treatments for controlling A.hydrophila infections. In addition to modeling AhyI, an appropriate inhibitor molecule was identified via high throughput virtual screening (HTVS) using mcule drug-like databases.The AhyI-inhibitor N-cis-octadec-9Z-enoyl-l-Homoserine lactone was selected withthe best drug score. In order to understand the pocket sites (ligand binding sites) and their interaction with the selected inhibitor, docking (predicted protein binding complex) servers were used and the selected ligand was docked with the predicted AhyI protein model. Remarkably, N-cis-octadec-9Z-enoyl-l-Homoserine lactone established interfaces with the protein via16 residues (V24, R27, F28, R31, W34, V36, D45, M77, F82, T101, R102, L103, 104, V143, S145, and V168), which are involved with regulating mechanisms of inhibition. These proposed predictions suggest that this inhibitor molecule may be used as a novel drug candidate for the inhibition of auto-inducer-1 (AI-1) activity.The N-cis-octadec-9Z-enoyl-l-Homoserine lactone inhibitor molecule was studied on cultured bacteria to validate its potency against AI-1 production. At a concentration of 40 µM, optimal inhibition efficiency of AI-1 was observedin bacterial culture media.These results suggest that the inhibitor molecule N-cis-octadec-9Z-enoyl-l-Homoserine lactone is a competitive inhibitor of AI-1 biosynthesis.


Assuntos
Aeromonas hydrophila , Proteínas de Bactérias , 4-Butirolactona/análogos & derivados , Animais , Humanos , Percepção de Quorum
11.
Small ; 17(41): e2102300, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510727

RESUMO

Nitrogen-coordinated metal-modified carbon is regarded as a novel frontier electrocatalyst in energy conversion devices. However, the construction of intrinsic defects in a carbon matrix remains a great challenge. Herein, N-coordinated magnetic metal (Fe, Co) modified porous carbon dodecahedrons (Fe/Co-NPCD) with a large surface area, rich intrinsic defects, and evenly distributed metal-Nx species are successfully synthesized via the rational design of iron precursor and the bimetallic-organic frameworks. Because of a synergistic effect between N-coordinated dual magnetic metal active sites, the Fe/Co-NPCD exhibits exceptional electrocatalytic activity and electrochemical stability. A solar cell fabricates with the Fe/Co-NPCD yields an impressive power conversion efficiency of 8.35% in dye-sensitized solar cells, superior to that of mono-metal-doped carbon-based cells and conventional Pt-based cells. Furthermore, density functional theory calculations illustrate that Fe, Co, and N doping are in favor of improving the adsorption capacity of the catalyst for I3 - species by optimizing the magnetic momentum between the magnetic metal atoms, thereby upgrading its catalytic activity. This work develops a general strategy for synthesizing a high-performance defect-rich carbon-based catalyst, and offers valuable insight into the role of magnetic metals in catalysis, which can be used to guide the design of high-performance catalysts in the energy field.

12.
Bioorg Chem ; 107: 104530, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33323272

RESUMO

Eight new sesquiterpene derivatives (2, 4-6 and 10-13), along with five known analogues were isolated from the mangrove endophytic fungus Phomopsis sp. SYSU-QYP-23. Their structures of new compounds were established by spectroscopic methods, and the absolute configurations were confirmed by single-crystal X-ray diffraction analysis and comparison of the experimental ECD spectra. The absolute configuration of the side chain in 1 was first defined by modified Mosher's method. Compounds 1-7 showed potent inhibitory activities against nitric oxide (NO) production in lipopolysaccharides (LPS) induced RAW 264.7 cells with IC50 values ranging from 8.6 to 14.5 µM. The molecular docking results implied that the bioactive sesquiterpenes may directly bind with targeting residues in the active cavity of iNOS protein.


Assuntos
Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Phomopsis/química , Sesquiterpenos/farmacologia , Animais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Humanos , Ligação de Hidrogênio , Camundongos , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo II/química , Óxido Nítrico Sintase Tipo II/metabolismo , Ligação Proteica , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/metabolismo
13.
Biochem Biophys Res Commun ; 528(2): 311-317, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32475644

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) becomes a serious challenge in critical care medicine due to the lack of effective therapy. As the damage of alveolar epithelium is a characteristic feature of ARDS, inducing mesenchymal stem cells (MSCs) to differentiate into alveolar epithelial cells turns out to be a promising therapy for ARDS, but the differentiation efficiency is yet to be improved. The study aimed to investigate the effect of overexpressing FoxM1 on MSCs' differentiation into alveolar epithelial cells. METHODS: MSCs were isolated from mouse bone marrow, followed by transfected with lentivirus carrying the FoxM1 plasmid. Small airway epithelial cell growth medium was used as a culture system for inducing MSCs' differentiation into alveolar epithelial cells. Differentiation efficiency was assessed by detecting the expression levels of specific markers of alveolar epithelial cells mainly using quantitative reverse-transcription polymerase chain reaction and Western blot. To examine whether Wnt/ß-catenin signalling was involved in the regulation mechanism, a specific inhibitor of the pathway XAV-939 was used and nuclear and cytoplasmic proteins were also analysed respectively. Co-immunoprecipitation was performed to examine the potential interaction between FoxM1 and ß-catenin. RESULTS: Overexpressing FoxM1 statistically significantly increased the expression levels of specific markers of type II alveolar epithelial cells prosurfactant protein C and surfactant protein B, which was partially reversed by XAV-939 treatment, while the expression levels of specific marker of type I alveolar epithelial cells aquaporin 5 did not change significantly. Overexpressing FoxM1 also increased the nuclear translocation of ß-catenin and its transcriptional activity. A direct interaction between FoxM1 and ß-catenin was found in co-immunoprecipitation assay. CONCLUSION: Overexpression of FoxM1 could improve the efficiency of MSCs' differentiation into type II alveolar epithelial cells partly by activating Wnt/ß-catenin signalling.


Assuntos
Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/metabolismo , Diferenciação Celular , Proteína Forkhead Box M1/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Via de Sinalização Wnt , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Masculino , Células-Tronco Mesenquimais/ultraestrutura , Camundongos Endogâmicos C57BL , beta Catenina/metabolismo
14.
Environ Sci Technol ; 54(7): 4248-4255, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32131589

RESUMO

The widespread application of sewage sludge produced from wastewater treatment plants for agricultural use has been regarded as a primary source of microplastics (MPs) into soils. However, little is known regarding MPs in sludge-based fertilizers and their relevant fate in soils as being applied in agriculture. We comprehensively investigated the abundance, polymer size, type, and morphology of MPs in dewatered sludge, sewage sludge composts, sludge-based fertilizer-amended soils, and earthworms by stereoscopy and micro Fourier transform infrared (µ-FTIR) spectrometry methods. The results clearly showed that the quantity of MPs in soils exhibited a close correlation with the application rate of sludge-based fertilizers. The total abundances of MPs were 545.9 and 87.6 items/kg in soils after annual amendment with 30 (field A) and 15 t/ha (field B) of sludge composts, which is significantly higher than that without compost application (field C, 5.0 items/kg). Correspondingly, MPs were found in earthworms with low quantities of 1.8 and 0.4 items/individual in fields A and B, respectively, while no MP was detected in field C. We speculate that sludge composts may act as a vehicle of MPs into soils and then enter soil biota and in turn influence the spread of MPs in the environment.


Assuntos
Fertilizantes , Poluentes do Solo , Agricultura , Microplásticos , Plásticos , Esgotos , Solo
15.
Bioorg Chem ; 97: 103712, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32146180

RESUMO

Five new maleimide derivatives, (+)- and (-)- farinomalein F (1), (+)- and (-)- farinomalein G (2), farinomalein H (3) and one new linearly fused prenylated indole alkaloid phomoamide (8), along with five known compounds 4-7 and 9 were isolated from the mangrove endophytic fungus Phomopsis sp. SYSUQYP-23. Their structures and absolute configurations were determined by HRESIMS, spectroscopic and electronic circular dichroism (ECD) calculations. Bioassay results showed that compounds 3-9 exhibited significant inhibitory activities against nitric oxide (NO) production in lipopolysaccharides (LPS) induced RAW 264.7 cells, with IC50 values ranging from 4.5 to 25 µM. Moreover, the molecular docking study implied the probable binding interaction of compounds 4 and 5 with nitric oxide synthase.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Phomopsis/química , Animais , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Células RAW 264.7
16.
J Cell Physiol ; 234(8): 12692-12700, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30511368

RESUMO

27-Hydroxycholesterol (27-HC) has been implicated in the pathological process of estrogen receptor positive breast cancer. However, the role of 27-HC in lung adenocarcinoma is still unclear. Because bone metastasis is a main reason for the high mortality of lung adenocarcinoma, this study aimed to investigate the effect of 27-HC on osteoclastogenesis in lung adenocarcinoma microenvironment. The results showed that the conditioned media (CM) from lung adenocarcinoma cells cocultured with macrophages promoted osteoclast differentiation, which was enhanced by 27-HC. Further investigation showed that CM inhibited miR-139 expression and promoted c-Fos expression. Luciferase reporter assay identified c-Fos as a direct target of miR-139. CM also induced the expression and nuclear translocation of NFATc1 and STAT3 phosphorylation, which was enlarged by 27-HC but was attenuated by miR-139. Coimmunoprecipitation assay demonstrated that 27-HC increased the interaction between NFATc1 and phosphorylated STAT3, which was restricted by miR-139. Chromatin immunoprecipitation assay showed that pSTAT3 could bind to the promoter of c-Fos, c-Fos could bind to the promoter of NFATc1, and both pSTAT3 and NFATc1 could bind to the promoter of Oscar, which were enlarged by 27-HC but were blocked by miR-139. Knockdown of c-Fos mimicked the effect of miR-139. These results suggested that CM, especially containing 27-HC, promoted osteoclastogenesis by inhibiting miR-139 expression and activating the STAT3/c-Fos/NFATc1 pathway.


Assuntos
Adenocarcinoma de Pulmão/genética , Hidroxicolesteróis/metabolismo , Neoplasias Pulmonares/genética , Osteoclastos/patologia , Osteogênese/genética , Microambiente Tumoral/genética , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Diferenciação Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina/métodos , Células HEK293 , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/patologia , Camundongos , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , Células RAW 264.7 , Transdução de Sinais/genética
17.
Mol Carcinog ; 58(12): 2266-2275, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31523845

RESUMO

Non-SMC condensing I complex subunit H (NCAPH) is a member of the Barr protein family and part of the condensin I complex. The upregulation of NCAPH is associated with poor prognosis in patients with colon cancer. However, the relationship between NCAPH and hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore NCAPH expression in HCC tissues and to investigate NCAPH functions in HCC cells. In this study, we found that high expression of NCAPH in HCC indicated worse prognosis via bioinformatics analysis. Consistently, quantitative real-time polymerase chain reaction assays in 20 pairs of HCC specimens and the immunohistochemical analysis of 100 HCC tissues showed the upregulation of NCAPH. We established stable NCAPH-overexpressing and NCAPH knockdown cell lines. Cell Counting Kit-8 assays and colony formation assay were performed to analyze cell proliferation. Migration and invasion were analyzed by Transwell assays. Subcutaneous xenograft models were used to explore the role of NCAPH in tumor formation in vivo. Our results showed that NCAPH promoted tumor proliferation, migration, and invasion in vitro and in vivo. In conclusion, our findings indicate that NCAPH could serve as a novel prognostic biomarker and a potential therapeutic target for patients with HCC.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/genética , Proteínas Nucleares/genética , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Camundongos Nus , Invasividade Neoplásica , Proteínas Nucleares/metabolismo , Prognóstico , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
18.
Ann Plast Surg ; 82(3 Suppl 2): S157-S161, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30724823

RESUMO

OBJECTIVE: In this report, we present our experience on the use of bilateral lateral hallux osteo-onychocutaneous free flaps for reconstruction of distal finger and the aesthetic and functional results of this technique in a series of cases. PATIENTS AND METHODS: From February 2005 to May 2015, 7 patients underwent finger reconstruction distal to the distal interphalangeal joint using the bilateral lateral hallux osteo-onychocutaneous free flaps. The mean age was 29.3 years (range, 24-33 years). The lateral hallux osteo-onychocutaneous flaps were harvested from bilateral donor sites. The size of each flap was designed based on the size of half distal finger defect. The lateral hallux osteo-onychocutaneous free flaps from both donor sites were combined to reconstruct the distal finger. More than 50% of hallux nail was preserved in each of donor sites, which was covered with a local flap. RESULTS: All flaps used for reconstruction survived without complications after surgery. The average length of follow-up was 93.4 months (range, 16-163 months). All reconstructed distal fingers showed good aesthetic appearance, except one that underwent a secondary debulking procedure. The average total active motion of the finger was 215.7 degrees (range, 200-230 degrees). Neither pain nor numbness sensation in the reconstructed fingers was complained by the patients. The donor site morbidity was minimal. All patients had pain-free and good function outcome in both feet. CONCLUSIONS: The use of the bilateral lateral hallux osteo-onychocutaneous free flaps may provide an option for distal finger reconstruction with satisfactory function and anesthetic outcomes with minimal hallux donor site morbidity.


Assuntos
Traumatismos dos Dedos/cirurgia , Falanges dos Dedos da Mão/cirurgia , Retalhos de Tecido Biológico/transplante , Hallux/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Cicatrização/fisiologia , Adulto , Estética , Feminino , Traumatismos dos Dedos/diagnóstico , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Escala de Gravidade do Ferimento , Masculino , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Adulto Jovem
19.
Sensors (Basel) ; 18(6)2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29890649

RESUMO

In past decades, lidar techniques have become main tools for atmospheric remote sensing. However, traditional pulsed lidar systems are relatively expensive and require considerable maintenance. These shortcomings may be overcome by the development of a blue band Scheimpflug lidar system in Dalian, Northern China. Atmospheric remote measurements were carried out for 10 days in an urban area to validate the feasibility and performance of a 450-nm Scheimpflug lidar system. A 24-h continuous measurement was achieved in winter on a near horizontal path with an elevation angle of about 6.4°. The aerosol extinction coefficient retrieved by the Fernald-inversion algorithm shows good agreement with the variation of PM10/PM2.5 concentrations recorded by a national pollution monitoring station. The experimental result reveals that the linear ratio between the aerosol extinction coefficient and the PM10 concentration under high relative humidity (75⁻90%) is about two-times that in low relative humidity (≤75%) when the PM10 concentrations are less than 100 µg/m³.

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