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1.
J Hazard Mater ; 473: 134662, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38788574

RESUMO

Sediment cadmium contamination poses risks to aquatic ecosystems. Phytoremediation is an environmentally sustainable method to mitigate cadmium contamination. Submerged macrophytes are affected by cadmium stress, but plant growth-promoting rhizobacteria (PGPR) can restore the health status of submerged macrophytes. Herein, we aimed to reduce sediment cadmium concentration and reveal the mechanism by which the combined application of the PGPR Enterobacter ludwigii and the submerged macrophyte Vallisneria natans mitigates cadmium contamination. Sediment cadmium concentration decreased by 21.59% after submerged macrophytes were planted with PGPR, probably because the PGPR colonized the rhizosphere and roots of the macrophytes. The PGPR induced a 5.09-fold increase in submerged macrophyte biomass and enhanced plant antioxidant response to cadmium stress, as demonstrated by decreases in oxidative product levels (reactive oxygen species and malondialdehyde), which corresponded to shift in rhizosphere metabolism, notably in antioxidant defence systems (i.e., the peroxidation of linoleic acid into 9-hydroperoxy-10E,12Z-octadecadienoic acid) and in some amino acid metabolism pathways (i.e., arginine and proline). Additionally, PGPR mineralized carbon in the sediment to promote submerged macrophyte growth. Overall, PGPR mitigated sediment cadmium accumulation via a synergistic plantmicrobe mechanism. This work revealed the mechanism by which PGPR and submerged macrophytes control cadmium concentration in contaminated sediment.


Assuntos
Biodegradação Ambiental , Cádmio , Enterobacter , Sedimentos Geológicos , Poluentes Químicos da Água , Cádmio/toxicidade , Cádmio/metabolismo , Enterobacter/metabolismo , Enterobacter/crescimento & desenvolvimento , Enterobacter/efeitos dos fármacos , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Rizosfera , Hydrocharitaceae/metabolismo , Hydrocharitaceae/microbiologia , Hydrocharitaceae/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Biomassa
2.
Sci Total Environ ; 931: 172909, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38703834

RESUMO

The concentration of heavy metals (HMs) in aquaculture pond sediments significantly affects aquatic food safety and environmental quality. The contamination characteristics, drivers and potential sources of HMs in typical bulk freshwater aquaculture pond sediments in major provinces of China were systematically investigated using a variety of methods and models. Specifically, 130 surface sediment samples were collected from the study area, and the geoaccumulation index (Igeo) and potential ecological risk index (RI) were used to jointly evaluate the characteristics of the HMs. Spearman's correlation and redundancy analysis revealed the main drivers of the HMs. Additionally, the positive matrix factorization (PMF) model and absolute principal component score-multiple linear regression (APCS-MLR) model were used to identify the sources of HMs. The results revealed that the pond sediments were safe for fish culture in most of the study areas. Aquafeed protein content is an important driver of HM concentrations in sediments. The total organic carbon (TOC) content, percentage of clay particles, and pH of the aquaculture pond sediments determined the sediment HMs enrichment abilities as 13.6 %, 52 %, and 9.8 %, respectively. Cd, a significantly enriched pollutant, posed a greater ecological risk than the other five HMs (Cr, Cu, Zn, As, and Pb). Three sources of HMs were identified, including agricultural activity (e.g., aquafeeds, pesticides, and fertilizers), industrial production, and natural sources, with contributions of 44.29 %, 36.66 %, and 19.05 %, respectively. This study provides a scientific basis for minimizing the input and accumulation of HMs in freshwater aquaculture pond sediments, and this can provide insights into the prevention and control of the ecological risks posed by HMs.


Assuntos
Aquicultura , Monitoramento Ambiental , Sedimentos Geológicos , Metais Pesados , Lagoas , Poluentes Químicos da Água , China , Metais Pesados/análise , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Lagoas/química , Água Doce/química
3.
Sci Total Environ ; 934: 173357, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38772483

RESUMO

Submerged macrophytes are integral to the functioning of shallow lakes through their interaction with microorganisms. However, we have a limited understanding of how microbial communities in shallow lakes respond when macrophytes are restored after being historically extirpated. Here, we explored the interactions between prokaryotic communities and carbon utilization in two lakes where submerged macrophytes were restored. We found restoration reduced total carbon in sediment by 8.9 %-27.9 % and total organic carbon by 16.7 %-36.9 % relative to control treatment, but had no effects on carbon content in the overlying water. Sediment microbial communities were more sensitive to restoration than planktonic microbes and showed enhanced utilization of simple carbon substrates, such as Tween 40, after restoration. The increase in carbon utilization was attributed to declines in the relative abundance of some genera, such as Saccharicenans and Desertimonas, which were found weakly associated with the utilization of different carbon substrates. These genera likely competed with microbes with high carbon utilization in restored areas, such as Lubomirskia. Our findings highlight how restoring submerged macrophytes can enhance microbial carbon utilization and provide guidance to improve the carbon sequestration capacity of restored shallow lakes.


Assuntos
Carbono , Lagos , Microbiota , Lagos/microbiologia , Carbono/metabolismo , Microbiologia da Água , Sequestro de Carbono , Sedimentos Geológicos/microbiologia , Bactérias/metabolismo , Recuperação e Remediação Ambiental/métodos
5.
Exp Physiol ; 108(12): 1456-1465, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37909847

RESUMO

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which is a pulmonary manifestation of a systemic reactive inflammatory syndrome, is a serious disease with high mortality, and sepsis is an important risk factor in the development of ALI. Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. It plays an essential role in the regulation of the modification of synaptic efficacy and brain metabolic activity and enhances neuronal survival. However, the role and underlying mechanism of BDNF in sepsis-induced ALI remain unclear. Here, we sought to observe the expression of BDNF in the lung tissues of mice. C57BL/6J mice were divided randomly into two groups: saline (n = 4) and lipopolysaccharide (LPS) (n = 4). We found that BDNF expression was elevated in the lung tissues of septic mice. Furthermore, we found that BDNF colocalized with aquaporin 5, a marker for type I alveolar epithelial cells, by immunofluorescence staining. In addition, we also found that tropomyosin-related kinase B, the specific receptor of BDNF, colocalized with surfactant protein C, a marker for type II alveolar epithelial cells, by immunofluorescence staining. Finally, the present study indicated that BDNF may alleviate excessive LPS-induced autophagy in alveolar epithelial cells. Overall, we hypothesize that BDNF expression increases in the lung tissues of septic mice as a compensatory mechanism to ameliorate sepsis-induced ALI by inhibiting excessive alveolar epithelial cell autophagy.


Assuntos
Lesão Pulmonar Aguda , Endotoxemia , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Endotoxemia/complicações , Endotoxemia/metabolismo , Lipopolissacarídeos/efeitos adversos , Pulmão/metabolismo , Camundongos Endogâmicos C57BL
6.
PLoS Pathog ; 19(8): e1011594, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37611054

RESUMO

Treponema pallidum (Tp) has a well-known ability to evade the immune system and can cause neurosyphilis by invading the central nervous system (CNS). Microglia are resident macrophages of the CNS that are essential for host defense against pathogens, this study aims to investigate the interaction between Tp and microglia and the potential mechanism. Here, we found that Tp can exert significant toxic effects on microglia in vivo in Tg (mpeg1: EGFP) transgenic zebrafish embryos. Single-cell RNA sequencing results showed that Tp downregulated autophagy-related genes in human HMC3 microglial cells, which is negatively associated with apoptotic gene expression. Biochemical and cell biology assays further established that Tp inhibits microglial autophagy by interfering with the autophagosome-lysosome fusion process. Transcription factor EB (TFEB) is a master regulator of lysosome biogenesis, Tp activates the mechanistic target of rapamycin complex 1 (mTORC1) signaling to inhibit the nuclear translocation of TFEB, leading to decreased lysosomal biogenesis and accumulated autophagosome. Importantly, the inhibition of autophagosome formation reversed Tp-induced apoptosis and promoted microglial clearance of Tp. Taken together, these findings show that Tp blocks autophagic flux by inhibiting TFEB-mediated lysosomal biosynthesis in human microglia. Autophagosome accumulation was demonstrated to be a key mechanism underlying the effects of Tp in promoting apoptosis and preventing itself from clearing by human microglia. This study offers novel perspectives on the potential mechanism of immune evasion employed by Tp within CNS. The results not only establish the pivotal role of autophagy dysregulation in the detrimental effects of Tp on microglial cells but also bear considerable implications for the development of therapeutic strategies against Tp, specifically involving mTORC1 inhibitors and autophagosome formation inhibitors, in the context of neurosyphilis patients.


Assuntos
Microglia , Neurossífilis , Humanos , Animais , Treponema pallidum/genética , Peixe-Zebra , Autofagia , Apoptose
7.
Glob Chang Biol ; 29(17): 5044-5061, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37427534

RESUMO

Microbes play an important role in aquatic carbon cycling but we have a limited understanding of their functional responses to changes in temperature across large geographic areas. Here, we explored how microbial communities utilized different carbon substrates and the underlying ecological mechanisms along a space-for-time substitution temperature gradient of future climate change. The gradient included 47 lakes from five major lake regions in China spanning a difference of nearly 15°C in mean annual temperatures (MAT). Our results indicated that lakes from warmer regions generally had lower values of variables related to carbon concentrations and greater carbon utilization than those from colder regions. The greater utilization of carbon substrates under higher temperatures could be attributed to changes in bacterial community composition, with a greater abundance of Cyanobacteria and Actinobacteriota and less Proteobacteria in warmer lake regions. We also found that the core species in microbial networks changed with increasing temperature, from Hydrogenophaga and Rhodobacteraceae, which inhibited the utilization of amino acids and carbohydrates, to the CL500-29-marine-group, which promoted the utilization of all almost carbon substrates. Overall, our findings suggest that temperature can mediate aquatic carbon utilization by changing the interactions between bacteria and individual carbon substrates, and the discovery of core species that affect carbon utilization provides insight into potential carbon sequestration within inland water bodies under future climate warming.


Assuntos
Cianobactérias , Lagos , Lagos/microbiologia , Temperatura , Cianobactérias/metabolismo , Temperatura Baixa , Carbono/metabolismo
8.
BMC Pulm Med ; 23(1): 171, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37198573

RESUMO

Polycystin-2 (PC2), which is a transmembrane protein encoded by the PKD2 gene, plays an important role in kidney disease, but its role in lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. We overexpressed PKD2 in lung epithelial cells in vitro and in vivo and examined the role of PKD2 in the inflammatory response induced by LPS in vitro and in vivo. Overexpression of PKD2 significantly decreased production of the inflammatory factors TNF-α, IL-1ß, and IL-6 in LPS-treated lung epithelial cells. Moreover, pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, reversed the inhibitory effect of PKD2 overexpression on the secretion of inflammatory factors in LPS-treated lung epithelial cells. We further demonstrated that overexpression of PKD2 could inhibit LPS-induced downregulation of the LC3BII protein levels and upregulation of SQSTM1/P62 protein levels in lung epithelial cells. Moreover, we found that LPS-induced changes in the lung wet/dry (W/D) weight ratio and levels of the inflammatory cytokines TNF-α, IL-6 and IL-1ß in the lung tissue were significantly decreased in mice whose alveolar epithelial cells overexpressed PKD2. However, the protective effects of PKD2 overexpression against LPS-induced ALI were reversed by 3-MA pretreatment. Our study suggests that overexpression of PKD2 in the epithelium may alleviate LPS-induced ALI by activating autophagy.


Assuntos
Lesão Pulmonar Aguda , Autofagia , Lipopolissacarídeos , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Canais de Cátion TRPP/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
9.
Front Plant Sci ; 14: 1132909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950357

RESUMO

Longan yield estimation is an important practice before longan harvests. Statistical longan yield data can provide an important reference for market pricing and improving harvest efficiency and can directly determine the economic benefits of longan orchards. At present, the statistical work concerning longan yields requires high labor costs. Aiming at the task of longan yield estimation, combined with deep learning and regression analysis technology, this study proposed a method to calculate longan yield in complex natural environment. First, a UAV was used to collect video images of a longan canopy at the mature stage. Second, the CF-YD model and SF-YD model were constructed to identify Cluster_Fruits and Single_Fruits, respectively, realizing the task of automatically identifying the number of targets directly from images. Finally, according to the sample data collected from real orchards, a regression analysis was carried out on the target quantity detected by the model and the real target quantity, and estimation models were constructed for determining the Cluster_Fruits on a single longan tree and the Single_Fruits on a single Cluster_Fruit. Then, an error analysis was conducted on the data obtained from the manual counting process and the estimation model, and the average error rate regarding the number of Cluster_Fruits was 2.66%, while the average error rate regarding the number of Single_Fruits was 2.99%. The results show that the method proposed in this paper is effective at estimating longan yields and can provide guidance for improving the efficiency of longan fruit harvests.

10.
J Fish Dis ; 45(3): 387-394, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34871462

RESUMO

Cyprinid herpesvirus 2 (CyHV-2) is a viral pathogen worldwide and causing high mortality on goldfish and silver crucian carp (Carassius auratus gibelio). In order to establish a stable and sensitive immunological diagnostic approach, the recombinant ORF121 protein encoded by the CyHV-2 ORF121 gene, was selected as a capture antigen to identify cells and tissues infected with CyHV-2 by immunological methods in this study. Firstly, the open reading frame of CyHV-2 ORF121 was cloned into the PGEX-4T-3 vector and expressed in Escherichia coli. Purified recombinant ORF121 protein was then used as an antigen to prepare monoclonal antibodies, and an efficient hybridoma cell line was selected by dot-blot assay. The resulting mAb-3D9 was applied to detect CyHV-2 in infected caudal fin of Carassius auratus gibelio (GiCF) cells and fish tissues by western blotting, immunofluorescence assays and immunohistological asays. The monoclonal antibody could specifically identify CyHV-2 in infected GiCF cells and the gills, the kidney and the spleen tissues, and it could attenuate CPE by CyHV-2 in vitro, suggesting it can be applied for CyHV-2 detection in the crucian carp and ORF121 may be a candidate vaccine against CyHV-2.


Assuntos
Doenças dos Peixes , Infecções por Herpesviridae , Herpesviridae , Animais , Anticorpos Monoclonais , Doenças dos Peixes/diagnóstico , Carpa Dourada , Herpesviridae/genética , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/veterinária
11.
Front Microbiol ; 12: 749171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917045

RESUMO

Long non-coding RNAs are involved in many infectious diseases. Our previous studies showed that lncRNA-ENST00000421645 expression is increased in T lymphocytes of neurosyphilis patients compared to healthy controls. However, whether lncRNA-ENST00000421645 has biological functions remains unclear. The current study was undertaken to understand the mechanism of lncRNA-ENST00000421645 in T lymphocyte function in neurosyphilis patients. The lncRNA-ENST00000421645 pull-down assay showed that lncRNA-ENST00000421645 acted on the acetylase NAT10. The chromatin immunoprecipitation (ChIP)-PCR results showed that lncRNA-ENST00000421645 promoted the acetylation of histone H3K27 adjacent to the Kank1 promoter, thereby promoting Kank1 protein expression. Kank1 promotes 14-3-3 protein expression, inhibits NF-kB activation, inhibits IFN-γ secretion by T lymphocytes, and promotes T lymphocyte apoptosis. Taken together, our findings suggest a novel mechanism that LncRNA-ENST00000421645 upregulates Kank1 to inhibit IFN-γ expression and promote T cell apoptosis in neurosyphilis.

12.
Epigenomics ; 13(15): 1187-1203, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34382410

RESUMO

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.


Lay abstract The mechanisms underlying Treponema pallidum (a type of bacterium that causes syphilis) invasion into the CNS have not yet been established. In this study, we further clarified the role of long noncoding RNA (lncRNA) in the pathogenic process causing nerve damage. The results suggested that lncRNA-ENST00000421645 interacts with an important protein named PCM1. Suppressing the expression of PCM1 significantly increased the level of IFN-γ cytokines (substances secreted by immune cells that effect other cells) with an increased level of lncRNA-ENST00000421645 when immune cells were stimulated by phorbol-12-myristate-13-acetate a specific activator of the PKC signaling enzyme involved in gene transcription pathways. This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by interacting with PCM1 protein.


Assuntos
Autoantígenos/genética , Proteínas de Ciclo Celular/genética , Interferon gama/biossíntese , Neurossífilis/etiologia , Neurossífilis/metabolismo , RNA Longo não Codificante , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Ciclo Celular , Linhagem Celular , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Modelos Biológicos , Neurossífilis/patologia , Interferência de RNA
13.
Materials (Basel) ; 14(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443068

RESUMO

In this study, we prepared new antioxidant active plastic bottle caps by incorporating butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) and 2% (w/w) white masterbatch in high-density polyethylene (HDPE). Fourier-transform infrared (FT-IR) spectrometry revealed that the antioxidants and HDPE were uniformly mixed with noncovalent bonding. In addition, the differential scanning calorimetry (DSC) test revealed that the change in melting point and initial extrapolation temperature of the antioxidant active caps was not significant. Sensory evaluation and removal torque tests validated the suitability of the antioxidant active plastic bottle caps in industrial application. The antioxidant activity increased with a greater concentration of BHA and BHT incorporated in both antioxidant active caps (p < 0.05) and with more impact on the BHA cap compared to BHT cap in terms of antioxidant activity. Migration experiments for 10 days at 40 °C and 2 h at 70 °C showed that active antioxidants in the plastic bottle cap were more easily released into fatty foods and milk products that are highly sensitive to oxidation, and the migration of BHA and BHT did not exceed the maximum amount specified in (EC) No 1333/2008 (<200 mg/kg). As such, the antioxidant active plastic bottle caps inhibited oxidation, thereby ensuring higher food quality.

14.
Front Immunol ; 12: 692286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305926

RESUMO

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by diffuse inflammation of the lung parenchyma and refractory hypoxemia. Butorphanol is commonly used clinically for perioperative pain relief, but whether butorphanol can regulate LPS-induced alveolar macrophage polarization is unclear. In this study, we observed that butorphanol markedly attenuated sepsis-induced lung tissue injury and mortality in mice. Moreover, butorphanol also decreased the expression of M1 phenotype markers (TNF-α, IL-6, IL-1ß and iNOS) and enhanced the expression of M2 marker (CD206) in alveolar macrophages in the bronchoalveolar lavage fluid (BALF) of LPS-stimulated mice. Butorphanol administration reduced LPS-induced numbers of proinflammatory (M1) macrophages and increased numbers of anti-inflammatory (M2) macrophages in the lungs of mice. Furthermore, we found that butorphanol-mediated suppression of the LPS-induced increases in M1 phenotype marker expression (TNF-α, IL-6, IL-1ß and iNOS) in bone marrow-derived macrophages (BMDMs), and this effect was reversed by κ-opioid receptor (KOR) antagonists. Moreover, butorphanol inhibited the interaction of TLR4 with MyD88 and further suppressed NF-κB and MAPKs activation. In addition, butorphanol prevented the Toll/IL-1 receptor domain-containing adaptor inducing IFN-ß (TRIF)-mediated IFN signaling pathway. These effects were ameliorated by KOR antagonists. Thus, butorphanol may promote macrophage polarization from a proinflammatory to an anti-inflammatory phenotype secondary to the inhibition of NF-κB, MAPKs, and the TRIF-mediated IFN signaling pathway through κ receptors.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Analgésicos Opioides/farmacologia , Anti-Inflamatórios/farmacologia , Butorfanol/farmacologia , Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Pneumonia/prevenção & controle , Receptores Opioides kappa/antagonistas & inibidores , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fenótipo , Pneumonia/imunologia , Pneumonia/metabolismo , Receptores Opioides kappa/metabolismo , Transdução de Sinais
15.
Mol Neurobiol ; 58(10): 4944-4958, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34227060

RESUMO

Stress contributes to major depressive disorder (MDD) and chronic pain, which affect a significant portion of the global population, but researchers have not clearly determined how these conditions are initiated or amplified by stress. The chronic social defeat stress (CSDS) model is a mouse model of psychosocial stress that exhibits depressive-like behavior and chronic pain. We hypothesized that metabotropic glutamate receptor 5 (mGluR5) expressed in the nucleus accumbens (NAc) normalizes the depressive-like behaviors and pain following CSDS. Here, we show that CSDS induced both pain and social avoidance and that the level of mGluR5 decreased in susceptible mice. Overexpression of mGluR5 in the NAc shell and core prevented the development of depressive-like behaviors and pain in susceptible mice, respectively. Conversely, depression-like behaviors and pain were exacerbated in mice with mGluR5 knockdown in the NAc shell and core, respectively, compared to control mice subjected to 3 days of social defeat stress. Furthermore, (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), an mGluR5 agonist, reversed the reduction in the level of the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) in the NAc of susceptible mice, an effect that was blocked by 3-((2-methyl-1, 3-thiazol-4-yl) ethynyl) pyridine hydrochloride (MTEP), an mGluR5 antagonist. In addition, the injection of CHPG into the NAc shell and core normalized depressive-like behaviors and pain, respectively, and these effects were inhibited by AM251, a cannabinoid type 1 receptor (CB1R) antagonist. Based on these results, mGluR5-mediated eCB production in the NAc relieves stress-induced depressive-like behaviors and pain.


Assuntos
Transtorno Depressivo Maior/metabolismo , Endocanabinoides/metabolismo , Núcleo Accumbens/metabolismo , Dor/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Estresse Psicológico/metabolismo , Animais , Antagonistas de Receptores de Canabinoides/administração & dosagem , Doença Crônica , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Endocanabinoides/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microinjeções/métodos , Núcleo Accumbens/efeitos dos fármacos , Dor/tratamento farmacológico , Dor/psicologia , Piperidinas/administração & dosagem , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Derrota Social , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/psicologia , Tiazóis/administração & dosagem
16.
Int J Biol Macromol ; 174: 370-376, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33539953

RESUMO

Intelligent colorimetric indicator films were prepared to monitor freshness/spoilage of milk and fish by incorporating purple tomato anthocyanin (PTA) into chitosan (CS) matrix via solution casting method with PTA concentration (w/w, based on CS) of 10%, 30%, and 50%, respectively. The pH-response, UV absorption, Swelling Index, and the mechanical properties of CS/PTA films were determined. It was found that the color of the original CS/PTA films became darker with an improvement of PTA content and expressed well pH-sensitivity. With increasing of pH, the color of the CS/PTA films exposed to pH = 3-11 solutions became darker and the change in color of the CS/10% PTA film was the most discernable. The tensile strength and Young's modulus of the CS/PTA film was much lower than that of CS film, however, the elongation at breaking and Swelling Index were both improved by adding PTA. The intelligent films with 10% PTA changed their color during progressive spoilage of milk or fish, revealing their potential application for monitoring food freshness/spoilage.


Assuntos
Antocianinas/química , Quitosana/química , Leite/química , Alimentos Marinhos/análise , Solanum lycopersicum/química , Animais , Cor , Colorimetria , Módulo de Elasticidade , Embalagem de Alimentos , Qualidade dos Alimentos , Concentração de Íons de Hidrogênio , Resistência à Tração
17.
Oxid Med Cell Longev ; 2021: 7184760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33488942

RESUMO

Recent studies have claimed that iron overload was correlated with the risk of hepatocellular carcinoma (HCC), and our previous studies have also demonstrated that dandelion polysaccharide (DP) suppressed HCC cell line proliferation via causing cell cycle arrest and inhibiting the PI3K/AKT/mTOR pathway, but the effect of DP on metabolism is still not very clear. Here, we aim to clarify the effects of DP on iron metabolism and the underlying mechanism. In this study, we found that DP could reduce iron burden in hepatoma cells and grafted tumors. Hepcidin is a central regulator in iron metabolism. We confirmed that the expression of hepcidin in HCC tumor tissues was significantly higher than that in the adjacent nontumor tissues. The expression of hepcidin was downregulated in the liver of mouse model treatment with DP, as well as in hepatoma cells. Moreover, RNA sequencing and western blot data revealed that DP inhibited the IL-6-activated JAK-STAT signaling pathway. In summary, our results revealed that DP might be a new potential drug candidate for the regulation of iron burden and the treatment of HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ferro/metabolismo , Janus Quinases/metabolismo , Polissacarídeos/farmacologia , Fatores de Transcrição STAT/metabolismo , Taraxacum/química , Animais , Apoptose , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Humanos , Janus Quinases/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fatores de Transcrição STAT/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Biochem Pharmacol ; 184: 114399, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33382969

RESUMO

Dedicator of cytokinesis 2 (DOCK2), an atypical Rac activator, has important anti-inflammatory properties in blepharitis, enteric bacterial infection and colitis. However, the roles of DOCK2 in macrophage activation and acute lung injury (ALI) are still poorly elucidated. In vitro studies demonstrated that DOCK2 was essential for the nucleotide-sensing Toll-like receptor (TLR) 4-mediated inflammatory response in macrophages. We also confirmed that exposure of macrophages to LPS induced Rac activation through a TLR4-independent, DOCK2-dependent mechanism. Phosphorylation of IκB kinase (IKK) ß and nuclear translocation of transcription factor nuclear factor kappa B (NF-κB) were impaired in Ad-shDOCK2-expressing macrophages, resulting in a decreased inflammatory response. Similar results were obtained when EHop-016 (a Rac inhibitor) was used to treat uninfected macrophages. In summary, these data indicate that the DOCK2-Rac signaling pathway acts in parallel with TLR4 engagement to control IKKß activation for inflammatory cytokine release. Next, we investigated whether pharmacological inhibition of DOCK2 protects against endotoxemia-induced lung injury in mice. Treatment with 4-[3'-(2″-chlorophenyl)-2'-propen-1'-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP), a small-molecule inhibitor of DOCK2, reduced the severity of lung injury, as indicated by decreases in the lung injury score and myeloperoxidase (MPO) activity. Moreover, CPYPP attenuated LPS-induced proinflammatory cytokine release in mice. Our studies suggest that inhibition of DOCK2 may suppress LPS-induced macrophage activation and that DOCK2 may be a novel target for treating endotoxemia-related ALI.


Assuntos
Lesão Pulmonar Aguda/etiologia , Endotoxemia/complicações , Proteínas Ativadoras de GTPase/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Macrófagos/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Endotoxemia/patologia , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Proteínas Ativadoras de GTPase/genética , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Fatores de Troca do Nucleotídeo Guanina/genética , Quinase I-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Pirazóis/farmacologia , Células RAW 264.7 , Receptor 4 Toll-Like/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo
19.
Front Cell Infect Microbiol ; 10: 592864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282751

RESUMO

Monocytes are widely involved in the body's defense response, and abnormally regulated monocyte subsets are closely related to the pathogenesis of various diseases. It is unclear whether Treponema pallidum (Tp) dysregulates monocyte subsets and impacts the functions of monocytes. This study aims to analyze the distribution of monocyte subsets in syphilis patients and the effect of Tp on monocyte functions to explore the pathogenesis of syphilis. Flow cytometry was employed to detect monocyte subsets. With or without pre-treatment with rapamycin, THP-1 cell migration stimulated by Tp was investigated by a Transwell migration assay, and THP-1 cell phagocytosis was studied using fluorescent microspheres. IL-1ß and TNF-α expression was quantified by PCR and flow cytometry, while LC3 and mTOR were investigated in Tp-exposed THP-1 cells using western blotting. Tp infection led to an increase in the proportion of CD14++CD16+ monocytes and a decrease in the proportion of CD14++CD16- monocytes. In addition, Tp promoted monocyte (THP-1) CD14 and CD16 expression in vitro, induced the expression of IL-1ß and TNF-α in a dose-dependent manner and promoted the migration and autophagy of monocytes. Furthermore, mTOR phosphorylation on monocytes was stimulated by Tp, and the levels peaked at 30 min. Pre-treatment with rapamycin (mTOR inhibitor) attenuated the expression of IL-1ß and migration in Tp-exposed THP-1 cells. Tp abnormally regulates monocyte subsets and promotes migration, autophagy, and the expression of IL-1ß and TNF-α in THP-1 cells. Meanwhile, the mTOR affected the expression of IL-1ß and migration in Tp-exposed THP-1 cells. This study is important as it sheds light on the mechanism by which monocytes interact with Tp during infection.


Assuntos
Monócitos , Transdução de Sinais , Humanos , Interleucina-1beta , Receptores de Lipopolissacarídeos , Monócitos/metabolismo , Células THP-1 , Serina-Treonina Quinases TOR/metabolismo , Treponema pallidum/metabolismo
20.
Front Pharmacol ; 11: 460, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322211

RESUMO

Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion in vitro, respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis in vitro and in vivo. Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis via lowering the expression of HIF-1α and VEGF. In summary, we found that DP treatment inhibited angiogenesis in vivo and in vitro through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-α was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

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