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1.
FASEB J ; 38(8): e23590, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38656553

RESUMO

Studies have suggested that microglial IL-6 modulates inflammatory pain; however, the exact mechanism of action remains unclear. We therefore hypothesized that PKCε and MEG2 competitively bind to STAT3 and contribute to IL-6-mediated microglial hyperalgesia during inflammatory pain. Freund's complete adjuvant (FCA) and lipopolysaccharide (LPS) were used to induce hyperalgesia model mice and microglial inflammation. Mechanical allodynia was evaluated using von Frey tests in vivo. The interaction among PKCε, MEG2, and STAT3 was determined using ELISA and immunoprecipitation assay in vitro. The PKCε, MEG2, t-STAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, GLUT3, and TREM2 were assessed by Western blot. IL-6 promoter activity and IL-6 concentration were examined using dual luciferase assays and ELISA. Overexpression of PKCε and MEG2 promoted and attenuated inflammatory pain, accompanied by an increase and decrease in IL-6 expression, respectively. PKCε displayed a stronger binding ability to STAT3 when competing with MEG2. STAT3Ser727 phosphorylation increased STAT3 interaction with both PKCε and MEG2. Moreover, LPS increased PKCε, MEG2, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and GLUT3 levels and decreased TREM2 during microglia inflammation. IL-6 promoter activity was enhanced or inhibited by PKCε or MEG2 in the presence of STAT3 and LPS stimulation, respectively. In microglia, overexpression of PKCε and/or MEG2 resulted in the elevation of tSTAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and TREM2, and the reduction of GLUT3. PKCε is more potent than MEG2 when competitively binding to STAT3, displaying dual modulatory effects of IL-6 production, thus regulating the GLUT3 and TREM2 in microglia during inflammatory pain sensation.


Assuntos
Hiperalgesia , Inflamação , Interleucina-6 , Microglia , Proteína Quinase C-épsilon , Fator de Transcrição STAT3 , Animais , Fator de Transcrição STAT3/metabolismo , Microglia/metabolismo , Proteína Quinase C-épsilon/metabolismo , Proteína Quinase C-épsilon/genética , Camundongos , Interleucina-6/metabolismo , Interleucina-6/genética , Inflamação/metabolismo , Hiperalgesia/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/farmacologia , Ligação Proteica , Fosforilação , Dor/metabolismo , Adjuvante de Freund
3.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(1): 56-61, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38475951

RESUMO

OBJECTIVES: This study aimed to evaluate the influence of ceramic type and thickness on the masking ability and final aesthetic effects of chairside machinable all-ceramic crowns. METHODS: Six kinds from three types chairside machinable ceramic materials (IPS e.max CAD HT/MT/LT, IPS Empress LT, and VITA Suprinity HT/T) in shade A2 were fabricated to slice specimens into 1.0, 1.5, and 2.0 mm-thick sections (n=10). The color parameters of the specimens against black and white tiles and four resin substrates (A2, A4, B3, and C4 shade) were measured with a spectrophotometer. The translucency parameter (TP) was calculated using color parameters measured over standard white and black backgrounds. The color differences (ΔE) were calculated between there substrate shades (A4, B3, C4 ) and A2 shade (control group). Two-way analysis of variance (ANOVA) was performed on the TP values. The two va-riables were ceramic type and ceramic thickness. Three-way ANOVA was used to determine the effects of ceramic materials, ceramic thickness, and substrate shades on the ΔE values, followed by Tukey test for multiple comparisons (α=0.05). RESULTS: Ceramic type, ceramic thickness, and substrate shade significantly affected the ΔE values (P<0.001). The L* and b* values of the specimens increased with increasing ceramic thickness, except in substrate A2, whereas the ΔE values decreased. The color difference of all 1.0 mm-thick specimens or all specimens over the substrates C4 shade exceeded the clinically acceptable threshold (ΔE>3.3). CONCLUSIONS: The masking ability of chairside machinable all-ceramic crowns is influenced by ceramic type and thickness, and ceramic material. The thickness of ceramic less than 2.0 mm cannot mask the gray shade abutment.


Assuntos
Porcelana Dentária , Estética Dentária , Cor , Teste de Materiais , Cerâmica , Coroas
4.
Sci Total Environ ; 926: 171894, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38531441

RESUMO

In order to eliminate the impact of the industrial revolution on the environment and improve the water ecological environment, pollutant discharge reduction is imperative. With the acceleration of global discharge reduction process, the huge pollutant release potential and potential environmental effects of municipal solid waste landfills gradually appear, but its release amount and intensity have not been quantitatively revealed. We propose a coupling method of parameter stochastic simulation and physical process model simulation to estimate the hidden leakage of large-scale regional municipal solid waste landfills, and provide a methodology for estimating the hidden leakage of landfills in other countries and even in the whole world by taking China, which has the largest amount of waste generation among developing countries, as an example. Prior to the implementation of stringent construction quality control and assurance management requirements, the average annual leachate generation potential over the entire life cycle of 2600 landfills in China was estimated to be 4.66 × 108 m3, in which the concentrations of COD and NH3-N are 5.38 × 102-6.48 × 104 mg/L and 6.10-3.50 × 103 mg/L, respectively, and the total amounts are 5.21 × 103-7.81 × 108 t and 8.09 × 102-6.65 × 107 t, respectively. About 14 % of these pollutants may leak into the environmental media through the landfill liner with the average number of holes of 21.5/ha. For different regions, the overall release, discharge and leakage of COD and NH3-N in East China account for 35.70 %, 36.68 % and 29.60 % respectively, making it the region with the highest potential for discharge and risk of leakage. Meanwhile, the implementation of mandatory regulations related to leachate generation and control has led to a significant reduction in the leakage of pollutants. For instance, comprehensively detecting and repair of holes in the impermeable liner has reduced the number of holes to 2/ha, resulting in a reduction of >90 % in the leakage of pollutants.

5.
Adv Mater ; : e2400521, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477468

RESUMO

Large-area printing fabrication is a distinctive feature of organic solar cells (OSCs). However, the advance of upscalable fabrication is challenged by the thickness of organic active layers considering the importance of both exciton dissociation and charge collection. In this work, a bulk-heterojunction-buried (buried-BHJ) structure is introduced by sequential deposition to realize efficient exciton dissociation and charge collection, thereby contributing to efficient OSCs with 500 nm thick active layers. The buried-BHJ distributes donor and acceptor phases in the vertical direction as charge transport channels, while numerous BHJ interfaces are buried in each phase to facilitate exciton dissociation simultaneously. It is found that buried-BHJ configurations possess efficient exciton dissociation and rapid charge transport, resulting in reduced recombination losses. In comparison with traditional structures, the buried-BHJ structure displays a decent tolerance to film thickness. In particular, a power conversion efficiency of 16.0% is achieved with active layers at a thickness of 500 nm. To the best of the authors' knowledge, this represents the champion efficiency of thick film OSCs.

6.
Cancer Pathog Ther ; 2(1): 15-23, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38328712

RESUMO

Brain metastases are a leading cause of cancer-related mortality. However, progress in their treatment has been limited over the past decade, due to an incomplete understanding of the underlying biological mechanisms. Employing accurate in vitro and in vivo models to recapitulate the complexities of brain metastasis offers the most promising approach to unravel the intricate cellular and physiological processes involved. Here, we present a comprehensive review of the currently accessible models for studying brain metastasis. We introduce a diverse array of in vitro and in vivo models, including cultured cells using the Transwell system, organoids, microfluidic models, syngeneic models, xenograft models, and genetically engineered models. We have also provided a concise summary of the merits and limitations inherent to each model while identifying the optimal contexts for their effective utilization. This review serves as a comprehensive resource, aiding researchers in making well-informed decisions regarding model selection that align with specific research questions.

7.
Phys Rev E ; 109(1-1): 014142, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38366441

RESUMO

A quantum thermal device based on three nearest-neighbor coupled spin-1/2 systems controlled by the magnetic field is proposed. We systematically study the steady-state thermal behaviors of the system. When the two terminals of our system are in contact with two thermal reservoirs, respectively, the system behaves as a perfect thermal modulator that can manipulate heat current from zero to specific values by adjusting magnetic-field direction over different parameter ranges, since the longitudinal magnetic field can completely block the heat transport. Significantly, the modulator can also be achieved when a third thermal reservoir perturbs the middle spin. We also find that the transverse field can induce the system to separate into two subspaces in which neither steady-state heat current vanishes, thus providing an extra level of control over the heat current through the manipulation of the initial state. In addition, the performance of this device as a transistor can be enhanced by controlling the magnetic field, achieving versatile amplification behaviors, in particular substantial amplification factors.

8.
Phys Rev E ; 109(1-1): 014137, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38366475

RESUMO

The mechanical strain can control the frequency of two-level atoms in amorphous material. In this work, we would like to employ two coupled two-level atoms to manipulate the magnitude and direction of heat transport by controlling mechanical strain to realize the function of a thermal switch and valve. It is found that a high-performance heat diode can be realized in the wide piezo voltage range at different temperatures. We also discuss the dependence of the rectification factor on temperatures and couplings of heat reservoirs. We find that the higher temperature differences correspond to the larger rectification effect. The asymmetry system-reservoir coupling strength can enhance the magnitude of heat transfer, and the impact of asymmetric and symmetric coupling strength on the performance of the heat diode is complementary. It may provide an efficient way to modulate and control heat transport's magnitude and flow preference. This work may give insight into designing and tuning quantum heat machines.

9.
Gut ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38267200

RESUMO

BACKGROUND: The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation. METHODS: Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro. RESULTS: Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P<0.001), and the increased species of Streptococcus were found to be from the oral site or oral/nasal sites, in which Streptococcus anginosus was identified as the significantly changed species (P<0.004). Microbial source tracker revealed that PPI significantly increased the contribution of oral bacteria to gut microbiota (P=0.026), and no significant difference was found in PM group (P=0.467). Compared to the baseline, there was a 42-fold increase in gut abundance of Streptococcus anginosus in PP group (P=0.002), and the times decreased to 16-fold in PM group (P=0.029). Mouse models showed that combination of PPI and Streptococcus anginosus significantly increased the gut abundance of Streptococcus anginosus compared with using PPI or Streptococcus anginosus only. Furthermore, Streptococcus anginosus cannot survive in vitro at a pH lower than 5. CONCLUSIONS: PPIs altered gut microbiota by promoting oral-originated Streptococcus translocation into gut.

11.
Ecotoxicol Environ Saf ; 271: 115962, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237394

RESUMO

High-precision mapping based on portable X-ray fluorescence (PXRF) data is currently being studied extensively; however, owing to poor correlation with soil metal concentration, the original PXRF data directly used for co-kriging interpolation (CKI) cannot accurately map contaminated sites with heterogeneous concentrations. Therefore, this study selected a landfill-contaminated site for research, explored the best correlation mode between PXRF variants and actual heavy metal concentration, analyzed the impact of improving the correlation model on the CKI of the spatial distribution of heavy metals, and explored the most appropriate CKI mode and point density. The results showed the following: (1) After nonlinear transformation, the correlation model between PXRF and the actual concentration was significantly improved, and the correlation coefficients of five heavy metals increased from 0.214-0.232 to 0.936-0.986. (2) The introduction of corrected PXRF data significantly improves the accuracy of CKI. Compared with the original PXRF co-kriging interpolation (OP-CKI), the ME of the corrected PXRF co-kriging interpolation (CP-CKI) for Zn, Pb, and Cu decreased by 78.2 %, 45.5 %, and 65.3 %, respectively. In terms of the spatial distribution of heavy metal pollutant concentrations, CP-CKI effectively improved the influence of local anomalous high-value points on the interpolation accuracy. (3) When the sample density measured by inductively coupled plasma mass spectrometry (ICP-MS) was less than 4 boreholes/hm2, CKI accuracy decreased significantly, indicating that the sample density should not be less than a certain threshold during CKI. (4) When the sample density measured by PXRF exceeded 7 boreholes/hm2, the mean error and root mean square error of CKI continued to decrease, suggesting that the introduction of enough sample density measured by PXRF can effectively improve the accuracy of CKI.


Assuntos
Metais Pesados , Poluentes do Solo , Raios X , Espectrometria por Raios X/métodos , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Análise Espacial , Solo/química
12.
Nucleic Acids Res ; 52(D1): D980-D989, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37956339

RESUMO

To fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.


Assuntos
Bases de Dados Genéticas , Suínos , Animais , Estudo de Associação Genômica Ampla , Genótipo , Herança Multifatorial , Fenótipo , Suínos/genética , Multiômica
13.
Adv Mater ; 36(4): e2310362, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37994270

RESUMO

Three nonfused ring electron acceptors (NFREAs), namely, 3TT-C2-F, 3TT-C2-Cl, and 3TT-C2, are purposefully designed and synthesized with the concept of halogenation. The incorporation of F or/and Cl atoms into the molecular structure (3TT-C2-F and 3TT-C2-Cl) enhances the π-π stacking, improves electron mobility, and regulates the nanofiber morphology of blend films, thus facilitating the exciton dissociation and charge transport. In particular, blend films based on D18:3TT-C2-F demonstrate a high charge mobility, an extended exciton diffusion distance, and a well-formed nanofiber network. These factors contribute to devices with a remarkable power conversion efficiency of 17.19%, surpassing that of 3TT-C2-Cl (16.17%) and 3TT-C2 (15.42%). To the best of knowledge, this represents the highest efficiency achieved in NFREA-based devices up to now. These results highlight the potential of halogenation in NFREAs as a promising approach to enhance the performance of organic solar cells.

14.
BMC Genomics ; 24(1): 743, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053015

RESUMO

BACKGROUND: Chinese indigenous pigs in Yunnan exhibit considerable phenotypic diversity, but their population structure and the biological interpretation of signatures of artificial selection require further investigation. To uncover population genetic diversity, migration events, and artificial selection signatures in Chinese domestic pigs, we sampled 111 Yunnan pigs from four breeds in Yunnan which is considered to be one of the centres of livestock domestication in China, and genotyped them using Illumina Porcine SNP60K BeadChip. We then leveraged multiple bioinformatics database tools to further investigate the signatures and associated complex traits. RESULTS: Population structure and migration analyses showed that Diannanxiaoer pigs had different genetic backgrounds from other Yunnan pigs, and Gaoligongshan may undergone the migration events from Baoshan and Saba pigs. Intriguingly, we identified a possible common target of sharing artificial selection on a 265.09 kb region on chromosome 5 in Yunnan indigenous pigs, and the genes on this region were associated with cardiovascular and immune systems. We also detected several candidate genes correlated with dietary adaptation, body size (e.g., PASCIN1, GRM4, ITPR2), and reproductive performance. In addition, the breed-sharing gene MMP16 was identified to be a human-mediated gene. Multiple lines of evidence at the mammalian genome, transcriptome, and phenome levels further supported the evidence for the causality between MMP16 variants and the metabolic diseases, brain development, and cartilage tissues in Chinese pigs. Our results suggested that the suppression of MMP16 would directly lead to inactivity and insensitivity of neuronal activity and skeletal development in Chinese indigenous pigs. CONCLUSION: In this study, the population genetic analyses and identification of artificial selection signatures of Yunnan indigenous pigs help to build an understanding of the effect of human-mediated selection mechanisms on phenotypic traits in Chinese indigenous pigs. Further studies are needed to fully characterize the process of human-mediated genes and biological mechanisms.


Assuntos
Metaloproteinase 16 da Matriz , Sus scrofa , Humanos , Suínos/genética , Animais , Metaloproteinase 16 da Matriz/genética , China , Sus scrofa/genética , Genoma , Biologia Computacional , Seleção Genética , Polimorfismo de Nucleotídeo Único
15.
Medicine (Baltimore) ; 102(48): e36456, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050239

RESUMO

Fragile X-related protein 1 (FXR1) is an RNA-binding protein that belongs to the fragile X-related (FXR) family. Studies have shown that FXR1 plays an important role in cancer cell proliferation, invasion and migration and is differentially expressed in cancers. This study aimed to gain a comprehensive and systematic understanding of the analysis of FXR1's role in cancers. This would lead to a better understanding of how it contributes to the development and progression of various malignancies. this study conducted through The Cancer Genome Atlas (TCGA), GTEx, cBioPortal, TISIDB, GEPIA2 and HPA databases to investigated FXR1's role in cancers. For data analysis, various software platforms and web platforms were used, such as R, Cytoscape, hiplot plateform. A significant difference in FXR1 expression was observed across molecular and immune subtypes and across types of cancer. FXR1 expression correlates with disease-specific survival (DSS), and overall survival (OS) in several cancer pathways, further in progression-free interval (PFI) in most cancers. Additionally, FXR1 showed a correlation with genetic markers of immunomodulators in different cancer types. Our study provides insights into the role of FXR1 in promoting, inhibiting, and treating diverse cancers. FXR1 has the potential to serve as a diagnostic and prognostic biomarker for cancer, with therapeutic value in immune-based, targeted, or cytotoxic treatments. Further clinical validation and exploration of FXR1 in cancer treatment is necessary.


Assuntos
Neoplasias , Humanos , Prognóstico , Neoplasias/diagnóstico , Neoplasias/genética , Adjuvantes Imunológicos , Proliferação de Células , Biologia Computacional , Proteínas de Ligação a RNA/genética
16.
Medicine (Baltimore) ; 102(46): e36118, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37986355

RESUMO

This study aimed to investigate the angelica sinensis - radix rehmanniae (AR) role in polycystic ovary syndrome (PCOS), employing network pharmacology and molecular docking techniques for active ingredient, targets, and pathway prediction. AR active components were obtained through TCMSP platform and literature search. The related targets of AR and PCOS were obtained through the disease and Swiss Target Prediction databases. An "active ingredient-target" network map was constructed using Cytoscape software, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was conducted through Hiplot. Finally, Auto Dock Tools software was used to conduct molecular docking between active ingredients and core targets. The main bioactive ingredients of AR in the treatment of PCOS are acteoside, baicalin, caffeic acid, cistanoside F, geniposide, etc. These ingredients involve 10 core targets, such as SRC, HSP90AA1, STAT3, MAPK1, and JUN. The effect of AR on anti-PCOS mainly involves the AGE-RAGE signaling pathway, Relaxin signaling pathway, TNF signaling pathway, and ErbB signaling pathway. Molecular docking results showed that the main active components and key targets of AR could be stably combined. AR can improve hyperandrogen status, regulate glucose homeostasis, and correct lipid metabolism and other physiological processes through multi-component, multi-target, and multi-pathway. Thus, it could play a significant role in PCOS treatment. The results of our study provide a scientific foundation for basic research and clinical applications of AR for the treatment of PCOS.


Assuntos
Angelica sinensis , Medicamentos de Ervas Chinesas , Síndrome do Ovário Policístico , Feminino , Humanos , Farmacologia em Rede , Simulação de Acoplamento Molecular , Síndrome do Ovário Policístico/tratamento farmacológico
17.
Waste Manag ; 172: 320-325, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37939603

RESUMO

In this study, we simulated the actual landfill disposal process using accelerated carbonization experiments, based on the leaching characteristics of heavy metals from "alkaline" fly ash, and used the LandSim-HELP coupling model to assess the environmental risk of the leaching. The results showed that the leaching data of "alkaline" fly ash before carbonization showed the illusion of admission to landfill with only a small amount of chemical addition or even without curing/stabilization. The leached concentrations of Zn and Cd from "alkaline" fly ash after carbonation were significantly higher. The risk assessment of the leakage of heavy metals in the case of a single artificial composite liner system showed that the exposure concentrations of Pb, Zn, and Cd in samples exceeded Standard for groundwater quality (GB/T 14848-2017) the Class III permissible limits after carbonation; exposure risk for Cd was exceeded in all samples. However, although the use of a double-layer artificial composite liner to improve the level of impermeability effectively reduced the risk of Cd leaching, so that none of the non-carcinogenic risks exceeded the standard, the carcinogenic risk of Cd in the carbonized samples exceeded the factor of 1.1-4.5 of the acceptable hazard quotient, and the contamination characteristics of the alkaline fly ash still need to be kept in view.


Assuntos
Metais Pesados , Eliminação de Resíduos , Cinza de Carvão , Cádmio , Incineração , Medição de Risco , Instalações de Eliminação de Resíduos , Carbono , Material Particulado , Eliminação de Resíduos/métodos
18.
Neuromolecular Med ; 25(4): 616-631, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37796401

RESUMO

Anxiety manifestations and cognitive dysfunction are common sequelae in patients with sepsis-associated encephalopathy (SAE). Microglia-mediated inflammatory signaling is involved in anxiety, depression, and cognitive dysfunction during acute infection with bacterial lipopolysaccharide (LPS). However, the molecular mechanisms underlying microglia activation and behavioral and cognitive deficits in sepsis have not been in fully elucidated. Based on previous research, we speculated that the CD137 receptor/ligand system modulates microglia function during sepsis to mediate classical neurological SAE symptoms. A murine model of SAE was established by injecting male C57BL/6 mice with LPS, and cultured mouse BV2 microglia were used for in vitro assays. RT-qPCR, immunofluorescence staining, flow cytometry, and ELISA were used to assess microglial activation and the expression of CD137L and inflammation-related cytokines in the mouse hippocampus and in cultured BV2 cells. In addition, behavioral tests were conducted in assess cognitive performance and behavioral distress. Immunofluorescence and RT-qPCR analyses showed that hippocampal expression of CD137L was upregulated in activated microglia following LPS treatment. Pre-treatment with the CD137L neutralizing antibody TKS-1 significantly reduced CD137L levels, attenuated the expression of M1 polarization markers in microglia, and inhibited the production of TNF-α, IL-1ß, and IL-6 in both LPS-treated mice and BV2 cells. Conversely, stimulation of CD137L signaling by recombinant CD137-Fc fusion protein activated the synthesis and release of pro-inflammatory cytokines in cultures BV2 microglia. Importantly, open field, elevated plus maze, and Y-maze spontaneous alternation test results indicated that TKS-1 administration alleviated anxiety-like behavior and spatial memory decline in mice with LPS-induced SAE. These findings suggest that CD137L upregulation in activated microglia critically contributes to neuroinflammation, anxiety-like behavior, and cognitive dysfunction in the mouse model of LPS-induced sepsis. Therefore, therapeutic modulation of the CD137L/CD137 signaling pathway may represent an effective way to minimize brain damage and prevent cognitive and emotional deficits associated with SAE.


Assuntos
Ligante 4-1BB , Encefalopatia Associada a Sepse , Sepse , Animais , Humanos , Masculino , Camundongos , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Microglia , Doenças Neuroinflamatórias , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Ligante 4-1BB/efeitos dos fármacos , Ligante 4-1BB/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico
19.
J Mol Histol ; 54(6): 725-738, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37676534

RESUMO

Neuroinflammation is associated with the pathophysiology of depression. The molecular mechanism of depressive-like behavior caused by sepsis-associated encephalopathy (SAE) is incompletely understood. J147 (an analog of curcumin) has been reported to improve memory and has neuroprotective activity, but its biological function in the depressive-like behavior observed in SAE is not known. We investigated the effects of J147 on lipopolysaccharide (LPS)-induced neuroinflammatory, depressive-like behaviors, and the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signal pathway in the mouse hippocampus and microglia (BV2 cells). The forced-swimming test (FST) and tail-suspension test (TST) were undertaken for assessment of depressive-like behaviors. Expression of the proinflammatory genes interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were measured using RT-qPCR and ELISA. Microglia activation was detected using immunofluorescence staining. The TLR4/NF-κB signaling pathway was studied using western blotting and immunofluorescence staining. J147 pretreatment markedly downregulated expression of IL-6, IL-1ß, and TNF-α, and the mean fluorescence intensity of ionized calcium-binding adapter protein-1 in microglia. J147 restrained LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), inhibitor of nuclear factor kappa B (IκB) degradation, and TLR4 activation in microglia. J147 administration inhibited bodyweight loss, mortality, microglia activation, and depressive-like behaviors in LPS-treated mice. In conclusion, J147 ameliorated the sepsis-induced depressive-like behaviors induced by neuroinflammation through attenuating the TLR4/NF-κB signaling pathway in microglia.


Assuntos
NF-kappa B , Sepse , Camundongos , Animais , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Sepse/complicações , Sepse/metabolismo , Microglia/metabolismo
20.
Opt Express ; 31(19): 30832-30846, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710617

RESUMO

The most important difference between ultrastrong and non-ultrastrong coupling regimes is that the ground state contains excitations. We consider a qubit-plasmon-phonon ultrastrong coupling (USC) system with a three-level atom coupled to the photon and phonon via its upper two energy levels and show that spontaneous emission of the atom from its intermediate to its ground state produces photon and phonon pairs. It is shown that the current system can produce a strong photon/phonon stream and the atom-phonon coupling plays the active role, which ensures the experimental detection. The emission spectrum and various high-order correlation functions confirm the generation of the pairs of photons and phonons. Our study has important implications for future research on virtual photon and phonon pairs creation in the ground state of the USC regime.

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