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1.
Front Immunol ; 15: 1370658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571945

RESUMO

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Verrucomicrobia/metabolismo , Intestinos , Obesidade , Akkermansia
2.
Food Res Int ; 184: 114209, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609210

RESUMO

To promote the rationalized and standardized application of star anise in braised poultry products, the effects of different concentrations of star anise (0 %, 0.1 %, 0.2 %, 0.3 %, and 0.4 %) on the aroma and taste compounds intensities of braised duck legs from the perspective of flavor were evaluated by using flavor omics approach combined with multivariate statistics. The volatile flavor results showed that there were 17 key aroma compounds with odor activity values (OAVs) > 1, including aldehydes, alcohols, ketones, furans, hydrocarbons, and ethers. Most of the aroma compounds related to lipid oxidation were significantly inhibited when the concentration of star anise reached 0.2 %, especially inhibited the concentrations of the unpleasant off-odorants containing hexanal, heptanal, 1-octen-3-ol, and 2-pentyl-furan by 30.27 %, 15.08 %, 30.30 %, and 41.63 %, respectively. And the flavor intensities of these compounds were negatively correlated with the concentration of star anise. Additionally, star anise gave braised duck legs characteristic aroma such as floral and herbal notes. The taste results revealed that the maximum umami value (4.36 g MSG/100 g) of braised duck legs was observed when the concentration of star anise reached 0.2 %. Six flavor markers were obtained via PLS-DA model, and the flavors of braised duck legs with different concentrations of star anise were distinguished. This study provided a vital theoretical basis for the rational application and flavor control of star anise in braised poultry products.


Assuntos
Patos , Illicium , Animais , Odorantes , Paladar , Éteres
3.
Mater Horiz ; 11(7): 1808-1816, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38323653

RESUMO

Accelerating the oxidation process at photoanode-electrolyte interfaces can prolong the lifetime of photoexcited electrons and improve the efficiency of photoelectrochemical cathodic protection (PECCP) systems without relying on hole scavengers. However, the systematic design of precisely structured heterostructures for efficient photoanodes remains challenging. Here we meticulously engineered a type-II heterostructure featuring precise spatial organization, wherein NiFe-layered double hydroxide nanosheets (NiFe-LDH NSs) were assembled onto annealed TiO2 nanorod arrays (ATNAs), demonstrating their effectiveness in achieving efficient PECCP. The interfacial electronic coupling and appropriate energy alignment between the NiFe-LDH NSs and ATNAs allowed rapid hole extraction from the ATNAs to the NiFe-LDH NSs. Furthermore, the uniform distribution of the NiFe-LDH NSs on top of ATNAs drastically reduced the overpotential of oxygen evolution reactions (OER) from 370 to 200 mV and Tafel slope from 162 to 56 mV dec-1, leading to significantly improved cathodic protection of 304 stainless steel (SS) under extended illumination and interesting post-illumination protection. In addition, with the increase of testing cycles, the as-prepared NiFe-LDH NSs@ATNAs demonstrated a progressively enhanced cathodic protection potential from 0.15 to 0.13 V vs. RHE over 50 cycles. These findings provide important guidelines for the design of future high-efficiency green metal protection through rational photoanode design.

4.
Avian Dis ; 67(4): 402-409, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38300659

RESUMO

The complexity of influenza A virus (IAV) infections in avian hosts leads to equally complex scenarios for the vaccination of poultry. Vaccination against avian influenza strains can be used to prevent infections from sources with a single strain of IAV. It has been used as a part of outbreak control strategies as well as a way to maintain production for both low and high pathogenicity outbreaks. Unlike other viral pathogens of birds, avian influenza vaccination when used against highly pathogenic avian influenza virus, is tied to international trade and thus is not freely available for use without specific permission.


Vacunación de aves comerciales contra la influenza aviar. La complejidad de las infecciones por el virus de la influenza A en las aves hospedadoras conduce a escenarios igualmente complejos para la vacunación en la avicultura. La vacunación contra cepas de influenza aviar se puede utilizar para prevenir infecciones provenientes de fuentes con una sola cepa del virus de influenza. Se ha utilizado como parte de las estrategias de control de brotes, así como como una forma de mantener la producción tanto en brotes de baja como de alta patogenicidad. A diferencia de otros patógenos virales de las aves, la vacunación contra la influenza aviar, cuando se usa contra el virus de la influenza aviar altamente patógeno, está vinculada al comercio internacional y por lo tanto, no está disponible para su uso sin un permiso específico.


Assuntos
Vírus da Influenza A , Influenza Aviária , Influenza Humana , Doenças das Aves Domésticas , Animais , Humanos , Aves Domésticas , Influenza Aviária/prevenção & controle , Comércio , Internacionalidade , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária
5.
BMC Biol ; 21(1): 196, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726733

RESUMO

BACKGROUND: The aim of study was to observe the effect of increased lactate levels during high-intensity interval training (HIIT) on protein lactylation, identify the target protein, and investigate the regulatory effect of lactylation on the function of the protein. METHODS: C57B/L6 mice were divided into 3 groups: the control group, HIIT group, and dichloroacetate injection + HIIT group (DCA + HIIT). The HIIT and DCA + HIIT groups underwent 8 weeks of HIIT treatment, and the DCA + HIIT group was injected DCA before HIIT treatment. The expression of lipid metabolism-related genes was determined. Protein lactylation in subcutaneous adipose tissue was identified and analyzed using 4D label-free lactylation quantitative proteomics and bioinformatics analyses. The fatty acid synthase (FASN) lactylation and activity was determined. RESULTS: HIIT had a significant effect on fat loss; this effect was weakened when lactate production was inhibited. HIIT significantly upregulated the protein lactylation while lactate inhibition downregulated in iWAT. FASN had the most modification sites. Lactate treatment increased FASN lactylation levels, inhibited FASN activity, and reduced palmitate and triglyceride synthesis in 3T3-L1 cells. CONCLUSIONS: This investigation revealed that lactate produced by HIIT increased protein pan-lactylation levels in iWAT. FASN lactylation inhibited de novo lipogenesis, which may be an important mechanism in HIIT-induced fat loss.


Assuntos
Treinamento Intervalado de Alta Intensidade , Lipogênese , Animais , Camundongos , Ácido Graxo Sintases/genética , Ácido Láctico , Lipídeos
6.
Anal Sci ; 39(12): 1993-2000, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37651055

RESUMO

Sensitive detection of heavy metal (HM) stress in aquatic plants by dissolved oxygen (DO)-quenched fluorescence/materials movement-induced beam deflection method is demonstrated. Egeria densa Planchon and Cu2+ were used as a model aquatic plant and HM ion, respectively. Reproducibility and experimental errors of the method were first investigated in a control culture solution only containing 10-6 M Ru (II) complex (Tris (2,2'-bipyridyl) ruthenium (II) chloride) without addition of any fertilizer and Cu2+. Changes of DO concentration (∆DO) and deflection (∆DE) during the monitoring periods were used as parameters to quantitatively evaluate the experimental errors and detection limits. Averages or means ([Formula: see text], [Formula: see text]) and standard deviations (σ∆DO, σ∆DE) of ∆DO and ∆DE in seven control experiments with different aquatic plants sheets during both the respiration and photosynthesis processes were obtained. Next, DO and deflection at the middle vicinities of the aquatic plant were monitored during 2 h of both respiration and photosynthesis in presence of 10-10 ~ 10-6 M Cu2+. Experimental results showed that the aquatic plant began to suffer from the HM stress in some extent in presence of 10-9 M Cu2+. When the concentration of Cu2+ was higher than 10-8 M, changing trends of both DO and deflection with time were not reversed during the respiration and photosynthesis, implying that the materials movements in the physiological activities had been altered greatly. It is demonstrated that the method could sensitively detect the HM stress in the aquatic plants given by nM HM ions in culture solution without addition of a fertilizer. Furthermore, detection limits of the method were quantitatively discussed by considering [Formula: see text] σ∆DO and [Formula: see text] σ∆DE as the minimum detectable changes of DO and deflection caused by the HM stress, respectively.


Assuntos
Metais Pesados , Oxigênio , Fertilizantes , Reprodutibilidade dos Testes , Fotossíntese
7.
Metabolites ; 13(5)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37233688

RESUMO

Protein lysine lactylation (Kla) is a novel protein acylation reported in recent years, which plays an important role in the development of several diseases with pathologically elevated lactate levels, such as tumors. The concentration of lactate as a donor is directly related to the Kla level. High-intensity interval training (HIIT) is a workout pattern that has positive effects in many metabolic diseases, but the mechanisms by which HIIT promotes health are not yet clear. Lactate is the main metabolite of HIIT, and it is unknown as to whether high lactate during HIIT can induce changes in Kla levels, as well as whether Kla levels differ in different tissues and how time-dependent Kla levels are. In this study, we observed the specificity and time-dependent effects of a single HIIT on the regulation of Kla in mouse tissues. In addition, we aimed to select tissues with high Kla specificity and obvious time dependence for lactylation quantitative omics and analyze the possible biological targets of HIIT-induced Kla regulation. A single HIIT induces Kla in tissues with high lactate uptake and metabolism, such as iWAT, BAT, soleus muscle and liver proteins, and Kla levels peak at 24 h after HIIT and return to steady state at 72 h. Kla proteins in iWAT may affect pathways related to glycolipid metabolism and are highly associated with de novo synthesis. It is speculated that the changes in energy expenditure, lipolytic effects and metabolic characteristics during the recovery period after HIIT may be related to the regulation of Kla in iWAT.

8.
Biomater Sci ; 11(11): 3952-3964, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37102693

RESUMO

Drug-loaded liposomes have been shown to be effective in the treatment of hepatocellular carcinoma (HCC). However, the systemic non-specific distribution of drug-loaded liposomes in tumor patients is a critical therapeutic challenge. To address this issue, we developed galactosylated chitosan-modified liposomes (GC@Lipo) that could selectively bind to the asialoglycoprotein receptor (ASGPR), which is highly expressed on the membrane surface of HCC cells. Our study demonstrated that the GC@Lipo significantly enhanced the anti-tumor efficacy of oleanolic acid (OA) by enabling targeted drug delivery to hepatocytes. Remarkably, treatment with OA-loaded GC@Lipo inhibited the migration and proliferation of mouse Hepa1-6 cells by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and AXL expressions, compared to a free OA solution and OA-loaded liposomes. Furthermore, using an axillary tumor xenograft mouse model, we observed that OA-loaded GC@Lipo led to a significant reduction in tumor progression, accompanied by concentrated enrichment in hepatocytes. These findings strongly support the clinical translation of ASGPR-targeted liposomes for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ácido Oleanólico , Camundongos , Humanos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Lipossomos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos , Hepatócitos , Modelos Animais de Doenças
9.
Food Chem ; 417: 135882, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36934708

RESUMO

Electrochemical methods have been extensively applied for the detection of chemical information from food or other analytes. However, existing electrochemical methods are limited to focusing solely on the absorption peaks and disregard much of the hidden chemical fingerprint information. Consequently, electrochemical sensors are constrained by their ability to detect samples containing multiple source-material mixtures with overlapping constituents. We hypothesized that the target substances can be effectively identified and detected using differential sensor data combined with artificial intelligence (AI). In this study, we developed a novel signal array composed of five metal electrodes and used a convolutional neural network (CNN) model for feature extraction to detect capsaicinoids in stews. Our results indicate that the proposed method achieved satisfactory predictions with a root mean square error (RMSE) of 5.407 in independent brine samples. This provides a promising strategy and practical approach for the nondestructive analysis of multidimensional electrochemical data of mixed analytes.


Assuntos
Inteligência Artificial , Redes Neurais de Computação , Eletroquímica , Técnicas Eletroquímicas , Eletrodos
10.
Food Chem ; 415: 135650, 2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-36868065

RESUMO

Bionic nose, a technology that mimics the human olfactory system, has been widely used to assess food quality due to their high sensitivity, low cost, portability and simplicity. This review briefly describes that bionic noses with multiple transduction mechanisms are developed based on gas molecules' physical properties: electrical conductivity, visible optical absorption, and mass sensing. To enhance their superior sensing performance and meet the growing demand for applications, a range of strategies have been developed, such as peripheral substitutions, molecular backbones, and ligand metals that can finely tune the properties of sensitive materials. In addition, challenges and prospects coexist are covered. Cross-selective receptors of bionic nose will help and guide the selection of the best array for a particular application scenario. It provides an odour-based monitoring tool for rapid, reliable and online assessment of food safety and quality.


Assuntos
Biônica , Compostos Orgânicos Voláteis , Humanos , Nariz Eletrônico , Compostos Orgânicos Voláteis/química , Odorantes , Percepção
11.
Int J Biol Macromol ; 235: 123697, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36806780

RESUMO

The effect of nano-TiO2 particle size on the properties of starch-based wood adhesives was studied in this work. Our findings indicate that a smaller size of nano-TiO2 particles corresponds with a larger specific surface area and more hydroxyl sites on the particle surface that interact with latex molecules, forming a more compact network structure. Therefore, the bonding performance and water resistance of the adhesive were enhanced. In addition, rheology results showed that the adhesive behaves as a pseudoplastic fluid. Small-angle X-ray scattering and energy dispersive spectroscopy confirmed the good compatibility and dispersion of nano-TiO2 in the adhesive films. Diffusing wave spectroscopy and scanning electron microscopy showed that smaller TiO2 particles were more favorable for the formation of smoother and denser films. These results are of great significance for improving the structure and properties of starch-based wood adhesives and preparing high-performance environmentally friendly biobased adhesives.


Assuntos
Adesivos , Amido , Amido/química , Adesivos/química , Madeira/química , Tamanho da Partícula
12.
Nanoscale ; 15(4): 1568-1582, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36723149

RESUMO

The development of graphitic carbon materials as anodes of sodium-ion batteries (SIBs) is greatly restricted by their inherent low specific capacity. Herein, nitrogen and sulfur co-doped 3D graphene frameworks (NSGFs) were successfully synthesized via a simple and facile one-step hydrothermal method and exhibited high Na storage capacity in ether-based electrolytes. A systematic comparison was made between NSGFs, undoped graphene frameworks (GFs) and nitrogen-doped graphene frameworks (NGFs). It is demonstrated that the high specific capacity of NSGFs can be attributed to the free diffusion of Na ions within the graphene layer and reversible reaction between -C-Sx-C- covalent chains and Na ions thanks to the large interplanar distance and the dominant -C-Sx-C- covalent chains in NSGFs. NSGF anodes, therefore, exhibit a high initial coulombic efficiency (ICE) (92.8%) and a remarkable specific capacity of 834.0 mA h g-1 at 0.1 A g-1. Kinetic analysis verified that the synergetic effect of N/S co-doping not only largely enhanced the Na ion diffusion rate but also reduced the electrochemical impedance of NSGFs. Postmortem techniques, such as SEM, ex situ XPS, HTEM and ex situ Raman spectroscopy, all demonstrated the extremely physicochemically stable structure of the 3D graphene matrix and ultrathin inorganic-rich solid electrolyte interphase (SEI) films formed on the surface of NSGFs. Yet it is worth noting that the Na storage performance and mechanism are exclusive to ether-based electrolytes and would be inhibited in their carbonate ester-based counterparts. In addition, the corrosion of copper foils under the synergetic effect of S atoms and ether-based electrolytes was reported for the first time. Interestingly, by-products derived from this corrosion could provide additional Na storage capacity. This work sheds light on the mechanism of improving the electrochemical performance of carbon-based anodes by heteroatom doping in SIBs and provides a new insight for designing high-performance anodes of SIBs.

13.
Macromol Rapid Commun ; 44(11): e2200718, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36271740

RESUMO

High-performance membranes are critical to membrane separation technology. In recent years, 2D covalent organic frameworks (2D COFs) have attracted extensive attention in the field of membrane separation due to their high porosity, ordered channels, and fine-tuned pore sizes, which are considered as excellent candidate to solve the trade-off between membrane selectivity and permeability. Herein, two kinds of ionic 2D COFs with different charge properties (termed as iCOFs) are integrated into polyacrylonitrile (PAN) substrates to form two composite membranes (PAN@iCOFs) with excellent selective perfluoroalkyl substances (PFASs) separation performance with high solvent permeability and good mechanical properties. The as-prepared PAN@iCOFs composite membranes can selectively reject more than 99.0% of positively and negatively charged PFASs in wastewater while maintaining good stability and recyclability.


Assuntos
Fluorocarbonos , Estruturas Metalorgânicas , Íons , Membranas , Permeabilidade
14.
Peptides ; 154: 170823, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35660637

RESUMO

Skeletal muscle is the major effector organ for exercise. It has been proposed that VEGFB is significantly related to apoptosis in various cell types but not yet in skeletal muscle. We hypothesize that the decrease of VEGFB in skeletal muscle participates in the occurrence of skeletal muscle apoptosis and that exercise inhibits apoptosis by elevating the expression of VEGFB in skeletal muscle cells. Based on this hypothesis, we developed in vitro experiments to mimic the effect of exercise through electrical pulse stimulation (EPS) to observe the effect of EPS on apoptosis and the change in VEGFB expression in differentiated myotubes. In addition, we employed RNA interference to explore whether VEGFB is directly involved in the regulation of myotube apoptosis during EPS. Our results showed that exogenous VEGFB167 significantly inhibited C2C12 myotube apoptosis induced by TNF-α treatment and that endogenous VEGFB in differentiated C2C12 myotubes was significantly upregulated by EPS. In addition, EPS significantly changed the expression of the apoptotic indicators Bax and Bcl-2 at the mRNA level and downregulated the protein expression of cleaved caspase-3. The antiapoptotic effect of EPS weakened substantially as VEGFB in C2C12 myotubes was inhibited. Taken together, these results indicate that exercise-like EPS inhibits apoptosis by increasing the expression of C2C12 myotube-derived VEGFB.


Assuntos
Fibras Musculares Esqueléticas , Fator B de Crescimento do Endotélio Vascular , Apoptose , Estimulação Elétrica/métodos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Fator B de Crescimento do Endotélio Vascular/farmacologia
15.
J Virol ; 96(13): e0016722, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35695505

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne febrile disease caused by SFTS virus (SFTSV), or Dabie bandavirus, in the Phenuiviridae family. Clinically neurological disorders in SFTS have been commonly reported, but their neuropathogenesis has rarely been studied. Microglia are a type of neuroglia accounting for 10 to 12% of all cells in the brain. As resident immune cells, microglial cells are the first line of immune defense present in the central nervous system (CNS). Here, we report that SFTSV was able to infect microglial cells and stimulate interleukin 1ß (IL-1ß) secretion in the brains of infected neonatal BALB/c mice. We characterized the cell death induced in infected human microglial HMC3 cells, also susceptible to SFTSV, and found that the NOD-like receptor protein 3 (NLRP3) inflammasome was activated, leading to secretion of IL-1ß and pyroptosis. Knockdown of NLRP3 or inhibition of the NLRP3 inflammasome activation suppressed the viral replication, suggesting that the activation of the NLRP3 inflammasome may support SFTSV replication in microglial cells. Viral nonstructural protein NSs, a known modulator of immune responses, interacted and colocalized with NLRP3 for the inflammasome activation. It appeared that the N-terminal fragment, amino acids 1 to 66, of NSs was critical to promote the assembly of the inflammasome complex by interacting with NLRP3 for its activation in microglial cells. Our findings provide evidence that SFTSV may cause neurological disorders through infecting microglia and activating the inflammasome through its nonstructural protein NSs for neural cell death and inflammation. This study may have revealed a novel mechanism of SFTSV NSs in dysregulating host response. IMPORTANCE Encephalitis or encephalopathy during severe fever with thrombocytopenia syndrome (SFTS) is considered a critical risk factor leading to high mortality, but there have been no studies to date on the pathogenesis of encephalitis or encephalopathy caused by SFTS virus. Here, we report that SFTSV infection can active the NLRP3 inflammasome and induce IL-1ß secretion in the brains of infected newborn mice. In infected human HMC3 microglia, SFTSV activated the NLRP3 inflammasome via the viral nonstructural protein NSs through interaction with its N-terminal fragment. Notably, our findings suggest that the activation of the NLRP3 inflammasome may promote SFTSV replication in infected microglial cells. This study may reveal a novel mechanism by SFTSV to dysregulate host responses through its nonstructural protein, which could help us understand viral neuropathogenesis in SFTS patients.


Assuntos
Encefalite , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Phlebovirus , Piroptose , Proteínas não Estruturais Virais , Animais , Células Cultivadas , Humanos , Inflamassomos/metabolismo , Camundongos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Phlebovirus/metabolismo , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Proteínas não Estruturais Virais/metabolismo
16.
PLoS Negl Trop Dis ; 16(5): e0010366, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35522620

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus and can cause neurodevelopmental disorders in fetus. As a neurotropic virus, ZIKV persistently infects neural tissues during pregnancy but the viral pathogenesis remains largely unknown. ZIKV has a positive-sense and single-stranded RNA genome, which encodes 7 non-structural (NS) proteins, participating in viral replication and dysregulation of host immunity. Like those in many other viruses, NS proteins are considered to be products evolutionarily beneficiary to viruses and some are virulence factors. However, we found that some NS proteins encoded by ZIKV genome appeared to function against the viral replication. In this report we showed that exogenously expressed ZIKV NS2A and NS4A inhibited ZIKV infection by inhibiting viral RNA replication in microglial cells and astrocytes. To understand how viral NS proteins suppressed viral replication, we analyzed the transcriptome of the microglial cells and astrocytes and found that expression of NS4A induced the upregulation of ISGs, including MX1/2, OAS1/2/3, IFITM1, IFIT1, IFI6, IFI27, ISG15 or BST2 through activating the ISGF3 signaling pathway. Upregulation of these ISGs seemed to be related to the inhibition of ZIKV replication, since the anti-ZIKV function of NS4A was partially attenuated when the cells were treated with Abrocitinib, an inhibitor of the ISGF3 signaling pathway, or were knocked down with STAT2. Aborting the protein expression of NS4A, but not its nucleic acid, eliminated the antiviral activity of NS4A effectively. Dynamic expression of viral NS proteins was examined in ZIKV-infected microglial cells and astrocytes, which showed comparatively NS4A occurred later than other NS proteins during the infection. We hypothesize that NS4A may possess intrinsic features to serve as a unique type of pathogen associated molecular pattern (PAMP), detectable by the cells to induce an innate immune response, or function with other mechanisms, to restrict the viral replication to a certain level as a negative feedback, which may help ZIKV maintain its persistent infection in fetal neural tissues.


Assuntos
Infecção por Zika virus , Zika virus , Animais , RNA Viral/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Zika virus/fisiologia
17.
Mol Cell Biochem ; 477(10): 2469-2480, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35590082

RESUMO

Tumor-associated macrophages (TAMs) are a type of functionally plastic immune cell population in tumor microenvironment (TME) and mainly polarized into two phenotypes: M2 and M1-like TAMs. The M2-like TAMs could stimulate tumor growth and metastasis, tissue remodeling and immune-suppression, whereas M1-like TAMs could initiate immune response to dampen tumor progression. TAMs with different polarization phenotypes can produce various kinds of cytokines, chemokines and growth factors to regulate immunity and inflammatory responses. It is an effective method to treat cancer through ameliorating TME and modulating TAMs by converting M2 into M1-like phenotype. However, intracellular signaling mechanisms underlying TAMs polarization are largely undefined. Phosphoinositide 3-kinase (PI3K)/Akt is an important signaling pathway participating in M2-like TAMs polarization, survival, growth, proliferation, differentiation, apoptosis and cytoskeleton rearrangement. In the present review, we analyzed the mechanism of TAMs polarization focusing on PI3K/Akt and its downstream mitogen­activated protein kinase (MAPK) as well as nuclear factor kappa B (NF-κB) signaling pathways, thus provides the first evidence of intracellular targets for cancer immunotherapy.


Assuntos
NF-kappa B , Fosfatidilinositol 3-Quinases , Linhagem Celular Tumoral , Citocinas/metabolismo , Macrófagos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Plásticos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Microambiente Tumoral , Macrófagos Associados a Tumor
18.
PLoS One ; 17(4): e0257408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35446851

RESUMO

Zika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetuses. As a mosquito-borne arbovirus, it enters the bloodstream and replicates in various organs. During pregnancy, it can be transmitted from the blood of the viremic mother to the fetus by crossing the placental barrier. Monocytes and macrophages are considered the earliest blood cell types to be infected by ZIKV. As a first line defense, these cells are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV could infect and induce cell death in human and murine macrophages. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdermin D (GSDMD) as well as increased secretion of IL-1ß and IL-18. This suggests that the inflammasome was activated and that may lead to pyroptosis in infected macrophages. The pyroptosis was NLRP3-dependent and could be suppressed in the macrophages treated with shRNA to target and knockdown caspase-1. It was also be inhibited by an inhibitor for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected macrophages, with two mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Apoptose , Caspase 1/metabolismo , Feminino , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Placenta/metabolismo , Gravidez , Piroptose , Zika virus/metabolismo , Infecção por Zika virus/metabolismo
19.
Sci Rep ; 12(1): 2573, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35173184

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus that causes a hemorrhagic fever known as the severe fever with thrombocytopenia syndrome (SFTS). Inflammasomes are a molecular platform that are assembled to process pro-caspase 1 and subsequently promote secretion of interleukin (IL)-1ß/IL-18 for proinflammatory responses induced upon infection. We hypothesize that inflammasome activation and pyroptosis induced in SFTS results in elevated levels of IL-1ß/IL-18 responsible for high fever and hemorrhage in the host, characteristic of SFTS. Here we report that IL-1ß secretion was elevated in SFTS patients and infected mice and IL-1ß levels appeared to be reversibly associated to disease severity and viral load in patients' blood. Increased caspase-1 activation, IL-1ß/IL-18 secretion, cell death, and processing of gasdermin D were detected, indicating that pyroptosis was induced in SFTSV-infected human peripheral blood monocytes (PBMCs). To characterize the mechanism of pyroptosis induction, we knocked down several NOD-like receptors (NLRs) with respective shRNAs in PBMCs and showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome was critical for processing pro-caspase-1 and pro-IL-1ß. Our data with specific inhibitors for NLRP3 and caspase-1 further showed that activation of the NLRP3 inflammasome was key to caspase-1 activation and IL-1ß secretion which may be inhibitory to viral replication in PBMCs infected with SFTSV. The findings in this study suggest that the activation of the NLPR3 inflammasome and pyroptosis, leading to IL-1ß/IL-18 secretion during the SFTSV infection, could play important roles in viral pathogenesis and host protection. Pyroptosis as part of innate immunity might be essential in proinflammatory responses and pathogenicty in humans infected with this novel phlebovirus.


Assuntos
Infecções por Bunyaviridae/complicações , Inflamassomos/imunologia , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Phlebovirus/isolamento & purificação , Febre Grave com Síndrome de Trombocitopenia/patologia , Replicação Viral , Animais , Infecções por Bunyaviridae/virologia , Estudos de Casos e Controles , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Febre Grave com Síndrome de Trombocitopenia/etiologia , Febre Grave com Síndrome de Trombocitopenia/metabolismo
20.
Int J Biol Macromol ; 205: 664-671, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35181331

RESUMO

Improving the performance of wood adhesive is important for the development of the veneer industry. This work investigated the effects of various durations of enzymatic hydrolysis to improve and enhance the properties of starch-based wood adhesive (SWA). The results showed that moderate enzymatic hydrolysis for 2 h of starch molecule could improve the properties of SWA. The bonding strength of SWA was increased from 2.72 MPa (0 h) to 6.87 MPa (2 h) in the dry state and from 0.87 MPa (0 h) to 2.69 MPa (2 h) in the wet state. A significant decrease in the viscosity of SWA was also observed after 2 h hydrolysis of starch molecules, which allowed smooth spreading and penetration of adhesive through the wood surface. Meanwhile, the dynamic mechanical analysis and scanning electron microscopy showed that SWA with 2 h enzymatic hydrolysis exhibited better elastic deformation and smooth surfaces compared with SWA with un-hydrolysis starch. This study provides important information regarding the possible applications of SWA in the wood industry and presents a potential alternative to less environmentally friendly formaldehyde-based wood adhesives.


Assuntos
Adesivos , Amido , Hidrólise , Viscosidade , Madeira
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