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1.
J Hazard Mater ; 421: 126704, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34325292

RESUMO

Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1ß, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.


Assuntos
NF-kappa B , Necroptose , Animais , Cádmio/toxicidade , Inflamação/induzido quimicamente , Intestino Delgado/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Suínos , Fator de Necrose Tumoral alfa
2.
Food Chem ; 369: 130874, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455321

RESUMO

As one of food sources, fish provides sufficient nutrition to human. Diverse nutrients in fish make fish an important nutrient source available easily across the globe. Fish is proven to possess several health benefits, such as anti-oxidation, anti-inflammation, wound healing, neuroprotection, cardioprotection, and hepatoprotection properties. Fish proteins, such as immunoglobins, act as defense agents against viral and bacterial infections and prevent protein-calorie malnutrition. Besides, fish oil constituents, such as polyunsaturated fatty acids (PUFAs), regulate various signaling pathways, such as nuclear factor kappa B pathway, Toll-like receptor pathway, transforming growth factor-ß (TGF-ß) pathway, and peroxisome proliferators activated receptor (PPAR) pathways. In this review, the literature about health benefits of fish consumption are accumulated from PubMed, Google Scholar, Scopus, and the mechanistic action of health benefits are summarized. Fish consumption at least twice per week as part of a healthy diet is beneficial for a healthy heart. More advances in this field could pose fish as a major nutrients source of foods.


Assuntos
Ácidos Graxos Ômega-3 , Óleos de Peixe , Animais , Ácidos Graxos Insaturados , Peixes/metabolismo , Humanos , NF-kappa B/metabolismo , Transdução de Sinais
3.
Food Chem ; 369: 130911, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455325

RESUMO

Postmortem alteration by apoptosis has significant effects on flesh quality. Currently, the information necessary to understand the apoptotic behavior and the molecular mechanisms during postmortem alteration in fish muscle is still lacking. Activation of apoptosis and the cytokines involved in regulating apoptosis in fish muscle were evaluated during postmortem condition at 4 °C for 5 days in terms of apoptotic morphology changes, nucleus DNA fragmentation, caspases activation and related gene expressions. The triggering apoptotic mechanisms associated with multiple cytokines transcriptional levels showed that the up-regulated pro-apoptotic mediators [IFN-γ2, TNF-α, IL-6, IL-1ß, IL-17D, IL-12p35 and IL-10 (except IL-15)] and the down-regulated anti-apoptotic mediators of [IL-8 and IL-11 (except TGF-ß and IL-4)] both regulated apoptosis at early stage, which were regulated by NF-κB and TOR, respectively. Results suggested that transcriptional regulation of multiple cytokines produce a positive outcome on triggering apoptosis.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Aeromonas hydrophila , Ração Animal/análise , Animais , Apoptose , Carpas/genética , Citocinas/genética , Dieta , Suplementos Nutricionais , Proteínas de Peixes/genética , Imunidade Inata , Músculos , NF-kappa B/genética
4.
Biol Trace Elem Res ; 200(1): 197-205, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33559025

RESUMO

The widespread industrial use of nitrite in preservatives, colorants, and manufacturing rubber products and dyes increases the possibilities of organ toxicity. Lithium borate (LB) is known as an antioxidant and an oxidative stress reliever. Therefore, this study is aimed at examining the effect of LB on nitrite-induced hepatorenal dysfunction. Twenty-eight male Swiss mice were divided into four equal groups. Group 1, the control group, received saline. Group 2 received LB orally for 5 consecutive days at a dose of 15 mg/kg bw. Group 3, the nitrite group, received sodium nitrite (NaNO2) on Day 5 (60 mg/kg bw intraperitoneally). Group 4, the protective group (LB + NaNO2 group), received LB for 5 days and then a single dose of NaNO2 intraperitoneally on Day 5, the same as in Groups 2 and 3, respectively. Samples of blood and kidney were taken for serum analysis of hepatorenal biomarkers, levels of antioxidants and cytokines, and the expression of genes associated with oxidative stress and inflammation. NaNO2 intoxication increased markers of liver and kidney functions yet decreased reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities in blood. NaNO2 also increased the expression of tumor necrosis factor (TNF-α), interleukin-1ß and interleukin-6 (IL-1ß and IL-6). Pre-administration of LB protected mice from oxidative stress, lipid peroxidation, and the decrease in antioxidant enzyme activity. Moreover, LB protected mice from cytokine changes, which remained within normal levels. LB ameliorated the changes induced by NaNO2 on the mRNA of nuclear factor erythroid 2-related factor 2 (Nfr2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), transforming growth factor-beta 2 (TGF-ß2), and glutathione-S-transferase (GST) as determined using quantitative real-time PCR (qRT-PCR). These results collectively demonstrate that LB ameliorated NaNO2-induced oxidative stress by controlling the oxidative stress biomarkers and the oxidant/antioxidant state through the involvement of the Nrf2/HO-1 and NF-κB signaling pathways.


Assuntos
Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Animais , Antioxidantes/farmacologia , Boratos/farmacologia , Heme Oxigenase-1/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Oxidantes , Estresse Oxidativo , Nitrito de Sódio/toxicidade
5.
J Int Med Res ; 49(11): 3000605211053549, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34743632

RESUMO

OBJECTIVE: Inflammation is an important factor in the pathological process of cerebral ischemia. Artesunate exhibits a broad range of anti-inflammatory properties in many diseases. We investigated the potential protective effect of artesunate against cerebral ischemia and the related mechanisms. METHODS: Mice were divided into distal middle cerebral artery occlusion (dMCAO), sham, low dose, and high dose groups and subjected to dMCAO, except for the sham group. The low and high dose groups were administered artesunate (15 and 30 mg/kg), and the neuroprotective effects were analyzed by evaluating infarct volumes and neurological deficits. Microglial activation and neutrophil infiltration were evaluated by immunofluorescence, immunohistochemical staining, and western blotting. Inflammatory mediators were measured by enzyme-linked immunosorbent assays. Nuclear factor (NF)-κB nuclear translocation was detected by immunofluorescence and western blotting. RESULTS: Compared with the dMCAO group, artesunate significantly improved neurological deficit scores and infarct volumes and ameliorated inflammation by reducing neutrophil infiltration, suppressing microglial activation, and downregulating tumor necrosis factor-α and interleukin-1ß expression. Furthermore, artesunate inhibited nuclear translocation of NF-κB and inhibitor protein α proteolysis. CONCLUSIONS: Artesunate protected against inflammatory injury by reducing neutrophil infiltration and microglial activation, suppressing inflammatory cytokines, and inhibiting the NF-κB pathway. Therefore, artesunate is a potential ischemic stroke treatment.


Assuntos
Isquemia Encefálica , NF-kappa B , Animais , Artesunato , Isquemia Encefálica/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Inflamação/tratamento farmacológico , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
6.
Clin Lab ; 67(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758237

RESUMO

BACKGROUND: CircPVT1's effects and mechanisms of acute lymphoblastic leukemia were explored in this research. METHODS: Real-time fluorescent quantitative PCR was utilized to test circPVT1 and miR-125b in ALL samples and ALL cell systems. Dual luciferase reporter assay verified the combination of circPVT1 and miR-125b. We utilized circPVAT1 as well as miR-125b's over-expression and low-expression to prove their influence on cell proliferation and invading. RESULTS: We found that more expression of circPVT1 occurred in ALL samples and ALL cell systems. CircPVT1 over-expression promoted ALL cell proliferation and migration besides invading. CircPVT1 low expression inhibited ALL cell proliferation and migration besides invading. MiR-125b was a target combination of circPVT1. CircPVT1 was able to enhance NF-κB signal pathway's expression through reducing miR-125b. CONCLUSIONS: CircPVT2 can promote ALL cell proliferation and invading through miR-125b modulation of NF-κB, which would be one new potential target for ALL therapy.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proliferação de Células , Humanos , MicroRNAs/genética , NF-kappa B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA Circular , Transdução de Sinais
7.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5072-5079, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738403

RESUMO

Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 µg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.


Assuntos
Neoplasias , Reishi , Animais , Células Endoteliais/metabolismo , Molécula 1 de Adesão Intercelular/genética , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Polissacarídeos , Transdução de Sinais , Linfócitos T , Fator de Necrose Tumoral alfa
8.
Phytomedicine ; 93: 153812, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753029

RESUMO

BACKGROUND: Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE: To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS: In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS: Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION: QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.


Assuntos
Aterosclerose , NF-kappa B , Transportador 1 de Cassete de Ligação de ATP , Animais , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo
9.
Molecules ; 26(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34771068

RESUMO

Caragana rosea Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of Caragana rosea (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/ß and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Caragana/química , Inflamação/tratamento farmacológico , Metanol/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Fator Regulador 3 de Interferon/antagonistas & inibidores , Fator Regulador 3 de Interferon/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/metabolismo
10.
J Agric Food Chem ; 69(46): 13821-13830, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34752070

RESUMO

Studies have revealed that a novel anti-inflammatory mediator─maresin-1 (MaR1)─can reduce the level of inflammatory factors. There is evidence that physical exercise (PE) promotes the biosynthesis of MaR1, leading to the prevention of rheumatoid arthritis (RA). Previously, we have proven that resveratrol can mitigate the formation of RA. Pterostilbene (Pte) is an analogue of resveratrol, but it is around four times more bioavailable. Hence, we hypothesize that Pte could be more effective in preventing RA, in particular, when accompanied by moderate PE. Based on this hypothesis, we explored the preventive effect of Pte combined with PE on a bovine type II collagen (BIIC)-stimulated rat RA model and its underlying molecular mechanism. Compared with the BIIC-stimulated group, the serum content of MaR1 with continuous intervention of Pte plus PE for 8 weeks was significantly increased to 46.3 pg/mL from 7.2 pg/mL in BIIC-treated alone. Besides, the variation in the relative expression levels of p-NF-κB and p-Akt was reversed with the administration of Pte plus PE. More importantly, the in vitro results confirmed that the treatment of Pte plus MaR1 inhibited proliferation and apoptosis and promoted the autophagy of the interleukin (IL)-1ß-stimulated primary rat synovial cells through the PI3K/Akt/NF-κB signal pathway. Collectively, the oral administration of Pte plus moderate PE helped to ameliorate the pathological process of RA by correcting the PI3K/Akt/NF-κB signal pathway.


Assuntos
NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Animais , Bovinos , Colágeno , NF-kappa B/genética , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Estilbenos
11.
J Agric Food Chem ; 69(45): 13500-13509, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34729976

RESUMO

The preventive effect and molecular mechanism of lycopene (LP) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were evaluated. Compared to the DSS group, the LP prevention groups not only significantly inhibited the DSS-induced weight loss, decreased the disease activity index (DAI) score, increased the colon length, and improved inflammation in the colon but also significantly increased the levels of superoxide dismutase (SOD),catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) in the colon and reduced inflammatory cytokine, myeloperoxidase (MPO), and malondialdehyde (MDA) levels. Notably, when compared to the DSS group, the protein expression levels of TLR4, TRIF, and p-NF-κB p65 in the mice colon tissue were downregulated and those of tight junction-related proteins were upregulated in the LP + DSS group, with the most significant effect observed in the 10 mg/kg LP + DSS group. These results confirmed that the upregulation of tight junction-related protein expression after blocking the TLR4/TRIF/NF-κB signaling pathway may be one of the mechanisms through which LP prevents UC.


Assuntos
Colite Ulcerativa , Colite , Proteínas Adaptadoras de Transporte Vesicular , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colo/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Licopeno , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Junções Íntimas/metabolismo , Receptor 4 Toll-Like/genética
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1492-1500, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755664

RESUMO

OBJECTIVE: To investigate the characteristics of immune cell subsets in the lung tissues of patients with chronic obstructive pulmonary disease (COPD) and the mechanism of Liuwei Buqi capsule in modulating immune and inflammatory imbalance in COPD. METHODS: We downloaded COPD-related single-cell RNA sequencing data from Gene Expression Omnibus (GEO) and identified COPD immune cell subsets using the Seurat package in the R software to construct an immune cell subsets-differential genes network. The target genes and active ingredients of Liuwei Buqi capsule were obtained from the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the Liuwei Buqi capsule-immune cell subsets-target genes network was constructed by mapping the target genes to the differentially expressed genes in each immune cell subset. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to analyze significantly enriched pathways of the target genes, and the key genes involved in the top 20 pathways were identified. In a rat model of COPD, we investigated the effects of Liuwei Buqi capsule on pulmonary function, lung tissue pathology, serum levels of IL-1ß, NF-κB, and TNF-α, and expressions of IKBα, JNK, c-JUN, and c-FOS proteins in the lung tissue. RESULTS: A total of 18 immune-related cell subsets, including macrophages and alveolar macrophages, were identified in both COPD patients and healthy control subjects, and the patients with COPD showed significant changes the percentages of macrophages, cDC1, pDC, mast cells, T cells, and mature dendritic cells (P < 0.05). Liuwei Buqi capsules targeted multiple immune cell subsets, and the identified target genes were enriched mostly in such immune and inflammation-related signaling pathways as lipids and atherosclerosis, IL-17 signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway; the genes CXCL8, IL1B, JUN, NFKBIA, MAPK8, and FOS were the key genes involved in the significantly enriched pathways. In the rat models of COPD, treatment with Liuwei Buqi capsule significantly improved pulmonary function, alleviated lung pathologies, reduced serum levels of IL-1ß, TNF-α, and NF-κB (P < 0.05) and pulmonary expressions of JNK, c-JUN, and c-FOS (P < 0.01) protein, and increased pulmonary expression of IκBα (P < 0.01). CONCLUSION: Liuwei Buqi capsule may play an immunomodulatory role by targeting multiple immune cell subsets in the lung tissue of COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Imunidade , Pulmão/metabolismo , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Transdução de Sinais
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 606-610, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821092

RESUMO

Objective: To investigate the expression of programmed death ligand-1 (PD-L1) in dendritic cells (DCS) and its related signaling pathway in lipopolysaccharide (LPS)-induced immunosuppression of bacterial sepsis.Methods: Stimulating with bacterial LPS, bone marrow-derived dendritic cells could induce T lymphocyte immunosuppression imitating bacterial sepsis model. The experiments were divided into 5 groups: control group, LPS group, 2-(4-morpholinyl)-8-phenyl-4H-1- benzopyran-4-one (LY294002)+LPS group, pyrrolidinedithiocarbamate(PDTC)+LPS group and LPS+anti-PD-L1 group with 6 multiple wells in each group. After mice bone marrow source monocytes were cultured with rmGM-CSF (10 ng/ml) and rmIL-4 (1 ng/ml) in 10% fetal bovine serum 1640 for 4 days, DCs cells were treated with with 10 ng/ml LPS for 12 h to obtain immunosuppressive cells with high expression of PD-L1. Pathway-inhibitors LY294002 (10 µmol/L) and PDTC (20 µmol/L) were used to block PI3K and NF-κB signals. Flow cytometry and confocal laser scanning microscopy were used to detect the PD-L1 expression and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signal activation on DCs. BrdU cell proliferation assay and γ-interferon enzyme-linked immunospot assay were used to detect ovalbumin specific T lymphocyte proliferation response and cytotoxic T cell response, respectively. Results: Compared with the control group, the percentage of PD-L1 positive cells and PD-L1 red fluorescence intensity of DCs were all increased(P<0.01), while DCs- mediated T cell proliferation and γ-interferon spot-forming cell number were decreased (P<0.01).PI3K inhibitor LY294002, NF-κB inhibitor PDTC and PD-L1 blocking antibody could significantly reverse the inhibition of DCs mediated T lymphocytes immunosuppression above (P<0.01). Conclusion: PD-L1 was a key molecule that mediates immunosuppression in lipopolysaccharide induced bacterial sepsis. PI3K Signal and NF- κB signal were also involved in this immunosuppressive process.


Assuntos
Antígeno B7-H1 , Sepse , Animais , Imunossupressão , Camundongos , NF-kappa B , Fosfatidilinositol 3-Quinases
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 611-615, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821093

RESUMO

Objective: To investigate the effects and mechanism of curcumol (CC) on liver function and fibrosis in rats of nonalcoholic fatty liver disease (NAFLD). Methods: The rat models of nonalcoholic steatohepatitis (NASH) combined with liver fibrosis were constructed by high-fat diet. Sixty SD rats were randomly divided into blank control group, model group (NASH), NASH + Compound Biejiarangan Troche (CBT) group (positive control group), and NASH + CC groups (25, 50, 100 mg/kg) , 10 rats in each group. The percentage of liver to body weight, and the levels of high density lipoprotein (HDL), triglyceride (TG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The liver fibrosis was observed by HE staining. The expressions of α-smooth muscle actin (α-SMA) and positive staining of nuclear factor κB p65 (NF-κB p65) were detected by immunohistochemistry. The expression levels of α-SMA, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and toll-like receptor-4 (TLR4), transforming growth factor-activated kinase-1 (TAK1), NF-κB p65 and vascular cell adhesion molecule-1 (VCAM-1) were detected by Western blot. The expression levels of interleukin (IL-6, IL-10, IL-1ß) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). Results: Compared with blank control group, the contents of HDL and IL-10 and the expression level of MMP-1 protein were decreased in model group significantly (P<0.05), while the levels of TG, ALT and AST, the positive rate of P65, α-SMA, TIMP-1, TLR4, TAK1, NF-κB p65, VCAM-1, IL-6, TNF-α and IL-1ß were increased significantly (P<0.05). Compared with model group, the levels of HDL, IL-10 and MMP-1 protein were significantly increased after treatment with CBT and CC (P<0.05), while the levels of TG, ALT, and AST, the positive rate of P65, α-SMA, TIMP-1, TLR4, TAK1, NF-κB p65, VCAM-1, IL-6, TNF-α and IL-1ß were decreased significantly (P<0.05). The improvement in model+high- concentration CC group was the most significant, and which in all concentration groups was lower than that in model+CBT group (P<0.05). Conclusion: CC can reduce inflammation response and improve liver function by regulating TLR4, TAK1 and NF-κB/p65 signaling pathway, and thus alleviating liver fibrosis, showing concentration-dependence within certain range.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Fibrose , Fígado , NF-kappa B , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Sesquiterpenos , Inibidor Tecidual de Metaloproteinase-1 , Fator de Necrose Tumoral alfa
15.
Sheng Wu Gong Cheng Xue Bao ; 37(11): 4056-4065, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34841805

RESUMO

Photorhabdus is a Gram-negative bacterium from the family Enterobacteriaceae that lives in a symbiotic association with nematode or insects. In addition to the role of being insect pathogens, one species called Photorhabdus asymbiotica (Pa) causes human infection around the world. Nevertheless, how does this transkingdom infection occur remains elusive. Here we focus on one pathogenic determinant called Photorhabdus virulence cassette (PVC) that is founded in the Pa genome and many other pathogens. The RNA-seq and qPCR data showed that the NF-κB and MAPK pathways were drastically activated in the PVC-treated mammalian macrophages. Western blotting assays using samples treated with various inhibitors of the affected pathways confirmed the results we have observed for MAPK pathway previously. p65 translocation assays validated the NF-κB activation in the macrophages after PVC treatment. Moreover, the bacterial phagocytosis by macrophage was also promoted by PVC at the early stage, and this phagocytosis was inhibited by cytoskeleton inhibitors. Thus, the results indicated that PVC is involved in the bacterial invasion by activating NF-κB and MAPK signaling pathway, providing a new perspective for analyzing the pathogenicity of Pa in human infections.


Assuntos
Photorhabdus , Animais , Humanos , Macrófagos , NF-kappa B/genética , Transdução de Sinais , Virulência
16.
Anticancer Res ; 41(10): 4917-4928, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593439

RESUMO

BACKGROUND/AIM: The functions of interleukin 33 (IL-33) in cholangiocarcinoma (CCA) are unclear. This study aimed to evaluate the roles of IL-33 in CCA progression. MATERIALS AND METHODS: The effect of intracellular IL-33 using shIL-33 knocked down KKU-055 (IL-33KD-KKU-055) compared to parental (Pa) KKU-055 and extracellular IL-33 using recombinant human IL-33 (rhIL-33) treatment on the proliferation and invasion of CCA cells grown in 3D cultures was studied. Relevant markers were determined by western blot or ELISA. RESULTS: IL-33KD-KKU-055 cells showed increased proliferation and invasion in 3D cultures compared to Pa-KKU-055 cells, with NF-κB and IL-6 up-regulation. Treatment with 2 ng/ml rhIL-33 promoted Pa-KKU-055 cell proliferation by inducing NF-κB and IL-6 expressions. Upon GSK-3ß inactivation and increased nuclear full-length IL-33 (flIL-33), 20 ng/ml rhIL-33 had no effect on proliferation. Both 2 and 20 ng/ml rhIL-33 induced proliferation and invasion of IL-33-negative KKU-213 cells in 3D cultures, as well as NF-κB and IL-6 up-regulation. CONCLUSION: Intracellular and extracellular IL-33 have distinct roles in the mechanisms of CCA progression.


Assuntos
Neoplasias dos Ductos Biliares/prevenção & controle , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/prevenção & controle , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Interleucina-33/farmacologia , NF-kappa B/metabolismo , Apoptose , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/genética , Proliferação de Células , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Glicogênio Sintase Quinase 3 beta/genética , Humanos , NF-kappa B/genética , Invasividade Neoplásica , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Oxid Med Cell Longev ; 2021: 5513868, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646423

RESUMO

COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.


Assuntos
COVID-19 , Hidrogênio/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , SARS-CoV-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo
19.
Front Immunol ; 12: 689453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616393

RESUMO

Evidence concerning the role of alcohol-induced neuroinflammation in alcohol intake and relapse has increased in the last few years. It is also proven that mu-opioid receptors (MORs) mediate the reinforcing properties of alcohol and, interestingly, previous research suggests that neuroinflammation and MORs could be related. Our objective is to study neuroinflammatory states and microglial activation, together with adaptations on MOR expression in the mesocorticolimbic system (MCLS) during the abstinence and relapse phases. To do so, we have used a sex-dependent rat model of complete Freund's adjuvant (CFA)-induced alcohol deprivation effect (ADE). Firstly, our results confirm that only CFA-treated female rats, the only experimental group that showed relapse-like behavior, exhibited specific alterations in the expression of phosphorylated NFκB, iNOS, and COX2 in the PFC and VTA. More interestingly, the analysis of the IBA1 expression revealed a decrease of the microglial activation in PFC during abstinence and an increase of its expression in the relapse phase, together with an augmentation of this activation in the NAc in both phases that only occur in female CFA-treated rats. Additionally, the expression of IL1ß also evidenced these dynamic changes through these two phases following similar expression patterns in both areas. Furthermore, the expression of the cytokine IL10 showed a different profile than that of IL1ß, indicating anti-inflammatory processes occurring only during abstinence in the PFC of CFA-female rats but neither during the reintroduction phase in PFC nor in the NAc. These data indicate a downregulation of microglial activation and pro-inflammatory processes during abstinence in the PFC, whereas an upregulation can be observed in the NAc during abstinence that is maintained during the reintroduction phase only in CFA-female rats. Secondly, our data reveal a correlation between the alterations observed in IL1ß, IBA1 levels, and MOR levels in the PFC and NAc of CFA-treated female rats. Although premature, our data suggest that neuroinflammatory processes, together with neural adaptations involving MOR, might play an important role in alcohol relapse in female rats, so further investigations are warranted.


Assuntos
Alcoolismo/metabolismo , Sistema Límbico/metabolismo , Microglia/metabolismo , Neuroimunomodulação , Dor/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores Opioides mu/metabolismo , Abstinência de Álcool , Alcoolismo/imunologia , Alcoolismo/fisiopatologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Feminino , Adjuvante de Freund , Mediadores da Inflamação/metabolismo , Sistema Límbico/imunologia , Sistema Límbico/fisiopatologia , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/imunologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Dor/induzido quimicamente , Dor/imunologia , Dor/fisiopatologia , Fosforilação , Córtex Pré-Frontal/imunologia , Córtex Pré-Frontal/fisiopatologia , Ratos Sprague-Dawley , Recidiva , Fatores Sexuais
20.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638824

RESUMO

An anthocyanin-rich diet is considered to protect against chronic inflammatory processes although the bioavailability of anthocyanins is regarded as rather low. Moreover, the immunomodulatory role of anthocyanins is not fully understood yet. In the present study, fractions of blackberry (Rubus fruticosus) juice were investigated in plasma-relevant concentrations with respect to their immunomodulatory properties in lipopolysaccharide (LPS)-challenged THP-1-derived macrophages. The complex blackberry extract acted ineffective as well as potential degradation products. Cyanidin-3O-glucoside (Cy3glc), the main constituent of blackberry anthocyanins, diminished TNF-α levels at a concentration of 0.02 µg/mL, indicating protective effects as measured with quantitative RT-PCR and multiplex cytokine assays. LPS-boosted activity of transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) of differentiated THP-1 reporter gene cells was marginally inhibited by Cy3glc. LPS-induced microRNA-155 was further increased, supporting the evidence of protection. Of note, fractions obtained from blackberry juice, in particular cyanidin-3O-(6″-dioxalylglucoside), were displaying potential pro-inflammatory properties as these elevated IL-6 and TNF-α levels. In conclusion, highly purified anthocyanin fractions of blackberry juice display both anti- and pro-inflammatory properties at plasma-relevant concentrations depending on their structure and substitution pattern.


Assuntos
Antocianinas/farmacologia , Anti-Inflamatórios/farmacologia , Macrófagos/metabolismo , Rubus/química , Antocianinas/química , Anti-Inflamatórios/química , Humanos , Interleucina-6/biossíntese , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Células THP-1 , Fator de Necrose Tumoral alfa/biossíntese
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