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1.
Animals (Basel) ; 12(15)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35892550

RESUMO

This study investigated whether unsaturated fatty acids in milk and the oxidative status of cows are affected by heavy metal exposure due to leather processing. The blood lead (Pb) concentrations in cows from two farms in the polluted area were 16.27 ± 8.63 µg/L, respectively, which were significantly (p < 0.05) higher than the blood Pb concentrations in cows from an unpolluted farm (6.25 ± 3.04 µg/L). There were significantly (p < 0.05) lower levels of glutathione S-transferase (GST), glutathione peroxidase (GPX), and glutathione (GSH) in the serum of cows from the polluted area compared to the levels in cows from an unpolluted area. The linoleic acid (C18:2n6c) content in milk from the polluted area was 15% lower than in the control area. There was a significant correlation between linoleic acid in milk with the blood Pb and serum GSH levels. Heavy metals can alter fatty acid synthesis through oxidative stress, which may be the mechanism by which heavy metals affect fatty acid synthesis in milk.

2.
ACS Appl Mater Interfaces ; 14(27): 30618-30625, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35763788

RESUMO

Reactive oxygen species (ROS)-based cancer treatments have attracted much attention in recent years. However, most patients respond poorly to the monotypic ROS during these treatments. In this work, a multiple ROS-based cancer immunotherapy synergistic strategy has been developed to enhance the therapeutic effect of cancer. We prepare a three-dimensional covalent organic framework (3D COF-TATB), and embed copper ions (Cu2+) into the skeleton to obtain multifunctional nanomaterial, 3D Cu@COF-TATB. In this system, porphyrins in 3D COF-TATB serve not only as the photosensitizer for photodynamic process to produce singlet oxygen(1O2), but also as the binding sites to complex with Cu2+. Cu2+ can be reduced by the GSH to generate Cu+ to produce hydroxyl radical (•OH) through the Fenton-like reaction. Moreover, the generated multiple types of ROS induce the immunogenic cell death (ICD) of cancer cells to improve the immunogenicity and further activate an immune response for attacking the tumor. Combining with the immunoblocking inhibitor (aPD-1), 3D Cu@COF-TATB can effectively inhibit the tumor growth. This work will provide a guidance for multimodal cancer therapy in future clinical treatment settings.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Linhagem Celular Tumoral , Cobre/química , Humanos , Imunoterapia , Estruturas Metalorgânicas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo
3.
J Am Chem Soc ; 144(25): 11138-11147, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35674660

RESUMO

Developing efficient hydrogen oxidation reaction (HOR) electrocatalysts in alkaline media is of great significance for anion exchange membrane fuel cells. Herein, we report the synthesis of hollow colloidosomes composed of Ru nanocrystals based on a novel gas/liquid interface self-assembly strategy. Structural characterizations reveal that much defects are present in the building block (Ru nanocrystals) of Ru colloidosomes. Theoretical calculations suggest that the defects in the Ru structure can optimize the adsorption binding energy of reaction intermediates for the HOR. Benefiting from the assembled colloidosome and optimized electronic structure, the Ru colloidosomes exhibit remarkable HOR catalytic performance in alkaline media with a mass activity higher than that of benchmark Pt/C. Our work may shed new light on the rational design of advanced electrocatalysts with an assembled structure for energy-related applications.

4.
Toxins (Basel) ; 14(6)2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35737029

RESUMO

Aflatoxin B1 (AFB1) is a common crop contaminant, while aflatoxin M1 (AFM1) is implicated in milk safety. Humans are likely to be simultaneously exposed to AFB1 and AFM1; however, studies on the combined interactive effects of AFB1 and AFM1 are lacking. To fill this knowledge gap, transcriptomic, proteomic, and microRNA (miRNA)-sequencing approaches were used to investigate the toxic mechanisms underpinning combined AFB1 and AFM1 actions in vitro. Exposure to AFB1 (1.25-20 µM) and AFM1 (5-20 µM) for 48 h significantly decreased cell viability in the intestinal cell line, NCM460. Multi-omics analyses demonstrated that additive toxic effects were induced by combined AFB1 (2.5 µM) and AFM1 (2.5 µM) in NCM460 cells and were associated with p53 signaling pathway, a common pathway enriched by differentially expressed mRNAs/proteins/miRNAs. Specifically, based on p53 signaling, cross-omics showed that AFB1 and AFM1 reduced NCM460 cell viability via the hsa-miR-628-3p- and hsa-miR-217-5p-mediated regulation of cell surface death receptor (FAS), and also the hsa-miR-11-y-mediated regulation of cyclin dependent kinase 2 (CDK2). We provide new insights on biomarkers which reflect the cytotoxic effects of combined AFB1 and AFM1 toxicity.


Assuntos
Aflatoxina M1 , MicroRNAs , Aflatoxina B1/análise , Aflatoxina B1/toxicidade , Aflatoxina M1/análise , Animais , Humanos , MicroRNAs/genética , Leite/química , Proteômica , Proteína Supressora de Tumor p53
5.
Front Public Health ; 10: 903036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769791

RESUMO

Objective: To compare the predictive performance of five handgrip strengths for cardiovascular disease (CVD) risk factors. Methods: A total of 804 Chinese middle-aged community residents' health medical examinations were collected. The absolute handgrip strength was denoted as HGS. HGS/body weight (HGS/BW), HGS/body mass index (HGS/BMI), HGS/lean body mass (HGS/LBM), and HGS/muscle mass (HGS/MM) represented relative handgrip strength (RHGS). To assess predictive performance, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were constructed. Results: HGS was not associated with most CVD risk biomarkers; however, RHGS showed a negative correlation trend after controlling for covariates (sex, age, smoking, and exercise). HGS/BMI and HGS/BW had better AUCs for predicting CVD risk factors than HGS/LBM or HGS/MM. HGS/BMI and HGS/BW can successfully predict all CVD risk factors in men with AUCs 0.55-0.65; similarly, women may effectively predict arteriosclerosis, hyperglycemia, hyperuricemia, and metabolic syndrome with AUCs 0.59-0.64, all p < 0.05. The optimal HGS/BW cut-off points for identifying different CVD risk factors were 0.59-0.61 in men and 0.41-0.45 in women, while the HGS/BMI were 1.75-1.79 in men and 1.11-1.15 in women. Conclusions: Almost all CVD risk biomarkers and CVD risk factors were unrelated to HGS. There is, however, a significant inverse relationship between RHGS and CVD risk factors. HGS/BMI or HGS/BW should be recommended to be the best choice for predicting the risk of CVD risk factors in five expressions of handgrip strength. We also acquired the recommended optimal cut-off points of HGS/BMI and HGS/BW for predicting CVD risk factors.


Assuntos
Doenças Cardiovasculares , Força da Mão , Biomarcadores , Peso Corporal , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Int J Mol Sci ; 23(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35562946

RESUMO

Depression is a psychiatric disorder that presents with a persistent depressed mood as the main clinical feature and is accompanied by cognitive impairment. Changes in neuroplasticity and neurogenesis greatly affect depression. Without genetic changes, epigenetic mechanisms have been shown to function by regulating gene expression during the body's adaptation to stress. Studies in recent years have shown that as important regulatory factors in epigenetic mechanisms, microRNAs (miRNAs) play important roles in the development and progression of depression through the regulation of protein expression. Herein, we review the mechanisms of miRNA-mediated neuroplasticity in depression and discus synaptic structural plasticity, synaptic functional plasticity, and neurogenesis. Furthermore, we found that miRNAs regulate neuroplasticity through several signalling pathways to affect cognitive functions. However, these pathways do not work independently. Therefore, we try to identify synergistic correlations between miRNAs and multiple signalling pathways to broaden the potential pathogenesis of depression. In addition, in the future, dual-function miRNAs (protection/injury) are promising candidate biomarkers for the diagnosis of depression, and their regulated genes can potentially be used as target genes for the treatment of depression.


Assuntos
Disfunção Cognitiva , MicroRNAs , Depressão/genética , Humanos , MicroRNAs/metabolismo , Neurogênese/genética , Plasticidade Neuronal/genética
8.
Nat Commun ; 13(1): 2947, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35618717

RESUMO

Dimethylsulfoniopropionate (DMSP) is an important marine anti-stress compound, with key roles in global nutrient cycling, chemotaxis and, potentially, climate regulation. Recently, diverse marine Actinobacteria, α- and γ-proteobacteria were shown to initiate DMSP synthesis via the methionine (Met) S-methyltransferase enzyme (MmtN), generating S-methyl-Met (SMM). Here we characterize a roseobacterial MmtN, providing structural and mechanistic insights into this DMSP synthesis enzyme. We propose that MmtN uses the proximity and desolvation mechanism for Met S-methylation with two adjacent MmtN monomers comprising the Met binding site. We also identify diverse functional MmtN enzymes in potentially symbiotic archaeal Candidatus Woesearchaeota and Candidate Phyla Radiation (CPR) bacteria, and the animalcule Adineta steineri, not anticipated to produce SMM and/or DMSP. These diverse MmtN enzymes, alongside the larger plant MMT enzyme with an N-terminus homologous to MmtN, likely utilize the same proximity and desolvation mechanism. This study provides important insights into the catalytic mechanism of SMM and/or DMSP production, and proposes roles for these compounds in secondary metabolite production, and SMM cycling in diverse organisms and environments.


Assuntos
Metionina , Metiltransferases , Bactérias/metabolismo , Metionina/metabolismo , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo
9.
Fish Shellfish Immunol ; 126: 47-56, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35568142

RESUMO

CD209 is a type II transmembrane protein in the C-type lectin family, which is involved in the regulation of innate and adaptive immune system. Although it has been widely studied in mammals, but little has been reported about fish CD209 genes. In the present study, Megalobrama amblycephala CD209 (MaCD209) gene was cloned and characterized, its expression patterns, evolutionary characteristics, agglutinative and bacteriostatic activities were analyzed. These results showed that the open reading frame (ORF) of MaCD209 gene was 795 bp, encoding 264 aa, and the calculated molecular weight of the encoded protein was 29.7 kDa. MaCD209 was predicted to contain 2 N-glycosylation sites, 1 functional domain (C-LECT-DC-SIGN-like) and 1 transmembrane domain. Multiple sequence alignment showed that the amino acid sequence of MaCD209 was highly homologous with that of partial fishes, especially the highly conserved C-LECT-DC-SIGN-like domain and functional sites of CD209. Phylogenetic analysis showed that the CD209 genes from M. amblycephala and other cypriniformes fishes were clustered into one group, which was reliable and could be used for evolutionary analysis. Then, adaptive evolutionary analysis of teleost CD209 was conducted, and several positively selected sites were identified using site and branch-site models. Quantitative real-time PCR analysis showed that MaCD209 gene was highly expressed in the liver and heart. Moreover, the expression of MaCD209 was significantly induced upon Aeromonas hydrophila infection, with the peak levels at 4 h or 12 h post infection. The immunohistochemical analysis also revealed increased distribution of MaCD209 protein post bacterial infection. In addition, recombinant MaCD209 (rMaCD209) protein was prepared using a pET32a expression system, which showed excellent bacterial binding and agglutinative activities in a Ca2+-independent manner. However, rMaCD209 could only inhibit the proliferation of Escherichia coli rather than A. hydrophila. In conclusion, this study identified the MaCD209 gene, detected its expression and evolutionary characteristics, and evaluated the biological activities of rMaCD209 protein, which would provide a theoretical basis for understanding the evolution and functions of fish CD209 genes.


Assuntos
Cyprinidae , Cipriniformes , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Aeromonas hydrophila/fisiologia , Animais , Sequência de Bases , Clonagem Molecular , Cipriniformes/genética , Proteínas de Peixes/química , Mamíferos/genética , Mamíferos/metabolismo , Filogenia , Proteínas Recombinantes/genética
10.
RSC Adv ; 12(8): 4874-4882, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35425518

RESUMO

Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers that make these materials suitable for use as excellent scaffold in heterogeneous catalysis. Here we synthesize a layered two-dimensional (2D) COF (TADP-COF) through the condensation reaction between four-branched 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) and linear 2,5-dihydroxyterephthalaldehyde (Dha) and 1,4-phthalaldehyde (PA) building blocks. Porphyrin units, imine and hydroxyl groups together with imines can provide wide coordination sites for metal docking. Using a programmed synthetic procedure, Cu(ii) ions first coordinated with the imine groups in conjunction with their adjacent hydroxyl groups, and porphyrin units and subsequently added Pd(ii) ions occupied the remaining imine sites in the space between adjacent COF layers. The bimetallic Pd(ii)/Cu(ii)@TADP-COF showed high catalytic activity in a one-pot coupling/oxidation cascade reaction in water. The high surface area, one-dimensional (1D) open channel structure and predesigned catalytic active sites of this material make it ideal candidate for use as heterogeneous catalyst in a wide range of catalytic reactions.

11.
Chem Commun (Camb) ; 58(39): 5877-5880, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35470817

RESUMO

A well-designed three-dimensional (3D) covalent organic framework (COF) was constructed as a nanocapsule for the encapsulation of horseradish peroxidase (HRP), which could realize sustained release of HRP to prolong the duration of the therapeutic agents and promote long-term enzyme prodrug therapy.


Assuntos
Estruturas Metalorgânicas , Nanocápsulas , Neoplasias , Pró-Fármacos , Preparações de Ação Retardada , Peroxidase do Rábano Silvestre , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
12.
Int J Mol Sci ; 23(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35408869

RESUMO

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene, which is involved in the RAS/MAPK cell signaling transduction process. SHP2 has been shown to contribute to the progression of various cancers and is emerging as an important target for anti-tumor drug research. However, past efforts to develop SHP2 inhibitors into drugs have been unsuccessful owing to the positively charged nature of the active site pocket tending to bind negatively charged groups that are usually non-drug-like. Here, a series of uncharged pyrazoline derivatives were designed and developed as new SHP2 inhibitors using a structure-based strategy. Compound 4o, which exhibited the strongest SHP2 inhibitory activity, bound directly to the catalytic domain of SHP2 in a competitive manner through multiple hydrogen bonds. Compound 4o affected the RAS/MAPK signaling pathway by inhibiting SHP2, and subsequently induced apoptosis and growth inhibition of HCT116 cells in vitro and in vivo. Notably, the oral administration of compound 4o in large doses showed no obvious toxicity. In summary, our findings provide a basis for the further development of compound 4o as a safe, effective and anti-tumor SHP2 inhibitor.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Domínio Catalítico , Inibidores Enzimáticos/farmacologia , Células HCT116 , Humanos , Neoplasias/tratamento farmacológico , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Transdução de Sinais
13.
Biomaterials ; 283: 121426, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35240471

RESUMO

Transcatheter medical micro-devices through circulatory system show great potential for therapy but lack strategies to stably anchor them at the desired site in vascularized tissues to take actions. Here a shape memory functionalized biodegradable magnetic micro-anchor (SM2A) is developed to achieve magnetic guided endovascular localization through precisely controlled shape transformation. The SM2A comprises anisotropic polylactide-based microparticle embedded with superparamagnetic Fe3O4 nanoparticles, exhibiting thermally activated tunable shape recovery modes at a body-friendly temperature range to accomplished an efficient endovascular anchoring effect in both decellularized liver organ and rabbit ear embolization models. The SM2A can be anchored at the target micro-vessel, exhibiting a controlled radial expansion of the vessel wall yielding with estimated stresses of 7-26 kPa in contact stress and 38-218 kPa in von Mises stress. The SM2A is a promising platform to incorporate diagnostic or therapeutic agents for precision deployment and in-situ action.


Assuntos
Embolização Terapêutica , Nanopartículas , Animais , Fenômenos Magnéticos , Fenômenos Físicos , Coelhos
14.
Toxins (Basel) ; 14(3)2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35324670

RESUMO

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which are occasionally detected in milk and commercial baby foods, could easily enter and reach the gastrointestinal tract, posing impairment to the first line of defense and causing dysfunction of the tissue. The objective of this study was to investigate the immunostimulatory roles of individual and combined AFM1 and OTA on the immature intestine. Thus, we used ELISA assays to evaluate the generation of cytokines from ex vivo CD-1 fetal mouse jejunum induced by AFM1 and OTA and explored the related regulatory pathways and pivot genes using RNA-seq analysis. It was found that OTA exhibited much stronger ability in stimulating pro-inflammatory cytokine IL-6 from jejunum tissues than AFM1 (OTA of 4 µM versus AFM1 of 50 µM), whereas the combination of the two toxins seemed to exert antagonistic actions. In addition, transcriptomics also showed that most gene members in the enriched pathway 'cytokine-cytokine receptor interaction' were more highly expressed in OTA than the AFM1 group. By means of PPI network analysis, NFKB1 and RelB were regarded as hub genes in response to OTA but not AFM1. In the human FHs 74 Int cell line, both AFM1 and OTA enhanced the content of reactive oxygen species, and the oxidative response was more apparent in OTA-treated cells in comparison with AFM1. Furthermore, OTA and AFM1 + OTA raised the protein abundance of p50/RelB, and triggered the translocation of the dimer from cytosol to nucleus. Therefore, the experimental data ex vivo and in vitro showed that OTA-induced inflammation was thought to be bound up with the up-regulation and translocation of NF-κB, though AFM1 seemed to have no obvious impact. Since it was the first attempt to uncover the appearances and inner mechanisms regarding inflammation provoked by AFM1 and OTA on immature intestinal models, further efforts are needed to understand the detailed metabolic steps of the toxin in cells and to clarify their causal relationship with the signals proposed from current research.


Assuntos
Aflatoxina M1 , Intestinos , Aflatoxina M1/análise , Animais , Citocinas/genética , Contaminação de Alimentos/análise , Inflamação/induzido quimicamente , Intestinos/química , Camundongos , Leite/química , Ocratoxinas
15.
J Biomater Sci Polym Ed ; 33(11): 1383-1397, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35321618

RESUMO

Nanocarrier-based photodynamic therapy (PDT) has emerged as a promising treatment in cancer therapy. However, the PDT therapeutic efficacy is limited by the lack of specificity, limited intracellular cytotoxic reactive oxygen species (ROS) generation, and the immunosuppressive tumor microenvironment. Herein, a platelet membrane (Pm) decorated and chlorin e6 loaded liposome (Pm/Lps/Ce6) is developed to improve specific tumor-targeting capability and antitumor responses. Pm/Lps/Ce6 could efficiently improve the cellular internalization of Ce6. Under 660-nm laser irradiation, enough ROS was produced to suppress the growth of tumor cells in vitro. In vivo, the Pm decoration increased cellular uptake of the Ce6 loaded liposome in cancer cells by the tumor-targeting and immune escape capacity and produced a satisfactory inhibitory effect on breast cancer. Our study provides a biomimetic strategy via the biological properties of Pm to improve the antitumor performance of photodynamic therapy for treating breast cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Porfirinas , Biomimética , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Lipopolissacarídeos , Lipossomos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Espécies Reativas de Oxigênio , Microambiente Tumoral
16.
Am J Cancer Res ; 12(2): 681-694, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35261795

RESUMO

Ovarian cancer is a relatively common tumor in women with the highest mortality among female reproductive system tumors. The lack of apparent early symptoms and effective screening strategies often leads to ovarian cancer being diagnosed at an advanced stage. Immunotherapy relying on tumor-associated antigens might improve the treatment of ovarian cancer. Cancer-testis antigens (CTAs) are ideal tumor-associated antigens, and MAGE-A, NY-ESO-1, CT45, and Sp17 are classic CTAs highly expressed in ovarian cancer. Here, we review the research on CTAs in ovarian cancer, including prognostic value and advances in immunotherapy, all of which are essential for developing a theoretical basis for targeted therapy strategies.

17.
Opt Express ; 30(3): 3854-3865, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35209635

RESUMO

We analyze and suppress the magnetic noise response in optical rotation detection system (ORDS) in atomic magnetometers in this study. Because of the imperfections of the optical elements, the probe light is actually elliptically polarized in ORDS, which can polarize the atom ensemble and cause the responses to the three-axis magnetic noise. We theoretically analyze the frequency responses to the magnetic noise, and prove that the responses are closely associated with the DC magnetic field. The values of the DC magnetic fields are calculated with special frequency points, called 'break points', in the transverse responses. We reveal the relationships between the DC magnetic field and the sensitivities of ORDS, and effectively suppress the magnetic noise responses with the residual magnetic field compensation. Finally, the sensitivity of ORDS is improved by approximately two times at 10-20 Hz.

18.
BMC Complement Med Ther ; 22(1): 36, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123452

RESUMO

BACKGROUND: Abelmoschus manihot (L.) Medicus (AM) is a medicinal plant with various biological activities, including anti-inflammatory, antioxidant, antiviral and immunomodulatory. Previous studies have identified total flavones as the primary bioactive ingredient of AM (termed TFA). However, its role and mechanism in counteracting Influenza A virus (IAV) infection are yet to be explored. Therefore, the study aims to study the antiviral and anti-inflammatory effects of TFA on IAV in vitro and in vivo. METHODS: A network pharmacology-based approach was applied to identify the antiviral mechanism of TFA against IAV. For the mechanism validation, the cytopathic effect reduction assay evaluated the antiviral activity of TFA in vitro. Meanwhile, the mice were intranasally infected with IAV to induce lung infection. The antiviral effect of TFA was observed in vivo. Further investigation whether the reprogramming microbiome in the TFA treatment group affected antiviral, we conducted a microbial-transfer study with co-housing experiments. RESULTS: By applying the network pharmacology-based methods (PPI, GO, and KEGG), we identified 167 potential targets of TFA action, among which 62 targets were related to IAV pathogenesis. A core network containing the pro-inflammatory TNFα, IL-6, IL-1ß, MAPKs, and RIG-I receptor signaling pathway was further confirmed as the crucial targets for anti-influenza efficacy of TFA. We demonstrate that TFA provided profound protection against pulmonary IAV infection, which alleviated inflammatory responses, decreased MAPK signaling pathway and expedited viral eradiation. CONCLUSIONS: Our study unveils a pivotal role for TFA in controlling viral infection and dampening pathology, making it a promising strategy for treating IAV-induced pneumonia.


Assuntos
Abelmoschus , Flavonas , Vírus da Influenza A , Pneumonia , Animais , Flavonas/farmacologia , Camundongos
19.
Food Sci Nutr ; 10(2): 564-576, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35154692

RESUMO

Necrotizing enterocolitis (NEC) is an intestinal disease that frequently occurs in premature infants. Presently, there is no effective therapy for NEC. Therefore, the key to reduce the incidence rate of NEC is to take effective intervention measures as early as possible. Short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), the principal terminal products of enterobacteria fermentation, play anti-inflammatory actions in mature intestinal cells. However, few studies focus on their roles in immature intestine. Here, we evaluated the anti-inflammatory actions of SCFAs ex vivo with ICR fetal mouse jejunum cultures and explored the potential anti-inflammatory regulators through RNA-seq and then verified them in vitro with human fetal small intestinal epithelial FHs 74 Int cells. In this study, we found that acetate, propionate, and butyrate decreased IL-1ß-induced production of CXCL2 ex vivo and IL-8 and IL-6 in vitro significantly (p < .05). Furthermore, the inhibitors of NF-κB p65, JNK1/2, and ERK1/2 pathways, which were selected from RNA-seq and depressed by SCFAs, also significantly decreased IL-8 and IL-6 productions induced by IL-1ß (p < .05). Therefore, our results showed that acetate, propionate, and butyrate ameliorated the fetal small intestine inflammatory response induced by IL-1ß through inhibiting ERK1/2 pathway; NF-κB p65, JNK1/2, and ERK1/2 pathways; or NF-κB p65 and ERK1/2 pathways, respectively. These findings suggested that SCFAs may be a new therapy agent for NEC.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 298-304, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35123643

RESUMO

OBJECTIVE: To investigate the effect of Rheb1 in the development of mouse megakaryocyte-erythroid progenitor cells and its related mechanism. METHODS: Rheb1 was specifically knocked-out in the hematopoietic system of Vav1-Cre;Rheb1fl/fl mice(Rheb1Δ/Δ mice). Flow cytometry was used to detect the percentage of red blood cells in peripheral blood and erythroid cells in bone marrow in Vav1-Cre;Rheb1fl/fl mice and control mice. The CFC assay was used to detect the differentiation ability of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Real-time fluorescence quantification PCR was used to detect the relative expression of PU.1,GATA-1,GATA-2,CEBPα and CEBPß of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Rapamycin was added to the culture medium, and it was used to detect the changes in cloning ability of megakaryocyte-erythroid progenitor cells from wild-type mice in vitro. RESULTS: After Rheb1 was knocked out, the development and stress response ability of megakaryocyte-erythroid progenitor cells in mice were weaken and the differentiation ability of megakaryocyte-erythroid progenitor cells in vitro was weaken. Moreover, the expression of GATA-1 of megakaryocyte-erythroid progenitor cells was decreased. Further, rapamycin could inhibit the differentiative capacity of megakaryocyte-erythroid progenitor cells in vitro. CONCLUSION: Rheb1 can regulate the development of megakaryocyte-erythroid progenitor cells probably through the mTOR signaling pathway in mice.


Assuntos
Células Progenitoras de Megacariócitos e Eritrócitos , Transdução de Sinais , Animais , Diferenciação Celular , Eritrócitos , Citometria de Fluxo , Megacariócitos , Camundongos
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