Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 257
Filtrar
1.
J Cell Physiol ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843053

RESUMO

O-GlcNAcylation is a posttranslational modification that regulates numerous nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes, such as transcription, signal transduction, and cell motility. Although increasing evidence has shown that elevated levels of global O-GlcNAcylation are linked to the metastasis in hepatocellular carcinoma (HCC) cells, the underlying mechanism is still ambiguous. In this study, we demonstrated that forkhead box protein A2 (FOXA2), an essential transcription factor for liver homeostasis and HCC developing, was O-GlcNAcylated by O-GlcNAc transferase (OGT) and regulates HCC cells migration and invasion. Opposite FOXA2 and OGT expression tendency were observed in HCC tissues, and lower FOXA2 levels predicted a poor prognosis in HCC patients. The reduction of FOXA2 in HCC cells was found to be inversely correlated with the cellular O-GlcNAcylation and cell migratory ability. Notably, we found that FOXA2 was modified by O-GlcNAcylation and that O-GlcNAcylation activated the ubiquitination degradation of FOXA2 in highly metastatic HCC cells. Although this modification did not affect FOXA2 nuclear localization capability, O-GlcNAcylation on FOXA2 was key for attenuating FOXA2-mediated transcription. O-GlcNAcylation decreased the transcription of FOXA2 downstream target gene E-cadherin and it ultimately promoted O-GlcNAcylation-mediated HCC cell migration and invasion. The results provide insights into the role of O-GlcNAcylation in regulating FOXA2 activity and suggest its important implications in HCC metastasis.

2.
Genes (Basel) ; 12(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809523

RESUMO

This study aimed to investigate the changes in abomasum transcriptome and the associated microbial community structure in young calves with artificially dosed, adult rumen contents. Eight young bull calves were randomly dosed with freshly extracted rumen contents from an adult cow (high efficiency (HE), n = 4), or sterilized rumen content (Con, n = 4). The dosing was administered within 3 days of birth, then at 2, 4, and 6 weeks following the initial dosing. Abomasum tissues were collected immediately after sacrifice at 8 weeks of age. Five genera (Tannerella, Desulfovibrio, Deinococcus, Leptotrichia, and Eubacterium; p < 0.05) showed significant difference in abundance between the treatments. A total of 975 differentially expressed genes were identified (p < 0.05, fold-change > 1.5, mean read-counts > 5). Pathway analysis indicated that up-regulated genes were involved in immune system process and defense response to virus, while the down-regulated genes involved in ion transport, ATP biosynthetic process, and mitochondrial electron transport. Positive correlation (r > 0.7, p < 0.05) was observed between TRPM4 gene and Desulfovibrio, which was significantly higher in the HE group. TRPM4 had a reported role in the immune system process. In conclusion, the dosing of adult rumen contents to calves can alter not only the composition of active microorganisms in the abomasum but also the molecular mechanisms in the abomasum tissue, including reduced protease secretion and decreased hydrochloric acid secretion.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33741615

RESUMO

Cyclodipeptide synthases (CDPSs) catalyse the formation of cyclodipeptides using aminoacylated-tRNAs as substrates and have great potentials in the production of diverse 2,5-diketopiperazines (2,5-DKPs). Genome mining of Streptomyces leeuwenhoekii NRRL B-24963 revealed a two-gene locus saz encoding a CDPS SazA and a unique fused enzyme SazB harboring two domains: phytoene-synthase-like prenyltransferase (PT) and methyltransferase (MT). Heterologous expression of the saz gene(s) in Streptomyces albus J1074 led to the production of four prenylated indole alkaloids, among which streptoazines A-C (3-5) are new compounds. Expression of different gene combinations showed that the SazA catalyzes the formation of cyclo (L-Trp-L-Trp) (cWW, 1), followed by consecutive prenylation and methylation by SazB. Biochemical assays demonstrated that SazB is a bifunctional enzyme, catalyzing sequential C3/C3'-prenylation(s) by SazB-PT and N1/N1'-methylation(s) by SazB-MT. Of note substrate selectivity of SazB-PT and SazB-MT was probed, revealing the stringent specificity of SazB-PT but relative flexibility of SazB-MT.IMPORTANCENatural products with 2,5-DKP skeleton have long sparked the interest in drug discovery and development. Recent advances in microbial genome sequencing have revealed that the potentials of CDPS-dependent pathways encoding new 2,5-DKPs are underexplored. In this study, we report the genome mining of a new CDPS-containing two-gene operon and activation of this cryptic gene cluster through heterologous expression, leading to the discovery of four indole 2,5-DKP alkaloids. The cWW-synthesizing CDPS SazA and the unusual PT-MT fused enzyme SazB were characterized. Our results expand the repertoire of CDPSs and associated tailoring enzymes, setting the stage for accessing diverse prenylated alkaloids using synthetic biology strategies.

4.
Biol Reprod ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33690863

RESUMO

Understanding luteal maintenance during early pregnancy is of substantial biological and practical importance. Characterizing effects of early pregnancy, however, has historically been confounded by use of controls with potential exposure to early PGF pulses or differences in CL age. To avoid this, the present study utilized bihourly blood sampling to ensure control CL (n = 6) were of a similar age to CL from pregnant animals (n = 5), yet without exposure to PGF pulses. Additionally, CL from second month of pregnancy (n = 4) were analyzed to track fate of altered genes after cessation of embryonic interferon tau (IFNT) secretion. The major alteration in gene expression in first month of pregnancy occurred in interferon-stimulated genes (ISGs), with immune/interferon signaling pathways enriched in three independent over-representation analyses. Most ISGs decreased during second month of pregnancy, though, surprisingly, some ISGs remained elevated in the second month even after cessation of IFNT secretion. Investigation of luteolytic genes found few altered transcripts, in contrast to previous reports, likely due to removal of controls exposed to PGF pulses. An exception to this trend was decreased expression of transcription factor NR4A1. Beyond luteolytic genes and ISGs, over representation analyses highlighted the prevalence of altered genes within the extracellular matrix and regulation of IGF availability, confirming results of other studies independent of luteolytic genes. These results support the idea that CL maintenance in early pregnancy is related to lack of PGF exposure, although potential roles for CL expression of diverse ISGs and other pathways activated during early pregnancy remain undefined.

5.
Adv Exp Med Biol ; 1278: 205-227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523450

RESUMO

Uveitis is a chronic disease with relapsing and remitting ocular attack, which requires corticosteroids and systemic immunosuppression to prevent severe vision loss. Classically, uveitis is referred to an autoimmune disease, mediated by pro-inflammatory Th17 cells and immunosuppressive CD4+CD25+FoxP3+ T-regulatory cells (Tregs). More and more evidence indicates that Tregs are involved in development, resolution, and remission of uveitis. Clinically, many researchers have conducted quantitative and functional analyses of peripheral blood from patients with different subtypes of uveitis, in an attempt to find the changing rules of Tregs. Consistently, using the experimental autoimmune uveitis (EAU) model, researchers have explored the development and resolution mechanism of uveitis in many aspects. In addition, many drug and Tregs therapy investigations have yielded encouraging results. In this chapter, we introduced the current understanding of Tregs, summarized the clinical changes in the number and function of patients with uveitis and the immune mechanism of Tregs involved in EAU model, as well as discussed the progress and shortcomings of Tregs-related drug therapy and Tregs therapy. Although the exact mechanism of Tregs-mediated uveitis protection remains to be elucidated, the strategy of Tregs regulation may provide a specific and meaningful way for the prevention and treatment of uveitis.


Assuntos
Doenças Autoimunes , Uveíte , Fatores de Transcrição Forkhead , Humanos , Tolerância Imunológica , Linfócitos T Reguladores , Células Th17
6.
J Mol Model ; 27(2): 57, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33515354

RESUMO

Deoxyribonucleic acid (DNA) sequencing is a crucial issue for the cure of different kinds of diseases. Here, we computationally explored the effect of DNA nucleobases on the electronic properties and electrical conductivity of a zigzag (10,0) C3N nanotube (C3NNT) at B3LYP-gCP-D3 level of theory. Our calculations revealed that the binding energy of nucleobases shows the order of guanine (G) > cytosine (C) > thymine (T) > adenine (A). Based on the energy decomposition analysis (EDA), the G, C, and T strongly interact with the C3NNT, but the A nucleobase adsorbed mainly via electrostatic attraction and dispersion forces. We exposed that the nucleobase size and its carbonyl group determine its adsorption behavior. The DNA nucleobase adsorption meaningfully increased the electrical conductivity of C3NNT. The C3NNT sensing response toward G, C, T, or A was predicted to be 131, 66, 60, or 10. Therefore, the C3NNT might be applied to selectively detect the G, C, T, and A. Our findings expose the usefulness of C3NNT as a next-generation DNA sequencer, suggesting new leads for future progresses in sustainable designs, superior sensing architectures, and bioelectronics.

7.
Arthritis Res Ther ; 23(1): 15, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413573

RESUMO

BACKGROUND: T cell Ig and ITIM domain (TIGIT)/CD226 pathway has a critical role in regulating T cell responses and has come to the forefront in cancer as a promising immunotherapeutic target. However, its role in autoimmune diseases is just beginning to be elucidated. Dermatomyositis (DM) is an autoimmune disease, in which T cell dysregulation plays a pivotal role, and importantly, it is a common immune-related adverse event in response to treatment of cancers with immune checkpoint inhibitors, but no studies have implicated the TIGIT/CD226 axis in DM. METHODS: We recruited 30 treatment-naïve DM patients and 26 healthy controls. Flow cytometry analysis was used to investigate the co-expression of TIGIT and CD226 on T cells in blood samples. Magnetic bead or FACS-based cell isolation, T cell proliferation assay, and intracellular cytokine staining were performed to analyze the functions of different TIGIT/CD226 phenotypes. Recombinant proteins CD155, CD112, and anti-CD226 antibodies were used to suppress the function of TIGIT/CD226-expressing CD4 T cells. RESULTS: Four distinct subsets of T cells based on TIGIT/CD226 co-expression, TIGIT+CD226-, TIGIT+CD226+, TIGIT-CD226+, and TIGIT-CD226-, were identified and characterized in DM patients. Our data showed that the function of CD4 T cell subset varied by the TIGIT/CD226 phenotype. An elevated TIGIT+CD226+ CD4 subset with enhanced effector function was observed in patients with DM, especially the patients complicated with interstitial lung disease. This subpopulation was closely related to DM activity and decreased significantly in DM remission after treatment. Furthermore, the effector function of TIGIT+CD226+ CD4 subset could be suppressed by blocking CD226. CONCLUSION: Our data revealed that the TIGIT and CD226 expression profiles could be used to identify functionally distinct subsets of CD4 T cells and TIGIT+CD226+ CD4 T cells is a significant subset in DM with enhanced frequency and effector function. This abnormal subset could be suppressed by blocking CD226, providing insight into the therapeutic target of the TIGIT/CD226 axis.

8.
Biotechnol Biofuels ; 14(1): 22, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451355

RESUMO

BACKGROUND: Both APETALA2/Ethylene Responsive Factor (AP2/ERF) superfamily and R2R3-MYB family were from one of the largest diverse families of transcription factors (TFs) in plants, and played important roles in plant development and responses to various stresses. However, no systematic analysis of these TFs had been conducted in the green algae A. protothecoides heretofore. Temperature was a critical factor affecting growth and lipid metabolism of A. protothecoides. It also remained largely unknown whether these TFs would respond to temperature stress and be involved in controlling lipid metabolism process. RESULTS: Hereby, a total of six AP2 TFs, six ERF TFs and six R2R3-MYB TFs were identified and their expression profiles were also analyzed under low-temperature (LT) and high-temperature (HT) stresses. Meanwhile, differential adjustments of lipid pathways were triggered, with enhanced triacylglycerol accumulation. A co-expression network was built between these 18 TFs and 32 lipid-metabolism-related genes, suggesting intrinsic associations between TFs and the regulatory mechanism of lipid metabolism. CONCLUSIONS: This study represented an important first step towards identifying functions and roles of AP2 superfamily and R2R3-MYB family in lipid adjustments and response to temperature stress. These findings would facilitate the biotechnological development in microalgae-based biofuel production and the better understanding of photosynthetic organisms' adaptive mechanism to temperature stress.

9.
Am J Physiol Endocrinol Metab ; 320(3): E438-E452, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33427054

RESUMO

Obesity is a prevailing problem across the globe. Women who are obese have difficulty initiating and sustaining lactation. However, the impact of genetics and diet on breastfeeding outcomes is understudied. Here we explore the effect of diet and genotype on lactation. We utilized the low-density lipoprotein receptor (Ldlr-KO) transgenic mouse model as an obesity and hypercholesterolemia model. Additionally, we used the tryptophan hydroxylase 1 (Tph1-KO) mouse, recently identified as a potential anti-obesogenic model, to investigate if addition of Tph1-KO could ameliorate negative effects of obesity in Ldlr-KO mice. We created a novel transgenic mouse line by combining the Ldlr and Tph1 [double knockout (DKO)] mice to study the interaction between the two genotypes. Female mice were fed a low-fat diet (LFD; 10% fat) or high-fat diet (HFD; 60% fat) from 3 wk of age through early [lactation day 3 (L3)] or peak lactation [lactation day 11 (L11)]. After 4 wk of consuming either LFD or HFD, female mice were bred. On L2 and L10, dams were milked to investigate the effect of diet and genotype on milk composition. Dams were euthanized on L3 or L11. There was no impact of diet or genotype on milk protein or triglycerides (TGs) on L2; however, by L10, Ldlr-KO and DKO dams had increased TG levels in milk. RNA-sequencing of L11 mammary glands demonstrated Ldlr-KO dams fed HFD displayed enrichment of genes involved in immune system pathways. Interestingly, the DKO may alter vesicle budding and biogenesis during lactation. We also quantified macrophages by immunostaining for F4/80+ cells at L3 and L11. Diet played a significant role on L3 (P = 0.013), but genotype played a role at L11 (P < 0.0001) on numbers of F4/80+ cells. Thus the impact of diet and genotype on lactation differs depending on stage of lactation, illustrating complexities of understanding the intersection of these parameters.NEW & NOTEWORTHY We have created a novel mouse model that is focused on understanding the intersection of diet and genotype on mammary gland function during lactation.


Assuntos
Dieta Hiperlipídica , Lactação , Glândulas Mamárias Animais/metabolismo , Receptores de LDL/genética , Triptofano Hidroxilase/genética , Animais , Gorduras na Dieta/farmacologia , Feminino , Interação Gene-Ambiente , Genótipo , Lactação/efeitos dos fármacos , Lactação/genética , Glândulas Mamárias Animais/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna/genética , Camundongos , Camundongos Knockout , Camundongos Obesos , Obesidade/genética , Obesidade/metabolismo
10.
Hum Immunol ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33288226

RESUMO

BACKGROUND: As the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it. OBJECTIVE: To investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants. MATERIALS AND METHOD: The study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3-4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry. RESULTS: The percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3-4 weeks after birth. CONCLUSIONS: It seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied.

11.
Environ Microbiol ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33331063

RESUMO

Large amounts of detrital organic matter and osmolytes accumulate in the sediments of hadal trenches (>6000 m depth) due to the funnelling effect. It is still unknown whether there are novel active microbes that depend on specific carbon sources in extreme and isolated environments. In this study, we present a novel active bacterial phylum, Candidatus Tianyabacteria in the FCB superphylum, which was enriched in sediments collected from the Challenger Deep. Genome binning resulted in high-quality Ca. Tianyabacteria genomes representing two Ca. Tianyabacteria lineages (L1 and L2) in sediments 0-21 cm below the surface (cmbsf); L1 tends to be abundant in the upper layers (0-9 cmbsf), and L2 seems to be more prevalent in the deeper layers (12-21 cmbsf). Gene annotation and transcriptomics results indicate that the two lineages might import and catalyse amino acids and myo-inositol into central carbon metabolism for a heterotrophic lifestyle. Probably due to differences in environmental oxygen levels, the L2 genomes harbour gene clusters responsible for denitrification and fermentation, while the L1 genomes encode octahaem cytochrome c and multicopper oxidase using unknown substrates. The Ca. Tianyabacteria are thus novel heterotrophic organisms that participate in processes of carbon, nitrogen and organic osmolyte cycling in hadal sediments.

12.
J Biol Chem ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234595

RESUMO

GalNAc-type O-glycosylation, initially catalyzed by polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts), is one of the most abundant and complex post-translational modifications of proteins. Emerging evidence has proven that aberrant ppGalNAc-Ts are involved in malignant tumor transformation. However, the exact molecular functions of ppGalNAc-Ts are still unclear. Here, the role of one isoform, ppGalNAc-T4, in breast cancer cell lines was investigated. The expression of ppGalNAc-T4 was found to be negatively associated with migration of breast cancer cells. Loss-of function studies revealed that ppGalNAc-T4 attenuated the migration and invasion of breast cancer cells by inhibiting the epithelial-mesenchymal transition (EMT) process. Correspondingly, transforming growth factor beta (TGF-ß) signaling, which is the upstream pathway of EMT, was impaired by ppGalNAc-T4 expression. ppGalNAc-T4 knock-out decreased O-GalNAc modification of TGF-ß type Ⅰ and Ⅱ receptor (TßR Ⅰ and Ⅱ) and led to the elevation of TGF-ß receptor dimerization and activity. Importantly, a peptide from TßR Ⅱ was first identified as the naked peptide substrate of ppGalNAc-T4 with a higher affinity than ppGalNAc-T2. Further, Ser31, corresponding to the extracellular domain of TßR Ⅱ, was identified as the O-GalNAcylation site upon in vitro glycosylation by ppGalNAc-T4. The O-GalNAc-deficient S31A mutation enhanced TGF-ß signaling activity and EMT in breast cancer cells. Together, these results identified a novel mechanism of ppGalNAc-T4-catalyzed TGF-ß receptors O-GalNAcylation that suppresses breast cancer cell migration and invasion via the EMT process. Targeting ppGalNAc-T4 may be a potential therapeutic strategy for breast cancer treatment.

13.
Eur J Radiol ; 133: 109368, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33207287

RESUMO

OBJECTIVES: To explore the ability of liver acquisition with volume acceleration contrast-enhanced sequence (LAVA-ce) to improve the accuracy of reassessing adjacent organ involvement by rectal mucinous adenocarcinoma (MC) after neoadjuvant therapy (NAT). METHODS: This study retrospectively enrolled twenty-five patients with MC who underwent pre- and post-NAT MRI, were staged as T4b using pre-NAT T2 weighted imaging, received NAT and underwent radical resection. All MR images were divided into two schemes, T2 weighted plus diffusion weighted imaging (T2Dw protocol) and plus LAVA-ce (T2DwLce protocol). All patients were scored on a 0-4 scale to reassess organ-invasive mucus components. Postoperative pathology was used to identify the involvement of surrounding organs (ypT4b). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the consistency of the results with pathology after adding fs-CE sequence. RESULTS: Among 25 MC patients (15 males and 10 females, aged 21-89 years), 21 were restaged as yT4b after NAT by using T2Dw, with an accuracy of 44.0 % (11/25), which was lower than the accuracy of staging patients with non-mucinous rectal adenocarcinoma (94.1 %, 96/102). The accuracy of MC restaging was improved by using T2DwLce (23/25). The AUC of T2DwLce was 0.857 (95 % CI, 0.660∼0.964), which was higher than that of T2Dw (AUC, 0.611 [95 % CI, 0.397∼0.798]) (P = 0.019). CONCLUSION: The LAVA-ce sequence can improve the accuracy of reevaluation and should be included in the MRI protocol for MC patients.

14.
Poult Sci ; 99(11): 6119-6127, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33142530

RESUMO

A 3 × 2 factorial arrangement of treatments was conducted to investigate the effects of iron (Fe, 40, 60, and 80 mg/kg) and Bacillus subtilis (2.5 × 109 and 5.0 × 109 CFU/kg) supplementation on reproductive performance, egg quality, nutrient digestibility, hormone levels, antioxidant indices, and hematological parameters in breeder geese. A total of one hundredtwenty 46-week-old Wulong breeder geese were randomly assigned to 1 of 6 dietary treatments with 4 replicates per treatment and 5 geese per replicate for 10 wk following 1 wk of adaption. Dietary Fe supplementation increased egg weight (P = 0.036), fertility (P = 0.022), serum total antioxidant capacity (P = 0.022), red blood cell (P = 0.001), hematocrit (HCT, P < 0.001), hemoglobin (HGB, P = 0.005), and mean corpuscular volume (MCV, P < 0.001). Dietary B. subtilis supplementation increased egg production (P = 0.025), eggshell thickness (P = 0.020), apparent phosphorus digestibility (P < 0.001), serum follicle stimulating hormone (P = 0.043), total antioxidant capacity (P < 0.001), HCT (P < 0.001), HGB (P < 0.001), and MCV (P = 0.025), and reduced malondialdehyde level (P = 0.008). The birds fed diets supplemented with 60 mg/kg Fe and 5 × 109 CFU/kg B. subtilis showed the highest percentage of hatched eggs (P = 0.004) and mean corpuscular hemoglobin (P < 0.001) among the 6 groups. Supplementation of 40 and 60 mg/kg Fe significantly increased the apparent digestibility of calcium compared with that of 80 mg/kg Fe in the birds fed 5.0 × 109 CFU/kg B. subtilis (P = 0.004). Supplementation with 60 and 80 mg/kg Fe in the birds fed 5 × 109 CFU/kg B. subtilis significantly decreased serum urea nitrogen level compared with other 4 groups (P = 0.022). In conclusion, the combination of Fe and B. subtilis effectively improves reproductive performance, eggshell quality, nutrient digestibility, antioxidant status, and hematopoietic function of breeder geese. Dietary addition of 60 mg/kg Fe and 5.0 × 109 CFU/kg B. subtilis was an optimum supplementation dose.

15.
Poult Sci ; 99(11): 6196-6204, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33142537

RESUMO

This experiment was conducted to investigate the effects of manganese (Mn) and Bacillus subtilis (BS) on the production performance, egg quality, antioxidant capacity, and gut microbiota of breeding geese during laying period. A total of 120 forty-six-week-old breeding geese (Wulong) were randomly assigned to 1 of 6 treatment diets formulated to supply 10, 20, and 30 mg/kg Mn with 5 × 109 CFU/kg or 2.5 × 109 CFU/kg BS for a 10-wk trial. Results showed that dietary supplementation with 20 and 30 mg/kg Mn could decrease the daily feed intake (DFI) of geese. Moreover, 30 mg/kg Mn significantly increased the laying rate. Besides, although Mn addition had no obvious effect on egg quality, 5 × 109 CFU/kg BS was found to elevate the hatching egg hatching rate and eggshell thickness. For the serum hormones, 30 mg/kg Mn promoted estradiol secretion, while 5 × 109 CFU/kg BS increased the level of follicle-stimulating hormone. Furthermore, 20 and 30 mg/kg Mn and 5 × 109 CFU/kg BS significantly enhanced the total antioxidant capacity by increasing the activity of total superoxide dismutases or decreasing the content of malondialdehyde. Dietary supplementation with 5 × 109 CFU/kg BS also increased the intestinal villus height and upregulated the abundance of Fusobacteria, Fusobacteriaceae, Fusobacterium, and Faecalibacterium in cecal content. In addition, 20 and 30 mg/kg Mn elevated the levels of Bacteroidetes, Bacteroidaceae, Bacteroides, and Ruminococcaceae but decreased Streptococcaceae. Importantly, an interaction effect was observed between Mn and BS on the DFI, egg mass, average egg size, and the abundance of Bacteroides as well as Faecalibacterium. In conclusion, dietary inclusion of Mn and BS could improve the production performance, egg quality, antioxidant capacity, intestinal structure, as well as gut microbiota. Supplementation of 30 mg/kg Mn and 5.0 × 109 CFU/kg BS provided the optimal effect.

16.
Nat Commun ; 11(1): 5898, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214551

RESUMO

O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress.

17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1738-1741, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018333

RESUMO

Ventromedial prefrontal cortex (vmPFC) is an important brain region involved in many psychological functions. Previous neuroimaging studies have shown disrupted function and altered metabolic level within vmPFC of schizophrenia (SCZ) patients. However, the linkage between the functional connectivity and its underlying neurobiological mechanism in SCZ remains unclear. In this study, we aimed to investigate the altered relationship between the functional connectivity strength (FCS) and metabolic concentrations within vmPFC in drug-naïve first-episode psychosis (FEP) patients using a combined functional magnetic resonance imaging (fMRI) and single-voxel proton magnetic resonance spectroscopy (1H- MRS) technique. There were 26 drug-naïve FEP patients and 27 matched healthy controls participated this study. We have found altered correlation between FCS and N-acetylaspartate (NAA) in drug-naïve FEP patients. In addition, the glutamate and glutamine compounds (Glx) and NAA concentrations were positively correlated with Positive and Negative Symptoms Scale (PANSS) total scores. Our findings revealed the disrupted functional-metabolic coupling within vmPFC in drug-naïve FEP patients and provided useful insights in understanding the etiology of SCZ.


Assuntos
Ácido Aspártico , Psicoses Induzidas por Substâncias , Ácido Aspártico/análogos & derivados , Ácido Glutâmico , Humanos , Córtex Pré-Frontal/diagnóstico por imagem
18.
Cell Biol Int ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079401

RESUMO

Breast cancer, one of the most frequently diagnosed and aggressive malignancies, is the major cause of cancer-related death greatly threatening women health. Polypeptide N-acetylgalactosaminyltransferase 4 (ppGalNAc-T4), responsible for the initial step of mucin-type O-glycosylation, has been reported to be implicated in diverse types of human tumors. However, the biological role of ppGalNAc-T4 in breast cancer is still undetermined. In this study, we investigate the effects and mechanism of ppGalNAc-T4 to breast cancer cell proliferation. From analysis of high throughput RNA sequencing datasets of Gene Expression Omnibus and ArrayExpress, a positive correlation between ppGalNAc-T4 and the recurrence-free survival was observed in multigroup of human breast cancer datasets. Moreover, transcriptomes analysis using RNA-sequencing in MCF7 cells revealed that cell cycle-related genes induced the effects of ppGalNAc-T4 on breast cancer cell proliferation. Additionally, investigations showed that ppGalNAc-T4 impaired cell proliferation in MCF-7 and MDA-MB-231 breast cells. Furthermore, our results suggested that the ppGalNAc-T4 knockout activated Notch signaling pathway and enhanced cell proliferation. Collectively, our data indicated that ppGalNAc-T4 affected the proliferation of human breast cancer cells, which appears to be a novel target for understanding the underlying molecular mechanism of breast cancer.

19.
Redox Biol ; 37: 101761, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33080440

RESUMO

Macrophage recruitment and pro-inflammatory differentiation are hallmarks of various diseases, including infection and sepsis. Although studies suggest that mitochondria may regulate macrophage immune responses, it remains unclear whether mitochondrial mass affects macrophage pro-inflammatory differentiation. Here, we found that lipopolysaccharide (LPS)-activated macrophages possess higher mitochondrial mass than resting cells. Therefore, this study aimed to explore the functional role and molecular mechanisms of increased mitochondrial mass in pro-inflammatory differentiated macrophages. Results show that an increase in the mitochondrial mass of macrophages positively correlates with inflammatory cytokine generation in response to LPS. RNA-seq analysis revealed that LPS promotes signal transducers and activators of transcription 2 (Stat2) and dynamin-related protein 1 (Drp1) expression, which are enriched in positive mitochondrial fission regulation. Meanwhile, knockdown or pharmacological inhibition of Drp1 blunts LPS-induced mitochondrial mass increase and pro-inflammatory differentiation. Moreover, Stat2 boosts Drp1 phosphorylation at serine 616, required for Drp1-mediated mitochondrial fission. LPS also causes Stat2-and Drp1-dependent biogenesis, which contributes to the generation of additional mitochondria. However, these mitochondria are profoundly remodeled, displaying fragmented morphology, loose cristae, reduced Δψm, and metabolic programming. Furthermore, these remodeled mitochondria shift their function from ATP synthesis to reactive oxygen species (ROS) production, which drives NFκB-dependent inflammatory cytokine transcription. Interestingly, an increase in mitochondrial mass with constitutively active phosphomimetic mutant of Drp1 (Drp1S616E) boosted pro-inflammatory response in macrophages without LPS stimulation. In vivo, we also demonstrated that Mdivi-1 administration inhibits LPS-induced macrophage pro-inflammatory differentiation. Importantly, we observed Stat2 phosphorylation and Drp1-dependent mitochondrial mass increase in macrophages isolated from LPS-challenged mice. In conclusion, we comprehensively demonstrate that a Stat2-Drp1 dependent mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages. Therefore, targeting the Stat2-Drp1 axis may provide novel therapeutic approaches for treating infection and inflammatory diseases.

20.
Medicine (Baltimore) ; 99(42): e22783, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080749

RESUMO

RATIONALE: Anaplastic thyroid carcinoma (ATC) is a rare highly aggressive thyroid malignancy. Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia is also a rare low grade malignant thyroid neoplasm. To date, comorbidity of these 2 tumors in the thyroid gland has not been reported in the English literature. PATIENT CONCERNS: Here, we present a case of a 67-year-old women with a 6-month history of mass of left neck. She complained of a painless mass in the right neck. DIAGNOSES: Based on histopathological examination of H&E stained sections, immunohistochemical staining assay and molecular tests, the patient was diagnosed with ATC combined with sclerosing mucoepidermoid carcinoma with eosinophilia. INTERVENTIONS: The patient underwent radical surgery for thyroid cancer. OUTCOMES: No complications, local recurrence or metastases were observed during a 1 year and 3 months follow-up after surgery. LESSONS: To the best of our knowledge, this is the first case report on ATC combined with sclerosing mucoepidermoid carcinoma with eosinophilia in the English literature. This condition can be easily misdiagnosed during thyroid fine needle cytology. Clinicians should perform morphological examination, immunohistochemistry and molecular tests on resected specimen to make a definitive diagnosis.


Assuntos
Carcinoma Mucoepidermoide/patologia , Eosinofilia/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Carcinoma Mucoepidermoide/cirurgia , Feminino , Humanos , Neoplasias Primárias Múltiplas/cirurgia , Esclerose , Carcinoma Anaplásico da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...