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BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. METHODS: Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). RESULTS: Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. CONCLUSIONS: Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.
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Deficiência de Colina , Colina , Lactação , Músculo Esquelético , Efeitos Tardios da Exposição Pré-Natal , Transcriptoma , Animais , Feminino , Gravidez , Músculo Esquelético/metabolismo , Masculino , Ratos , Colina/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Ratos Wistar , Dieta , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologiaRESUMO
Global antimicrobial resistance has led to a ban on the use of antibiotics as growth promoters (AGPs) in poultry farming, encouraging the use of natural phytogenic feed additives that provide similar effects to AGPs without causing resistance. The aim of this study was to determine the effects of the addition of encapsulated fennel seed (Foeniculum vulgare Mill.) essential oil (FEO) into the diets on the performance, intestinal microflora, morphology, and transcriptomic profiling of broiler chickens. In the study, 400 one-d-old male chicks of the Ross-308 genotype were randomly distributed into five groups, each with 16 replicates of five birds. The experiment included a control group fed on basal diets without the addition of FEO and treatment groups supplemented with 50 (FEO50), 100 (FEO100), 200 (FEO200), or 400 (FEO400) mg of encapsulated FEO/kg. Body weight and the European Production Efficiency Factor values were higher in the FEO100, FEO200, and FEO400 groups (Pâ <â 0.05). The feed conversion ratio significantly improved at all FEO levels (Pâ <â 0.05). FEO supplementation improved duodenum, jejunum, and ileum morphologies. It enhanced mucosal layer thickness in the duodenum and jejunum, and muscular layer thickness in the jejunum and ileum (Pâ <â 0.05). It also increased the number of Lactobacillus spp. in the jejunum and ileum (Pâ <â 0.05). According to the transcriptome profile obtained from the microarray analysis of samples taken from small intestine tissues, the mRNA expression levels of 261 genes in the FEO50 group (206 upregulated and 55 downregulated), 302 genes in the FEO100 group (218 upregulated and 84 downregulated), 292 genes in the FEO200 group (231 upregulated and 61 downregulated), and 348 genes in the FEO400 group (268 upregulated and 80 downregulated) changed compared to the control group. Most upregulated genes were associated with catalytic activity, binding, transcription regulators and transcription factors, anatomical structure and cellular development, and protein binding activity modulators. The downregulated genes mostly belonged to the transporter, carrier, and protein-modifying enzyme classes. Besides, the anti-inflammatory IL-10 gene (4.41-fold) increased significantly in the FEO100 group compared to the control group (Pâ <â 0.05). In conclusion, FEO improved the performance of broiler chickens by regulating biological processes such as performance and intestinal health, with the 100 mg FEO/kg supplementation being the most prominent.
The long-term use of low-level antibiotics in the poultry industry to promote growth, rather than for treatment, has led to the development of antimicrobial resistance (AMR), a significant risk to human and animal health. This concern has led to a ban on antibiotics as growth promoters (AGPs) in broiler diets, resulting in an increase in metabolic diseases in broiler chickens. Phytogenic feed additives have been tested as alternatives to compensate for the loss of AGPs. One such additive, fennel seed essential oil (FEO), known for its strong antimicrobial properties, was examined in this study for its impact on broiler growth performance and the underlying genetic and molecular mechanisms. The results showed that FEO enhanced feed conversion efficiency, thereby improving broiler performance. It positively affected the intestinal wall structure and function and helped establish a balanced microbiota by suppressing harmful and supporting beneficial microorganisms. Transcriptome datasets revealed that FEO modulated gene expression related to economically important traits such as performance and intestinal health. In conclusion, considering the urgent need for antibiotic-free production systems owing to escalating AMR and the growing interest in genotype-specific feeding in the postgenomic era, FEO may be a promising, natural, safe, and effective alternative to AGPs.
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Foeniculum , Microbioma Gastrointestinal , Óleos Voláteis , Animais , Masculino , Galinhas/fisiologia , Óleos Voláteis/farmacologia , Transcriptoma , Dieta/veterinária , Suplementos Nutricionais/análise , Ração Animal/análiseRESUMO
Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase ß and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses.
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Neoplasias , Transcriptoma , Humanos , Ácido Gálico/farmacologia , Ácido Gálico/metabolismo , Perfilação da Expressão GênicaRESUMO
Chronic ultraviolet (UV) exposure causes photoaging, which is primarily responsible for skin damage. Nutritional intervention is a viable strategy for preventing and treating skin photoaging. Eugenol (EU) presents anti-inflammatory and antioxidant properties, promotes wound healing, and provides contact dermatitis relief. This study explored the ability of EU to mitigate skin photoaging caused by UVB exposure in vitro and in vivo. EU alleviated UVB-induced skin photodamage in skin cells, including oxidative stress damage and extracellular matrix (ECM) decline. Dietary EU alleviated skin photoaging by promoting skin barrier repair, facilitating skin tissue regeneration, and modulating the skin microenvironment in photoaged mice. The transcriptome sequencing results revealed that EU changed the skin gene expression profiles. Subsequent pathway enrichment analyses indicated that EU might reverse the pivotal ECM-receptor interaction and cytokine-cytokine receptor interaction signaling pathways. Furthermore, EU alleviated the intestinal dysbiosis induced by chronic UVB exposure. Spearman analysis results further revealed the close connection between gut microbiota and skin photoaging. Considering the near-inevitable UVB exposure in modern living, the findings showed that the EU effectively reverted skin photoaging, offering a potential strategy for addressing extrinsic skin aging.
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PURPOSE: Bipolar affective disorder (BP) causes major functional impairment and reduced quality of life not only for patients, but also for many close relatives. We aimed to investigate mRNA levels in BP patients to find differentially expressed genes linked to specific clinical course variants; assuming that several gene expression alterations might indicate vulnerability pathways for specific course and severity of the disease. MATERIALS: We searched for up- and down-regulated genes comparing patients with diagnosis of BP type I (BPI) vs type II (BPII), history of suicide attempts, psychotic symptoms, predominance of manic/hypomanic episodes, and history of numerous episodes and comorbidity of substance use disorders or anxiety disorders. RNA was extracted from peripheral blood mononuclear cells and analyzed with use of microarray slides. RESULTS: Differentially expressed genes (DEGs) were found in all disease characteristics compared. The lowest number of DEGs were revealed when comparing BPI and BPII patients (18 genes), and the highest number when comparing patients with and without psychotic symptoms (3223 genes). Down-regulated genes identified here with the use of the DAVID database were among others linked to cell migration, defense response, and inflammatory response. CONCLUSIONS: The most specific transcriptome profile was revealed in BP with psychotic symptoms. Differentially expressed genes in this variant include, among others, genes involved in inflammatory and immune processes. It might suggest the overlap of biological background between BP with a history of psychotic features and schizophrenia.
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Transtorno Bipolar , Perfilação da Expressão Gênica , Humanos , Transtorno Bipolar/genética , Biomarcadores/metabolismo , Feminino , Masculino , Transcriptoma , Adulto , Fenótipo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Numerous studies have explored the neural correlates of trait anxiety, a predisposing factor for several stress-related disorders. However, the findings from previous studies are inconsistent, which might be due to the limited regions of interest (ROI). A recent approach, named global-brain functional connectivity (GBC), has been demonstrated to address the shortcomings of ROI-based analysis. Furthermore, research on the transcriptome-connectome association has provided an approach to link the microlevel transcriptome profile with the macroscale brain network. In this paper, we aim to explore the neurobiology of trait anxiety with an imaging transcriptomic approach using GBC, biological neurotransmitters, and transcriptome profiles. METHODS: Using a sample of resting-state fMRI data, we investigated trait anxiety-related alteration in GBC. We further used behavioral analysis, spatial correlation analysis, and postmortem gene expression to separately assess the cognitive functions, neurotransmitters, and transcriptional profiles related to alteration in GBC in individuals with trait anxiety. RESULTS: GBC values in the ventromedial prefrontal cortex and the precuneus were negatively correlated with levels of trait anxiety. This alteration was correlated with behavioral terms including social cognition, emotion, and memory. A strong association was revealed between trait anxiety-related alteration in GBC and neurotransmitters, including dopaminergic, serotonergic, GABAergic, and glutamatergic systems in the ventromedial prefrontal cortex and the precuneus. The transcriptional profiles explained the functional connectivity, with correlated genes enriched in transmembrane signaling. LIMITATIONS: Several limitations should be taken into account in this research. For example, future research should consider using some different approaches based on dynamic or task-based functional connectivity analysis, include more neurotransmitter receptors, additional gene expression data from different samples or more genes related to other stress-related disorders. Meanwhile, it is of great significance to include a larger sample size of individuals with a diagnosis of major depression disorder or other disorders for analysis and comparison and apply stricter multiple-comparison correction and threshold settings in future research. CONCLUSIONS: Our research employed multimodal data to investigate GBC in the context of trait anxiety and to establish its associations with neurotransmitters and transcriptome profiles. This approach may improve understanding of the neural mechanism, together with the biological and molecular genetic foundations of GBC in trait anxiety.
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Conectoma , Transtorno Depressivo Maior , Humanos , Transcriptoma , Encéfalo/diagnóstico por imagem , Ansiedade/diagnóstico por imagem , Ansiedade/genética , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Conectoma/métodosRESUMO
Background: Many psychiatric disorders share a working memory (WM) impairment phenotype, yet the genetic causes remain unclear. Here, we generated genetic profiles of WM deficits using attention-deficit/hyperactivity disorder samples and validated the results in zebrafish models. Methods: We used 2 relatively large attention-deficit/hyperactivity disorder cohorts, 799 and 776 cases, respectively. WM impairment was assessed using the Rey Complex Figure Test. First, association analyses were conducted at single-variant, gene-based, and gene-set levels. Deeper insights into the biological mechanism were gained from further functional exploration by bioinformatic analyses and zebrafish models. Results: Genomic analyses identified and replicated a locus with rs75885813 as the index single nucleotide polymorphism showing significant association with WM defects but not with attention-deficit/hyperactivity disorder. Functional feature exploration found that these single nucleotide polymorphisms may regulate the expression level of RBFOX1 through chromatin interaction. Further pathway enrichment analysis of potential associated single nucleotide polymorphisms revealed the involvement of posttranscription regulation that affects messenger RNA stability and/or alternative splicing. Zebrafish with functionally knocked down or genome-edited rbfox1 exhibited WM impairment but no hyperactivity. Transcriptome profiling of rbfox1-defective zebrafish indicated that alternative exon usages of snap25a might partially lead to reduced WM learning of larval zebrafish. Conclusions: The locus with rs75885813 in RBFOX1 was identified as associated with WM. Rbfox1 regulates synaptic and long-term potentiation-related gene snap25a to adjust WM at the posttranscriptional level.
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A small subset of high-grade B-cell lymphoma (HGBL) with blastoid morphology remains poorly understood. We assessed 55 cases of blastoid HGBL, not otherwise specified (NOS) and compared their clinicopathologic characteristics with those of 81 non-blastoid HGBL-NOS and 62 blastoid HGBL with MYC and BCL2, with or without BCL6 rearrangements (double/triple-hit lymphoma [D/THL]). Patients with blastoid HGBL-NOS showed similar clinicopathologic features to patients with blastoid D/THLs and non-blastoid HGBL-NOS, except more frequently with a history of low-grade B-cell lymphoma, bone marrow involvement, and BCL2 rearrangement (P < .05) compared to the latter. MYC rearrangement (MYC-R), detected in 40% of blastoid HGBL-NOS, was associated with aggressive clinicopathologic features and poorer overall survival, even worse than that of blastoid D/THL (P < .05). Transcriptome profiling revealed a distinct gene expression pattern with differentially expressed genes enriched in MYC and P53-targeted genes in MYC-R blastoid HGBL-NOS. Fifty-two percent of blastoid HGBL-NOS had a double hit-like signature, similar to non-blastoid HGBL-NOS (P = .73). The overall survival of the blastoid HGBL-NOS group was similar to that of the blastoid D/THL group but appeared poorer than that of its non-blastoid counterparts (P = .07). Taken together, blastoid HGBL-NOS is an aggressive B-cell lymphoma that shares overlapping clinicopathologic and genetic features with non-blastoid HGBL-NOS. MYC-R in patients with blastoid HGBL-NOS identifies a highly aggressive subgroup with distinct aggressive clinicopathologic features, unique molecular signatures, and a dismal clinical outcome.
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Linfoma de Células B , Linfoma Difuso de Grandes Células B , Humanos , Rearranjo Gênico , Linfoma de Células B/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Biomarcadores Tumorais/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-6/genéticaRESUMO
In the central nervous system, microglia are responsible for removing infectious agents, damaged/dead cells, and amyloid plaques by phagocytosis. Other cell types, such as astrocytes, are also recently recognized to show phagocytotic activity under some conditions. Oligodendrocyte precursor cells (OPCs), which belong to the same glial cell family as microglia and astrocytes, may have similar functions. However, it remains largely unknown whether OPCs exhibit phagocytic activity against foreign materials like microglia. To answer this question, we examined the phagocytosis activity of OPCs using primary rat OPC cultures. Since innate phagocytosis activity could trigger cell death pathways, we also investigated whether participating in phagocytosis activity may lead to OPC cell death. Our data shows that cultured OPCs phagocytosed myelin-debris-rich lysates prepared from rat corpus callosum, without progressing to cell death. In contrast to OPCs, mature oligodendrocytes did not show phagocytotic activity against the bait. OPCs also exhibited phagocytosis towards lysates of rat brain cortex and cell membrane debris from cultured astrocytes, but the percentage of OPCs that phagocytosed beta-amyloid was much lower than the myelin debris. We then conducted RNA-seq experiments to examine the transcriptome profile of OPC cultures and found that myelination- and migration-associated genes were downregulated 24 h after phagocytosis. On the other hand, there were a few upregulated genes in OPCs 24 h after phagocytosis. These data confirm that OPCs play a role in debris removal and suggest that OPCs may remain in a quiescent state after phagocytosis.
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Células Precursoras de Oligodendrócitos , Ratos , Animais , Células Precursoras de Oligodendrócitos/fisiologia , Diferenciação Celular/fisiologia , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Fagocitose/genética , Células CultivadasRESUMO
Expression of fission yeast Pho1 acid phosphatase is repressed under phosphate-replete conditions by transcription of an upstream prt lncRNA that interferes with the pho1 mRNA promoter. lncRNA-mediated interference is alleviated by genetic perturbations that elicit precocious lncRNA 3'-processing and transcription termination, such as (i) the inositol pyrophosphate pyrophosphatase-defective asp1-H397A allele, which results in elevated levels of IP8, and (ii) absence of the 14-3-3 protein Rad24. Combining rad24Δ with asp1-H397A causes a severe synthetic growth defect. A forward genetic screen for SRA (Suppressor of Rad24 Asp1-H397A) mutations identified a novel missense mutation (Tyr86Asp) of Pla1, the essential poly(A) polymerase subunit of the fission yeast cleavage and polyadenylation factor (CPF) complex. The pla1-Y86D allele was viable but slow-growing in an otherwise wild-type background. Tyr86 is a conserved active site constituent that contacts the RNA primer 3' nt and the incoming ATP. The Y86D mutation elicits a severe catalytic defect in RNA-primed poly(A) synthesis in vitro and in binding to an RNA primer. Yet, analyses of specific mRNAs indicate that poly(A) tails in pla1-Y86D cells are not different in size than those in wild-type cells, suggesting that other RNA interactors within CPF compensate for the defects of isolated Pla1-Y86D. Transcriptome profiling of pla1-Y86D cells revealed the accumulation of multiple RNAs that are normally rapidly degraded by the nuclear exosome under the direction of the MTREC complex, with which Pla1 associates. We suggest that Pla1-Y86D is deficient in the hyperadenylation of MTREC targets that precedes their decay by the exosome.
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RNA Longo não Codificante , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Domínio Catalítico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Longo não Codificante/genética , Mutação , Fatores de Poliadenilação e Clivagem de mRNA/genética , Fatores de Poliadenilação e Clivagem de mRNA/metabolismoRESUMO
Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots, and they are known for their peculiar aromas and flavors. The axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation has prompted searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) was isolated and cultured, and its transcriptome was analyzed under different in vitro culture conditions. The results showed that the highest growth of T. borchii SP1 was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22 °C. We analyzed the transcriptome of this strain cultured in different media to establish a framework for future comparative studies, paying particular attention to the central metabolic pathways, principal secondary metabolite gene clusters, and the genes involved in producing volatile aromatic compounds (VOCs). The results showed a transcription signal for around 80% of the annotated genes. In contrast, most of the transcription effort was concentrated on a limited number of genes (20% of genes account for 80% of the transcription), and the transcription profile of the central metabolism genes was similar in the different conditions analyzed. The gene expression profile suggests that T. borchii uses fermentative rather than respiratory metabolism in these cultures, even in aerobic conditions. Finally, there was a reduced expression of genes belonging to secondary metabolite clusters, whereas there was a significative transcription of those involved in producing volatile aromatic compounds.
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Ascomicetos , Micorrizas , Transcriptoma , Ascomicetos/metabolismo , Micorrizas/genética , SimbioseRESUMO
BACKGROUND: Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT. METHODS: We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA). RESULTS: There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA.Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.
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Neoplasias do Ânus , Carcinoma de Células Escamosas , Infecções por HIV , MicroRNAs , RNA Longo não Codificante , Humanos , Transcriptoma , RNA Longo não Codificante/genética , Proteínas Hedgehog/genética , Carcinoma de Células Escamosas/genética , Neoplasias do Ânus/genética , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , MicroRNAs/genética , Recidiva , Análise de Sequência de RNA , RNA Mensageiro/genéticaRESUMO
Inactivated vaccines are one of the most effective strategies for controlling the coronavirus disease 2019 (COVID-19) pandemic. However, the response genes for the protective effect of inactivated vaccines are still unclear. Herein, we analysed the neutralization antibody responses elicited by vaccine serum and carried out transcriptome sequencing of RNAs isolated from the PBMCs of 29 medical staff receiving two doses of the CoronaVac vaccine. The results showed that SARS-CoV-2 neutralization antibody titers varied considerably among individuals, and revealed that many innate immune pathways were activated after vaccination. Furthermore, the blue module revealed that NRAS, YWHAB, SMARCA5, PPP1CC and CDC5L may be correlated with the protective effect of the inactivated vaccine. Additionally, MAPK1, CDC42, PPP2CA, EP300, YWHAZ and NRAS were demonstrated as the hub genes having a significant association with vaccines. These findings provide a basis for understanding the molecular mechanism of the host immune response induced by inactivated vaccines.
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COVID-19 , Transcriptoma , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Vacinas de Produtos Inativados , Proteínas de Ligação a RNA , Proteínas de Ciclo CelularRESUMO
Blastoid B-cell neoplasms mainly include B-lymphoblastic leukemia/lymphoma (B-ALL), blastoid mantle cell lymphoma, and high-grade B-cell lymphoma with blastoid morphologic features (blastoid HGBL). Distinguishing blastoid HGBL from B-ALL can be challenging and we previously developed six-point flow cytometry-focused and three-point immunohistochemistry-focused scoring systems to aid in differential diagnosis. However, the six-point scoring system was derived from bone marrow cases and occasional cases may have a misleading score using either system. In this study, we assessed 121 cases of blastoid-HGBL (37 BM and 84 extramedullary) to validate the six-point scoring system in all tissue types and to further compare the two scoring systems. Compared with 47 B-ALL cases enriched for CD34-negative neoplasm, the 121 blastoid-HGBL cases showed distinctive pathologic features. The six-point scoring system showed a sensitivity of 100%. A comparison of the two scoring systems in blastoid HGBL (n = 64) and B-ALL (n = 37) showed a concordance score rate of 88%. Thirteen cases showed misleading scores, including five HGBL and eight B-ALL, and the diagnosis was further validated by gene transcriptome profiling. Twelve of thirteen cases had discordant scores between the two scoring systems. Simultaneous employment of both scoring systems improved the accuracy of classification of blastoid B-cell neoplasms to 99%. In conclusion, the previously defined six-point scoring system showed an excellent performance regardless of the tissue origin. Using both scoring systems together improves the accuracy of classification of blastoid B-cell neoplasms. Cases with discordant scores between the two scoring systems were extremely challenging neoplasms and classification required correlation with all available clinical and genetic features.
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Vitamin E is an essential micronutrient for animals. The aim of this study was to determine the effect of vitamin E on intramuscular fat (IMF) deposition and the transcriptome profile of the pectoral muscle in broiler chickens. Arbor Acres chickens were divided into five treatment groups fed a basal diet supplemented with 0, 20, 50, 75, and 100 IU/kg dietary DL-α-tocopheryl acetate (vitamin E), respectively. Body weight, carcass performance, and IMF content were recorded. Transcriptome profiles of the pectoral muscles of 35-day-old chickens in the control and treatment groups (100 IU/kg of vitamin E) were obtained by RNA sequencing. The results showed that diets supplemented with 100 IU/kg of vitamin E significantly increased IMF deposition in chickens on day 35. In total, 159 differentially expressed genes (DEGs), including 57 up-regulated and 102 down-regulated genes, were identified in the treatment (100 IU/kg vitamin E) group compared to the control group. These DEGs were significantly enriched in 13 Gene Ontology terms involved in muscle development and lipid metabolism; three signaling pathways, including the mitogen-activated protein kinase and FoxO signaling pathways, which play key roles in muscular and lipid metabolism; 28 biofunctional categories associated with skeletal and muscular system development; 17 lipid metabolism functional categories; and three lipid metabolism and muscle development-related networks. The DEGs, pathways, functional categories, and networks identified in this study provide new insights into the regulatory roles of vitamin E on IMF deposition in broilers. Therefore, diets supplemented with 100 IU/kg of vitamin E will be more beneficial to broiler production.
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BACKGROUND: As an economically important crop, tea is strongly nitrogen (N)-dependent. However, the physiological and molecular mechanisms underlying the response of N deficiency in tea are not fully understood. Tea cultivar "Chunlv2" [Camellia sinensis (L.) O. Kuntze] were cultured with a nutrient solution with 0 mM [N-deficiency] or 3 mM (Control) NH4NO3 in 6 L pottery pots containing clean river sands. RESULTS: N deficiency significantly decreased N content, dry weight, chlorophyll (Chl) content, L-theanine and the activities of N metabolism-related enzymes, but increased the content of total flavonoids and polyphenols in tea leaves. N deficiency delayed the sprouting time of tea buds. By using the RNA-seq technique and subsequent bioinformatics analysis, 3050 up-regulated and 2688 down-regulated differentially expressed genes (DEGs) were isolated in tea leaves in response to N deficiency. However, only 1025 genes were up-regulated and 744 down-regulated in roots. Gene ontology (GO) term enrichment analysis showed that 205 DEGs in tea leaves were enriched in seven GO terms and 152 DEGs in tea roots were enriched in 11 GO items based on P < 0.05. In tea leaves, most GO-enriched DEGs were involved in chlorophyll a/b binding activities, photosynthetic performance, and transport activities. But most of the DEGs in tea roots were involved in the metabolism of carbohydrates and plant hormones with regard to the GO terms of biological processes. N deficiency significantly increased the expression level of phosphate transporter genes, which indicated that N deficiency might impair phosphorus metabolism in tea leaves. Furthermore, some DEGs, such as probable anion transporter 3 and high-affinity nitrate transporter 2.7, might be of great potential in improving the tolerance of N deficiency in tea plants and further study could work on this area in the future. CONCLUSIONS: Our results indicated N deficiency inhibited the growth of tea plant, which might be due to altered N metabolism and expression levels of DEGs involved in the photosynthetic performance, transport activity and oxidation-reduction processes.
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Camellia sinensis , Camellia sinensis/metabolismo , Clorofila A , Nitrogênio/metabolismo , Chá/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Farmed Atlantic salmon (Salmo salar) welfare and performance can be strongly influenced by stress episodes caused by handling during farming practices. To better understand the changes occurring after an acute stress response, we exposed a group of Atlantic salmon parr to an acute stressor, which involved netting and transferring fish to several new holding tanks. We describe a time-course response to stress by sampling parr in groups before (T0) and 10, 20, 30, 45, 60, 120, 240, 300, and 330 min post-stress. A subgroup of fish was also subjected to the same stressor for a second time to assess their capacity to respond to the same challenge again within a short timeframe (ReStressed). Fish plasma was assessed for adrenocorticotropic hormone (ACTH), cortisol, and ions levels. Mucus cortisol levels were analyzed and compared with the plasma cortisol levels. At 5 selected time points (T0, 60, 90, 120, 240, and ReStressed), we compared the head kidney transcriptome profile of 10 fish per time point. The considerably delayed increase of ACTH in the plasma (60 min post-stress), and the earlier rise of cortisol levels (10 min post-stress), suggests that cortisol release could be triggered by more rapidly responding factors, such as the sympathetic system. This hypothesis may be supported by a high upregulation of several genes involved in synaptic triggering, observed both during the first and the second stress episodes. Furthermore, while the transcriptome profile showed few changes at 60 min post-stress, expression of genes in several immune-related pathways increased markedly with each successive time point, demonstrating the role of the immune system in fish coping capacity. Although many of the genes discussed in this paper are still poorly characterized, this study provides new insights regarding the mechanisms occurring during the stress response of salmon parr and may form the basis for a useful guideline on timing of sampling protocols.
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Salmo salar , Animais , Hidrocortisona , Rim Cefálico , Transcriptoma , Muco , Hormônio AdrenocorticotrópicoRESUMO
To grow in various harsh environments, extremophiles have developed extraordinary strategies such as biofilm formation, which is an extremely complex and progressive process. However, the genetic elements and exact mechanisms underlying extreme biofilm formation remain enigmatic. Here, we characterized the biofilm-forming ability of Deinococcus radiodurans in vitro under extreme environmental conditions and found that extremely high concentrations of NaCl or sorbitol could induce biofilm formation. Meantime, the survival ability of biofilm cells was superior to that of planktonic cells in different extreme conditions, such as hydrogen peroxide stress, sorbitol stress, and high UV radiation. Transcriptome profiles of D. radiodurans in four different biofilm development stages further revealed that only 13 matched genes, which are involved in environmental information processing, carbohydrate metabolism, or stress responses, share sequence homology with genes related to the biofilm formation of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Overall, 64% of the differentially expressed genes are functionally unknown, indicating the specificity of the regulatory network of D. radiodurans. The mutation of the drRRA gene encoding a response regulator strongly impaired biofilm formation ability, implying that DrRRA is an essential component of the biofilm formation of D. radiodurans. Furthermore, transcripts from both the wild type and the drRRA mutant were compared, showing that the expression of drBON1 (Deinococcus radioduransBON domain-containing protein 1) significantly decreased in the drRRA mutant during biofilm development. Further analysis revealed that the drBON1 mutant lacked the ability to form biofilm and DrRRA, and as a facilitator of biofilm formation, could directly stimulate the transcription of the biofilm-related gene drBON1. Overall, our work highlights a molecular mechanism mediated by the response regulator DrRRA for controlling extreme biofilm formation and thus provides guidance for future studies to investigate novel mechanisms that are used by D. radiodurans to adapt to extreme environments.
Assuntos
Deinococcus , Deinococcus/genética , Biofilmes , Agregação Celular , Cognição , Escherichia coli , SorbitolRESUMO
Isaria cicadae is a famous edible and medicinal fungus in China and Asia. The molecular basis of morphogenesis and synnemal formation needs to be understood in more detail because this is the main source of biomass production in I. cicadae. In the present study, a fruiting body formation-related gene with a glycosylphosphatidylinositol (GPI) anchoring protein (GPI-Ap) gene homolog IcFBR1 was identified by screening random insertion mutants. Targeted deletion of IcFBR1 resulted in abnormal formation of synnemata, impairing aerial hyphae growth and sporulation. The IcFBR1 mutants were defective in the utilization of carbon sources with reduced polysaccharide contents and the regulation of amylase and protease activities. Transcriptome analysis of ΔIcfbr1 showed that IcFBR1 deletion influenced 49 gene ontology terms, including 23 biological processes, 9 molecular functions, and 14 cellular components. IcFBR1 is therefore necessary for regulating synnemal development, secondary metabolism, and nutrient utilization in this important edible and medicinal fungus. This is the first report illustrating that the function of IcFBR1 is associated with the synnemata in I. cicadae.
RESUMO
Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.