RESUMO
This study aimed to establish a novel noninvasive model based on the serum N-glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N-glycan profiles of the sera of 295 treatment-naïve CHB patients were analyzed. N-glycan profiles were tested for different liver necroinflammation stages using DNA sequence-assisted fluorophore-assisted carbohydrate electrophoresis. A serum N-glycan model named N-glycan-LI (NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune-tolerant [IT] and inactive-carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune-active, and had the highest SP of 93.94% in grey zone IT + IC. N-glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve-treatment patients with CHB.
Assuntos
Biomarcadores , Hepatite B Crônica , Fígado , Polissacarídeos , Humanos , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Polissacarídeos/sangue , Masculino , Feminino , Adulto , Biomarcadores/sangue , Fígado/patologia , Pessoa de Meia-Idade , Curva ROC , Necrose , Adulto Jovem , Inflamação/sangue , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Excessive lipid deposition in farmed fish is a challenge in the aquaculture industry. To study the effect of dietary calcium pyruvate (CaP) on lipid accumulation in fish, we used a high fat diet (HFD) to establish a lipid accumulation model in juvenile golden pompano (Trachinotus ovatus) and supplemented with 0%, 0.25%, 0.50%, 0.75% and 1.0% CaP (diets D0-D4, respectively). After 8-week feeding in floating cages, dietary CaP significantly improved growth performance, which peaked in fish fed diet D3. Supplementation of CaP significantly decreased whole body lipid content in fish fed D2-D4 and hepatosomatic index and liver lipid content in fish fed D3 and D4. Serum and hepatic antioxidant indices, including glutathione, catalase and superoxide dismutase, showed generally increasing trends in fish fed diets with CaP. In addition, increasing dietary CaP increasingly reduced hepatic activities of hexokinase, phosphofructokinase and pyruvate kinase involved in glycolysis, and increased glycogen contents of the liver and muscle. Dietary CaP up-regulated the liver mRNA expression of pparα, cpt1, hsl and fabp1, but down-regulated expression of srebp-1, fas and acc. In conclusion, 0.75% CaP improved growth performance and reduced excessive lipid deposition by affecting fatty acid synthesis and lipolysis in juvenile T. ovatus fed HFD.
Assuntos
Dieta Hiperlipídica , Perciformes , Ração Animal/análise , Animais , Cálcio da Dieta/metabolismo , Cálcio da Dieta/farmacologia , Dieta , Suplementos Nutricionais , Peixes , Metabolismo dos Lipídeos , Lipídeos/farmacologia , Fígado/metabolismo , Perciformes/metabolismo , Ácido Pirúvico/metabolismo , Ácido Pirúvico/farmacologiaRESUMO
MicroRNAs have been recently shown to be important regulators of lipid metabolism. However, the mechanisms of microRNA-mediated regulation of long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis in vertebrates remain largely unknown. Herein, we for the first time addressed the role of miR-26a in LC-PUFA biosynthesis in the marine rabbitfish Siganus canaliculatus The results showed that miR-26a was significantly down-regulated in liver of rabbitfish reared in brackish water and in S. canaliculatus hepatocyte line (SCHL) incubated with the LC-PUFA precursor α-linolenic acid, suggesting that miR-26a may be involved in LC-PUFA biosynthesis because of its abundance being regulated by factors affecting LC-PUFA biosynthesis. Opposite patterns were observed in the expression of liver X receptor α (lxrα) and sterol regulatory element-binding protein-1 (srebp1), as well as the LC-PUFA biosynthesis-related genes (Δ4 fads2, Δ6Δ5 fads2, and elovl5) in SCHL cells incubated with α-linolenic acid. Luciferase reporter assays revealed rabbitfish lxrα as a target of miR-26a, and overexpression of miR-26a in SCHL cells markedly reduced protein levels of Lxrα, Srebp1, and Δ6Δ5 Fads2 induced by the agonist T0901317. Moreover, increasing endogenous Lxrα by knockdown of miR-26a facilitated Srebp1 activation and concomitant increased expression of genes involved in LC-PUFA biosynthesis and consequently promoted LC-PUFA biosynthesis both in vitro and in vivo These results indicate a critical role of miR-26a in regulating LC-PUFA biosynthesis through targeting the Lxrα-Srebp1 pathway and provide new insights into the regulatory network controlling LC-PUFA biosynthesis and accumulation in vertebrates.
Assuntos
Ácidos Graxos Insaturados/biossíntese , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Receptores X do Fígado/metabolismo , MicroRNAs/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Linhagem Celular , Ácidos Graxos Insaturados/genética , Proteínas de Peixes/genética , Peixes/genética , Hepatócitos/metabolismo , Receptores X do Fígado/genética , MicroRNAs/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Anderson-type polyoxometalate containing Fe3+ and Mo6+, (NH4)3[H6Fe(III)Mo6O24] (FeMo6), was found to work as an oxidase-mimicking nanoenzyme for the first time, exhibiting the ability of catalytic oxidation of o-phenylenediamine (OPD), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTs), and 3,3',5,5'-tetramethylbenzidine (TMB), which features easy synthesis, low cost, simple operation, and low consumption. Attributed to the nature of FeMo6 and Fenton-like effect, a novel sensor based on two consecutive "turn on" fluorescence was developed for detecting dopamine (DA) by employing the FeMo6-OPD system, and the linear range was from 1 to 100 µM with the detection limit 0.0227 µM (3σ/s). Moreover, to increase oxidase-mimic activity of FeMo6, reduced graphene oxide (rGO) loading FeMo6 composites (FeMo6@rGO (n), n = 5%, 10%, 15%) was fabricated, and results show that oxidase-like activities of FeMo6@rGO (n) are dependent on the mass ratio of FeMo6/rGO, and FeMo6@rGO (10%) exhibits the highest oxidase-mimic activity and the fastest respond time (4 min) among all reported oxidase mimic of DA to date. Graphical abstract Anderson-type Mo-POMs FeMo6 was found to work as an oxidase-mimicking nanoenzyme for the first time and was used to detect DA for two consecutive "turn on" fluorescence sensor modes.
Assuntos
Ânions/química , Dopamina/sangue , Polieletrólitos/química , Materiais Biomiméticos/química , Dopamina/análise , Grafite/química , Humanos , Ferro/química , Molibdênio/química , Oxirredução , Oxirredutases/química , Espectrometria de Fluorescência/métodosRESUMO
OBJECTIVE: This study aimed to investigate the association between different metastatic sites and survival in endometrial cancer (EC) patients with International Federation of Gynecology and Obstetrics (FIGO) stage IVB disease. METHODS: FIGO stage IVB patients with EC were selected from the surveillance, epidemiology, and end results database. Overall survival (OS) and cause-specific survival (CSS) were analyzed with Kaplan-Meier analysis and log-rank tests. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors for OS and CSS. RESULTS: A total of 929 FIGO stage IVB patients with EC were identified. Patients with peritoneum metastasis were associated with significantly better OS and CSS compared to those with organ-specific metastasis (median OS: 29 vs 19 months, P = .005; median CSS: 47 vs 25 months, P < .001). Moreover, the survival superiority of peritoneum metastasis remained significant when organ-specific metastasis was further classified into specific single-organ metastasis. The multivariate analysis also indicated that compared with peritoneum metastasis, bone, brain, and lung metastasis were independent prognostic factors for worse OS. Similarly, distant lymph node, bone, brain, liver, and lung metastasis were associated with worse CSS. CONCLUSION: Metastatic sites affected prognosis in FIGO stage IVB patients with EC. Patients with peritoneum metastasis had significantly better survival outcomes than those with organ-specific metastasis.
Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
To compare the growth and biosynthetic ability of long-chain PUFA (LC-PUFA) of the genetically improved farmed tilapia (GIFT) (Oreochromis niloticus) in different water salinities, an 8-week feeding trial was conducted on the GIFT juveniles at 0, 12 and 24 (parts per thousand; ppt), respectively, with three isonitrogenous (32 %) and isolipidic (8 %) diets (D1-D3). Diet D1 with fish oils (rich in LC-PUFA) as lipid source was used as the control, while D2 and D3 with vegetable oil (free LC-PUFA) blends as lipid source contained different ratios of linoleic acid (LA, 18 : 2n-6) and α-linolenic acid (ALA, 18 : 3n-3) at 4·04 (D2) and 0·54 (D3), respectively. At the end of feeding trial, the growth performance of D2 and D3 groups under all salinity treatments was as good as that of D1 group, which indicates that the GIFT juveniles may convert dietary LA and ALA into LC-PUFA to meet the requirement of essential fatty acids for normal growth and physiology. When fed the same diets, GIFT at 12 ppt had a better growth performance coupled with a higher liver and muscle arachidonic acid content than those in freshwater. Furthermore, brackish water (24 ppt) significantly promoted the mRNA levels of elongase 5 of very long-chain fatty acids (elovl5) and peroxisome proliferator-activated receptor α (pparα) in liver, when compared with freshwater. These results suggest that the GIFT may display better growth performance together with a relatively higher endogenous LC-PUFA biosynthetic ability under brackish water (12 and 24 ppt), probably through improving the expression of elovl5 and pparα in liver.
Assuntos
Aquicultura/métodos , Dieta/métodos , Ácidos Graxos Insaturados/biossíntese , Salinidade , Tilápia/crescimento & desenvolvimento , Ração Animal/análise , Animais , Animais Geneticamente Modificados , Elongases de Ácidos Graxos/metabolismo , Óleos de Peixe/administração & dosagem , Fígado/metabolismo , PPAR alfa/metabolismo , Óleos de Plantas/administração & dosagem , Tilápia/genéticaRESUMO
The rabbitfish Siganus canaliculatus is the first marine teleost shown to be able to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors catalyzed by two fatty acyl desaturases (fad) including Δ4 Fad and Δ6/Δ5 Fad as well as two elongases (Elovl4 and Elovl5). Previously, hepatocyte nuclear factor 4α (Hnf4α) was demonstrated to be predominant in the transcriptional regulation of two fads. To clarify the regulatory mechanisms involved in rabbitfish lipogenesis, the present study focused on the regulatory role of Hnf4α to elovl5 expression and LC-PUFA biosynthesis. Bioinformatics analysis predicted two potential Hnf4α elements in elovl5 promoter, one binding site was confirmed to interact with Hnf4α by gel shift assays. Moreover, overexpression of hnf4α caused a remarkable increase both in elovl5 promoter activity and mRNA contents, while knock-down of hnf4α in S. canaliculatus hepatocyte line (SCHL) resulted in a significant decrease of elovl5 gene expression. Meanwhile, hnf4α overexpression enhanced LC-PUFA biosynthesis in SCHL cell, and intraperitoneal injection to rabbitfish juveniles with Hnf4α agonists (Alverine and Benfluorex) increased the expression of hnf4α, elvol5 and Δ4 fad, coupled with an increased proportion of total LC-PUFA in liver. The results demonstrated that Hnf4α is involved in LC-PUFA biosynthesis by up-regulating the transcription of the elovl5 gene in rabbitfish, which is the first report of Hnf4α as a transcription factor of the elovl5 gene in vertebrates.
Assuntos
Acetiltransferases/genética , Ácidos Graxos Insaturados/biossíntese , Peixes/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Transcrição Gênica , Regulação para Cima/genética , Região 5'-Flanqueadora/genética , Acetiltransferases/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Ácidos Graxos Dessaturases/metabolismo , Técnicas de Silenciamento de Genes , Fator 4 Nuclear de Hepatócito/agonistas , Injeções Intraperitoneais , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Evaluation of liver fibrosis played a monumental role in the diagnosis and monitoring of chronic hepatitis B (CHB). We aimed to explore the value of serum N-glycan markers in liver fibrosis. METHODS: This multi-center (33 hospitals) study recruited 760 treatment-naïve CHB patients who underwent liver biopsy. Serum N-glycan markers were analyzed by DNA sequencer-assisted fluorophore-assisted with capillary electrophoresis (DSA-FACE) technology. First, we explore the relationship between 12 serum N-glycan markers and the fibrosis stage. Then, we developed a Px score for diagnosing significant fibrosis using the LASSO regression. Next, we compared the diagnostic performances between Px, LSM, APRI, and FIB-4. Finally, we explored the relationships between glycosyltransferase gene and liver fibrosis with RNA-transcriptome sequencing. RESULTS: We included 622 CHB participants: male-dominated (69.6%); median age 42.0 (IQR 34.0-50.0); 287 with normal ALT; 73.0% with significant fibrosis. P5(NA2), P8(NA3), and P10(NA4) were opposite to the degree of fibrosis, while other profiles (except for P0[NGA2]) increased with the degree of fibrosis. Seven profiles (P1[NGA2F], P2[NGA2FB], P3[NG1A2F], P4[NG1A2F], P7[NA2FB], P8[NA3], and P9[NA3Fb]) were selected into Px score. Px score was associated with an increased risk of significant fibrosis (for per Px score increase, the risk of significant fibrosis was increased by 3.54 times (OR = 4.54 [2.63-7.82]) in the fully-adjusted generalized linear model. p for trend was <0.001. The diagnostic performance of the Px score was superior to others. Glycosyltransferase genes were overexpressed in liver fibrosis, and glycosylation and glycosyltransferase-related pathways were significantly enriched. CONCLUSIONS: Serum N-glycan markers were positively correlated with liver fibrosis. Px score had good performance in distinguishing significant fibrosis.
RESUMO
Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.
RESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. AIM: To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. METHODS: An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". RESULTS: The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. CONCLUSION: In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.
RESUMO
Dendrobium findlayanum Par. et Rchb. f. 1874 has the high ornamental and medicinal value. Here, we report the first complete chloroplast genome of D. findlayanum. The complete chloroplast genome of D. findlayanum is 153,713 bp in length with 120 genes, including 75 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The total content of GC of the whole genome is 37.46%. Phylogenetic analysis indicated that D. findlayanum was closely related to other species in Dendrobium, and this study provides new genetic resources for species identification and phylogenetic analyses in Dendrobium.
RESUMO
Objective: To explore the effect of hospital-family rehabilitation intervention on walking function and lower limb surface electromyography in children with cerebral palsy (CP). Methods: About 100 children with CP treated in our hospital from February 2019 to April 2021 were enrolled. The patients were randomly assigned into control group and study group. The control group received routine intervention, and the study group received hospital-family rehabilitation intervention. The intervention effect, GMFM88 scale score, IMMG value, CR value, lower limb surface EMG value, and compliance of gastrocnemius muscle and tibialis anterior muscle were compared. Results: First of all, we compared the intervention effects. In the study group, 43 cases were markedly effective, 5 cases were effective, 1 case was improved, 1 case was ineffective, and the effective rate was 98.00%. In the control group, 22 cases were markedly effective, 14 cases were effective, 7 cases were improved, 7 cases were ineffective, and the effective rate of 86.00%. The intervention effect of the study group was better compared to the control group (P < 0.05). Secondly, we compared the scores of the GMFM88 scale. The scores of D area and E area and total score of the study group were higher compared to the control group (P < 0.05). The IEMG values of gastrocnemius muscle and tibialis anterior muscle were compared, and the IMMG values of passive and active gastrocnemius muscle and tibialis anterior muscle in the study group were higher compared to the control group (P < 0.05). There exhibited no significant difference in CR value before intervention (P > 0.05). After intervention, the CR values of gastrocnemius muscle and tibialis anterior muscle in the study group were significantly lower compared to the control group (P < 0.05). In terms of the surface EMG of lower limbs, the EMG value of passive activity (gastrocnemius muscle, tibialis anterior muscle) in the study group was higher compared to the control group, and the EMG value of active activity was significantly lower compared to the control group (P < 0.05). Finally, we compared the compliance. In the study group, there were 43 cases of complete compliance, 7 cases of compliance, and 0 cases of noncompliance, with a compliance rate of 100.00%. In the control group, there were 32 cases of complete compliance, 11 cases of compliance, and 7 cases of noncompliance with a compliance rate of 86.00%. The compliance rate of the study group was better compared to the control group (P < 0.05). Conclusion: The intervention of hospital-family rehabilitation model is helpful to improve the self-care ability, cognitive function, and daily activities of children with CP, enhance the walking function and lower limb surface electromyography of children with SCP, and strengthen their qualities of life.
Assuntos
Paralisia Cerebral , Paralisia Cerebral/terapia , Criança , Eletromiografia , Hospitais , Humanos , Extremidade Inferior , Músculo Esquelético , Caminhada/fisiologiaRESUMO
Insulin is well known an important metabolic regulator in glucose and lipid metabolism. It has been proved to activate long-chain (≥ C20) polyunsaturated fatty acids (LC-PUFA) biosynthesis in mammals, but little is known about such a role in fish. To explore the effects and molecular mechanisms of insulin in fish LC-PUFA biosynthesis, we treated the rabbitfish S. canaliculatus hepatocyte line (SCHL) cells with 65 nM insulin for 12 h, and the results showed that the mRNA levels of genes encoding the key enzymes and transcription factor involved in rabbitfish LC-PUFA biosynthesis such as Δ6Δ5 fads2, elovl5 and srebp1, as well as those of PI3K pathway genes including pdk1, akt2 and mtor increased significantly. Moreover, SCHL cells treated with different PI3K/Akt pathway inhibitors (LY294002, Wortmannin, AKTi-1/2) alone or combined with insulin decreased the mRNA levels of PI3K/Akt/mTOR downstream signaling genes, including Δ6Δ5 fads2, Δ4 fads2, elovl5, elovl4 and srebp1. While PI3K/Akt agonists (740 Y-P, IGF-1, SC-79) had the opposite results. The results of fatty acid composition analysis of hepatocytes showed that insulin stimulation increased the Δ6Δ5 Fads2-dependent PUFA desaturation indexes, while Elovl5-dependent PUFA elongation indexes had upward trends, and consequently LC-PUFA contents increased. Taken together, these results indicated that insulin activated LC-PUFA biosynthesis probably through PI3K/Akt/mTOR/Srebp1 pathway in S. canaliculatus hepatocytes.
Assuntos
Proteínas de Peixes , Fosfatidilinositol 3-Quinases , Animais , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Hepatócitos/metabolismo , Insulina/metabolismo , Mamíferos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Background: Alkuraya-Kucinskas syndrome is an autosomal recessive disorder characterized by brain abnormalities associated with cerebral parenchymal underdevelopment, arthrogryposis, club foot, and global developmental delay. Most reported cases were cases of premature termination of pregnancies or neonatal deaths. To date, limited studies of nine surviving patients with global developmental delay and intellectual disability have been reported. In this study, we report another surviving patient. Methods: Whole-exome sequencing was utilized for the proband, and variants were filtered, annotated, and classified. Candidate variants were validated by Sanger sequencing of the proband and his family. The literature was reviewed; the prognosis among different regions and the variant type was analyzed. Results: A non-synonymous variant [NM_015312.3: exon29: c.4892C>G (p.Pro1631Arg)] was identified and validated in the patient's father. A frameshift duplication [NM_015312.3: exon62: c.10872dupA (p.Arg3625Lysfs*5)] that caused early translation termination was identified in his mother. The literature was reviewed, variants were classified into three regions of KIAA1109, and their survival status was summarized. Conclusion: We reported another survival proband with Alkuraya-Kucinskas syndrome driven by KIAA1109. Our case expands the genotypic spectrum of Alkuraya-Kucinskas syndrome and explored the relationship between the variant region and survival.
RESUMO
Marek's disease virus (MDV), one of the most potent oncogenic herpesviruses, leads to highly contagious immunosuppressive and neoplastic disease in susceptible chickens. Previous studies mainly focused on the roles of host genes modulated by MDV in the virological rather than the neoplastic stage of disease. To investigate the molecular mechanisms of tumorigenesis in Marek's disease further, a microarray analysis with Affymetrix Gene-Chip Chicken Genome Arrays was performed in a non-lymphoid tissue liver during the neoplastic stage. Of the 32â773 chicken transcriptions arrayed on a chip, 269 genes were significantly differentially expressed during the neoplastic stage caused by MDV infection (upregulated, 175; downregulated, 94). The altered genomic expression of 15 randomly selected genes was confirmed by real-time RT-PCR. Biological functions and pathways of the group of 269 differentially expressed genes were analysed by using a bioinformatics tool (ipa, Ingenuity Pathway Analysis). The results revealed that 19 possible gene networks with intermolecular connections and 22 significant metabolic and signalling pathways (P≤0.05) among 137 differentially expressed genes. These 137 genes were classified into a number of functional groups that included genetic disorder, cancer, cellular growth and proliferation, and cell death. In summary, the investigation of global host-gene expression, providing the biological functions of differentially expressed genes in lymphoid tumours of the liver in response to MDV infections, may contribute to a basic understanding of the molecular mechanisms involved in tumorigenesis following MDV infection.
Assuntos
Galinhas/genética , Perfilação da Expressão Gênica/métodos , Herpesvirus Galináceo 2/patogenicidade , Doença de Marek/genética , Vírus Oncogênicos/patogenicidade , Animais , Galinhas/virologia , Biologia Computacional , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Fígado/patologia , Fígado/virologia , Doença de Marek/patologia , Doença de Marek/virologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: The swine influenza (SI) is an infectious disease of swine and human. The novel swine-origin influenza A (H1N1) that emerged from April 2009 in Mexico spread rapidly and caused a human pandemic globally. To determine whether the tremendous virus had existed in or transmitted to pigs in southern China, eight H1N1 influenza strains were identified from pigs of Guangdong province during 2008-2009. RESULTS: Based on the homology and phylogenetic analyses of the nucleotide sequences of each gene segments, the isolates were confirmed to belong to the classical SI group, with HA, NP and NS most similar to 2009 human-like H1N1 influenza virus lineages. All of the eight strains were low pathogenic influenza viruses, had the same host range, and not sensitive to class of antiviral drugs. CONCLUSIONS: This study provides the evidence that there is no 2009 H1N1-like virus emerged in southern China, but the importance of swine influenza virus surveillance in China should be given a high priority.
Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Pandemias , Doenças dos Suínos/virologia , Animais , China/epidemiologia , Genômica , Especificidade de Hospedeiro , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/fisiologia , Dados de Sequência Molecular , Infecções por Orthomyxoviridae/virologia , Filogenia , Suínos , Proteínas Virais/genéticaRESUMO
BACKGROUND: protein glycosylation varies with the physiological and pathological status of the cell. Consequently, analysis of protein-linked glycans has growing importance both in basic glycobiological research and as a potential tool for monitoring the physiological state in humans. DESIGN, SETTING AND PARTICIPANTS: a total of 265 healthy northern Chinese men and women were grouped by age and gender. The mean age in males and females was similar. OBJECTIVE: the study is aimed to evaluate the effects of the age and gender on the human serum N-glycans profiles in the clinical diagnose of ageing and disease. METHODS: the 265 human serum N-glycan profiles were obtained by DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis. Comparison of N-glycan profiles was carried out among the different genders and age groups and the data were analysed with the GeneMapper software. RESULTS: age-related changes in the three N-glycan structures (NGA2F, NGA2FB and NA2F) were observed. Interestingly, fucosylation of N-glycans was significantly different (P < 0.0001) between men and women: more core-α-1,6-fucosylated glycans were detected in women, whereas more branching-α-1,3-fucosylated N-glycans were seen in men. CONCLUSIONS: the N-glycome profile in serum is gender and age dependent. This should be taken into consideration in the development of serum glycome markers.
Assuntos
Envelhecimento/sangue , Polissacarídeos/sangue , Processamento de Proteína Pós-Traducional , Acetilglucosamina/sangue , Adulto , Distribuição por Idade , Fatores Etários , Biomarcadores/sangue , China , Eletroforese , Feminino , Fucose/sangue , Glicômica/métodos , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Fatores SexuaisRESUMO
Microbiologically influenced corrosion (MIC) is one of the reasons leading to the service failure of pipelines buried in the soil. The effects of sulfate-reducing bacteria (SRB) on steel corrosion without organic carbon are not clear. In this work, SRB cells were enriched in the simulated soil solution, aiming to study SRB corrosion behavior without organic carbon source using weight loss, electrochemical measurements, and surface analysis. Effects of DO on SRB corrosion were also studied. Results indicate that SRB can survive after 14 days of incubation without organic carbon source, but approximately 90% SRB have died. SRB without organic carbon source could inhibit the uniform corrosion but enhance the pitting corrosion compared with the control specimen. The corrosion rate of the control calculated from weight loss is highest with a value of (0.081 ± 0.013) mm/y. The highest localized corrosion rate of (0.306 ± 0.006) mm/y is obtained with an initial SRB count of 107 cells/mL. The presence of DO influences the steel corrosion process. Oxygen corrosion dominates for the specimens in the absence and presence of SRB with an initial count of 103 cells/mL, while SRB MIC is primary for the specimens with high SRB counts.
Assuntos
Desulfovibrio desulfuricans/metabolismo , Microbiologia do Solo , Solo/química , Aço/química , Contagem de Colônia Microbiana , Corrosão , Espectroscopia Dielétrica , Microscopia Eletrônica de Varredura , Oxigênio/metabolismo , Sulfatos/metabolismo , Propriedades de SuperfícieRESUMO
Omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA, C20-24), including eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), are involved in numerous biological processes and have a range of health benefits. Fish have long been considered as the main source of n-3 LC-PUFA in human diets. However, the capacity for endogenous biosynthesis of LC-PUFA from C18 PUFA varies in fish species based on the presence, expression and activity of key enzymes including fatty acyl desaturases (Fads) and elongation of very long-chain fatty acids (Elovl) proteins. In this article, we review progress on the identified Fads and Elovl, as well as the regulatory mechanisms of LC-PUFA biosynthesis both at transcriptional and post-transcriptional levels in teleosts. The most comprehensive advances have been obtained in rabbitfish Siganus canaliculatus, a marine teleost demonstrated to have the entire pathway for LC-PUFA biosynthesis, including the roles of transcription factors hepatocyte nuclear factor 4α (Hnf4α), liver X receptor alpha (Lxrα), sterol regulatory element-binding protein 1 (Srebp-1), peroxisome proliferator-activated receptor gamma (Pparγ) and stimulatory protein 1 (Sp1), as well as post-transcriptional regulation by individual microRNA (miRNA) or clusters. This research has, for the first time, demonstrated the involvement of Hnf4α, Pparγ and miRNA in the regulation of LC-PUFA biosynthesis in vertebrates. The present review provides readers with a relatively comprehensive overview of the progress made into understanding LC-PUFA biosynthetic systems in teleosts, and some insights into improving endogenous LC-PUFA biosynthesis capacity aimed at reducing the dependence of aquafeeds on fish oil while maintaining or increasing flesh LC-PUFA content and the nutritional quality of farmed fish.
Assuntos
Ácidos Graxos Ômega-3 , MicroRNAs , Animais , Ácidos Graxos Dessaturases/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Peixes , Regulação da Expressão Gênica , HumanosRESUMO
BACKGROUND: There is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model. RESULTS: Rat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory.In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p < 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. CONCLUSIONS: We found an increase in core-alpha-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.