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SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.
Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.
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Animales , Masculino , Ratas , Extractos Vegetales/administración & dosificación , ATPasa Intercambiadora de Sodio-Potasio/efectos de los fármacos , Nefropatías Diabéticas/tratamiento farmacológico , Acacia/química , Superóxido Dismutasa , Hemoglobina Glucada/análisis , Extractos Vegetales/farmacología , Expresión Génica , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/genética , Estrés Oxidativo , Microscopía Electrónica de Transmisión , Modelos Animales de Enfermedad , Quimioterapia Combinada , Control Glucémico , Insulina/administración & dosificación , Riñón/efectos de los fármacos , MalondialdehídoRESUMEN
PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.
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Ratas , Animales , Lesión Pulmonar/genética , Cabras/genética , Queratina-4 , Perfilación de la Expresión Génica , Expresión GénicaRESUMEN
Recent scientific evidence suggests a close relationship between estrogen deficiency and vitamin D- related genes. Estrogen and vitamin D were involved with alterations in odontogenesis and tooth eruption process. Objective: The aim of the present study was to evaluate the influence of estrogen deficiency on the expression of genes related to the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model. Material and Methods: This is an experimental clinical study that used female Wistar Hannover rats. The animals were randomly divided into two groups according to the intervention received: Hypoestrogenism Group animals submitted to estrogen deficiency by ovariectomy surgery and Control Group animals submitted to sham surgery. Surgical intervention was performed in the prepubertal period; the animals were followed throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the mRNA expression of the vitamin D-related genes AMDHD1, CYP24A1, NADSYN1 and SEC23A in the odontogenic region of incisors through real time PCR. Student's t test was used to compare means. Kruskal-Wallis test and Dunn's posttest were also used. The level of significance was 5%. Results: SEC23A was overexpressed in the estrogen deficiency condition in the odontogenic region (p=0.021). Conclusion: Estrogen deficiency may influence the expression of the SEC23A gene involved in the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model(AU)
Evidências científicas recentes sugerem uma estreita relação entre a deficiência de estrógeno e os genes relacionados à vitamina D. O estrógeno e a vitamina D estão envolvidos com alterações na odontogênese e no processo de erupção dentária. Objetivo: O objetivo do presente estudo foi avaliar a influência da deficiência de estrógeno na expressão de genes relacionados à ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino. Material e Métodos: Trata-se de um estudo clínico experimental que utilizou ratas Wistar Hannover fêmeas. Os animais foram divididos aleatoriamente em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo animais submetidos à deficiência de estrógeno pela cirurgia de ovariectomia e Grupo Controle animais submetidos à cirurgia simulada. A intervenção cirúrgica foi realizada no período pré-púbere; os animais foram acompanhados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão de mRNA dos genes AMDHD1, CYP24A1, NADSYN1 e SEC23A, relacionados à vitamina D, na região odontogênica de incisivos por meio de PCR em tempo real. O teste t de Student foi utilizado para comparar as médias. Também foram utilizados o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: SEC23A foi superexpresso na condição de deficiência de estrógeno na região odontogênica (p=0,021). Conclusão: A deficiência de estrógeno pode influenciar a expressão do gene SEC23A envolvido na ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino (AU)
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Animales , Femenino , Ratas , Vitamina D , Expresión Génica , Estrógenos , OdontogénesisRESUMEN
SUMMARY: Obesity is commonly associated with chronic tissue inflammation and skeletal muscle dysfunction. The study aimed to investigate the effects of High-Intensity Interval training (HIIT) on myokines and endoplasmic reticulum (ER) stress of diet- induced obese (DIO) mice. Three-month-old C57BL/6 male mice were fed a control (C) diet (n=20) or a high-fat (HF) diet (n=20) for 16 weeks. Then, half of the groups underwent HIIT (treadmill running) for an additional four weeks. HIIT increased calf muscles' contribution to BW (+24 %) and reduced weight gain in HF/HIIT than in HF (-120 %). Intramuscular fat accumulation was observed in HF and HF/ HIIT. Peak velocity was higher in HF/HIIT compared to HF (+26 %). Plasma insulin did not change, but glycemia was lower in HF/HIIT than in HF (-30 %). Fndc5 (+418 %) and Irisin (+72 %) were higher in HF/HIIT than in HF. Muscle Fgf21 was higher in HF/HIIT compared to HF (+30 %). In addition, NfKb (-53 %) and Tnfa (-63 %) were lower in HF/HIIT than in HF. However, Il1b (-86 %), Il6 (- 48 %), Il7 (-76 %), and Il15 (-21 %) were lower in HF/HIIT than in HF. Finally, HIIT reduced ER stress in HF/HIIT compared to HF: Atf4, -61 %; Chop, -61 %; Gadd45, -95 %. In conclusion, HIIT leads to weight loss and avoids muscle depletion. HIIT improves blood glucose, Irisin-Fndc5, and peak velocity. In addition, HIIT mitigates muscle inflammation and ER stress.
La obesidad es asociada comúnmente con inflamación tisular crónica y disfunción del músculo esquelético. El estudio tuvo como objetivo investigar los efectos del entrenamiento de intervalos de alta intensidad (HIIT) en las mioquinas y el estrés del retículo endoplásmico (ER) de ratones obesos inducidos por dieta (DIO). Se alimentó a ratones macho C57BL/6 de tres meses de edad con una dieta control (C) (n=20) o una dieta rica en grasas (HF) (n=20) durante 16 semanas. Luego, la mitad de los grupos se sometieron a HIIT (carrera en una trotadora) durante cuatro semanas más. HIIT aumentó la contribución de los músculos de la pantorrilla al BW (+24 %) y redujo el aumento de peso en HF/HIIT en HF (-120 %). Se observó acumulación de grasa intramuscular en HF y HF/HIIT. La velocidad máxima fue mayor en HF/HIIT en comparación con HF (+26 %). La insulina plasmática no cambió, pero la glucemia fue menor en HF/HIIT que en HF (-30 %). Fndc5 (+418 %) e Irisin (+72 %) fueron mayores en HF/HIIT que en HF. El Fgf21 muscular fue mayor en HF/ HIIT en comparación con HF (+30 %). Además, NfKb (-53 %) y Tnfa (-63 %) fueron menores en HF/HIIT que en HF. Sin embar- go, Il1b (-86 %), Il6 (-48 %), Il7 (-76 %) e Il15 (-21 %) fueron más bajos en HF/HIIT que en HF. Finalmente, HIIT redujo el estrés de RE en HF/HIIT en comparación con HF: Atf4, -61 %; Picar, - 61 %; Gadd45, -95 %. En conclusión, HIIT conduce a la pérdida de peso y evita el agotamiento muscular. HIIT mejora la glucosa en sangre, Irisin-Fndc5 y la velocidad máxima. Además, HIIT mitiga la inflamación muscular y el estrés ER.
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Animales , Masculino , Ratones , Citocinas/fisiología , Músculo Esquelético/fisiología , Estrés del Retículo Endoplásmico/fisiología , Entrenamiento de Intervalos de Alta Intensidad , Obesidad , Expresión Génica , Inflamación , Ratones Endogámicos C57BL , Biología MolecularRESUMEN
INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.
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Neoplasias Gástricas/diagnóstico , Biomarcadores de Tumor , Biología Computacional , Pronóstico , Simulación por Computador , Expresión Génica , Análisis de Matrices TisularesRESUMEN
OBJECTIVE@#Here, we explored molecular changes that could potentially mediate healing effects of Gua Sha - a method employed by the Chinese traditional medicine with proven track records of safe and efficient applications dating back to ancient times as well as support from randomized controlled trials performed by modern medical studies - yet remaining almost entirely unexplored by the modern-day high-throughput methods of the -omics sciences.@*METHODS@#We investigated transcriptome changes occurring shortly after Gua Sha treatment in the whole blood of healthy volunteers using bulk RNA-seq analysis. We applied various analytical tools to identify genes with consistent expression changes in multiple individuals in response to Gua Sha and their networks.@*RESULTS@#We found that while the changes were very subtle and individual-specific, we could identify consistent upregulation of three histone genes. Further analysis of the potential regulatory networks of these histone genes revealed the enrichment of functions involved in the immune response and inflammation.@*CONCLUSION@#The significance of these results in the context of potential effects of Gua Sha and the next steps in exploring the molecular mechanisms of action of this technique are discussed.
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Humanos , Medicina Tradicional China/métodos , Histonas , Expresión GénicaRESUMEN
Deacetylation of chitin is closely related to insect development and metamorphosis. Chitin deacetylase (CDA) is a key enzyme in the process. However, to date, the CDAs of Bombyx mori (BmCDAs), which is a model Lepidopteran insect, were not well studied. In order to better understand the role of BmCDAs in the metamorphosis and development of silkworm, the BmCDA2 which is highly expressed in epidermis was selected to study by bioinformatics methods, protein expression purification and immunofluorescence localization. The results showed that the two mRNA splicing forms of BmCDA2, namely BmCDA2a and BmCDA2b, were highly expressed in the larval and pupal epidermis, respectively. Both genes had chitin deacetylase catalytic domain, chitin binding domain and low density lipoprotein receptor domain. Western blot showed that the BmCDA2 protein was mainly expressed in the epidermis. Moreover, fluorescence immunolocalization showed that BmCDA2 protein gradually increased and accumulated with the formation of larval new epidermis, suggesting that BmCDA2 may be involved in the formation or assembly of larval new epidermis. The results increased our understandings to the biological functions of BmCDAs, and may facilitate the CDA study of other insects.
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Animales , Bombyx/metabolismo , Metamorfosis Biológica/genética , Larva/metabolismo , Expresión Génica , Proteínas de Insectos/metabolismo , QuitinaRESUMEN
Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes, and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis, protein-protein interaction (PPI) network, and survival analysis based on the Gene Expression Omnibus (GEO) database.Methods By screening with highly expressed genes, we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis, PPI network, and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.
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Humanos , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Molécula de Adhesión Celular Epitelial/metabolismo , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Objective: To investigate the expression change of the Mas1 receptor in the placenta of healthy pregnant women during different gestation periods, analyze the expression level of the Mas1 receptor in the placenta of pre-eclampsia (PE) patients, and its biological function in trophoblast cells. Methods: Placental villous tissues were collected from normal pregnant women in early, mid and late pregnancy. Human trophoblast stem cells were isolated and cultured from early pregnancy villous tissues. The expression of the Mas1 receptor was detected by fluorescence immunoassay and real-time fluorescence quantitative PCR. In a case-control study, patients with full-term PE were selected as the case group and healthy women with full-term pregnancy were selected as the control group. Placental villus tissues were collected from both groups. Immunofluorescence chemistry and immunoprotein blotting were used to study the changes in Mas1 receptor expression in PE. Mas1 receptor agonists and blockers induced HTR8/Svneo cells and BeWo cells, and the effects of the Mas1 receptor on the proliferation and migration of trophoblast cells were detected by the CCK8 proliferation test and scratch test. Results: Eight cases were included in early pregnancy, seven cases in mid-pregnancy and six cases in late pregnancy. Mas1 receptors in normal placental villi tissue were mainly expressed in human trophoblast stem cell membranes and cytoplasm, and the expression of Mas1 receptor mRNA in villi tissue was significantly higher in late pregnancy than in mid-pregnancy. There were 24 cases included in the case group and 12 cases in the control group. Mas1 receptor expression in placental villi was significantly lower in the case group compared to the control group; Activation/inhibition of the Mas1 receptor had no significant effect on the proliferation of HTR8/Svneo cells and BeWo cells. Activated Mas1 receptor had no significant effect on the migration ability of HTR8/Svneo cells. Conclusion: Mas1 receptors are expressed in placental villous tissue and their expression varies with gestation. Mas1 receptor expression is reduced in PE patients, but it does not affect the value-added or migratory function of trophoblast cells.
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Humanos , Femenino , Embarazo , Placenta , Trofoblastos , Estudios de Casos y Controles , Preeclampsia , Expresión GénicaRESUMEN
Objective: To investigate the expression change of the Mas1 receptor in the placenta of healthy pregnant women during different gestation periods, analyze the expression level of the Mas1 receptor in the placenta of pre-eclampsia (PE) patients, and its biological function in trophoblast cells. Methods: Placental villous tissues were collected from normal pregnant women in early, mid and late pregnancy. Human trophoblast stem cells were isolated and cultured from early pregnancy villous tissues. The expression of the Mas1 receptor was detected by fluorescence immunoassay and real-time fluorescence quantitative PCR. In a case-control study, patients with full-term PE were selected as the case group and healthy women with full-term pregnancy were selected as the control group. Placental villus tissues were collected from both groups. Immunofluorescence chemistry and immunoprotein blotting were used to study the changes in Mas1 receptor expression in PE. Mas1 receptor agonists and blockers induced HTR8/Svneo cells and BeWo cells, and the effects of the Mas1 receptor on the proliferation and migration of trophoblast cells were detected by the CCK8 proliferation test and scratch test. Results: Eight cases were included in early pregnancy, seven cases in mid-pregnancy and six cases in late pregnancy. Mas1 receptors in normal placental villi tissue were mainly expressed in human trophoblast stem cell membranes and cytoplasm, and the expression of Mas1 receptor mRNA in villi tissue was significantly higher in late pregnancy than in mid-pregnancy. There were 24 cases included in the case group and 12 cases in the control group. Mas1 receptor expression in placental villi was significantly lower in the case group compared to the control group; Activation/inhibition of the Mas1 receptor had no significant effect on the proliferation of HTR8/Svneo cells and BeWo cells. Activated Mas1 receptor had no significant effect on the migration ability of HTR8/Svneo cells. Conclusion: Mas1 receptors are expressed in placental villous tissue and their expression varies with gestation. Mas1 receptor expression is reduced in PE patients, but it does not affect the value-added or migratory function of trophoblast cells.
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Humanos , Femenino , Embarazo , Placenta , Trofoblastos , Estudios de Casos y Controles , Preeclampsia , Expresión GénicaRESUMEN
OBJECTIVE@#To assess the influence of FLT3 expression on the prognosis of patients with acute myeloid leukemia (AML) by cell experiment and clinical data analysis.@*METHODS@#Models for FLT3 over-expression and interference-expression in AML cells were constructed. The level of BAK gene expression and its protein product was determined, along with the proliferation and apoptosis of leukemia cells. FLT3 gene expression and FLT3-ITD variant were determined among patients with newly diagnosed AML.@*RESULTS@#Compared with the interference-expression group, the level of BAK gene expression and its protein in FLT3 over-expression AML cells was significantly lower (P < 0.001), which also showed significantly faster proliferation (P < 0.001) and lower rate of apoptosis (P < 0.001). The expression level of FLT3 gene among patients with newly diagnosed AML was also significantly higher compared with the healthy controls (P < 0.001). The FLT3 gene expression of FLT3-ITD positive AML patients was higher than that of FLT3-WT patients (P = 0.002). Survival analysis showed that AML patients with high FLT3 expression in the medium-risk group had a lower complete remission rate and overall survival rate compared with those with a low FLT3 expression (P < 0.001).@*CONCLUSION@#Over-expression of FLT3 may influence the course of AML by promoting the proliferation of leukemia cells and inhibiting their apoptosis, which in turn may affect the prognosis of patients and serve as a negative prognostic factor for AML.
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Humanos , Apoptosis/genética , Análisis de Datos , Leucemia Mieloide Aguda/genética , Expresión Génica , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
OBJECTIVE@#To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity.@*METHODS@#Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software.@*RESULTS@#No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10).@*CONCLUSION@#A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.
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Embarazo , Humanos , Femenino , Infertilidad Femenina/genética , Endometrio/metabolismo , Aminoácidos/metabolismo , Expresión Génica , Carnitina , Alanina/metabolismo , Valina/metabolismoRESUMEN
Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T. cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.
O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T. cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.
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Animales , Cruzamientos Genéticos , Daño del ADN , Expresión Génica , Trypanosoma cruzi/genéticaRESUMEN
@#Objective To perform quality control in live attenuated yellow fever vaccine(chicken embryo cell)virus seed bank at the genomic level using the new generation Illumina/Solexa sequencing platform.Methods The live attenuated yellow fever vaccine strain YF17D-204 was inoculated into primary chicken embryo cells,and the chicken embryo cell adapted strains of live attenuated yellow fever vaccine were screened to establish YFV17D-CEC tertiary virus seed bank. The genome RNA of virus seeds was extracted,and the RNA library was prepared. The new generation Illumina/Solexa sequencing platform was used for high-throughput RNA sequencing. The whole genome nucleic acid sequence of yellow fever virus was systematically analyzed by using biological softwares such as FastQC,Trimmomatic,SPAdes,GapFiller,PrInSeS-G,Prokka,RepeatMasker,CRT,NCBI Blast~+,KAAS,HMMER3,TMHMM,SignalP,LipoP,ProtCamp and MegAlign.Results The whole genome of YFV17D-CEC tertiary virus seed bank contained 10 862 nucleotides,including an open reading frame(ORF)from 119 to 10 354(10 236 bp),encoding 3 412 amino acids. Sequence alignment analysis showed that the sequence of YF17D-CEC tertiary virus seed bank was 100% identical with YFV17D RKI(JN628279.1),YF/Vaccine/USA/Sanofi-Pasteur-17D-204/UF795AA/YFVax(JX503529.1)and YFV17D-204(KF769015.1),and no mutation occurred in the whole genome of the tertiary virus seed bank. Comparison of the sequences of different live attenuated yellow fever vaccine strains showed that yellow fever virus had multiple polymorphic sites.Conclusion YFV17DCEC has good genetic stability in primary chicken embryo cells. High-throughput RNA sequencing technology can quickly detect the whole genome information of YF17D-CEC virus seed bank,and the sequence analysis data can be used in the gene level quality control of yellow fever vaccine virus seed banks.
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Secuenciación de Nucleótidos de Alto Rendimiento , Expresión Génica , Control de CalidadRESUMEN
Objective: To analyze the expression levels of the F9 gene and F9 protein in hepatocellular carcinoma by combining multiple gene chip data, real-time fluorescence quantitative PCR (RT qPCR), and immunohistochemistry. Additionally, explore their correlation with the occurrence and development of hepatocellular carcinoma, as well as with various clinical indicators and prognosis. Methods: The mRNA microarray dataset from the GEO database was analyzed to identify the F9 gene with significant expression differences associated with hepatocellular carcinoma. Liver cancer and adjacent tissues were collected from 18 cases of hepatocellular carcinoma. RT-qPCR method was used to detect the F9 gene expression level. Immunohistochemistry was used to detect the F9 protein level. Combined with the TCGA database information, the correlation between F9 gene expression level and prognostic and clinicopathological parameters was analyzed. The biological function of F9 co-expressed genes associated with hepatocellular carcinoma was analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Statistical analysis was performed using Graphpad Prism software. Results: Meta-analysis results showed that the expression of the F9 gene was lower in HCC tissues than in non-cancerous tissues. Immunohistochemistry results were basically consistent with those of RT-qPCR. The data obtained from TCGA showed that the F9 gene had lower expression values in stages III-IV, T3-T4, and patients with vascular invasion. A total of 127 genes were selected for bioinformatics analysis as co-expressed genes of F9, which were highly enriched in redox processes and metabolic pathways. Conclusion: This study validates that the F9 gene and F9 protein are lower in HCC. The down-regulation of the F9 gene predicts adverse outcomes, which may provide a new therapeutic target for HCC.
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Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Regulación hacia Abajo , Pronóstico , Expresión Génica , Regulación Neoplásica de la Expresión GénicaRESUMEN
Objetivo: Evidências científicas sugerem que a deficiência de estrógeno e fatores genéticos influenciam o desenvolvimento do sistema estomatognático. Este estudo teve como objetivo avaliar a influência da deficiência de estrógeno na expressão gênica de TNF-α, IL-1ß, IL-6 e IL-10 durante o desenvolvimento dentário em modelo murino. Material e Métodos: Ratas Wistar Hannover foram divididas em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo - cirurgia de ovariectomia e Grupo Controle - cirurgia fictícia. Para avaliar o desenvolvimento dentário, o incisivo inferior foi escolhido. O modelo de hipofunção dos incisivos inferiores foi realizado por ajuste incisal. O incisivo homólogo exercia hiperfunção dentária. Os animais foram avaliados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão gênica do TNF-α, IL-1ß, IL-6 e IL-10 na região odontogênica dos incisivos por meio de PCR em tempo real. Foi realizado o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: Houve diferenças estatisticamente significativas na expressão gênica de TNF-α e IL-1ß entre os grupos hipoestrogenismo e controle sob condição de hipofunção dentária (p=0,0084, p=0,0072, respectivamente). Conclusão: A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes hipofuncionais (AU)
Objective: Scientific evidence suggests that estrogen deficiency and genetic factors have an influence on the development of the stomatognathic system. This study aimed to evaluate the influence of estrogen deficiency on the gene expression of TNF-α, IL-1ß, IL-6 and IL-10 during dental development in a murine model. Material and Methods: Wistar Hannover rats were divided into two groups according to the intervention received: Hypoestrogenism Group - ovariectomy surgery and Control Group - fictitious surgery. To evaluate the dental development, the lower incisor was chosen. The mandibular incisor hypofunction model was performed by incisal adjustment. The homologous incisor exerted a hyperfunction. The animals were evaluated throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the gene expression of the TNF-α, IL-1ß, IL-6 and IL-10 in the odontogenic region of the incisors through real time PCR. Kruskal-Wallis test and Dunn's posttest were performed. The level of significance was 5%. Results: There were statistically significant differences of TNF-α and IL-1ß gene expression between the hypoestrogenism and control groups under hypofunction condition (p=0.0084, p=0.0072, respectively). Conclusion: Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of the hypofunctional teeth. (AU)
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Animales , Ratas , Osteogénesis , Expresión Génica , Citocinas , Estrógenos , GenesRESUMEN
A Insuficiência Cardíaca (IC) é uma das principais causas de internação hospitalar no mundo e tem um elevado grau de morbidade e mortalidade, sendo um grave problema de saúde pública. Os lncRNAs (RNAs longo não codificantes), têm funções regulatórias transcricionais e/ou pós transcricionais bem complexas e que ainda não são totalmente claras, mas que podem exercer influência sobre as doenças cardiovasculares, dentre elas a IC. Assim o estudo teve como objetivo identificar na literatura o papel dos lncRNAs na patogênese da IC por meio de uma revisão integrativa com busca sistemática. Foram considerados elegíveis para leitura e composição do estudo 33 artigos e os principais papéis dos lncRNA na IC foram relatados como possíveis marcadores biológicos para diagnóstico e prognóstico da doença devido a sua expressividade na corrente sanguínea. Além disso, os lncRNAs podem estar relacionados à capacidade funcional uma vez que o aumento ou diminuição de sua expressão promove redução da apoptose de células endoteliais, melhora a disfunção cardíaca, distúrbios de contratilidade e dos canais de cálcio em pacientes com IC. Portanto, os lncRNAs parecem estar envolvidos na patogênese e/ou fisiopatologia da IC, podendo ser utilizados como biomarcadores genéticos com sensibilidade e especificidade semelhantes ou superiores aos empregados atualmente no diagnóstico e prognóstico da IC.
Heart Failure (HF) is one of the main causes of hospitalization worldwide and has a high degree of morbidity and mortality being considered a public health pro- blem. lncRNAs (non-coding long RNAs) have very complex transcriptional and/or post- transcriptional regulatory functions that are still not entirely clear but may influence car- diovascular diseases, including HF. Thus, the study aimed to identify in the literature the role of lncRNAs in the pathogenesis of HF through an integrative review with a systema- tic search. A total of 33 articles were considered eligible for reading and composition of the study. The roles of lncRNA in HF were reported as possible biological markers for the diagnosis and prognosis of the disease due to its expressiveness in the bloodstream. In addition, lncRNAs may be related to functional capacity since the increase or decrease in their expression promotes a reduction in endothelial cell apoptosis, and improves car- diac dysfunction, contractility, and calcium channel disorders in patients with HF. The- refore, lncRNAs seem to be involved in the pathogenesis and/or pathophysiology of HF and can be used as genetic biomarkers with sensitivity and specificity similar or superior to those currently employed in the diagnosis and prognosis of HF.
La Insuficiencia Cardiaca (IC) es una de las principales causas de hospita- lización en el mundo y tiene un alto grado de morbimortalidad considerándose un pro- blema de salud pública. Los lncRNAs (ARN largos no codificantes) tienen funciones re- guladoras transcripcionales y/o post-transcripcionales muy complejas que aún no están del todo claras pero que pueden influir en las enfermedades cardiovasculares, incluida la IC. Así pues, el estudio se propuso identificar en la literatura el papel de los lncRNAs en la patogénesis de la IC mediante una revisión integradora con una búsqueda sistemática. Un total de 33 artículos fueron considerados elegibles para su lectura y composición del estudio. Las funciones de los lncRNA en la IC se señalaron como posibles marcadores biológicos para el diagnóstico y pronóstico de la enfermedad debido a su expresividad en el torrente sanguíneo. Además, los lncRNAs pueden estar relacionados con la capacidad funcional, ya que el aumento o disminución de su expresión promueve una reducción de la apoptosis de las células endoteliales y mejora la disfunción cardiaca, la contractilidad y los trastornos de los canales de calcio en pacientes con IC. Por tanto, los lncRNAs parecen estar implicados en la patogénesis y/o fisiopatología de la IC y pueden ser utili- zados como biomarcadores genéticos con sensibilidad y spe-cificidad similares o superi- ores a los empleados actualmente en el diagnóstico y pronóstico de la IC.
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Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Pacientes/psicología , Literatura de Revisión como Asunto , Biomarcadores , Enfermedades Cardiovasculares/diagnóstico , Expresión Génica , Salud Pública/estadística & datos numéricos , Cardiopatías/diagnóstico , HospitalizaciónRESUMEN
Background: Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, and is one of the major health problems in Asia, Africa, Europe, and America. The tumor antigens recently are of interesting indicators as diagnostic and prognostic tools, The aim of the present study is to detect the expression levels of carbonic anhydrase IX (CA9), the Wilms tumor gene (WT1), and the preferentially expressed antigen in melanoma (PRAME) in the peripheral blood of CRC patients in comparison with healthy controls. Methods: A prospective case-control study of CRC patients was conducted. We included 25 newly-diagnosed CRC eligible patients and obtained peripheral blood samples of them as well as 10 blood samples from the control group. All samples were then submitted to deoxyribonucleic acid (DNA) extraction and a molecular study through real-time polymerase chain reaction (PCR). Results: The CRC group consisted of 15 (60%) female and 10 (40%) male patients with a mean age of 50.52 ± 9.8 years, while the control group included 4 (40%) female and 6 (60%) male patients with a mean age of 47.7 ± 7.9 years. The CRC group, 24 (96%) of patient samples were CA9-positive with strong statistically significant differences (p < 0.00001; sensitivity: 96%; specificity: 90%). Regarding the WT1 gene, there were 11 (44%) positive samples in the CRC group, with no statistically significant differences (p = 0.055; sensitivity: 44%; specificity: 90%). The PRAME gene was positive in 9 (36%) samples in the CRC group, with no statistically significant differences (p = 0.357; sensitivity: 36%; specificity: 80%. Among CA9 (24 patients; 96%) of patients with CRC expressed positive results, in WT1 11(91.6%) CRC patients expressed gene, and in PRAME gene, 9 patients with CRC (81.8%) expressed positive results. Conclusion: Overexpression of the CA9 gene in CRC of high sensitivity and specificity to be used as a tool to discriminate CRC from benign associate with high accuracy compare to WT1 and PRAME genes. (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Neoplasias Colorrectales/diagnóstico , Biomarcadores de Tumor , Proteínas WT1/genética , Anhidrasa Carbónica IX/genética , Antígenos de Neoplasias/genética , Pronóstico , Estudios de Casos y Controles , Expresión Génica , Estudios Prospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
A obesidade é definida pelo excesso de gordura corporal acumulada no tecido adiposo quando o indivíduo atinge valores de IMC igual ou superior a 30 Kg/m2. Constitui um dos principais fatores de risco para várias doenças não transmissíveis (DNTs) como por exemplo, diabetes mellitus tipo 2 (DM2), doenças cardiovasculares, hipertensão arterial, acidente vascular cerebral e até mesmo o câncer. Embora a obesidade esteja diretamente relacionada com o consumo calórico excessivo em relação ao gasto energético diário, sua etiologia pode estar associada aos baixos níveis de atividade física, às alterações neuroendócrinas e aos fatores genéticos. Considerando o componente genético, esta pode ser classificada como sindrômicas e estar associada às alterações cromossômicas estruturais ou numéricas, ou como não sindrômica, quando relacionada, principalmente, com os polimorfismos de nucleotídeos simples (SNPs) em alelos que atuam como herança monogênica, ou ainda com a interação vários genes (poligênica multifatorial). Apesar de existirem muitas etiologias diferentes, normalmente a obesidade é tratada a partir da mesma abordagem, desconsiderando a fisiologia que a desencadeou. Dessa forma, o objetivo do presente trabalho foi abordar a obesidade genética não sindrômica por meio a) da descrição breve de perspectiva histórica sobre seu entendimento; b) da exposição dos principais mecanismos moleculares envolvidos com o controle de peso; c) da compilação dos principais genes e SNPs relacionados; d) da definição dos principais genes; e e) da abordagem das principais perspectivas de intervenção.
Obesity is defined as excess body fat accumulated in the adipose tissue when the individual reaches BMI values equal to or greater than 30 kg/m2. It is one of the main risk factors for several non-communicable diseases (NCDs), such as Type 2 Diabetes mellitus (T2D), cardiovascular diseases, high blood pressure, stroke and even cancer. Although obesity is directly related to excessive calorie intake in relation to daily energy expenditure, its etiology may be associated with low levels of physical activity, neuroendocrine changes, and genetic factors. Considering the genetic component, it can be classified as syndromic and be associated with chromosomal or numerical changes, or as non-syndromic and being related mainly to single nucleotide polymorphisms (SNPs) in alleles that act as monogenic inheritance, or with an interaction of several genes (multifactorial polygenic). Although there are many different etiologies, obesity is usually treated using the same approach, disregarding the physiology that triggered it. Thus, the aim of this study was to address non-syndromic genetic obesity through a) a brief description of a historical perspective on its understanding; b) the exposure of the main molecular mechanisms involved in weight control, c) the compilation of the key genes and related SNPs, d) the definition of the key genes and e) the approach of the main intervention representations.
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Humanos , Masculino , Femenino , Peso Corporal/genética , Epigenómica , Genes/genética , Obesidad/genética , Índice de Masa Corporal , Expresión Génica/genética , Polimorfismo de Nucleótido Simple/genética , Receptor de Melanocortina Tipo 4/genética , Melanocortinas/genética , Receptores de Leptina/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Hipotálamo/fisiopatología , Obesidad/fisiopatologíaRESUMEN
The mutations are genetic changes in the genome sequences and have a significant role in biotechnology, genetics, and molecular biology even to find out the genome sequences of a cell DNA along with the viral RNA sequencing. The mutations are the alterations in DNA that may be natural or spontaneous and induced due to biochemical reactions or radiations which damage cell DNA. There is another cause of mutations which is known as transposons or jumping genes which can change their position in the genome during meiosis or DNA replication. The transposable elements can induce by self in the genome due to cellular and molecular mechanisms including hypermutation which caused the localization of transposable elements to move within the genome. The use of induced mutations for studying the mutagenesis in crop plants is very common as well as a promising method for screening crop plants with new and enhanced traits for the improvement of yield and production. The utilization of insertional mutations through transposons or jumping genes usually generates stable mutant alleles which are mostly tagged for the presence or absence of jumping genes or transposable elements. The transposable elements may be used for the identification of mutated genes in crop plants and even for the stable insertion of transposable elements in mutated crop plants. The guanine nucleotide-binding (GTP) proteins have an important role in inducing tolerance in rice plants to combat abiotic stress conditions.
Mutações são alterações genéticas nas sequências do genoma e têm papel significativo na biotecnologia, genética e biologia molecular, até mesmo para descobrir as sequências do genoma de um DNA celular junto com o sequenciamento do RNA viral. As mutações são alterações no DNA que podem ser naturais ou espontâneas e induzidas devido a reações bioquímicas ou radiações que danificam o DNA celular. Há outra causa de mutações, conhecida como transposons ou genes saltadores, que podem mudar sua posição no genoma durante a meiose ou a replicação do DNA. Os elementos transponíveis podem induzir por si próprios no genoma devido a mecanismos celulares e moleculares, incluindo hipermutação que causou a localização dos elementos transponíveis para se moverem dentro do genoma. O uso de mutações induzidas para estudar a mutagênese em plantas cultivadas é muito comum, bem como um método promissor para a triagem de plantas cultivadas com características novas e aprimoradas para a melhoria da produtividade e da produção. A utilização de mutações de inserção por meio de transposons ou genes saltadores geralmente gera alelos mutantes estáveis que são marcados quanto à presença ou ausência de genes saltadores ou elementos transponíveis. Os elementos transponíveis podem ser usados para a identificação de genes mutados em plantas de cultivo e até mesmo para a inserção estável de elementos transponíveis em plantas de cultivo mutadas. As proteínas de ligação ao nucleotídeo guanina (GTP) têm papel importante na indução de tolerância em plantas de arroz para combater as condições de estresse abiótico.