RESUMEN
Even though N6-methyladenosine (m6A) RNA modifications are increasingly being implicated in human disease, their mechanisms are not fully understood in smokers with coronary artery disease (CAD). Thirty m6A-related regulators' expression (MRRE) in CAD individuals (smokers and non-smokers) were analyzed from GEO. Support Vector Machine, random forest, and nomogram models were constructed to assess its clinical value. Consensus clustering, principal component analysis, and ssGSEA were used to construct a full picture of m6A-related regulators in smokers with CAD. Oxygen-glucose deprivation (OGD) and qRT-PCR were used to validate hypoxia's effect on MRRE. A comparison between smokers with CAD and controls revealed lower expression levels of RBM15B, YTHDC2, and ZC3H13. Based on three key MRREs, all models showed good clinical value, and smokers with CAD were divided into two distinct molecular subgroups. The correlations were found between key MRRE and the degree of immune infiltration. Three key MRREs in HUVECs and FMC84 mouse cardiomyocytes were reduced in the OGD group. Through hypoxia, smoking might reduce the expression levels of RBM15B, YTHDC2, and ZC3H13 in smokers with CAD. Our findings provide an important theoretical basis for the treatment of smokers with CAD.
Asunto(s)
Adenosina , Enfermedad de la Arteria Coronaria , Proteínas de Unión al ARN , Humanos , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Ratones , Animales , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Fumar/efectos adversos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Masculino , Metilación de ARN , ARN HelicasasRESUMEN
Calcific aortic valve disease (CAVD) and osteoarthritis (OA) are common diseases in the ageing population and share similar pathogenesis, especially in inflammation. This study aims to discover potential diagnostic and therapeutic targets in patients with CAVD and OA. Three CAVD datasets and one OA dataset were obtained from the Gene Expression Omnibus database. We used bioinformatics methods to search for key genes and immune infiltration, and established a ceRNA network. Immunohistochemical staining was performed to verify the expression of candidate genes in human and mice aortic valve tissues. Two key genes obtained, leucine rich repeat containing 15 (LRRC15) and secreted phosphoprotein 1 (SPP1), were further screened using machine learning and verified in human and mice aortic valve tissues. Compared to normal tissues, the infiltration of immune cells in CAVD tissues was significantly higher, and the expressions of LRRC15 and SPP1 were positively correlated with immune cells infiltration. Moreover, the ceRNA network showed extensive regulatory interactions based on LRRC15 and SPP1. The authors' findings identified LRRC15 and SPP1 as hub genes in immunological mechanisms during CAVD and OA initiation and progression, as well as potential targets for drug development.
Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Calcinosis , Biología Computacional , Osteoartritis , Osteopontina , Animales , Humanos , Ratones , Válvula Aórtica/patología , Válvula Aórtica/metabolismo , Enfermedad de la Válvula Aórtica/genética , Enfermedad de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Calcinosis/genética , Calcinosis/metabolismo , Calcinosis/patología , Redes Reguladoras de Genes , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Osteopontina/genética , Osteopontina/metabolismoRESUMEN
Catheter-related thrombosis is a common complication caused by central venous catheters. Although right atrial thrombosis is uncommon, it may lead to life-threatening situations. Here, we report 2 cases of neonates with massive catheter-related right atrial thrombosis after congenital heart disease surgery. During therapeutic management, we attempted different treatments but failed to clear the mass. Finally, we found thrombectomy to be the most effective method for treating massive catheter-related right atrial thrombosis with favourable results.
Asunto(s)
Cateterismo Venoso Central , Catéteres Venosos Centrales , Cardiopatías , Trombosis , Cateterismo Venoso Central/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Cardiopatías/cirugía , Humanos , Recién Nacido , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/cirugíaRESUMEN
There are limited cases of heart-lung transplantation (HLT) in children worldwide owing to lack of donors, demanding surgical teamwork, and arduous post-operative management. Post-transplant management difficulties stem from the possible development of several post-operative complications, with infection being a common complication. Intracranial fungal infections are difficult to diagnose and prone to treatment delays because of their relatively insidious onset and atypical clinical presentation. Here, we present a case of a cerebral infection developed 3 months after HLT in a 10-year-old child, showing no positive results on conventional imaging or cerebrospinal fluid (CSF) examination and culture. On metagenomic next-generation sequencing of the cerebrospinal fluid, the causative organism was finally determined as Aspergillus. After administering 1-year anti-Aspergillus treatment, no recurrence of intracranial fungal infection was noted during the 3-year follow-up. This case illustrates the multifaceted diagnostic techniques for cerebral aspergillosis after HLT and shows the significance of dynamic monitoring of symptoms, such as headache, and of metagenomic sequencing results, trends in intracranial pressure and (1-3)-ß-D-glucan levels for guiding diagnosis and treatment.
RESUMEN
OBJECTIVE: To determine the sequence of S2 gene of SARS-associated coronavirus (SARS-CoV) GD322 and analyze the phyletic evolution of S2 gene. METHOD: S2 gene fragment was amplified from SARS-CoV GD322 genome with RT-PCR and ligated to pGEM-T vector for sequence analysis after transformation of the plasmid into E. coli DH5a. The variability of S2 genes and S2 proteins from 12 strains isolated in the early, intermediate and advanced stages of the SARS outbreak were analyzed and the phylogenetic tree was constructed with Lasergene, Clustal X, DNAman and Treeview. T cell antigen epitopes of S2 protein were predicted on the basis of Internet database. RESULT: With the epidemic spread of SARS-CoV, the S2 genes of the virus tended to become stable. Homology of S2 genes of SARS-CoV isolated in advanced stage of the outbreak reached 99.9%. Prediction of T cell antigen epitope showed that mutation at the 57th amino acid effected T cell antigen epitope. CONCLUSION: S2 gene of GD322 SARS-CoV is relatively stable during the epidemic spread of the virus, and mutation at the 57th amino acids of S2 protein may affect the T cell antigen epitope.
Asunto(s)
Mutación Puntual , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Proteínas del Envoltorio Viral/genética , Escherichia coli/genética , Variación Genética , Humanos , Filogenia , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , Análisis de Secuencia de ADN , Síndrome Respiratorio Agudo Grave/virologíaRESUMEN
OBJECTIVE: To construct the cDNA subclones spanning the entire genome of dengue 2 virus NGC strain for further construction of full-length infectious viral cDNA clone. METHODS: Two pairs of primers were designed according to the restriction endonuclease sites in the viral genome of dengue 2 virus NGC strain. After viral RNA extraction from the brain of infected new-born mice, two parts of full-length viral cDNA were amplified by long RT-PCR and cloned into the vector pCR-XL-TOPO. The partial sequence of the recombinant plasmid was determined. RESULTS AND CONCLUSION: Sequence analysis and digestion with restriction enzymes demonstrated that the two cDNA subclones were specific for dengue 2 virus NGC strain, suggesting the successful construction of the two cDNA subclones of dengue 2 virus NGC strain.