RESUMEN
G-quadruplex (G4) is a unique secondary structure formed by guanine-rich nucleic acid sequences. Growing studies reported that the genomes of some viruses harbor G4 structures associated with viral replication, opening up a new field to dissect viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV), a representative member of Arteriviridae, is an economically significant pathogen that has devastated the swine industry worldwide for over 30 years. In this study, we identified a highly conserved G-rich sequence with parallel-type G4 structure (named PRRSV-G4) in the negative strand genome RNA of PRRSV. Pyridostatin (PDS), a well-known G4-binding ligand, stabilized the PRRSV-G4 structure and inhibited viral replication. By screening the proteins interacting with PRRSV-G4 in PRRSV-infected cells and single-molecule magnetic tweezers analysis, we found that two helicases, host DDX18 and viral nsp10, interact with and efficiently unwound the PRRSV-G4 structure, thereby facilitating viral replication. Using a PRRSV reverse genetics system, we confirmed that recombinant PRRSV with a G4-disruptive mutation exhibited resistance to PDS treatment, thereby displaying higher replication than wild-type PRRSV. Collectively, these results demonstrate that the PRRSV-G4 structure plays a crucial regulatory role in viral replication, and targeting this structure represents a promising strategy for antiviral therapies.
Asunto(s)
Virus del Síndrome Respiratorio y Reproductivo Porcino , Porcinos , Animales , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Proteínas no Estructurales Virales/metabolismo , ADN Helicasas/genética , Replicación Viral/genética , ARNRESUMEN
Background: Intracranial Aneurysm (IA) is characterized by abnormal dilation of intracranial arterial walls, a tumor-like protrusion, often occurring in the anterior communicating artery. Intracranial Dissecting Aneurysm (IDA) refers to hemodynamic changes within intracranial arteries, leading to ruptures between blood vessel walls, disrupting normal arterial blood flow within the arterial lumen. IDA is relatively uncommon in the anterior circulation. To date, there have been no reported cases of dissecting aneurysms misdiagnosed as cerebral aneurysms before surgical intervention. This case report presents a patient's detailed clinical diagnosis, treatment, and imaging data. Case Presentation: A 56-year-old female patient experienced post-work headaches. Cranial Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Digital Subtraction Angiography (DSA) examinations revealed a small hemorrhage following infarction and aneurysms in the initial part of the right A2 segment. Initially, the patient was diagnosed with a ruptured cerebral aneurysm, accompanied by hemorrhage and cerebral vasospasm (cerebral infarction in the right frontal lobe). Subsequently, cerebral aneurysm clipping was performed. During surgery, it was observed that the aneurysm originated from the ipsilateral A2 starting site and displayed dissecting-like changes extending towards the distal end. The final diagnosis confirmed an aneurysm evolving from intracranial artery dissection. Artificial meninges were employed to encase and clip the aneurysm. Post-surgery, the patient was transferred to a superior hospital for A3 bypass. Follow-up assessments indicated a successful recovery. Conclusion: Cerebral aneurysms typically involve larger arteries with rare possibilities of stenosis. Moreover, the cerebral artery is relatively small, making it challenging for Brain Computed Tomography Angiography (CTA) to distinguish true and false lumen within blood vessels. The diagnosis of dissecting aneurysms is difficult and often susceptible to clinical misdiagnosis.
Asunto(s)
Disección Aórtica , Aneurisma Intracraneal , Femenino , Humanos , Persona de Mediana Edad , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Hemorragia , Errores DiagnósticosRESUMEN
The available findings on the association between iron status and risk of stroke remain controversial. We used multivariable logistic regression and restricted cubic spline models to explore the association between iron exposures and risk of stroke in the US National Health and Nutrition Examination Survey (NHANES 2007-2016, n = 24,627). A total of 941 (3.82%) stroke cases were identified in this study. In women, the ORs with 95% CIs of prevalence of stroke were 0.92 (0.65-1.28), 0.66 (0.44-0.98) and 0.72 (0.49-1.08) across quartiles 2-4 compared with quartile 1 of iron intake, respectively. An inverse and L-shaped association between iron intake and risk of stroke in women was observed, and the curve plateaued at 20 mg/day. However, neither serum iron concentrations nor iron intake were significantly associated with riskof stroke in men. Our study found that iron intake was inversely associated with risk of stroke in a sex-dependent fashion.
Asunto(s)
Hierro , Accidente Cerebrovascular , Adulto , Estudios Transversales , Dieta , Femenino , Humanos , Masculino , Encuestas Nutricionales , Accidente Cerebrovascular/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Nucleic acids are an indispensable component in all known life forms. The biological processes are regulated by Nucleic acids, which associate to form special high-order structures. since the high-level structures of nucleic acids are related to gene expression in cancer cells or viruses, it is very likely to become a potential drug target. Traditional biochemical methods are limited to distinguish the conformational distribution and dynamic transition process of single nucleic acid structure. The ligands based on the intermediate and transition states between different conformations are not designed by traditional biochemical methods. The single-molecule techniques enable real-time observation of the individual nucleic acid behavior due to its high resolution. Here, we introduce the application of single-molecule techniques in the study of small molecules to recognize nucleic acid structures, such as single-molecule FRET, magnetic tweezers, optical tweezers and atomic force microscopy. At the same time, we also introduce the specific advantages of single-molecule technology compared with traditional biochemical methods and some problems arisen in current research.
Asunto(s)
Ácidos Nucleicos , Virus , Nanotecnología/métodos , Microscopía de Fuerza Atómica/métodos , Conformación Molecular , Conformación de Ácido NucleicoRESUMEN
OBJECTIVE: To study the incidence and prognostic factors of patients with benign pituitary tumors based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: This was a retrospective cohort study. Patients with benign pituitary tumors reported in the Surveillance, Epidemiology, and End Results database from 2004 to 2016, who presented completed demographic and clinical data, were included in our study. The age-adjusted incidence rate was calculated and stratified by year at diagnosis, age, gender, and the pathological type of benign pituitary tumor. We used Kaplan-Meier curves and multivariable Cox regressions to determine the factors associated with overall survival. RESULTS: A total of 29,967 patients were included in the study, of whom 26,691 (89.07%) survived and 3276 (10.93%) died. The age-adjusted incidence rate increased from 3.15 per 100,000 person-years in 2004 to 4.66 per 100,000 person-years in 2011 (annual percent change = 5.51, P < 0.001), and the subsequent growth trend from 2011 to 2016 was not statistically significant (annual percent change = 0.26, P = 0.711). Most patients were female, aged 60-79 years, and pituitary adenomas accounted for the main proportion of the incidence of benign pituitary tumors. Surgery was associated with the overall survival on the multivariable Cox regression model (hazard ratio = 0.677, 95% confidential interval: 0.629-0.727) and Kaplan-Meier curves, especially in pituitary adenoma. Radiation was not associated with the overall survival of benign pituitary tumor. CONCLUSIONS: The overall incidence of benign pituitary tumors was low but showed an increasing trend. Surgery may be beneficial to the prognosis. It should be noted that benign pituitary tumors may not require excessive treatment, such as radiation.
Asunto(s)
Adenoma , Craneofaringioma , Neoplasias Hipofisarias , Neoplasias de la Base del Cráneo , Neoplasias de los Tejidos Blandos , Adenoma/epidemiología , Femenino , Humanos , Incidencia , Masculino , Neoplasias Hipofisarias/epidemiología , Pronóstico , Estudios Retrospectivos , Programa de VERFRESUMEN
Copper as an essential trace element is hypothesized to be involved in stroke risk. However, the evidence for associations between copper and stroke risk factors such as lipid levels has been mixed. This study aimed to examine the relationships between serum copper and lipid levels among 3425 participants aged 20 years and older from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Data on administered questionnaires, serum copper concentrations, and lipid levels (total cholesterol, HDL cholesterol, triglycerides, and LDL cholesterol) were used. Associations between serum copper and lipid levels were evaluated using both multivariable linear regression and logistic regression models. In the linear regression models, total cholesterol and LDL cholesterol levels increased with increasing copper concentrations among women. Each 1 unit (µg/dL) increase in serum copper concentrations was associated with roughly 0.11 mg/dL higher total cholesterol (95%CI: 0.04-0.18; P < 0.05) and roughly 0.09 mg/dL higher LDL cholesterol (95%CI: 0.01-0.17; P < 0.05) among women, respectively. Serum copper was positively associated with high LDL cholesterol among women, and the multivariate-adjusted OR (95% CI) for the third quartile of serum copper concentrations was 4.25 (1.15-15.77) compared with the lowest quartile. Moreover, compared with the lowest quartile, the multivariate-adjusted OR (95% CI) for the third quartile of serum copper concentrations was 1.82 (1.16-2.85) for risk of having high total cholesterol among men. No significant association between serum copper and triglycerides levels was observed. These findings suggest that copper may impact stroke health via effects on lipid levels but need to be confirmed with prospective data.
Asunto(s)
Cobre , Accidente Cerebrovascular , Adulto , HDL-Colesterol , Femenino , Humanos , Masculino , Encuestas Nutricionales , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , TriglicéridosRESUMEN
ABSTRACT: Postoperative intracranial infection after intracranial aneurysm is relatively common in clinical setting; it is necessary to analyze the clinical risk factors of postoperative intracranial infection, to provide reliable evidence to the management of aneurysm.Patients with intracranial aneurysm admitted from January 1, 2016, to November 30, 2020, are included. We collected the patient's personal and treatment data, and analyzed the risk factors of intracranial infection by multivariate logistic regression analysis. We compared the cerebrospinal fluid (CSF) indicators and serological indicators and analyzed their correlation with intracranial infection by spearman analysis.A total of 236 patients with intracranial aneurysm were included; the incidence of postoperative intracranial infection was 12.71%. There were significant differences in the diabetes, intraoperative aneurysm rupture, intraoperative CSF leakage, duration of surgery, and estimated blood loss between infection and non-infection group. Logistic regression indicated that diabetes [odds ratio (OR) 2.053, 95% confidence interval (95% CI) 1.092â¼3.385], intraoperative aneurysm rupture (OR 2.239, 95% CI 1.173â¼4.312), intraoperative CSF leakage (OR 2.168, 95% CI 1.033â¼3.451), duration of surgery ≥360âminutes (OR 1.926, 95% CI 1.108â¼2.655), and estimated blood loss ≥125âmL (OR 2.459, 95% CI 1.854â¼3.447) were the independent risk factors of postoperative intracranial infection in patients with aneurysm surgery (all Pâ<â.05). Klebsiella pneumoniae, Escherichia coli, and Staphylococcus epidermidis were the top 3 commonly seen pathogens. Spearman analyses indicated that PCT, CRP, LA, LDH were all correlated with intracranial infection (all Pâ<â.05).There are multiple factors for the postoperative intracranial infection in patients with aneurysm. Coping strategies should be formulated targeted on those risks to improve the prognosis of patients.
Asunto(s)
Aneurisma Roto/cirugía , Aneurisma Intracraneal/cirugía , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Aspartato Aminotransferasas/sangre , Proteína C-Reactiva/metabolismo , Líquido Cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Recently, deregulated microRNA (miRNA) expression contributes to the development and progression of human glioblastoma. The aim of the present study was to evaluate the level of miR-154 and Wnt5a in glioblastoma tissues and cells. We further investigated the molecular mechanisms of miR-154 and Wnt5a in glioblastoma cell lines. In the present study, we found that miR-154 expression was downregulated in glioblastoma tissues and U87, U251, and A172 cells (all p < 0.001). By contrast, Wnt5a was upregulated. Furthermore, we found that overexpression of miR-154 suppressed cell migration and invasion of U87 and U251 cells. Mechanically, overexpression of miR-154 inhibited epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Importantly, we identified that the 3' untranslated region (3'-UTR) of Wnt5a was a direct target of miR-154. Luciferase reporter assays confirmed that miR-154 binding to the 3'-UTR regions of Wnt5a inhibited the expression of Wnt5a in U87 and U251 cells. At the same time, overexpressed Wnt5a also reversed EMT inhibited by miR-154. In conclusion, this study suggested that high miR-154 expression suppressed glioblastoma cell migration, invasion, and EMT development through targeting Wnt5a, which may be recommended as a therapeutic target for glioblastoma.