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1.
Nucleic Acids Res ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38966995

RESUMEN

Nuclear actin-based movements support DNA double-strand break (DSB) repair. However, molecular determinants that promote filamentous actin (F-actin) formation on the damaged chromatin remain undefined. Here we describe the DYRK1A kinase as a nuclear activity that promotes local F-actin assembly to support DSB mobility and repair, accomplished in part by its targeting of actin nucleator spire homolog 1 (Spir1). Indeed, perturbing DYRK1A-dependent phosphorylation of S482 mis-regulated Spir1 accumulation at damaged-modified chromatin, and led to compromised DSB-associated actin polymerization and attenuated DNA repair. Our findings uncover a role of the DYRK1A-Spir1 axis in nuclear actin dynamics during early DSB responses, and highlight the intricate details of nuclear cytoskeletal network in DSB repair and genome stability maintenance.

2.
Int J Biol Macromol ; 274(Pt 2): 133401, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925184

RESUMEN

Porcine epidemic diarrhea virus (PEDV) is one of the most devastating diseases affecting the pig industry globally. Due to the emergence of novel strains, no effective vaccines are available for prevention and control. Investigating the pathogenic mechanisms of PEDV may provide insights for creating clinical interventions. This study constructed and expressed eukaryotic expression vectors containing PEDV proteins (except NSP11) with a 3' HA tag in Vero cells. The subcellular localization of PEDV proteins was examined using endogenous protein antibodies to investigate their involvement in the viral life cycle, including endocytosis, intracellular trafficking, genome replication, energy metabolism, budding, and release. We systematically analyzed the potential roles of all PEDV viral proteins in the virus life cycle. We found that the endosome sorting complex required for transport (ESCRT) machinery may be involved in the replication and budding processes of PEDV. Our study provides insight into the molecular mechanisms underlying PEDV infection. IMPORTANCE: The global swine industry has suffered immense losses due to the spread of PEDV. Currently, there are no effective vaccines available for clinical protection. Exploring the pathogenic mechanisms of PEDV may provide valuable insights for clinical interventions. This study investigated the involvement of viral proteins in various stages of the PEDV lifecycle in the state of viral infection and identified several previously unreported interactions between viral and host proteins. These findings contribute to a better understanding of the pathogenic mechanisms underlying PEDV infection and may serve as a basis for further research and development of therapeutic strategies.

3.
J Med Virol ; 96(3): e29497, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38436142

RESUMEN

This study aimed at using single-sample gene set enrichment analysis scores to cluster naso/pharyngeal swab specimen samples from coronavirus disease 2019 (COVID-19) patients into two clusters. One cluster with higher fractions of immune cells and more active inflammatory-related pathways was called the Immunity-High (Immunity-H) group, and the other one was called the Immunity-Low group. We explored impacts of the method on COVID-19 treatment. First, given that the Immunity-H group was mainly enriched in inflammatory-related pathways and had higher fractions of inflammatory cells, the Immunity-H group may obtain more curative effects from anti-inflammatory treatment. Second, we searched some hot genes from the PubMed platform that had been studied by researchers and found these genes upregulated in the Immunity-H group, so we speculated the Immunity-H group and Immunity-Low group may have different curative effects from drugs targeting these genes. Finally, we screened out hub genes for the Immunity-H group and predicted potential drugs for these hub genes by a public data set (http://dgidb.genome.wustl.edu). These hub genes are significantly upregulated in the Immunity-H group and neutrophils so that the Immunity-H group may obtain different treatment results from potential drugs compared with the Immunity-Low group. Therefore, the cluster method may provide help in drug development and administration for COVID-19 patients.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Humanos , Preparaciones Farmacéuticas , COVID-19/diagnóstico , COVID-19/genética , Desarrollo de Medicamentos , Neutrófilos
4.
J Virol ; 97(4): e0021023, 2023 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-36975780

RESUMEN

Porcine enteric alphacoronavirus (PEAV) is a new bat HKU2-like porcine coronavirus, and its endemic outbreak has caused severe economic losses to the pig industry. Its broad cellular tropism suggests a potential risk of cross-species transmission. A limited understanding of PEAV entry mechanisms may hinder a rapid response to potential outbreaks. This study analyzed PEAV entry events using chemical inhibitors, RNA interference, and dominant-negative mutants. PEAV entry into Vero cells depended on three endocytic pathways: caveolae, clathrin, and macropinocytosis. Endocytosis requires dynamin, cholesterol, and a low pH. Rab5, Rab7, and Rab9 GTPases (but not Rab11) regulate PEAV endocytosis. PEAV particles colocalize with EEA1, Rab5, Rab7, Rab9, and Lamp-1, suggesting that PEAV translocates into early endosomes after internalization, and Rab5, Rab7, and Rab9 regulate trafficking to lysosomes before viral genome release. PEAV enters porcine intestinal cells (IPI-2I) through the same endocytic pathway, suggesting that PEAV may enter various cells through multiple endocytic pathways. This study provides new insights into the PEAV life cycle. IMPORTANCE Emerging and reemerging coronaviruses cause severe human and animal epidemics worldwide. PEAV is the first bat-like coronavirus to cause infection in domestic animals. However, the PEAV entry mechanism into host cells remains unknown. This study demonstrates that PEAV enters into Vero or IPI-2I cells through caveola/clathrin-mediated endocytosis and macropinocytosis, which does not require a specific receptor. Subsequently, Rab5, Rab7, and Rab9 regulate PEAV trafficking from early endosomes to lysosomes, which is pH dependent. The results advance our understanding of the disease and help to develop potential new drug targets against PEAV.


Asunto(s)
Alphacoronavirus , Caveolas , Clatrina , Pinocitosis , Internalización del Virus , Proteínas de Unión al GTP rab , Alphacoronavirus/fisiología , Proteínas de Unión al GTP rab/metabolismo , Endosomas/metabolismo , Infecciones por Coronavirus/metabolismo , Concentración de Iones de Hidrógeno , Dinaminas/metabolismo , Caveolas/metabolismo , Colesterol/metabolismo , Clatrina/metabolismo , Pinocitosis/fisiología , Células Vero , Chlorocebus aethiops , Animales
5.
J Med Virol ; 95(2): e28487, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36625395

RESUMEN

We identified 14 immune-related differentially Expressed Genes (DEGs) between COVID-19 patients and normal controls and the receiver operator characteristic curve results showed that they could be used to discriminate COVID-19 patients from healthy controls. Single-sample gene set enrichment analysis and CIBERSORT analysis displayed immune landscape of COVID-19 patients that the fraction of immune cells (like B cell subtypes and T cell subtypes) decreased distinctly in the first SARS-CoV-2 infection which may further weaken immunity of cancer patients and increasing inflammatory cells (Neutrophils and Macrophages) may further promote inflammatory response of cancer patients. Based on expression levels of 14 DEGs we found that first SARS-CoV-2 infection may accelerate progression of cancer patients by Kaplan-Meier survival, immune subtypes and tumor microenvironment analyses, and may weaken anti-PD-1 monoclonal antibody treatment effect of cancer patients by weighted gene co-expression network, tumor mutation burden and microsatellite instability analysis. The second SARS-CoV-2 infection was beneficial to control development of tumor seemingly, but it may be difficult for cancer patients to experience destroy successfully from first SARS-CoV-2 infection, let alone benefits from second SARS-CoV-2 infection. In addition, this study also emphasized significance of multi-factor analysis when analyzing impacts of SARS-CoV-2 infection on cancer patients.


Asunto(s)
COVID-19 , Neoplasias , Humanos , SARS-CoV-2 , Anticuerpos Monoclonales , Linfocitos B , Microambiente Tumoral
6.
Virol J ; 19(1): 130, 2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35918744

RESUMEN

BACKGROUND: At present, there are still no specific therapeutic drugs and appropriate vaccines for Dengue. Therefore, it is important to explore distinct clinical diagnostic indicators. METHODS: In this study, we combined differentially expressed genes (DEGs) analysis, weighted co-expression network analysis (WGCNA) and Receiver Operator Characteristic Curve (ROC) to screen a stable and robust biomarker with diagnosis value for Dengue patients. CIBERSORT was used to evaluate immune landscape of Dengue patients. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were applied to explore potential functions of hub genes. RESULTS: CD38 and Plasma cells have excellent Area Under the Curve (AUC) in distinguishing clinical stages for Dengue patients, and activated memory CD4+ T cells and Monocytes have good AUC for this function. ZNF595 has acceptable AUC in discriminating dengue hemorrhagic fever (DHF) from dengue fever (DF) in whole acute stages. Analyzing any serotype, we can obtain consistent results. Negative inhibition of viral replication based on GO, KEGG and GSEA analysis results, up-regulated autophagy genes and the impairing immune system are potential reasons resulting in DHF. CONCLUSIONS: CD38, Plasma cells, activated memory CD4+ T cells and Monocytes can be used to distinguish clinical stages for dengue patients, and ZNF595 can be used to discriminate DHF from DF, regardless of serotypes.


Asunto(s)
Dengue , Dengue Grave , Biomarcadores , Ontología de Genes , Humanos
9.
Stem Cell Res Ther ; 12(1): 394, 2021 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-34256854

RESUMEN

BACKGROUND: The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. METHODS: Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. RESULTS: Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. CONCLUSIONS: CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.


Asunto(s)
Neoplasias Encefálicas , Glioma , Animales , Apoptosis , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos/genética , Transición Epitelial-Mesenquimal , Glioma/tratamiento farmacológico , Glioma/genética , Ratones , Ratones Desnudos , Células Madre , Temozolomida/farmacología , Microambiente Tumoral
10.
Indian J Microbiol ; 61(2): 195-202, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33927460

RESUMEN

Biphenanthrene compound, 4, 8, 4', 8'-tetramethoxy (1, 1'-biphenanthrene)-2, 7, 2', 7'-tetrol (LF05), recently isolated from fibrous roots of Bletilla striata, exhibits antibacterial activity against several Gram-positive bacteria. In this study, we investigated the antibacterial properties, potential mode of action and cytotoxicity. Minimum inhibitory concentrations (MICs) tests showed LF05 was active against all tested Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA) and staphylococcal clinical isolates. Minimum bactericidal concentration (MBC) tests demonstrated LF05 was bactericidal against S. aureus ATCC 29213 and Bacillus subtilis 168 whereas bacteriostatic against S. aureus ATCC 43300, WX 0002, and other strains of S. aureus. Time-kill assays further confirmed these observations. The flow cytometric assay indicated that LF05 damaged the cell membrane of S. aureus ATCC 29213 and B. subtilis 168. Consistent with this finding, 4 × MIC of LF05 caused release of ATP in B. subtilis 168 within 10 min. Checkerboard test demonstrated LF05 exhibited additive effect when combined with vancomycin, erythromycin and berberine. The addition of rat plasma or bovine serum albumin to bacterial cultures caused significantly loss in antibacterial activity of LF05. Interestingly, LF05 was highly toxic to several tumor cells. Results of these studies indicate that LF05 is bactericidal against some Gram-positive bacteria and acts as a membrane structure disruptor. The application of biphenanthrene in the treatment of S. aureus infection, especially local infection, deserves further study.

11.
J Virol ; 95(10)2021 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-33627389

RESUMEN

Cytoskeleton, as a ubiquitous structure in the cells, plays an important role in the process of virus entry, replication, and survival. However, the action mechanism of cytoskeleton in the invasion of Pestivirus into host cells remains unclear. In this study, we systematically dissected the key roles of the main cytoskeleton components, microfilaments and microtubules in the endocytosis of porcine Pestivirus, Classical swine fever virus (CSFV). We observed the dynamic changes of actin filaments in CSFV entry. Confocal microscopy showed that CSFV invasion induced the dissolution and aggregation of stress fibers, resulting in the formation of lamellipodia and filopodia. Chemical inhibitors and RNA interference were used to find that the dynamic changes of actin were caused by EGFR-PI3K/MAPK-RhoA/Rac1/Cdc42-cofilin signaling pathway, which regulates the microfilaments to help CSFV entry. Furthermore, co-localization of the microfilaments with clathrin and Rab5 (early endosome), as well as microtubules with Rab7 (late endosome) and Lamp1 (lysosome) revealed that microfilaments were activated and rearranged to help CSFV trafficking to early endosome after endocytosis. Subsequently, recruitment of microtubules by CSFV also assisted membrane fusion of the virions from late endosome to lysosome with the help of a molecular motor, dynein. Unexpectedly, vimentin, which is an intermediate filament, had no effect on CSFV entry. Taken together, our findings comprehensively revealed the molecular mechanisms of cytoskeletal components that regulated CSFV endocytosis and facilitated further understanding of Pestivirus entry, which would be conducive to explore antiviral molecules to control classical swine fever.IMPORTANCEEndocytosis, an essential biological process mediating cellular internalization events, is often exploited by pathogens for their entry into target cells. Previously, we have reported different mechanisms of CSFV endocytosis into the porcine epithelial cells (PK-15) and macrophages (3D4/21); however, the details of microfilaments/microtubules mediated virus migration within the host cells remained to be elucidated. In this study, we found that CSFV infection induced rearrangement of actin filaments regulated by cofilin through EGFR-PI3K/MAPK-RhoA/Rac1/Cdc42 pathway. Furthermore, we found that CSFV particles were trafficked along actin filaments in early and late endosomes, and through microtubules in lysosomes after entry. Here, we provide for the first time a comprehensive description of the cytoskeleton that facilitates entry and intracellular transport of highly pathogenic swine virus. Results from this study will greatly contribute to the understanding of virus-induced early and complex changes in host cells that are important in CSFV pathogenesis.

12.
Acta Neurochir (Wien) ; 163(6): 1677-1685, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33608765

RESUMEN

INTRODUCTION: Total resection of meningiomas involving the major dural sinuses (MIMDS) is still challenging for neurosurgeons. Gamma knife radiosurgery (GKRS) was shown to have a high probability of tumor control. The current study evaluated the clinical outcomes of patients who underwent subtotal resection alone or in combination with postoperative GKRS for the treatment of WHO grade I MIMDS. METHODS: From January 2006 to December 2016, 204 patients with MIMDS underwent Simpson IV subtotal resection in Wuhan Union Hospital. In 151 patients, no additional treatment was performed, while the tumor remnant was treated with GKRS in 53 patients. All patients were monitored with regular MR follow-ups. We retrospectively reviewed the clinical data, radiological characteristics, and outcomes of these 204 patients. Progression-free survival (PFS) was determined by Kaplan-Meier analysis. Related factors were determined by univariate Cox regression analyses. RESULTS: The mean follow-up period was 75.5 months. The tumor recurrence/progression rates were 13.9% in the microsurgery group and 3.8% in the combined therapy group (p = 0.045). The 5- and 10- year progression-free survival (PFS) rates were 92.3 and 80.7%, respectively, in the microsurgery group and 100.0 and 88.5% in the combined therapy group. Treatment approach was found to be an independent prognostic factor for tumor recurrence/progression in the univariable analyses (p=0.04). CONCLUSIONS: Compared with microsurgery alone, targeted Simpson grade IV resection combined with early gamma knife treatment resulted in longer progression-free survival without increased complications for WHO grade I MIMDS.


Asunto(s)
Senos Craneales/cirugía , Duramadre/cirugía , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Meningioma/radioterapia , Meningioma/cirugía , Cuidados Posoperatorios , Radiocirugia , Adolescente , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Complicaciones Posoperatorias/etiología , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Radiocirugia/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
13.
Neuromodulation ; 24(2): 300-306, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33159411

RESUMEN

OBJECTIVE: Deep brain stimulation (DBS) is considered an effective and safe treatment for patients with primary Meige syndrome (MS). Both the subthalamic nucleus (STN) and globus pallidus pars internus (Gpi) have been shown to be optional targets for electrode implantation to improve clinical symptoms, but the relationship between clinical outcomes and target is still unclear. The current study aims to compare the clinical outcomes of DBS with different electrode targets for primary MS. MATERIALS AND METHODS: We performed a retrospective study to assess the clinical outcomes for 17 consecutive patients with primary MS in Wuhan Union Hospital from January 2016 to September 2019. Six patients were treated by Gpi-DBS and 11 patients were treated by STN-DBS. All patients were assessed before surgery and at the last follow-up after surgery. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) including the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing. The median follow-up duration was 30.1 ± 13.1 months (range 6 months-52 months). RESULTS: In our study, DBS improved the BFMDRS-M scores by 70.52 ± 7.45% and the BFMDRS-D scores by 70.51 ± 8.38% for patients with MS. STN-DBS and Gpi-DBS had similar effects not only on the BFMDRS-M and BFMDRS-D scores, but also on the subitems including eyes, mouth, speech, and swallowing. The stimulation voltage for the Gpi was significantly higher than that for the STN. The improvements were similar in the general anesthesia and local anesthesia groups (p > 0.05). CONCLUSION: The curative effects of STN-DBS and Gpi-DBS on patients with primary MS are similar. Both the STN and Gpi could be effective targets of DBS for primary MS.


Asunto(s)
Estimulación Encefálica Profunda , Síndrome de Meige , Electrodos , Globo Pálido , Humanos , Síndrome de Meige/terapia , Estudios Retrospectivos , Resultado del Tratamiento
14.
J Neurosurg ; 136(4): 1211-1212, 2021 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-35366643
15.
Oncol Lett ; 20(4): 83, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32863916

RESUMEN

Glioma is one of the most common types of tumor of the central nervous system. Due to the aggressiveness and invasiveness of high-level gliomas, the survival time of patients with these tumors is short, at ~15 months, even after combined treatment with surgery, radiotherapy and/or chemotherapy. Recently, a number of studies have demonstrated that long non-coding RNA (lncRNAs) serve crucial roles in the multistep development of human gliomas. Gliomas acquire numerous biological abilities during multistep development that collectively constitute the hallmarks of glioma. Thus, in this review, the roles of lncRNAs associated with glioma hallmarks and the current and future prospects for their development are summarized.

16.
Medicine (Baltimore) ; 99(8): e19254, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080132

RESUMEN

OBJECTIVE: Quantitative apparent diffusion coefficient (ADC) values of diffusion weighted imaging (DWI) could be applied to grade gliomas. This meta-analysis was conducted to assess the accuracy of ADC analysis in differentiating high-grade (HGGs) from low-grade gliomas (LGGs). METHODS: PubMed, Cochrane library, Science Direct, and Embase were searched to identify suitable studies up to September 1, 2018. The quality of studies was evaluated by the quality assessment of diagnostic accuracy studies (QUADAS 2). We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic accuracy ratio (DOR) with 95% confidence intervals (CI), and determined the accuracy of the data by using the summary receiver operating characteristic (SROC) and calculating the area under the curve (AUC) to identity the accuracy of ADC analysis in grading gliomas. RESULTS: Eighteen studies including 1172 patients were included and analyzed. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC with 95% CIs of DWI with b values of 1000 s/mm for separating HGGs from LGGs were 0.81 (95% CI 0.75-0.86), 0.87 (95% CI 0.81-0.91), 6.1 (95% CI 4.2-8.9), 0.22 (95% CI 0.17-0.29), 28 (95% CI 17-45), and 0.91 (95% CI 0.88-0.93), respectively. DWI with b values of 3000 s/mm showed slightly higher accuracy than that of 1000 (sensitivity 0.80, specificity 0.90 and AUC 0.92). Meta-regression analyses showed that field strengths and b values had significant impacts on diagnostic efficacy. Deeks testing confirmed no significant publication bias in all studies. CONCLUSIONS: This meta-analysis suggested that ADC analysis of DWI have high accuracy in differentiating HGGs from LGGs. Standardized methodology is warranted to guide the use of this technique for clinical decision-making.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Glioma/diagnóstico por imagen , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
17.
Vet Microbiol ; 238: 108436, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31648726

RESUMEN

The level of cholesterol in host cells has been demonstrated to affect viral infection. Our previous studies showed that cholesterol-rich membrane rafts mediated the entry of classical swine fever virus (CSFV) into PK-15 or 3D4/21 cells, but the role of cholesterol post entry was still not clear. In this study, we found that CSFV replication before fusion was affected when the cholesterol trafficking in infected cells was disrupted using a cholesterol transport inhibitor, U18666A. Our data showed that U18666A affected both the fusion and replication steps in the life cycle of the virus, but not its binding and entry steps. The subsequent experiments confirmed that niemann-pick C1 (NPC1), a lysosomal membrane protein that helps cholesterol to leave the lysosome, was affected by U18666A, which led to the accumulation of cholesterol in lysosomes and inhibition of CSFV replication. Imipramine, a cationic hydrophobic amine similar to U18666A, also inhibited CSFV replication via similar mechanism. Surprisingly, the antiviral effect of U18666A was restored by the histone deacetylase inhibitor (HDACi), Vorinostat, which suggested that HDACi reverted the dysfunction of NPC1, and intra-cellular cholesterol accumulation disappeared and CSFV replicability resumed. Together, these data indicated that CSFV transformed from early endosome and late endosome into lysosome after endocytosis for further replication and that U18666A was a potential drug candidate for anti-pestivirus treatment.


Asunto(s)
Androstenos/farmacología , Antivirales/farmacología , Colesterol/metabolismo , Virus de la Fiebre Porcina Clásica/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , Transporte Biológico/efectos de los fármacos , Porcinos
18.
Artículo en Inglés | MEDLINE | ID: mdl-31248229

RESUMEN

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (dl-PCBs) are bioaccumulative compounds that may affect fetal growth and infant development. The aim of this study was to determine whether the pregnant women living near a chemical plant in Tianjin had a risk of exposure to dioxins. Concentrations of PCDD/Fs and dl-PCBs in 24 umbilical cord serum samples collected from pregnant women were measured using a high-resolution gas chromatograph with a high-resolution mass spectrometer (HRGC-HRMS) and an isotopic dilution method. The levels of ∑(PCDD/Fs + dl-PCBs) were in the range 476-8307 pg·g-1 lipid, with a mean of 3037 pg·g-1. The mean World Health Organization toxicity equivalent (WHO-TEQ) for PCDD/Fs and dl-PCBs was 14.0 and 2.14 pg·g-1 lipid, respectively. The PCDD/Fs and dl-PCBs contributed 86.7% and 13.3%, respectively, to the total TEQ. The octa-CDFs and penta-CBs were predominant for the PCDD/Fs and dl-PCBs, accounting for 57.6% and 74.3%, respectively. Several PCDD/F and dl-PCB congeners were highly correlated, such as PCB 105 and PCB 118 (r = 0.982, p < 0.001). Although the results hint at decreasing trends for PCDD/F and dl-PCBs by comparison with a similar study in Tianjin, a total TEQ of 41.7% of study participants had a body burden that exceeded the biomonitoring equivalents for dioxins. It was shown that pregnant women and infants had a health risk of exposure to dioxins.


Asunto(s)
Carga Corporal (Radioterapia) , Dibenzofuranos Policlorados/sangre , Exposición a Riesgos Ambientales/análisis , Sangre Fetal/química , Bifenilos Policlorados/sangre , Dibenzodioxinas Policloradas/sangre , Cordón Umbilical/química , Adulto , China , Femenino , Humanos , Lactante , Bifenilos Policlorados/toxicidad , Embarazo , Mujeres Embarazadas , Medición de Riesgo/métodos
19.
J Neurol Surg A Cent Eur Neurosurg ; 80(3): 213-219, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30913572

RESUMEN

OBJECTIVE: To assess the value of high-resolution magnetic resonance imaging (MRI) and three-dimensional (3D) reconstruction of the trigeminal nerve and the superior petrosal vein (SPV) in visualizing their anatomical relationship in patients with trigeminal neuralgia (TN). PATIENTS AND METHODS: This study included 97 patients with primary TN who underwent preoperative 3D constructive interference in steady state (CISS) MRI. Image analysis was performed by an independent observer blinded to the operative findings and then compared with surgical data. The 3D reconstruction was assessed dynamically using MIMICS software (Materialise Inc., Leuven, Belgium). RESULTS: The 3D relationship between visible structures seen on MRI was consistent with the intraoperative findings in all patients. All cases were divided into three groups by the degree of trigeminal nerve encroachment by SPV. Statistical analysis revealed that the distance from the SPV to the trigeminal nerve was significantly different among the three groups. The diameter of the SPV also differed among the three groups. CONCLUSION: Preoperative 3D imaging provides reliable and detailed information about the intraoperative anatomical relationship between the trigeminal nerve and the SPV. This evaluation is useful for preoperative planning.


Asunto(s)
Venas Cerebrales/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Nervio Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/diagnóstico por imagen , Adulto , Anciano , Venas Cerebrales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Nervio Trigémino/cirugía , Neuralgia del Trigémino/cirugía
20.
Acta Neurochir (Wien) ; 161(3): 509-515, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30511142

RESUMEN

Bilateral hemifacial spasm (biHFS) is an infrequent cranial nerve disorder that causes patients to suffer from severe psychological stress, and there are no reported cases of synchronous biHFS. In this study, a 46-year-old right-handed woman was diagnosed with a synchronous biHFS. After one unilateral microvascular decompression (MVD) surgery, the left facial twitching movements relieved immediately, and the right side twitching movements self-relieved the next day. Although there was a delayed hemorrhage, the patient achieved a satisfactory outcome defined as cessation of the twitching movements without recurrence. Based on the present case and related literature, we speculate that anatomical connections between bilateral facial nuclei and hyperactivity of facial nuclei play important roles in the biHFS, and they may, at least in some cases, be the decisive factors regarding the origin, development, and relief of the consequent contralateral spasm.


Asunto(s)
Espasmo Hemifacial/cirugía , Hemorragia/etiología , Cirugía para Descompresión Microvascular/efectos adversos , Complicaciones Posoperatorias/etiología , Adulto , Femenino , Humanos , Persona de Mediana Edad
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