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1.
Eur J Med Chem ; 218: 113401, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33831779

RESUMO

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by neuronal loss and cognitive impairment that harshly affect the elderly individuals. Currently, the available anti-AD pharmacological approaches are purely symptomatic to alleviate AD symptoms, and the curative effects of novel anti-AD drugs focused on Aß target are disappointing. Hence, there is a tremendous need to adjust AD therapeutic targets and discover novel anti-AD agents. In AD, mitochondrial dysfunction gradually triggers neuronal death from different aspects and worsens the occurrence and progress of AD. Consequently, it has been proposed that the intervention of impaired mitochondria represents an attractive breakthrough point for AD treatments. Due to chemical diversity, poly-pharmacological activities, few adverse effects and multiple targeting, natural products (NPs) have been identified as a valuable treasure for drug discovery and development. Multiple lines of studies have scientifically proven that NPs display ameliorative benefits in AD treatment in relation to mitochondrial dysfunction. This review surveys the complicated implications for mitochondrial dysregulation and AD, and then summarizes the potentials of NPs and their underlying molecular mechanisms against AD via reducing or improving mitochondrial dysfunction. It is expected that this work may open the window to speed up the development of innovative anti-AD drugs originated from NPs and improve upcoming AD therapeutics.

2.
Sci Rep ; 11(1): 7520, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824394

RESUMO

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

3.
J Virol Methods ; 292: 114125, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33745967

RESUMO

A host's adaptive immune system can protect against a wide variety of pathogens by producing diverse antibodies. The antibody repertoire is so vast that traditional low-throughput methods cannot fully sequence it. In this study, we developed a high-throughput sequencing (HTS) method for antibody repertoire assessment in swine, and tested it with or without porcine epidemic diarrhea virus (PEDV) infection. We isolated peripheral blood mononuclear cells from normal or PEDV-seropositive pigs and applied multiplex PCR to amplify the porcine B cell receptor heavy chain library, followed by HTS using the Illumina Miseq system to obtain full sequence information. The results from sequence analysis demonstrated that in normal conditions, several V gene segments were preferentially used, with IGHV1-4 and IGHV1S2 being the two most frequent. The IGHV usage in PEDV-seropositive pigs was not exactly the same as that of PEDV-seronegative pigs, with an increased usage of IGHV1-6. Our study provides an effective approach to comprehensively understand the overall porcine antibody repertoire, as well as to monitor broad antibody responses to viral challenge in pigs.

4.
Medicine (Baltimore) ; 100(10): e24940, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725855

RESUMO

ABSTRACT: Although non-alcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM), the diagnosis of NAFLD for T2DM patients remains a challenge.This study aimed to investigate the prevalence and risk factors for the NAFLD in T2DM outpatients.This is a retrospective, cross-sectional study that included 2405 T2DM patients treated and admitted for glucose control into the Endocrinology Department of our hospital from April 2017 to March 2019. Using strict exclusion criteria, the target patients were screened and divided into two groups: NAFLD patients (study group) and non-NAFLD patients (control group). Subsequently, 34 factors were compared between the two groups. Furthermore, multivariate analysis of the NAFLD risk factors was performed using logistic regression. Finally, the diagnostic significance of individual biochemical predictors, as well as the combined predictive indicator (CPI), for NAFLD was estimated using receiver operating characteristic (ROC) curve analysis.In this study, the overall prevalence of NAFLD in T2DM patients was 58.67%. Of the target patients, 17 factors were identified by univariate analysis to be associated with NAFLD, and 8 factors were found to be significant predictors for NAFLD using binary logistic regression modeling. Furthermore, the CPI and C-Peptide represent high diagnostic value for NAFLD in T2DM patients.This study provides a more comprehensive risk factor analysis for NAFLD in T2DM patients. These data can be used to provide timely diagnosis and effective management of NAFLD.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Prevalência , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco
5.
Medicine (Baltimore) ; 100(10): e25003, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725878

RESUMO

ABSTRACT: The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.


Assuntos
Antitrombinas/administração & dosagem , Doença das Coronárias/cirurgia , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/efeitos adversos , Feminino , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/efeitos adversos , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/induzido quimicamente , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Stents , Trombose/etiologia , Trombose/prevenção & controle , Resultado do Tratamento
6.
Plant J ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547688

RESUMO

Centromeres in eukaryotes are composed of tandem DNAs and retrotransposons. However, centromeric repeats exhibit considerable diversity, even among closely related species, and their origin and evolution are largely unknown. We conducted a genome-wide characterization of the centromeric sequences in sugarcane (Saccharum officinarum). Four centromeric tandem repeat sequences, So1, So103, So137 and So119, were isolated. So1 has a monomeric length of 137 bp, typical of a centromeric satellite, and has evolved four variants. However, these So1 variants had distinct centromere distributions and some were unique to an individual centromere. The distributions of the So1 variants were unexpectedly consistent among the Saccharum species that had different basic chromosome numbers or ploidy levels, thus suggesting evolutionary stability for approximately 7 million years in sugarcane. So103, So137 and So119 had unusually longer monomeric lengths that ranged from 327 to 1371 bp and lacked translational phasing on the CENH3 nucleosomes. Moreover, So103, So137 and So119 seemed to be highly similar to retrotransposons, which suggests that they originated from these mobile elements. Notably, all three repeats were flanked by direct repeats, and formed extrachromosomal circular DNAs (eccDNAs). The presence of circular molecules for these retrotransposon-derived centromeric satellites suggests an eccDNA-mediated centromeric satellite formation pathway in sugarcane.

7.
Transbound Emerg Dis ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555108

RESUMO

Toroviruses (ToVs), closely related but genetically distinct from coronaviruses, are known to infect horses, cows, pigs, goats and humans, mainly causing enteritic disorders. However, due to the lack of an adaptive culture system, porcine ToV (PToV) has received less attention. In this study, we developed a novel serological detection method based on the PToV envelope spike subunit 1 (S1) protein for the first time, and compared it to an existing indirect enzyme-linked immunosorbent assay (ELISA) based on the nucleocapsid protein. By using the S1-based ELISA, we carried out the first seroepidemiological survey of PToV in China, assaying both specific IgG and IgA responses in 1,037 serum samples collected from diarrheic pigs in eastern China. There was a relatively high incidence of seropositivity in pigs of different ages, especially one-week-old piglets and sows (78% and 43%), the former probably reflecting maternal antibodies. Furthermore, 3/20 (15%) of faecal samples collected from one PToV-seropositive swine herd in Zhejiang province tested positive by RT-PCR. The complete PToV genome was sequenced from one of these samples, and its phylogenetic relationship with other full-length PToV sequences available in GenBank was determined. Our data provide the first serological evidence for PToV infection in pigs from China, which will help elucidate the potential pathogenicity of PToV in pigs.

8.
Int J Rheum Dis ; 24(3): 380-390, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33523580

RESUMO

AIM: Gastrodia elata and Radix aconiti lateralis preparrata are respectively named as Tian-Ma and Fu-Zi (TF) in Chinese. We explored the active components against rheumatoid arthritis (RA) from an extensively used couplet of Chinese herbs, Gastrodia elata and Radix aconiti lateralis preparata (TF) via untargeted metabolomics and network pharmacological approaches. METHODS: Water extracts of TF were mixed at ratios 1:1, 3:2 and 2:3 (w/w). Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was then utilized as metabolomics screening. Human Metabolome (http://www.hmdb.ca/) and Lipidmaps (http://www.lipidmaps.org/) databases were used to annotate detected compounds. Further identification of vital genes and important pathways associated with the anti-RA properties of the TF preparations was done via network pharmacology, and verified by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Four key compounds involved in unsaturated fatty acid biosynthesis and isoflavonoid biosynthesis were identified through metabolomics analyses. Three key components of TF associated with anti-RA activity were linoleic acid, daidzein, and daidzin. Results of RT-qPCR revealed that all 3 tested TF couplets (1:1, 3:2, and 2:3) markedly suppressed the transcription of PTGS2. These results were consistent with our network pharmacological predictions. CONCLUSIONS: The anti-RA properties of Tian-Ma and Fu-Zi are associated with the inhibition of arachidonic acid metabolism pathway.

9.
Langmuir ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586440

RESUMO

Enhanced vapor condensation is a critical issue for improving the efficiency of energy conversion, thermal management, water recovery, and treatment. Low-energy surfaces incorporating micro/nanoscale roughness have been reported to significantly promote vapor condensation. In this research, the mesh structures of super-aligned carbon nanotube (SACNT) films were prepared by crossing monolayer SACNT films on a copper substrate. Then, the sustaining dropwise condensation was achieved on the SACNT mesh-coated surface. The SACNT mesh-coated surface could obviously enhance the coalescence and sweeping departure of the condensing droplets. Additionally, the measured overall heat transfer coefficient (HTC) of the SACNT mesh-coated surface demonstrated a 36% enhancement compared to that on the bare copper surface. The parallel stacking of SACNT films with different groove structures was also studied, and a 15% enhancement in the HTC was shown as compared with the bare copper surface. Furthermore, we developed a morphology-based model to theoretically analyze the condensation-enhancement mechanism on a SACNT mesh-coated surface. The SACNT surfaces also have advantages of low cost, durability, flexibility, and extensibility. Our findings revealed that the SACNT films could be readily used as vapor condensation-strengthening surfaces, further extending their potential applications to industrial equipment.

10.
J Dermatol ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608936

RESUMO

Kaposiform haemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors that can cause life-threatening Kasabach-Merritt phenomenon. No evidence-based treatment strategies have yet been established, and its management is still a challenge. The purpose of this multicenter prospective randomized controlled study was to evaluate and compare the efficacy of corticosteroid and vincristine (VCR) in the treatment of KHE and TA. All patients with KHE/TA who met the diagnostic criteria were consecutively recruited. The patients were randomized into a methylprednisolone (MP) group and a VCR group. The primary outcome was the single main parameter effective rate and overall effective rate of corticosteroid and VCR over 1 month after treatment. The single main parameters included platelets, fibrinogen, tumor size, texture, and appearance. From May 2016 to April 2018, a total of 59 patients completed the clinical trial, including 29 in the MP group and 30 in the VCR group. The results showed that VCR was superior to corticosteroid in the improvement of platelet (80.0% vs 44.0%, P = 0.019) and tumor texture (68.9% vs 30.8%, P = 0.007). Although the efficacy of VCR on fibrinogen (23.3% vs 20.7%, P = 1.000), tumor size (23.3% vs 13.8%, P = 0.273), and appearance (65.5% vs 46.2%, P = 0.120) was higher than that of corticosteroid, there was no significant difference (P > 0.05). Meanwhile, the overall effective rate of VCR was higher than that of corticosteroid (56.7% vs 31.0%), but the difference was also not statistically significant (P = 0.067). In conclusion, the therapeutic effect of VCR was significantly better than that of corticosteroid with regard to treating thrombocytopenia and tumor texture. We recommend that VCR could be an option for first-line treatment in KHE/TA patients.

11.
J Colloid Interface Sci ; 590: 144-153, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33524715

RESUMO

Addressing the inherent holes transport limitation of BiVO4 photoanode is crucial to achieve efficient photoelectrochemical (PEC) water splitting. The construction of the hole-transfer bridge between co-catalysts and BiVO4 photoanode could be an effective way to overcome sluggish hole-transfer kinetics of BiVO4 photoanode. Herein, CxNy/BiVO4 photoanode was prepared by coupling carbon nitride hydrogel (CNH) containing unsaturated N on the BiVO4 photoanode during annealing. CxNy/BiVO4 photoanode exhibited excellent PEC performance and stability. Photoelectrochemical tests proved that the coupling of CxNy accelerated holes transfer and enhanced oxygen evolution kinetics. X-ray photoelectron spectroscopy (XPS) and theoretical calculations confirmed the existence of the BiNV bond between BiVO4 photoanode and CxNy, which could serve as the hole-transfer bridge to significantly accelerate separation and transfer of carriers driven by the interfacial electric field. Moreover, it was found that the coupling of CxNy effectively inhibited the dissociation of metal ions through changing their coordination environment, resulting in the excellent stability of CxNy/BiVO4 photoanode. This result provides unique insights into vital roles of the interfacial structure, which might have a significant impact on the construction of PEC devices.

12.
Signal Transduct Target Ther ; 6(1): 58, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568628

RESUMO

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.


Assuntos
/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Cordão Umbilical , Idoso , Aloenxertos , /fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Bull Entomol Res ; : 1-10, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632348

RESUMO

The tobacco cutworm Spodoptera litura (Lepidoptera: Noctuidae) is a polyphagous pest with a highly selective and sensitive chemosensory system involved in complex physiological behaviors such as searching for food sources, feeding, courtship, and oviposition. However, effective management strategies for controlling the insect pest populations under threshold levels are lacking. Therefore, there is an urgent need to formulate eco-friendly pest control strategies based on the disruption of the insect chemosensory system. In this study, we identified 158 putative chemosensory genes based on transcriptomic and genomic data for S. litura, including 45 odorant-binding proteins (OBPs, nine were new), 23 chemosensory proteins (CSPs), 60 odorant receptors (ORs, three were new), and 30 gustatory receptors (GRs, three were new), a number higher than those reported by previous transcriptome studies. Subsequently, we constructed phylogenetic trees based on these genes in moths and analyzed the dynamic expression of various genes in head capsules across larval instars using quantitative real-time polymerase chain reaction. Nine genes-SlitOBP8, SlitOBP9, SlitOBP25, SlitCSP1, SlitCSP7, SlitCSP18, SlitOR34, SlitGR240, and SlitGR242-were highly expressed in the heads of 3- to 5-day-old S. litura larvae. The genes differentially expressed in olfactory organs during larval development might play crucial roles in the chemosensory system of S. litura larvae. Our findings substantially expand the gene inventory for S. litura and present potential target genes for further studies on larval feeding in S. litura.

14.
Plant Sci ; 304: 110806, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33568306

RESUMO

Control of gene transcription is crucial to regulate plant growth and development events, such as flowering, leaf senescence, and seed germination. Here we identified a NAC transcription factor (ScNAC23) isolated from sugarcane (cv. ROC22). Analysis by qRT-PCR indicated that ScNAC23 expression was strongly induced in mature leaves and flowering varieties and was also responsive to exogenous treatment with the hormone gibberellin (GA). Ectopic expression of ScNAC23 in Arabidopsis accelerated bolting, flowering, and leaf senescence compared to wild type plants. Furthermore, Arabidopsis overexpressed ScNAC23 were more sensitive to GA than the wild type, and exogenous GA significantly accelerated flowering and senescence in the ScNAC23-overexpressed ones. A direct interaction between ScNAC23 and ScGAI, an inhibitor of GA signaling, was confirmed by yeast-two hybrid, bimolecular fluorescence complementation, and GST-pull down assay. The putative GA-ScNAC23-LFY/SAGs regulator module might provide a new sight into the molecular action of GA to accelerating flowering and leaf senescence in sugarcane.

15.
Transl Psychiatry ; 11(1): 140, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627628

RESUMO

The transcription factor erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) play a key role in depression. However, the molecular mechanisms underlying the crosstalk between Nrf2 and BDNF in depression remain unclear. We examined whether Nrf2 regulates the transcription of Bdnf by binding to its exon I promoter. Furthermore, the role of Nrf2 and BDNF in the brain regions from mice with depression-like phenotypes was examined. Nrf2 regulated the transcription of Bdnf by binding to its exon I promoter. Activation of Nrf2 by sulforaphane (SFN) showed fast-acting antidepressant-like effects in mice by activating BDNF as well as by inhibiting the expression of its transcriptional repressors (HDAC2, mSin3A, and MeCP2) and revising abnormal synaptic transmission. In contrast, SFN did not affect the protein expression of BDNF and its transcriptional repressor proteins in the medial prefrontal cortex (mPFC) and hippocampus, nor did it reduce depression-like behaviors and abnormal synaptic transmission in Nrf2 knockout mice. In the mouse model of chronic social defeat stress (CSDS), protein levels of Nrf2 and BDNF in the mPFC and hippocampus were lower than those of control and CSDS-resilient mice. In contrast, the protein levels of BDNF transcriptional repressors in the CSDS-susceptible mice were higher than those of control and CSDS-resilient mice. These data suggest that Nrf2 activation increases the expression of Bdnf and decreases the expression of its transcriptional repressors, which result in fast-acting antidepressant-like actions. Furthermore, abnormalities in crosstalk between Nrf2 and BDNF may contribute to the resilience versus susceptibility of mice against CSDS.

17.
Virology ; 556: 1-8, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33515858

RESUMO

Porcine deltacoronavirus (PDCoV) is one of the emerged coronaviruses posing a significant threat to the swine industry. Previous work showed the presence of a viral accessory protein NS6 in PDCoV-infected cells. In this study, we detected the expression of the NS6 protein in small intestinal tissues of PDCoV-infected piglets. In addition, SDS-PAGE and Western blot analysis of sucrose gradient-purified virions showed the presence of a 13-kDa NS6 protein. Further evidences of the presence of NS6 in the PDCoV virions were obtained by immunogold staining of purified virions with anti-NS6 antiserum, and by immunoprecipitation of NS6 from purified virions. Finally, the anti-NS6 antibody was not able to neutralize PDCoV in cultured cells. These data establish for the first time that the accessory protein NS6 is expressed during infection in vivo and incorporated into PDCoV virions.


Assuntos
Infecções por Coronavirus/veterinária , Doenças dos Suínos/virologia , Proteínas não Estruturais Virais/metabolismo , Vírion/metabolismo , Animais , Anticorpos Antivirais/imunologia , Linhagem Celular , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/virologia , Camundongos , Coelhos , Suínos , Doenças dos Suínos/metabolismo , Proteínas não Estruturais Virais/imunologia
18.
Surg Endosc ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492500

RESUMO

BACKGROUND AND AIMS: Esophageal stricture is a distressing issue for patients with early esophageal cancer following extensive endoscopic submucosal dissection (ESD), and the current steroid-based approaches are unsatisfactory for stricture prophylaxis. We evaluated the efficacy of oral hydrocortisone sodium succinate and aluminum phosphate gel (OHA) for stricture prophylaxis after extensive ESD. METHODS: Patients undergoing > 3/4 circumferential ESD were randomized to either the endoscopic loco-regional triamcinolone acetonide injection (ETI) plus oral prednisone group or the OHA group. The primary endpoint was incidence of esophageal stricture, and the secondary endpoints included adverse events (AEs) and endoscopic balloon dilations (EBDs). RESULTS: The incidence of esophageal stricture in OHA group (per-protocol analysis, 9.4%, 3/32; intention-to-treat analysis, 12.1%, 4/33) was significantly less than that of control group (per-protocol analysis, 35.5%, 11/31, P = 0.013; intention-to-treat analysis, 39.4%, 13/33, P = 0.011). Two sessions of EBD were necessary to release all strictures in the OHA group, while the similar EBDs (median 2, range 1-4) for 11 of the control. Operation-related AEs included infection (control vs. OHA group = 9.7% vs. 31.3%, P = 0.034), operation-related hypokalemia (19.4% vs. 31.3%, P = 0.278), perforation (3.2% vs. 3.1%), post-ESD hemorrhage (6.5% vs. 0%), and cardiac arrhythmia (0% vs. 6.3%). Steroid-related AEs included steroid-related hypokalemia (16.1% vs. 25%) and bone fracture (3.2% vs. 0%). Multivariate logistic regression analysis demonstrated that OHA was an independent protective factor for stricture (OR 0.079; 95%CI 0.011, 0.544; P = 0.01) and mucosal defect > 11/12 circumference was an independent risk factor (OR 49.91; 95%CI 6.7, 371.83; P < 0.001). CONCLUSIONS: OHA showed significantly better efficacy in preventing esophageal stricture after > 3/4 circumferential ESD compared to ETI plus oral prednisone.

19.
Cell Calcium ; 94: 102360, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33516131

RESUMO

Ion channels are necessary for correct lysosomal function including degradation of cargoes originating from endocytosis. Almost all enveloped viruses, including coronaviruses (CoVs), enter host cells via endocytosis, and do not escape endosomal compartments into the cytoplasm (via fusion with the endolysosomal membrane) unless the virus-encoded envelope proteins are cleaved by lysosomal proteases. With the ongoing outbreak of severe acute respiratory syndrome (SARS)-CoV-2, endolysosomal two-pore channels represent an exciting and emerging target for antiviral therapies. This review focuses on the latest knowledge of the effects of lysosomal ion channels on the cellular entry and uncoating of enveloped viruses, which may aid in development of novel therapies against emerging infectious diseases such as SARS-CoV-2.


Assuntos
Antivirais/uso terapêutico , Canais Iônicos/fisiologia , Lisossomos/virologia , /fisiologia , Internalização do Vírus , Desenvelopamento do Vírus , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Antivirais/farmacologia , Desenho de Fármacos , Endocitose , Endossomos/metabolismo , Endossomos/virologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Hidrazonas/farmacologia , Hidrazonas/uso terapêutico , Canais Iônicos/classificação , Lisossomos/enzimologia , Lisossomos/metabolismo , Modelos Biológicos , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , ATPases Vacuolares Próton-Translocadoras/fisiologia , Internalização do Vírus/efeitos dos fármacos , Desenvelopamento do Vírus/efeitos dos fármacos
20.
J Craniomaxillofac Surg ; 49(3): 177-183, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33451942

RESUMO

BACKGROUND: Anterior Disc Displacement without Reduction (ADDwoR) in adolescence can result in condylar resorption which produces mandibular retrusion/deviation (MR/D) in adulthood. This study aims to analyze the therapeutic effect of simultaneous genioplasty and temporomandibular joint (TMJ) anchorage surgery on ADDwoR with MR/D patients. METHODS: During 2016-2018, ADDwoR with MR/D cases were included and underwent TMJ anchorage surgery and genioplasty guided by digital design. Pre-/Post-surgical clinical manifestations, facial photography, radiographic data, facial shape satisfaction of clinicians/patients/third-party were recorded and analyzed. RESULTS: A total of 32 cases (52 joints) were included. The average age was 24.09. Ratio of male/female was 4/28. Visual analog pain scale (VAS) score pre-/post-surgical ranged from 3 to 9 and 0-3, with an average of 6.03 and 1.18 (p < 0.01). Maximal mouth opening pre-/post-surgical ranged from 16 to 33 mm and 33-40 mm, with an average of 22.43 mm and 36.46 mm (p < 0.01). MRI was completed and showed stable disc reduction without recurrence 1 year postoperatively. MR/D was corrected and a better face shape was obtained. The satisfaction rate of clinicians, patients and third-parties was 92.375%, 94.156% and 94.218%, with an average of 93.583%. CONCLUSION: For ADDwoR with MR/D patients, simultaneous TMJ anchorage surgery and genioplasty can improve TMJ symptoms/functions, correct facial appearance, and enhance the degree of satisfaction. The postoperative effect is stable, safe and reliable, which is worthy of clinical promotion.


Assuntos
Luxações Articulares , Transtornos da Articulação Temporomandibular , Adolescente , Adulto , Feminino , Mentoplastia , Humanos , Imagem por Ressonância Magnética , Masculino , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/cirurgia , Resultado do Tratamento , Adulto Jovem
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