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1.
Int Immunopharmacol ; 93: 107419, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548580

RESUMO

BACKGROUND: Airway epithelial cells (AECs) act as the first barrier protecting against invasion of environment agents and maintain integrity of lung structure and function. Dysfunction of airway epithelial barrier has been shown to be involved in ALI/ARDS pathogenesis. Yet, the exact mechanism is still obscure. Our study evaluated whether the receptor for advanced glycation end products (RAGE) mediates impaired airway epithelial barrier in LPS-induced murine ALI model. METHODS: Male BALB/c mice were subjected to intratracheal instillation of LPS to generate an ALI model. Inhibitors of RAGE, FPS-ZM1 and Azeliragon were respectively given to the mice through intraperitoneal injection. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected for further analysis. RESULTS: LPS exposure led to markedly increased expression of RAGE and its ligands HMGB1, HSP70, S100b. Treatment of FPS-ZM1 or Azeliragon not only effectively descended the expression of RAGE and its ligands but also attenuated LPS-induced neutrophil-predominant airway inflammation and injury, decreased levels of IL-6, IL-1ß and TNF-α in BALF, alleviated increased alveolar-capillary permeability and pulmonary edema. LPS stimulation significantly impaired the integrity of airway epithelium, paralleled with dislocation of adheren junction (AJ) protein E-cadherin at cell-cell contacts and down-expression of both AJ and tight junction (TJ) proteins Claudin-2 and occludin, all of which were dramatically rescued by RAGE inhibition. CONCLUSION: RAGE signaling mediates airway epithelial barrier dysfunction in a LPS-induced ALI murine model.

2.
J Magn Reson Imaging ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586159

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global population. The standard of diagnosis, biopsy, is invasive and affected by sampling error and inter-reader variability. We hypothesized that widely available rapid MRI techniques could be used to predict nonalcoholic steatohepatitis (NASH) noninvasively by measuring liver stiffness, with magnetic resonance elastography (MRE), and liver fat, with chemical shift-encoded (CSE) MRI. Besides, we validate an automated image analysis technique to maximize the utility of these methods. PURPOSE: To implement and test an automated system for analyzing CSE-MRI and MRE data coupled with model-based prediction of NASH. STUDY TYPE: Prospective. SUBJECTS: Eighty-three patients with suspected NAFLD. FIELD STRENGTH/SEQUENCE: A 1.5 T using a flow-compensated motion-encoded gradient echo MRE sequence and a multiecho CSE-MRI sequence. ASSESSMENTS: The MRE and CSE-MRI data were analyzed by two readers (5+ and 1 years of experience) and an automated algorithm. A logistic regression model to predict pathology-diagnosed NASH was trained based on stiffness and proton density fat fraction, and the area under the receiver operating characteristic curve (AUROC) was calculated using 10-fold cross validation for models based on both automated and manual measurements. A separate model was trained to predict the NASH severity score (NAS). STATISTICAL TESTS: Pearson's correlation, Bland-Altman, AUROC, C-statistic. RESULTS: The agreement between automated measurements and the more experienced reader (R2 = 0.87 for stiffness and R2 = 0.99 for proton density fat fraction [PDFF]) was slightly better than the agreement between readers (R2 = 0.85 and 0.98). The model for predicting biopsy-diagnosed NASH had an AUROC of 0.87. The NAS-prediction model had a C-statistic of 0.85. DATA CONCLUSION: We demonstrated a workflow that used a limited MRI acquisition protocol and fully automated analysis to predict NASH with high accuracy. These methods show promise to provide a reliable noninvasive alternative to biopsy for NASH-screening in populations with NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

3.
Pestic Biochem Physiol ; 172: 104766, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518053

RESUMO

According to the pharmacophore binding strategy and principle of bioelectronic isobaric, used the sulfonylurea bridge as the parent structure, a series of novel thiourea compounds containing aromatic-substituted pyrimidines were designed and synthesized. The preliminary herbicidal activity tests showed that some compounds had good herbicidal activity against Digitaria adscendens, Amaranthus retroflexus, especially for compound 4d and 4f. The results showed that compound 4d had an inhibition rate of 81.5% on the root growth of Brassica napus L. at the concentration of 100 mg L-1, and compound 4f had an inhibition rate of 81% on the root growth of Digitaria adscendens at the concentration of 100 mg L-1. Compounds 4d and 4f had higher comparative activity on Echinochloa crus-galli than the commercial herbicide bensulfuron-methyl. The preliminary structure-activity relationship (SAR) was also summarized. We also tested the in vivo AHAS enzyme activity inhibition experiment of 14 compounds at 100 mg L-1, and the results showed that they all have inhibitory activity on the enzyme, with the highest inhibition rate reaching 44.4% (compound 4d). Based on the results of molecular docking to yeast acetohydroxyacid synthase (AHAS), the possible herbicidal activity mechanism of these compounds was evaluated.


Assuntos
Acetolactato Sintase , Herbicidas , Acetolactato Sintase/metabolismo , Herbicidas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Tioureia/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-33593048

RESUMO

Conversion of dinitrogen (N2) molecules into ammonia through electrochemical methods is a promising alternative to the traditional Haber-Bosch process. However, searching for an eligible electrocatalyst with high stability, low-onset potential, and superior selectivity is still one of the most challenging and attractive topics for the electrochemical N2 reduction reaction (NRR). Here, by means of first-principles calculations and the conductor-like screening model, four comprehensive criteria were proposed to screen out eligible NRR electrocatalysts from 29 atomic transition metals embedded on the defective boron phosphide (BP) monolayer with B-monovacancy (M/BP single-atom catalysts, SAC, M = Sc-Zn, Y-Cd, and Hf-Hg). Consequently, the Nb/BP and W/BP SACs are identified as the promising candidates, on which the N2 molecule can only be activated through the enzymatic pathway with the onset potentials of -0.25 and -0.19 V, and selectivities of 90.5 and 100%, respectively. It is worth noting that the W/BP SAC has the lowest overpotential among the 29 systems investigated. The electronic properties were also calculated in detail to analyze the activity origin. Importantly, the Nb/BP and W/BP SACs possess high thermal stabilities due to that their structures can be retained very well up to 1000 and 700 K, respectively. This work not only provides an efficient and reliable method to screen eligible NRR electrocatalysts but also paves a new way for advancing sustainable ammonia synthesis.

5.
Nature ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33505026

RESUMO

METTL3 (methyltransferase-like 3) mediates the N6-methyladenosine (m6A) methylation of mRNA, which affects the stability of mRNA and its translation into protein1. METTL3 also binds chromatin2-4, but the role of METTL3 and m6A methylation in chromatin is not fully understood. Here we show that METTL3 regulates mouse embryonic stem-cell heterochromatin, the integrity of which is critical for silencing retroviral elements and for mammalian development5. METTL3 predominantly localizes to the intracisternal A particle (IAP)-type family of endogenous retroviruses. Knockout of Mettl3 impairs the deposition of multiple heterochromatin marks onto METTL3-targeted IAPs, and upregulates IAP transcription, suggesting that METTL3 is important for the integrity of IAP heterochromatin. We provide further evidence that RNA transcripts derived from METTL3-bound IAPs are associated with chromatin and are m6A-methylated. These m6A-marked transcripts are bound by the m6A reader YTHDC1, which interacts with METTL3 and in turn promotes the association of METTL3 with chromatin. METTL3 also interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28, and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m6A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals.

6.
Microb Pathog ; 152: 104743, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33484812

RESUMO

OBJECT: To analyze the difference in biofilm formation between carbapenem-resistant and carbapenem-sensitive Klebsiella pneumoniae based on analysis of mrkH distribution and to further explore the function of mrkH for biofilm formation from the perspective of gene regulation. METHODS: 40 imipenem-resistant strains and 40 imipenem-sensitive strains were selected to conduct experiments. Carbapenem (imipenem) susceptibility test was performed by the agar-dilution method. blaKPC resistance gene, type 3 fimbriae-related coding genes (mrkA and mrkD) and regulation gene (mrkH) were screened by PCR. Biofilm formation assay was performed using crystal violet staining method in MHB. The relative expression of genes that critically involved in biofilm formation (mrkA, luxS, pgaA) and carbapenem resistance (ompk35, ompk36, acrB) were measured by quantitative real-time PCR (qRT-PCR). Furthermore, the mrkH cassette was cloned into pGEM-T Easy plasmid to yield pGEM:pmrkH and expressed in Escherichia coli DH5α and K. pneumoniae FK1911, and the biofilm formation assay after transformation was further tested. RESULTS: The MICs of imipenem were all more than 16 µg/mL in 40 imipenem-resistant strains and ranged from 0.125 µg/mL to 0.5 µg/mL in 40 imipenem-sensitive strains. Moreover, the blaKPC was identified in the 40 imipenem-resistant K. pneumoniae strains. All 80 K. pneumoniae strains were found to carry mrkA and mrkD genes. Interestingly, the mrkH gene was detected in 43 strains, of which 32 were carbapenem-sensitive strains. The biofilm formation capacity of strains carried mrkH cassette was significantly higher than other 37 strains in MHB media. The relative expression of mrkA in K. pneumoniae carrying mrkH gene was significantly up-regulated. Importantly, the biofilm formation ability of FK1911-pGEM:pmrkH strain was more higher than the strain of FK1911 in MHB medium. CONCLUSIONS: Our data demonstrated that MrkH played a crucial role in the regulation of biofilm formation by K. pneumoniae. In contrast to carbapenem-sensitive K. pneumoniae, carbapenem-resistant K. pneumoniae was less likely to have strong biofilm-forming capacity because it does not carry the mrkH gene.

7.
J Sci Food Agric ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275282

RESUMO

BACKGROUND: Glycidyl esters (GEs) have attracted worldwide attention for their potential harm to human health. The GEs in edible oils mainly form during the deodorization of oil refining processes. We used sesamol and sesamolin to inhibit the formation of GEs in a model corn oil (MCO), model palm oil (MPO) and model rice bran oil (MRO) during a deodorization process. RESULTS: The results showed that in the three model oils, the total GEs content was in the following order from highest to lowest: MRO (1437.98 µg kg-1 ) > MPO (388.64 µg kg-1 ) > MCO (314.81 µg kg-1 ). The inhibitory effect of the three antioxidants on the formation of GEs in the MCO was in the following order from strongest to weakest: tert-butylhydroquinone (TBHQ) > sesamol > sesamolin. CONCLUSION: When the mass percentage of sesamol was 0.05%, its inhibition percentage on GEs was close to the inhibition percentage of 0.02% added TBHQ. This research will provide a foundation for understanding how to inhibit the formation of GEs in oils by adding sesamol during the deodorization process. This article is protected by copyright. All rights reserved.

8.
Zhonghua Nan Ke Xue ; 26(7): 605-610, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-33377715

RESUMO

Objective: To analyze the whole genome sequences of Staphylococcus aureus strains from the sperm of infertile males and identify the gene which may induce the inhibition of sperm motility (ISM). METHODS: Twenty-two Staphylococcus aureus strains were isolated from the sperm of infertile males in the First Hospital Affiliated to Wenzhou Medical University and, according to the ability of ISM, divided into an ISM and a non-ISM group. Two strains most representative of the biological function of each group were selected, namely MJ015 from the ISM and MJ163 from the non-ISM group, and DNA extracted from them for whole genome sequencing. The data obtained were subjected to whole-genome sequence assembly and submitted to NCBI for annotation, with the accession number of CP038183 for MJ015 and CP038229 for MJ163. The whole genome sequences of MJ015 and MJ163 were compared in full detail using BRIG and Artemis software suite to identify the target gene. RESULTS: The whole genome sequence of MJ015 was 2 784 836 bp in length, containing 2 plasmids, and that of MJ163 was 2 746 673, containing 1 plasmid, each with a 32.13%, 32.08% content of guanine-cytosine (GC), and annotated with 2 921 and 2 844 genes respectively. Comparison between the whole genome sequences of MJ015 and MJ163 revealed an almost 130 kb gap, in which a gene named sak was found to express a potential serum inhibition factor, whose transcription product was proved to be a differentially expressed protein in the two strains. CONCLUSIONS: The gene sak in MJ015 may play a key role in the inhibition of sperm mobility, but the inhibition intensity of its transcription product staphylococcus kinase has to be further studied.


Assuntos
Genes Bacterianos , Infertilidade Masculina/microbiologia , Motilidade Espermática , Infecções Estafilocócicas/complicações , Staphylococcus aureus/genética , DNA Bacteriano/genética , Humanos , Masculino , Espermatozoides
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 247: 119126, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33160136

RESUMO

In this work, the monodisperse polystyrene colloidal particles/Ag/zeolite imidazole framework (PS/Ag/ZIF-8) substrate was successfully prepared and served as SERS active substrate. The composition, structure and morphology of the PS/Ag/ZIF-8 substrates were studied by XRD, SEM, UV-Vis and XPS measurements. The main finding of this study was that the as-prepared PS/Ag/ZIF-8 substrate could exhibit outstanding SERS property when 4-mercaptobenzoic acid (4-MBA) was used as the SERS probes. The SERS mechanism was attributed to the combined effect of the electromagnetic enhancement and chemical enhancement (CT). In addition, the SERS behavior of the sandwich PS/Ag/ZIF-8 substrate exhibit a laser wavelength-dependence CT effect with changing the laser source (473 nm, 514 nm, 633 nm and 785 nm). The wavelength-dependence CT mechanism were discussed briefly in the article. The results showed that the chemical interaction in the structure is a necessary condition for occurrence of the CT. The CT process can be evaluated quantitatively by the charge transfer degree (ρCT). Moreover, the enhancement factor (EF) of 1.23 × 106 was obtained with 4-MBA probes adsorbed on the synthesized PS/Ag/ZIF-8 substrate. More importantly, our research may open the door for developing the SERS substrate research with the well-studied metal-organic frameworks nanostructures materials.

10.
Ann Acad Med Singap ; 49(8): 530-537, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33164022

RESUMO

INTRODUCTION: In this study, a comparison of clinical, epidemiological and laboratory parameters between symptomatic and asymptomatic children with SARS-CoV-2 infection was performed. MATERIALS AND METHODS: Data from all children with laboratory confirmed SARS-CoV-2 infection admitted to KK Women's and Children's Hospital (KKH), Singapore, from January to May 2020 were analysed. RESULTS: Of the 39 COVID-19 children included, 38.5% were asymptomatic. Household transmission accounted for 95% of cases. The presenting symptoms of symptomatic children were low-grade fever (54.2%), rhinorrhoea (45.8%), sore throat (25%), diarrhoea (12.5%) and acute olfactory dysfunction (5.4%). Children of Chinese ethnicity (37.5% vs 6.7%), complete blood count (45.8% vs 6.7%) and liver enzyme abnormalities (25% vs 7.7%) were more common in symptomatic versus asymptomatic children. All children had a mild disease course and none required oxygen supplementation or intensive care. CONCLUSIONS: The high proportion of asymptomatic infected children coupled with household transmission as the main source of paediatric COVID-19 infection underscores the importance of early screening and isolation of children upon detection of an index case of COVID-19 in a household. Symptomatic children were more likely to have abnormal laboratory parameters but they did not have a poorer outcome compared to asymptomatic cases.


Assuntos
Infecções Assintomáticas/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adolescente , Fatores Etários , Betacoronavirus , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Coronavirus/complicações , Hospitalização , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Pandemias , Pneumonia Viral/complicações , Singapura , Avaliação de Sintomas
11.
Nanotechnology ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33212428

RESUMO

With extremely high optical absorption coefficient in infrared regime, lead sulfide (PbS) quantum dots (QDs)-based photodetectors are promising for diverse applications. In recent years, synthesis of materials has made great progress, but the problem of low sensitivity of quantum dots photodetector still unresolved. In this work, the introduction of a tunneling organic layer effectively address this problem. The dark current is decreased by the appropriate thickness of polymethyl methacrylate (PMMA) barrier layer by suppressing the spontaneous migration of ions, and the photogenerated carriers are little effected, thereby the responsivity of the device is improved. As a result, the device exhibits a high responsivity of 3.73*105 mA/W and a giant specific detectivity of 4.01*1013 Jones at a low voltage of -1 V under 1064 nm illumination. In the self-powered mode, the light/dark current ratio is about 107, the responsivity reaches a value of 157.6 mA/W, and the detectivity up to 5.9*1011 Jones. The performance of the photodetectors is obviously better than most of the reported QDs photodetectors. The design of this device structure provides a new solution to the problem of low sensitivity and high leakage current of quantum dots based infrared photodetectors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33213867

RESUMO

Lithium ion batteries are attracting ever increasing attention due to their advantages of high energy/ power density, environmental friendly, lifetime and low cost. As a star in the field of materials and energy, perovskites have received extensive attention due to their attracting physical and chemical properties. Herein, CaMnO3, one material from the perovskite family is introduced as a novel anode material for lithium ion batteries, and its electrochemical performance at different temperatures is systematically investigated. CaMnO3 has been synthesized using a liquid phase synthesis method followed by high temperature calcination. The as-obtained CaMnO3 exhibits an initial high discharge capacity of 708.4 mAh g-1, superior rate capability and stable cycling performance at room temperature, the specific capacity is 102.5 mAh g-1 after 500 cycles at a current density of 0.1 A g-1. Additionally, at an extreme temperature of 0 °C, the discapacity can reach 138.2 mAh g-1 at a current density of 0.05 A g-1. At high temperature of 50 °C, the reversible discharge capacity is up to 216.5 mAh g-1under the same condition. It is believed that this contribution may lay the foundation for the application of perovskites in other rechargeable batteries and energy storage devices.

13.
Nucleic Acids Res ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33137193

RESUMO

Anti-CRISPR (Acr) proteins naturally inhibit CRISPR-Cas adaptive immune systems across bacterial and archaeal domains of life. This emerging field has caused a paradigm shift in the way we think about the CRISPR-Cas system, and promises a number of useful applications from gene editing to phage therapy. As the number of verified and predicted Acrs rapidly expands, few online resources have been developed to deal with this wealth of information. To overcome this shortcoming, we developed AcrHub, an integrative database to provide an all-in-one solution for investigating, predicting and mapping Acr proteins. AcrHub catalogs 339 non-redundant experimentally validated Acrs and over 70 000 predicted Acrs extracted from genome sequence data from a diverse range of prokaryotic organisms and their viruses. It integrates state-of-the-art predictors to predict potential Acrs, and incorporates three analytical modules: similarity analysis, phylogenetic analysis and homology network analysis, to analyze their relationships with known Acrs. By interconnecting all modules as a platform, AcrHub presents enriched and in-depth analysis of known and potential Acrs and therefore provides new and exciting insights into the future of Acr discovery and validation. AcrHub is freely available at http://pacrispr.erc.monash.edu/AcrHub/.

14.
Food Res Int ; 137: 109742, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233307

RESUMO

Quorum sensing exists widely in all kinds of microorganisms and is a communication channel for microorganisms. Many bacterial processes, including virulence factor expression, biofilm formation, and viable but non-culturable (VBNC) cell resuscitation, are mediated by quorum sensing, and biofilm formation complicates the treatment of various infections. Foodborne pathogens can enter VBNC state in extreme environments, and pathogens in VBNC state can evade traditional detection and resuscitate under appropriate conditions, causing potential harm to human health. The disruption of quorum sensing may decisively help control biofilm formation and VBNC cell resuscitation. This review describes the quorum sensing systems of various bacteria and major fungi, and summarizes the role of bacterial quorum sensing system in biofilm formation and VBNC resuscitation. In addition, the relationship between quorum sensing inhibitors (QSI) with biofilms and VBNC is also discussed.

15.
Front Microbiol ; 11: 581802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193216

RESUMO

The global shrimp industry has suffered bacterial diseases caused mainly by Vibrio species. The typical vibriosis, acute hepatopancreatic necrosis disease (AHPND), has resulted in mass mortality and devastating economic losses. Thus, therapeutic strategies are highly needed to decrease the risk of vibriosis outbreaks. Herein, we initially identified that the growth of the causative agent of AHPND, Vibrio parahaemolyticus (VP AHPND ) and other vibrios in Pacific white shrimp (Litopenaeus vannamei) was inhibited by a Bacillus subtilis strain BSXE-1601. The natural products amicoumacins A, B, and C were purified from the cell-free supernatant from the strain BSXE-1601, but only amicoumacin A was demonstrated to be responsible for this anti-Vibrio activity. Our discovery provided the first evidence that amicoumacin A was highly active against shrimp pathogens, including the representative strain VP AHPND . Furthermore, we elucidated the amicoumacin A biosynthetic gene cluster by whole genome sequencing of the B. subtilis strain BSXE-1601. In addition to amicoumacin A, the strain BSXE-1601 genome harbored other genes encoding bacillibactin, fengycin, surfactin, bacilysin, and subtilosin A, all of which have previously reported antagonistic activities against pathogenic strains. The whole-genome analysis provided unequivocal evidence in support of the huge potential of the strain BSXE-1601 to produce diverse biologically antagonistic natural products, which may facilitate further studies on the effective therapeutics for detrimental diseases in shrimp.

16.
J Psychosom Res ; 139: 110270, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070044

RESUMO

BACKGROUND: The outbreak of COVID 19 in December 2019 spread quickly and overwhelmed the local healthcare system of the epicenter. A total of 346 medical assistance teams with 42,600 reserve medics were mobilized from around the country for emergency assistance. This study aims to examine the incidence of mental health symptoms and predictors of Post-Traumatic Stress Disorders (PTSD) symptoms among the reserve medics working in Wuhan, the capital city of Hubei Province. METHODS: An anonymous survey was conducted from April 4-6, 2020 among the medics upon their returning home. A total of 225 surveys were returned with a response rate of 83%. The survey consisted of questionnaires about the medics' demographic information, social relations, mental health status (e.g. IES-R and DASS-21) and other work-related information. Mann-Whitney U Test, Kruskal-Wallis Test and hierarchical logistic regression models were used to examine the predictors of PTSD symptoms. RESULTS: During the stay in Wuhan, the medics experienced high levels of depression (46.7%), anxiety (35.6%) and stress symptoms (16.0%). Upon returning home, the overall prevalence of clinically concerned PTSD symptoms was as high as 31.6%. Further analyses revealed that PTSD symptoms and its subscales were significantly associated with age, collegial relationship and mental health status during their service. CONCLUSION: The reserve medics reported a high prevalence of depression, anxiety and stress as well as clinically concerned PTSD symptoms. Comprehensive screening and intervention programs should be in place to help reserve medics cope with mental health challenges and build resilience during the COVID 19 pandemic.

17.
Clin Exp Rheumatol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33124557

RESUMO

OBJECTIVES: The purpose of this study was to determine the expression of related genes in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), to identify hub genes, and to systematically analyse the functions, pathways, and networks of these genes. METHODS: The PubMed identifiers (PMIDs) of relevant publications were obtained from the PubMed database, and gene data were extracted from these documents using the text mining software PubTator. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to obtain enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway information. In addition, the STRING database was used to construct a protein-protein interaction (PPI) network. Genes with which at least 10 other genes interacted were identified as hub genes. RESULTS: A total of 216 genes were identified as being associated with treatment efficacy for MTX, of which 14 pathways exhibited significant correlation (p<0.05, FDR<0.05). In addition, the constructed MTX treatment-related network consisted of 267 interactions. Fourteen genes were found to interact with at least 10 other genes (p<0.05, FDR<0.05) and identified as hub genes in the PPI network. These genes were JAK1, MAPK1, JUN, AKT1, MAPK14, MAPK8, FGB, FN1, ALB, B2M, IL2RB, GGH, IL2RA, and TP53. CONCLUSIONS: This study will assist in elucidating the molecular mechanisms associated with the treatment efficacy of MTX for RA and provide a scientific rationale for guiding patient medication. However, the relationship between particular genes and the efficacy of MTX treatment for RA patients requires additional investigation.

18.
Pancreas ; 49(10): 1307-1314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122518

RESUMO

OBJECTIVES: The interferon-induced protein with multiple tetratricopeptide repeats 3 (IFIT3) seems to be associated with the prognosis in pancreatic cancer. Here we clarify whether the heterogeneity of IFIT3 expression affects previous IFIT3 analysis. METHODS: This retrospective study analyzes pancreatic cancer tissue samples retrieved by surgery from 2 independent patient cohorts. Patients underwent either primary surgery (n = 72) or received neoadjuvant chemotherapy (n = 12). Immunohistochemistry assessed IFIT3 expression and its heterogeneity. Complementarily, we analyzed publicly available transcriptomic data (n = 903). RESULTS: Of the primarily resected tumors, 16.4% were heterogeneous. Patients with IFIT3-negative tumors did not survive longer compared with patients with IFIT3-positive tumors. An analysis of publicly available data confirmed this result. Patients developing lung metastases had the best prognosis (4.8 years) with significantly lower IFIT3 expression compared with liver metastasis (P = 0.0117). Patients receiving neoadjuvant therapy who are IFIT3 negative had a longer disease-free survival (1.2 vs 0.3 years, P = 0.0081). CONCLUSIONS: Low IFIT3 expression is not associated with longer survival. Divergent results from tissue microarray analyses could be explained with tumor heterogeneity. As a single biomarker, IFIT3 is not suitable for predicting disease prognosis. Recurrence of lung metastases and response to neoadjuvant chemotherapy are associated with low IFIT3 expression.

19.
Eur Radiol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026502

RESUMO

OBJECTIVES: To determine the potential of bi-parametric dual-frequency hepatic MR elastography (MRE) for predicting portal pressure (PP) in mouse models of portal hypertension (PHTN) with the presence of varying hepatic fibrosis. METHODS: We studied 73 wild-type male mice, including 22 mice with hepatic congestion, 20 mice with cholestatic liver injury, and 31 age-matched sham mice. Hepatic shear stiffness (SS) and volumetric strain (VS) were calculated by 3D MRE acquired at 80 and 200 Hz. We measured PP immediately after MRE. Liver fibrosis was verified by hydroxyproline assay. We predicted PP by fitting generalized linear models with single- and dual-frequency SS and VS, respectively. The relationship between predicted and actual PP was evaluated by Spearman's correlation. We compared the prediction accuracy of portal hypertension for all models with DeLong tests at a significance level of 0.05. RESULTS: Animals with congestive or cholestatic liver disease developed significant PHTN and hepatic fibrosis to varying degrees. In both models, SS increased, while VS decreased significantly compared with shams. All bi-parametric models had high diagnostic accuracy for PHTN. The dual-frequency models (AUCs: 0.90 [81-95%], 0.91 [81-95%]) had substantially or significantly higher accuracy than single-frequency ones (AUCs: 0.83 [71-91%], and 0.78 [66-87%]). The predicted PP of dual-frequency models also showed stronger correlations with actual PP than single-frequency predictions. CONCLUSIONS: The bi-parametric dual-frequency model improved the diagnostic accuracy of liver MRE in diagnosing PHTN in preclinical models. This technical advance has the potential to monitor PHTN progression and treatment efficacy in the presence of varying fibrosis. KEY POINTS: • Bi-parametric hepatic MR elastography can predict portal pressure. • The prediction models of shear stiffness and volumetric strain with dual-frequency measurements demonstrate high diagnostic accuracy (AUCs > 0.9) in two different portal hypertension mouse models with varying fibrosis.

20.
Sci Rep ; 10(1): 16119, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999343

RESUMO

Obesity is common comorbidity in patients with schizophrenia. Previous studies have reported that homocysteine (Hcy) is increased in schizophrenia. However, no study has reported the association between BMI and Hcy levels in schizophrenia. This cross-sectional naturalistic study aimed to evaluate the relationship between BMI, Hcy and clinical symptoms in Chinese Han patients with chronic schizophrenia. Clinical and anthropometric data as well as plasma Hcy level and glycolipid parameters were collected. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Our results showed that compared with the low BMI group, the high BMI group had a higher PANSS general psychopathology subscore, higher levels of blood glucose, total cholesterol and high-density lipoprotein (HDL) cholesterol (all p < 0.05). Hcy levels were negatively associated with BMI in patients (p < 0.001). Hcy level, the PANSS general psychopathology subscale, total cholesterol and education (all p < 0.05) were the influencing factors of high BMI. Our study suggest that Hcy level may be associated with BMI in patients with schizophrenia. Moreover, patients with high BMI show more severe clinical symptoms and higher glucose and lipid levels.

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