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1.
Stem Cell Res Ther ; 12(1): 4, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407872

RESUMO

BACKGROUND: As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson's trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated. RESULTS: Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-ß1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-ß1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-ß1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice. CONCLUSION: Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.

2.
Cell Res ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420426

RESUMO

The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.

3.
Eur J Obstet Gynecol Reprod Biol ; 256: 256-262, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33259994

RESUMO

OBJECTIVES: This study aimed to investigate the predictive value of laparoscopy for the prediction of optimal cytoreduction and prognosis of epithelial ovarian cancer (EOC) in a Chinese population. STUDY DESIGN: This study enrolled 162 EOC patients in Obstetrics and Gynecology Hospital of Fudan University from January 2015 to December 2016. All patients underwent preoperative CT scans and laparoscopic assessments. Each patient was scored according to the CT-based predictive model by Bristow and laparoscopy-based predictive model by Fagotti. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of each model were calculated. The predictive scores and clinicopathologic factors were all analyzed using the Kaplan-Meier method and multivariate Cox analysis. A prognostic predictive nomogram was formulated in R software. RESULTS: The AUCs of the laparoscopy-based predictive model and CT-based predictive model was 0.955 and 0.755 respectively. At a laparoscopic score ≥ 10, the possibility of optimal cytoreduction was 0, and the risk of unnecessary explorative attempts was 6%. Additionally, laparoscopic score, independent of residual tumor size and FIGO stage, was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) in EOC. Notably, the predictive nomogram that we established further confirmed the prognostic value of laparoscopy for prognostic predictions in EOC. CONCLUSIONS: Laparoscopy has a better discriminating performance than CT in the prediction of optimal cytoreduction in EOC. Moreover, the laparoscopic score is directly correlated with the survival of EOC patients. The laparoscopic score-based nomogram we established showed good potential to predict the prognosis of EOC patients.

4.
Bull World Health Organ ; 98(12): 830-841D, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33293743

RESUMO

Objective: To design models of the spread of coronavirus disease-2019 (COVID-19) in Wuhan and the effect of Fangcang shelter hospitals (rapidly-built temporary hospitals) on the control of the epidemic. Methods: We used data on daily reported confirmed cases of COVID-19, recovered cases and deaths from the official website of the Wuhan Municipal Health Commission to build compartmental models for three phases of the COVID-19 epidemic. We incorporated the hospital-bed capacity of both designated and Fangcang shelter hospitals. We used the models to assess the success of the strategy adopted in Wuhan to control the COVID-19 epidemic. Findings: Based on the 13 348 Fangcang shelter hospitals beds used in practice, our models show that if the Fangcang shelter hospitals had been opened on 6 February (a day after their actual opening), the total number of COVID-19 cases would have reached 7 413 798 (instead of 50 844) with 1 396 017 deaths (instead of 5003), and the epidemic would have lasted for 179 days (instead of 71). Conclusion: While the designated hospitals saved lives of patients with severe COVID-19, it was the increased hospital-bed capacity of the large number of Fangcang shelter hospitals that helped slow and eventually stop the COVID-19 epidemic in Wuhan. Given the current global pandemic of COVID-19, our study suggests that increasing hospital-bed capacity, especially through temporary hospitals such as Fangcang shelter hospitals, to isolate groups of people with mild symptoms within an affected region could help curb and eventually stop COVID-19 outbreaks in communities where effective household isolation is not possible.


Assuntos
/epidemiologia , Número de Leitos em Hospital/estatística & dados numéricos , Unidades Móveis de Saúde/organização & administração , China/epidemiologia , Humanos , Cadeias de Markov , Modelos Estatísticos , Pandemias
5.
Macromol Rapid Commun ; 41(24): e2000534, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33225490

RESUMO

Peptide assembly has been extensively exploited as a promising platform for the creation of hierarchical nanostructures and tailor-made bioactive materials. Ionic coassembly of cationic peptides and anionic species is paving the way to provide particularly important contribution to this topic. In this review, the recent progress of ionic coassembly soft materials derived from the electrostatic coupling between cationic peptides and anionic species in aqueous solution is systematically summarized. The presentation of this review starts from a brief background on the general importance and advantages of peptide-based ionic coassembly. After that, diverse combinations of cationic peptides with small anions, macro- and/or oligo-anions, anionic polymers, and inorganic polyoxometalates are described. Emphasis is placed on the hierarchical structures, value-added properties, and applications. The molecular design of cationic peptides and the general principles behind the ionic coassembled structures are discussed. It is summarized that the combination of interesting and unique characteristics that arise both from the chemical diversity of peptides and the wide range of anionic species may contribute in a variety of output, including drug delivery, tissue engineering, gene transfection, and antibacterial activity. The emergent new phenomena and findings are illustrated. Finally, the outlook for the peptide-based ionic coassembly systems is also presented.

6.
Angew Chem Int Ed Engl ; 59(52): 23564-23568, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-32896066

RESUMO

A single-step method for isolation of specific cells based on multiple surface markers will have unique advantages because of its scalability, efficacy, and mildness. Herein, we developed multi-aptamer-mediated proximity ligation method on live cell membranes that leverages a multi-receptor co-recognition design for enhanced specificity, as well as a robust in situ signal amplification design for improved sensitivity of cell isolation. We demonstrated the promising efficacy of our method on differentiating tumor cell subtypes in both cell mixtures and clinical samples. Owing to its simple and fast operation with excellent cell isolation sensitivity and accuracy, this approach will have broad applications in biological science, biomedical engineering, and personalized medicine.

7.
Aging (Albany NY) ; 12(18): 18649-18659, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897242

RESUMO

Glioma is the most common malignant brain tumor. Because of its high degree of malignancy, the effect of surgical treatment, radiotherapy, chemotherapy, or immunotherapy is not ideal. TXNDC9 belongs to thioredoxin domain-containing proteins, which is involved in tumor progression. However, no research associated with TXNDC9 has been reported in glioma. In this study, we found that TXNDC9 was upregulated in glioma. Knockdown of TXNDC9 would prevent proliferation and metastasis, induce the apoptosis rate of glioma cells, and promote the expression Cleaved-caspase3, Cleaved-caspase8, Cleaved-caspase9. Meanwhile, knockdown of TXNDC9 induced autophagy by increasing the level of LC3 and Beclin-1. Cell morphology and expression analysis of GFAP, Vimentin, verified that TXNDC9 could regulate glioma cell differentiation. During this program, the expression of p53 changes dramatically. The apoptosis, autophagy, and cell differentiation program were blocked by p53 inhibitor treatment. In conclusion, the silencing of TXNDC9 induces apoptosis and autophagy in glioma and promotes cell differentiation by controlling p53 and may function as a new mechanism in glioma.

8.
Chem Commun (Camb) ; 56(75): 11034-11037, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32808609

RESUMO

Dynamic adhesives were fabricated based on the ionic co-assembly of glutathione and heteropoly acids (HPAs). The underwater attachment and detachment of the adhesives were achieved based on the redox properties of glutathione. We demonstrated that the formation of disulfide bonds of glutathione plays a pivotal role in the formation of robust 3D network structures as well as the improvement of cohesion.

9.
ACS Nano ; 14(8): 9572-9584, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32806042

RESUMO

Real-time in situ monitoring of low-abundance cancer biomarkers (e.g., miRNAs and proteins) in living cells by nonenzymatic assembly entirely from original DNA probes remains unexplored due to an extremely complex intracellular environment. Herein, a nonenzymatic palindrome-catalyzed DNA assembly (NEPA) technique is developed to execute the in situ imaging of intracellular miRNAs by assembling a three-dimensional nanoscale DNA spherical structure (NS) with low mobility from three free hairpin-type DNAs rather than from DNA intermediates based on the interaction of designed terminal palindromes. Target miRNA was detected down to 1.4 pM, and its family members were distinguished with almost 100% accuracy. The subcellular localization of NS products can be visualized in real time. The NEPA-based sensing strategy is also suitable for the intracellular in situ fluorescence imaging of cancer-related protein receptors, offering valuable insight into developing sensing protocols for understanding the biological function of vital biomolecules in disease pathogenesis and future therapeutic applications.

10.
Medicine (Baltimore) ; 99(29): e21334, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702930

RESUMO

RATIONALE: The outbreak of coronavirus disease 2019 (COVID-19) in 2019 has become a global pandemic. It is not known whether the disease is associated with a higher risk of infection in pregnant women or whether intrauterine vertical transmission can occur. We report 2 cases of pregnant women diagnosed with COVID-19. PATIENT CONCERNS: In all of Yichang city from January 20, 2020, to April 9, 2020, only 2 pregnant women, who were in the late stage of pregnancy, were diagnosed with COVID-19; one patient was admitted for fever with limb asthenia, and the other patient was admitted for abnormal chest computed tomography results. DIAGNOSES: Both pregnant women were diagnosed with COVID-19. INTERVENTIONS: After the medical staff prepared for isolation and protection, the 2 pregnant women quickly underwent cesarean sections. A series of tests, such as laboratory, imaging, and SARS-CoV-2 nucleic acid examinations, were performed on the 2 women with COVID-19 and their newborns. OUTCOMES: One of the 2 infected pregnant women had severe COVID-19, and the other had mild disease. Both babies were delivered by cesarean section. Both of the women with COVID-19 worsened 3 to 6 days after delivery. Chest computed tomography suggested that the lesions due to SARS-CoV-2 infection increased. These women began to exhibit fever or reduced blood oxygen saturation again. One of the 2 newborns was born prematurely, and the other was born at full term. Neither infant was infected with COVID-19, but both had increased prothrombin time and fibrinogen, lactate dehydrogenase, phosphocreatine kinase, and creatine kinase isoenzyme contents. LESSONS: SARS-CoV-2 infection was not found in the newborns born to the 2 pregnant women with COVID-19, but transient coagulation dysfunction and myocardial damage occurred in the 2 newborns. Effective management strategies for pregnant women with COVID-19 will help to control the outbreak of COVID-19 among pregnant women.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Adulto , Astenia/etiologia , Betacoronavirus/isolamento & purificação , Cesárea/métodos , China/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Surtos de Doenças/prevenção & controle , Feminino , Febre/etiologia , Humanos , Recém-Nascido/sangue , Recém-Nascido/metabolismo , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Pandemias , Pneumonia Viral/tratamento farmacológico , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
11.
BMC Nephrol ; 21(1): 288, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689969

RESUMO

BACKGROUND: Most end-stage renal disease (ESRD) patients undergo open surgical techniques for peritoneal dialysis (PD) catheter placement. An alternative method to PD catheter implantation is the half-percutaneous ("Half-Perc") technique based on a modified trocar that is performed by a nephrologist. The single-center, retrospective, observational, cohort study presented here aimed to compare the effects of the "Half-Perc" technique with the traditional open surgery on peritoneal catheter insertion. METHODS: From January 2015 to January 2018, 240 ESRD patients who received initial PD catheter placement were divided into two groups based on the "Half-Perc" technique or open surgery. All patients were followed up for 365 days or until loss of initial PD catheter or death. Prism 5 software was used to analyze baseline characteristics, operation-related parameters, mechanical complications and clinical outcomes. RESULTS: The "Half-Perc" technique showed shorter operation time, shorter incision length, lower postoperative pain scores and quick initiation of the PD program compared to the open surgery. After the 365-day follow-up, the "Half-Perc" group showed a higher rate of catheter dysfunction (4% versus 0.9%) that was corrected by conservative treatment in most patients and a lower rate of peritonitis (4% versus 9.6%) but mechanical complications and clinical outcomes did not differ between the two groups. There was also no significant difference based on overall patient mortality or catheter removal. One-year initial catheter survival and true catheter survival were not statistically different between the groups. CONCLUSION: The "Half-Perc" placement of the PD catheter using a modified metal trocar appears to be a non-inferior alternative method and carries minimal invasiveness and risk compared to open surgical placement.

12.
Chem Soc Rev ; 49(22): 8065-8087, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-32567633

RESUMO

Optical techniques using developed laser and optical devices have made a profound impact on modern medicine, with "biomedical optics" becoming an emerging field. Sophisticated technologies have been developed in cancer nanomedicine, such as photothermal therapy and photodynamic therapy, among others. However, single-mode phototherapy cannot completely treat persistent tumors, with the challenges of relapse or metastasis remaining; therefore, combinatorial strategies are being developed. In this review, the role of light in cancer therapy and the challenges of phototherapy are discussed. The development of combinatorial strategies with other therapeutic methods, including chemotherapy, immunotherapy, gene therapy, and radiotherapy, is presented and future directions are further discussed. This review aims to highlight the significance of light in cancer therapy and discuss the combinatorial strategies that show promise in addressing the challenges of phototherapy.

13.
Chem Commun (Camb) ; 56(58): 8083-8086, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32543623

RESUMO

An enzyme-free amplification strategy based on two-photon fluorescent carbon dots for monitoring miR-9 in live neurons and brain tissues of Alzheimer's disease (AD) mice. Notably, using our developed probe, miR-9 was found to be up-regulated in early onset AD, while it was found to be down regulated to lower than the normal level in late onset AD.

14.
Front Pharmacol ; 11: 522, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410994

RESUMO

The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

15.
Medicine (Baltimore) ; 99(20): e19808, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443287

RESUMO

BACKGROUND: The interleukin-10 (IL-10)-819T/C polymorphism has been indicated to be correlated with ischemic stroke susceptibility, but this relationship remains controversial. A meta-analysis was conducted to investigate the potential association between IL-10-819T/C polymorphism and ischemic stroke risk. METHODS: Databases including Pubmed, Embase, and CNKI were searched. Data were extracted and odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Eight case-control studies with 1832 cases and 1520 controls were included in this meta-analysis. IL-10-819T/C polymorphism may decrease the risk of ischemic stroke (C vs T: OR = 1.01, 95% CI: 0.91-1.12; CC vs TT: OR = 0.91, 95% CI: 0.73-1.14; CT vs TT: OR = 1.10, 95% CI: 0.95-1.28; CC + CT vs TT: OR = 1.06, 95% CI: 0.92-1.22; CC vs CT + TT: OR = 0.91, 95% CI: 0.75-1.11). In the stratified analysis by sample size, and case-control matched status, significant associations were still not observed in all genetic models. In the subgroup meta-analysis based on source of controls, IL-10-819T/C polymorphism had decreased ischemic stroke risk for recessive model in population-based controls' subgroup (CC vs CT + TT: OR = 0.69, 95% CI: 0.50-0.95), but not in the hospital-based controls' subgroup. In the stratified analysis based on ethnicity, IL-10-819T/C polymorphism had decreased ischemic stroke risk for recessive model in Asian populations (CC vs CT + TT: OR = 0.78, 95% CI: 0.62-0.99), but not in Caucasian populations. CONCLUSIONS: In conclusion, the results suggest that the IL-10-819T/C polymorphism is not associated with ischemic stroke risk. Larger scale studies are needed for confirmation.


Assuntos
Isquemia Encefálica/genética , Interleucina-10/genética , Acidente Vascular Cerebral/genética , Isquemia Encefálica/complicações , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único
16.
J Ovarian Res ; 13(1): 45, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334623

RESUMO

OBJECTIVE: Currently, the function and mechanisms of long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer (EOC), especially those of the lncRNAs participated in the epithelial-mesenchymal transition (EMT) process, remains largely unknown. Here, we focused on a lncRNA named AOC4P and analysed its role in EOC. MATERIALS AND METHODS: The expression of AOC4P gene was examined with quantitative real-time quantitative PCR (qRT-PCR). The cell migration and invasion were detected by Transwell and scratch assays. The in vivo metastatic activity was evaluated by intraperitoneal metastasis model. The downstream genes were investigated by a tumour EMT real-time polymerase chain reaction (RT-PCR) array, and validated by qRT-PCR and Western blot. RESULTS: The results showed that AOC4P expression levels were decreased in EOC tissues and cell lines, and that the under-expression of AOC4P was positively correlated with FIGO stage and lymph node metastasis. Furthermore, the knockdown of AOC4P expression in poorly metastatic EOC cell lines remarkably facilitated cell migration/invasion while the overexpression of AOC4P in highly metastatic EOC cell lines reduced the metastatic ability of these cells in vitro. Consistently, the anti-metastatic role of AOC4P in vivo was also verified by bioluminescence imaging and tumour dissection. Mechanistically, the anti-metastatic effect of AOC4P in EOC was partially mediated by the EMT process accompanied by the alterations in MMP9 and COL1A2 expression. CONCLUSION: These data highlight that AOC4P plays a critical role in EOC invasion/metastasis and could function as a novel and effective target for the lncRNA-based anti-metastatic clinical management of EOC.


Assuntos
Carcinoma Epitelial do Ovário/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante , Animais , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Feminino , Humanos , Leiomioma/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia
17.
J Proteome Res ; 19(5): 2092-2104, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32233371

RESUMO

Fungal spores and hyphal fragments play an important role as allergens in respiratory diseases. In this study, we performed trypsin shaving and secretome analyses to identify the surface-exposed proteins and secreted/shed proteins of Aspergillus fumigatus conidia, respectively. We investigated the surface proteome under different conditions, including temperature variation and germination. We found that the surface proteome of resting A. fumigatus conidia is not static but instead unexpectedly dynamic, as evidenced by drastically different surface proteomes under different growth conditions. Knockouts of two abundant A. fumigatus surface proteins, ScwA and CweA, were found to function only in fine-tuning the cell wall stress response, implying that the conidial surface is very robust against perturbations. We then compared the surface proteome of A. fumigatus to other allergy-inducing molds, including Alternaria alternata, Penicillium rubens, and Cladosporium herbarum, and performed comparative proteomics on resting and swollen conidia, as well as secreted proteins from germinating conidia. We detected 125 protein ortholog groups, including 80 with putative catalytic activity, in the extracellular region of all four molds, and 42 nonorthologous proteins produced solely by A. fumigatus. Ultimately, this study highlights the dynamic nature of the A. fumigatus conidial surface and provides targets for future diagnostics and immunotherapy.

18.
FEMS Microbiol Lett ; 367(7)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239209

RESUMO

This study aimed to determine the effects of Bifidobacterium bifidum TMC3115, Lactobacillus plantarum 45 (LP45) and their combined use on cognitive performance and gut microbiota in APP/PS1 mice. The APP/PS1 mice were randomly divided into four groups: Alzheimer's disease (AD) model group, TMC3115 group [1 × 109 colony forming unit (CFU)], LP45 group (1 × 109 CFU) and a mixture group of TMC3115 (5 × 108 CFU) and LP45 (5 × 108 CFU). The wild-type littermates were chosen as normal control. The mice were sacrificed at the end of 22 weeks after behavioral evaluation. Collected cecum content was analyzed using 16S rRNA sequencing. Combined use of TMC3115 and LP45 significantly increased the times across the platform, time spent in the target quadrant compared with the AD, TMC3115 and LP45 groups in Morris water maze test. Microbiota analysis showed that combined TMC3115 and LP45 supplementation significantly increased observed species and beta diversity, and reversed gut dysbiosis by decreasing the abundance of Bacteroides and increasing the abundance of Acetatifactor and Millionella. These results indicate the long-term combined administration of TMC3115 and LP45 can improve spatial memory impairment in APP/PS1 mice and suggest that modifying the gut microbiome may provide potential benefits for AD patients.

19.
Anal Chem ; 92(8): 5910-5920, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32227892

RESUMO

The aggregation of Aß has been reported to closely correlate with Alzheimer's disease (AD). However, clear monitoring of the entire aggregation process of Aß from monomer to fibril has been scarcely reported until now. Herein, we developed a label-free ratiometric surface enhanced Raman spectroscopic (SERS) platform for real-time monitoring of the entire process of Aß aggregation in neurons and brain tissues. Different gold nanoparticles, generated in situ with Aß monomer and fibril as templates separately, were served as effective SERS substrates to achieve a high sensitivity with a limit of detection (LOD) down to 70 ± 4 pM and 3.0 ± 0.5 pM for Aß40 monomer and fibrils, respectively. Besides, the introduction of ratiometric determination of Aß monomer and fibril (I1244/I1268) realized real-time monitoring of the entire aggregation process of Aß monomer with high accuracy and selectivity against other proteins and amino acids. The significant analytical performance of the developed platform, together with good biocompatibility, long-term stability, and remarkable spatial resolution, enabled the present SERS platform imaging and real-time monitoring and imaging of Aß aggregation influenced by different metal ions (Cu2+, Zn2+, and Fe3+) in neurons and brain tissues at the single cell level. Our results suggested that Cu2+ and Zn2+ ion of low concentration (10 µM) promoted fibril formation, while Fe3+ and Zn2+ of high concentration (100 µM) showed inhibition of fibrosis.

20.
BMC Geriatr ; 20(1): 86, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131744

RESUMO

BACKGROUND: Among the previous studies about the ADL recovery and its predictors, the researches and resources used to study and protect the baseline-independent older patients from being permanently ADL-dependent was few. We aimed to describe the level of activities of daily living (ADL) at discharge and ADL change within 6 months after discharge in older patients who were ADL-independent before admission but became dependent because of acute illness, and to identify the predictors of early rehabilitation,so as to provide the basis to early intervention. METHODS: Stratified cluster sampling was used to recruit 520 hospitalised older patients who were ADL-independent from departments of internal medicine at two tertiary hospitals from August 2017 to May 2018. Demographics, clinical data, and ADL status at 1, 3, and 6 months after discharge were collected. Data were analysed using descriptive statistics, Student's t-test, Pearson's chi-square test,Spearman's correlation analysis, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: There were 403 out of 520 patients completing the 6-month follow-up, and 229 (56.8%) regained independence at 6 months after discharge. There was an overall increasing trend in ADL with time. The recovery rate was the highest within the first month after discharge, gradually declined after 1 month, and changed less obviously from 3 to 6 months after discharge (p < 0.001). ADL score at discharge (OR = 1.034, p < 0.001), age (OR = 0.269, p = 0.001), post-discharge residence (OR = 0.390, p < 0.05), and cognition status at discharge (OR = 1.685, p < 0.05) were predictors of ADL recovery. The area under the curve of the four predictors combined was 0.763 (p < 0.001). CONCLUSION: Studying ADL recovery rate and its predicting indicators of the baseline independent inpatients at different time points provide a theoretical reference for the formulation of nursing plans and allocation of care resources.


Assuntos
Atividades Cotidianas , Alta do Paciente , Assistência ao Convalescente , Idoso , Hospitalização , Humanos , Pacientes Internados
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