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1.
Artículo en Inglés | MEDLINE | ID: mdl-38888585

RESUMEN

With the continued evolution of DNA sequencing technologies, the role of genome sequence data has become more integral in the classification and identification of Bacteria and Archaea. Six years after introducing EzBioCloud, an integrated platform representing the taxonomic hierarchy of Bacteria and Archaea through quality-controlled 16S rRNA gene and genome sequences, we present an updated version, that further refines and expands its capabilities. The current update recognizes the growing need for accurate taxonomic information as defining a species increasingly relies on genome sequence comparisons. We also incorporated an advanced strategy for addressing underrepresented or less studied lineages, bolstering the comprehensiveness and accuracy of our database. Our rigorous quality control protocols remain, where whole-genome assemblies from the NCBI Assembly Database undergo stringent screening to remove low-quality sequence data. These are then passed through our enhanced identification bioinformatics pipeline which initiates a 16S rRNA gene similarity search and then calculates the average nucleotide identity (ANI). For genome sequences lacking a 16S rRNA sequence and without a closely related genomic representative for ANI calculation, we apply a different ANI approach using bacterial core genes for improved taxonomic placement (core gene ANI, cgANI). Because of the increase in genome sequences available in NCBI and our newly introduced cgANI method, EzBioCloud now encompasses a total of 109 835 species, of which 21 964 have validly published names. 47 896 are candidate species identified either through 16S rRNA sequence similarity (phylotypes) or through whole genome ANI (genomospecies), and the remaining 39 975 were positioned in the taxonomic tree by cgANI (species clusters). Our EzBioCloud database is accessible at www.ezbiocloud.net/db.


Asunto(s)
Archaea , Bacterias , Genoma Bacteriano , Microbiota , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Archaea/genética , Archaea/clasificación , Filogenia , Bases de Datos Genéticas , Genoma Arqueal , Análisis de Secuencia de ADN , Biología Computacional/métodos
2.
J Gastroenterol Hepatol ; 39(2): 319-327, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38054580

RESUMEN

BACKGROUND AND AIM: The gut microbiome of patients with clinically stable ulcerative colitis (UC) differs from that of healthy individuals depending on the state of the colonic mucosa, especially with or without advanced scarring; however, the underlying mechanism is unclear. Therefore, this study examined the gut microbiome compositional signatures in patients with significant mucosal scarring and UC-related symptoms. METHODS: Stool samples for gut microbiome analysis were prospectively collected from 57 patients with clinically stable UC between January 1 and December 31, 2022. Data from 57 individuals without inflammatory bowel disease (non-IBD) paired by age and sex were selected from our previous study as the control group. The fecal samples were subjected to 16S rRNA gene sequencing. Associations between gut microbiome profiles and clinical or colonoscopic assessments were examined using diversity and differential abundance analyses. RESULTS: Gut microbiome compositions between the patients with clinically stable UC and non-IBD controls differed significantly. Furthermore, gut microbiome compositions varied between the preserved and altered mucosa groups identified based on mucosal changes in the UC group. Differential abundance test of patients with UC for symptomatic remission based on stool frequency from the two-item patient-reported outcome identified several overlapping taxa specified as gut microbiome signatures, including the Enterobacteriaceae unknown genera (Enterobacteriaceae_g), Klebsiella, and several Lachnospiraceae spp. both in mucosal and symptom change analyses. CONCLUSIONS: The gut microbiome can change with mucosal changes, even in clinically stable UC, and some gut microbial signatures may explain the symptom manifestations in patients with UC showing significant mucosal changes.


Asunto(s)
Colitis Ulcerosa , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Cicatriz , Mucosa Intestinal , Heces
3.
Phys Rev Lett ; 130(9): 093603, 2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36930901

RESUMEN

Solid-state spin defects are promising quantum sensors for a large variety of sensing targets. Some of these defects couple appreciably to strain in the host material. We propose to use this strain coupling for mechanically mediated dispersive single-shot spin readout by an optomechanically induced transparency measurement. Surprisingly, the estimated measurement times for negatively charged silicon-vacancy defects in diamond are an order of magnitude shorter than those for single-shot optical fluorescence readout. Our scheme can also be used for general parameter-estimation metrology and offers a higher sensitivity than conventional schemes using continuous position detection.

4.
BMC Gastroenterol ; 21(1): 396, 2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34686128

RESUMEN

BACKGROUND: Dysbiosis of ulcerative colitis (UC) has been frequently investigated using readily accessible stool samples. However, stool samples might insufficiently represent the mucosa-associated microbiome status. We hypothesized that luminal contents including loosely adherent luminal bacteria after bowel preparation may be suitable for diagnosing the dysbiosis of UC. METHODS: This study included 16 patients with UC (9 men and 7 women, mean age: 52.13 ± 14.09 years) and 15 sex- and age-matched healthy individuals (8 men and 7 women, mean age: 50.93 ± 14.11 years). They donated stool samples before colonoscopy and underwent luminal content aspiration and endoscopic biopsy during the colonoscopy. Then, the composition of each microbiome sample was analyzed by 16S rRNA-based next-generation sequencing. RESULTS: The microbiome between stool, luminal contents, and biopsy was significantly different in alpha and beta diversities. However, a correlation existed between stool and luminal contents in the Procrustes test (p = 0.001) and Mantel test (p = 0.0001). The stool microbiome was different between patients with UC and the healthy controls. Conversely, no difference was found in the microbiome of luminal content and biopsy samples between the two subject groups. The microbiome of stool and lavage predicted UC, with AUC values of 0.85 and 0.81, respectively. CONCLUSION: The microbiome of stool, luminal contents, and biopsy was significantly different. However, the microbiome of luminal contents during colonoscopy can predict UC, with AUC values of 0.81. Colonoscopic luminal content aspiration analysis could determine microbiome differences between patients with UC and the healthy control, thereby beneficial in screening dysbiosis via endoscopy. TRIAL REGISTRATION: This trial was registered at http://cris.nih.go.kr . Registration No.: KCT0003352), Date: 2018-11-13.


Asunto(s)
Colitis Ulcerosa , Microbioma Gastrointestinal , Microbiota , Adulto , Anciano , Disbiosis , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/genética
5.
J Sci Food Agric ; 99(5): 2602-2609, 2019 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-30414175

RESUMEN

BACKGROUND: Although non-alcoholic fatty liver disease (NAFLD) has become more prevalent with the rapid increase of obesity worldwide, no specific treatment has been developed. Several studies have shown that wheatgrass extract Triticum aestivum (TA) improves lipid metabolism. In the present study, we evaluated the efficacy of GM-T (an ethanolic TA extract) in a murine NAFLD model. Mice were separated into 12 groups (n = 10): two groups of normal diet, choline-deficient diet (CDD) or high-fat diet (HFD) with vehicle, CCD or HFD with silymarin (400 mg kg-1 day-1 ), and CCD or HFD with GM-T (100, 200 or 400 mg kg-1 day-1 ). The study was performed for 8 weeks for the CDD groups and 12 weeks for the HFD groups. RESULTS: In the CDD-fed mice, GM-T improved serum liver enzyme activities and liver inflammation score compared to vehicle. In the HFD-fed mice, GM-T improved blood lipid profiles, liver inflammation score, steatosis score and obesity compared to vehicle. CONCLUSION: The present study demonstrated that GM-T effectively improved NAFLD in mice via a mechanism that improved insulin resistance and lipid metabolism, suggesting the possibility of a functional dietary supplement to improve liver health, overall metabolic syndrome and obesity. © 2018 Society of Chemical Industry.


Asunto(s)
Colina/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Triticum/química , Animales , Colina/análisis , Dieta Alta en Grasa/efectos adversos , Humanos , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo
6.
Eur Spine J ; 25(8): 2668-75, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26883266

RESUMEN

PURPOSE: To determine the correlation of the difference between postoperative lumbar lordosis (LL) and ideal LL with the sagittal vertical axis (SVA) at the final follow-up in patients with adult spinal deformity (ASD). METHODS: Fifty-one patients with degenerative lumbar kyphosis (DLK) (mean age 66.5 years) who underwent surgical correction with a minimum 2-year follow-up were evaluated. Based on the difference between postoperative LL and ideal LL using the Korean version of Legaye's formula, we divided the 51 patients into two groups: overcorrection (degree of postoperative LL > ideal LL) and undercorrection (degree of postoperative LL < ideal LL). RESULTS: Our clinical series of patients comprised 24 in the overcorrection and 27 in the undercorrection group. No significant differences were found in preoperative pelvic incidence (PI 52.6° vs. 57.3°), sacral slope (SS 23.3° vs. 18.3°), LL (-6.9° vs. -2.3°), thoracic kyphosis (TK 4.7° vs. 4.9°) and SVA (140 vs. 139 mm) except pelvic tilt (PT 29.4° vs. 39.0°), between the two groups. All the patients in the overcorrection group and 16 in the undercorrection group achieved postoperative optimal sagittal balance based on SVA ≤ 50 mm. In addition, significant differences in PT (10.5° vs. 26.7°), SS (42.1° vs. 30.6°), LL (-64.3° vs. -37.1°), TK (22.6° vs. 15.8°), and SVA (-1 vs. 41 mm) between the two groups were observed postoperatively. Furthermore, four patients (16.7 %) in the overcorrection group and eight (50 %) in the undercorrection group had sagittal decompensation at the final follow-up. Our results showed that the difference between postoperative LL and ideal LL had a significant correlation with postoperative and final follow-up SVA in our clinical series. CONCLUSION: Overcorrection of LL is an effective treatment modality to maintain optimal sagittal alignment in patients with DLK; this suggests that it should be considered in preoperative planning for patients with ASD with sagittal imbalance.


Asunto(s)
Cifosis , Lordosis , Vértebras Lumbares , Complicaciones Posoperatorias , Anciano , Humanos , Cifosis/diagnóstico por imagen , Cifosis/fisiopatología , Cifosis/cirugía , Lordosis/diagnóstico por imagen , Lordosis/etiología , Lordosis/fisiopatología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/fisiopatología , Tomografía Computarizada por Rayos X
7.
J Korean Med Sci ; 31(1): 125-30, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26770048

RESUMEN

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).


Asunto(s)
Dexmedetomidina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Hiperplasia Prostática/cirugía , Agitación Psicomotora/tratamiento farmacológico , Resección Transuretral de la Próstata , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Bradicardia/etiología , Dexmedetomidina/efectos adversos , Hemodinámica , Humanos , Hipnóticos y Sedantes/efectos adversos , Hipotensión/etiología , Masculino , Persona de Mediana Edad , Náusea/etiología , Vómitos/etiología
8.
Int J Syst Evol Microbiol ; 64(Pt 2): 346-351, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24505072

RESUMEN

Among available genome relatedness indices, average nucleotide identity (ANI) is one of the most robust measurements of genomic relatedness between strains, and has great potential in the taxonomy of bacteria and archaea as a substitute for the labour-intensive DNA-DNA hybridization (DDH) technique. An ANI threshold range (95-96%) for species demarcation had previously been suggested based on comparative investigation between DDH and ANI values, albeit with rather limited datasets. Furthermore, its generality was not tested on all lineages of prokaryotes. Here, we investigated the overall distribution of ANI values generated by pairwise comparison of 6787 genomes of prokaryotes belonging to 22 phyla to see whether the suggested range can be applied to all species. There was an apparent distinction in the overall ANI distribution between intra- and interspecies relationships at around 95-96% ANI. We went on to determine which level of 16S rRNA gene sequence similarity corresponds to the currently accepted ANI threshold for species demarcation using over one million comparisons. A twofold cross-validation statistical test revealed that 98.65% 16S rRNA gene sequence similarity can be used as the threshold for differentiating two species, which is consistent with previous suggestions (98.2-99.0%) derived from comparative studies between DDH and 16S rRNA gene sequence similarity. Our findings should be useful in accelerating the use of genomic sequence data in the taxonomy of bacteria and archaea.


Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Genómica/métodos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN/métodos , Archaea/genética , Bacterias/genética , Hibridación de Ácido Nucleico/métodos
9.
Psychiatry Res ; 335: 115775, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38503005

RESUMEN

Understanding the relationship between the gut microbiome and autism spectrum disorder (ASD) is challenging due to the heterogeneous nature of ASD. Here, we analyzed the microbial and clinical characteristics of individuals with ASD using enterotypes. A total of 456 individuals participated in the study, including 249 participants with ASD, 106 typically developing siblings, and 101 controls. The alpha and beta diversities of the ASD, sibling, and control groups did not show significant differences. Analysis revealed a negative association between the Bifidobacterium longum group and the Childhood Autism Rating Scale, as well as a negative association between the Streptococcus salivarus group and the Social Responsiveness Scale (SRS) within the ASD group. When clustered based on microbial composition, participants with ASD exhibited two distinct enterotypes, E1 and E2. In the E2 group, the SRS score was significantly higher, and the Vineland Adaptive Behavior Scale score was significantly lower compared to the E1 group. Machine learning results indicated that the microbial species predicting SRS scores were distinct between the two enterotypes. Our study suggests that the microbial composition in individuals with ASD exhibits considerable variability, and the patterns of associations between the gut microbiome and clinical symptoms may vary depending on the enterotype.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Microbioma Gastrointestinal , Humanos , Niño , Trastorno del Espectro Autista/diagnóstico , Hermanos
10.
Health Psychol ; 43(5): 323-327, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38190200

RESUMEN

OBJECTIVE: While a significant link between emotional well-being (EWB) and the gut microbiome has been reported recently, their temporal relationships remain elusive. This study aims to fill this gap by examining the longitudinal associations between EWB and the Shannon Index (SI), an indicator of gut microbiome diversity. METHOD: The analysis focused on a dataset that collected participants' current EWB and fecal samples in both 2019 and 2022 (N = 57, 56.1% female, Mage = 52.47 years, SD = 12.65). Gut microbiome profiles were generated by sequencing the 16S rRNA gene, from which SI was subsequently calculated. RESULTS: The cross-lagged panel analysis revealed significant positive cross-sectional associations between EWB and SI in both 2019 (ß = .296, SE = 0.121, p = .014) and 2022 (ß = .324, SE = 0.119, p = .006). However, no significant longitudinal associations were found between 2019 EWB and 2022 SI (ß = .068, SE = 0.138, p = .623), nor between 2019 SI and 2022 EWB (ß = -.016, SE = 0.13, p = .899). CONCLUSIONS: Our findings indicate that emotional happiness may be associated with gut microbiome profiles at a particular time point, but they may not serve as predictive factors for each other over time. Future research is needed to establish causal relationships between them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Microbioma Gastrointestinal , Humanos , Femenino , Persona de Mediana Edad , Masculino , ARN Ribosómico 16S/genética , Estudios Transversales , Heces , Emociones
11.
ACS Nano ; 18(3): 2091-2104, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38212302

RESUMEN

Biopsy is the clinical standard for diagnosing lymph node (LN) metastasis, but it is invasive and poses significant risk to patient health. Magnetic resonance imaging (MRI) has been utilized as a noninvasive alternative but is limited by low sensitivity, with only ∼35% of LN metastases detected, as clinical contrast agents cannot discriminate between healthy and metastatic LNs due to nonspecific accumulation. Nanoparticles targeted to the C-C chemokine receptor 2 (CCR2), a biomarker highly expressed in metastatic LNs, have the potential to guide the delivery of contrast agents, improving the sensitivity of MRI. Additionally, cancer cells in metastatic LNs produce monocyte chemotactic protein 1 (MCP1), which binds to CCR2+ inflammatory monocytes and stimulates their migration. Thus, the molecular targeting of CCR2 may enable nanoparticle hitchhiking onto monocytes, providing an additional mechanism for metastatic LN targeting and early detection. Hence, we developed micelles incorporating gadolinium (Gd) and peptides derived from the CCR2-binding motif of MCP1 (MCP1-Gd) and evaluated the potential of MCP1-Gd to detect LN metastasis. When incubated with migrating monocytes in vitro, MCP1-Gd transport across lymphatic endothelium increased 2-fold relative to nontargeting controls. After administration into mouse models with initial LN metastasis and recurrent LN metastasis, MCP1-Gd detected metastatic LNs by increasing MRI signal by 30-50% relative to healthy LNs. Furthermore, LN targeting was dependent on monocyte hitchhiking, as monocyte depletion decreased accumulation by >70%. Herein, we present a nanoparticle contrast agent for MRI detection of LN metastasis mediated by CCR2-targeting and demonstrate the potential of monocyte hitchhiking for enhanced nanoparticle delivery.


Asunto(s)
Medios de Contraste , Ganglios Linfáticos , Animales , Ratones , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Medios de Contraste/química , Monocitos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Terapia Molecular Dirigida , Imagen por Resonancia Magnética/métodos , Receptores de Quimiocina
12.
Adv Healthc Mater ; 13(14): e2302803, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38329411

RESUMEN

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Anticuerpos Neutralizantes , COVID-19 , SARS-CoV-2 , Animales , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Humanos , Ratones , COVID-19/virología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Antivirales/farmacología , Antivirales/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Chlorocebus aethiops , Células Vero , Internalización del Virus/efectos de los fármacos , Células HEK293 , Anticuerpos Antivirales/inmunología
13.
Sci Rep ; 13(1): 626, 2023 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-36635330

RESUMEN

Emerging evidence reveals a close association between gut microbiota and human neurological disorders. The present study aimed to assess whether the composition of gut microbiota in participants with episodic migraine (EM) and chronic migraine (CM) was altered in comparison to that of the controls. This study was a cross-sectional, case-control study. The gut microbiota were evaluated by the partial, targeted sequencing of the 16S rRNA V3-V4 region. This study enrolled 42 and 45 participants with EM and CM, respectively, and 43 controls. Alpha and beta diversities revealed no significant difference among the three groups; however, the microbiota composition at the class, order, family, and genus levels differed significantly between EM and the control, CM and the control, and the EM and CM groups. Moreover, higher composition of PAC000195_g was significantly associated with a lower headache frequency among the five genera that exhibited significantly different microbiota composition in EM and CM. Agathobacter revealed a significant negative association with severe headache intensity. The findings of the present study provide evidence of altered gut microbiota in EM and CM. These findings will help in understanding the course and treatment of migraine.


Asunto(s)
Microbioma Gastrointestinal , Trastornos Migrañosos , Humanos , Estudios Transversales , ARN Ribosómico 16S/genética , Estudios de Casos y Controles , Cefalea
14.
Front Aging Neurosci ; 15: 1266955, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38020771

RESUMEN

Background: The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer's disease patients. Methods: Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed. Results: The RBANS total scale index score improved significantly in group A compared with group B (p < 0.032) and compared with the control group (p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium. Conclusion: SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer's disease who were amyloid-positive by PET.

15.
J Microbiol ; 60(5): 533-549, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35362897

RESUMEN

The disruption of the human gut microbiota has been linked to host health conditions, including various diseases. However, no reliable index for measuring and predicting a healthy microbiome is currently available. Here, the sequencing data of 1,663 Koreans were obtained from three independent studies. Furthermore, we pooled 3,490 samples from public databases and analyzed a total of 5,153 fecal samples. First, we analyzed Korean gut microbiome covariates to determine the influence of lifestyle on variation in the gut microbiota. Next, patterns of microbiota variations across geographical locations and disease statuses were confirmed using a global cohort and di-sease data. Based on comprehensive comparative analysis, we were able to define three enterotypes among Korean cohorts, namely, Prevotella type, Bacteroides type, and outlier type. By a thorough categorization of dysbiosis and the evaluation of microbial characteristics using multiple datasets, we identified a wide spectrum of accuracy levels in classifying health and disease states. Using the observed microbiome patterns, we devised an index named the gut microbiome index (GMI) that could consistently predict health conditions from human gut microbiome data. Compared to ecological metrics, the microbial marker index, and machine learning approaches, GMI distinguished between healthy and non-healthy individuals with a higher accuracy across various datasets. Thus, this study proposes a potential index to measure health status of gut microbiome that is verified from multiethnic data of various diseases, and we expect this model to facilitate further clinical application of gut microbiota data in future.


Asunto(s)
Microbioma Gastrointestinal , Disbiosis , Heces , Microbioma Gastrointestinal/genética , Humanos , Prevotella , República de Corea/epidemiología
16.
Small Methods ; 6(4): e2101516, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35107214

RESUMEN

Many antibody-based antivirals, including broadly neutralizing antibodies (bnAbs) against various influenza virus strains, suffer from limited potency. A booster of the antiviral activity of an antibody is expected to facilitate development of antiviral therapeutics. In this study, a nanodisc (ND), a discoidal lipid bilayer encircled by membrane scaffold proteins, is engineered to provide virucidal properties to antibodies, thereby augmenting their antiviral activity. NDs carrying the Fc-binding peptide sequence form an antibody-ND complex (ANC), which can co-endocytose into cells infected with influenza virus. ANC efficiently inhibits endosome escape of viral RNA by dual complimentary mode of action. While the antibody moiety in an ANC inhibits hemagglutinin-mediated membrane fusion, its ND moiety destroys the viral envelope using free hemagglutinins that are not captured by antibodies. Providing virus-infected host cells with the ability to self-eliminate by the synergistic effect of ANC components dramatically amplifies the antiviral efficacy of a bnAb against influenza virus. When the efficacy of ANC is assessed in mouse models, administration of ANCs dramatically reduces morbidity and mortality compared to bnAb alone. This study is the first to demonstrate the novel nanoparticle ANC and its role in combating viral infections, suggesting that ANC is a versatile platform applicable to various viruses.


Asunto(s)
Anticuerpos Antivirales , Envoltura Viral , Animales , Anticuerpos Antivirales/farmacología , Antivirales/farmacología , Anticuerpos ampliamente neutralizantes , Hemaglutininas , Ratones
17.
Virology ; 560: 124-130, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34087565

RESUMEN

The Zika virus (ZIKV) outbreak in 2015-2016 raised public health concerns and created a pressing need for vaccine development. However, no vaccine has been developed and most of the ones under development use a single serotype of ZIKV. In this study, we established a Vero cell-adapted ZIKV strain (GMZ-002) and developed a purified inactivated virus (PIV) vaccine. GMZ-002 presented significantly increased productivity in Vero cells, and IFNAR1-blocked C57BL/6 mice administered two doses of the PIV were fully protected against lethal challenge. Vaccine efficacy was illustrated by the high level of serum neutralizing antibodies and strong innate immune response, along with an absence of detectable viremia in vaccinated mice. Furthermore, anti-sera neutralized both African and Asian genetic lineages of the virus in vitro. Our results suggest that GMZ-002 PIV elicited robust and persistent protective immunity, and therefore represents a promising vaccine candidate for ZIKV.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacunas Virales/inmunología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/prevención & control , Virus Zika/inmunología , Adaptación Fisiológica , Animales , Línea Celular , Chlorocebus aethiops , Femenino , Inmunogenicidad Vacunal/inmunología , Ratones , Ratones Endogámicos C57BL , Receptor de Interferón alfa y beta/genética , Vacunación , Eficacia de las Vacunas , Vacunas de Productos Inactivados/inmunología , Células Vero
18.
ACS Appl Mater Interfaces ; 13(31): 36757-36768, 2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34319090

RESUMEN

Lipid-bilayer nanodiscs (NDs) wrapped in membrane scaffold proteins (MSPs) have primarily been used to study membrane proteins of interest in a physiological environment. Recently, NDs have been employed in broader applications including drug delivery, cancer immunotherapy, bio-imaging, and therapeutic virucides. Here, we developed a method to synthesize a dimeric nanodisc, whose MSPs are circularly end-spliced, with long-term thermal stability and resistance to aggregation. The end-spliced nanodiscs (esNDs) were assembled using MSPs that were self-circularized inside the cytoplasm ofEscherichia colivia highly efficient protein trans-splicing. The esNDs demonstrated a consistent size and 4-5-fold higher stability against heat and aggregation than conventional NDs. Moreover, cysteine residues on trans-spliced circularized MSPs allowed us to modulate the formation of either monomeric nanodiscs (essNDs) or dimeric nanodiscs (esdNDs) by controlling the oxidation/reduction conditions and lipid-to-protein ratios. When the esdNDs were used to prepare an antiviral nanoperforator that induced the disruption of the viral membrane upon contact, antiviral activity was dramatically increased, suggesting that the dimerization of nanodiscs led to cooperativity between linked nanodiscs. We expect that controllable structures, long-term stability, and aggregation resistance of esNDs will aid the development of novel versatile membrane-mimetic nanomaterials with flexible designs and improved therapeutic efficacy.


Asunto(s)
Antivirales/uso terapéutico , Proteínas de la Membrana/uso terapéutico , Nanoestructuras/uso terapéutico , Animales , Antivirales/química , Escherichia coli/genética , Femenino , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/uso terapéutico , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Nanoestructuras/química , Orthomyxoviridae/efectos de los fármacos , Trans-Empalme , Envoltura Viral/efectos de los fármacos
19.
Sci Rep ; 10(1): 14884, 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32913230

RESUMEN

Efficiently detecting and characterizing individual spins in solid-state hosts is an essential step to expand the fields of quantum sensing and quantum information processing. While selective detection and control of a few 13C nuclear spins in diamond have been demonstrated using the electron spin of nitrogen-vacancy (NV) centers, a reliable, efficient, and automatic characterization method is desired. Here, we develop an automated algorithmic method for decomposing spectral data to identify and characterize multiple nuclear spins in diamond. We demonstrate efficient nuclear spin identification and accurate reproduction of hyperfine interaction components for both virtual and experimental nuclear spectroscopy data. We conduct a systematic analysis of this methodology and discuss the range of hyperfine interaction components of each nuclear spin that the method can efficiently detect. The result demonstrates a systematic approach that automatically detects nuclear spins with the aid of computational methods, facilitating the future scalability of devices.

20.
Pathogens ; 9(3)2020 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-32164338

RESUMEN

Shotgun metagenomics is of great importance in order to understand the composition of the microbial community associated with a sample and the potential impact it may exert on its host. For clinical metagenomics, one of the initial challenges is the accurate identification of a pathogen of interest and ability to single out that pathogen within a complex community of microorganisms. However, in absence of an accurate identification of those microorganisms, any kind of conclusion or diagnosis based on misidentification may lead to erroneous conclusions, especially when comparing distinct groups of individuals. When comparing a shotgun metagenomic sample against a reference genome sequence database, the classification itself is dependent on the contents of the database. Focusing on the genus Streptococcus, we built four synthetic metagenomic samples and demonstrated that shotgun taxonomic profiling using the bacterial core genes as the reference database performed better in both taxonomic profiling and relative abundance prediction than that based on the marker gene reference database included in MetaPhlAn2. Additionally, by classifying sputum samples of patients suffering from chronic obstructive pulmonary disease, we showed that adding genomes of genomospecies to a reference database offers higher taxonomic resolution for taxonomic profiling. Finally, we show how our genomospecies database is able to identify correctly a clinical stool sample from a patient with a streptococcal infection, proving that genomospecies provide better taxonomic coverage for metagenomic analyses.

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