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1.
Microbiol Resour Announc ; : e0045924, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967471

RESUMO

Here, we present the draft genome of Bacillus proteolyticus IMGN4, the gram-positive, soil-dwelling bacterium discovered in mountain Maemi, Republic of Korea in May 2019. The assembly resulted in 7 contigs, comprising a total of 6,063,502 base pairs and have 6,115 coding sequences.

2.
Gut Liver ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953118

RESUMO

Background/Aims: Young Korean men are obligated to serve in the military for 18 to 21 months. We investigated the effects of military service on steatotic liver disease (SLD) and other metabolic parameters. Methods: Pre-enlistment health check-up performed from 2019 to 2022 and in-service health check-up performed from 2020 to 2022 were merged as paired data. SLD was defined as a hepatic steatosis index of 36 or higher. Hypertension (HTN) and hypertriglyceridemia were also included in the analysis. Results: A total of 503,136 paired cases were included in the analysis. Comparing pre-enlistment and in-service health check-ups, the prevalence of SLD (22.2% vs 17.6%, p<0.001), HTN (7.6% vs 4.3%, p<0.001), and hypertriglyceridemia (8.1% vs 2.9%, p<0.001) decreased during military service. In terms of body mass index, the proportion of underweight (8.2% vs 1.4%, p<0.001) and severely obese (6.1% vs 4.9%, p<0.001) individuals decreased over time. Regarding factors associated with SLD development and resolution, age was positively associated with SLD development (odds ratio, 1.146; p<0.001) and a health check-up interval of <450 days was a protective factor for SLD development (odds ratio, 0.746; p<0.001). Those serving in the marines were less likely to develop SLD, whereas those serving in the navy were more likely to develop SLD. Serving in the army or the navy was negatively associated with SLD resolution, whereas serving in the air force was positively associated with SLD resolution. Conclusions: The prevalence of SLD, HTN, and hypertriglyceridemia decreased substantially during Korean military service.

3.
Mil Med ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829168

RESUMO

INTRODUCTION: This study aimed to examine the prevalence of cold injuries and review the cold injury monitoring system in the South Korean military. MATERIALS AND METHODS: This study conducted a retrospective and cross-sectional analysis using data from the Defense Medical Statistic Information System (DMSIS) on cold injuries among military personnel from 2018 to 2023. It incorporated findings from the Korean Armed Forces Medical Command's cold injury surveillance system and analyzed cases from the Armed Forces Capital Hospital, covering all branches of the military by status and rank. RESULTS: An analysis of cold injury in the South Korean military over the past 5 years revealed varying numbers of cases treated, from 799 in 2018-2019 to 467 in 2022-2023. According to the surveillance system in 2023-2024, the Army experienced the majority of these cases, with 94.5% of the total. The incidence per 1,000 personnel was the highest in the Army at 0.98 compared to the Air Force and Navy/Marine Corps. Rank-based analysis indicated the most affected were private first-class soldiers. Frostbite was the most frequent condition, alongside chilblains, hypothermia, and immersion injuries, with no marked difference in the type of illness across branches. CONCLUSIONS: The study underscores the need for focused prevention and treatment, particularly in the Army. By analyzing data from a newly implemented surveillance system, it revealed a higher incidence of frostbite and chilblains among lower ranks. The findings highlight the importance of targeted educational measures and enhanced response strategies to protect personnel against cold injuries.

4.
Leuk Res ; 143: 107542, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38924942

RESUMO

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.

5.
Virol J ; 21(1): 86, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622686

RESUMO

BACKGROUND: Viruses have notable effects on agroecosystems, wherein they can adversely affect plant health and cause problems (e.g., increased biosecurity risks and economic losses). However, our knowledge of their diversity and interactions with specific host plants in ecosystems remains limited. To enhance our understanding of the roles that viruses play in agroecosystems, comprehensive analyses of the viromes of a wide range of plants are essential. High-throughput sequencing (HTS) techniques are useful for conducting impartial and unbiased investigations of plant viromes, ultimately forming a basis for generating further biological and ecological insights. This study was conducted to thoroughly characterize the viral community dynamics in individual plants. RESULTS: An HTS-based virome analysis in conjunction with proximity sampling and a tripartite network analysis were performed to investigate the viral diversity in chunkung (Cnidium officinale) plants. We identified 61 distinct chunkung plant-associated viruses (27 DNA and 34 RNA viruses) from 21 known genera and 6 unclassified genera in 14 known viral families. Notably, 12 persistent viruses (7 DNA and 5 RNA viruses) were exclusive to dwarfed chunkung plants. The detection of viruses from the families Partitiviridae, Picobirnaviridae, and Spinareoviridae only in the dwarfed plants suggested that they may contribute to the observed dwarfism. The co-infection of chunkung by multiple viruses is indicative of a dynamic and interactive viral ecosystem with significant sequence variability and evidence of recombination. CONCLUSIONS: We revealed the viral community involved in chunkung. Our findings suggest that chunkung serves as a significant reservoir for a variety of plant viruses. Moreover, the co-infection rate of individual plants was unexpectedly high. Future research will need to elucidate the mechanisms enabling several dozen viruses to co-exist in chunkung. Nevertheless, the important insights into the chunkung virome generated in this study may be relevant to developing effective plant viral disease management and control strategies.


Assuntos
Coinfecção , Nanismo , Vírus de Plantas , Vírus de RNA , Humanos , Viroma , Ecossistema , Cnidium/genética , RNA Viral/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Vírus de Plantas/genética , DNA , Filogenia
6.
Front Genet ; 15: 1355823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628577

RESUMO

Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients' cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild.

7.
Mil Med ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651564

RESUMO

INTRODUCTION: The population of the Republic of Korea often experiences heat-related illnesses during summer that are exacerbated by significant variations. With rising temperatures attributed to global warming and other environmental changes within the military, combined with the military medical services' mission to uphold combat capabilities and promote health, it has become crucial to accurately understand the status of heat-related illnesses and integrate more comprehensive and systematic preventive measures. This study aimed to analyze data on heat-related illnesses between 2018 and 2022 to assess and reflect on the said diseases in the South Korean Military. MATERIALS AND METHODS: We performed a secondary analysis using data provided by the Defense Medical Statistic Information System. This single-institution retrospective, cross-sectional study was approved by the Institutional Review Board of the Armed Forces Medical Command (approval number: AFMC-2023-11-001). RESULTS: Over the past 5 years, the annual number of soldiers treated for heat-related illnesses, whether as outpatients or inpatients, at division medical facilities and military hospitals ranged from 846 to 1,250 cases per year. The proportion of severe cases fluctuates annually between 1.1% and 1.8%. Notably, 94 to 96% of all heat-related illnesses were recorded between May and September, with peak rates in July and August. CONCLUSION: The army reported the highest number of heat-related illnesses among military branches, with soldiers comprising the majority of cases. This highlights the urgent need for enhanced heat illness prevention measures within army ranks. Notably, the incidence of these illnesses peaked during July and August, underlining the critical periods for intensified preventive efforts.

8.
Plant J ; 118(5): 1528-1549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38507319

RESUMO

Rapid alkalinization factors (RALFs), belonging to a family of small secreted peptides, have been considered as important signaling molecules in diverse biological processes, including immunity. Current studies on RALF-modulated immunity mainly focus on Arabidopsis, but little is reported in crop plants. The rice immune receptor XA21 confers immunity to the bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo). Here, we pursued functional characterization of rice RALF26 (OsRALF26) up-regulated by Xoo during XA21-mediated immune response. When applied exogenously as a recombinant peptide, OsRALF26 induced a series of immune responses, including pathogenesis-related genes (PRs) induction, reactive oxygen species (ROS) production, and callose deposition in rice and/or Arabidopsis. Transgenic rice and Arabidopsis overexpressing OsRALF26 exhibited significantly enhanced resistance to Xoo and Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), respectively. In yeast two-hybrid, pull-down assays, and co-immunoprecipitation analyses, rice FER-like receptor 1 (OsFLR1) was identified as a receptor of OsRALF26. Transient expression of OsFLR1 in Nicotiana benthamiana leaves displayed significantly increased ROS production and callose deposition after OsRALF26 treatment. Together, we propose that OsRALF26 induced by Xoo in an XA21-dependent manner is perceived by OsFLR1 and may play a novel role in the enforcement of XA21-mediated immunity.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Oryza , Doenças das Plantas , Imunidade Vegetal , Proteínas de Plantas , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio , Xanthomonas , Oryza/genética , Oryza/microbiologia , Oryza/imunologia , Oryza/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/microbiologia , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Xanthomonas/fisiologia , Xanthomonas/patogenicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Espécies Reativas de Oxigênio/metabolismo , Resistência à Doença/genética , Glucanos/metabolismo , Pseudomonas syringae/patogenicidade , Pseudomonas syringae/fisiologia
9.
Compr Psychiatry ; 130: 152457, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38325041

RESUMO

Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.


Assuntos
COVID-19 , Depressão , Adulto , Humanos , Feminino , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , COVID-19/epidemiologia , Pandemias , Suíça/epidemiologia , Ansiedade
10.
Adv Sci (Weinh) ; 11(17): e2310094, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38408139

RESUMO

Electrolyte additives with multiple functions enable the interfacial engineering of Li-metal batteries (LMBs). Owing to their unique reduction behavior, additives exhibit a high potential for electrode surface modification that increases the reversibility of Li-metal anodes by enabling the development of a hierarchical solid electrolyte interphase (SEI). This study confirms that an adequately designed SEI facilitates the homogeneous supply of Li+, nonlocalized Li deposition, and low electrolyte degradation in LMBs while enduring the volume fluctuation of Li-metal anodes on cycling. An in-depth analysis of interfacial engineering mechanisms reveals that multilayered SEI structures comprising mechanically robust LiF-rich species, electron-rich P-O species, and elastic polymeric species enabled the stable charge and discharge of LMBs. The polymeric outer SEI layer in the as-fabricated multilayered SEI could accommodate the volume fluctuation of Li-metal anodes, significantly enhancing the cycling stability Li||LiNi0.8Co0.1Mn0.1O2 full cells with an electrolyte amount of 3.6 g Ah-1 and an areal capacity of 3.2 mAh cm-2. Therefore, this study confirms the ability of interfacial layers formed by electrolyte additives and fluorinated solvents to advance the performance of LMBs and can open new frontiers in the fabrication of high-performance LMBs through electrolyte-formulation engineering.

11.
Plant Cell Rep ; 43(3): 72, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376569

RESUMO

KEY MESSAGE: Rice CC-type NLR XinN1, specifically induced by a PRR XA21, activates defense pathways against Xoo. Plants have evolved two layers of immune systems regulated by two different types of immune receptors, cell surface located pattern recognition receptors (PRRs) and intracellular nucleotide-binding domain leucine-rich repeat-containing receptors (NLRs). Plant PRRs recognize conserved molecular patterns from diverse pathogens, resulting in pattern-triggered immunity (PTI), whereas NLRs are activated by effectors secreted by pathogens into plant cells, inducing effector-triggered immunity (ETI). Rice PRR, XA21, recognizes a tyrosine-sulfated RaxX peptide (required for activation of XA21-mediated immunity X) as a molecular pattern secreted by Xanthomonas oryzae pv. oryzae (Xoo). Here, we identified a rice NLR gene, XinN1, that is specifically induced during the XA21-mediated immune response against Xoo. Transgenic rice plants overexpressing XinN1 displayed increased resistance to infection by Xoo with reduced lesion length and bacterial growth. Overexpression of autoactive mutant of XinN1 (XinN1D543V) also displayed increased resistance to Xoo, accompanied with severe growth retardation and cell death. In rice protoplast system, overexpression of XinN1 or XinN1D543V significantly elevated reactive oxygen species (ROS) production and cytosolic-free calcium (Ca2+) accumulations. In addition, XinN1 overexpression additionally elevated the ROS burst caused by the interaction between XA21 and RaxX-sY and induced the transcription of PTI signaling components, including somatic embryogenesis receptor kinases (OsSERKs) and receptor-like cytoplasmic kinases (OsRLCKs). Our results suggest that XinN1 induced by the PRR XA21 activates defense pathways and provides enhanced resistance to Xoo in rice.


Assuntos
Oryza , Oryza/genética , Espécies Reativas de Oxigênio , Receptores de Reconhecimento de Padrão/genética , Transdução de Sinais , Transporte Biológico
12.
Biomaterials ; 305: 122450, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38169190

RESUMO

In vitro atherosclerosis models are essential to evaluate therapeutics before in vivo and clinical studies, but significant limitations remain, such as the lack of three-layer vascular architecture and limited atherosclerotic features. Moreover, no scalable 3D atherosclerosis model is available for making high-throughput assays for therapeutic evaluation. Herein, we report an in vitro 3D three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features (VSA), including endothelial dysfunction, monocyte recruitment, macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells, and calcification initiation. Notably, we present the creation of high-throughput functional assays with VSAs and the use of these assays for evaluating therapeutics for atherosclerosis treatment. The therapeutics include conventional drugs (statin and sirolimus), candidates for treating atherosclerosis (curcumin and colchicine), and potential gene therapy (miR-146a-loaded liposomes). The high efficiency and flexibility of the scalable VSA functional assays should facilitate drug discovery and development for atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Aterosclerose/tratamento farmacológico , Macrófagos , Células Espumosas , Monócitos , Expressão Gênica , Miócitos de Músculo Liso
13.
Arch Virol ; 169(2): 24, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206482

RESUMO

The complete nucleotide sequence of a newly discovered virus infecting Quercus aliena Blume, tentatively named "quercus leafroll virus" (QLRV), was determined through high-throughput and Sanger sequencing. The sequence comprises 3,940 nucleotides, has five open reading frames, and has a typical pelarspovirus genome organization, with neither 3' polyadenylation nor a 5' cap. The proteins encoded by QLRV share 17.9 to 44.2% amino acid sequence identity with known pelarspovirus proteins. The highest amino acid sequence identity values for the RNA-dependent RNA polymerase (RdRp) and coat protein were 67.5% and 55.2%, respectively, which are below the current thresholds for pelarspovirus species demarcation. On the basis of these results, we propose classifying QLRV as a new member of the genus Pelarspovirus, family Tombusviridae.


Assuntos
Quercus , Tombusviridae , República da Coreia , Sequência de Aminoácidos , Nucleotídeos
14.
Arch Virol ; 169(2): 28, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214788

RESUMO

A putative new polerovirus, named "chrysanthemum virus D" (ChVD), was detected in a Chrysanthemum morifolium plant in South Korea. The virus was identified by high-throughput sequencing and confirmed by reverse transcription polymerase chain reaction. The entire ChVD genome is composed of 5,963 nucleotides and contains seven open reading frames (ORF0-5 and ORF3a), which are arranged similarly to those of other poleroviruses. These ORFs encode the putative proteins P0-5 and P3a, respectively. Pairwise amino acid sequence comparisons showed that the ChVD P0-5 and P3a proteins have 30.45-75% sequence identity to the corresponding proteins of other members of the genus Polerovirus. Since one of the species demarcation criteria for the genus Polerovirus is > 10% difference in the amino acid sequence of any gene product, the sequence comparisons indicate that ChVD represents a new species in this genus. Phylogenetic analysis of the P1-P2 and P3 amino acid sequences further indicate that ChVD is a novel polerovirus.


Assuntos
Chrysanthemum , Luteoviridae , Sequência de Bases , Filogenia , Chrysanthemum/genética , Genoma Viral , Doenças das Plantas , RNA Viral/genética , Luteoviridae/genética , Fases de Leitura Aberta , Sequenciamento de Nucleotídeos em Larga Escala
15.
Korean J Intern Med ; 39(3): 501-512, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38287501

RESUMO

BACKGROUND/AIMS: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). METHODS: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). RESULTS: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. CONCLUSION: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.


Assuntos
Avaliação Geriátrica , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Feminino , Idoso , Masculino , Estudos Prospectivos , Idoso de 80 Anos ou mais , Medição de Risco , Fatores de Risco , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Progressão , Atividades Cotidianas , Valor Preditivo dos Testes , Fatores de Tempo , Técnicas de Apoio para a Decisão , Doxorrubicina/efeitos adversos , Doxorrubicina/administração & dosagem , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Comorbidade , República da Coreia/epidemiologia
16.
Adv Sci (Weinh) ; 11(14): e2308978, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279580

RESUMO

Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with ß-glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin-induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. ß-Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with ß-glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of ß-glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury-mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury-mediated disorders.


Assuntos
Lesão Pulmonar , beta-Glucanas , Camundongos , Animais , Sirtuína 1 , Eferocitose , Lesão Pulmonar/prevenção & controle , beta-Glucanas/farmacologia , Fibrose
17.
J Inherit Metab Dis ; 47(1): 93-118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37421310

RESUMO

Glycogen storage disorders (GSDs) are inherited disorders of metabolism resulting from the deficiency of individual enzymes involved in the synthesis, transport, and degradation of glycogen. This literature review summarizes the development of gene therapy for the GSDs. The abnormal accumulation of glycogen and deficiency of glucose production in GSDs lead to unique symptoms based upon the enzyme step and tissues involved, such as liver and kidney involvement associated with severe hypoglycemia during fasting and the risk of long-term complications including hepatic adenoma/carcinoma and end stage kidney disease in GSD Ia from glucose-6-phosphatase deficiency, and cardiac/skeletal/smooth muscle involvement associated with myopathy +/- cardiomyopathy and the risk for cardiorespiratory failure in Pompe disease. These symptoms are present to a variable degree in animal models for the GSDs, which have been utilized to evaluate new therapies including gene therapy and genome editing. Gene therapy for Pompe disease and GSD Ia has progressed to Phase I and Phase III clinical trials, respectively, and are evaluating the safety and bioactivity of adeno-associated virus vectors. Clinical research to understand the natural history and progression of the GSDs provides invaluable outcome measures that serve as endpoints to evaluate benefits in clinical trials. While promising, gene therapy and genome editing face challenges with regard to clinical implementation, including immune responses and toxicities that have been revealed during clinical trials of gene therapy that are underway. Gene therapy for the glycogen storage diseases is under development, addressing an unmet need for specific, stable therapy for these conditions.


Assuntos
Carcinoma Hepatocelular , Doença de Depósito de Glicogênio Tipo II , Doença de Depósito de Glicogênio Tipo I , Doença de Depósito de Glicogênio , Neoplasias Hepáticas , Animais , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/terapia , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio/terapia , Doença de Depósito de Glicogênio/metabolismo , Doença de Depósito de Glicogênio Tipo I/genética , Doença de Depósito de Glicogênio Tipo I/terapia , Doença de Depósito de Glicogênio Tipo I/complicações , Fígado/metabolismo , Glicogênio/metabolismo , Terapia Genética/métodos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia
18.
Plant Dis ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38054925

RESUMO

The common bean (Phaseolus vulgaris; family: Fabaceae) is an economically and nutritionally important food crop worldwide (Ganesan et al. 2017). In 2021, several plants collected from different provinces in South Korea had symptoms of viral infections (e.g., mild yellow-greenish speckling, stunting, crinkling, and deformed leaves). To identify the causal pathogens, total RNA was isolated from pooled leaf tissues from all samples (n = 29) for paired-end high-throughput sequencing (HTS). The cDNA library was constructed after eliminating ribosomal RNA using the TruSeq RNA Sample Prep Kit and then sequenced using the Illumina NovaSeq 6000 platform (Macrogen, Korea). The 297,868,156 paired-end clean reads (150 nt) were de novo assembled using Trinity with default parameters. BLASTx was used for the contig analysis, which revealed the pooled samples were infected with several plant viruses (e.g., turnip mosaic virus, zucchini yellow mosaic virus, cucumber mosaic virus, lily mottle virus). Notably, the assembled contigs included a single viral contig (8,472 nt) comprising the nearly complete KLV genome (HTS mean coverage: 39.46%). Kalanchoe latent virus (KLV; genus: Carlavirus; family: Betaflexiviridae) has been detected in Kalanchoë blossfeldiana (Hearon 1982), Chenopodium quinoa (Dinesen et al. 2009), and Graptopetalum paraguayense (Sorrentino et al. 2017). The sequence was most similar (96.28% nucleotide identity; 99% query coverage) to KLV isolate DSMZ PV-0290 (GenBank: OP525283) from Denmark. The contig sequence was validated via reverse transcription-polymerase chain reaction (RT-PCR) using total RNA extracted from the 29 individually stored samples and nine primer sets specific for the KLV contig. All nine contig-specific overlapping fragments were amplified from only a P. vulgaris plant with mild yellowing mosaic symptoms collected on July 6, 2021, in Jeongseon County, South Korea. Additionally, 5' and 3' rapid amplification of cDNA ends (RACE)-specific primers were designed for the KLV contig sequence to determine the terminal ends of the genome of the South Korean KLV isolate using the 5'/3' RACE System (Invitrogen, Carlsbad, CA, USA). All of the amplified and overlapping fragments were cloned into the RBC T&A Cloning Vector (RBC Bioscience, Taipei, Taiwan) and sequenced using the Sanger method. The obtained full-length genomic sequence of the KLV isolate (KLV-SK22) was 8,517 nt long and was deposited in GenBank OQ718816. According to the BLASTn analysis, KLV-SK22 was highly similar (96.30% sequence identity; 100% query coverage) to the DSMZ PV-0290 isolate. Phylogenetic trees constructed on the basis of coat protein and RNA-dependent RNA polymerase amino acid sequences revealed that KLV-SK22 is closely related to the DSMZ PV-0290 and PV-0290B isolates from Denmark, respectively. At the genome and gene levels, the individual sequence identities between the carlaviruses and other KLV isolates were 96.29% to 100% (Adams et al. 2004). Additionally, an RT-PCR analysis using detection primers specific for KLV-SK22 did not detect KLV in 15 samples (P. vulgaris = 3, Glycine max = 8, Pueraria montana = 2, Trifolium repens = 1, and Vigna angularis = 1) randomly collected from different regions in South Korea. Based on these results, KLV infection may not be widespread at this time in South Korea. To the best of our knowledge, this is the first report of KLV in P. vulgaris in South Korea or elsewhere. Our findings will aid future research on the epidemiology and long-term management of KLV-related diseases.

19.
Molecules ; 28(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38138458

RESUMO

The purpose of this study was to evaluate the physicochemical properties of whey protein hydrolysate and determine changes in absorption rate due to enzymatic hydrolysis. The molecular weight distribution analysis of whey protein concentrate (WPC) and low-molecule whey protein hydrolysate (LMWPH) using the Superdex G-75 column revealed that LMWPH is composed of peptides smaller than those in WPC. Fourier-transform infrared spectroscopy indicated differences in peak positions between WPC and LMWPH, suggesting hydrolysis-mediated changes in secondary structures. Moreover, LMWPH exhibited higher thermal stability and faster intestinal permeation than WPC. Additionally, oral LMWPH administration increased serum protein content at 20 min, whereas WPC gradually increased serum protein content after 40 min. Although the total amount of WPC and LMWPH absorption was similar, LMWPH absorption rate was higher. Collectively, LMWPH, a hydrolysate of WPC, has distinct physicochemical properties and enhanced absorptive characteristics. Taken together, LMWPH is composed of low-molecular-weight peptides with low antigenicity and has improved absorption compared to WPC. Therefore, LMWPH can be used as a protein source with high bioavailability in the development of functional materials.


Assuntos
Hidrolisados de Proteína , Subtilisinas , Hidrolisados de Proteína/química , Subtilisinas/metabolismo , Soro do Leite/metabolismo , Proteínas do Soro do Leite , Peptídeos/química , Proteínas Sanguíneas
20.
J Thorac Dis ; 15(10): 5485-5493, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969267

RESUMO

Background: Chest computed tomography (CT) is routinely performed to evaluate intrathoracic metastasis in patients with breast cancer, but radiation exposure and its potential carcinogenic risks are major drawbacks. Furthermore, pulmonary imaging by magnetic resonance imaging (MRI) is limited by low proton density, rapid signal decay, and sensitivity to respiratory and cardiac motions in lung tissue. Recently, a respiratory gating spiral three-dimensional (3D) ultrashort echo time (UTE) volume interpolated breath-hold examination (VIBE) sequence for lung MRI provides high spatial-resolution images with reasonable scan times. Our objective was to investigate the feasibility of chest spiral 3D UTE VIBE MRI to detect intrathoracic metastasis in breast cancer patients. Methods: This retrospective study of a prospectively collected database was conducted between February and July 2019 after institutional review board approval. All participants provided informed consent for MRI scans. Ninety-three female patients with breast cancer were retrospectively enrolled and underwent preoperative breast MRI, including a chest spiral 3D UTE VIBE sequence. Two chest radiologists evaluated image qualities of intrapulmonary vessels and bronchial wall visibilities, the presence of pulmonary nodules, significant lymph nodes (LNs), and other lung abnormalities on spiral 3D UTE magnetic resonance (MR) images and compared them using chest CT as a reference standard. Results: Intrapulmonary vessels and bronchial walls were visible up to sub-subsegmental and sub-subsegmental levels, respectively, on spiral 3D UTE MR images, and better than fair quality was obtained for artifact/noise and overall image quality for 95.7% and 98.9% of the patients, respectively. The overall detection rate for pulmonary nodules was 62.8% (59/94). Furthermore, 59 of the 81 solid nodules detected by CT were detected by spiral 3D UTE MRI (72.8%), and 31 of the 33 solid nodules (≥5 mm in diameter) detected by CT were identified by spiral 3D UTE MRI (93.9%). Significant LNs in the axillary area were similarly detected by spiral 3D UTE MRI and chest CT. Conclusions: Preoperative breast MRI with a chest spiral 3D UTE sequence could be used to evaluate breast cancer and axillary LNs and intrathoracic metastasis simultaneously and offers a potential alternative to chest CT for breast cancer patients without additional radiation exposure.

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