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BACKGROUND: Concerns regarding antimicrobial resistance (AMR) have resulted in the World Health Organization (WHO) designating so-called global priority pathogens (GPPs). However, little discussion has focused on the diagnosis of GPPs. To enable the simultaneous identification of pathogens and AMR, we developed a modular real-time nucleic acid amplification test (MRT-NAAT). METHODS: Sequence-specific primers for each modular unit for MRT-NAAT pathogen identification and AMR sets were designed. The composition of the reaction mixture and the real-time PCR program were unified irrespective of primer type so to give MRT-NAAT modularity. Standard strains and clinical isolates were used to evaluate the performance of MRT-NAAT by real-time PCR and melting curve analysis. Probit analysis for the MRT-NAAT pathogen identification set was used to assess the limit of detection (LoD). RESULTS: The MRT-NAAT pathogen identification set was made up of 15 modular units 109-199 bp in product size and with a Tms of 75.5-87.5 °C. The LoD was < 15.548 fg/µL, and nine modular units successfully detected the target pathogens. The MRT-NAAT AMR set included 24 modular units 65-785 bp in product size with a Tms of 75.5-87.5 °C; it showed high performance for detecting GPP target genes and variants. CONCLUSIONS: MRT-NAAT enables pathogen identification and AMR gene detection and is time-effective. By unifying the reaction settings of each modular unit, the modularity where combinations of primers can be used according to need could be achieved. This would greatly help in reflecting the researcher's need and the AMR status of a certain region while successfully detecting pathogens and AMR genes.
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Antibacterianos , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Organización Mundial de la Salud , Pruebas Diagnósticas de RutinaRESUMEN
Angiogenesis and the expression of vascular endothelial growth factor (VEGF) are increased in renal cell carcinoma (RCC). Transglutaminase 2 (TGase 2), which promotes angiogenesis in endothelial cells during wound healing, is upregulated in RCC. Tumor angiogenesis involves three domains: cancer cells, the extracellular matrix, and endothelial cells. TGase 2 stabilizes VEGF in the extracellular matrix and promotes VEGFR-2 nuclear translocation in endothelial cells. However, the role of TGase 2 in angiogenesis in the cancer cell domain remains unclear. Hypoxia-inducible factor (HIF)-1α-mediated VEGF production underlies the induction of angiogenesis in cancer cells. In this study, we show that p53 downregulated HIF-1α in RCC, and p53 overexpression decreased VEGF production. Increased TGase 2 promoted angiogenesis by inducing p53 degradation, leading to the activation of HIF-1α. The interaction of HIF-1α and p53 with the cofactor p300 is required for stable transcriptional activation. We found that TGase 2-mediated p53 depletion increased the availability of p300 for HIF-1α-p300 binding. A preclinical xenograft model suggested that TGase 2 inhibition can reverse angiogenesis in RCC.
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Carcinoma de Células Renales/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Proteínas de Unión al GTP/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Renales/metabolismo , Transglutaminasas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Renales/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Proteína Glutamina Gamma Glutamiltransferasa 2 , Mapas de Interacción de ProteínasRESUMEN
Octopus ocellatus meat (OM) is well known as a plentiful protein source. In this study, we evaluated the hepatoprotective effect of an aqueous extract of OM (OMA) against H2O2-triggered oxidative stress in human hepatocytes. First of all, taurine rich OMA showed a good ORAC value and reducing power and it was similar with that of ascorbic acid, which is known as a strong antioxidant. Also, OMA significantly improved H2O2-decreased cell viability by reducing the generation of intracellular reactive oxygen species (ROS) in hepatocytes. Interestingly, the stimulation of H2O2-induced the formations of apoptotic bodies and sub-G1 DNA content, whereas they were inhibited by the treatment with OMA. Furthermore, OMA regulated the protein expression levels of apoptotic molecules, such as Bax and Bcl-2. Taken together, this study suggests that OMA, which contains an abundant amount of taurine, protects hepatocytes from H2O2-triggered oxidative stress and might be a functional food material with hepatoprotective effects.
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Extractos Celulares/farmacología , Hepatocitos/efectos de los fármacos , Octopodiformes/química , Estrés Oxidativo , Animales , Apoptosis , Células Cultivadas , Hepatocitos/citología , Humanos , Peróxido de Hidrógeno/efectos adversos , Carne , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
This study examined two possible sources of asymmetrical lexical access: phonetic proximity to the nearest L1 category and orthographic information. Three groups of native Korean speakers learned Arabic non-words with sound pairs with/without an L1-dominant category (/l-r/ vs. /χ-h/), and then their phonetic categorization and lexical encoding abilities were evaluated. One group was presented with the same letters for the target pair (e.g.,
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Lenguaje , Multilingüismo , Fonética , Psicolingüística , Pueblo Asiatico , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.
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Procedimientos Quirúrgicos Dermatologicos/métodos , Ácido Hialurónico/uso terapéutico , Polinucleótidos/uso terapéutico , Cirugía Plástica/métodos , Adulto , Animales , Método Doble Ciego , Elasticidad/efectos de los fármacos , Femenino , Humanos , Ácido Hialurónico/efectos adversos , Inyecciones Intradérmicas , Masculino , Ratones , Persona de Mediana Edad , Polinucleótidos/efectos adversos , Piel , Envejecimiento de la Piel , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.
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Productos Biológicos , Oryza , Trastornos del Sueño-Vigilia , Ratones , Animales , Depresión/tratamiento farmacológico , Natación , Ácido gamma-Aminobutírico , Modelos Animales de Enfermedad , Estrés Psicológico/tratamiento farmacológicoRESUMEN
Tropane alkaloids (TA) are natural toxins found in certain plants, including cereals, of which atropine and scopolamine are the main species of concern due to their acute toxicity. This study aimed to determine the occurrence of TA in cereal foods and assess the potential health risks associated with their consumption in Korea. TA levels were analyzed in 80 raw and 71 processed cereal samples, which were distributed throughout Korea in 2021, using ultra-performance liquid chromatography-tandem mass spectrometry. At least one of the six TA species, namely atropine, scopolamine, pseudotropine, tropinone, scopine, and 6-hydroxytropinone, was detected in 10 out of the 151 samples at levels ranging from 0.12 to 88.10 µg kg-1. Dietary exposure (mean, 0.23 ng kg-1 bw day-1) to atropine and scopolamine in the Korean population was estimated to be low across all age groups. This is despite considering worst-case scenarios using the total concentrations of atropine and scopolamine in a millet sample, both of which were detected, and 95th percentile consumption for consumers of millet only. Both the hazard index and margin of exposure methods indicated that the current levels of TA exposure from millet consumption were unlikely to pose significant health risks to the Korean population.
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Grano Comestible , Tropanos , Atropina , Grano Comestible/química , República de Corea , Medición de Riesgo , Escopolamina/toxicidad , Tropanos/análisis , Tropanos/química , Alcaloides/análisis , Alcaloides/químicaRESUMEN
Bacterial contamination of blood products poses a significant risk in transfusion medicine. Platelets are particularly vulnerable to bacterial growth because they must be stored at room temperature with constant agitation for >5 days. The limitations of bacterial detection using conventional methods, such as blood cultures and lateral flow assays, include the long detection times, low sensitivity, and the requirement for substantial volumes of blood components. To address these limitations, we assessed the performance of a bacterial enrichment technique using antibiotic-conjugated magnetic nanobeads (AcMNBs) and real-time PCR for the detection of bacterial contamination in plasma. AcMNBs successfully captured >80% of four bacterial strains, including Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Klebsiella pneumoniae, in both plasma and phosphate-buffered saline. After 24-h incubation with bacterial enrichment, S. aureus and B. cereus were each detected at 101 CFU/mL in all trials (5/5), E. coli at 101 CFU/mL in 1/5 trials, and K. pneumoniae at 10² CFU/mL in 4/5 trials. Additionally, without incubation, the improvement was also achieved in samples with bacterial enrichment, S. aureus at 10² CFU/mL and B. cereus at 101 CFU/mL in 1/5 trials each, E. coli at 10³ CFU/mL in 3/5 trials, and K. pneumoniae at 10¹ CFU/mL in 2/5 trials. Overall, the findings from this study strongly support the superiority of bacterial enrichment in detecting low-level bacterial contamination in plasma when employing AcMNBs and PCR.IMPORTANCEThe study presents a breakthrough approach to detect bacterial contamination in plasma, a critical concern in transfusion medicine. Traditional methods, such as blood cultures and lateral flow assays, are hampered by slow detection times, low sensitivity, and the need for large blood sample volumes. Our research introduces a novel technique using antibiotic-conjugated magnetic nanobeads combined with real-time PCR, enhancing the detection of bacteria in blood products, especially platelets. This method has shown exceptional efficiency in identifying even low levels of four different species of bacteria in plasma. The ability to detect bacterial contamination rapidly and accurately is vital for ensuring the safety of blood transfusions and can significantly reduce the risk of infections transmitted through blood products. This advancement is a pivotal step in improving patient outcomes and elevating the standards of care in transfusion medicine.
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Lung cancer represents a significant global health concern and stands as the leading cause of cancer-related mortality worldwide. The identification of specific genomic alterations such as EGFR and KRAS in lung cancer has paved the way for the development of targeted therapies. While targeted therapies for lung cancer exhibiting EGFR, MET and ALK mutations have been well-established, the options for RET mutations remain limited. Importantly, RET mutations have been found to be mutually exclusive from other genomic mutations and to be related with high incidences of brain metastasis. Given these facts, it is imperative to explore the development of RET-targeting therapies and to elucidate the mechanisms underlying metastasis in RET-expressing lung cancer cells. In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Receptores ErbB/metabolismo , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-yesRESUMEN
The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.
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Antineoplásicos , Doxorrubicina/análogos & derivados , Ácidos Grasos Omega-3 , Neoplasias , Humanos , Ratones , Ratas , Animales , Liposomas/química , Ácidos Grasos Omega-3/uso terapéutico , Liberación de Fármacos , Fosfatidilcolinas/química , Modelos Animales de Enfermedad , PolietilenglicolesRESUMEN
PURPOSE: Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM. MATERIALS AND METHODS: Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed. RESULTS: Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05). CONCLUSION: GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Perfilación de la Expresión Génica , Pronóstico , Transcriptoma , Genómica , Microambiente Tumoral , Proteína 2 de Unión a Retinoblastoma/genéticaRESUMEN
Introduction: Recent studies have proposed several plausible mechanisms supporting the association between periodontal disease and systemic disease. However, characterizing the microbial communities in individuals with periodontal disease before onset of other diseases is an important first step in determining how the altered microbial state contributes to disease progression. This study established microbiome profiles for five body habitats of carefully selected, otherwise healthy individuals with periodontal disease. Methods: Blood, oral (buccal mucosa, dental plaque, and saliva), and stool samples were collected from ten healthy subjects with periodontal disease. Using 16S rRNA metagenomics, the taxonomic and functional compositions of microbiomes were investigated. Results: The most predominant phylum in blood and stool was Bacillota. Pseudomonadota accounted for the largest proportion of microbes in the buccal mucosa and saliva, whereas Bacteroidota were the most prevalent in dental plaque. Differential abundance analysis revealed that 12 phyla and 139 genera were differentially abundant between body habitats. Comparison of alpha diversity showed that the blood microbiome has the most diverse community close to neither oral nor stool microbiomes. We also predicted the functional configurations of the microbiome in otherwise healthy subjects with periodontal disease. Principal coordinate analysis based on functional abundance revealed distinct clustering of the microbial communities between different body habitats, as also observed for taxonomic abundance. In addition, 13 functional pathways, including lipopolysaccharide biosynthesis, glutathione metabolism, and proteasome, showed differential expression between habitats. Discussion: Our results offer insight into the effects of the microbiome on systemic health and disease in people with periodontal disease.
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Placa Dental , Microbiota , Enfermedades Periodontales , Humanos , ARN Ribosómico 16S/genética , Microbiota/genética , MetagenomaRESUMEN
Chestnut inner shell (CIS) was fermented at 30 °C for 12 day using Monascus kaoliang, either in solid or submerged state, and alcohol extracts (70% ethanol) of the fermented CIS were examined for their antioxidant (total phenol content and diphenylpicrylhydrazyl radical scavenging activity) and in vitro cosmeceutical activities (tyrosinase and elastase inhibitory activities). Both activities were significantly increased by the M. kaoliang-fermentation, more apparently by submerged fermentation (SMF) than by solid-state fermentation (SSF). The cosmeceutical activity reached its maximum value on the 3rd day of fermentation. The residual amounts of phenolic acids and catechins in the CIS extracts were increased by the fermentation, up to 395.0 and 344.3 µg/g, respectively. More phenolic acids were produced by SMF than SSF, whereas more catechins were produced by SSF than SMF. Therefore, SMF using M. kaoliang was an efficient process for the utilization of CIS as a source of cosmeceuticals.
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The exploration of oral microbiome has been increasing due to its relatedness with various systemic diseases, but standardization of saliva sampling for microbiome analysis has not been established, contributing to the lack of data comparability. Here, we evaluated the factors that influence the microbiome data. Saliva samples were collected by the two collection methods (passive drooling and mouthwash) using three saliva-preservation methods (OMNIgene, DNA/RNA shield, and simple collection). A total of 18 samples were sequenced by both Illumina short-read and Nanopore long-read next-generation sequencing (NGS). The component of the oral microbiome in each sample was compared with alpha and beta diversity and the taxonomic abundances, to find out the effects of factors on oral microbiome data. The alpha diversity indices of the mouthwash sample were significantly higher than that of the drooling group with both short-read and long-read NGS, while no significant differences in microbial diversities were found between the three saliva-preservation methods. Our study shows mouthwash and simple collection are not inferior to other sample collection and saliva-preservation methods, respectively. This result is promising since the convenience and cost-effectiveness of mouthwash and simple collection can simplify the saliva sample preparation, which would greatly help clinical operators and lab workers.
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Microbiota , Sialorrea , Humanos , Saliva/química , Antisépticos Bucales , ADN Bacteriano/genética , Bacterias/genética , ARN Ribosómico 16S/genética , Microbiota/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.
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Leucemia Mieloide Aguda , Tirosina Quinasa 3 Similar a fms , Adulto , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Leucemia Mieloide Aguda/metabolismo , Inhibidores de Proteínas Quinasas/efectos adversos , Mutación , Proteínas Proto-Oncogénicas c-ret/genéticaRESUMEN
A Gram-staining-positive, strictly aerobic, non-spore-forming, rod-shaped bacterial strain, CAU 9163(T), was isolated from marine sediment collected in the Republic of Korea and its taxonomic position was investigated using a polyphasic approach. The novel strain grew optimally at 30 °C and pH 8.0. In phylogenetic analysis based on 16S rRNA gene sequences, strain CAU 9163(T) formed a hitherto unknown lineage within the order Bacillales, which contains the genera Planomicrobium, Planococcus, Sporosarcina, Rummeliibacillus, Viridibacillus, Lysinibacillus and Bacillus. The levels of 16S rRNA gene sequence similarity between the novel strain and any established bacterial species were all <95.7%. The major isoprenoid quinines of strain CAU 9163(T) were MK-8 (65.2%) and MK-7 (22.8%) and the predominant fatty acid was anteiso-C(15:0). The peptidoglycan was of the A4α type and based on L-Lys-D-Asp. The major whole-cell sugars were ribose and glucose. The polar lipid profile mainly consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, an unidentified glycolipid and an unidentified polar lipid. The genomic DNA G+C content of the novel strain was 44.3 mol%. These data were sufficient to differentiate the novel strain from established genera in the phylum Firmicutes. Based on the phenotypic, chemotaxonomic and genotypic evidence, strain CAU 9163(T) represents a novel species in a new genus for which the name Chungangia koreensis gen. nov., sp. nov. is proposed. The type strain of Chungangia koreensis is 9163(T) (â=âKCTC 13729(T) â=âCCUG 59778(T)).
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Sedimentos Geológicos/microbiología , Bacterias Grampositivas/clasificación , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/análisis , Bacterias Grampositivas/genética , Bacterias Grampositivas/aislamiento & purificación , Datos de Secuencia Molecular , Peptidoglicano/análisis , Fosfolípidos/análisis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by aplasia of the uterus and the upper part of the vagina in an XX individual with normal development of secondary sexual characteristics. Individuals with this syndrome may also present with renal and skeletal abnormalities. We report a case of a 16-year-old girl presenting with thyrotoxicosis and primary amenorrhea. After being diagnosed with Graves disease, this patient was placed on antithyroid medication. Although her thyroid function normalized, she did not start to menstruate. Therefore, we assessed her primary amenorrhea and diagnosed the patient with MRKH syndrome through pelvic imaging. To our knowledge, an association between Graves disease and MRKH syndrome has not yet been reported.
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Anomalías Múltiples/diagnóstico , Amenorrea/diagnóstico , Enfermedad de Graves/diagnóstico , Tirotoxicosis/diagnóstico , Trastornos del Desarrollo Sexual 46, XX , Adolescente , Antitiroideos/uso terapéutico , Anomalías Congénitas , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/tratamiento farmacológico , Humanos , Riñón/anomalías , Metimazol/uso terapéutico , Conductos Paramesonéfricos/anomalías , Pelvis/diagnóstico por imagen , Somitos/anomalías , Columna Vertebral/anomalías , Tomografía Computarizada por Rayos X , Útero/anomalías , Vagina/anomalíasRESUMEN
Chestnut inner shell was fermented in solid state with Aspergillus sojae, and then extracted using ethanol (95%) to analyze its cosmeceutical activity and phenolic composition. The fermentation significantly increased the antioxidant activity, and in vitro cosmeceutical activities. The ethanol extract showed the higher activities than ethyl acetate and water extracts. DPPH radical scavenging activity of the alcoholic extract was 80.53%, and tyrosinase and elastase inhibition activities were 101.01%, and 76.73%, respectively, after 10 days of fermentation. Kojic acid, a secondary metabolite of A. sojae was produced by the fermentation as a major bioactive component. Gallic acid, ellagic acid, and coumaric acid appeared the major phenolic acids in the alcoholic extract from fermented chestnut inner shell. The alcoholic extract from chestnut inner shell fermented by A. sojae may be used as an effective and bioactive cosmeceutical. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01044-9.
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Vancomycin-resistant enterococci (VRE) are nosocomial pathogens with genetic plasticity and widespread antimicrobial resistance (AMR). To prevent the spread of VRE in the hospital setting, molecular epidemiological approaches such as pulsed-field gel electrophoresis and multilocus sequence typing have been implemented for pathogen outbreak surveillance. However, due to the insufficient discriminatory power of these methods, whole-genome sequencing (WGS), which enables high-resolution analysis of entire genomic sequences, is being used increasingly. Herein, we performed WGS of VRE using both short-read next-generation sequencing (SR-NGS) and long-read next-generation sequencing (LR-NGS). Since standardized workflows and pipelines for WGS-based bacterial epidemiology are lacking, we established three-step pipelines for SR- and LR-NGS, as a standardized WGS-based approach for strain typing and AMR profiling. For strain typing, we analyzed single-nucleotide polymorphisms (SNPs) of VRE isolates and constructed SNP-based maximum-likelihood phylogenies. The phylogenetic trees constructed using short and long reads showed good correspondence. Still, SR-NGS exhibited higher sensitivity for detecting nucleotide substitutions of bacterial sequences. During AMR profiling, we examined AMR genes and resistance-conferring mutations. We also assessed the concordance between genotypic and phenotypic resistance, which was generally better for LR-NGS than SR-NGS. Further validation of our pipelines based on outbreak cases is necessary to ensure the overall performance of pipelines.
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Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Humanos , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Filogenia , Enterococos Resistentes a la Vancomicina/genética , Polimorfismo de Nucleótido SimpleRESUMEN
AIMS: This study established blood group analysis methods using whole-genome sequencing (WGS) data and conducted blood group analyses to determine the domestic allele frequency using public data from the Korean whole sequence analysis of the Korean Reference Genome Project conducted by the Korea Disease Control and Prevention Agency (KDCA). MATERIALS AND METHODS: We analyzed the differences between the human reference sequences (hg19) and the conventional reference cDNA sequences of blood group genes using the Clustal Omega website, and established blood group analysis methods using WGS data for 41 genes, including 39 blood group genes involved in 36 blood group antigens, as well as the GATA1 and KLF1 genes, which are erythrocyte-specific transcription factor genes. Using CLC genomics Workbench 11.0 (Qiagen, Aarhus, Denmark), variant analysis was performed on these 41 genes in 250 Korean WGS data sets, and each blood group's genotype was predicted. The frequencies for major alleles were also investigated and compared with data from the Korean rare blood program (KRBP) and the Erythrogene database (East Asian and all races). RESULTS: Among the 41 blood group-related genes, hg19 showed variants in the following genes compared to the conventional reference cDNA: GYPA, RHD, RHCE, FUT3, ACKR1, SLC14A1, ART4, CR1, and GCNT2. Among 250 WGS data sets from the Korean Reference Genome Project, 70.6 variants were analyzed in 205 samples; 45 data samples were excluded due to having no variants. In particular, the FUT3, GNCT2, B3GALNT1, CR1, and ACHE genes contained numerous variants, with averages of 21.1, 13.9, 13.4, 9.6, and 7.0, respectively. Except for some blood groups, such as ABO and Lewis, for which it was difficult to predict the alleles using only WGS data, most alleles were successfully predicted in most blood groups. A comparison of allele frequencies showed no significant differences compared to the KRBP data, but there were differences compared to the Erythrogene data for the Lutheran, Kell, Duffy, Yt, Scianna, Landsteiner-Wiener, and Cromer blood group systems. Numerous minor blood group systems that were not available in the KRBP data were also included in this study. CONCLUSIONS: We successfully established and performed blood group analysis using Korean public WGS data. It is expected that blood group analysis using WGS data will be performed more frequently in the future and will contribute to domestic data on blood group allele frequency and eventually the supply of safe blood products.