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1.
Toxicol Pathol ; 52(2-3): 123-137, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38888280

RESUMO

Complex in vitro models (CIVMs) offer the potential to increase the clinical relevance of preclinical efficacy and toxicity assessments and reduce the reliance on animals in drug development. The European Society of Toxicologic Pathology (ESTP) and Society for Toxicologic Pathology (STP) are collaborating to highlight the role of pathologists in the development and use of CIVM. Pathologists are trained in comparative animal medicine which enhances their understanding of mechanisms of human and animal diseases, thus allowing them to bridge between animal models and humans. This skill set is important for CIVM development, validation, and data interpretation. Ideally, diverse teams of scientists, including engineers, biologists, pathologists, and others, should collaboratively develop and characterize novel CIVM, and collectively assess their precise use cases (context of use). Implementing a morphological CIVM evaluation should be essential in this process. This requires robust histological technique workflows, image analysis techniques, and needs correlation with translational biomarkers. In this review, we demonstrate how such tissue technologies and analytics support the development and use of CIVM for drug efficacy and safety evaluations. We encourage the scientific community to explore similar options for their projects and to engage with health authorities on the use of CIVM in benefit-risk assessment.


Assuntos
Patologistas , Patologia , Toxicologia , Humanos , Toxicologia/métodos , Animais , Bioengenharia , Testes de Toxicidade , Avaliação Pré-Clínica de Medicamentos , Técnicas In Vitro
2.
Blood Purif ; 53(6): 511-519, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38185099

RESUMO

INTRODUCTION: This study aimed to evaluate prognostic factors and outcomes in a single-center PICU cohort that received continuous renal replacement therapy (CRRT). METHODS: This retrospective study analyzed clinical characteristics, laboratory data, and outcomes. Ninety-day mortality and advanced chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2) were defined as primary and secondary outcomes, respectively. RESULTS: Seventy-five patients were enrolled, all of whom received CRRT for indications including acute kidney injury with complicated refractory metabolic acidosis, electrolyte derangement, and existed or impending fluid overload. The 90-day mortality and advanced CKD were 53% and 29%, respectively. Multivariate Cox regression analysis demonstrated that only underlying bone marrow transplantation (BMT) (HR 4.58; 95% CI: 2.04-10.27) and a high pSOFA score (HR 1.12; 95% CI: 1.01-1.23) were independent risk factors for 90-day mortality. Among survivors, ten developed advanced CKD on the 90th day, and this group had a higher serum fibrinogen level (OR 1.01; 95% CI: 1.01-1.03) at the start of CRRT. CONCLUSION: In critically ill children with AKI requiring CRRT, post-BMT and high pSOFA scores are independent risk factors for 90-day mortality. Additionally, a high serum fibrinogen level at the initiation of CRRT is associated with the development of advanced CKD.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Humanos , Injúria Renal Aguda/terapia , Injúria Renal Aguda/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Criança , Terapia de Substituição Renal Contínua/métodos , Pré-Escolar , Prognóstico , Fatores de Risco , Lactente , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/mortalidade , Adolescente , Estado Terminal , Terapia de Substituição Renal/métodos , Transplante de Medula Óssea
3.
Am J Pathol ; 192(4): 687-700, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35063406

RESUMO

Skin toxicity is a common safety concern associated with drugs that inhibit epidermal growth factor receptors as well as other targets involved in epidermal growth and differentiation. Recently, the use of a three-dimensional reconstructed human epidermis model enabled large-scale drug screening and showed potential for predicting skin toxicity. Although a decrease in epidermal thickness was often observed when the three-dimensional reconstructed tissues were exposed to drugs causing skin toxicity, the thickness evaluation of epidermal layers from a pathologist was subjective and not easily reproducible or scalable. In addition, the subtle differences in thickness among tissues, as well as the large number of samples tested, made cross-study comparison difficult when a manual evaluation strategy was used. The current study used deep learning and image-processing algorithms to measure the viable epidermal thickness from multiple studies and found that the measured thickness was not only significantly correlated with a pathologist's semi-quantitative evaluation but was also in close agreement with the quantitative measurement performed by pathologists. Moreover, a sensitivity of 0.8 and a specificity of 0.75 were achieved when predicting the toxicity of 18 compounds with clinical observations with these epidermal thickness algorithms. This approach is fully automated, reproducible, and highly scalable. It not only shows reasonable accuracy in predicting skin toxicity but also enables cross-study comparison and high-throughput compound screening.


Assuntos
Aprendizado Profundo , Dermatopatias , Algoritmos , Epiderme , Humanos , Processamento de Imagem Assistida por Computador , Pele
4.
Plant Dis ; 107(5): 1481-1490, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36302731

RESUMO

Red crown rot (RCR), caused by the soilborne fungus Calonectria ilicicola, is an emerging soybean disease in Taiwan, and fungicide screening is desired to identify effective management for C. ilicicola. This study screened 11 fungicides, including azoxystrobin, boscalid, cyprodinil, cyprodinil + fludioxonil, difenoconazole, fluopyram, flutolanil, mancozeb, prochloraz, pyraclostrobin, and tebuconazole, for their inhibitory effects on the mycelial growth of 10 C. ilicicola field isolates. Subsequently, a microplate-based high-throughput screening (MHTS) method was established to measure the fungicide sensitivity in a population composed of 80 C. ilicicola isolates to three effective fungicides, cyprodinil + fludioxonil, fluopyram, and tebuconazole. The MHTS was optimized for multiple factors, including the optical scanning pattern, absorption wavelength, conidial concentration, and measurement timing based on the quality controls of Z' factor and the log-phase growth curve. The population mean EC50 estimated by MHTS were 0.14, 2.34, and 2.46 ppm to cyprodinil + fludioxonil, fluopyram, and tebuconazole, respectively. In addition to the in vitro assessment, fungicide efficacy was evaluated by coating cyprodinil + fludioxonil, fluopyram, or tebuconazole on soybean seeds in the pot assay. The results showed that cyprodinil + fludioxonil significantly reduced both postemergence damping-off and disease severity, while fluopyram and tebuconazole reduced only the postemergence damping-off but not disease severity. Based on the MHTS and the pot assay results, this study demonstrated cyprodinil + fludioxonil to be a potential fungicide to manage soybean RCR.


Assuntos
Fungicidas Industriais , Fungicidas Industriais/farmacologia , Glycine max , Ensaios de Triagem em Larga Escala
5.
J Formos Med Assoc ; 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37845138

RESUMO

BACKGROUND/PURPOSE: Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce. METHODS: We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan. RESULTS: Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation. CONCLUSIONS: The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality.

6.
J Formos Med Assoc ; 122(5): 366-375, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36323601

RESUMO

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Humanos , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Síndrome Hemolítico-Urêmica Atípica/genética , Taiwan , Consenso , Proteínas do Sistema Complemento , Prognóstico
7.
Plant Dis ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372682

RESUMO

From August to November 2020, reduced emergence and damping-off of soybean seedlings were observed in two fields (Benzhou and Wandan) in Taiwan. Disease incidence was approximately 40% in Benzhou by field scouting. The roots of damping-off seedlings were brown. Affected seedlings could be easily pulled out from the soil and the lesions on the roots/stem were generally dry and sunken. These symptoms suggested the possibility of Rhizoctonia infection. Soil surrounding symptomatic seedlings were collected to bait the potential pathogen and symptomatic plants were used for pathogen isolation. The diseased tissues were washed with tap water and surface-disinfected with 1% bleach before placing on the Dexon selection medium at 26°C for 2 days (Ko and Hora 1971). Hyphae were transferred to potato dextrose agar (PDA), and a brown colony with brown and irregular-shaped sclerotia grew from 90 out of 99 isolates. The hyphae exhibited typical characteristics of Rhizoctonia solani, including a constriction and a septum near the end of branching hyphae (Ajayi-Oyetunde and Bradely, 2018). Two isolates from Benzhou and two isolates from Wandan were tested for their pathogenicity, and eight surface-disinfected seeds were distributed evenly on the water agar plates covered by 2-day-old mycelia at 25°C in dark for 7 days. All isolates caused cotyledon rot and reduced germination. To verify their pathogenicity in pots, double-sterilized sorghum seeds were inoculated with two strains and incubated at 25°C for 2 weeks to be used as fungal inoculum (Ajayi-Oyetunde and Bradely, 2017). A layer of 15 ml of fungal inoculum was placed 5 cm beneath the soil surface in pots. Four soybean seeds were planted approximately 3 cm above the inoculum in each pot. After two weeks, reddish lesions on the hypocotyls or taproots of all seedlings in the inoculated pots were observed, while seedlings in the control pots inoculated with sterile sorghum seeds remained healthy. The pathogen was re-isolated from lesions and had identical morphology to the original isolates. To characterize the fungal identity, the internal transcribed spacer (ITS) was sequenced using the primers ITS1/ITS4 (Sharon et al., 2006). Using BLASTN in the NCBI database, the sequence (GenBank no. MW410857 and MW410858) showed 100% (639/639 bp) similarity to KF907734 and 99.83% (635/636 bp) similarity to AF354099, both belong to R. solani anastomosis group 7 (AG-7) (Hua et al. 2014; Gonzalez et al. 2001). Phylogenetic analysis comparing sequences with different AGs (Ajayi-Oyetunde and Bradely, 2017) grouped our isolates within the AG-7 clade with a 100% bootstrap confidence. In the anastomosis test, an incompatible zonation and unequal mycelial growth rates were observed when AG-7 isolates were paired with an AG-1 IA isolate. On the other hand, the compatible tuft reaction was observed when two AG-7 isolates were paired, and the compatible merge reaction was observed in the self-pairing tests (Macnish et al. 1997). Accordingly, the molecular and morphological characterizations confirmed the causal pathogen as R. solani AG-7. R. solani AG-7 was first reported on radishes in Japan (Homma et al., 1983), first found on carnation in Taiwan (Lo et al., 1990), and in field soils of various crops but not soybean (Chuang, 1997). It was suggested that Rhizoctonia diseases of soybean may be present in Taiwan, but molecular confirmation was lacking (Anonymus, 1979). As R. solani AG-7 causes diseases of soybean in the US and Japan (Baird et al., 1996), the importance of AG-7 as an endemic pathogen of soybean in Taiwan should be recognized and its prevalence determined as a first step to managing this disease.

8.
FASEB J ; 33(1): 1051-1061, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30148674

RESUMO

The Kelch-like 3 ( KLHL3) mutations contributed to the most common causative genes in patients with pseudohypoaldosteronism type II (PHAII); however, the molecular mechanisms of PHAII-causing mutations in BTB domain of KLHL3 in vivo have not been investigated. We generated and analyzed Klhl3 knock-in (KI) mice carrying a missense M131V mutation in the BTB domain (corresponding to human KLHL3 M78V mutation). Klhl3M131V/+ KI mice exhibited typical PHAII phenotype with an exaggerated diuretic response to hydrochlorothiazide. Their kidney tissues showed an unchanged KLHL3, decreased cullin 3 (Cul3), and increased with-no-lysine kinases (WNKs) WNK1 and WNK4 along with an enhanced downstream ste20-related proline/alanine-rich kinase/oxidative stress response kinase 1-N(K)CC phosphorylation. Their Cul3 protein in the cytosol of distal convoluted tubule cells was also significantly attenuated on immunogold-labeling electron microscopy. In microdissected renal tubules, Klhl3M131V/+ KI mice expressed high levels of Wnk4 mRNA in the distal nephron. In vitro coimmunoprecipitation showed the KLHL3 BTB domain mutation retained intact interaction with WNKs but reduced binding to Cul3, thus leading to the increased abundance of total WNKs. In summary, Klhl3M131V/+ KI mice feature typical PHAII with a simultaneous increase of WNK1 and WNK4 through the impaired KLHL3 BTB domain binding to Cul3.-Lin, C.-M., Cheng, C.-J., Yang, S.-S., Tseng, M.-H., Yen, M.-T., Sung, C.-C., Lin, S.-H. Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by KLHL3 mutation in BTB domain.


Assuntos
Domínio BTB-POZ , Proteínas dos Microfilamentos/genética , Mutação de Sentido Incorreto , Pseudo-Hipoaldosteronismo/genética , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas Culina/metabolismo , Modelos Animais de Doenças , Furosemida/administração & dosagem , Técnicas de Introdução de Genes , Células HEK293 , Humanos , Hidroclorotiazida/administração & dosagem , Túbulos Renais/metabolismo , Camundongos , Fenótipo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Pseudo-Hipoaldosteronismo/metabolismo , RNA Mensageiro/genética , Membro 2 da Família 12 de Carreador de Soluto/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Proteína Quinase 1 Deficiente de Lisina WNK/metabolismo
9.
Pediatr Res ; 87(7): 1251-1255, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31852011

RESUMO

BACKGROUND: Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking. METHODS: Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up. RESULTS: The study cohort included 12 infants (9 males, age 1-8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645T>G (S549A), c.538G>A (V180I), and c.1-2C>G, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring. CONCLUSIONS: Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.


Assuntos
Acidose Tubular Renal/genética , Acidose Tubular Renal/patologia , Infecções Urinárias/genética , Infecções Urinárias/patologia , Acidose Tubular Renal/etiologia , Aldosterona/sangue , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Receptores de Mineralocorticoides/genética , Renina/sangue , Infecções Urinárias/complicações
10.
Pediatr Nephrol ; 35(2): 271-278, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31728747

RESUMO

BACKGROUND: Percutaneous ultrasound-guided renal biopsy (PURB) is an invasive but essential procedure in establishing the histologic diagnosis of pediatric renal diseases. Large studies which describe PURB complications and its contributory risk factors are scarce in the pediatric literature. METHODS: Patients who underwent real-time PURB from September 2011 to August 2017 were retrospectively reviewed. Data pertaining to clinical characteristics, histologic diagnosis and biopsy-related complications were collected. In addition, the risk factors for complications were also analyzed. RESULTS: Overall, 183 patients (109 females) were enrolled and 201 biopsies were obtained. The mean age was 14.4 ± 13.7 years. Over 98% of the biopsies were considered adequate in quality. The major complications were perirenal hematoma requiring blood transfusion (4 cases, 2.0%), followed by perirenal abscess (1 case, 0.5%) and arteriovenous fistula (1 case, 0.5%). All patients recovered without sequelae after treatment. Hypertension, low estimated glomerular filtration rate (eGFR) and anemia were more common in patients with complication than in those without. Further logistic regression model analysis demonstrated that eGFR <30 ml/1.73m2/min was an independent risk factor for major complications. CONCLUSIONS: Perirenal hematoma needing blood transfusion is the most common major complication for children undergoing renal biopsy. Low eGFR is an independent risk factor for major complications. Early recognition and timely treatment should be delivered to children with renal function impairment accordingly.


Assuntos
Biópsia Guiada por Imagem/efeitos adversos , Nefropatias/diagnóstico , Complicações Pós-Operatórias/etiologia , Ultrassonografia de Intervenção/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Recém-Nascido , Nefropatias/fisiopatologia , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
11.
BMC Womens Health ; 20(1): 52, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164632

RESUMO

BACKGROUND: Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia. CASE PRESENTATION: Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, and aggressive high sodium fluid resuscitation. CONCLUSION: Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca/etiologia , Hipocinesia/diagnóstico por imagem , Complicações Intraoperatórias , Edema Pulmonar/diagnóstico por imagem , Irrigação Terapêutica/efeitos adversos , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia , Intoxicação por Água/complicações , Adulto , Terapia de Substituição Renal Contínua/métodos , Ecocardiografia , Feminino , Humanos , Histeroscopia , Gravidez , Tomografia Computadorizada por Raios X , Água , Intoxicação por Água/terapia
12.
BMC Nephrol ; 20(1): 64, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30791890

RESUMO

BACKGROUND: Renal artery stenosis is one of the secondary causes of pediatric hypertension. Cases with critical unilateral renal artery stenosis manifesting with the hyponatremic hypertensive syndrome are rare and a comprehensive description of this disorder in the pediatric population is lacking in the literature. CASE PRESENTATION: We describe a 4-year-old boy who presented with severe hypertension, profound hyponatremia, hypokalemia, nephrotic range proteinuria, and polyuria. Distinctly, the diagnosis of hyponatremic hypertensive syndrome secondary to unilateral renal artery stenosis was confirmed in light of laboratory and radiographic findings of severe natriuresis, elevated renin, and unilateral small kidney. Two weeks following nephrectomy, there was resolution of hyponatremia, hypokalemia, nephrotic range proteinuria and hypertension. CONCLUSIONS: Findings of hyponatremia, hypokalemia, hypertension, polyuria, and unilateral renal hypoplasia can be attributed to a unifying pathology of unilateral renal artery stenosis.


Assuntos
Hipertensão Renovascular , Hiponatremia , Rim , Nefrectomia/métodos , Obstrução da Artéria Renal , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Hipertensão Renovascular/sangue , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/fisiopatologia , Hipertensão Renovascular/cirurgia , Hipopotassemia/diagnóstico , Hipopotassemia/etiologia , Hiponatremia/diagnóstico , Hiponatremia/etiologia , Rim/diagnóstico por imagem , Rim/patologia , Masculino , Tamanho do Órgão , Poliúria/diagnóstico , Poliúria/etiologia , Proteinúria/diagnóstico , Proteinúria/etiologia , Obstrução da Artéria Renal/sangue , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/cirurgia , Resultado do Tratamento
13.
Cytometry A ; 93(10): 1004-1018, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30230197

RESUMO

Understanding the mechanisms and other variants of programmed cell death will help provide deeper insight into various disease processes. Although complex procedures are required to distinguish each type of cell death, the formation of vacuoles is one of the important features in some process of cell death under different conditions. Thus, monitoring and counting the number of vacuoles and the ratio of cells with vacuoles is a commonly used method to indicate and quantify the efficacy of the therapy. Several studies have shown that image processing can provide a quick, convenient and precise mean of performing cell detection. Hence, this study uses an image processing technique to detect and quantify vacuolated cells without the need for dyes. The system both counts the number of vacuolated cells and determines the ratio of cells with vacuoles. The performance of the proposed image processing system was evaluated using 38 images. It has been shown that a strong correlation exists between the automated counts and the manual counts. Furthermore, the absolute percentage errors between automated counts and manual counts for cell detection and vacuolated cell detection using data pooled from all images are 3.61 and 3.33%, respectively. A user-friendly graphical user interface (GUI) is also developed and freely available for download, providing researchers in biomedicine with a more convenient instrument for vacuolization analysis.


Assuntos
Automação/métodos , Processamento de Imagem Assistida por Computador/métodos , Vacúolos/patologia , Linhagem Celular Tumoral , Células HeLa , Humanos
14.
Int J Syst Evol Microbiol ; 68(5): 1418-1422, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29533170

RESUMO

Strain 06168H-1T was isolated from a fishpond sediment sample collected from the southern area of Taiwan, and a polyphasic approach was used to determine its taxonomic position. The isolate grew between 20-40 °C and 0-8 % (w/v) NaCl. It produced branched and unfragmented substrate mycelia. Short spore chains (3-10 spores per chain) formed on branched aerial mycelia. The spore chains contained non-motile, smooth-surfaced, oval spores. Galactose, arabinose and ribose were the whole-cell sugars and meso-diaminopimelic acid was present in its peptidoglycan. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, hydroxyphosphati dylethanolamine and a ninhydrin-positive phosphoglycolipid. The predominant menaquinone was MK-9(H4) and minor components were MK-8(H4) and MK-9(H6). Mycolic acids were not detected. The major cellular fatty acids were iso-C16 : 0 and C17 : 1ω6c and C17 : 0ω8c. The DNA G+C content of the strain was 70.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed this strain clustered with the members of the genus Saccharomonospora and was closely related to Saccharomonospora xinjiangensis, Saccharomonospora azurea and Saccharomonosporacyanea. The levels of similarity between this strain and the closely related species were: Sxinjiangensis BCRC16887T, 98.34 %; S. azurea BCRC 16220T, 98.27 %; and S. cyanea BCRC 16886T, 97.99 %. Based on phylogenetic characteristics, strain 06168H-1T represents a novel species of the genus Saccharomonospora. We thus propose the name Saccharomonospora piscinae sp. nov. for this novel strain, with strain 06168H-1T (=BCRC 16893T=KCTC 19743T) as the type strain.


Assuntos
Actinomycetales/classificação , Sedimentos Geológicos/microbiologia , Filogenia , Lagoas/microbiologia , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Aquicultura , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
Pediatr Nephrol ; 33(7): 1189-1198, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29511890

RESUMO

BACKGROUND: Lupus nephritis (LN) is a major risk factor for systemic lupus erythematous (SLE)-related morbidity and mortality. With the aim of bypassing renal biopsy, we analyzed urinary biomarkers for their ability to predict renal histopathologic features and end-stage kidney disease (ESKD). METHODS: Urinary albumin, ß2-microglobulin (B2M), cystatin C, kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), clusterin, calbindin, interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), trefoil factor 3 (TFF3), osteopontin, and glutathione S-transferase π (GST-π) levels were measured at time of renal biopsy. Renal histopathologies were carefully reviewed. RESULTS: Urine from 60 pediatric SLE cases with LN, 29 without and 22 healthy controls were collected. Median age at SLE diagnosis was 12.92 years (range = 4.27-17.30 years) and 10 cases progressed to ESKD during a period of 4.12 ± 2.17 years. Urinary albumin and clusterin were significantly elevated (p = 0.035 and 0.048, respectively) in patients with tubulointerstitial renal lesions. Urinary clusterin among all urinary markers, performed best at predicting ESKD with cutoff of 0.61 × 10-4 (AUC = 0.804; p = 0.002). Interestingly, elevation of urinary clusterin likely resulted from local over-expression in tubulointerstitial tissue since the level of serum clusterin was not concomitantly higher (p = 0.424). CONCLUSION: Urinary biomarkers are emerging as non-invasive indicators for lupus-related renal histopathology and renal outcome prediction in pediatric SLE patients. Urinary clusterin, a newly identified biomarker, is an indicator that shows an association with tubulointerstitial renal lesions and demonstrates the best ability to predict ESKD.


Assuntos
Clusterina/urina , Falência Renal Crônica/diagnóstico , Túbulos Renais/patologia , Nefrite Lúpica/complicações , Nefrite Intersticial/urina , Adolescente , Biomarcadores/urina , Biópsia , Criança , Pré-Escolar , Clusterina/sangue , Clusterina/metabolismo , Progressão da Doença , Feminino , Seguimentos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/patologia , Túbulos Renais/metabolismo , Nefrite Lúpica/sangue , Nefrite Lúpica/urina , Masculino , Nefrite Intersticial/sangue , Nefrite Intersticial/etiologia , Nefrite Intersticial/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
16.
Chin J Physiol ; 61(2): 65-74, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29526075

RESUMO

Notch signaling is a candidate pathway that transmits environmental information into the cell and interferes with the epigenome of gastric cancer. This study aimed to explore if the Notch pathway was abnormally regulated during gastric tumorigenesis. To achieve the goal, Delta-like ligand 1 (DLL1) gene expression, Notch upstream signal, promoter methylation and its correlation with DLL1 expression were examined by methylation-specific polymerase chain reaction (PCR) and real-time PCR (RT-PCR) in cultured gastric cancer cell lines or gastric cancer patient samples. Immunostainings and tissue arrays (n = 40) were used to confirm the DLL1 expression was down-regulated in cancer cells. Transient or stable Notch1 active domain (NICD)-overexpression suppressed proliferation of the gastric cells but the in vivo tumor growth was enhanced. The results of abnormal DLL1 methylation and expression observed in early gastric lesions and in gastric cancers may be relevant to the pathogenesis of gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Epigênese Genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Neoplasias Gástricas/genética , Animais , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação ao Cálcio , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo , Carga Tumoral
17.
J Psycholinguist Res ; 46(3): 643-659, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27858256

RESUMO

This study investigated the self-regulatory behaviors of arts students, namely memory strategy, goal-setting, self-evaluation, seeking assistance, environmental structuring, learning responsibility, and planning and organizing. We also explored approaches to learning, including deep approach (DA) and surface approach (SA), in a comparison between students' professional training and English learning. The participants consisted of 344 arts majors. The Academic Self-Regulation Questionnaire and the Revised Learning Process Questionnaire were adopted to examine students' self-regulatory behaviors and their approaches to learning. The results show that a positive and significant correlation was found in students' self-regulatory behaviors between professional training and English learning. The results indicated that increases in using self-regulatory behaviors in professional training were associated with increases in applying self-regulatory behaviors in learning English. Seeking assistance, self-evaluation, and planning and organizing were significant predictors for learning English. In addition, arts students used the deep approach more often than the surface approach in both their professional training and English learning. A positive correlation was found in DA, whereas a negative correlation was shown in SA between students' self-regulatory behaviors and their approaches to learning. Students with high self-regulation adopted a deep approach, and they applied the surface approach less in professional training and English learning. In addition, a SEM model confirmed that DA had a positive influence; however, SA had a negative influence on self-regulatory behaviors.


Assuntos
Aprendizagem/fisiologia , Estudantes/psicologia , Avaliação Educacional , Objetivos , Humanos , Autocontrole
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