RESUMO
Bladder cancer (BCa) is a highly prevalent type of cancer worldwide, and it is responsible for numerous deaths and cases of disease. Due to the diverse nature of this disease, it is necessary to conduct significant research that delves deeper into the molecular aspects, to potentially discover novel diagnostic and therapeutic approaches. Lately, there has been a significant increase in the focus on non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), due to their growing recognition for their involvement in the progression and manifestation of BCa. The interest in exosomes has greatly grown due to their potential for transporting a diverse array of active substances, including proteins, nucleic acids, carbohydrates, and lipids. The combination of these components differs based on the specific cell and its condition. Research indicates that using exosomes could have considerable advantages in identifying and forecasting BCa, offering a less invasive alternative. The distinctive arrangement of the lipid bilayer membrane found in exosomes is what makes them particularly effective for administering treatments aimed at managing cancer. In this review, we have tried to summarize different ncRNAs that are involved in BCa pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in BCa.
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Exossomos , Neoplasias da Bexiga Urinária , Exossomos/metabolismo , Exossomos/genética , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , AnimaisRESUMO
Magnesium chelatase (MgCh) catalyzes the insertion of magnesium into protoporphyrin IX, a vital step in chlorophyll (Chl) biogenesis. The enzyme consists of 3 subunits, MgCh I subunit (CHLI), MgCh D subunit (CHLD), and MgCh H subunit (CHLH). The CHLI subunit is an ATPase that mediates catalysis. Previous studies on CHLI have mainly focused on model plant species, and its functions in other species have not been well described, especially with regard to leaf coloration and metabolism. In this study, we identified and characterized a CHLI mutant in strawberry species Fragaria pentaphylla. The mutant, noted as p240, exhibits yellow-green leaves and a low Chl level. RNA-Seq identified a mutation in the 186th amino acid of the CHLI subunit, a base conserved in most photosynthetic organisms. Transient transformation of wild-type CHLI into p240 leaves complemented the mutant phenotype. Further mutants generated from RNA-interference (RNAi) and CRISPR/Cas9 gene editing recapitulated the mutant phenotype. Notably, heterozygous chli mutants accumulated more Chl under low light conditions compared with high light conditions. Metabolite analysis of null mutants under high light conditions revealed substantial changes in both nitrogen and carbon metabolism. Further analysis indicated that mutation in Glu186 of CHLI does not affect its subcellular localization nor the interaction between CHLI and CHLD. However, intramolecular interactions were impaired, leading to reduced ATPase and MgCh activity. These findings demonstrate that Glu186 plays a key role in enzyme function, affecting leaf coloration via the formation of the hexameric ring itself, and that manipulation of CHLI may be a means to improve strawberry plant fitness and photosynthetic efficiency under low light conditions.
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Fragaria , Liases , Mutação Puntual , Fragaria/genética , Fragaria/metabolismo , Liases/genética , Liases/metabolismo , Mutação/genética , Adenosina Trifosfatases/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Clorofila/metabolismoRESUMO
Depolymerization of the cellulose part in lignocellulose to glucose is a significant step for lignocellulose valorization. As one of the main by-products of agricultural biomass in crop-producing filed, valorization of corn straw has attracted considerable attention. In this study, a two-step depolymerizing strategy of high-pressure CO2-H2O pretreatment and oxidation-hydrolysis was applied for selective depolymerization of the cellulose component of corn straw to glucose production. Most part of the hemicellulose component could be removed through high-pressure CO2-H2O pretreatment in the presence of low concentration of acetic acid, and then as high as 32.2 % yield of glucose was achieved in water at 170 °C for 6â h without additional catalyst. The active acid sites generated during the partial oxidation of hydroxymethyl groups to carboxyl groups on glucose units of cellulose was shown to be crucial for the efficient valorization of corn straw for glucose production.
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Biomassa , Celulose , Glucose , Lignina , Polimerização , Zea mays , Zea mays/química , Glucose/química , Glucose/metabolismo , Celulose/química , Lignina/química , Hidrólise , Oxirredução , Dióxido de Carbono/química , Água/química , Ácido Acético/química , Catálise , Polissacarídeos/químicaRESUMO
OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.
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Hemangioma , Doenças do Recém-Nascido , Neoplasias Hepáticas , Gravidez , Recém-Nascido , Criança , Feminino , Humanos , Lactente , Propranolol/uso terapêutico , Estudos Retrospectivos , Hemangioma/diagnóstico por imagem , Hemangioma/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologiaRESUMO
Due to microplastics (MPs) being widely distributed in soil, the use of advanced oxidation to remediate organic-contaminated soils may accelerate the aging of MPs in soil and impact the release of di-(2-ethylhexyl) phthalate (DEHP), a potential carcinogen used as a plasticizer in plastics, from MPs. In this study, persulfate oxidation (PO) and temperature treatment (TT) were used to treat biodegradable and petroleum-based MPs, including polylactic acid (PLA), polyvinyl chloride (PVC), and polystyrene (PS). The methods used for evaluating the characteristics changes of MP were X-ray diffraction (XRD) analysis and water contact angle measurement. The effects of aging on DEHP release from MPs were investigated via soil incubation. The results showed PO and TT led to increased surface roughness, oxygen-containing functional group content, and hydrophilicity of the MPs with prolonged aging, consequently accelerating the release of DEHP from the MPs. Interestingly, PLA aged faster than PVC and PS under similar conditions. After 30 days of PO treatment, DEHP release from PLA into the soil increased 0.789-fold, exceeding the increase from PVC (0.454-fold) and PS (0.287-fold). This suggests that aged PLA poses a higher ecological risk than aged PVC or PS. Furthermore, PO treatment resulted in the oxidation and degradation of DEHP on the MP surface. After 30 days of PO treatment, the DEHP content in PLA, PVC, and PS decreased by 19.1%, 25.8%, and 23.5%, respectively. Specifying the types of MPs studied and the environmental conditions would provide a more precise context for the results. These findings provide novel insights into the fate of biodegradable and petroleum-based MPs and the potential ecotoxicity arising from advanced oxidation remediation in contaminated soils.
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Dietilexilftalato , Ácidos Ftálicos , Plásticos , Microplásticos , Dietilexilftalato/toxicidade , Solo , Poliésteres , PoliestirenosRESUMO
The patient was a male infant, born full-term, admitted to the hospital at 28 days of age due to jaundice for 20 days and abdominal distension for 15 days. The patient developed symptoms of jaundice, hepatosplenomegaly, massive ascites, and progressively worsening liver function leading to liver failure, severe coagulation disorders, and thrombocytopenia one week after birth. Various treatments were administered, including anti-infection therapy, fluid restriction, use of diuretics, use of hepatoprotective and choleretic agents, intermittent paracentesis, blood exchange, and intravenous immunoglobulin, albumin, and plasma transfusions. However, the patient's condition did not improve, and on the 24th day of hospitalization, the family decided to discontinue treatment and provide palliative care. Sequencing of the patient's liver tissue and parental blood samples using whole-exome sequencing did not identify any pathogenic variants that could explain the liver failure. However, postmortem liver tissue pathology suggested congenital hepatic fibrosis (CHF). Given the rarity of CHF causing neonatal liver failure, further studies on the prognosis and pathogenic genes of CHF cases are needed in the future. This article provides a comprehensive description of the differential diagnosis of neonatal liver failure and introduces a multidisciplinary diagnostic and therapeutic approach to neonatal liver failure.
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Doenças Genéticas Inatas , Icterícia , Falência Hepática , Lactente , Recém-Nascido , Humanos , Masculino , Cirrose Hepática , Falência Hepática/etiologiaRESUMO
Castleman disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric CD (UCD) and multicentric CD (MCD) are two phenotypes of CD diagnosed by the histopathology of lymph nodes. We attempted to describe a pediatric CD cohort to optimize the management of this disease. We reviewed the medical records of pediatric patients diagnosed with CD between April, 2004, and October, 2022, at the Children's Hospital of Fudan University. Prognosis information was collected in January, 2023, by telephone inquiry. Twenty-two patients with UCD and 2 patients with MCD were identified, all with hyaline vascular (HV) type. The median ages at diagnosis were 10.75 years (IQR 8, 12.81) for UCD and 14.42 years (IQR 13.42, 15.42) for MCD. The most common lesion location of UCD was the neck (9/22, 40.91%) and abdomen (9/22, 40.91%). Systematic symptoms occurred on 10/22 (45.45%) patients with UCD and 1/2 (50%) patients with MCD, and abnormal laboratory indexes were detected in both. Resection and biopsy were performed on all patients. One out of two patients with MCD also received rituximab for upfront therapy. After a median of 4 years (IQR 1.5, 6) of follow-up time, the overall survival was 100% and the complete remission rate in UCD was 63%. There was no relapse or progression. CONCLUSIONS: Our series demonstrated that HV-UCD was the most common type in children. Resection and biopsy were used for both deterministic diagnoses and treatments. Despite the high possibility to develop systematic inflammation, children with CD showed promising outcomes. WHAT IS KNOWN: ⢠Castleman disease is a rare lymphoproliferative disorder with limited cohort studies, especially in pediatrics. ⢠The ubiquity of delayed confirmations and misdiagnoses points to a lack of knowledge about etiology and characteristics, which is a prerequisite for novel therapeutics. WHAT IS NEW: ⢠We retrospectively reviewed and analyzed the clinical and pathological symptoms, laboratory and imaging features, and treatment outcomes of a Chinese pediatric cohort with Castleman disease. ⢠Our work may improve the recognition and optimize the management of this rare disease in children.
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Hiperplasia do Linfonodo Gigante , Humanos , Criança , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/terapia , Hiperplasia do Linfonodo Gigante/patologia , Estudos Retrospectivos , Linfonodos/patologia , Resultado do Tratamento , ChinaRESUMO
Xanthomonas fragariae (X. fragariae) is the causal agent of angular leaf spots (ALS) in strawberry plants. Recently, a study in China isolated X. fragariae strain YL19, which was observed to cause both typical ALS symptoms and dry cavity rot in strawberry crown tissue; this was the first X. fragariae strain to have both these effects in strawberry. In this study, from 2020 to 2022, we isolated 39 X. fragariae strains from diseased strawberries in different production areas in China. Multilocus sequence typing (MLST) and phylogenetic analysis showed that X. fragariae strain YLX21 was genetically different from YL19 and other strains. Tests indicated that YLX21 and YL19 had different pathogenicities toward strawberry leaves and stem crowns. YLX21 did not cause ALS symptoms, rarely caused dry cavity rot in strawberry crown after wound inoculation, and never caused dry cavity rot after spray inoculation, but it did cause severe ALS symptoms after spray inoculation. However, YL19 caused more severe symptoms in strawberry crowns under both conditions. Moreover, YL19 had a single polar flagellum, while YLX21 had no flagellum. Motility and chemotaxis assays showed that YLX21 had weaker motility than YL19, which may explain why YLX21 tended to multiply in situ within the strawberry leaf rather than migrate to other tissues, causing more severe ALS symptoms and mild crown rot symptoms. Taken together, the new strain YLX21 helped us reveal critical factors underlying the pathogenicity of X. fragariae and the mechanism by which dry cavity rot in strawberry crowns forms.
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Fragaria , Xanthomonas , Fragaria/microbiologia , Tipagem de Sequências Multilocus , Filogenia , Virulência , Xanthomonas/patogenicidadeRESUMO
Xanthomonas fragariae usually causes angular leaf spot (ALS) of strawberry, a serious bacterial disease in many strawberry-producing regions worldwide. Recently, a new strain of X. fragariae (YL19) was isolated from strawberry in China and has been shown to cause dry cavity rot in strawberry crown. In this study, we constructed a green fluorescent protein (GFP)-labeled Xf YL19 (YL19-GFP) to visualize the infection process and pathogen colonization in strawberries. Foliar inoculation of YL19-GFP resulted in the pathogen migrating from the leaves to the crown, whereas dip inoculation of wounded crowns or roots resulted in the migration of bacteria from the crowns or roots to the leaves. These two invasion types both resulted in the systematic spread of YL19-GFP, but inoculation of a wounded crown was more harmful to the strawberry plant than foliar inoculation. Results increased our understanding of the systemic invasion of X. fragariae, and the resultant crown cavity caused by Xf YL19.
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Fragaria , Xanthomonas , Fragaria/microbiologia , ChinaRESUMO
Energy management methods (EMMs) utilizing sensing, communication, and networking technologies appear to be one of the most promising directions for energy saving and environmental protection of fuel cell vehicles (FCVs). In real-world driving situations, EMMs based on driving cycle information are critical for FCVs and have been extensively studied. The collection and processing of driving cycle information is a fundamental and critical work that cannot be separated from sensors, global positioning system (GPS), vehicle-to-vehicle (V2V), vehicle-to-everything (V2X), intelligent transportation system (ITS) and some processing algorithms. However, no reviews have comprehensively summarized the EMMs for FCVs from the perspective of driving cycle information. Motivated by the literature gap, this paper provides a state-of-the-art understanding of EMMs for FCVs from the perspective of driving cycle information, including a detailed description for driving cycle information analysis, and a comprehensive summary of the latest EMMs for FCVs, with a focus on EMMs based on driving pattern recognition (DPR) and driving characteristic prediction (DCP). Based on the above analysis, an in-depth presentation of the highlights and prospects is provided for the realization of high-performance EMMs for FCVs in real-world driving situations. This paper aims at helping the relevant researchers develop suitable and efficient EMMs for FCVs using driving cycle information.
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The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.
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Proteinose Alveolar Pulmonar , Insuficiência Respiratória , Lactente , Recém-Nascido , Humanos , Masculino , Lavagem Broncoalveolar/efeitos adversos , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Proteinose Alveolar Pulmonar/patologia , Dispneia/etiologiaRESUMO
Xanthomonas fragariae is a global quarantine pathogen, which typically inflicts angular leaf spots. In the present study, we report a new 4.11-Mb high-quality genome sequence of X. fragariae YL19. YL19 can cause the typical angular leaf spot symptoms on strawberry plants in China as well as crown infection pocket symptoms. This new symptom has not been reported in other X. fragariae. Compared with typical X. fragariae strains, including PD885, NBC2815, PD5205, Fap21, and Fap29, the genome and plasmid in YL19 were smaller in size, lacking 109 coding genes, and have more carbohydrate-active enzyme and secondary metabolism genes. The YL19 genome ought to clarify the molecular mechanisms of genome evolution, host adaptation, and pathological process of X. fragariae and help improve strawberry management strategies.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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Fragaria , Xanthomonas , Fragaria/genética , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Xanthomonas/genéticaRESUMO
An efficient and selective protocol for the synthesis of perfluoroalkyl-group-substituted benzo[4,5]imidazo[1,2-a]pyridines has been developed in which ß-perfluoroalkyl peroxides act as novel fluorinated C3-building blocks to implement regioselective [3 + 3] annulation with 2-cyanomethyl benzimidazole under metal-free conditions. The application of the synthesized perfluoroalkylated BIPs as potent anticancer reagents versus the nonfluorinated ones demonstrated the biological utility of this method.
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Fluorocarbonos , Piridinas , Indicadores e Reagentes , Estrutura Molecular , PeróxidosRESUMO
Per-acetylated epigallocatechin-3-gallate (AcEGCG), a fully acetylated derivative of EGCG, a more potent agent for protection of melanocytes from oxidative damage. We present two patients with vitiligo treated with AcEGCG 0.5% cream, who demonstrated skin repigmentation and control of depigmentation progression.
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Catequina , Pigmentação da Pele , Vitiligo , Catequina/análogos & derivados , Catequina/uso terapêutico , Emolientes , Humanos , Melanócitos , Estresse Oxidativo , Vitiligo/tratamento farmacológicoRESUMO
Porcine-induced pluripotent stem cells (piPSCs) are of great significance to animal breeding and human medicine; however, an important problem is that the maintenance of piPSCs mainly depends on exogenous expression of pluripotent transcription factors (TFs), and germline transmission-competent piPSCs have not yet been successfully established. In this study, we explore the defect of epigenetic reprogramming during piPSCs formation, including chromatin accessibility, DNA methylation, and imprinted gene expression, with high-throughput sequencing (ATAC-seq, WGBS, RNA-seq, and Re-seq) methods. We found the somatic features were successfully silenced by connecting closed chromatin loci with downregulated genes, while DNA methylation has limited effects on somatic silence. However, the incomplete chromatin remodeling and DNA demethylation in pluripotency genes hinder pluripotent activation, resulting in the low expression of endogenous pluripotency genes. In addition, the expression of potential imprinted genes was abnormal, and many allelic-biased expressed genes in porcine embryonic fibroblasts (PEFs) were erased, accompanied by establishment of new allelic-biased expressed genes in piPSCs. This study reveals the aberrant epigenetic reprogramming during dox-dependent piPSCs formation, which lays the foundation for research of porcine-iPSC reprogramming and genome imprinting.
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Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Animais , Reprogramação Celular/genética , Cromatina/metabolismo , Impressão Genômica , Células-Tronco Pluripotentes/metabolismo , Suínos , Fatores de Transcrição/metabolismoRESUMO
N6-methyladenosine (m6A) catalyzed by METTL3 regulates the maternal-to-zygotic transition in zebrafish and mice. However, the role and mechanism of METTL3-mediated m6A methylation in blastocyst development remains unclear. Here, we show that METTL3-mediated m6A methylation sustains porcine blastocyst development via negatively modulating autophagy. We found that reduced m6A levels triggered by METTL3 knockdown caused embryonic arrest during morula-blastocyst transition and developmental defects in trophectoderm cells. Intriguingly, overexpression of METTL3 in early embryos resulted in increased m6A levels and these embryos phenocopied METTL3 knockdown embryos. Mechanistically, METTL3 knockdown or overexpression resulted in a significant increase or decrease in expression of ATG5 (a key regulator of autophagy) and LC3 (an autophagy marker) in blastocysts, respectively. m6A modification of ATG5 mRNA mainly occurs at 3'UTR, and METTL3 knockdown enhanced ATG5 mRNA stability, suggesting that METTL3 negatively regulated autophagy in an m6A dependent manner. Furthermore, single-cell qPCR revealed that METTL3 knockdown only increased expression of LC3 and ATG5 in trophectoderm cells, indicating preferential inhibitory effects of METTL3 on autophagy activity in the trophectoderm lineage. Importantly, autophagy restoration by 3MA (an autophagy inhibitor) treatment partially rescued developmental defects of METTL3 knockdown blastocysts. Taken together, these results demonstrate that METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development.
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Autofagia/genética , Blastocisto/metabolismo , Glicoproteínas de Membrana/genética , Metiltransferases/genética , Proteínas do Tecido Nervoso/genética , Sus scrofa/fisiologia , Animais , Glicoproteínas de Membrana/metabolismo , Metiltransferases/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sus scrofa/genéticaRESUMO
INTRODUCTION: Unresectable hilar cholangiocarcinoma (UHC) is a malignant tumor and has a poor prognosis. IRE is a novel non-thermal ablative therapy that causes cellular apoptosis via electrical impulses. To compare the curative effect for UHC, chemotherapy plus concurrent IRE and chemotherapy alone were set up. MATERIALS AND METHODS: From July 2015 to May 2019, 47 patients with UHC were analyzed to chemotherapy + IRE group (n = 23) or chemotherapy alone group (n = 24) in this study. Treatment response was assessed with computed tomography (CT) or magnetic resonance imaging (MRI) 1 month after treatment and every 3 months thereafter. Local tumor progression (LTP), time to LTP, overall survival (OS) and procedure-related complications were compared between the two groups. RESULTS: Chemotherapy plus concurrent IRE group showed a tendency toward a decreased rate of LTP (16.7% vs. 39.5%; p = 0.039) and an increased complete response rate (52.2% vs. 12.5%; p = 0.011) compared with chemotherapy alone group. Time to LTP was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (11.2 months vs. 4.2 months; p = 0.001). Median OS was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (19.6 months vs. 10.2 months; p = 0.001). CONCLUSIONS: Chemotherapy plus concurrent IRE improved local control and prolonged time to LTP and OS in patients with UHC.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Eletroporação , Humanos , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/tratamento farmacológico , Estudos Prospectivos , Resultado do TratamentoRESUMO
AIMS: To analyze the clinicopathological characteristics of poorly differentiated chordomas (PDCs) with SMARCB1/INI1 loss in children. MATERIALS: Four cases of PDCs were included in the study. METHODS: Immunohistochemistry was performed with respect to brachyury, Glut-1, keratin 18, keratin 19, INI1, vimentin, S-100, CK, EMA, GFAP, etc. Fluorescence in situ hybridization (FISH) was performed for SMARCB1/INI1 from 3 patients. RESULTS: Histologically, contrary to typical histologic features for conventional chordomas, 4 tumors were composed of ovoid or atypical fusiform cells. Sporadic physaliphorous cells were evident. Tumor cells had large vacuoles in the cytoplasm that were even remarkable on the imprint cytology slide. By immunohistochemistry, each case revealed loss of SMARCB1/INI1 expression and nuclear expression of brachyury. Glut-1, keratin 18, keratin 19, CK, EMA, and vimentin were positive in these PDCs. Except for 1 patient who had not yet completed FISH, the other 3 cases demonstrated the loss of SMARCB1/INI1 gene by fluorescence in situ hybridization. CONCLUSION: Poorly differentiated SMARCB1/INI1-negative chordoma is a unique subset of chordoma representing a clinically, histopathologically, and molecularly distinct entity with rapid progression and poor prognosis which should not be confused with conventional chordomas. Sporadic physaliphorous cells (tumor cells with large vacuoles in the cytoplasm) provided important diagnostic clues of PDCs. Combination use of characteristic markers of notochord cells (brachyury, Glut-1, keratin 18, and keratin 19) along with INI1 were effective diagnostic tools.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Cordoma/diagnóstico , Cordoma/genética , Proteína SMARCB1/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
BACKGROUND: Clinically amyopathic juvenile dermatomyositis (CAJDM) is a clinical subgroup of juvenile dermatomyositis (JDM), characterized by JDM rashes with little or no clinically evident muscle weakness. Interstitial lung disease (ILD) is an uncommon but potentially fatal complication of juvenile dermatomyositis (JDM). While adults with dermatomyositis-associated ILD usually present respiratory symptoms before or at the same time as skin muscle manifestations, only a few studies have covered the onset of respiratory symptoms of ILD in JDM patients, especially CAJDM. There is currently no clear effective treatment regime or any prognostic factors for CAJDM-associated ILD. CASE PRESENTATION: Here, we report the first case of a CAJDM patient who presented with respiratory symptoms as the initial manifestation. A 10-year-old male patient presented to the hospital with a complaint of progressive cough and chest pain. Violaceous macule and papules appeared a few days later and he was positive for anti-Ro-52 antibodies. Imaging showed diffuse interstitial infiltration in both lungs and lung function tests showed restrictive and obstructive ventilatory dysfunction. Muscular abnormalities were excluded by thigh magnetic resonance imaging (MRI) and electromyography. Skin biopsy showed pathognomonic findings consistent with DM. Lung biopsy indicated chronic inflammation of the mucosa. This patient was finally diagnosed with CAJDM complicated by ILD and prescribed methylprednisolone, immunoglobulin, prednisolone and mycophenolate mofetil (MMF) for treatment. The patient's cutaneous and respiratory manifestations were largely improved. We retrospectively reviewed this and another six cases with CAJDM-associated ILD reported previously to better understand its clinical characteristics and effective management. CONCLUSIONS: Initial respiratory symptoms with rapid progression in patients presenting Gottron papules should be considered manifestations of CAJDM-associated ILD. We also found a combination of corticosteroids, IVIG and MMF to be an effective method of arresting the progress of CAJDM-associated ILD and improving the prognosis of the patients.
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Dermatomiosite , Doenças Pulmonares Intersticiais , Adulto , Criança , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Estudos Retrospectivos , PeleRESUMO
N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.