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Microprocessor (MP), DROSHA-DGCR8, processes primary miRNA transcripts (pri-miRNAs) to initiate miRNA biogenesis. The canonical cleavage mechanism of MP has been extensively investigated and comprehensively validated for two decades. However, this canonical mechanism cannot account for the processing of certain pri-miRNAs in animals. In this study, by conducting high-throughput pri-miRNA cleavage assays for approximately 260,000 pri-miRNA sequences, we discovered and comprehensively characterized a noncanonical cleavage mechanism of MP. This noncanonical mechanism does not need several RNA and protein elements essential for the canonical mechanism; instead, it utilizes previously unrecognized DROSHA dsRNA recognition sites (DRESs). Interestingly, the noncanonical mechanism is conserved across animals and plays a particularly significant role in C. elegans. Our established noncanonical mechanism elucidates MP cleavage in numerous RNA substrates unaccounted for by the canonical mechanism in animals. This study suggests a broader substrate repertoire of animal MPs and an expanded regulatory landscape for miRNA biogenesis.
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MicroRNAs , Animais , MicroRNAs/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/metabolismo , RNA de Cadeia Dupla , Processamento Pós-Transcricional do RNARESUMO
Microprocessor (MP) is a complex involved in initiating the biogenesis of microRNAs (miRNAs) by cleaving primary microRNAs (pri-miRNAs). miRNAs are small single-stranded RNAs that play a key role in the post-transcriptional regulation of gene expression. Thus, understanding the molecular mechanism of MP is critical for interpreting the roles of miRNAs in normal cellular processes and during the onset of various diseases. MP comprises a ribonuclease enzyme, DROSHA, and a dimeric RNA-binding protein, which is called DGCR8 in humans and Pasha in Caenorhabditis elegans. DROSHA cleaves stem-loop structures located within pri-miRNAs to generate pre-miRNAs. Although the molecular mechanism of human MP (hMP; hDROSHA-DGCR8) is well understood, that of Caenorhabditis elegans MP (cMP; cDrosha-Pasha) is still largely unknown. Here, we reveal the molecular mechanism of cMP and show that it is distinct from that of hMP. We demonstrate that cDrosha and Pasha measure â¼16 and â¼25 bp along a pri-miRNA stem, respectively, and they work together to determine the site of cMP cleavage in pri-miRNAs. We also demonstrate the molecular basis for their substrate measurement. Thus, our findings reveal a previously unknown molecular mechanism of cMP; demonstrate the differences between the mechanisms of hMP and cMP; and provide a foundation for revealing the mechanisms regulating miRNA expression in different animal species.
The Microprocessor complex that initiates miRNA biogenesis was discovered in animals in 2004. However, the molecular mechanism of C. elegans Microprocessor (cMP) has remained elusive since its discovery 18 years ago. In this study, we revealed the unique molecular mechanism of cMP by conducting high-throughput pri-miRNA cleavage assays. We demonstrated that cMP, consisting of cDrosha and Pasha, each can measure the stem lengths of pri-miRNAs. cDrosha measures â¼16 bp of the lower stem length, whereas Pasha measures â¼25 bp of the upper stem in pri-miRNAs. In addition, we identified the cleavage sites and cleavage efficiency of cMP in C. elegans pri-miRNAs. These results will be helpful for future studies of miRNA biogenesis in C. elegans.
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Caenorhabditis elegans , MicroRNAs , Proteínas de Ligação a RNA , Animais , Humanos , Caenorhabditis elegans/química , Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Ribonuclease III/metabolismo , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/metabolismoRESUMO
Air pollution poses a threat to children's respiratory health. This study aims to quantify the association between short-term air pollution exposure and respiratory hospital admissions among children in Hanoi, Vietnam, and estimate the population-attributable burden using local data. A case-crossover analysis was conducted based on the individual records where each case is their own control. The health data was obtained from 13 hospitals in Hanoi and air pollution data was collected from four monitoring stations from 2007 to 2019. We used conditional logistic regression to estimate Percentage Change (PC) and 95% Confidence Interval (CI) in odd of hospital admissions per 10 µg/m3 increase in daily average particulate matter (e.g. PM1, PM2.5, PM10), Sulfur Dioxide (SO2), Nitrogen Dioxide (NO2), 8-h maximum Ozone and per 1000 µg/m3 increase in daily mean of Carbon Monoxide (CO). We also calculated the number and fraction of admissions attributed to air pollution in Hanoi by using the coefficient at lag 0. A 10 µg/m3 increase in the concentration of PM10, PM2.5, PM1, SO2, NO2, O3 8-h maximum and 1000 µg/m3 increase in CO concentration was associated with 0.6%, 1.2%, 1.4%, 0.8%, 1.6%, 0.3%, and 1.7% increase in odd of admission for all respiratory diseases among children under 16 years at lag 0-2. All PM metrics and NO2 are associated with childhood admission for pneumonia and bronchitis. Admissions due to asthma and upper respiratory diseases are related to increments in NO2 and CO. For attributable cases, PM2.5 concentrations in Hanoi exceeding the World Health Organization Air Quality Guidelines accounted for 1619 respiratory hospital admissions in Hanoi children in 2019. Our findings show that air pollution has a detrimental impact on the respiratory health of Hanoi children and there will be important health benefits from improved air quality management planning to reduce air pollution in Vietnam.
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Poluentes Atmosféricos , Poluição do Ar , Transtornos Respiratórios , Doenças Respiratórias , Criança , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/análise , Poluição do Ar/análise , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/epidemiologia , Material Particulado/análise , Transtornos Respiratórios/induzido quimicamente , Transtornos Respiratórios/epidemiologia , Hospitais , ChinaRESUMO
From the leaves of Tithonia diversifolia, nine sesquiterpenoids (1-9), including two new ones (1, 2) were isolated and structurally determined. Their chemical structures were elucidated by extensive analyses of HRESIMS and NMR spectral data, as well as comparison with the literature. All of the isolated compounds (except compounds 7, 8, 9) significantly exhibited cytotoxic activity against four human cancer cell lines (KB, HepG2, A549 and MCF7), with IC50 values ranging from 0.29-17.0 µM, which was in the same range as the positive control ellipticine or even lower. Further, the apoptosis induction of two new compounds 1 and 2 were also investigated and reported. While compound 2 did not induce cell apoptosis in KB cells at test concentrations, compound 1 was found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at S phase, morphological changes, activation of caspase 3, and an increase in the early-stage apoptosis of KB cells at a concentration of 7.26 µM.
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BACKGROUND: Research evidence shows a strong association between adverse childhood experiences (ACEs) and later-life substance use. But little is known about the prevalence and impact of ACEs among young people using drugs (YPUD) in Vietnam. METHOD: A cross-sectional study using respondent-driven sampling and peer recruitment methods was conducted among YPUD aged 16-24 in three cities in Vietnam. Eligible participants were screened for ACEs using the ACE-IQ, tested for HIV and hepatitis C, and assessed for sociodemographic and behavioral characteristics. RESULTS: Data were collected on 553 individuals whose median age was 20: 79% were male, 18.3% women and 2.7% transgender. Methamphetamine use was reported by 75.8% of participants. 85.5% reported at least one ACE and 27.5% had four ACEs or more. An ACE score of 4 or higher was associated with female and transgender, lower educational level, methamphetamine use, buying sex, depression, psychotic symptoms and expressed need for mental health support. CONCLUSIONS: ACEs were found to be very common among YPUD in Vietnam. It is therefore strongly recommended that these young people should be provided with a comprehensive and secure assessment and care that includes not only essential harm reduction and addiction treatment needs but also addresses their mental health needs.
Assuntos
Experiências Adversas da Infância , Metanfetamina , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Estudos Transversais , Vietnã/epidemiologia , Saúde Mental , Metanfetamina/efeitos adversosRESUMO
BACKGROUND: Nearly one-in-two Vietnamese men smoke cigarettes placing them among the highest tobacco consumers in the world. Despite the need for smoking cessation to curb the burden of tobacco-related diseases in Vietnam, this rate remains at less than 30%. Therefore, this study examines individual-, social- and policy factors associated with smoking cessation among adult male smokers in Vietnam. METHODS: We established a longitudinal International Tobacco Control study of male smokers in Hanoi, Vietnam, in September 2018. This paper analyses 1525 men who participated in baseline and one-year follow-up. We applied a weighted multivariable logistic regression to examine the association between smoking cessation and individual-, social- and policy predictors. RESULTS: At follow-up, 14.8% of participants had quit smoking for at least 30 consecutive days during the last year. Among the persistent smokers, 56.6% expressed intention to quit smoking. Factors associated with smoking cessation included a lower number of cigarettes smoked per day (aOR = 0.96, 95% CI: 0.94, 0.99) and having several attempts to quit smoking (aOR = 2.16, 95% CI 1.13, 4.12). Intention to quit smoking was associated with multiple quit attempts, a chronic condition diagnosis, more tobacco-related knowledge, greater self-efficacy, and more worries about their future health. The perceived impact of smoke-free policy and health warning labels were positively associated with intention to quit at any stage. CONCLUSIONS: Interventions aimed at increasing smoking cessation should focus on all aspects of individual, social, and policy factors. Persistent smokers are more motivated to quit if they have made multiple quit attempts, more self-efficacy of quitting and worried about their future health, indicating that increasing smokers' beliefs and knowledge may be important for behavioural change. Health warning labels and tobacco taxation policies should be maintained and promoted as they are perceived to be particularly useful for persistent smokers' intention to quit.
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Política Antifumo , Abandono do Hábito de Fumar , Produtos do Tabaco , Adulto , Humanos , Masculino , Fumantes , Estudos Longitudinais , Vietnã/epidemiologia , IntençãoRESUMO
Plants respond to drought by the major reprogramming of gene expression, enabling the plant to survive this threatening environmental condition. The phytohormone abscisic acid (ABA) serves as a crucial upstream signal, inducing this multifaceted process. This report investigated the drought response in barley plants (Hordeum vulgare, cv. Morex) at both the epigenome and transcriptome levels. After a ten-day drought period, during which the soil water content was reduced by about 35%, the relative chlorophyll content, as well as the photosystem II efficiency of the barley leaves, decreased by about 10%. Furthermore, drought-related genes such as HvS40 and HvA1 were already induced compared to the well-watered controls. Global ChIP-Seq analysis was performed to identify genes in which histones H3 were modified with euchromatic K4 trimethylation or K9 acetylation during drought. By applying stringent exclusion criteria, 129 genes loaded with H3K4me3 and 2008 genes loaded with H3K9ac in response to drought were identified, indicating that H3K9 acetylation reacts to drought more sensitively than H3K4 trimethylation. A comparison with differentially expressed genes enabled the identification of specific genes loaded with the euchromatic marks and induced in response to drought treatment. The results revealed that a major proportion of these genes are involved in ABA signaling and related pathways. Intriguingly, two members of the protein phosphatase 2C family (PP2Cs), which play a crucial role in the central regulatory machinery of ABA signaling, were also identified through this approach.
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Hordeum , Hordeum/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Código das Histonas , Secas , Transcriptoma , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genéticaRESUMO
The Microprocessor complex of DROSHA and DGCR8 initiates the biosynthesis of microRNAs (miRNAs) by processing primary miRNAs (pri-miRNAs). The Microprocessor can be oriented on pri-miRNAs in opposite directions to generate productive and unproductive cleavages at their basal and apical junctions, respectively. However, only the productive cleavage gives rise to miRNAs. A single nucleotide polymorphism (SNP, rs2910164) in pri-mir-146a is associated with various human diseases. Although this SNP was found to reduce the expression of miRNA, it is still not known if it affects the activity of the Microprocessor directly, and how it functions. In this study, we revealed that the SNP creates an unexpected mGHG motif at the apical junction of pri-mir-146a. This mGHG motif interacts with the double-stranded RNA-binding domain (dsRBD) of DROSHA, switching its orientation on pri-mir-146a from the basal to the apical junction. As a result, the SNP facilitates Microprocessor to cleave SNP-pri-mir-146a at its unproductive sites. Our findings help to elucidate the molecular mechanism that explains how the disease-associated SNP modulates the biogenesis of pri-mir-146a and thereby affects its cellular functions.
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Doença/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Processamento Pós-Transcricional do RNA , Ribonuclease III/química , Humanos , MicroRNAs/química , MicroRNAs/metabolismo , Ribonuclease III/metabolismoRESUMO
The human Microprocessor complex cleaves primary microRNA (miRNA) transcripts (pri-miRNAs) to initiate miRNA synthesis. Microprocessor consists of DROSHA (an RNase III enzyme), and DGCR8. DROSHA contains two RNase III domains, RIIIDa and RIIIDb, which simultaneously cleave the 3p- and 5p-strands of pri-miRNAs, respectively. In this study, we show that the internal loop located in the lower stem of numerous pri-miRNAs selectively inhibits the cleavage of Microprocessor on their 3p-strand, thereby, facilitating the single cleavage on their 5p-strand. This single cleavage does not lead to the production of miRNA but instead, it downregulates miRNA expression. We also demonstrate that by manipulating the size of the internal loop in the lower stem of pri-miRNAs, we can alter the ratio of single-cut to double-cut products resulted from the catalysis of Microprocessor, thus changing miRNA production in the in vitro pri-miRNA processing assays and in human cells. Therefore, the oscillating level of the single cleavage suggests another way of regulation of miRNA expression and offers an alternative approach to miRNA knockdown.
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MicroRNAs/genética , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/metabolismo , Sequência de Bases , Regulação da Expressão Gênica , Células HCT116 , Humanos , MicroRNAs/metabolismo , Conformação de Ácido NucleicoRESUMO
Mentha is a complex genus encompassing many species as a consequence of their interspecific hybridization and polyploidy. Southeast Asian mints have been poorly distinguished though they are widely used for culinary and medical purposes. In this study, we have analyzed Southeast Asian mints and known varieties as well as a related Lamiaceae species (Nepeta sp.) using simple sequence repeat (SSR) markers and leaf morphology. Two types of mints were clearly distinguished based on their venation pattern and leaf shape index. We developed 12 SSR markers that allowed good amplification in the Mentha and another Lamiaceae species. In the SSR-based phylogram, the Mentha lines could be delimited into groups I-VI. The Southeast Asian mints divided into groups I and II, and the phylogram separated most of the available species, with groups I and II containing the known species M. × cordifolia and M. arvensis, respectively. The separation of the two groups was supported by a population structure analysis. The SSR markers developed in this study enabled the simultaneous classification of mints and will help improve our understanding of the genetic composition of known mint varieties and as yet unclassified Southeast Asian mints.
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Single-stranded microRNAs (miRNAs) regulate gene expression by triggering mRNA degradation and/or inhibiting mRNA translation. miRNAs play important roles in various critical cellular processes and are associated with numerous human diseases, including cancer and neurodegenerative diseases. miRNA sequences are embedded in the primary miRNA transcripts (pri-miRNAs) that are initially processed by the Microprocessor complex in the nucleus. Microprocessor can orient itself on pri-miRNAs in two ways: one orientation results in subsequent miRNA production, and the other leads to cleavage of the miRNA sequence. Therefore, orienting Microprocessor on pri-miRNAs is a fundamental mechanism for determining the accuracy and efficiency of pri-miRNA processing and, in turn, miRNA production. Multiple mechanisms controlling Microprocessor orientation on pri-miRNAs, involving both cis-acting RNA elements and trans-acting factors, have recently been revealed. In this review, we discuss these exciting mechanisms and consider potential unknown mechanisms that might regulate Microprocessor orientation on pri-miRNAs.
Assuntos
MicroRNAs/química , MicroRNAs/metabolismo , Complexos Multiproteicos/metabolismo , Precursores de RNA/metabolismo , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Hemina/genética , Hemina/metabolismo , Humanos , MicroRNAs/genética , Complexos Multiproteicos/genética , Motivos de Nucleotídeos , Processamento de Proteína Pós-Traducional , Precursores de RNA/química , Precursores de RNA/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/genética , Ribonuclease III/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismoRESUMO
The aim of the study was to investigate health-related quality of life among Vietnamese breast cancer women who were treated at National Cancer Hospital, Hanoi, Vietnam, in 2018. Information about physical functioning, Role Physical, Bodily Pain, General Health, vitality, Social Functioning, Role Emotional, and Mental Health of 200 patients with breast cancer was collected through face-to-face interview, using short form-36 questionnaire. We found that the older patients (older than 50 years) had higher score of Mental Health than patients at age 50 and lower (P < .05). The patients who had better economic status had significantly higher score of Vitality (P < .05). Patients who were married and living with their partners/husband had better quality of life in General Health (P<0.05). The patients who had less than 6 months of treatment had better physical functioning score (P < .05) than the patients who had treatment longer than 6 months. Patients with caring supports from family members had higher scores of Bodily Pain, Social Functioning, Role Emotional, and Mental Health. Patients who have stressed feelings had significantly lower scores of all domains, except for Physical Functioning. The participants who usually stay up late reported lower scores of all components except for Physical Functioning and Role Physical. In conclusion, it is needed to develop psychosocial services, enhance early screening, and diagnose for the women in Vietnam.
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Neoplasias da Mama/psicologia , Saúde Mental/estatística & dados numéricos , Qualidade de Vida , Adulto , Fatores Etários , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Sistemas de Apoio Psicossocial , Inquéritos e Questionários/estatística & dados numéricos , Fatores de Tempo , Vietnã , Adulto JovemRESUMO
Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.
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Aconitum/química , Cinamatos/química , Raízes de Plantas/química , ortoaminobenzoatos/química , Animais , Cinamatos/farmacologia , Medicamentos de Ervas Chinesas , Glucosídeos/química , Glucosídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Espectrometria de Massas por Ionização por Electrospray , ortoaminobenzoatos/farmacologiaRESUMO
OBJECTIVE: Epilepsy is a major public health issue in low- and middle-income countries, where the availability and accessibility of quality treatment remain important issues, the severity of which may be aggravated by poor quality antiepileptic drugs (AEDs). The primary objective of this study was to measure the quality of AEDs in rural and urban areas in 3 African countries. METHODS: This cross-sectional study was carried out in Gabon, Kenya, and Madagascar. Both official and unofficial supply chains in urban and rural areas were investigated. Samples of oral AEDs were collected in areas where a patient could buy or obtain them. Pharmacological analytical procedures and Medicine Quality Assessment Reporting Guidelines were used to assess quality. RESULTS: In total, 102 batches, representing 3782 units of AEDs, were sampled. Overall, 32.3% of the tablets were of poor quality, but no significant difference was observed across sites: 26.5% in Gabon, 37.0% in Kenya, and 34.1% in Madagascar (P = .7). The highest proportions of substandard medications were found in the carbamazepine (38.7%; 95% confidence interval [CI] 21.8-57.8) and phenytoin (83.3%; 95% CI 35.8-99.5) batches, which were mainly flawed by their failure to dissolve. Sodium valproate was the AED with the poorest quality (32.1%; 95% CI 15.8-42.3). The phenobarbital (94.1%; 95% CI 80.3-99.2) and diazepam (100.0%) batches were of better quality. The prevalence of substandard quality medications increased in samples supplied by public facilities (odds ratio [OR] 9.9; 95% CI 1.2-84.1; P < .04) and manufacturers located in China (OR 119.8; 95% CI 8.7-1651.9; P < .001). The prevalence of AEDs of bad quality increased when they were stored improperly (OR 5.4; 95% CI 1.2-24.1; P < .03). SIGNIFICANCE: No counterfeiting was observed. However, inadequate AED storage conditions are likely to lead to ineffective and possibly dangerous AEDs, even when good-quality AEDs are initially imported.
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Anticonvulsivantes/normas , Países em Desenvolvimento/estatística & dados numéricos , Controle de Qualidade , Administração Oral , Anticonvulsivantes/análise , Anticonvulsivantes/uso terapêutico , Estudos Transversais , Epilepsia/tratamento farmacológico , Gabão , Humanos , Quênia , Madagáscar , Saúde da População Rural , Saúde da População UrbanaRESUMO
Legionella pneumophila is a Gram-negative bacterium that replicates within human alveolar macrophages by evasion of the host endocytic pathway through the formation of a replicative vacuole. Generation of this vacuole is dependent upon the secretion of over 275 effector proteins into the host cell via the Dot/Icm type IVB secretion system (T4SS). The type IV coupling protein (T4CP) subcomplex, consisting of DotL, DotM, DotN, IcmS and IcmW, was recently defined. DotL is proposed to be the T4CP of the L. pneumophila T4SS based on its homology to known T4CPs, which function as inner-membrane receptors for substrates. As a result, DotL is hypothesized to play an integral role(s) in the L. pneumophila T4SS for the engagement and translocation of substrates. To elucidate this role, a genetic approach was taken to screen for dotL mutants that were unable to survive inside host cells. One mutant, dotLY725Stop, did not interact with the type IV adaptor proteins IcmS/IcmW (IcmSW) leading to the identification of an IcmSW-binding domain on DotL. Interestingly, the dotLY725Stop mutant was competent for export of one class of secreted effectors, the IcmSW-independent substrates, but exhibited a specific defect in secretion of IcmSW-dependent substrates. This differential secretion illustrates that DotL requires a direct interaction with the type IV adaptor proteins for the secretion of a major class of substrates. Thus, by identifying a new target for IcmSW, we have discovered that the type IV adaptors perform an additional role in the export of substrates by the L. pneumophila Dot/Icm T4SS.
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Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos , Legionella pneumophila/metabolismo , Chaperonas Moleculares/metabolismo , Acanthamoeba castellanii/microbiologia , Proteínas de Bactérias/genética , Sítios de Ligação/genética , Regulação Bacteriana da Expressão Gênica , Humanos , Legionella pneumophila/genética , Macrófagos/microbiologia , Mutação , Ligação Proteica , Transporte ProteicoRESUMO
HER2 overexpression is associated with aggressive breast cancer with high recurrence rate and poor patient prognosis. Treatment of HER2 overexpressing patients with the HER2 targeting therapy trastuzumab results in acquired resistance within a year. The HER2/EGFR dual kinase inhibitor lapatinib was shown to inhibit some trastuzumab resistant breast cancer cell lines and is currently in clinical trials. Our group has found two new quinone compounds that show excellent inhibition of breast tumor cells expressing HER2 or the trastuzumab resistant HER2 oncogenic isoform, HER2Δ16. Compound 4 ((1R,2S,3S)-1,2,3,5,8-pentahydroxy-1,2,3,4-tetrahydroanthracene-9,10-dione) and compound 5 (5,8-dihydroxy-2,3-bis(hydroxymethyl)naphthalene-1,4-dione) showed sub-micromolar inhibition potency against these cell lines. These compounds also inhibit auto-phosphorylation of the Y1248 and Y1068 residues of HER2 and EGFR, respectively.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Quinonas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Relação Dose-Resposta a Droga , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Modelos Moleculares , Estrutura Molecular , Quinonas/química , Receptor ErbB-2/metabolismo , Relação Estrutura-Atividade , TrastuzumabRESUMO
We conducted a large-scale online survey in February 2023 to investigate the public's perceptions of COVID-19 infection and fatality risks in Japan. We identified two key findings. First, univariate analysis comparing perceived and actual risk suggested overestimation and nonnegligible underestimation of COVID-19 risk. Second, multivariate logistic regression analyses revealed that age, income, education levels, health status, information sources, and experiences related to COVID-19 were associated with risk perceptions. Given that risk perceptions are closely correlated with daily socioeconomic activities and well-being, it is important for policy-makers and public health experts to understand how to communicate COVID-19 risk to the public effectively.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Japão/epidemiologia , Estudos Transversais , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Idoso , SARS-CoV-2/isolamento & purificação , Adulto Jovem , Adolescente , PercepçãoRESUMO
Aim: To describe the operative technique and outcome of one trocar-assisted retroperitoneoscopic ureteroureterostomy (OTAU) in 40 cases of complete ureteral duplication in children. Patients and Methods: From September 2016 to December 2020, 40 patients (12 male and 28 female) less than 10 years of age underwent OTAU. A transverse skin incision of 12 mm in length was created approximately 1 cm above the iliac crest. Muscle was spared and retracted with stay sutures to expose the retroperitoneal space. Subsequently, a balloon trocar was then inserted, and pneumoperitoneum was achieved. A 10 mm operating laparoscope (Stema, Germany) with a Maryland was used to dissect and isolate the ureters from surrounding tissues. The ureters were then exteriorized and end-to-side ureteroureterostomy was performed using Polydioxanone (PDS) 6/0 running sutures. Patient's demographic, operative, and follow-up data were collected prospectively. Results: The mean age of patients was 25.2 months (range: 1-105 months). The mean operating time was 81.9 ± 11.3 minutes. There were no intraoperative conversions or complications. After a median follow-up time of 47.5 months, the differential renal function of the pathological upper pole moiety (UPM) was preserved in all patients. Ultrasound revealed a significant reduction in UPM's renal pelvis anterior-posterior diameter from 19.6 ± 9.1 mm preoperatively to 11.1 ± 6.7 mm postoperatively (p < 0.05), accompanied by a reduction in ureter's diameter from 10.8 ± 4.4 mm to 4.8 ± 1.2 mm (p < 0.05). Overall, all 32 patients with preoperative symptoms experienced complete symptom resolution. Conclusion: OTAU is a safe and feasible approach that yields excellent outcomes for complete ureteral duplication.
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OBJECTIVE: Neurosurgery residents in Germany face numerous challenges including receiving comprehensive surgical training with adequate learning opportunities, achieving balanced work life equilibrium, maintaining a positive work environment and navigating career prospects. The objectives of this study are to assess overall satisfaction with the training program, identify factors contributing to dissatisfaction, explore various dimensions of the training program, evaluate the psychological well-being of residents, and ascertain their preferences for future subspecialties. METHODS: A questionnaire-based survey was conducted anonymously among neurosurgery residents from various training hospitals, nationwide. The survey utilized a quantitative questionnaire as data collection tool. The data collection took place from June 2021 to January 2023. RESULTS: The survey encompassed 120 neurosurgery residents, with a gender distribution of 55â¯% male and 45â¯% female. The respondents were primarily from university hospitals (53â¯%), followed by community hospitals (38â¯%) and private hospitals (9â¯%). In terms of training program satisfaction, 37â¯% reported moderate satisfaction, 39â¯% indicated below-moderate satisfaction, and 28â¯% experienced above-moderate satisfaction. The predominant causes of dissatisfaction identified were insufficient surgical exposure (reported by 39â¯% of respondents), suboptimal educational content (38â¯%), and inadequate research opportunities (32â¯%). Additionally, 24â¯% of respondents highlighted psychological stress, and 36â¯% reported frequent experiences of burnout. A majority (63â¯%) indicated a workload of 60-80â¯h weekly. About half of the residents indicated a future specialization interest in neurosurgical oncology. CONCLUSION: The results of the survey findings provide valuable insights into the challenges and aspirations of neurosurgery trainees in Germany. These results serve as a basis for improving the training system, enhancing the working environment, and guiding future planning in this field. To optimize the training of residents, it is important to address issues such as limited surgical and research opportunities and psychological well-being. The expressed interest in subspecializing offers guidance for shaping the training program's future direction.
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Two new flavonoids, 4',5,7-trihydroxy-5'-methoxy-6,8-dimethylisoflavone (1) and 2',5',7-trihydroxy-5-methoxy-6,8-dimethylflavanone (2) together with the known flavonoids 4´,5,7-trihydroxy-3´-methoxy-6.8-dimethylflavone (3), epigallocatechin (4), 4´-O-methylepicatechin (5) and quercetin (6) were isolated from the roots of Byttneria aspera. The structures of these compounds were determined by means of spectroscopic methods. Compounds 1-6 were submitted to cytotoxic activity assays against three cancer cell lines including KB, MCF7 and A549, as well as their antimicrobial activity against a panel of clinically significant microorganisms. Compound 6 showed moderate cytotoxic activity with IC50 values of 12.7, 56.9 and 17.5 µM against KB, MCF7 and A549. Interestingly, the new compounds 1 and 2 exhibits antimicrobial activity, with compound 1 displaying selective antifungal activity against Candida albicans giving an MIC value of 128 µg/mL, compared to cyclohexamide with 32 µg/mL, while compound 2 shows potent inhibition of the Gram-positive bacterium Enterococcus faecalis displaying an MIC of 64 µg/mL, compared to streptomycin with 256 µg/mL.