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1.
Hum Factors ; : 187208231181496, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37287261

RESUMO

OBJECTIVE: To investigate how the visual complexity of head-up displays (HUDs) influence the allocation of driver's attention in two separate visual domains (near and far domains). BACKGROUND: The types and amount of information displayed on automobile HUDs have increased. With limited human attention capacity, increased visual complexity in the near domain may lead to interference in the effective processing of information in the far domain. METHOD: Near-domain and far-domain vision were separately tested using a dual-task paradigm. In a simulated road environment, 62 participants were to control the speed of the vehicle (SMT; near domain) and manually respond to probes (PDT; far domain) simultaneously. Five HUD complexity levels including a HUD-absent condition were presented block-wise. RESULTS: Near domain performance was not modulated by the HUD complexity levels. However, the far domain detection accuracies were impaired as the HUD complexity level increased, with greater accuracy differences observed between central and peripheral probes. CONCLUSION: Increased HUD visual complexity leads to a biased deployment of driver attention toward the central visual field. Therefore, the formulation of HUD designs must be preceded by an in-depth investigation of the dynamics of human cognition. APPLICATION: To ensure driving safety, HUD designs should be rendered with minimal visual complexity by incorporating only essential information relevant to driving and removing driving-irrelevant or additional visual details.

2.
Int J Mol Sci ; 23(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35216342

RESUMO

Cell membrane cloaking technique is bioinspired nanotechnology that takes advantage of naturally derived design cues for surface modification of nanoparticles. Unlike modification with synthetic materials, cell membranes can replicate complex physicochemical properties and biomimetic functions of the parent cell source. This technique indeed has the potential to greatly augment existing nanotherapeutic platforms. Here, we provide a comprehensive overview of engineered cell membrane-based nanotherapeutics for targeted drug delivery and biomedical applications and discuss the challenges and opportunities of cell membrane cloaking techniques for clinical translation.


Assuntos
Membrana Celular/metabolismo , Nanopartículas/metabolismo , Preparações Farmacêuticas/metabolismo , Animais , Materiais Biomiméticos/metabolismo , Biomimética/métodos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanotecnologia/métodos
3.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440780

RESUMO

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1-10%), salicylic acid (0.2-2%), and lactobionic acid (1.2-12%) were used as representative substances for α-hydroxyacid (AHA), ß-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50-80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.


Assuntos
Fenômenos Fisiológicos da Pele , Pele/metabolismo , Animais , Biomarcadores , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Imunofluorescência , Histocitoquímica , Humanos , Hidroxiácidos/química , Hidroxiácidos/farmacologia , Técnicas In Vitro , Permeabilidade , Rodaminas/farmacologia , Ácido Salicílico/química , Ácido Salicílico/farmacologia , Pele/citologia , Pele/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Suínos , Técnicas de Cultura de Tecidos
4.
Dig Dis Sci ; 65(8): 2302-2310, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32157497

RESUMO

BACKGROUND: The personality traits of endoscopists have been suggested to affect the adenoma detection rate (ADR). We thus evaluated the relationship between endoscopists' personality traits and the ADR during colonoscopy using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). METHODS: In total, 1230 patients (asymptomatic and aged 50-80 years) who underwent screening or surveillance (≥ 5 years) colonoscopy were recruited from 13 university hospitals by 20 endoscopists between September 2015 and December 2017. We retrospectively measured the ADR, polyp detection rate (PDR), and number of adenomas per colonoscopy (APC). All 20 endoscopists completed all 567 true/false MMPI-2 items. RESULTS: The overall mean colonoscopy withdrawal time, PDR, ADR, and APC were 7.3 ± 2.8 min, 55%, 45.3%, and 0.97 ± 1.58, respectively. No significant difference was observed in the MMPI-2 clinical scales (e.g., hypochondriasis and psychasthenia), content scales (e.g., obsessiveness and type A character), or supplementary scales (e.g., dominance and social responsibility) between the high ADR group (ADR ≥45%, n = 10) and the low ADR group (ADR < 45%, n = 10). In multivariate logistic regression analysis, the ADR was associated significantly with patient age and sex. The ADR was related significantly to endoscopists' colonoscopy experience and the per-minute increase in the colonoscopy withdrawal time (OR 1.21, 95% CI 1.06-1.38, p = 0.005). In a logistic regression analysis adjusted for patient factors, the ADR was associated significantly with ego strength (OR 1.04, 95% CI 1.00-1.09, p = 0.044), as measured by the MMPI-2. CONCLUSIONS: With the exception of ego strength, the endoscopists' personality traits were not associated with adenoma or polyp detection.


Assuntos
Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/estatística & dados numéricos , Gastroenterologistas/psicologia , Idoso , Colonoscopia/psicologia , Feminino , Humanos , MMPI , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Biochim Biophys Acta ; 1863(6 Pt A): 1071-81, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26975580

RESUMO

The angiotensin II type I receptor (AGTR1) has been implicated in diverse aspects of human disease, from the regulation of blood pressure and cardiovascular homeostasis to cancer progression. We sought to investigate the role of AGTR1 in cell proliferation, epithelial-mesenchymal transition (EMT), migration, invasion, angiogenesis and tumor growth in the breast cancer cell line MCF7. Stable overexpression of AGTR1 was associated with accelerated cell proliferation, concomitant with increased expression of survival factors including poly(ADP-ribose) polymerase (PARP) and X-linked inhibitor of apoptosis (XIAP), as well as extracellular signal-regulated kinase (ERK) activation. AGTR1-overexpressing MCF7 cells were more aggressive than their parent line, with significantly increased activity in migration and invasion assays. These observations were associated with changes in EMT markers, including reduced E-cadherin expression and increased p-Smad3, Smad4 and Snail levels. Treatment with the AGTR1 antagonist losartan attenuated these effects. AGTR1 overexpression also accelerated tumor growth and increased Ki-67 expression in a xenograft model. This was associated with increased tumor angiogenesis, as evidenced by a significant increase in microvessels in the intratumoral and peritumoral areas, and enhanced tumor invasion, with the latter response associated with increased EMT marker expression and matrix metallopeptidase 9 (MMP-9) upregulation. In vivo administration of losartan significantly reduced both tumor growth and angiogenesis. Our findings suggest that AGTR1 plays a significant role in tumor aggressiveness, and its inhibition may have therapeutic implications.


Assuntos
Neoplasias da Mama/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Neovascularização Patológica/genética , Receptor Tipo 1 de Angiotensina/genética , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Western Blotting , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , Caderinas/genética , Caderinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Losartan/farmacologia , Células MCF-7 , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal , Neovascularização Patológica/metabolismo , Neovascularização Patológica/prevenção & controle , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Smad4/genética , Proteína Smad4/metabolismo , Transplante Heterólogo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
6.
Biochem Biophys Res Commun ; 486(4): 1069-1076, 2017 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-28373070

RESUMO

In the presence of copper (Cu), disulfiram (DSF) suppresses properties associated with cancer stem cells (CSCs) in breast cancer, but the mechanism of action is poorly understood. In the present study, we observed that DSF/Cu treatment induced apoptosis, mediated by caspase-3 activation in triple-negative breast cancer (TNBC) cells. DSF/Cu treatment also specifically targeted CSC-like cell populations, marked by the inhibition of ALDH1 activity, the suppression of CD44+/CD24-and CD49f+/CD24 + subpopulations, and the subsequent impairment of mammosphere formation. These effects were functionally associated with a significant impact on the STAT3 signaling pathway, characterized by the downregulation of phospho-STAT3, cyclin D1 and survivin. In an MDA-MB-231-derived xenograft model, DSF administration significantly downregulated ALDH1A1, CD44 and phospho-STAT3 levels. These findings show for the first time that DSF suppresses stem-like properties in TNBC by targeting the STAT3 signaling pathway.


Assuntos
Dissulfiram/administração & dosagem , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Antineoplásicos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia
7.
Biochem Biophys Res Commun ; 466(4): 696-703, 2015 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-26407842

RESUMO

Cancer stem cells (CSCs) play important roles in the formation, growth and recurrence of tumors, particularly following therapeutic intervention. Salinomycin has received recent attention for its ability to target breast cancer stem cells (BCSCs), but the mechanisms of action involved are not fully understood. In the present study, we sought to investigate the mechanisms responsible for salinomycin's selective targeting of BCSCs and its anti-tumor activity. Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27(kip1) nuclear accumulation. Mammosphere formation assays revealed that salinomycin suppresses self-renewal of ALDH1-positive BCSCs and downregulates the transcription factors Nanog, Oct4 and Sox2. TUNEL analysis of MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis. Our findings shed further light on the mechanisms responsible for salinomycin's effects on BCSCs.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Piranos/farmacologia , Família Aldeído Desidrogenase 1 , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Isoenzimas/antagonistas & inibidores , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Retinal Desidrogenase/antagonistas & inibidores , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Artigo em Inglês | MEDLINE | ID: mdl-38900528

RESUMO

Simon effects have been observed to arise from different modes of spatial information (e.g., physical location, arrow direction, and location word). The present study investigated whether different modes of spatial information elicit a unitary set of spatial codes when triggering a spatially corresponding response code. A pair of two different Simon tasks was presented in alternation: location- and arrow-based Simon tasks in Experiments 1 and 2, word- and location-based Simon tasks in Experiment 3, and arrow- and word-based Simon tasks in Experiment 4. Responses were collected using unimanual aimed-movement responses. Cross-task congruency sequence effects (CSEs) were found in Experiments 1 and 2, indicating a shared set of spatial codes between physical locations and arrow directions. Conversely, the absence of CSEs in Experiment 3 suggested that physical locations and location words elicited different sets of spatial codes. In Experiment 4, a CSE was evident in the arrow-based Simon task but not in the word-based one, implying an overlap in the spatial attributes of arrow directions with those of location words. Distributional analyses of the Simon effects revealed that different modes of spatial information yielded distinct temporal patterns of its activation and dissipation, implying quantitative differences in the Simon effects. The cross-comparisons of the CSE and delta function data indicated that the quantitative similarities in spatial modes did not correspond to the qualitative similarities, suggesting a crucial finding that each set of data reflects different aspects of the nature of the spatial codes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

9.
Adv Mater ; : e2400428, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747751

RESUMO

The discovery of superconducting states in diverse topological materials generates a burgeoning interest to explore a topological superconductor and to realize a fault-tolerant topological quantum computation. A variety of routes to realize topological superconductors are proposed, and many types of topological materials are developed. However, a pristine topological material with a natural superconducting state is relatively rare as compared to topological materials with artificially induced superconductivity. Here, it is reported that the planar honeycomb structured 3D topological Dirac semimetal (TDS) SrCuBi, which is the Zintl phase, shows a natural surface superconductivity at 2.1 K under ambient pressure. It is clearly identified from theoretical calculations that a topologically nontrivial state exists on the (100) surface. Further, its superconducting transition temperature (Tc) increases by applying pressure, exhibiting a maximal Tc of 4.8 K under 6.2 GPa. It is believed that this discovery opens up a new possibility of exploring exotic Majorana fermions at the surface of 3D TDS superconductors.

10.
Microbiol Res ; 283: 127692, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38508088

RESUMO

NADP/NADPH plays an indispensable role in cellular metabolism, serving as a pivotal cofactor in numerous enzymatic processes involved in anabolic pathways, antioxidant defense, and the biosynthesis of essential cellular components. NAD/NADH kinases (NADKs) phosphorylate NAD/NADH, constituting the sole de novo synthetic pathway for NADP/NADPH generation. Despite the pivotal role of NADP/NADPH in cellular functions, the physiological role of NADK remains largely unexplored in filamentous fungi. In this study, we identified three putative NADKs in Fusarium graminearum-FgNadk1, FgNadk2, and FgNadk3-responsible for NAD/NADH phosphorylation. NADK-mediated formation of intracellular NADPH proved crucial for vegetative growth, sexual reproduction, and virulence. Specifically, FgNadk2, the mitochondrial NADK, played a role in oxidative stress resistance and the maintenance of mitochondrial reactive oxygen species levels. Moreover, the deletion of FgNADK2 resulted in arginine auxotrophy, contributing to the reduced fungal virulence. These findings underscore the necessity of mitochondrial NADK in fungal virulence in F. graminearum, revealing its involvement in mitochondrial redox homeostasis and the arginine biosynthetic pathway. This study provides critical insights into the interconnectedness of metabolic pathways essential for fungal growth, stress response, and pathogenicity.


Assuntos
Fusarium , NAD , Virulência , NAD/metabolismo , NADP/metabolismo , Estresse Oxidativo , Oxirredução , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
11.
mBio ; 15(1): e0240123, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38112432

RESUMO

IMPORTANCE: Fusarium graminearum is a destructive fungal pathogen that causes Fusarium head blight (FHB) on a wide range of cereal crops. To control fungal diseases, it is essential to comprehend the pathogenic mechanisms that enable fungi to overcome host defenses during infection. Pathogens require an oxidative stress response to overcome host-derived oxidative stress. Here, we identify the underlying mechanisms of the Fgbzip007-mediated oxidative stress response in F. graminearum. ChIP-seq and subsequent genetic analyses revealed that the role of glutathione in pathogenesis is not dependent on antioxidant functions in F. graminearum. Altogether, this study establishes a comprehensive framework for the Fgbzip007 regulon on pathogenicity and oxidative stress responses, offering a new perspective on the role of glutathione in pathogenicity.


Assuntos
Fusarium , Virulência/genética , Estresse Oxidativo , Enxofre , Doenças das Plantas/microbiologia
12.
J Ethnopharmacol ; 323: 117711, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38176663

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peixe-Zebra , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/farmacologia , Caspase 1/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Adenosina Trifosfatases , Interleucina-1beta/metabolismo
13.
Sci Rep ; 14(1): 5237, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433281

RESUMO

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.


Assuntos
Lauraceae , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos , Peixe-Zebra , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Adenosina Trifosfatases , Extratos Vegetais/farmacologia
14.
Sage Open ; 13(3): 21582440231181592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448888

RESUMO

The study examined the comparative assessment of destination image according to the perception of COVID-19 and travel risk among international students. The online survey was administered to 786 international students enrolled in universities in Korea. Cluster analysis was performed, and three distinct clusters were identified based on risk perception. Destination image attributes were generated into four underlying dimensions: social environment, tourist environment, destination environment, and imagery, using the exploratory factor analysis. A revised Importance-Performance Analysis (IPA) method was utilized to assess the destination image of Korea and used to compare the expected performance of the attributes on each cluster. In addition, a revised IPA grid of each cluster was presented to unveil the satisfaction attributes of the destination image and suggest communication strategies. This study provides practical insights to destination marketers and organizations to design marketing strategies for international students. Further practical and theoretical implications are discussed.

15.
Forensic Sci Int ; 353: 111877, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37989071

RESUMO

In order to prepare a response strategy for future drug analyses, the number and results of drug cases handled by the Seoul Institute of National Forensic Service were comprehensively evaluated, with a focus on Seoul and its metropolitan areas. In 2022, the Seoul Institute received approximately 12,150 requests for drug testing related to drug abuse and possession, and the urine samples were tested for approximately 16,000 drug species. The most frequently requested test was for cannabis (Δ-9-THC and Δ-8-THC), followed by methamphetamine, MDMA, ketamine, and synthetic cannabinoids. ADB-5'Br-BUTINACA and propyl butylone were newly emerging substances in 2022. These results were consistent with the main drug detection findings of the confiscated materials. During this period, 24 cases of drug-related deaths were reported, of which 6 were suspected to be the result of acute overdose poisoning caused by methamphetamine, MDMA, fentanyl, and heroin. In addition to the controlled substances regulated by the Narcotics Control Act, new psychoactive substances are being found to be circulating, and various measures are required to address this issue. This study is expected to improve future drug analyses methods and assist in establishing drug policies, and responding to future investigations.


Assuntos
Canabinoides , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Seul , Canabinoides/análise , Anfetamina , Detecção do Abuso de Substâncias/métodos
16.
J Agric Food Chem ; 71(49): 19302-19311, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38018120

RESUMO

As resistance to chemical fungicides continues to increase inFusarium graminearum, there is a growing need to develop novel disease control strategies. To discover essential genes that could serve as new disease control targets, we selected essential gene candidates that had failed to be deleted in previous studies. Thirteen genes were confirmed to be essential, either by constructing conditional promoter replacement mutants or by employing a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated editing strategy. We synthesized double-stranded RNAs (dsRNAs) targeting these essential genes and analyzed their protective effects in plants using a spray-induced gene silencing (SIGS) method. When dsRNAs targeting Fg10360, Fg13150, and Fg06123 were applied to detached barley leaves prior to fungal inoculation, disease lesions were greatly reduced. Our findings provide evidence of the potential of essential genes identified by a SIGS method to be effective targets for the control of fungal diseases.


Assuntos
Fusarium , Genes Essenciais , Inativação Gênica , Fusarium/genética , RNA de Cadeia Dupla , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia
17.
Plant Pathol J ; 39(1): 1-20, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36760045

RESUMO

In the past, rice bakanae was considered an endemic disease that did not cause significant losses in Korea; however, the disease has recently become a serious threat due to climate change, changes in farming practices, and the emergence of fungicide-resistant strains. Since the bakanae outbreak in 2006, its incidence has gradually decreased due to the application of effective control measures such as hot water immersion methods and seed disinfectants. However, in 2013, a marked increase in bakanae incidence was observed, causing problems for rice farmers. Therefore, in this review, we present the potential risks from climate change based on an epidemiological understanding of the pathogen, host plant, and environment, which are the key elements influencing the incidence of bakanae. In addition, disease management options to reduce the disease pressure of bakanae below the economic threshold level are investigated, with a specific focus on resistant varieties, as well as chemical, biological, cultural, and physical control methods. Lastly, as more effective countermeasures to bakanae, we propose an integrated disease management option that combines different control methods, including advanced imaging technologies such as remote sensing. In this review, we revisit and examine bakanae, a traditional seed-borne fungal disease that has not gained considerable attention in the agricultural history of Korea. Based on the understanding of the present significance and anticipated risks of the disease, the findings of this study are expected to provide useful information for the establishment of an effective response strategy to bakanae in the era of climate change.

18.
Microbiol Spectr ; : e0148523, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37671872

RESUMO

In plant-pathogen interactions, oxidative bursts are crucial for plants to defend themselves against pathogen infections. Rapid production and accumulation of reactive oxygen species kill pathogens directly and cause local cell death, preventing pathogens from spreading to adjacent cells. Meanwhile, the pathogens have developed several mechanisms to tolerate oxidative stress and successfully colonize plant tissues. In this study, we investigated the mechanisms responsible for resistance to oxidative stress by analyzing the transcriptomes of six oxidative stress-sensitive strains of the plant pathogenic fungus Fusarium graminearum. Weighted gene co-expression network analysis identified several pathways related to oxidative stress responses, including the DNA repair system, autophagy, and ubiquitin-mediated proteolysis. We also identified hub genes with high intramodular connectivity in key modules and generated deletion or conditional suppression mutants. Phenotypic characterization of those mutants showed that the deletion of FgHGG4, FgHGG10, and FgHGG13 caused sensitivity to oxidative stress, and further investigation on those genes revealed that transcriptional elongation and DNA damage responses play roles in oxidative stress response and pathogenicity. The suppression of FgHGL7 also led to hypersensitivity to oxidative stress, and we demonstrated that FgHGL7 plays a crucial role in heme biosynthesis and is essential for peroxidase activity. This study increases the understanding of the adaptive mechanisms to cope with oxidative stress in plant pathogenic fungi. IMPORTANCE Fungal pathogens have evolved various mechanisms to overcome host-derived stresses for successful infection. Oxidative stress is a representative defense system induced by the host plant, and fungi have complex response systems to cope with it. Fusarium graminearum is one of the devastating plant pathogenic fungi, and understanding its pathosystem is crucial for disease control. In this study, we investigated adaptive mechanisms for coping with oxidative stress at the transcriptome level using oxidative stress-sensitive strains. In addition, by introducing genetic modification technique such as CRISPR-Cas9 and the conditional gene expression system, we identified pathways/genes required for resistance to oxidative stress and also for virulence. Overall, this study advances the understanding of the oxidative stress response and related mechanisms in plant pathogenic fungi.

19.
PLoS One ; 17(6): e0268855, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657788

RESUMO

Genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has greatly facilitated the genetic analysis of fungal pathogens. The head blight fungus, Fusarium graminearum, causes destructive losses of economically important cereal crops. The recent development of the CRISPR-Cas9 system for use with F. graminearum has enabled more efficient genome editing. In this study, we described a CRISPR-Cas9-based genome-editing tool for the direct delivery of preassembled Cas9 ribonucleoproteins (RNPs) into the protoplasts of F. graminearum. The use of RNPs significantly increased both the number of transformants and percentage of transformants in which the target gene was successfully replaced with a selectable marker. We showed that a single double-strand DNA break mediated by the Cas9 ribonucleoprotein was sufficient for gene deletion. In addition, short-homology recombination required only 50 base pair regions flanking the target gene. The high efficiency of Cas9 RNPs enables large-scale functional analysis, the identification of essential genes, and gene deletion that is difficult with conventional methods. We expect that our approach will accelerate genetic studies of F. graminearum.


Assuntos
Fusarium , Edição de Genes , Sistemas CRISPR-Cas/genética , Fusarium/genética , Edição de Genes/métodos , Ribonucleoproteínas/genética
20.
Psychiatry Investig ; 19(12): 1046-1054, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36588439

RESUMO

OBJECTIVE: The victims and their families of child sexual abuse (CSA) may confront persistent psychological sequela. We aimed to investigate the psychological symptoms, diagnosis, and family functions in children and adolescents with CSA. METHODS: We assessed the symptom scales at 6-month intervals, and conducted diagnostic re-assessments at 1-year intervals. Trauma Symptom Checklist for Children (TSCC), Trauma Symptom Checklist for Young Children (TSCYC), Family Adaptability and Cohesion Evaluation Scales IV (FACES-IV), and Family Communication Scale (FCS) scores were reported by children or parents. RESULTS: We found in parent-reported TSCYC, that posttraumatic stress symptoms domain scores significantly decreased with time progression. The scores decreased more in the evidence-based treatment group over time in anxiety and posttraumatic stress symptom domains of TSCC. In FACES-IV and FCS scores, indices of family function have been gradually increasing both after 6 months and after 1 year compared to the initial evaluation. Further, about 64% of the children diagnosed with psychiatric diseases, including posttraumatic stress disorder (PTSD) at the initial assessment maintained the same diagnosis at follow-up. CONCLUSION: We observed changes in psychological symptoms and family functioning in sexually abused children with time progression during 1 year. It is postulated that PTSD may be a persistent major mental illness in the victims of CSA.

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