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We aimed to determine the risk factors for non-responsiveness to intravenous immunoglobulin (IVIG) and coronary ectasia in Korean children with Kawasaki disease (KD) and compare the efficacy of previously published Japanese and Chinese risk scoring systems in the same cohort. We retrospectively reviewed 459 KD cases diagnosed from January 1, 2013, to December 31, 2022. Age (odds ratio [OR]: 0.983; 95% confidence interval [CI]: 0.968-0.999), change in extremities (OR: 3.308; 95% CI: 1.530-7.151), neutrophils (OR: 1.078; 95% CI: 1.049-1.108), and alanine aminotransferase (OR: 1.002; 95% CI: 1.000-1.004) were identified as independent risk factors for IVIG non-responsiveness, and age (OR: 0.945; 95% CI: 0.902-0.989), C-reactive protein (OR: 1.092; 95% CI: 1.004-1.188), and creatinine kinase (OR: 1.004; 95% CI: 1.001-1.006) were identified as independent risk factors for coronary ectasia. Among previously published risk scoring systems, the Egami (area under the receiver operating characteristics curve [AUC]: 0.695; 95% CI: 0.651-0.737) for IVIG non-responsiveness and the Tang score (AUC: 0.726; 95% CI: 0.578-0.874) for coronary ectasia showed the highest predictive value for our study cohort.
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BACKGROUND: Tissue clearing enables deep imaging in various tissues by increasing the transparency of tissues, but there were limitations of immunostaining of the large-volume tissues such as the whole brain. METHODS: Here, we cleared and immune-stained whole mouse brain tissues using a novel clearing technique termed high-speed clearing and high-resolution staining (HCHS). We observed neural structures within the cleared brains using both a confocal microscope and a light-sheet fluorescence microscope (LSFM). The reconstructed 3D images were analyzed using a computational reconstruction algorithm. RESULTS: Various neural structures were well observed in three-dimensional (3D) images of the cleared brains from Gad-green fluorescent protein (GFP) mice and Thy 1-yellow fluorescent protein (YFP) mice. The intrinsic fluorescence signals of both transgenic mice were preserved after HCHS. In addition, large-scale 3D imaging of brains, immune-stained by the HCHS method using a mild detergent-based solution, allowed for the global topological analysis of several neuronal markers such as c-Fos, neuronal nuclear protein (NeuN), Microtubule-associated protein 2 (Map2), Tuj1, glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) in various anatomical regions in the whole mouse brain tissues. Finally, through comparisons with various existing tissue clearing methodologies such as CUBIC, Visikol, and 3DISCO, it was confirmed that the HCHS methodology results in relatively less tissue deformation and higher fluorescence retention. CONCLUSION: In conclusion, the development of 3D imaging based on novel tissue-clearing techniques (HCHS) will enable detailed spatial analysis of neural and vascular networks present within the brain.
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[This corrects the article DOI: 10.1007/s43188-023-00223-y.].
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Korean winter hazel (Corylopsis coreana) is an endemic species of the South Korea (Seo et al. 2016; Kim et al. 2021), which is cultivated as an ornamental plant in this country, but also in China and Japan (Yoon et al. 2016). In July 2022, typical symptoms of a rust disease were observed on C. coreana at Jirisan National Park (35°22'07.7"N 127°34'57.7"E) in Namwon, South Korea. Spermogonia were epiphyllous, densely grouped, pale brown or orange-yellow, round, and 0.23 - 0.38 × 0.19 - 0.41 mm in size. Aecia were hypophyllous, mostly densely grouped, yellow or pale orange, resembling small wart-like galls, and 0.04 - 0.06 × 0.89 - 1.68 mm in size. Aeciospores were hyaline, mostly angularly globose, ellipsoid or oblong-ellipsoid, and 17.8 - 25.2 × 15 - 26.5 µm (average 19.2 × 19.1 µm; n=50) in size. Aeciospore walls were echinulate-verrucose, and 1.1 - 2.2 µm (average 1.7 µm; n=50) in thickness. In December 2022, dark brown telia were observed on the lower surface of Sasa borealis leaves near C. coreana. Telia were mostly scattered but often compacted, brown to dark brown, round, and 1.5 - 1.95 × 1.24 - 1.55 mm in size. Teliospores were either one- or two-celled with a long tapering apex, and light brown to brown in color. One-celled teliospores were globose, and 95.1 - 186.5 × 20.5 - 36.4 µm (average 136.4 × 27.7 µm; n=50) in size. Two-celled teliospores were ellipsoid-cylindrical, and 111.4 - 180.3 × 13.5 - 32.6 µm (average 149 × 21.1 µm; n=50) in size. Side walls of teliospores were golden and 2.2 - 5.5 µm thick (average 3.5 µm; n=50), and pedicels were hyaline, measuring 150 - 300 µm long. Uredinial stage was not observed. Disease symptomology and pathogen morphology were mostly consistent with that of Puccinia sasicola reported in Japan (Hino. 1955). For phylogenetic analysis, genomic DNA was extracted from the aeciospores collected from C. coreana and the teliospores collected from S. borealis. The internal transcribed spacer (ITS) rDNA and the large subunit (LSU) rDNA regions were amplified using ITS5u/ITS4rust (Pfunder and Schürch 2001) and LRust1R/LRust3 (Beenken et al. 2012) primers, respectively. Both sequences were identical for the spores collected from the two different hosts. The sequences were deposited in GenBank (PP171665, PP174211 [ITS], PP171709, PP174356 [LSU]). A GenBank BLAST search revealed 89.53% and 96.78% similarity with Puccinia kusanoi (KX610657) and Puccinia sp. (MT7298241) for ITS and LSU sequences, respectively. In maximum-likelihood phylogenetic analysis of ITS and LSU sequences, the isolates from C. coreana and S. borealis formed a separate clade from other Puccinia species. To test Koch's postulates, leaf disks with telia from S. borealis were directly attached to the adaxial surface of six healthy C. coreana leaves with tape. As controls, healthy S. borealis leaf disks were attached to the adaxial surface of six C. coreana leaves. After four weeks, four inoculated leaves developed small yellow wart-like galls on the abaxial surface, while the control leaves remained symptom-free. The isolates obtained from the inoculated leaves had identical sequences to the original isolate. There are no publicly available sequences for P. sasicola, nor did we find any sequences that match our Puccinia samples. Nevertheless, based on morphological characteristics and life cycle, our isolates closely matched with the previous description of P. sasicola by Hino (1955). To our knowledge, this is the first report of P. sasicola causing leaf rust in C. coreana in South Korea.
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Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.
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Vesículas Extracelulares , Fator de Crescimento Insulin-Like I , Células-Tronco Mesenquimais , Osteoartrite , RNA Interferente Pequeno , Fator de Crescimento Insulin-Like I/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoartrite/terapia , Osteoartrite/metabolismo , RNA Interferente Pequeno/genética , Animais , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/genéticaRESUMO
During the cold season in South Korea, NO3- concentrations are known to significantly increase, often causing PM2.5 to exceed air quality standards. This study investigated the formation mechanisms of NO3- in a suburban area with low anthropogenic emissions. The average PM2.5 was 25.3 µg m-3, with NO3- identified as the largest contributor. Ammonium-rich conditions prevailed throughout the study period, coupled with low atmospheric temperature facilitating the transfer of gaseous HNO3 into the particulate phase. This result indicates that the formation of HNO3 played a crucial role in determining particulate NO3- concentration. Nocturnal increases in NO3- were observed alongside increasing ozone (O3) and relative humidity (RH), emphasizing the significance of heterogeneous reactions involving N2O5. NO3- concentrations at the study site were notably higher than in Seoul, the upwind metropolitan area, during a high concentration episode. This difference could potentially attributed to lower local NO concentrations, which enhanced the reaction between O3 and NO2, to produce NO3 radicals. High concentrations of Cl- and dust were also identified as contributors to the elevated NO3- concentrations.
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Poluentes Atmosféricos , Cidades , Monitoramento Ambiental , Nitratos , Ozônio , Material Particulado , Estações do Ano , Material Particulado/análise , Poluentes Atmosféricos/análise , República da Coreia , Nitratos/análise , Ozônio/análise , Poluição do Ar/estatística & dados numéricos , Temperatura BaixaRESUMO
There is an urgent need to develop efficient and environmentally friendly decontaminants for poultry products. In this study, we aimed to evaluate the practical application of peroxyacetic acid (PAA) as a replacement for sodium hypochlorite (SH) to sterilize fresh chicken carcasses, using microbial, color, and electronic-nose analyses. We evaluated the decontamination effects of different concentrations of PAA and SH on chicken carcasses. The bactericidal effects of PAA at pH 3, 7, and 9, and SH at pH 10, at concentrations ranging from 100 to 500 ppm on coliform bacteria, total bacteria, and Salmonella spp. were evaluated. PAA induced a similar bactericidal effect at lower concentrations than SH. Therefore, at the same concentration and treatment time, PAA showed better bactericidal effects than SH. Although treatment with PAA (pH 3) and SH (pH 10) resulted in considerable discoloration, the degree of discoloration decreased when the pH of PAA was increased to 7 and 9. Therefore, by increasing the pH of PAA, the discoloration effect on chicken carcasses can be reduced without altering the microbial-reduction effect. Electronic-nose analysis showed that the flavor of the chicken was almost unaffected by volatile components at a treatment time < 30 min. Therefore, this study experimentally identified the optimal PAA concentration for the decontamination of chicken carcasses. The study findings provide a theoretical basis for the replacement of traditional bactericides, such as SH, with PAA for the production of poultry products.
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Rationale: Resistance to targeted therapies like trastuzumab remains a critical challenge for HER2-positive breast cancer patients. Despite the progress of several N-terminal HSP90 inhibitors in clinical trials, none have achieved approval for clinical use, primarily due to issues such as induction of the heat shock response (HSR), off-target effects, and unfavorable toxicity profiles. We sought to examine the effects of HVH-2930, a novel C-terminal HSP90 inhibitor, in overcoming trastuzumab resistance. Methods: The effect of HVH-2930 on trastuzumab-sensitive and -resistant cell lines in vitro was evaluated in terms of cell viability, expression of HSP90 client proteins, and impact on cancer stem cells. An in vivo model with trastuzumab-resistant JIMT-1 cells was used to examine the efficacy and toxicity of HVH-2930. Results: HVH-2930 was rationally designed to fit into the ATP-binding pocket interface cavity of the hHSP90 homodimer in the C-terminal domain of HSP90, stabilizing its open conformation and hindering ATP binding. HVH-2930 induces apoptosis without inducing the HSR but by specifically suppressing the HER2 signaling pathway. This occurs with the downregulation of HER2/p95HER2 and disruption of HER2 family member heterodimerization. Attenuation of cancer stem cell (CSC)-like properties was associated with the downregulation of stemness factors such as ALDH1, CD44, Nanog and Oct4. Furthermore, HVH-2930 administration inhibited angiogenesis and tumor growth in trastuzumab-resistant xenograft mice. A synergistic effect was observed when combining HVH-2930 and paclitaxel in JIMT-1 xenografts. Conclusion: Our findings highlight the potent efficacy of HVH-2930 in overcoming trastuzumab resistance in HER2-positive breast cancer. Further investigation is warranted to fully establish its therapeutic potential.
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Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Proteínas de Choque Térmico HSP90 , Receptor ErbB-2 , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Animais , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Linhagem Celular Tumoral , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Camundongos Nus , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologiaRESUMO
Bioassay and HPLC-UV guided fractionations of the crude extract of marine-derived Streptomyces sp. SNA-077 have led to the isolation of a red pigment, undecylprodigiosin (1). The chemical structure of undecylprodigiosin (1) was revealed by the interpretation of NMR and mass spectroscopic (MS) data. Further, anti-melanogenic effects of undecylprodigiosin (1) were investigated. First, the melanin contents of undecylprodigiosin (1)-treated B16 cells were evaluated. Furthermore, undecylprodigiosin (1) significantly inhibited the key enzymes involved in melanogenesis, including tyrosinase, tyrosinase related protein-1 (TYRP-1), and dopachrome tautomerase (DCT). The mRNA and protein expression levels of Microphthalmia-associated transcriptian factor (MiTF), a critical transcription factor for tyrosinase gene expression, were also suppressed by undecylprodigiosin (1) treatment in B16 analyses. Collectively, our results suggest for the first time that undecylprodigiosin (1), a potent component isolated from an extract of marine Streptomyces sp. SNA-077, critically exerts the anti-melanogenic ability for melanin synthesis.
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Unmanned Aerial Vehicle (UAV) deployment has risen rapidly in recent years. They are now used in a wide range of applications, from critical safety-of-life scenarios like nuclear power plant surveillance to entertainment and hobby applications. While the popularity of drones has grown lately, the associated intentional and unintentional security threats require adequate consideration. Thus, there is an urgent need for real-time accurate detection and classification of drones. This article provides an overview of drone detection approaches, highlighting their benefits and limitations. We analyze detection techniques that employ radars, acoustic and optical sensors, and emitted radio frequency (RF) signals. We compare their performance, accuracy, and cost under different operating conditions. We conclude that multi-sensor detection systems offer more compelling results, but further research is required.
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BACKGROUND: This research investigates the correlation between the severity of internal carotid artery (ICA) stenosis and retinal parameters in patients with proliferative diabetic retinopathy (PDR), aiming to uncover potential risk factors. METHODS: A retrospective analysis of 68 patients (136 eyes) diagnosed with bilateral PDR from January 1, 2017, to December 31, 2021, was conducted. Carotid artery stenosis (CAS) was assessed using neck computed tomography angiography (CTA) and carotid duplex ultrasound (CDUS), with stenosis classified into two groups: normal (group 1) and mild or above (group 2), based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Optical coherence tomography (OCT) and OCT angiography (OCTA) measured several retinal parameters, including sub foveal choroidal thickness (SFCT), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, vessel density (VD), and foveal avascular zone (FAZ) area. Statistical analyses determined correlations between ICA degrees and retinal parameters. RESULTS: This study showed significant differences between groups in total VD, FAZ area, total RNFL thickness, and temporal RNFL thickness, indicating that patients with more severe ICA stenosis had noticeable retinal changes. Other parameters such as hyperlipidemia, total cholesterol levels, and intraocular pressure (IOP) also differed significantly, while no notable differences were observed in SFCT, central VD, average GCIPL, and superior, nasal, and inferior RNFL thickness. CONCLUSION: The study findings highlight retinal changes, such as an increased FAZ area, decreased total VD, and a total and thinner temporal RNFL, which suggest the need for carotid artery evaluation in patients. These findings have important clinical implications for the need for carotid work up in patients with PDR.
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Estenose das Carótidas , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica , Angiografia , Fatores de Risco , Vasos Retinianos , Angiofluoresceinografia/métodosRESUMO
Smoking is a well-established risk factor for various pathologies, including pulmonary diseases, cardiovascular disorders, and cancers. The toxic effects of cigarette smoke (CS) are mediated through multiple pathways and diverse mechanisms. A key pathogenic factor is oxidative stress, primarily induced by excessive formation of reactive oxygen species. However, it remains unclear whether smoking directly induces systemic oxidative stress or if such stress is a secondary consequence. This study aimed to determine whether short-term inhalation exposure to CS induces oxidative stress in extrapulmonary organs in addition to the lung in a murine model. In the experiment, 3R4F reference cigarettes were used to generate CS, and 8-week-old male BALB/c mice were exposed to CS at a total particulate matter concentration of either 0 or 800 µg/L for four consecutive days. CS exposure led to an increase in neutrophils, eosinophils, and total cell counts in bronchoalveolar lavage fluid. It also elevated levels of lactate dehydrogenase and malondialdehyde (MDA), markers indicative of tissue damage and oxidative stress, respectively. Conversely, no significant changes were observed in systemic oxidative stress markers such as total oxidant scavenging capacity, MDA, glutathione (GSH), and the GSH/GSSG ratio in blood samples. In line with these findings, CS exposure elevated NADPH oxidase (NOX)-dependent superoxide generation in the lung but not in other organs like the liver, kidney, heart, aorta, and brain. Collectively, our results indicate that short-term exposure to CS induces inflammation and oxidative stress in the lung without significantly affecting oxidative stress in extrapulmonary organs under the current experimental conditions. NOX may play a role in these pulmonary-specific events.
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Ventricular septal defect (VSD) is a common congenital heart disease. However, consensus on the utility of echocardiography in predicting spontaneous closure (SC) of VSD remains lacking. This study aimed to identify and validate significant predictors of SC through a predictive scoring system. This retrospective study included medical records of 712 echocardiography instances performed on 304 patients diagnosed with VSD from 2016 to 2020 in their first year of life. A novel scoring system for predicting the SC of VSD was developed and validated using another dataset from different hospitals. Of the 304 patients, 215 (70.7%) had perimembranous (PM) VSDs and 89 had muscular (29.3%) VSDs. The median follow-up periods were 36.2 (interquartile range [IQR], 13-59) months and 13.7 9 (IQR, 5-37.4) days for PM and muscular VSDs, respectively. The overall SC rate during follow-up was 29.3%. Pulmonary hypertension (HTN), concomitant left ventricle (LV)-right atrium (RA) shunt, VSD size to aortic valve (AV) annulus size ratio, and left ventricular end-diastolic dimension (LVEDD) z-score were significant risk factors affecting SC of VSD. The "P-VSD" score, a new scoring system, demonstrated an area under the curve for predictability of 0.769. Pulmonary HTN, concomitant LV-RA shunt, LVEDD z-score, and VSD size-to-AV annulus size ratio at diagnosis were significantly associated with non-SC VSD after infancy. The P-VSD score can predict the SC of VSD in clinical settings and simplify the identification and appropriate management of high-risk patients.
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For many applications, drones are required to operate entirely or partially autonomously. In order to fly completely or partially on their own, drones need to access location services for navigation commands. While using the Global Positioning System (GPS) is an obvious choice, GPS is not always available, can be spoofed or jammed, and is highly error-prone for indoor and underground environments. The ranging method using beacons is one of the most popular methods for localization, especially for indoor environments. In general, the localization error in this class is due to two factors: the ranging error, and the error induced by the relative geometry between the beacons and the target object to be localized. This paper proposes OPTILOD (Optimal Beacon Placement for High-Accuracy Indoor Localization of Drones), an optimization algorithm for the optimal placement of beacons deployed in three-dimensional indoor environments. OPTILOD leverages advances in evolutionary algorithms to compute the minimum number of beacons and their optimal placement, thereby minimizing the localization error. These problems belong to the Mixed Integer Programming (MIP) class and are both considered NP-hard. Despite this, OPTILOD can provide multiple optimal beacon configurations that minimize the localization error and the number of deployed beacons concurrently and efficiently.
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The aberrant increase or dysregulation of cytosolic Zn2+ concentration ([Zn2+]cyt) has been associated with cellular dysfunction and cytotoxicity. In this study, we postulated that Zn2+ mediates the cytotoxicity of thiol-reactive electrophiles. This notion was grounded on earlier research, which revealed that thiol-reactive electrophiles may disrupt Zn2+-binding motifs, consequently causing Zn2+ to be released from Zn2+-binding proteins, and leading to a surge in [Zn2+]cyt. The thiol-reactive electrophiles N-ethylmaleimide (NEM) and diamide were observed to induce an increase in [Zn2+]cyt, possibly through the impairment of Zn2+-binding motifs, and subsequent stimulation of reactive oxygen species (ROS) formation, resulting in cytotoxicity in primary cultured rat vascular smooth muscle cells. These processes were negated by the thiol donor N-acetyl-L-cysteine and the Zn2+ chelator TPEN. Similar outcomes were detected with co-treatment involving Zn2+ and Zn2+ ionophores such as pyrithione or disulfiram. Moreover, TPEN was found to inhibit cytotoxicity triggered by short-term exposure to various thiol-reactive electrophiles including hydrogen peroxide, acrylamide, acrylonitrile, diethyl maleate, iodoacetic acid, and iodoacetamide. In conclusion, our findings suggest that cytosolic Zn2+ acts as a universal mediator in the cytotoxic effects produced by thiol-reactive electrophiles.
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Etilenodiaminas , Compostos de Sulfidrila , Zinco , Ratos , Animais , Compostos de Sulfidrila/metabolismo , Zinco/metabolismo , Músculo Liso Vascular/metabolismo , Citosol , Ácidos/metabolismoRESUMO
Extensive, long-term exposure to cigarette smoke (CS) was recently suggested to be a risk factor for pulmonary hypertension, although further validation is required. The vascular effects of CS share similarities with the etiology of pulmonary hypertension, including vascular inflammation and remodeling. Thus, we examined the influence of CS exposure on the pathogenesis of monocrotaline (MCT)-induced pulmonary hypertension, hypothesizing that smoking might accelerate the development of primed pulmonary hypertension. CS was generated from 3R4F reference cigarettes, and rats were exposed to CS by inhalation at total particulate matter concentrations of 100-300 µg/L for 4 h/day, 7 days/week for 4 weeks. Following 1 week of initial exposure, rats received 60 mg/kg MCT and were sacrificed and analyzed after an additional 3 weeks of exposure. MCT induced hypertrophy in pulmonary arterioles and increased the Fulton index, a measure of right ventricular hypertrophy. Additional CS exposure exacerbated arteriolar hypertrophy but did not further elevate the Fulton index. No significant alterations were observed in levels of endothelin-1 and vascular endothelial growth factor, or in hematological and serum biochemical parameters. Short-term inhalation exposure to CS exacerbated arteriolar hypertrophy in the lung, although this effect did not directly aggravate the overworked heart under the current experimental conditions.
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Fumar Cigarros , Hipertensão Pulmonar , Ratos , Animais , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Monocrotalina/toxicidade , Monocrotalina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Exposição por Inalação/efeitos adversos , Ratos Sprague-Dawley , Hipertrofia , Artéria Pulmonar/patologiaRESUMO
Archaeoentomological investigations were conducted on soil contents from a grave belonging to the Joseon Dynasty as part of the Urban Environment Maintenance Project (UEMP) in Cheongjin 12-16 dong (districts), Jongno-gu, Seoul, Korea, from December 01, 2008 to February 19, 2011. A total of 28 insect puparia with hard shells of the common green bottle fly Lucilia sericata were identified in the soil. Evidence suggested that the corpse was placed outside for some days instead of being buried immediately after death. This is the first report of fly puparia in soil samples from a tomb of the Joseon Dynasty during 16-17 AD in Korea. Our findings may help determine the timeframe of burial and offer archaeological insights into the funerary customs of the period.
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Dípteros , Animais , Dípteros/anatomia & histologia , Calliphoridae , Solo , Coreia (Geográfico) , SeulRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by aggressive growth and a high propensity for recurrence and metastasis. Simultaneous overexpression of c-MET and EGFR in TNBC is associated with worse clinicopathological features and unfavorable outcomes. Although the development of new c-MET inhibitors and the emergence of 3rd-generation EGFR inhibitors represent promising treatment options, the high costs involved limit the accessibility of these drugs. In the present study, we sought to investigate the therapeutic potential of doxazosin (DOXA), a generic drug for benign prostate hyperplasia, in targeting TNBC. METHODS: The effect of DOXA on TNBC cell lines in vitro was evaluated in terms of cell viability, apoptosis, c-MET/EGFR signaling pathway, molecular docking studies and impact on cancer stem cell (CSC)-like properties. An in vivo metastatic model with CSCs was used to evaluate the efficacy of DOXA. RESULTS: DOXA exhibits notable anti-proliferative effects on TNBC cells by inducing apoptosis via caspase activation. Molecular docking studies revealed the direct interaction of DOXA with the tyrosine kinase domains of c-MET and EGFR. Consequently, DOXA disrupts important survival pathways including AKT, MEK/ERK, and JAK/STAT3, while suppressing CSC-like characteristics including CD44high/CD24low subpopulations, aldehyde dehydrogenase 1 (ALDH1) activity and formation of mammospheres. DOXA administration was found to suppress tumor growth, intra- and peri-tumoral angiogenesis and distant metastasis in an orthotopic allograft model with CSC-enriched populations. Furthermore, no toxic effects of DOXA were observed in hepatic or renal function. CONCLUSIONS: Our findings highlight the potential of DOXA as a therapeutic option for metastatic TNBC, warranting further investigation.
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Doxazossina , Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Doxazossina/farmacologia , Doxazossina/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Simulação de Acoplamento Molecular , Células-Tronco Neoplásicas/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
Smoking is recognized as a significant risk factor for numerous disorders, including cardiovascular diseases, respiratory conditions, and various forms of cancer. While the exact pathogenic mechanisms continue to be explored, the induction of oxidative stress via the production of excess reactive oxygen species (ROS) is widely accepted as a primary molecular event that predisposes individuals to these smoking-related ailments. This review focused on how cigarette smoke (CS) promotes ROS formation rather than the pathophysiological repercussions of ROS and oxidative stress. A comprehensive analysis of existing studies revealed the following key ways through which CS imposes ROS burden on biological systems: (1) ROS, as well as radicals, are intrinsically present in CS, (2) CS constituents generate ROS through chemical reactions with biomolecules, (3) CS stimulates cellular ROS sources to enhance production, and (4) CS disrupts the antioxidant system, aggravating the ROS generation and its functions. While the evidence supporting these mechanisms is chiefly based on in vitro and animal studies, the direct clinical relevance remains to be fully elucidated. Nevertheless, this understanding is fundamental for deciphering molecular events leading to oxidative stress and for developing intervention strategies to counter CS-induced oxidative stress.