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OBJECTIVES: During the COVID-19 pandemic, various non-pharmaceutical interventions such as individual hygiene practices like hand washing, social distancing, and mandates for the use of masks in public spaces were implemented to reduce the spread of the disease. Otitis media (OM) is a common infectious disease. How the changed environment due to the COVID-19 pandemic has influenced the prevalence of infectious diseases like OM is not known. This study aimed to investigate how OM prevalence and trends changed during COVID-19 in Korea. METHODS: OM patient data from 2017 to 2021 were extracted from the Health Insurance Review and Assessment Service database. Patients diagnosed with disease code H66 (suppurative and unspecified otitis media) were selected for analysis. Data on OM prevalence, gender, region, medical institution, and number of ventilating-tube prescriptions were analyzed. All age groups were included, and ages were categorized into 5-year ranges. RESULTS: The number of patients diagnosed with the OM disease code decreased continuously from 2017 to 2021 (1 598 205, 1 560 178, 1 520 948, 983 701, and 734 901). The average OM prevalence per 1000 persons decreased by 45.0% from 30.2 in 2017 to 2019 to 16.6 in 2020 to 2021. The change of OM prevalence was greater for the 0 to 5 age group than other age groups. The decrease in average prevalence per 1000 persons was greatest in the 0 to 5 age group (48.6% decrease from 358.2 in 2017-2019 to 184.1 in 2020-2021). The impact of environmental changes on ventilation-tube insertion was smaller than on OM prevalence. The average number of ventilating-tube insertions decreased by 28.1% from 27 311 in 2017 to 2019 to 19 650 in 2020 to 2021. CONCLUSIONS: OM prevalence decreased by 45.0%, and the number of ventilating-tube insertions decreased by 28.1% in Korea during COVID-19.
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COVID-19 , Otite Média , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Otite Média/epidemiologia , República da Coreia/epidemiologia , Feminino , Prevalência , Masculino , Adulto , Criança , Pessoa de Meia-Idade , Pré-Escolar , Lactente , Adolescente , Idoso , Adulto Jovem , SARS-CoV-2 , Ventilação da Orelha Média/estatística & dados numéricos , Recém-NascidoRESUMO
The ability to perceive temperature is crucial for most animals. It enables them to maintain their body temperature and swiftly react to noxiously cold or hot objects. Caenorhabditis elegans is a powerful genetic model for the study of thermosensation as its simple nervous system is well characterized and its transparent body is suited for in vivo functional imaging of neurons. The behavior triggered by experience-dependent thermosensation has been well studied in C. elegans under temperature-gradient environments. However, how C. elegans senses temperature via its nervous system is not well understood due to the limitations of currently available technologies. One major bottleneck is the difficulty in creating fast temperature changes, especially cold stimuli. Here, we developed a microfluidic-based platform that allowed the in vivo functional imaging of C. elegans responding to well-controlled temporally varying temperature stimulation by rapidly switching fluid streams at different temperatures. We used computational models to enable rational design and optimization of experimental conditions. We validated the design and utility of our system with studies of the functional role of thermosensory neurons. We showed that the responses of PVD polymodal nociceptor neurons observed in previous studies can be recapitulated. Further, we highlighted how this platform may be used to dissect neuronal circuits with an example of activity recording in PVC interneurons. Both of these neuron types show sensitization phenotypes. We envision that both the engineered system and the findings in this work will spur further studies of molecular and cellular mechanisms underlying cold-sensing through the nervous system.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Temperatura , Caenorhabditis elegans/genética , Microfluídica , Sensação Térmica/fisiologia , Temperatura Baixa , Proteínas de Caenorhabditis elegans/genéticaRESUMO
Middle ear tumors are diverse, but relatively uncommon. The most frequent tumor in the middle ear is glomus tumor, followed by others such as schwannoma and cholesteatoma. We experienced a case of Mucosa-associated lymphoid tissue hyperplasia as a middle ear tumor. The mass behind tympanic membrane appeared a hypervascular tumor, mimicking a glomus tumor, but the form of multiple separate masses in middle ear and mastoid cavity was the distinguishing feature that set it apart from a glomus tumor. Additionally, another characteristic was its tendency to easily shrink under pressure. This characteristic should be considered when encounter a hypervascular looking middle ear mass. Laryngoscope, 134:1894-1896, 2024.
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Neoplasias da Orelha , Tumor Glômico , Glomo Timpânico , Humanos , Glomo Timpânico/patologia , Tumor Glômico/patologia , Orelha Média/patologia , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/patologia , Erros de Diagnóstico , Mucosa/patologia , Tecido LinfoideRESUMO
PURPOSE: Local allergic rhinitis (LAR) is characterized by a localized nasal allergic response without evidence of systemic atopy. LAR is an underdiagnosed entity and is a diagnostic and therapeutic challenge for clinicians. This study aimed to investigate the prevalence and clinical characteristics of patients with LAR to house dust mites (LAR-HDM) in Korea. METHODS: We performed a retrospective chart review of 336 adult patients with rhinitis symptoms who visited the Rhinologic Clinic at Korea University Guro Hospital from October 2019 to April 2021. Using results of the skin prick test, serologic test, and nasal provocation test, patients were classified as allergic rhinitis (AR) to HDM (AR-HDM), AR to other allergens, non-allergic rhinitis (NAR), or LAR-HDM. We excluded patients with AR to other allergens and compared the clinical characteristics of the remaining three groups. Patient demographic data were reviewed, and patients' nasal symptoms, olfactory function, serum total IgE, and severity of accompanying rhinosinusitis were evaluated. RESULTS: In total, 336 patients were examined. AR-HDM was diagnosed in 138 (41.1%) patients, AR to other allergens in 36 (10.7%) patients, NAR in 21 (42.0%) patients, and LAR-HDM in 21 (6.3%) patients. The mean age of patients with LAR-HDM was significantly higher than that of patients with AR-HDM. There were no significant differences in sex, smoking history, asthma, and family history of allergic diseases between the groups. Compared to NAR patients, there were significantly more patients with LAR-HDM who had persistent nasal symptoms. The frequency of nasal itching and sneezing was significantly higher in the LAR-HDM group than in the NAR group. The olfactory function score in the LAR-HDM group was significantly worse than that in the AR-HDM group, and the Lund-Mackay score was significantly higher in the LAR-HDM group than in the other groups. CONCLUSION: Clinical history and nasal symptoms are very similar in LAR-HDM and AR-HDM. Clinicians should take more care to differentiate them. LAR-HDM should also be considered in patients with persistent and severe nasal symptoms without systemic atopy.
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Rinite Alérgica , Rinite , Adulto , Animais , Humanos , Pyroglyphidae , Estudos Retrospectivos , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Alérgenos , Ásia , Testes CutâneosRESUMO
Acidovorax citrulli (Ac) is a causal agent of watermelon bacterial fruit blotch (BFB) disease. Because resistance cultivars/lines have not yet been developed, it is imperative to elucidate Ac's virulence factors and their mechanisms to develop resistant cultivars/lines in different crops, including watermelon. The glucose-6-phosphate isomerase (GPI) is a reversible enzyme in both glycolysis and gluconeogenesis pathways in living organisms. However, the functions of GPI are not characterized in Ac. In this study, we determined the roles of GpiAc (GPI in Ac) by proteomic and phenotypic analyses of the mutant lacking GPI. The mutant displayed significantly reduced virulence to watermelon in two different virulence assays. The mutant's growth patterns were comparable to the wild-type strain in rich medium and M9 with glucose but not with fructose. The comparative proteome analysis markedly identified proteins related to virulence, motility, and cell wall/membrane/envelope. In the mutant, biofilm formation and twitching halo production were reduced. We further demonstrated that the mutant was less tolerant to osmotic stress and lysozyme treatment than the wild-type strain. Interestingly, the tolerance to alkali conditions was remarkably enhanced in the mutant. These results reveal that GpiAc is involved not only in virulence and glycolysis/gluconeogenesis but also in biofilm formation, twitching motility, and tolerance to diverse external stresses suggesting the pleiotropic roles of GpiAc in Ac. Our study provides fundamental and valuable information on the functions of previously uncharacterized glucose 6-phosphate isomerase and its virulence mechanism in Ac.
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Single-molecule imaging technologies, especially those based on fluorescence, have been developed to probe both the equilibrium and dynamic properties of biomolecules at the single-molecular and quantitative levels. In this review, we provide an overview of the state-of-the-art advancements in single-molecule fluorescence imaging techniques. We systematically explore the advanced implementations of in vitro single-molecule imaging techniques using total internal reflection fluorescence (TIRF) microscopy, which is widely accessible. This includes discussions on sample preparation, passivation techniques, data collection and analysis, and biological applications. Furthermore, we delve into the compatibility of microfluidic technology for single-molecule fluorescence imaging, highlighting its potential benefits and challenges. Finally, we summarize the current challenges and prospects of fluorescence-based single-molecule imaging techniques, paving the way for further advancements in this rapidly evolving field.
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Imagem Individual de Molécula , Tecnologia , Microscopia , Dispositivos Lab-On-A-Chip , Imagem ÓpticaRESUMO
Acidovorax citrulli (Ac) is a phytopathogenic bacterium that causes bacterial fruit blotch (BFB) in cucurbit crops, including watermelon. However, there are no effective methods to control this disease. YggS family pyridoxal phosphate-dependent enzyme acts as a coenzyme in all transamination reactions, but its function in Ac is poorly understood. Therefore, this study uses proteomic and phenotypic analyses to characterize the functions. The Ac strain lacking the YggS family pyridoxal phosphate-dependent enzyme, AcΔyppAc(EV), virulence was wholly eradicated in geminated seed inoculation and leaf infiltration. AcΔyppAc(EV) propagation was inhibited when exposed to L-homoserine but not pyridoxine. Wild-type and mutant growth were comparable in the liquid media but not in the solid media in the minimal condition. The comparative proteomic analysis revealed that YppAc is primarily involved in cell motility and wall/membrane/envelop biogenesis. In addition, AcΔyppAc(EV) reduced biofilm formation and twitching halo production, indicating that YppAc is involved in various cellular mechanisms and possesses pleiotropic effects. Therefore, this identified protein is a potential target for developing an efficient anti-virulence reagent to control BFB.
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Acidovorax citrulli (Ac) is a gram-negative bacterium that causes bacterial fruit blotch (BFB) disease in cucurbit crops including watermelon. However, despite the great economic losses caused by this disease worldwide, Ac-resistant watermelon cultivars have not been developed. Therefore, characterizing the virulence factors/mechanisms of Ac would enable the development of effective control strategies against BFB disease. The 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (BdpM) is known to participate in the glycolysis and gluconeogenesis pathways. However, the roles of the protein have not been characterized in Ac. To elucidate the functions of BdpmAc (Bdpm in Ac), comparative proteomic analysis and diverse phenotypic assays were conducted using a bdpmAc knockout mutant (bdpmAc:Tn) and a wild-type strain. The virulence of the mutant to watermelon was remarkably reduced in both germinated seed inoculation and leaf infiltration assays. Moreover, the mutant could not grow with fructose or pyruvate as a sole carbon source. However, the growth of the mutant was restored to levels similar to those of the wild-type strain in the presence of both fructose and pyruvate. Comparative proteomic analyses revealed that diverse proteins involved in motility and wall/membrane/envelop biogenesis were differentially abundant. Furthermore, the mutant exhibited decreased biofilm formation and twitching halo size. Interestingly, the mutant exhibited a higher tolerance against osmotic stress. Overall, our findings suggest that BdpmAc affects the virulence, glycolysis/gluconeogenesis, biofilm formation, twitching halo size, and osmotic tolerance of Ac, suggesting that this protein has pleiotropic properties. Collectively, our findings provide fundamental insights into the functions of a previously uncharacterized phosphoglycerate mutase in Ac.
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AbstractMaternal age effects on offspring life history are known in a variety of organisms, with offspring of older mothers typically having lower life expectancy (the Lansing effect). However, there is no consensus on the generality and mechanisms of this pattern. We tested predictions of the Lansing effect in several Daphnia magna clones and observed clone-specific magnitude and direction of the maternal age effect on offspring longevity. We also report ambidirectional, genotype-specific effects of maternal age on the propensity of daughters to produce male offspring. Focusing on two clones with contrasting life histories, we demonstrate that maternal age effects can be explained by lipid provisioning of embryos by mothers of different ages. Individuals from a single-generation maternal age reversal treatment showed intermediate life span and intermediate lipid content at birth. In the clone characterized by the "inverse Lansing effect," neonates produced by older mothers showed higher mitochondrial membrane potential in neural tissues than their counterparts born to younger mothers. We conclude that an inverse Lansing effect is possible and hypothesize that it may be caused by age-specific maternal lipid provisioning creating a calorically restricted environment during embryonic development, which in turn reduces fecundity and increases life span in offspring.
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Longevidade , Reprodução , Animais , Masculino , Idade Materna , Núcleo Familiar , LipídeosRESUMO
Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserve health as measured by frailty index scores, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome and epigenome of treated mice were younger at the completion of treatment. Analogous to mice, rapamycin exposure during development robustly extended the life span of Daphnia magna and reduced its body size. Overall, the results demonstrate that short-term rapamycin treatment during development is a novel longevity intervention that acts by slowing down development and aging, suggesting that aging may be targeted already early in life.
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Insulinas , Longevidade , Animais , Daphnia/genética , Glucose , Masculino , Camundongos , Sirolimo/farmacologiaRESUMO
Erwinia amylovora, the causal agent of fire-blight disease in apple and pear trees, was first isolated in South Korea in 2015. Although numerous studies, including omics analyses, have been conducted on other strains of E. amylovora, studies on South Korean isolates remain limited. In this study, we conducted a comparative proteomic analysis of the strain TS3128, cultured in three media representing different growth conditions. Proteins related to virulence, type III secretion system, and amylovoran production, were more abundant under minimal conditions than in rich conditions. Additionally, various proteins associated with energy production, carbohydrate metabolism, cell wall/membrane/envelope biogenesis, and ion uptake were identified under minimal conditions. The strain TS3128 expresses these proteins to survive in harsh environments. These findings contribute to understanding the cellular mechanisms driving its adaptations to different environmental conditions and provide proteome profiles as reference for future studies on the virulence and adaptation mechanisms of South Korean strains.
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BK002 consists of Achyranthes japonica Nakai (AJN) and Melandrium firmum Rohrbach (MFR) that have been used as herbal medicines in China and Korea. AJN and MFR have been reported to have anti-inflammatory, anti-oxidative, and anti-cancer activities, although the synergistic targeting multiple anti-cancer mechanism in castration-resistant prostate cancer (CRPC) has not been well reported. However, the drug resistance and transition to the androgen-independent state of prostate cancer contributing to CRPC is not well studied. Here, we reported that BK002 exerted cytotoxicity and apoptosis in CRPC PC3 cell lines and prostate cancer DU145 cell lines examined by cytotoxicity, western blot, a LIVE/DEAD cell imaging assay, reactive oxygen species (ROS) detection, quantitative real-time polymerase chain reaction (RT-PCR), and transfection assays. The results from our investigation found that BK002 showed more cellular cytotoxicity than AJN and MFR alone, suggesting that BK002 exhibited potential cytotoxic properties. Consistently, BK002 increased DNA damage, and activated p-γH2A.X and depletion of survivin-activated ubiquitination of pro-PARP, caspase9, and caspase3. Notably, live cell imaging using confocal microscopy found that BK002 effectively increased DNA-binding red fluorescent intensity in PC3 and DU145 cells. Also, BK002 increased the anti-proliferative effect with activation of the C/EBP homologous protein (CHOP) and significantly attenuated PI3K/AKT expression. Notably, BK002-treated cells increased ROS generation and co-treatment of N-Acetyl-L-cysteine (NAC), an ROS inhibitor, significantly preventing ROS production and cellular cytotoxicity, suggesting that ROS production is essential for initiating apoptosis in PC3 and DU145 cells. In addition, we found that BK002 significantly enhanced miR-192-5p expression, and co-treatment with BK002 and miR-192-5p inhibitor significantly reduced miR-192-5p expression and cellular viability in PC3 and DU145 cells, indicating modulation of miR-192-5p mediated apoptosis. Finally, we found that BK002-mediated CHOP upregulation and PI3K downregulation were significantly reduced and restrained by miR-192-5p inhibitor respectively, suggesting that the anti-cancer effect of BK002 is associated with the miR-192-5p/PI3K/CHOP pathway. Therefore, our study reveals that a combination of AJN and MFR might be more effective than single treatment against apoptotic activities of both CRPC cells and prostate cancer cells.
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ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houttuyn is a medicinal ingredient in more than 300 prescriptions in traditional Korean medicine. It is especially important for women's health and blood-related diseases. Recent research revealed that Leonurus japonicus Houttuyn extracts have antioxidative, anticancer, analgesic, anti-inflammatory, and neuroprotective properties. AIM OF THE STUDY: However, its underlying anti-cancerous mechanisms remain unclear. This study elucidated the anticancer mechanism of Leonurus japonicus Houttuyn in U937 and THP-1 cancer cells. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used for detecting main compound of Leonurus japonicus Houttuyn, rutin. EZ-Cytox cell viability assay, Western blot analysis, live and dead cell assay, 2', 7' dichlorofluorescin diacetate (DCFDA) assay, quantitative real-time PCR (qRT-PCR) analysis, and microRNA (miR) mimic transfection assay were applied to further investigate anti-cancer efficacies and underlying mechanism in U937 and THP-1 cells. RESULTS: The main compound of Leonurus japonicus Houttuyn, rutin was detected using HPLC. The cytotoxic effect of Leonurus japonicus Houttuyn was exerted in U937 and THP-1 cancer cells but not in MDBK and IEC-6 normal cells. Leonurus japonicus Houttuyn decreased mitochondria membrane potential (ΔΨm). Consistently, Leonurus japonicus Houttuyn reduced the expression of survivin and cleaved caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Cell death was increased in Leonurus japonicus Houttuyn treated groups. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and CCAAT-enhancer-binding protein homologous protein (CHOP) was increased and phosphatidylinositol-3-kinase (PI3K) and Protein kinase B (AKT) were decreased by Leonurus japonicus Houttuyn. Reactive oxygen speices generation was elevated by Leonurus japonicus Houttuyn and its cytotoxicity was reversed by N-acetyl-l-cysteine (NAC) pretreatment. Moreover, onco-microRNA (miR), miR-19a-3p was suppressed by Leonurus japonicus Houttuyn and transfection of miR-19a-3p mimic reversed the regulated PTEN, p-AKT, CHOP expression, attenuating Leonurus japonicus Houttuyn induced apoptosis. CONCLUSIONS: These findings indicated that Leonurus japonicus Houttuyn has anti-cancer effects by regulation of PTEN/PI3K/AKT signal pathway and ROS-related ER stress-induced apoptosis via regulation of miR-19a-3p. Leonurus japonicus Houttuyn may be an effective candidate for triggering PTEN-dependent apoptosis of cancer cells related to acute myeloid leukemia.
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Leonurus , MicroRNAs , Espécies Reativas de Oxigênio , Apoptose , Feminino , Humanos , Leonurus/química , MicroRNAs/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células THP-1 , Células U937RESUMO
We present a novel platform for testing the effects of interventions on the life- and healthspan of a short-lived freshwater organism with complex behavior and physiology-the planktonic crustacean Daphnia magna. Within this platform, dozens of complex behavioral features of both routine motion and response to stimuli are continuously quantified over large synchronized cohorts via an automated phenotyping pipeline. We build predictive machine-learning models calibrated using chronological age and extrapolate onto phenotypic age. We further apply the model to estimate the phenotypic age under pharmacological perturbation. Our platform provides a scalable framework for drug screening and characterization in both life-long and instant assays as illustrated using a long-term dose-response profile of metformin and a short-term assay of well-studied substances such as caffeine and alcohol.
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Daphnia , Animais , Daphnia/fisiologiaRESUMO
Aging is a multifaceted process of accumulation of damage and waste in cells and tissues; age-related changes in mitochondria and in respiratory metabolism have the focus of aging research for decades. Studies of aging in nematodes, flies and mammals all revealed age-related decline in respiratory functions, with somewhat controversial causative role. Here we investigated age-related changes in respiration rates, lactate/pyruvate ratio, a commonly used proxy for NADH/NAD+ balance, and mitochondrial membrane potential in 4 genotypes of an emerging model organism for aging research, a cyclic parthenogen Daphnia magna. We show that total body weight-adjusted respiration rate decreased with age, although this decrease was small in magnitude and could be fully accounted for by the decrease in locomotion and feeding activity. Neither total respiration normalized by protein content, nor basal respiration rate measured in anaesthetized animals decreased with age. Lactate/pyruvate ratio and mitochondrial membrane potential (∆Ψmt) showed no age-related changes, with possible exceptions of ∆Ψmt in epipodites (excretory and gas exchange organs) in which ∆Ψmt decreased with age and in the optical lobe of the brain, in which ∆Ψmt showed a maximum at middle age. We conclude that actuarial senescence in Daphnia is not caused by a decline in respiratory metabolism and discuss possible mechanisms of maintaining mitochondrial healthspan throughout the lifespan.
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Daphnia , Taxa Respiratória , Animais , Daphnia/metabolismo , Lactatos/metabolismo , Longevidade , Mamíferos , Piruvatos/metabolismoRESUMO
Pancreatic cancer, the seventh most lethal cancer around the world, is considered complicated cancer due to poor prognosis and difficulty in treatment. Despite all the conventional treatments, including surgical therapy and chemotherapy, the mortality rate is still high. Therefore, the possibility of using natural products for pancreatic cancer is increasing. In this study, 68 natural products that have anti-pancreatic cancer effects reported within five years were reviewed. The mechanisms of anti-cancer effects were divided into four types: apoptosis, anti-metastasis, anti-angiogenesis, and anti-resistance. Most of the studies were conducted for natural products that induce apoptosis in pancreatic cancer. Among them, plant extracts such as Eucalyptus microcorys account for the major portion. Some natural products, including Moringa, Coix seed, etc., showed multi-functional properties. Natural products could be beneficial candidates for treating pancreatic cancer.
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Produtos Biológicos/uso terapêutico , Descoberta de Drogas/tendências , Medicina Tradicional/tendências , Neoplasias Pancreáticas/tratamento farmacológico , Fitoterapia/tendências , Inibidores da Angiogênese , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Extratos Vegetais/farmacologiaRESUMO
Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.
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Antineoplásicos Fitogênicos/farmacologia , Nanopartículas/química , Nanotecnologia/métodos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Humanos , Sistema Fagocitário Mononuclear/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Nanotubos de Carbono , Compostos Fitoquímicos/administração & dosagem , Pontos QuânticosRESUMO
Aberrant production of reactive oxygen species (ROS) leads to tissue damage accumulation, which is associated with a myriad of human pathologies. Although several sensors have been developed for ROS quantification, their applications for ROS-related human physiologies and pathologies still remain problematic due to the unstable nature of ROS. Herein, we developed Trx1-cpYFP-fRMsr (TYfR), a genetically-encoded fluorescent biosensor with the remarkable specificity and sensitivity toward fMetRO (free Methionine-R-sulfoxide), allowing for dynamic quantification of physiological levels of fMetRO, a novel indicator of ROS and methionine redox status in vitro and in vivo. Moreover, using the sensor, we observed a significant fMetRO enrichment in serum from patients with acute coronary syndrome, one of the most severe cardiovascular diseases, which becomes more evident following percutaneous coronary intervention. Collectively, this study proposes that fMetRO is a novel biomarker of tissue damage accumulation in ROS-associated human pathologies, and that TYfR is a promising tool for quantifying fMetRO with potentials in versatile applications.
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Técnicas Biossensoriais , Metionina Sulfóxido Redutases , Humanos , Metionina , Metionina Sulfóxido Redutases/metabolismo , Oxirredução , Estresse Oxidativo , Espécies Reativas de OxigênioRESUMO
Hanwoo, an indigenous Korean cattle breed, has been genetically improved by selecting superior sires called Korean-proven bulls. However, cows still contribute half of the genetic stock of their offspring, and allelic-specific expressed genes have potential, as selective targets of cows, to enhance genetic gain. The aim of this study is to identify genes that have MAEs based on both the genome and transcriptome and to estimate their effects on breeding values (BVs) for economically important traits in Hanwoo. We generated resequencing data for the parents and RNA-sequencing data for the muscle, fat, and brain tissues of the offspring. A total of 3801 heterozygous single nucleotide polymorphisms (SNPs) in offspring were identified and they were located in 1569 genes. Only 14 genes showed MAE (seven expressing maternal alleles and seven expressing paternal alleles). Tissue-specific MAE was observed, and LANCL1 showed maternal allele expression across all tissues. MAE genes were enriched for the biological process of cell death and angiogenesis, which included ACKR3 and PDCL3 genes, whose SNPs were significantly associated with BVs of lean meat production-related traits, such as weight at 12 months of age, carcass weight, and loin eye area. In the current study, monoallelically expressed genes were identified in various adult tissues and these genes were associated with genetic capacity in Hanwoo.
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Health and longevity in all organisms are strongly influenced by the environment. To fully understand how environmental factors interact with genetic and stochastic factors to modulate the aging process, it is crucial to precisely control environmental conditions for long-term studies. In the commonly used model organism Caenorhabditis elegans, existing assays for healthspan and lifespan have inherent limitations, making it difficult to perform large-scale longitudinal aging studies under precise environmental control. To address these constraints, we developed the Health and Lifespan Testing Hub (HeALTH), an automated, microfluidic-based system for robust longitudinal behavioral monitoring. Our system provides long-term (i.e. entire lifespan) spatiotemporal environmental control. We demonstrate healthspan and lifespan studies under a variety of genetic and environmental perturbations while observing how individuality plays a role in the aging process. This system is generalizable beyond aging research, particularly for short- or long-term behavioral assays, and could be adapted for other model systems.