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Photoelectrochemical (PEC) water splitting to produce hydrogen fuel was first reported 50 years ago1, yet artificial photosynthesis has not become a widespread technology. Although planar Si solar cells have become a ubiquitous electrical energy source economically competitive with fossil fuels, analogous PEC devices have not been realized, and standard Si p-type/n-type (p-n) junctions cannot be used for water splitting because the bandgap precludes the generation of the needed photovoltage. An alternative paradigm, the particle suspension reactor (PSR), forgoes the rigid design in favour of individual PEC particles suspended in solution, a potentially low-cost option compared with planar systems2,3. Here we report Si-based PSRs by synthesizing high-photovoltage multijunction Si nanowires (SiNWs) that are co-functionalized to catalytically split water. By encoding a p-type-intrinsic-n-type (p-i-n) superlattice within single SiNWs, tunable photovoltages exceeding 10 V were observed under 1 sun illumination. Spatioselective photoelectrodeposition of oxygen and hydrogen evolution co-catalysts enabled water splitting at infrared wavelengths up to approximately 1,050 nm, with the efficiency and spectral dependence of hydrogen generation dictated by the photonic characteristics of the sub-wavelength-diameter SiNWs. Although initial energy conversion efficiencies are low, multijunction SiNWs bring the photonic advantages of a tunable, mesoscale geometry and the material advantages of Si-including the small bandgap and economies of scale-to the PSR design, providing a new approach for water-splitting reactors.
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Intracellular cargo trafficking is a highly regulated process responsible for transporting vital cellular components to their designated destinations. This intricate journey has been a central focus of cellular biology for many years. Early investigations leaned heavily on biochemical and genetic approaches, offering valuable insight into molecular mechanisms of cellular trafficking. However, while informative, these methods lack the capacity to capture the dynamic nature of intracellular trafficking. The advent of fluorescent protein tagging techniques transformed our ability to monitor the complete lifecycle of intracellular cargos, advancing our understanding. Yet, a central question remains: How do these cargos manage to navigate through traffic challenges, such as congestion, within the crowded cellular environment? Fluorescence-based imaging, though valuable, has inherent limitations when it comes to addressing the aforementioned question. It is prone to photobleaching, making long-term live-cell imaging challenging. Furthermore, they render unlabeled cellular constituents invisible, thereby missing critical environmental information. Notably, the unlabeled majority likely exerts a significant influence on the observed behavior of labeled molecules. These considerations underscore the necessity of developing complementary label-free imaging methods to overcome the limitations of fluorescence imaging or to integrate them synergistically.In this Account, we outline how label-free interference-based imaging has the potential to revolutionize the study of intracellular traffic by offering unprecedented levels of detail. We begin with a brief introduction to our previous findings in live-cell research enabled by interferometric scattering (iSCAT) microscopy, showcasing its aptitude and adeptness in elucidating intricate nanoscale intracellular structures. As we delved deeper into our exploration, we succeeded in the label-free visualization of the entire lifespan of nanoscale protein complexes known as nascent adhesions (NAs) and the dynamic events associated with adhesions within living cells. Our continuous efforts have led to the development of Dynamic Scattering-particle Localization Interference Microscopy (DySLIM), a generalized concept of cargo-localization iSCAT (CL-iSCAT). This label-free, high-speed imaging method, armed with iSCAT detection sensitivity, empowers us to capture quantitative and biophysical insights into cargo transport, providing a realistic view of the intricate nanoscale logistics occurring within living cells. Our in vivo studies demonstrate that intracellular cargos regularly contend with substantial traffic within the crowded cellular environment. Simultaneously, they employ inherent strategies for efficient cargo transport, such as collective migration and hitchhiking, to enhance overall transport ratesâintriguingly paralleling the principle and practice of urban traffic management. We also highlight the synergistic benefits of combining DySLIM with chemical-selective fluorescent methods. This Account concludes with a "Conclusions and Outlook" section, outlining promising directions for future research and developments, with a particular emphasis on the functional application of iSCAT live-cell imaging. We aim to inspire further investigation into the efficient transport strategies employed by cells to surmount transportation challenges, shedding light on their significance in cellular phenomena.
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Imagem Óptica , Humanos , Animais , Transporte Biológico , Microscopia de FluorescênciaRESUMO
OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is characterized by slow, progressive bulbar and limb muscle weakness; however, the pattern of progression of muscle fat infiltration remains unclear. We assessed the progression of muscle involvement in 81 patients with SBMA using whole-body muscle magnetic resonance imaging (MRI), alongside clinical and laboratory findings. METHODS: This prospective study included patients with genetically confirmed SBMA who underwent whole-body muscle MRI. We analyzed muscle fat infiltration and the pattern of involved muscles using cluster analysis, visualizing the sequential progression of fat infiltration. Muscle clusters demonstrated correlation with clinical scales and laboratory findings. Additionally, linear regression analysis was performed to identify the MRI section most strongly associated with 6-minute walk test (6MWT). RESULTS: We included 81 patients with SBMA (age = 54.3 years). After categorizing the patients into 6 clusters based on the pattern of muscle fat infiltration, we observed that muscle involvement began in the posterior calf and progressed to the posterior thigh, pelvis, trunk, anterior thigh, medial thigh, anterior calf, and upper extremity muscles. These muscle clusters correlated significantly with disease duration (τ = 0.47, p < 0.001), 6MWT (τ = -0.49, p < 0.001), and serum creatinine level (τ = -0.46, p < 0.001). The whole-body MRI indicated the thigh as the section most significantly correlated with 6MWT. INTERPRETATION: We used whole-body muscle MRI to determine the sequential progression of the fat infiltration in SBMA. Our findings may enable the identification of objective and reliable imaging outcome measures in the study of the natural history or future clinical trials of SBMA. ANN NEUROL 2024;95:596-606.
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Atrofia Bulboespinal Ligada ao X , Atrofia Muscular Espinal , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Atrofia Bulboespinal Ligada ao X/diagnóstico por imagem , Atrofia Bulboespinal Ligada ao X/patologia , Atrofia Muscular/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Atrofia Muscular Espinal/diagnóstico por imagem , Atrofia Muscular Espinal/patologia , Imageamento por Ressonância MagnéticaRESUMO
The precise and reversible detection of hydrogen sulfide (H2S) at high humidity condition, a malodorous and harmful volatile sulfur compound, is essential for the self-assessment of oral diseases, halitosis, and asthma. However, the selective and reversible detection of trace concentrations of H2S (≈0.1 ppm) in high humidity conditions (exhaled breath) is challenging because of irreversible H2S adsorption/desorption at the surface of chemiresistors. The study reports the synthesis of Fe-doped CuO hollow spheres as H2S gas-sensing materials via spray pyrolysis. 4 at.% of Fe-doped CuO hollow spheres exhibit high selectivity (response ratio ≥ 34.4) over interference gas (ethanol, 1 ppm) and reversible sensing characteristics (100% recovery) to 0.1 ppm of H2S under high humidity (relative humidity 80%) at 175 °C. The effect of multi-valent transition metal ion doping into CuO on sensor reversibility is confirmed through the enhancement of recovery kinetics by doping 4 at.% of Ti- or Nb ions into CuO sensors. Mechanistic details of these excellent H2S sensing characteristics are also investigated by analyzing the redox reactions and the catalytic activity change of the Fe-doped CuO sensing materials. The selective and reversible detection of H2S using the Fe-doped CuO sensor suggested in this work opens a new possibility for halitosis self-monitoring.
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Spinal and bulbar muscular atrophy, namely Kennedy disease, is a rare progressive neurodegenerative disorder caused by the expansion of a CAG repeat in the first exon of the androgen receptor gene on the X chromosome. We assessed the clinical history, laboratory findings, functional scales and electrophysiological data, as well as the levels of luteinizing hormone, follicle-stimulating hormone and testosterone, in 157 Korean patients with genetically confirmed spinal and bulbar muscular atrophy (mean age at data collection = 56.9 years; range = 33-83 years). Hand tremor was the first symptom noticed by patients at a median age of 35 years, followed by gynaecomastia, orofacial fasciculation, cramps and fatigability in ascending order. Clinical symptoms such as paraesthesia and dysphagia appeared during the later stages of the disease. Cane use during ambulation began at a median age of 62 years. There were statistically significant differences between patients and controls in the results of sensory nerve studies, motor conduction velocity, and distal latencies. Furthermore, among the hormone markers analysed, the level of luteinizing hormone exhibited a negative correlation with the spinal and bulbar muscular atrophy functional rating scale, Korean version. However, among the patients with a disease duration of ≤5 years, the levels of luteinizing hormone showed a significant correlation with assessments using the amyotrophic lateral sclerosis functional rating scale-revised, spinal and bulbar muscular atrophy functional rating scale, Korean version and the 6-minute walk test. In conclusion, our findings provide clinical information from a substantial number of patients with spinal and bulbar muscular atrophy in Korea that accorded with that of patients with this disease worldwide but with updated clinical features.
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Atrofia Bulboespinal Ligada ao X , Atrofia Muscular Espinal , Humanos , Adulto , Pessoa de Meia-Idade , Atrofia Bulboespinal Ligada ao X/diagnóstico , Atrofia Bulboespinal Ligada ao X/genética , Estudos Transversais , Tremor , Atrofia Muscular , Hormônio Luteinizante , Atrofia Muscular Espinal/genética , Receptores Androgênicos/genéticaRESUMO
BACKGROUND: In the context of neuromyelitis optica spectrum disorder (NMOSD), there are several measures that serve as a biomarker. However, each of the methods has the intrinsic limitations. While neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as an additional biomarker for NMOSD, a thorough investigation of their role remains incomplete. Our aim is to provide a comprehensive review of the current literature regarding NfL and GFAP as a biomarker and explore their potential utility in NMOSD. METHODS: We performed a comprehensive search using PubMed and Google Scholar to identify peer-reviewed articles investigating NfL and GFAP as a biomarker in NMOSD. RESULTS: Our search identified 13 relevant studies. NfL consistently showed promise in distinguishing NMOSD patients from healthy individuals, although it had limited specificity in distinguishing NMOSD from other demyelinating diseases. NfL offered certain advantages over GFAP, notably its ability to predict disability worsening during attacks. In contrast, GFAP provided valuable insight, particularly in distinguishing NMOSD from multiple sclerosis and identifying clinical relapses. In addition, GFAP showed predictive potential for future attacks. Some studies even suggested that NfL may serve as an indicator of treatment response in NMOSD. CONCLUSIONS: NfL and GFAP hold promise as biomarkers for NMOSD, demonstrating their usefulness in distinguishing patients from healthy individuals, assessing disease severity, and possibly reflecting treatment response. However, it is important to recognize that NfL and GFAP may, at some point, have different roles.
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Esclerose Múltipla , Neuromielite Óptica , Humanos , Neuromielite Óptica/diagnóstico , Proteína Glial Fibrilar Ácida , Filamentos Intermediários , Biomarcadores , Esclerose Múltipla/diagnóstico , Proteínas de NeurofilamentosRESUMO
OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.
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Leuprolida , Humanos , Leuprolida/uso terapêutico , Leuprolida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Feminino , Idoso , Adulto , Antagonistas de Androgênios/uso terapêutico , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Bulboespinal Ligada ao X/tratamento farmacológico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
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Vacinas contra COVID-19 , COVID-19 , Hospitalização , Miastenia Gravis , SARS-CoV-2 , Vacinação , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Idoso , SARS-CoV-2/isolamento & purificação , Adulto , Prognóstico , Unidades de Terapia Intensiva , Respiração ArtificialRESUMO
The brain cells are affected by continuous fluid shear stress that is driven by varying hydrostatic and osmotic pressure conditions, depending on the brain's pathophysiological conditions. Although all brain cells are sensitive to the subtle changes in various physicochemical factors in the microenvironment, microglia, the resident brain immune cells, exhibit the most significant morphodynamic transformation. However, little is known about the phenotypic alterations in microglia in response to changes in fluid shear stress. In this study, we established a flow-controlled microenvironment to investigate the effects of shear flow on microglial phenotypes, including morphology, motility, and activation states. We observed two distinct morphologies of microglia in a static condition: bipolar cells that oscillate along their long axis and unipolar cells that migrate persistently. When exposed to flow, a significant fraction of bipolar cells showed unstable oscillation with an increased amplitude of oscillation and a decreased frequency, which consequently led to the phenotypic transformation of oscillating cells into migrating cells. Furthermore, we observed that the level of proinflammatory genes increased in response to shear stress, although there were no significant changes in the level of antiinflammatory genes. Our findings suggest that an interstitial fluid-level stimulus can cause a dramatic phenotypic shift in microglia toward proinflammatory states, shedding light on the pathological outbreaks of severe brain diseases. Given that the fluidic environment in the brain can be locally disrupted in pathological circumstances, the mechanical stimulus by fluid flow should also be considered a crucial element in regulating the immune activities of the microglia in brain diseases.
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Encefalopatias , Microglia , Humanos , Microglia/patologia , Microglia/fisiologia , Encéfalo , Encefalopatias/patologia , Anti-InflamatóriosRESUMO
Interferometric scattering (iSCAT) microscopy has undergone significant development in recent years. It is a promising technique for imaging and tracking nanoscopic label-free objects with nanometer localization precision. The current iSCAT-based photometry technique allows quantitative estimation for the size of a nanoparticle by measuring iSCAT contrast and has been successfully applied to nano-objects smaller than the Rayleigh scattering limit. Here we provide an alternative method that overcomes such size limitations. We take into account the axial variation of iSCAT contrast and utilize a vectorial point spread function model to uncover the position of a scattering dipole and, consequently, the size of the scatterer, which is not limited to the Rayleigh limit. We found that our technique accurately measures the size of spherical dielectric nanoparticles in a purely optical and non-contact way. We also tested fluorescent nanodiamonds (fND) and obtained a reasonable estimate for the size of fND particles. Together with fluorescence measurement from fND, we observed a correlation between the fluorescent signal and the size of fND. Our results showed that the axial pattern of iSCAT contrast provides sufficient information for the size of spherical particles. Our method enables us to measure the size of nanoparticles from tens of nanometers and beyond the Rayleigh limit with nanometer precision, making a versatile all-optical nanometric technique.
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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.
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Aquaporinas , Neuromielite Óptica , Pessoa de Meia-Idade , Humanos , Feminino , Adulto , Masculino , Rituximab/uso terapêutico , Estudos Retrospectivos , Autoanticorpos , Aquaporina 4RESUMO
Cisplatin is one of the most potent anti-cancer drugs developed so far. Recent studies highlighted several intriguing roles of histones in cisplatin's anti-cancer effect. Thus, the effect of nucleosome formation should be considered to give a better account of the anti-cancer effect of cisplatin. Here we investigated this important issue via single-molecule measurements. Surprisingly, the reduced activity of cisplatin under [NaCl] = 180 mM, corresponding to the total concentration of cellular ionic species, is still sufficient to impair the integrity of a nucleosome by retaining its condensed structure firmly, even against severe mechanical and chemical disturbances. Our finding suggests that such cisplatin-induced fastening of chromatin can inhibit nucleosome remodelling required for normal biological functions. The in vitro chromatin transcription assay indeed revealed that the transcription activity was effectively suppressed in the presence of cisplatin. Our direct physical measurements on cisplatin-nucleosome adducts suggest that the formation of such adducts be the key to the anti-cancer effect by cisplatin.
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Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias/tratamento farmacológico , Histonas/metabolismo , Proteínas de Membrana/metabolismo , Nucleossomos/metabolismoRESUMO
BACKGROUND: Despite the promising results with selective thoracic fusion (STF) in patients with adolescent idiopathic scoliosis (AIS) of the Lenke 1C curve, postoperative coronal imbalance and progression of the unfused lumbar curve have been concerns in long-term follow-up. In this study, we aimed to investigate the radiographic and clinical outcomes after STF for AIS with Lenke 1C curve with long-term follow-up. METHODS: A total of 30 patients with AIS with Lenke 1C curves who underwent STF between 2005 and 2017 were included. Minimum follow-up duration was 5 years. Time-dependent changes in radiographic parameters were investigated preoperatively, immediately postoperatively, and at the last follow-up. In addition, radiographic adverse events such as coronal decompensation (CD), lumbar decompensation (LD), distal adding-on (DA) phenomenon, and trunk shift were evaluated at the last follow-up. The Scoliosis Research Society-22 score was used for clinical outcome evaluation. RESULTS: The mean age at the time of surgery was 13.8 years. The mean follow-up duration was 6.7 ± 0.8 years. The main thoracic curve significantly improved from 57 degrees to 23 degrees (60% correction), and the thoracolumbar/lumbar curve significantly improved from 47 degrees to 28 degrees (41% correction). Coronal balance was 15 mm after surgery but significantly improved to 10 mm at the last follow-up ( P = 0.033). At the final follow-up, 11 patients (37%) sustained at least one of the radiographic adverse events: CD in 5 patients (17%), LD in 3 (10%), DA in 4 (13%), and trunk shift in 3 (10.%). However, there were no cases requiring revision surgery. In addition, there were no significant differences in any items or total Scoliosis Research Society-22 score between the patients with and without radiographic adverse events. CONCLUSION: STF in Lenke 1C curves showed an acceptable risk of adverse radiographic events such as CD, LD, DA, and trunk shift in long-term follow-up. We suggest that STF without fusion to the thoracolumbar/lumbar curve would be sufficient in treating AIS with Lenke 1C curve. LEVEL OF EVIDENCE: Level III.
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Cifose , Escoliose , Fusão Vertebral , Humanos , Adolescente , Resultado do Tratamento , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Escoliose/etiologia , Fusão Vertebral/métodos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Radiografia , Cifose/etiologia , Estudos Retrospectivos , SeguimentosRESUMO
Cannabidiol (CBD) is a chemical obtained from Cannabis sativa; it has therapeutic effects on anxiety and cognition and anti-inflammatory properties. Although pharmacological applications of CBD in many types of tumors have recently been reported, the mechanism of action of CBD is not yet fully understood. In this study, we perform an mRNA-seq analysis to identify the target genes of CBD after determining the cytotoxic concentrations of CBD using an MTT assay. CBD treatment regulated the expression of genes related to DNA repair and cell division, with metallothionein (MT) family genes being identified as having highly increased expression levels induced by CBD. It was also found that the expression levels of MT family genes were decreased in colorectal cancer tissues compared to those in normal tissues, indicating that the downregulation of MT family genes might be highly associated with colorectal tumor progression. A qPCR experiment revealed that the expression levels of MT family genes were increased by CBD. Moreover, MT family genes were regulated by CBD or crude extract but not by other cannabinoids, suggesting that the expression of MT family genes was specifically induced by CBD. A synergistic effect between CBD and MT gene transfection or zinc ion treatment was found. In conclusion, MT family genes as novel target genes could synergistically increase the anticancer activity of CBD by regulating the zinc ions in human colorectal cancer cells.
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Canabidiol , Canabinoides , Cannabis , Neoplasias Colorretais , Humanos , Canabidiol/farmacologia , Metalotioneína/genética , Metalotioneína/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Cannabis/química , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genéticaRESUMO
The serum uric acid (SUA) level is an important determinant of gout, hypertension, metabolic syndrome, and cardiovascular disease. Although previous genome-wide studies have identified multiple genetic variants associated with SUA, most genetic analyses have focused on individuals with European ancestry; thus, understanding of the genetic architecture of SUA is currently limited for Asian populations. We conducted a genome-wide meta-analysis based on Korea Biobank data consistent with three cohorts; namely, the Korean Genome and Epidemiology Study (KoGES) Ansan and Ansung, KoGES Health Examinee, and KoGES Cardiovascular Disease Association studies. In total, 60,585 participants aged ≥40 years were included in the analysis of the three cohorts. We used logistic regression analyses to perform genome-wide association study (GWAS) adjustments for confounding variables. Subsequently, a meta-analysis was conducted by combining the analyses of the three GWASs. We identified 8,105 variants at 22 genetic loci with a P value < 5 × 10-8. Among these, six novel genetic loci associated with SUA in the Korean population were identified (rs4715517 in HCRTR2, rs145099458 in 3.2 kb 3' of MLXIPL, rs1137642 in B4GALT1, rs659107 in LOC105378410, rs7919329 in LOC107984274, and rs2240751 in MFSD12). Our meta-analysis provides insights into the genetic architecture of SUA in the Korean population. Further studies are warranted to replicate the study results and elucidate the specific role of these variants in SUA homeostasis.
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Estudo de Associação Genômica Ampla , Ácido Úrico , Adulto , Bancos de Espécimes Biológicos , Loci Gênicos , Estudo de Associação Genômica Ampla/métodos , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by the gradual loss of upper and lower motor neurons that leads to progressive muscle atrophy and weakness. Edaravone, a free-radical scavenger, was approved as an ALS treatment in 2015 in South Korea. METHODS: This study investigated the long-term effects and safety of edaravone by reviewing the medical records of 16 Korean patients with ALS who received extended edaravone between 2015 and 2021 in a single tertiary ALS center. RESULTS: Among sixteen patients, eleven patients underwent extended edaravone therapy for more than 18 cycles (72 weeks). The mean monthly changes in the revised ALS Functional Rating Scale (ALSFRS-R) were - 0.96 ± 0.83 (0-24 weeks), - 0.70 ± 0.76 (24-48 weeks), - 1.18 ± 1.67 (48-72 weeks), and - 0.81 ± 0.60 (0-72 weeks). The mean decline in forced vital capacity (FVC) was 17.4 ± 24.1. The changes were significant in both ALSFRS-R (p < 0.001) and FVC (p = 0.048); however, the mean change in compound muscle action potential of phrenic nerves was not. Patients experienced only minor adverse events, which were well tolerated. CONCLUSIONS: This study verifies previous reported outcomes of edaravone in 16 Korean ALS patients, indicating a modest effect with a favorable safety profile.
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Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Esclerose Lateral Amiotrófica/tratamento farmacológico , Antipirina/efeitos adversos , Método Duplo-Cego , Edaravone/uso terapêutico , Humanos , República da Coreia/epidemiologiaRESUMO
As the bioaccumulation of microplastics (MPs) is considered as a potential health risk, many efforts have been made to understand the cellular dynamics and cytotoxicity of MPs. Here, we demonstrate that label-free multicolor coherent anti-Stokes Raman scattering (CARS) microscopy enables separate vibrational imaging of internalized MPs and lipid droplets (LDs) with indistinguishable shapes and sizes in live cells. By simultaneously obtaining polystyrene (PS)- and lipid-specific CARS images at two very different frequencies, 1000 and 2850 cm-1, respectively, we successfully identify the local distribution of ingested PS beads and native LDs in Caenorhabditis elegans. We further show that the movements of PS beads and LDs in live cells can be separately tracked in real time, which allows us to characterize their individual intracellular dynamics. We thus anticipate that our multicolor CARS imaging method could be of great use to investigate the cellular transport and cytotoxicity of MPs without additional efforts for pre-labeling to MPs.
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Microplásticos , Microscopia , Animais , Caenorhabditis elegans , Lipídeos , Microscopia/métodos , Organelas , Plásticos , Poliestirenos , Análise Espectral Raman/métodosRESUMO
OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue. Our objective was to investigate the incidence of MG using the National Health Insurance database of South Korea. MATERIALS AND METHODS: We conducted a retrospective cohort analysis of patients with the G70.0 code designated as MG and administered with MG medications for >3 months from 2007 to 2018 using nationwide data from South Korea. RESULTS: A total of 8,376 patients with MG during the period of 2010-2018 were identified. There were 3,862 (46.1%) male and 4,517 (53.9%) female patients. The standardized incidence rate was 1.18/100,000 in 2010, and increased to 1.81/100,000 in 2018. The standardized prevalence was 7.50/100,000 in 2010, and changed to 11.15/100,000 in 2018. Pyridostigmine was used to treat 82.3 ± 1.2% of patients with MG during 2010-2018. Among MG patients, 85.7 ± 0.9% used steroids, 31.6 ± 4.8% used azathioprine, 12.9 ± 9.5% used tacrolimus, 7.2 ± 2.1% used cyclosporine, 6.2 ± 1.8% used mycophenolate mofetil, and 0.4 ± 0.1% used methotrexate. Thymectomy was performed in 1,130 MG patients, and the time from MG diagnosis to thymectomy decreased from 2010 to 2018. CONCLUSION: Based on the national registry data from 2010 to 2018, the incidence and prevalence rate in South Korea has increased. Whereas the use of IVIG has remained stable, thymectomy is performed earlier than before, and the distribution of immunosuppressant therapies has changed over the years with an increase in tacrolimus and mycophenolate mofetil. We expect that this study will serve as a basis for future South Korean MG epidemiological studies.
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Miastenia Gravis , Feminino , Humanos , Masculino , Programas Nacionais de Saúde , Brometo de Piridostigmina , Estudos Retrospectivos , TimectomiaRESUMO
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder caused by 27-hydroxylase deficiency. We report the clinical characteristics of six Korean CTX patients. The median age of onset was 22.5 years, the median age at diagnosis was 42 years, and the diagnostic delay was 18.1 years. The most common clinical symptoms were tendon xanthoma and spastic paraplegia. Four of five patients exhibited latent central conduction dysfunction. All patients carried the same mutation in CYP27A1 (c.1214 G>A [p.R405Q]). CTX is a treatable neurodegenerative disorder; however, our results revealed that patients with CTX in Korea might receive the diagnosis after a prolonged delay. .
Assuntos
Xantomatose Cerebrotendinosa , Adulto , Humanos , Adulto Jovem , Colestanotriol 26-Mono-Oxigenase/genética , Diagnóstico Tardio , Mutação , República da Coreia , Xantomatose Cerebrotendinosa/diagnóstico , Xantomatose Cerebrotendinosa/genética , Fenômenos EletrofisiológicosRESUMO
Methylene blue (MB) is a blue cationic thiazine dye and currently used in different medical settings. Notably, there have been several attempts to introduce MB for attenuating pain in the last decade. Some clinical studies reported remarkable results, which, however, have been much debated. In addition, accumulating evidence have revealed that MB diminishes voltage-gated sodium channel currents. Accordingly, in the present study, we conducted in vivo experiments, including in vivo single nerve recording and behavioral test, to investigate whether MB dampens neural firing rates and ultimately contributes to pain relief. As a result, neural firing rates significantly decreased and finally converged to zero after MB administration. This event lasted longer than that of lidocaine and was dose-dependently modulated. Furthermore, there was a marked improvement in pain behaviors. The withdrawal threshold and latency of hind paws significantly rose post-MB administration. Therefore, these results demonstrate that MB lessens pain by significantly weakening neural excitability, which implies a strong possibility that this dye may be developed as a pain-relieving medication in the future. This is the first in vivo study to elucidate the effect of MB on nerves and pain relief.