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The use of integrative Korean medicine treatment (IKMT) for patients with knee osteoarthritis (OA) has been reported previously; however, to date, no studies have investigated the long-term prognosis of these patients following IKMT for primary knee OA. We aimed to examine the long-term effects of IKMT in patients diagnosed with primary knee OA and receiving IKMT during hospitalization. This retrospective observational study, complemented by a follow-up survey, included patients with primary knee OA who received IKMT during hospitalization across 7 Korean medicine hospitals. The primary outcome was the Numerical Rating Scale knee-pain score, whereas the secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol-5 dimension-5 level questionnaire (EQ-5D-5L), and Patient Global Impression of Change scores. Patients were evaluated at admission, discharge, and during follow-up. Of the 180 included patients, 81 responded to the survey. Compared with the corresponding values at admission, the Numerical Rating Scale score decreased by 2.44 (2.08-2.81) points at discharge and 1.89 (1.5-2.26) points at follow-up. Additionally, compared with their scores at admission, the WOMAC score decreased by 17.20 (13.68-20.71) points at discharge and 25.74 (22.22-29.26) points at follow-up, whereas the EuroQol-5 dimension-5 level questionnaire score improved by -0.15 (-0.18 to -0.12) points at discharge and -0.12 (-0.15 to -0.09) points at follow-up. The patients expressed high satisfaction with pharmacopuncture (65.4%), acupuncture (54.03%), physical therapy (35.8%), and herbal medicine (34.6%). Regarding Patient Global Impression of Change, 96.30% of the patients reported improvement. IKMT was effective in improving pain, functional disability, and quality of life in patients with primary knee OA. Its effects were maintained throughout the long-term follow-up period, and physical functions continuously improved.
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Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , República da Coreia , Medicina Tradicional Coreana , Resultado do Tratamento , Medicina Integrativa/métodos , Medição da Dor , Qualidade de Vida , Pacientes Internados/estatística & dados numéricosRESUMO
BACKGROUND: Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well established, it remains unknown whether non-vitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. METHODS: A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10mg and 119 patients completed the entire study protocol. Twelve months after the assigned OAC treatment, follow-up CCTA was performed, and changes in plaque and calcium volumes of the coronary arteries were analyzed. RESULTS: Baseline characteristics of the two groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the two groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group, but the difference was not significant. CONCLUSION: In OAC-naïve, moderate-intensity statin treated patients with AF and atherosclerotic coronary lesions, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.
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PURPOSE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .
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Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.
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Esclerose Lateral Amiotrófica , Modelos Animais de Doenças , Eletromiografia , Dispositivos Eletrônicos Vestíveis , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Animais , Eletromiografia/métodos , Avaliação Pré-Clínica de Medicamentos , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Músculo Esquelético/inervação , Humanos , Masculino , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , RatosRESUMO
PURPOSE: As introduced, multimodal pain management bundle for ileostomy reversal may be considered to reduce postoperative pain and hospital stay. The aim of this study was to evaluate clinical efficacy of perioperative multimodal pain bundle for ileostomy. METHODS: Medical records of patients who underwent ileostomy reversal after rectal cancer surgery from April 2017 to March 2020 were analyzed. Sixty-seven patients received multimodal pain bundle protocol with ileostomy reversal (group A) and 41 patients underwent closure of ileostomy with conventional pain management (group B). RESULTS: Baseline characteristics, including age, sex, body mass index, American Society of Anesthesiologists classification, diabetes mellitus, and smoking history, were not significantly different between the groups. The pain score on postoperative day 1 was significant lower in group A (visual analog scale, 2.6 ± 1.3 vs. 3.2 ± 1.2; P = 0.013). Overall consumption of opioid in group A was significant less than group B (9.7 ± 9.5 vs. 21.2 ± 8.8, P < 0.001). Hospital stay was significantly shorter in group A (2.3 ± 1.5 days vs. 4.1 ± 1.5 days, P < 0.001). There were no significant differences between the groups in postoperative complication rate. CONCLUSION: Multimodal pain protocol for ileostomy reversal could reduce postoperative pain, usage of opioid and hospital stay compared to conventional pain management.
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The Hedgehog (Hh) signaling pathway plays important roles in various physiological functions. Several malignancies, such as basal cell carcinoma (BCC) and medulloblastoma (MB), have been linked to the aberrant activation of Hh signaling. Although therapeutic drugs have been developed to inhibit Hh pathway-dependent cancer growth, drug resistance remains a major obstacle in cancer treatment. Here, we show that the newly identified, 2-{3-[1-(benzylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone analog (LKD1214) exhibits comparable potency to vismodegib in suppressing the Hh pathway activation. LKD1214 represses Smoothened (SMO) activity by blocking its ciliary translocation. Interestingly, we also identified that it has a distinctive binding interface with SMO compared with other SMO-regulating chemicals. Notably, it maintains an inhibitory activity against the SmoD477H mutant, as observed in a patient with vismodegib-resistant BCC. Furthermore, LKD1214 inhibits tumor growth in the mouse model of MB. Collectively, these findings suggest that LKD1214 has the therapeutic potential to overcome drug-resistance in Hh-dependent cancers.
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Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non-invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives. Here, an all-in-one, multi-sensor integrated wearable system utilizing a set of nanomembrane soft sensors and electronics, enabling wireless, real-time, continuous monitoring of saliva osmolality, skin temperature, and heart functions is introduced. This system, using a soft patch and a sensor-integrated mouthguard, provides comprehensive monitoring of an athlete's hydration and physiological stress levels. A validation study in detecting real-time physiological levels shows the device's performance in capturing moments (400-500 s) of synchronized acute elevation in dehydration (350%) and physiological strain (175%) during field training sessions. Demonstration with a few human subjects highlights the system's capability to detect early signs of health abnormality, thus improving the healthcare of sports athletes.
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Background: Recurrent laryngeal nerve (RLN) paralysis following oesophagectomy may increase postoperative morbidity and mortality. However, clinical studies on this complication are uncommon. The aim of this study was to report the clinical course of patients with RLN paralysis following oesophageal cancer surgery. Methods: We retrospectively examined patients who underwent oesophagectomy for oesophageal carcinoma at Asan Medical Center between January 2013 and November 2018. We enrolled 189 patients with RLN paralysis confirmed using laryngoscopy in this study. Results: Of the 189 patients, 22 patients had bilateral RLN paralysis, and 167 patients had unilateral RLN paralysis. Every patient received oral feeding rehabilitation, and 145 (76.7%) patients received hyaluronic acid injection laryngoplasty. During the postoperative period, 21 (11.1%) patients experienced aspiration pneumonia and recovered. One patient died of severe pulmonary complication. Twenty-four (12.7%) patients underwent feeding jejunotomy, while 11 (5.9%) patients underwent tracheostomy. In total, 173 (91.5%) patients were discharged with oral nutrition, and the median time to begin oral diet was 9 days. Statistical analysis using logistic regression revealed that only the advanced T stage affected nerve recovery. More than 50% of the patients showed nerve recovery within 6 months, and 165 (87.9%) patients fully or partially recovered during the observation period. Conclusions: RLN paralysis following oesophagectomy in oesophageal carcinoma is a predictable complication. In patients with RLN paralysis, early detection and intervention through multidisciplinary cooperation are required, and the incidence of postoperative complications can be reduced by implementing the appropriate management.
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BACKGROUND: Effective bowel cleansing is essential for a successful colonoscopy. Laxatives, such as polyethylene glycol, are commonly used for bowel preparation. Vomiting is a frequent complication during bowel preparation, and forceful vomiting can potentially lead to esophageal perforation, as reported in several previous cases. However, pharyngeal perforation during bowel preparation has not been previously documented. Here, we present a case of pharyngeal perforation induced by forceful vomiting during bowel preparation. CASE SUMMARY: A 38-year-old man with a history of hypertension, dyslipidemia, diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for evaluation of recurrent abdominal pain. The patient complained of sudden pain in the neck, throat, and anterior chest following forceful vomiting during bowel preparation. Physical examination revealed crepitus under the skin of the neck and anterior chest on palpation, and upper gastrointestinal endoscopy revealed pharyngeal perforation. The perforation site was located above the upper esophageal sphincter, which distinguished it from Boerhaave's syndrome. Conservative medical management was chosen after consultation with a thoracic surgeon and an otolaryngologist, considering the patient's mild symptoms, stable vital signs, and the small size of the lesion; the perforation resolved without endoscopic or surgical intervention. The patient was discharged from hospital two weeks after the perforation. CONCLUSION: Despite its rarity, pharyngeal perforation should be considered a potential complication of bowel preparation for colonoscopy.
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Stable transgenesis is a transformative tool in model organism biology. While the sea urchin is one of the oldest animal models in cell and developmental biology, studies in this animal have largely relied on transient manipulation of wild animals, without a strategy for stable transgenesis. Here we build on recent progress to develop a more genetically tractable sea urchin species, Lytechinus pictus and establish a robust transgene integration method. Three commonly used transposons (Minos, Tol2, piggyBac) were tested for non-autonomous transposition, using plasmids containing a polyubiquitin promoter upstream of a H2B-mCerulean nuclear marker. Minos was the only transposable element that resulted in significant expression past metamorphosis. F0 animals were raised to sexual maturity and spawned to determine germline integration, transgene inheritance frequency, and to characterize expression patterns of the transgene in F1 progeny. The results demonstrated transgene transmission through the germline, the first example of a germline transgenic sea urchin, and indeed of any echinoderm. This milestone paves the way for the generation of diverse transgenic resources that will dramatically enhance the utility, reproducibility, and efficiency of sea urchin research.
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A woman in South Korea who underwent a colonoscopy for occasional gastrointestinal discomfort had 4 adult flukes of Echinostoma cinetorchis showing 37 collar spines around the oral sucker recovered from the terminal ileum through the ascending colon. Partial gene sequencing showed high identity with E. cinetorchis.
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Echinostoma , Equinostomíase , Animais , Echinostoma/genética , Echinostoma/isolamento & purificação , República da Coreia , Humanos , Feminino , Equinostomíase/diagnóstico , Equinostomíase/parasitologia , Equinostomíase/tratamento farmacológico , Pessoa de Meia-Idade , FilogeniaRESUMO
This retrospective, cross-sectional, and descriptive study aimed to analyze the trend of utilizing traditional Korean medicine services in patients with lumbar disc herniation (LDH) and/or lumbar spinal stenosis (LSS). In this study, based on the national patient sample data provided by Health Insurance Review and Assessment Service (HIRA), the trend of Korean medicine service utilization was investigated, including the following information: demographic characteristics of the patients, the total expenditure, number of claim statements per category, medical care expenditure per category, and routes of visiting traditional Korean medicine institutions. The study population comprised patients who visited Korean medicine institutions at least once from January 2010 to December 2019, with LSS and LDH as the primary diagnosis. LDH patients who used traditional Korean medicine services for treatment increased by about 1.36 times. LDH and LSS patients under 45 years of age were more likely to be males, but women accounted for a higher percentage among those over 45 years of age. Overall, women accounted for a slightly higher percentage than their counterparts for both diseases. From details of treatments received that were extracted from the claims data, acupuncture treatment accounted for the highest percentage for both disorders. Moreover, 50.7% of the patients who visited Korean medicine institutions to treat the two diseases also visited conventional Western medicine institutions. These patients, who were diagnosed with their condition at a Korean medicine institution, visited a conventional institution and then returned; the conventional institutions were primarily used for examination (40.5%). Increased utilization of traditional Korean medicine services was confirmed among patients with LDH and/or LSS; in particular, a sharp increase was noted among patients with LSS. The results of this study will be useful as basic research data for clinicians, researchers, and policy makers.
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Deslocamento do Disco Intervertebral , Medicina Tradicional Coreana , Estenose Espinal , Humanos , Deslocamento do Disco Intervertebral/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estenose Espinal/terapia , Estudos Retrospectivos , República da Coreia/epidemiologia , Estudos Transversais , Adulto , Idoso , Vértebras Lombares , Gastos em Saúde/estatística & dados numéricos , Gastos em Saúde/tendências , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Terapia por Acupuntura/estatística & dados numéricos , Adulto JovemRESUMO
Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Nanopartículas , Transportadores de Ânions Orgânicos Dependentes de Sódio , Rosuvastatina Cálcica , Simportadores , Animais , Nanopartículas/química , Transportadores de Ânions Orgânicos Dependentes de Sódio/antagonistas & inibidores , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Simportadores/antagonistas & inibidores , Simportadores/metabolismo , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Rosuvastatina Cálcica/administração & dosagem , Humanos , Camundongos Endogâmicos C57BL , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/química , Colesterol/química , Ratos Sprague-Dawley , CamundongosRESUMO
A pH-sensitive dye-based freshness indicator has been developed to monitor the quality status of pork neck through distinct color transitions, addressing a crucial need for improved food safety and real-time monitoring within the food industry. This system aims to boost consumer confidence and improve shelf-life estimates by offering transparent and immediate quality indicators. Aerobically packaged pork neck samples underwent accelerated testing at 25 °C for 36 h, followed by refrigeration experiments at typical distribution temperatures of 4 and 8 °C over 10 days. Measured pork neck quality parameters included total bacterial count (TBC), total volatile basic nitrogen (TVB-N), and pH levels. Visual observation and colorimetric analysis were used to assess the chromatic variations of the freshness indicator, which showed a significant shift from orange to green in response to the presence of TVB-N in the headspace of the pork packaging. The chromatic parameters of the freshness indicator exhibited a significant correlation with the pork quality values throughout the storage periods. The results highlight the ability of the freshness indicator to effectively convey quality information about pork through noticeable colorimetric changes.
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Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical-grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami-structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high-quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post-stroke patients captures the system's significance in measuring multiple physiological signals in real-time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non-invasive alternative for monitoring swallowing and aspiration events.
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Continuous monitoring of physiological signals from the human body is critical in health monitoring, disease diagnosis, and therapeutics. Despite the needs, the existing wearable medical devices rely on either bulky wired systems or battery-powered devices needing frequent recharging. Here, we introduce a wearable, self-powered, thermoelectric flexible system architecture for wireless portable monitoring of physiological signals without recharging batteries. This system harvests an exceptionally high open circuit voltage of 175-180 mV from the human body, powering the wireless wearable bioelectronics to detect electrophysiological signals on the skin continuously. The thermoelectric system shows long-term stability in performance for 7 days with stable power management. Integrating screen printing, laser micromachining, and soft packaging technologies enables a multilayered, soft, wearable device to be mounted on any body part. The demonstration of the self-sustainable wearable system for detecting electromyograms and electrocardiograms captures the potential of the platform technology to offer various opportunities for continuous monitoring of biosignals, remote health monitoring, and automated disease diagnosis.
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Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio , Humanos , Tecnologia sem Fio/instrumentação , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Fontes de Energia Elétrica , Eletrocardiografia/instrumentação , Eletromiografia/instrumentação , Desenho de EquipamentoRESUMO
A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.
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Antineoplásicos Fitogênicos , Fallopia multiflora , Mesotelioma Maligno , Raízes de Plantas , Estilbenos , Humanos , Estilbenos/farmacologia , Estilbenos/isolamento & purificação , Raízes de Plantas/química , Estrutura Molecular , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Mesotelioma Maligno/tratamento farmacológico , Fallopia multiflora/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Mesotelioma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , ChinaRESUMO
Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.
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Encéfalo , Encefalite por Herpes Simples , Herpesvirus Humano 1 , Proteínas de Membrana , Internalização do Vírus , Animais , Feminino , Humanos , Masculino , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/virologia , Encefalite por Herpes Simples/virologia , Encefalite por Herpes Simples/metabolismo , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 1/fisiologia , Homozigoto , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Nectinas/genética , Nectinas/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neurônios/virologia , Células-Tronco Pluripotentes/citologia , Replicação Viral , Pré-Escolar , Adulto Jovem , LinhagemRESUMO
Foot-and-mouth disease virus (FMDV) is a highly contagious virus that affects cloven-hoofed animals and causes severe economic losses in the livestock industry. Given that this high-risk pathogen has to be handled in a biosafety level (BSL)-3 facility for safety reasons and the limited availability of BSL-3 laboratories, experiments on FMDV call for more attention. Therefore, we aimed to develop an FMDV experimental model that can be handled in BSL-2 laboratories. The NanoBiT luciferase (Nano-luc) assay is a well-known assay for studying protein-protein interactions. To apply the NanoBiT split luciferase assay to the diagnosis and evaluation of FMD, we developed an inactivated HiBiT-tagged Asia1 Shamir FMDV (AS-HiBiT), a recombinant Asia1 shamir FMDV with HiBiT attached to the VP1 region of Asia1 shamir FMDV. In addition, we established LgBiT-expressing LF-BK cell lines, termed LgBit-LF-BK cells. It was confirmed that inactivated AS-HiBiT infected LgBiT-LF-BK cells and produced a luminescence signal by binding to the intracellular LgBiT of LgBiT-LF-BK cells. In addition, the luminescence signal became stronger as the number of LgBiT-LF-BK cells increased or the concentration of inactivated AS-HiBiT increased. Moreover, we confirmed that inactivated AS-HiBiT can detect seroconversion in sera positive for FMDV-neutralizing antibodies. This NanoBiT split luciferase assay system can be used for the diagnosis and evaluation of FMD and expanded to FMD-like virus models to facilitate the evaluation of FMDV vaccines and antibodies.