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Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.
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Histona Desacetilasas , Fibrosis Peritoneal , Animales , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/prevención & control , Fibrosis Peritoneal/patología , Ratones , Humanos , Masculino , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Diálisis Peritoneal/efectos adversos , Peritoneo/patología , Peritoneo/metabolismoRESUMEN
OBJECTIVE: To investigate superb microvascular imaging (SMI), a novel Doppler ultrasound technique that can visualize low-velocity microvascular flow, for assessing pediatric focal nodular hyperplasia (FNH). PATIENTS AND METHODS: Nine FNH lesions in 6 patients were enrolled. On SMI and color Doppler imaging (CDI), intralesional vascularity was assessed visually and categorized as typical spoke-wheel pattern (central vessel radiating from the center to the periphery), multifocal spoke-wheel pattern, and nonspecific pattern. We compared the vascular features of the lesions between SMI and CDI and evaluated vascular patterns according to lesion size. RESULTS: In terms of vascularity pattern, the typical spoke-wheel pattern of FNH was noted more frequently on SMI (67%) than on CDI (11%; P < 0.05). In addition, a multifocal spoke-wheel pattern was noted in all remaining lesions (33%) on SMI. On the contrary, a nonspecific vascular pattern was detected in the majority (78%) of CDI. Regarding the lesion size and vascularity on SMI, the typical spoke-wheel pattern was seen more frequently in the small FNH group than in the large FNH group. The intralesional vascular signal was detected more frequently on SMI (100%) than on CDI (89%). CONCLUSION: SMI is feasible in evaluating FNH in children and has a greater ability to demonstrate the spoke-wheel pattern than CDI.
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Hiperplasia Nodular Focal , Humanos , Niño , Hiperplasia Nodular Focal/diagnóstico por imagen , Hiperplasia Nodular Focal/patología , Medios de Contraste , Diagnóstico Diferencial , Ultrasonografía , Ultrasonografía Doppler en Color/métodosRESUMEN
BACKGROUND: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea. METHODS: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates. RESULTS: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years. CONCLUSION: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion.
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Oclusión de la Arteria Retiniana , Oclusión de la Vena Retiniana , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Incidencia , Oclusión de la Vena Retiniana/diagnóstico , Estudios de Cohortes , Oclusión de la Arteria Retiniana/diagnóstico , República de Corea/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Current methods for evaluating efficacy of cosmetics have limitations because they cannot accurately measure changes in the dermis. Skin sampling using microneedles allows identification of skin-type biomarkers, monitoring treatment for skin inflammatory diseases, and evaluating efficacy of anti-aging and anti-pigmentation products. MATERIALS AND METHODS: Two studies were conducted: First, 20 participants received anti-aging treatment; second, 20 participants received anti-pigmentation treatment. Non-invasive devices measured skin aging (using high-resolution 3D-imaging in the anti-aging study) or pigmentation (using spectrophotometry in the anti-pigmentation study) at weeks 0 and 4, and adverse skin reactions were monitored. Skin samples were collected with biocompatible microneedle patches. Changes in expression of biomarkers for skin aging and pigmentation were analyzed using qRT-PCR. RESULTS: No adverse events were reported. In the anti-aging study, after 4 weeks, skin roughness significantly improved in 17 out of 20 participants. qRT-PCR showed significantly increased expression of skin-aging related biomarkers: PINK1 in 16/20 participants, COL1A1 in 17/20 participants, and MSN in 16/20 participants. In the anti-pigmentation study, after 4 weeks, skin lightness significantly improved in 16/20 participants. qRT-PCR showed significantly increased expression of skin-pigmentation-related biomarkers: SOD1 in 15/20 participants and Vitamin D Receptor (VDR) in 15/20 participants. No significant change in TFAP2A was observed. CONCLUSION: Skin sampling and mRNA analysis for biomarkers provides a novel, objective, quantitative method for measuring changes in the dermis and evaluating the efficacy of cosmetics. This approach complements existing evaluation methods and has potential application in assessing the effectiveness of medical devices, medications, cosmeceuticals, healthy foods, and beauty devices.
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Cosméticos , Trastornos de la Pigmentación , Envejecimiento de la Piel , Humanos , Piel/diagnóstico por imagen , Pigmentación de la Piel , BiomarcadoresRESUMEN
BACKGROUND: Classifying diverse skin types is crucial for promoting skin health. However, efficiently identifying and analyzing relevant biomarkers from a vast array of available genetic data is challenging. Therefore, this study aimed to develop a precise and efficient platform for analyzing specific skin biomarkers using quantitative real-time PCR (qRT-PCR) with the minimal invasive skin sampling method (MISSM). MATERIALS AND METHODS: MISSM was used for RNA extraction from skin samples, followed by qRT-PCR analysis to quantify the expression of 20 biomarkers associated with skin characteristics (four biomarkers each for five skin characteristics). Noninvasive measurements from 299 Korean participants were utilized to correlate biomarker expression with skin parameters. Statistical analyses were conducted between biomarker expression levels and noninvasive skin measurements to select the relatively best-performing biomarker for each skin characteristic. RESULTS: Collagen type 1 alpha 1 (COL1A1) and moesin (MSN) were identified as skin aging biomarkers. Krüppel-like factor 4 (KLF4) and serine peptidase inhibitor Kazal type 5 (SPINK5) were identified as skin dryness biomarkers, whereas melan-A (MLANA) was selected as a biomarker for understanding pigmentation dynamics. Myelin protein zero like 3 (MPZL3) and high mobility group box 2 (HMGB2) were identified as markers of oily skin and skin sensitivity, respectively. Statistically significant correlations were found between the biomarker expression levels and noninvasive skin characteristic measurements. CONCLUSION: This study successfully developed a platform for the precise evaluation of individual skin characteristics using MISSM and qRT-PCR biomarker analysis. By selecting biomarkers that correlate with noninvasive measurements of skin characteristics, we demonstrated the platform's efficacy in assessing diverse skin conditions.
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Biomarcadores , Factor 4 Similar a Kruppel , Reacción en Cadena en Tiempo Real de la Polimerasa , Envejecimiento de la Piel , Piel , Humanos , Biomarcadores/metabolismo , Biomarcadores/análisis , Femenino , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Piel/metabolismo , Adulto , Persona de Mediana Edad , Envejecimiento de la Piel/genética , Envejecimiento de la Piel/fisiología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Anciano , Adulto JovenRESUMEN
Resistant hypertension is diagnosed in patients whose blood pressure target is unmet despite the use of three or more antihypertensive medications. Systemic sympathetic hyperactivation is associated with the development of resistant hypertension. As the kidney is largely pervasive of the sympathetic nervous system renal denervation procedure was developed to control blood pressure by attenuating the renal and systemic sympathetic hyperactivity. Renal denervation is a minimally invasive procedure that uses radiofrequency or ultrasound energy waves to reduce the activity of the renal artery nerves. Previous clinical trials have shown conflicting results regarding the efficacy of the procedure. Symplicity HTN-1 and -2 trials showed effective blood pressure lowering results in the renal denervation group with a good safety profile. However, the Symplicity HTN-3 trial showed no difference in blood pressure lowering effect between the renal denervation and control Sham procedure groups. Notwithstanding, some recent clinical trials with Sham control and meta-analysis showed clinical benefits of renal denervation. Other clinical benefits of renal denervation include glucose control, cardiovascular protective effect, reduction of obstructive sleep apnea, and neuralgia control. A subset of patients with satisfactory blood pressure control response to the procedure may experience improved glucose control due to the overall reduced sympathetic activity and insulin resistance. Sympathetic activity control after renal denervation has cardioprotective effects, especially for those with arrhythmia and left ventricular hypertrophy. Also, renal denervation could be helpful in renalorigin pain control. Renal denervation is an effective, safe, non-invasive procedure with many clinical benefits beyond blood pressure control. Further development in the procedure technique and selection of target patients are needed for wider clinical use of renal denervation in resistant hypertension.
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Prompt medical attention is crucial for congenital intracranial vascular malformations in children and newborns due to potential severe outcomes. Imaging is pivotal for accurate identification, given the diverse risks and treatment strategies. This article aims to enhance the identification and understanding of congenital intracranial vascular abnormalities including arteriovenous malformation, arteriovenous fistula, cavernous malformation, capillary telangiectasia, developmental venous anomaly, and sinus pericranii in pediatric patients.
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Malrotation and midgut volvulus are surgical emergencies that commonly occur within the first month of life. The classic symptom is acute bilious vomiting, while nonspecific symptoms such as recurrent abdominal pain may be present in older children. Malrotation can be associated with duodenal obstruction caused by an abnormal peritoneal fibrous band or congenital anomalies, such as an annular pancreas or a preduodenal portal vein. Volvulus can lead to bowel ischemia and a life-threatening condition, thus prompt and accurate diagnosis is crucial. Diagnosis can be made through upper gastrointestinal series, ultrasonography, and CT, with ultrasonography being preferred as a screening tool due to its rapid and accurate diagnosis, without radiation exposure, in children. This pictorial essay discusses the key imaging findings and diagnostic approaches for malrotation and midgut volvulus, as well as diagnostic pitfalls based on actual cases.
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PURPOSE: This study aimed to assess the alteration in keratinized mucosa (KM) dimensions in the early healing period after implant placement, and the influence of variables obtained during implant surgery on KM alteration. MATERIALS AND METHODS: Study participants were consecutively recruited from patients who had received implants following a non-submerged surgical protocol. The implant had to be installed in the extraction socket that had healed for more than 6 months without any soft or hard tissue augmentation. Keratinized mucosa width (KMW), keratinized mucosa thickness (KMT), soft tissue level (STL), and probing pocket depth (PPD) were measured at implant placement and 3 and 6 months after implant surgery. The influence of variables obtained during implant surgery on the 6-month KMW alteration was assessed. RESULTS: A total of 66 implants in 55 patients who completed the follow-up examination after 6 months were included in this study. KMW, KMT, and STL significantly decreased at 3- and 6-months examination by 0.7-1.2 mm. KMW was reduced by 24.6%. Mesial PPD significantly increased between the 3- and 6-months follow-up. In the multivariate generalized estimating estimations analysis, the implant diameter negatively influenced the 6-month KMW alteration, but the KMW at implant surgery positively influenced the 6-month KMW alteration. CONCLUSIONS: The KMW decreased significantly at 3 and 6 months after implant placement. If the initial KMW was wider, the KMW was reduced more at 6 months after implant placement. Therefore, it is important to carefully monitor KMW alterations during the early healing period to ensure optimal esthetics and peri-implant tissue health.
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Gallium-based liquid metals (GaLMs) are promising for a variety of applications-especially as a component material for soft devices-due to their fluidic nature, low toxicity and reactivity, and high electrical and thermal conductivity comparable to solid counterparts. Understanding the interfacial properties and behaviors of GaLMs in different environments is crucial for most applications. When exposed to air or water, GaLMs form a gallium oxide layer with nanoscale thickness. This "oxide nano-skin" passivates the metal surface and allows for the formation of stable microstructures and films despite the high-surface tension of liquid metal. The oxide skin easily adheres to most smooth surfaces. While it enables effective printing and patterning of the GaLMs, it can also make the metals challenging to handle because it adheres to most surfaces. The oxide also affects the interfacial electrical resistance of the metals. Its formation, thickness, and composition can be chemically or electrochemically controlled, altering the physical, chemical, and electrical properties of the metal interface. Without the oxide, GaLMs wet metallic surfaces but do not wet non-metallic substrates such as polymers. The topography of the underlying surface further influences the wetting characteristics of the metals. This review outlines the interfacial attributes of GaLMs in air, water, and other environments and discusses relevant applications based on interfacial engineering. The effect of surface topography on the wetting behaviors of the GaLMs is also discussed. Finally, we suggest important research topics for a better understanding of the GaLMs interface.
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MRI plays a crucial role in bone marrow (BM) assessment, and has very high sensitivity in diagnosing marrow disorders. However, for radiologists who may not frequently encounter pediatric imaging, distinguishing pathologic BM lesion from normal BM can be challenging. Conditions involving the BM in pediatric patients, such as leukemia and metastatic neuroblastoma, often manifest with diverse musculoskeletal symptoms and may be diagnosed using musculoskeletal MRI examinations. Accurate interpretation of pediatric MRI requires not only an understanding of the normal composition of BM but also an awareness of agerelated developmental changes in the marrow and familiarity with conditions that commonly involve pediatric BM. We aim to describe the composition of normal BM and outline the normal and abnormal MRI findings in pediatric BM. Additionally, we aim to present clinical cases of malignant BM disorders including leukemia, neuroblastoma metastasis, and other malignant BM disorders.
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Lentil is a leguminous crop with a high content of health-beneficial polyphenols. Lentil sprouts are popularly consumed in fresh vegetable markets, although their phytochemical qualities are not well understood. In this study, we investigated the accumulation of phenolics in lentil sprouts in response to photosynthetic and stress light qualities, including fluorescent light (FL), red LED (RL), blue LED (BL), ultraviolet A (UV-A), and ultraviolet B (UV-B). Three lentil cultivars, Lentil Green (LG), French Green (FG), and Lentil Red (LR), were used to evaluate sprouts grown under each light condition. The adequate light intensities for enhancing the antioxidant activity of lentil sprouts were found to be 11 W/m2 under photosynthetic lights (FL, RL, BL), and 1 W/m2 under stress lights (UV-A, UV-B). Subsequently, HPLC-ESI/Q-TOF MS analysis was conducted for the quantitative analysis of the individual phenolics that were accumulated in response to light quality. Four main phenolic compounds were identified: ferulic acid, tricetin, luteolin, and kaempferol. Notably, tricetin accumulation was significantly enhanced under BL across all three lentil cultivars examined. Furthermore, the study revealed that the other phenolic compounds were highly dependent on FL, BL, or UV-B exposure, exhibiting cultivar-specific variations. Additionally, the antioxidant activities of lentil extracts indicated that BL was most effective for LG and FG cultivars, whereas FL was most effective for enhancing antioxidant activity of LR cultivars as the sprouts grew.
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Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 109 particles/mL), and followed by UVB irradiation or H2O2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.
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Purpose: Recent advances in the treatment of breast cancer have led to the improvement of breast cancer patient's survival. With the prolonged survival of these patients, pregnancy became an important issue, especially in young cancer patient aged 35 years or under. Increased hormone levels during pregnancy, however, raise concerns about elevating the risk of cancer recurrence. The aim of this study was to validate the notion of increased risk associated with pregnancy after breast cancer treatment in young patients. Methods: From January 2009 to December 2020, newly diagnosed breast cancer patients 35 years old or under who underwent optimal surgery in Korea University Guro Hospital were enrolled in this study. Patients were categorized into 3 groups: nulliparous, pregnancy prior to treatment of breast cancer, and patients with pregnancy after breast cancer treatment. Their overall survival and disease-free survival were evaluated. Results: A total of 107 patients were enrolled in this study. Thirteen patients (12.1%) conceived and successfully delivered. The mean follow-up period after surgery was 58.9 (± 33.5) months. There was no significant difference in overall survival (P = 0.608) and disease-free survival (P = 0.591) among different groups. Conclusion: In young patients, pregnancy after treatment for breast cancer did not affect their overall survival or diseasefree survival as compared to nullipara or previously delivered groups. Therefore, pregnancy counseling should not be prevented in young breast cancer patients 35 years old or under.
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Research on tooth regeneration using human-induced pluripotent stem cells (hiPSCs) is valuable for autologous dental regeneration. Acquiring mesenchymal and epithelial cells as a resource for dental regeneration is necessary because mesenchymal-epithelial interactions play an essential role in dental development. We reported the establishment of hiPSCs-derived dental epithelial-like cell (EPI-iPSCs), but hiPSCs-derived dental mesenchymal stem cells (MSCs) have not yet been reported. This study was conducted to establish hiPSCs-derived MSCs and to differentiate them into dental cells with EPI-iPSCs. Considering that dental MSCs are derived from the neural crest, hiPSCs were induced to differentiate into MSCs through neural crest formation to acquire the properties of dental MSCs. To differentiate hiPSCs into MSCs through neural crest formation, established hiPSCs were cultured and differentiated with PA6 stromal cells and differentiated hiPSCs formed neurospheres on ultralow-attachment plates. Neurospheres were differentiated into MSCs in serum-supplemented medium. Neural crest-mediated MSCs (NC-MSCs) continuously showed typical MSC morphology and expressed MSC markers. After 8 days of odontogenic induction, the expression levels of odontogenic/mineralization-related genes and dentin sialophosphoprotein (DSPP) proteins were increased in the NC-MSCs alone group in the absence of coculturing with dental epithelial cells. The NC-MSCs and EPI-iPSCs coculture groups showed high expression levels of amelogenesis/odontogenic/mineralization-related genes and DSPP proteins. Furthermore, the NC-MSCs and EPI-iPSCs coculture group yielded calcium deposits earlier than the NC-MSCs alone group. These results indicated that established NC-MSCs from hiPSCs have dental differentiation capacity with dental epithelial cells. In addition, it was confirmed that hiPSCs-derived dental stem cells could be a novel cell source for autologous dental regeneration.
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Células Madre Pluripotentes Inducidas , Células Madre Mesenquimatosas , Humanos , Diferenciación Celular , Transición Epitelial-Mesenquimal , Técnicas de Cocultivo , Células CultivadasRESUMEN
Apart from being utilized as a commercial fiber at maturity, kenaf shoots have potential as a food and feed source because of their diverse bioactivities. Previous studies have focused on mature stems because of their high biomass, whereas the antioxidant activities (AA) and the destination of AA contributors of kenaf stems and their high-yielding byproduct leaves during the growth stage have rarely been studied. Therefore, we investigated changes in AA and its relative components in kenaf leaves and stems during the four vital growth stages. Higher ABTS radical cation and DPPH radical scavenging abilities and ferric reducing antioxidant power, total phenolic content, total flavonoid content, and total polysaccharide content were observed at all leaf stages and in the late stem stages. Chlorogenic acid (CGA) and kaempferol glycosides, especially kaempferitrin (Kfr), were identified as representative phenolic acids and flavonoids in both kenaf leaves and stems. The content of CGA in both leaves and stems increased corresponding to the plant's growth stage, whereas kaempferol glycosides were enhanced in leaves but declined in stems. The highest correlation was observed between TPC and AA in all organs. Further evaluation of CGA and Kfr verified that CGA was the predominant contributor to AA, surpassing Kfr. These findings suggest that kenaf leaves increase antioxidant levels as they grow and can be a useful source of stem harvesting byproducts.
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BACKGROUND: Chronic stroke can impair cardiopulmonary function, mobility, and daily activities. This study assessed the impact of robot-assisted gait training (RAGT) on such impairments. OBJECTIVE: To investigate the effects of robot-assisted gait training on cardiopulmonary function, walking ability, lower extremity function and strength, activities of daily living (ADLs), and blood test results among individuals with chronic stroke. METHODS: A multicenter, prospective, single-blinded, randomized controlled trial with 22 chronic stroke participants compared RAGT against a control exercise regimen. RAGT involved three days weekly sessions of high-intensity interval training for 8 weeks (24 sessions) with a Morning Walk® device. The control group also performed home exercises. (24 sessions) Measures included VO2max, Functional Ambulatory Category, 2-minute walk test, 10-meter walk test, Motricity Index-Lower, Korean version of the Fugl-Meyer Assessment Scale, Modified Barthel Index, Berg Balance Scale, muscle strength, InBody body composition, and blood tests (cholesterol, lipid, glucose). RESULTS: RAGT significantly improved VO2max, gait, balance, and lower limb strength compared with controls, with significant improvements in 2-minute walk test, 10-meter walk test, Motricity Index-Lower, and Fugl-Meyer Assessment outcomes. No changes were seen in muscle mass or blood markers. CONCLUSION: RAGT enhances cardiopulmonary function and ambulatory capacity in chronic stroke patients, underscoring its potential in stroke rehabilitation.
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Effect of puffing on conversion of gingerols to shogaols, physicochemical properties as well as antioxidant and anti-inflammatory activities of puffed ginger was investigated. Puffing significantly increased extraction yield and the highest value was 12.52% at 980 kPa. The significant decrease in gingerols and increase in shogaols were occurred after puffing, respectively. Especially, 6-shogaol was dramatically increased from 4.84 to 99.10 mg/g dried ginger. Puffed ginger exhibited the higher antioxidant activities (analyzed by DPPH, ABTS, TPC, and TFC) than those of control, and they were significantly increased with increasing puffing pressure. In case of anti-inflammatory activity, puffed ginger did not inhibit NO production, but significantly inhibited TNF-α and IL-6 productions. Among gingerols and shogaols, 6-shogaol showed significantly strong correlations with both antioxidant and anti-inflammatory activities. Consequently, puffed ginger can be applied to functional food industry, which dramatically increased the contents of 6, 8, 10-shogaols, the main bioactive compounds in ginger.
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Antiinflamatorios , Antioxidantes , Catecoles , Alcoholes Grasos , Extractos Vegetales , Zingiber officinale , Zingiber officinale/química , Catecoles/química , Catecoles/análisis , Antioxidantes/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Alcoholes Grasos/química , Alcoholes Grasos/análisis , Alcoholes Grasos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , RatonesRESUMEN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it kills cancer cells while sparing normal cells. However, many cancers, including pancreatic ductal adenocarcinoma (PDAC), exhibit intrinsic or acquired resistance to TRAIL, and the molecular mechanisms underlying TRAIL resistance in cancers, particularly in PDAC, remain unclear. In this study, we demonstrated that glutamine (Gln) endows PDAC cells with resistance to TRAIL through KDM4C-mediated epigenetic regulation of cFLIP. Inhibition of glutaminolysis significantly reduced the cFLIP level, leading to TRAIL-mediated formation of death-inducing signaling complexes. Overexpression of cFLIP dramatically rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Alpha-Ketoglutarate (aKG) supplementation significantly reversed the decrease in the cFLIP level induced by glutaminolysis inhibition and rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Knockdown of glutamic-oxaloacetic transaminase 2, which facilitates the conversion of oxaloacetate and glutamate into aspartate and aKG, decreased aKG production and the cFLIP level and activated TRAIL-induced apoptosis. AKG-mediated epigenetic regulation was necessary for maintaining a high level of cFLIP. Glutaminolysis inhibition increased the abundance of H3K9me3 in the cFLIP promoter, indicating that Gln-derived aKG production is important for Jumonji-domain histone demethylase (JHDM)-mediated cFLIP regulation. The JHDM KDM4C regulated cFLIP expression by binding to its promoter, and KDM4C knockdown sensitized PDAC cells to TRAIL-induced apoptosis. The present findings suggest that Gln-derived aKG production is required for KDM4C-mediated epigenetic regulation of cFLIP, which leads to resistance to TRAIL.
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Apoptosis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Resistencia a Antineoplásicos , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Glutamina , Histona Demetilasas con Dominio de Jumonji , Neoplasias Pancreáticas , Ligando Inductor de Apoptosis Relacionado con TNF , Humanos , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Glutamina/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Resistencia a Antineoplásicos/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ácidos Cetoglutáricos/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Aspartato Aminotransferasa Citoplasmática/metabolismo , Aspartato Aminotransferasa Citoplasmática/genética , Animales , Regiones Promotoras GenéticasRESUMEN
This study aimed to elucidate the effect of hatching status on in vitro fertilization (IVF) outcomes in frozen-thawed blastocyst transfer cycles. Frozen-thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6,821 frozen-thawed blastocyst transfers in women aged 24-47 years. For optimal comparability, double embryo transfer (ET) cycles consisting of one hatching and one hatched blastocyst were excluded. The implantation and pregnancy rates were evaluated and compared between the hatching and hatched blastocyst transfer groups based on patients' age (<38 vs. ≥38 years), blastocyst grade (good vs. bad grade), and the number of transferred embryos (single ET vs. double ET). Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the single ET group (15.7% and 15.6%, respectively; p<0.001). The transfer of two hatched blastocysts had higher implantation and clinical pregnancy rates compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p<0.001) in the double ET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of each woman's age and embryo quality. The IVF treatment outcomes were improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles could be considered a superior method in IVF practice.