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While numerous types of chemical cosmetic cleansers have been presented, those with sensitive skin may still experience some irritation while using them. Moreover, the environmental issue of chemical agents has been documented repeatedly. To address these, we suggest the potential application of a micro-sized bubble-laden water jet to cleanse the cosmetics without (or less) using chemical detergents. We devised a venturi-type nozzle with a mesh and air holes capable of generating massive fine bubbles. By testing with the foundation and lip tint (known to be highly adhesive) coated on the synthetic leather and artificial skin surfaces, we measured that the cleansing performance of the bubbly jet is much better (even without the chemical agent) than the single-phase liquid jet. As a mechanism for enhanced removal, it is understood that the greater kinetic energy of the jet due to the acceleration of the effective liquid-air mixture flow and the direct bubble-cosmetic collisions play essential roles. We believe that the present results will spur the development of environment-friendly cleaning methods.
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BACKGROUND: Orthostatic hypotension (OH) is prevalent among community-dwelling older adults and is associated with multiple negative health outcomes. Older adults are susceptible to developing OH because aging alters autonomic nervous system function. Biofeedback is a noninvasive, nonpharmacological intervention that can modulate autonomic nervous system dysfunction in older adults. OBJECTIVES: Our aim in this study was to examine the effect of a biofeedback-based integrated program on community-dwelling older adults with OH. METHODS: We conducted a controlled pilot study. Community-dwelling older adults 65 years or older who had nonneurogenic OH were eligible. Data from 51 participants, comprising 27 in the intervention group and 24 in the control group, were analyzed. Weekly biofeedback-based integrated program consisting of biofeedback training along with group education about behavioral modification, physical activities, and telephone counseling was provided for 12 weeks. Orthostatic hypotension was evaluated by measuring the drop in systolic and diastolic blood pressure after postural changes. Autonomic nervous system function was measured using heart rate variability. RESULTS: Among the indicators of heart rate variability, total power (P = .037) and low frequency (P = .017) increased significantly, suggesting that autonomic function improved. Severity of orthostatic symptoms (P < .001) and drops in systolic (P = .003) and diastolic (P = .012) blood pressure after postural changes decreased significantly in the intervention group. CONCLUSION: Biofeedback-based integrated program was effective in improving autonomic nervous system function and alleviated OH. Therefore, biofeedback-based integrated program should be tested in a larger randomized controlled study with long-term follow-up.
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Objectives: The purpose of this study was to compare the effects of mothers' and Mozart's lullabies on physiological parameters, feeding volume, and body weight of premature infants in a neonatal intensive care unit (NICU). Methods: This study used a non-equivalent control group, non-synchronized design as a quasi-experimental study. Two intervention groups (recorded mother's lullaby and Mozart's lullaby) and a control group were formed from a total of 65 premature infants: a mother's lullaby group of 22 infants, a Mozart's lullaby group of 22 infants, and a control group of 21 infants not provided with any lullabies. Their physiological parameters included heart rate, blood pressure, respiratory rate, and O2 saturation. The infants' feeding volume and body weight were measured as indicators related to the growth of premature infants. The mother's and Mozart's lullabies were played on a speaker in an incubator for 15 min for 7 consecutive days per group. Results: There were significant differences in the mean difference before and after intervention in neonatal heart rate (χ2 = 45.03, P < 0.001), systolic pressure (F = 43.29, P < 0.001), diastolic pressure (χ2 = 33.01, P < 0.001), respiratory rate (F = 76.06, P < 0.001), and O2 saturation (χ2 = 40.82, P < 0.001) between the three groups. The mean differences of both mother's and Mozart's lullaby groups were significantly higher than those of the routine care group in all physiological parameters, and those of the mother's lullaby group was significantly higher when compared with the Mozart's lullaby group. In repeated-measures ANOVA, there was a significant interaction between time and group in feeding volume (F = 2.46, P = 0.041). However, body weight did not significantly differ in an interaction between time and group (F = 1.75, P = 0.151). Conclusion: This study showed beneficial effects of mother's lullaby and Mozart's lullaby on physiological parameters. Especially, the mother's lullaby was found to significantly improve all physiological parameters and feeding volume of premature infants in the NICU compared to Mozart's lullaby group. Therefore, we recommend the regular integration of the mother's lullaby into supportive care of premature infants in the NICU, as this intervention highlights the need for mothers to participate in their care. Trial Registration: ClinicalTrials.gov, identifier: KCT0004842 (https://cris.nih.go.kr).
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Unidades de Cuidado Intensivo Neonatal , Madres , Peso Corporal , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido PrematuroRESUMEN
OBJECTIVE: The purpose of this study was to assess health-related quality of life (HRQoL) in Korean patients with cervical cancer according to the duration of treatment and cancer progression of cervical cancer. METHODS: This study included 452 outpatients with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer from six tertiary hospitals in South Korea. The questionnaire included the EQ-5D-3L instrument, patients' age, cancer progression (CIN or invasive cervical cancer), treatment duration (<1 year, ≥1 year but <2 years, and ≥2 years), treatment method (surgery, chemotherapy, radiation therapy), and presence of recurrence. HRQoL indices were calculated for these independent factors, and the mean was compared using ANOVA. Multiple regression analysis was performed to analyze factors affecting HRQoL in patients with cervical cancer. RESULTS: The EQ-5D index was 0.93 for patients with CIN, 0.87 for patients with invasive cervical cancer, and 0.78 for patients with recurrent invasive cervical cancer. HRQoL was significantly lower as the CIN progresses to cervical cancer. HRQoL of patients with invasive cervical cancer was lowest within 1 year of treatment in all stages. In addition, the HRQoL of patients with CIN or invasive cervical cancer who received chemotherapy and radiotherapy was lower than that of patients who underwent surgery. Multiple regression analysis showed that the HRQoL decreased significantly as increasing age, the first year of treatment after diagnosis, cancer recurrence, or chemotherapy. CONCLUSION: The HRQoL of patients with cervical cancer is affected not only by the stage of cancer progression but also by the duration of treatment and the type of treatment. As a result, when trying to apply the quality of life of patients with cervical cancer to cost-utility analysis, it is necessary to consider the duration and the type of treatment they receive.
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Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Duración de la Terapia , Femenino , Humanos , Recurrencia Local de Neoplasia/terapia , Calidad de Vida , Neoplasias del Cuello Uterino/terapiaRESUMEN
It has been frequently emphasized that highly contagious respiratory disease pathogens (such as SARS-CoV-2) are transmitted to the other hosts in the form of micro-sized aerosols (< 5 µm) in the air without physical contacts. Hospital environments such as negative-pressure unit are considered being consistently exposed to pathogens, so it is essential to quickly discharge them through the effective ventilation system. To achieve that, in the present study, we propose the optimized ventilation mechanism and design for the fastest removal of pathogen-laden aerosol using numerical simulations. We quantitatively evaluated the aerosol removal performance of various ventilation configurations (combinations of air exhaust and supply ducts), and found that the key mechanism is to form the coherent (preferentially upward) airflow structure to surround the respiratory flow containing the aerosol cluster. We believe that the present findings will play a critical role in developing the high-efficiency negative-pressure facility irrespective of its size and environments.
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Filtros de Aire , COVID-19 , Aerosoles , Humanos , SARS-CoV-2 , VentilaciónRESUMEN
A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard treatment for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and it has improved the outcomes of chemotherapy. Maintenance treatment with anti-PD-1 antibody (aPD-1) enhances the effect of immunochemical combination therapy and improves therapeutic efficacy, which contributes toward a significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), which is expressed in tumor cells, plays an essential role in the resistance of cancers to chemotherapy and immunotherapy, and stimulates signaling associated with epithelial-mesenchymal transition (EMT) in metastatic cancer. AXL is thus an attractive target for controlling resistance to anti-tumor therapies. In this study, we examined the effect of AXL inhibitors on immune activation and tumor growth in TC1 and C3PQ mouse tumor models, in the context of clinical immunotherapy/chemotherapy and maintenance treatment, using an aPD-1 with/without pemetrexed. To determine the optimal timing for administration of SKI-G-801, an AXL inhibitor, we investigated its anti-tumor effects based on inclusion at the immunochemotherapy and maintenance therapy stages. We also performed flow cytometry-based immune profiling of myeloid cells and lymphoid cells at different points in the treatment schedule, to investigate the immune activation and anti-tumor effects of the AXL inhibitor. The addition of SKI-G-801 to the immune checkpoint inhibitor and chemotherapy stage, as well as the maintenance therapy stage, produced the best anti-tumor results, and significant tumor growth inhibition was observed in both the TC1 and C3PQ models. Both models also exhibited increased proportion of effector memory helper T cells and increased expression of CD86+ macrophages. Especially, regulatory T cells were significantly reduced in the TC1 tumor model and there was an increase in central memory cytotoxic T cell infiltration and an increased proportion of macrophages with high CD80 expression in the C3PQ tumor model. These results suggest increased infiltration of T cells, consistent with previous studies using AXL inhibitors. It is expected that the results from this study will serve as a stepping stone for clinical research to improve the existing standard of care.
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In today's era of active personal protections against airborne respiratory disease, general interest in the multiphase flow physics underlying face masks is greater than ever. The exhalation valves, installed on some masks to mitigate the breathing resistance, have also received more attention. However, the current certification protocol of evaluating airflow leakage only when suction pressure is applied is insufficient to capture practical aspects (particle penetration or leakage). Here, we experimentally measure two-phase flow across valve-type masks under conditions mimicking actual breathing. During exhalation, a high-speed jet through the valve accelerates the transmission of particles from inside while reasonable protection from external pollutants is achieved during inhalation, which supports the warnings from various public health officials. Based on the mechanism of particle penetration found here, we hope a novel design that both achieves high-efficiency shielding and facilitates easy breathing can be developed.
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This study analyses the biogenic amines (BAs) formed in mackerel cooked by various methods and conditions. Five BAs, including tryptamine, ß-phenylethylamine, putrescine, histamine, and spermidine, were analysed by high-performance liquid chromatography with UV detection. The level of total BAs was higher in the mackerel fillet (108.14 µg/g) than the headed and gutted fish (91.58 µg/g). Roasted, fried, and stewed mackerel recorded total BA concentrations of 54.28, 82.25, and 163.05 µg/g, respectively. Stewed mackerel contained about 3-fold more BAs than roasted mackerel. The level of total BAs in mackerel increased significantly up to 190%, 236% and 152% as the roasting temperature increased, upon frying, and as stewing temperature increased, respectively (p < 0.05).
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Crizotinib is used in the clinic for treating patients with ALK- or ROS1-positive non-small-cell lung carcinoma. The objective of the present study was to determine if crizotinib enantiomers could induce changes to the properties of cancer and cancer stem cell (CSC)-like cells at a high concentration (â¼ 3 µM). While (R)-crizotinib induced changes in morphologies or sizes of cells, (S)-crizotinib did not. Pretreatment with (R)-crizotinib suppressed the proliferation of cancer or CSC-like cells in vitro and tumor growth in vivo. In vivo administration of (R)-crizotinib inhibited the growth of tumors formed from CSC-like cells by 72%. %. Along with the morphological changes induced by (R)-crizotinib, the expression levels of CD44 (NCI-H23 and HCT-15), ALDH1 (NCI-H460), nanog (PC-3), and Oct-4A (CSC-like cells), which appear to be specific marker proteins, were greatly changed, suggesting that changes in cellular properties accompanied the morphological changes in the cells. The expression levels of Snail, Slug, and E-cadherin were also greatly altered by (R)-crizotinib. Among several signal transduction molecules examined, AMPK phosphorylation appeared to be selectively inhibited by (R)-crizotinib. BML-275 (an AMPK inhibitor) and AMPKα2 siRNA efficiently induced morphological changes to all types of cells examined, suggesting that (R)-crizotinib might cause losses of characteristics of cancer or CSCs via inhibition of AMPK. These results indicate that (R)-crizotinib might be an effective anticancer agent that can cause alteration in cancer cell properties.
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Proteínas Quinasas Activadas por AMPRESUMEN
Volatile compounds of coffee brewed under various roasting conditions and by different brewing methods were analyzed. Green coffee beans (Coffea arabica) were roasted at 235 °C for 13 min, 240 °C for 15 min, and 245 °C for 17 min. Roasted coffee beans were ground into particles of three different sizes (710, 500, and 355 µm) and brewed by an espresso coffee machine and the cold brew method. Three types of water (filtered, tap, and bottled) were used for coffee extraction. SPME-GC-MS results indicated that increasing the roasting temperature and time increased the levels of 2,2'-methylene-bis-furan, guaiacol, and 4-ethylguaiacol (p < 0.05) and decreased the levels of furfural (p < 0.05). Grind size was inversely proportional to the measured signal of volatiles by GC-MS (p < 0.05). The measured GC/MS intensities of 2-methylpyrazine, 2,5-dimethylpyrazine, and 2-methoxy-4-vinylphenol were significantly higher in coffee brewed with filtered water (p < 0.05) than tap and bottled water. 2-Methylpyrazine, 1-methylpyrrole, and 2-acetylfuran were the most abundant components in the cold brew. Overall, roasting conditions and extraction methods were determined to be significant factors for volatile compounds in coffee. This is the first study showing the analysis of volatile compounds in coffee according to various types of water and extraction methods, such as espresso and cold brew coffee.
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PURPOSE: To investigate the association of orthostatic hypotension (OH) with health-related quality of life (HRQoL) in older people living in the community. METHODS: A cross-sectional design was used. A total of 217 participants aged 65 and older were classified as having OH if their systolic or diastolic blood pressure showed a drop of ≥ 20 mmHg systolic blood pressure or ≥ 10 mmHg diastolic blood pressure, respectively, within 3 min of standing. Participants provided demographic and medical information and responded to questionnaires about their HRQoL (EuroQoL-5D-3L), as well as depression, anxiety, cognitive function, and recent physical activities. RESULTS: The number of participants with OH was 117, and those without OH numbered 100. The mean HRQoL levels were 0.56 (SD 0.29) in the OH group and 0.74 (SD 0.25) in the non-OH group (p < .001). Participants with OH were more likely to be older, women, and smokers. These participants had fewer years of education, a greater history of stroke and hypertension, and a greater number of comorbidities. The absence of OH, a higher physical activity level, a lower degree of depression, an absence of stroke history, and younger age were all significant determinants of greater HRQoL. CONCLUSIONS: The level of HRQoL of older people with OH was significantly lower than that of older people without. The presence of OH was an independent determinant of HRQoL in older adults after adjusting for covariates. This finding suggests that strategies for relieving OH could improve HRQoL in affected older adults.
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Hipotensión Ortostática/psicología , Calidad de Vida/psicología , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , República de CoreaRESUMEN
BACKGROUND: The prevalence of overactive bladder syndrome (OAB) increases with age. Sleep disturbances in elderly individuals with OAB is a common problem. The purpose of this study was to examine the effects of a biofeedback-based sleep improvement (BBSI) program on urinary symptoms and sleep patterns in elderly Korean women with OAB. METHODS: A non-equivalent control group pre-/post-test design was used. Elderly women with OAB were assigned to an intervention group (n = 20) or a control group (n = 18). The BBSI program was implemented in the intervention group for 12 weeks, while two educational sessions of general sleep hygiene and lifestyle modification were provided to the control group. Using SPSS 23.0, the data were analyzed by descriptive analysis using the chi-square test, Fisher's exact test, Mann-Whitney test, and Wilcoxon test. RESULTS: After the 12-week BBSI program, significant improvements were found in the intervention group's the square root of the mean squared differences of successive R-R intervals (p = 0.025), low frequency/high frequency ratio (p = 0.006), and epinephrine (p = 0.039). We also observed a significant difference in urinary symptoms, sleep efficiency, wake after sleep onset, number of awakenings, and number of awakenings within 3 h after sleep onset (p < 0.001, p = 0.004, p = 0.001, p = 0.001, and p = 0.048, respectively). However, no significant changes were found in these variables in the control group. CONCLUSIONS: The BBSI program effectively improved urinary symptoms and sleep patterns of elderly Korean women with OAB. Further longitudinal research is required to investigate the sustainability and effects of the BBSI program. TRIAL REGISTRATION: KCT0003882. Date of registration: 02/05/2019. Retrospectively registered.
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Biorretroalimentación Psicológica , Trastornos del Sueño-Vigilia/terapia , Vejiga Urinaria Hiperactiva/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , República de Corea , Trastornos del Sueño-Vigilia/etiología , Vejiga Urinaria Hiperactiva/complicacionesRESUMEN
Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.
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Proteína C-Reactiva/metabolismo , Diferenciación Celular , Movimiento Celular , Odontogénesis/fisiología , Osteogénesis/fisiología , Componente Amiloide P Sérico/metabolismo , Proteína C-Reactiva/genética , Pulpa Dental/crecimiento & desarrollo , Pulpa Dental/fisiología , Técnicas de Silenciamiento del Gen , Humanos , Receptores CXCR4/metabolismo , Componente Amiloide P Sérico/genética , Células Madre/fisiologíaRESUMEN
BACKGROUND: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer. MATERIALS AND METHODS: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects. RESULTS: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score-matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer. CONCLUSIONS: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.
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Antagonistas de Andrógenos/uso terapéutico , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/efectos adversos , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Pronóstico , Modelos de Riesgos Proporcionales , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The objective of this study was to determine whether PC-3 human prostate cancer cell-derived cancer stem cells (CSC)-like cells grown in a regular cell culture plate not coated with a matrix molecule might be useful for finding differentiation-inducing agents that could alter properties of prostate CSC. METHODS: Monolayer cells prepared from sphere culture of PC-3 cells were characterized for the presence of pluripotency and tumorigenicity. They were then applied to screen a compound library to find compounds that could induce morphology changes of cells. Mechanisms of action of compounds selected from the chemical library that induced the loss of pluripotency of cells were also investigated. RESULTS: C5A cells prepared from PC-3 cell-derived sphere culture expressed pluripotency markers such as Oct4, Sox2, and Klf4. C5A cells were highly proliferative. They were invasive in vitro and tumorigenic in vivo. Some dopamine receptor antagonists such as thioridazine caused reduction of pluripotency markers and tumorigenicity. Thioridazine, unlike promazine, inhibited phosphorylation of AMPK in a dose dependent manner. BML-275, an AMPK inhibitor, also induced differentiation of C5A cells as seen with thioridazine whereas A769663, an AMPK activator, blocked its differentiation-inducing ability. Transfection of C5A cells with siRNAs of dopamine receptor subtypes revealed that knockdown of DRD2 or DRD4 induced morphology changes of C5A cells. CONCLUSIONS: Some dopamine receptor antagonists such as thioridazine can induce differentiation of CSC-like cells by inhibiting phosphorylation of AMPK. Binding to DRD2 or DRD4 might have mediated the action of thioridazine involved in the differentiation of CSC-like cells.
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Diferenciación Celular/efectos de los fármacos , Antagonistas de Dopamina/farmacología , Células Madre Neoplásicas/fisiología , Células PC-3/efectos de los fármacos , Próstata/fisiopatología , Neoplasias de la Próstata/fisiopatología , Animales , Diferenciación Celular/fisiología , Humanos , Factor 4 Similar a Kruppel , Masculino , Ratones , Ratones Endogámicos BALB C , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Células PC-3/fisiología , Próstata/efectos de los fármacos , Próstata/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The number of people with Internet gaming addiction (IGA) is increasing around the world. IGA is known to be associated with personal characteristics, psychosocial factors, and physiological factors. However, few studies have examined the genetic factors related to IGA. This study aimed to investigate the association between IGA and stress-related genetic variants. METHODS: This cross-sectional study was conducted with 230 male high school students in a South Korean city. We selected five stress-related candidate genes: DAT1, DRD4, NET8, CHRNA4, and CRHR1. The DAT1 and DRD4 genes were genotyped by polymerase chain reaction, and the NET8, CHRNA4, and CRHR1 genes were genotyped by pyrosequencing analysis. We performed a Chi-square test to examine the relationship of these five candidate genes to IGA. RESULTS: Having the AA genotype and the A allele of the CRHR1 gene (rs28364027) was associated with higher odds of belonging to the IGA participant group (p = .016 and p = .021, respectively) than to the non-IGA group. By contrast, the DAT1, DRD4, NET8, and CHRNA4 gene polymorphisms showed no significant difference between the IGA group and control group. CONCLUSIONS: These results indicate that polymorphism of the CRHR1 gene may play an important role in IGA susceptibility in the Korean adolescent male population. These findings provide a justification and foundation for further investigation of genetic factors related to IGA.
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Conducta Adictiva , Juegos Recreacionales/psicología , Receptores de Hormona Liberadora de Corticotropina/genética , Adolescente , Conducta Adictiva/genética , Conducta Adictiva/psicología , Correlación de Datos , Estudios Transversales , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Internet , Masculino , Sistema Hipófiso-Suprarrenal/fisiología , Polimorfismo de Nucleótido Simple , República de Corea/epidemiologíaRESUMEN
Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach. Previously, stem or dendritic cells were used in MI for their anti-inflammatory and cardioprotective potentials and showed inflammation modulation and M2 macrophage progression for cardiac repair. However, cell-based therapeutics are limited due to invasive cell isolation, time-consuming cell expansion, labor-intensive and costly ex vivo cell manipulation, and low grafting efficiency. Here, we report that graphene oxide (GO) can serve as an antioxidant and attenuate inflammation and inflammatory polarization of macrophages via reduction in intracellular ROS. In addition, GO functions as a carrier for interleukin-4 plasmid DNA (IL-4 pDNA) that propagates M2 macrophages. We synthesized a macrophage-targeting/polarizing GO complex (MGC) and demonstrated that MGC decreased ROS in immune-stimulated macrophages. Furthermore, DNA-functionalized MGC (MGC/IL-4 pDNA) polarized M1 to M2 macrophages and enhanced the secretion of cardiac repair-favorable cytokines. Accordingly, injection of MGC/IL-4 pDNA into mouse MI models attenuated inflammation, elicited early polarization toward M2 macrophages, mitigated fibrosis, and improved heart function. Taken together, the present study highlights a biological application of GO in timely modulation of the immune environment in MI for cardiac repair. Current therapy using off-the-shelf material GO may overcome the shortcomings of cell therapies for MI.
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Antioxidantes/uso terapéutico , Grafito/uso terapéutico , Inflamación/terapia , Macrófagos/efectos de los fármacos , Infarto del Miocardio/terapia , Animales , Células Cultivadas , ADN/genética , ADN/uso terapéutico , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Factores Inmunológicos/uso terapéutico , Inflamación/complicaciones , Inflamación/inmunología , Inflamación/fisiopatología , Interleucina-4/genética , Interleucina-4/inmunología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones Endogámicos BALB C , Infarto del Miocardio/complicaciones , Infarto del Miocardio/inmunología , Infarto del Miocardio/fisiopatología , Especies Reactivas de Oxígeno/inmunologíaRESUMEN
Biological cells are complex living machines that have garnered significant attention for their potential to serve as a new generation of therapeutic and delivery agents. Because of their secretion, differentiation, and homing activities, therapeutic cells have tremendous potential to treat or even cure various diseases and injuries that have defied conventional therapeutic strategies. Therapeutic cells can be systemically or locally transplanted. In addition, with their ability to express receptors that bind specific tissue markers, cells are being studied as nano- or microsized drug carriers capable of targeted transport. Depending on the therapeutic targets, these cells may be clustered to promote intercellular adhesion. Despite some impressive results with preclinical studies, there remain several obstacles to their broader development, such as a limited ability to control their transport, engraftment, secretion and to track them in vivo. Additionally, creating a particular spatial organization of therapeutic cells remains difficult. Efforts have recently emerged to resolve these challenges by engineering cell surfaces with a myriad of bioactive molecules, nanoparticles, and microparticles that, in turn, improve the therapeutic efficacy of cells. This review article assesses the various technologies developed to engineer the cell surfaces. The review ends with future considerations that should be taken into account to further advance the quality of cell surface engineering.
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Tratamiento Basado en Trasplante de Células y Tejidos , Animales , Bioingeniería , Rastreo Celular , Propiedades de SuperficieRESUMEN
Miniature organlike three-dimensional cell clusters often called organoids have emerged as a useful tool for both fundamental and applied bioscience studies. However, there is still a great need to improve the quality of organoids to a level where they exhibit similar biological functionality to an organ. To this end, we hypothesized that a decellularized matrix derived from mesenchymal stem cell (MSC) could regulate the phenotypic and metabolic activity of organoids. This hypothesis was examined by culturing cells of interest in the decellularized matrix of MSCs cultured on a 2D substrate at confluency or in the form of spheroids. The decellularized matrix prepared with MSC spheroids showed a 3D porous structure with a higher content of extracellular matrix molecules than the decellularized matrix derived from MSCs cultured on a 2D substrate. HepG2 hepatocarcinoma cells, which retain the metabolic activity of hepatocytes, were cultured in these decellularized matrices. Interestingly, the decellularized matrix from the MSC spheroids served to develop the hepatic cell clusters with higher levels of E-cadherin-mediated cell-cell adhesion and detoxification activity than the decellularized matrix from the MSCs cultured on a 2D substrate. Overall, the results of this study are useful in improving biological functionality of a wide array of organoids.
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Extensive efforts have been made to regulate surface wettability using bivalent polymers composed of hydrophobic surface-reactive groups and hydrophilic groups. To further enhance the controllability, this study demonstrates that the balance between the surface reactivity and self-aggregation of bivalent poly(hydroxyethyl-co-methacryloxyethyl aspartamide) (PHMAA) is crucial in controlling the wettability of methacrylated glass and thus the adhesion of stem cells. In particular, the wettability of the glass and the subsequent cell spreading became maximal with PHMAA that led to the largest and most uniform coverage of hydroxyl groups. In summary, this study would be useful in advancing various molecules used for surface engineering.