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1.
Immunity ; 53(1): 143-157.e8, 2020 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-32640256

RESUMEN

Regulatory T (Treg) cells play a pivotal role in suppressing auto-reactive T cells and maintaining immune homeostasis. Treg cell development and function are dependent on the transcription factor Foxp3. Here, we performed a genome-wide CRISPR loss-of-function screen to identify Foxp3 regulators in mouse primary Treg cells. Foxp3 regulators were enriched in genes encoding subunits of the SWI/SNF nucleosome-remodeling and SAGA chromatin-modifying complexes. Among the three SWI/SNF-related complexes, the Brd9-containing non-canonical (nc) BAF complex promoted Foxp3 expression, whereas the PBAF complex was repressive. Chemical-induced degradation of Brd9 led to reduced Foxp3 expression and reduced Treg cell function in vitro. Brd9 ablation compromised Treg cell function in inflammatory disease and tumor immunity in vivo. Furthermore, Brd9 promoted Foxp3 binding and expression of a subset of Foxp3 target genes. Our findings provide an unbiased analysis of the genetic networks regulating Foxp3 and reveal ncBAF as a target for therapeutic manipulation of Treg cell function.


Asunto(s)
Sistemas CRISPR-Cas/genética , Factores de Transcripción Forkhead/metabolismo , Neoplasias/inmunología , Linfocitos T Reguladores/metabolismo , Factores de Transcripción/metabolismo , Animales , Autoinmunidad/inmunología , Línea Celular Tumoral , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/genética , Regulación de la Expresión Génica/genética , Células HEK293 , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Nucleosomas/inmunología , ARN Guía de Kinetoplastida/genética , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Factores de Transcripción/genética
2.
Small ; : e2403835, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984921

RESUMEN

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

3.
Molecules ; 29(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38999132

RESUMEN

Phyllanthus emblica L. fruits (PEFs) were processed by ultra-pressure (UHP) treatment and then extracted by the ultrasonic-assisted extraction method. The influence of UHP on the phenolic composition, enzyme inhibitory activity and antioxidant activity of the free, esterified, and bound phenolic fractions from PEFs were compared. UHP pretreatment of PEFs significantly increased the total phenolic and flavonoid contents (p < 0.05). A total of 24 chemical compositions were characterized in normal and UHP-treated PEFs by UHPLC-ESI-HRMS/MS. Compared with normal PEFs, these three different phenolic fractions had stronger antioxidant activities and inhibitory effects on the intracellular reactive oxygen species (ROS) production in H2O2-induced HepG2 cells (p < 0.05). The ROS inhibition might be due to an up-regulation of the expressions of superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, these three different phenolic fractions also significantly inhibited the activities of metabolic enzymes, including α-glucosidase, α-amylase and pancreatic lipase. This work may provide some insights into the potential economics and applications of PEFs in food and nutraceutical industries.


Asunto(s)
Antioxidantes , Frutas , Fenoles , Phyllanthus emblica , Extractos Vegetales , Fenoles/química , Fenoles/análisis , Fenoles/farmacología , Phyllanthus emblica/química , Humanos , Frutas/química , Antioxidantes/química , Antioxidantes/farmacología , Células Hep G2 , Extractos Vegetales/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Cromatografía Líquida de Alta Presión , Superóxido Dismutasa/metabolismo , Flavonoides/química , Flavonoides/farmacología , Presión , Peróxido de Hidrógeno
4.
J Youth Adolesc ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753280

RESUMEN

Prior research has observed reciprocal associations between sleep and mood. However, these findings are primarily based on the examination of one or two aspects of sleep behaviors (e.g., duration, quality), neglecting how multiple dimensions of sleep (particularly indicators pertinent to adolescence, e.g., sleep variability) are linked to adolescent mood both daily and longitudinally. Drawing on a multidimensional framework for sleep, this study addressed the knowledge gap by examining the directionality of and differential effects for associations between multiple dimensions of sleep and mood during early adolescence. Participants were 273 Chinese early adolescents (34.39% girls; Mage = 11.57, SD = 1.31), who filled out a pre-survey on demographics (T1) and 7-day diaries on sleep (i.e., duration, quality, disturbance, and latency) and mood (i.e., positive and negative mood). Adolescents completed another wave of diary reports 1 year later (T2). Findings revealed both bidirectional and unidirectional, within-person effects depending on specific sleep parameters, suggesting differential associations between multiple dimensions of sleep and mood. Specifically, on days when adolescents had longer sleep latency and greater disturbance than usual, they reported higher negative mood the next day, whereas higher negative mood was linked to poorer sleep quality the next day. The longitudinal investigation found that greater variability in sleep quality at T1 was associated with higher negative mood at T2. These findings underscore the importance of understanding the complex interplay between sleep and mood by examining the directionality of and differential effects for the daily and longer-term associations between multiple dimensions of sleep and mood among early adolescents.

5.
J Youth Adolesc ; 52(10): 2144-2157, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37481502

RESUMEN

Prior research examining parent-child separation and the hypothalamic-pituitary-adrenal (HPA) axis functioning has primarily focused on separation due to parental divorce or loss or forced migration. Less clear is the impact of parental economic migration on adolescents' HPA axis functioning. The present study fills this gap by examining diurnal cortisol patterns among left-behind adolescents who experienced separation from their migrant parents. Participants were 293 Chinese adolescents (33.4% girls, 66.21% left-behind adolescents; Mage = 10.80 years old, SD = 0.82 years). Two-level multilevel modeling was conducted to examine the associations between parent-child separation experiences and diurnal cortisol patterns. Although no significant differences were found between left-behind adolescents and their non-left-behind peers, results revealed that left-behind adolescents who experienced parent-child separation at earlier ages had more blunted diurnal cortisol slopes (usually signaling poorer mental and physical health), compared to their counterparts who experienced separation at older ages. Left-behind adolescent girls who had more adverse separation experiences exhibited smaller waking cortisol and blunted diurnal slopes; these findings were not observed among left-behind adolescent boys. Observing the association between timing of parent-child separation and adolescents' diurnal cortisol and the moderating effects of child sex, this study contributes uniquely to the developmental science of left-behind adolescents' physiological health.


Asunto(s)
Hidrocortisona , Sistema Hipotálamo-Hipofisario , Masculino , Femenino , Humanos , Adolescente , Niño , Sistema Hipotálamo-Hipofisario/fisiología , Divorcio , Sistema Hipófiso-Suprarrenal/fisiología , Saliva , Relaciones Padres-Hijo , Estrés Psicológico
6.
J Youth Adolesc ; 52(1): 91-104, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36370228

RESUMEN

Child abuse is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis functioning. However, the unique effects of psychological and physical abuse and protective factors against these effects remain largely unknown. To close these gaps, the present study examined the unique effects of psychological and physical abuse on cortisol stress response and explored the moderating role of psychosocial resources in these associations among a sample of Chinese preadolescent children (N = 150; aged 9-13 years; Mage = 10.69 years; 51% boys). The results showed that both psychological and physical abuse were associated with blunted cortisol reactivity slopes. Psychological abuse, but not physical abuse, was associated with lower peak cortisol values and flatter cortisol recovery slopes. Further, psychosocial resources moderated the association between abuse and hyporesponsiveness of the HPA axis. The association between psychological abuse and lower peak cortisol values and the association between physical abuse and steeper cortisol recovery slopes (faster cortisol recovery following the stressor) were observed only among children with low levels of psychosocial resources. These findings indicate the differential effects of psychological and physical abuse on various phases of cortisol stress response, and the protective role of psychosocial resources. This study also has practical implications, given that preadolescence serves as a critical period for maximizing benefit of interventions of adversity.


Asunto(s)
Hidrocortisona , Sistema Hipotálamo-Hipofisario , Masculino , Humanos , Niño , Femenino , Sistema Hipotálamo-Hipofisario/fisiología , Estrés Psicológico/psicología , Sistema Hipófiso-Suprarrenal/fisiología , Saliva
7.
J Youth Adolesc ; 52(9): 1873-1886, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37296270

RESUMEN

There is growing evidence of a clear association between students' perceived stress and their adjustment to life at college. However, the predictors and implications of distinct changing patterns of perceived stress during the transition to college life are less clear. To address these research gaps, the current study aims to identify distinct patterns of perceived stress trajectories among 582 Chinese first-year college students (Mage = 18.11, SDage = 0.65; 69.40% female) across the first 6 months upon enrollment. Three distinct profiles of perceived stress trajectories, i.e., low-stable (15.63%), middle-decreasing (69.07%), and high-decreasing (15.29%), were identified. Moreover, individuals who followed the low-stable trajectory showed better distal outcomes (specifically, higher levels of well-being and academic adjustment) 8 months after enrollment than those who followed the other two trajectories. Furthermore, two types of positive mindset (a growth mindset of intelligence and a stress-is-enhancing mindset) contributed to differences in perceived stress trajectory, either independently or jointly. These findings highlight the significance of identifying different patterns of perceived stress among students during the transition to college, as well as the protective roles of both a stress mindset and a mindset of intelligence.


Asunto(s)
Inteligencia , Estudiantes , Adolescente , Femenino , Humanos , Masculino , Pueblo Asiatico , Estrés Psicológico , Universidades , Adaptación Psicológica
8.
Hepatology ; 74(2): 797-815, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33650193

RESUMEN

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) is closely correlated with hepatic progenitor cell (HPC) expansion and liver fibrosis. Brahma-related gene 1 (Brg1), an enzymatic subunit of the switch/sucrose nonfermentable complex that is critical in stem cell maintenance and tumor promotion, is prominently up-regulated in both HPCs and iCCA; however, its role in this correlation remains undefined. APPROACH AND RESULTS: A retrospective cohort study indicated that high Brg1 expression suggests poor prognosis in patients with iCCA. In chronically injured livers induced by a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet or bile duct ligation surgery, HPCs were dramatically activated, as indicated by their enhanced expression of Brg1 and a subset of stem cell markers; however, Brg1 ablation in HPCs strongly suppressed HPC expansion and liver fibrosis. Furthermore, in a chemically induced iCCA model, inhibition of Brg1 by a specific inhibitor or inducible gene ablation markedly improved histology and suppressed iCCA growth. Mechanistically, in addition to transcriptionally promoting both Wnt receptor genes and target genes, Brg1 was found to bind to the ß-catenin/transcription factor 4 transcription complex, suggesting a possible approach for regulation of Wnt/ß-catenin signaling. CONCLUSIONS: We have demonstrated the function of Brg1 in promoting HPC expansion, liver cirrhosis, and, ultimately, iCCA development in chronically injured livers, which is largely dependent on Wnt/ß-catenin signaling. Our data suggest that therapies targeting Brg1-expressing HPCs are promising for the treatment of liver cirrhosis and iCCA.


Asunto(s)
Neoplasias de los Conductos Biliares/genética , Colangiocarcinoma/genética , ADN Helicasas/genética , Cirrosis Hepática/genética , Recurrencia Local de Neoplasia/epidemiología , Proteínas Nucleares/genética , Factores de Transcripción/genética , Adulto , Anciano , Animales , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Neoplasias de los Conductos Biliares/inducido químicamente , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/inducido químicamente , Colangiocarcinoma/mortalidad , Colangiocarcinoma/terapia , ADN Helicasas/antagonistas & inhibidores , ADN Helicasas/metabolismo , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hígado/patología , Hígado/cirugía , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Cirrosis Hepática/prevención & control , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/genética , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/metabolismo , Pronóstico , Piridinas/farmacología , Piridinas/uso terapéutico , Estudios Retrospectivos , Células Madre/metabolismo , Células Madre/patología , Tioacetamida/administración & dosificación , Tioacetamida/toxicidad , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Regulación hacia Arriba , Vía de Señalización Wnt/genética
9.
Child Dev ; 93(4): 973-994, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35238024

RESUMEN

Ethnic/racial discrimination is associated with negative psychosocial outcomes, and this study considered sleep disturbance as a mediating pathway. Employing a combination of daily diary and biannual surveys, multilevel structural equation models estimated the indirect effects of sleep/wake concerns on negative, anxious, and positive mood, rumination, and somatic symptoms. In a sample of 350 urban Asian (74% Chinese, 8% Korean, 4% Indian, 1% Filipinx, 1% Vietnamese, and 12% other), Black, and Latinx (25% Dominican, 24% South American, 22% Mexican, 15% Puerto Rican, 5% Central American, and 9% other) youth (M = 14.27 years, 69% female, 77% U.S. born, 76% monoethnic/racial, data collected from 2015 to 2018), there was evidence for sleep disturbances mediating the impact of ethnic/racial discrimination on adjustment. Nighttime disturbance, daytime dysfunction, and daytime sleepiness evidenced partial or full mediation for daily- and person-level outcomes (υ = 0.1%-17.9%). Reciprocal associations between sleep disturbances and negative mood and rumination were also observed.


Asunto(s)
Racismo , Trastornos del Sueño-Vigilia , Adolescente , Etnicidad , Femenino , Humanos , Masculino , Salud Mental , Racismo/psicología , Sueño , Trastornos del Sueño-Vigilia/psicología
10.
J Youth Adolesc ; 51(5): 871-887, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34846644

RESUMEN

Perceived discrimination is associated with poorer psychological adjustment and greater problem behaviors among rural-to-urban migrant adolescents. Yet, the predictors and the consequences of distinct changing patterns of perceived discrimination are less clear. The current study sought to identify distinct patterns of perceived discrimination trajectories and examine the developmental implications of these patterns among 385 Chinese rural-to-urban migrant early adolescents (Mage = 10.49, SDage = 0.69; 62% boys). Four distinct patterns of perceived discrimination trajectories, i.e., Low-stable (79.59%), Decreasing (9.08%), High-stable (6.11%), and Increasing (5.22%), were identified. Predictors including resilience, family support, peer support, and demographic characteristics (i.e., gender and school types) contributed to differences in pattern membership. Moreover, the Low-stable pattern exhibited more favorable distal outcomes (i.e., lower levels of social anxiety and loneliness and higher levels of self-esteem) than the other three patterns; the Decreasing group had lower levels of loneliness than the High-stable group. The findings extend the understanding of the predictors and consequences of perceived discrimination among rural-to-urban migrant early adolescents from a developmental perspective.


Asunto(s)
Migrantes , Adolescente , Pueblo Asiatico , Niño , China , Femenino , Humanos , Lactante , Masculino , Discriminación Percibida , Población Rural
11.
Curr Psychol ; : 1-15, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36468161

RESUMEN

Drastically disrupting daily routines, the global pandemic of COVID-19 has posed critical mental health threats to adolescents and young adults worldwide. Many of the extant empirical findings, however, have focused on individuals' psychological adjustment during the initial phase of the pandemic. It is less clear how COVID-19 stressful experiences impact young people's daily lives in the post-pandemic "new normal." Drawing on 7-day diary reports, the present study fills this gap by examining: (1) how daily perceived stress impacted daily emotional adjustment; and (2) the moderating effects of COVID-19 stressful experiences on these associations among 582 Chinese young adults (M age = 18.12, SD = .65; 69% females). Results indicated that higher levels of both trait (i.e., average levels) and state (i.e., daily fluctuations) perceived stress were associated with greater negative and anxious moods, and that prior pandemic-related experiences exacerbated the adverse impact of both trait and state perceived stress on daily moods. Specifically, young adults reporting greater COVID-19 stressful experiences demonstrated poorer emotional adjustment (i.e., lower levels of positive mood and higher levels of negative mood) on days when they had more fluctuations in perceived stress; the aggravating impact was stronger when the average levels of perceived stress were higher. By illuminating the moderating effects of COVID-19 stressful experiences, this study contributes to the limited, but burgeoning, research examining the prolonged impact of the COVID-19 health crisis on daily emotional adjustment in post-pandemic life.

12.
Child Dev ; 92(5): e1061-e1074, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34106461

RESUMEN

This study examines how everyday discrimination is associated with 6-day trajectories of sleep/wake problems, operationalized as sleep disturbance and daytime dysfunction, among 350 diverse adolescents (Mage  = 14.27, SD = 0.61, 69% female; 22% African American, 41% Asian American, 37% Latinx; 24% multiethnic/racial; across participating schools, 72% of students eligible for free/reduced price lunch) in the Northeastern United States. Adolescents encountering discrimination experienced changes in sleep/wake problem trajectories (i.e., significant increases in same-day sleep/wake problems), whereas adolescents reporting no discrimination experienced no changes in trajectories (Cohen's ds = .51-.55). Multiethnic/racial (compared to monoethnic/racial) adolescents experiencing everyday discrimination reported greater same-day sleep/wake problems, yet steeper decreases in sleep/wake problems suggesting stronger impact coupled with faster return to baseline levels.


Asunto(s)
Racismo , Trastornos del Sueño-Vigilia , Adolescente , Negro o Afroamericano , Asiático , Femenino , Humanos , Masculino , Sueño
13.
J Youth Adolesc ; 50(6): 1173-1188, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33847860

RESUMEN

Ethnic-racial identity, ethnic-racial socialization, and racialized experiences are fundamental to the development of youth of color. However, most prior studies have examined their developmental impact in isolation. The present study fills this gap using a person-centered approach to elucidate patterns of ethnic-racial identity, socialization, and model minority experiences among 145 Asian American adolescents (Mage = 14.3, SD = 0.59; 65% female). Three distinct profiles were identified. Overall, adolescents with stronger ethnic-racial identity and more cultural socialization but less preparation for bias (Salient, 13%) demonstrated better psychosocial and academic outcomes. Adolescents with moderate levels on the six indicators of ethnic-racial identity, socialization, and model minority experiences (Moderate, 72%) reported better sleep quality and less delinquency. Adolescents with low levels of ethnic-racial identity and cultural socialization but greater preparation for bias (Marginal, 15%) had the least adaptative outcomes across all domains. The findings observed the heterogeneity of ethnic-racial experiences within the Asian American group and highlighted the importance of examining the combined influences of ethnic-racial identity, socialization, and model minority experiences on health and well-being among Asian American adolescents from a multidimensional perspective.


Asunto(s)
Asiático , Socialización , Adolescente , Femenino , Humanos , Masculino , Grupos Minoritarios , Grupos Raciales , Identificación Social
14.
Carcinogenesis ; 41(7): 972-983, 2020 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-31628462

RESUMEN

Liver cancer and other malignant tumor cells rely on the glycolytic pathway to obtain energy (i.e. the Warburg effect); however, the underlying mechanism is unclear. Mitochondria are sites of oxidative phosphorylation and adenosine triphosphate (ATP) production. The 13 constituent respiratory chain proteins encoded by the mitochondrial genome (namely, mtDNA) play essential roles. We found that in human hepatocellular carcinoma (HCC) tissues, 11 out of the 13 mtDNA-encoded genes exhibited decreased mRNA levels and 5 genes displayed decreased protein levels, including the cytochrome B (mt-CYB) and cytochrome C oxidase II (mt-CO2) genes. Mitochondrial gene sequencing revealed abnormalities in the levels of a large number of mitochondrial miRNAs (mitomiRs). MicroRNA-181a-5p (mir-181a-5p), which potentially targets genes encoding mt-CYB and mt-CO2 protein, was screened out from 549 downregulated mitomiRs via bioinformatic analysis. After overexpression of mitomiR-181a-5p, mt-CYB and mt-CO2 levels were reduced in HCC cells, and the mitochondrial membrane potential (MMP) maintained by the electron transport chain (ETC) was decreased. Furthermore, the expression of hexokinase 2 (HK2) and glucose transporter type 1 (GLUT1) was upregulated, accompanied by elevated glucose, lactic acid release, and activity of lactate dehydrogenase (LDH). In vivo experiments confirmed that constitutive mitomiR-181a-5p expression caused reprogramming of glucose metabolism and promoted tumor growth and early lung metastasis in liver cancer. In summary, the present study reveals the important role of mitomiRs in glucose metabolism reprogramming in liver cancer, which is of considerable value in exploring new therapeutic targets for HCC.


Asunto(s)
Complejo IV de Transporte de Electrones/genética , Transporte de Electrón/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Proliferación Celular/genética , Reprogramación Celular/genética , Citocromos b/genética , ADN Mitocondrial/genética , Glucosa/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Potencial de la Membrana Mitocondrial/genética , Redes y Vías Metabólicas/genética , Mitocondrias/genética , Mitocondrias/metabolismo , Fosforilación Oxidativa
15.
Small ; 15(4): e1804216, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30569632

RESUMEN

Low-concentration gelatin methacryloyl (GelMA) has excellent biocompatibility to cell-laden structures. However, it is still a big challenge to stably fabricate organoids (even microdroplets) using this material due to its extremely low viscosity. Here, a promising electro-assisted bioprinting method is developed, which can print low-concentration pure GelMA microdroplets with low cost, low cell damage, and high efficiency. With the help of electrostatic attraction, uniform GelMA microdroplets measuring about 100 µm are rapidly printed. Due to the application of lower external forces to separate the droplets, cell damage during printing is negligible, which often happens in piezoelectric or thermal inkjet bioprinting. Different printing states and effects of printing parameters (voltages, gas pressure, nozzle size, etc.) on microdroplet diameter are also investigated. The fundamental properties of low-concentration GelMA microspheres are subsequently studied. The results show that the printed microspheres with 5% w/v GelMA can provide a suitable microenvironment for laden bone marrow stem cells. Finally, it is demonstrated that the printed microdroplets can be used in building microspheroidal organoids, in drug controlled release, and in 3D bioprinting as biobricks. This method shows great potential use in cell therapy, drug delivery, and organoid building.


Asunto(s)
Bioimpresión/métodos , Gelatina/química , Hidrogeles/química , Metacrilatos/química , Viscosidad
16.
Small ; 14(39): e1802630, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30133151

RESUMEN

Hydrogel microspheroids are widely used in tissue engineering, such as injection therapy and 3D cell culture, and among which, heterogeneous microspheroids are drawing much attention as a promising tool to carry multiple cell types in separated phases. However, it is still a big challenge to fabricate heterogeneous microspheroids that can reconstruct built-up tissues' microarchitecture with excellent resolution and spatial organization in limited sizes. Here, a novel airflow-assisted 3D bioprinting method is reported, which can print versatile spiral microarchitectures inside the microspheroids, permitting one-step bioprinting of fascinating hydrogel structures, such as the spherical helix, rose, and saddle. A microfluidic nozzle is developed to improve the capability of intricate cell encapsulation with heterotypic contact. Complex structures, such as a rose, Tai chi pattern, and single cell line can be easily printed in spheroids. The theoretical model during printing is established and process parameters are systematically investigated. As a demonstration, a human multicellular organoid of spirally vascularized ossification is reconstructed with this method, which shows that it is a powerful tool to build mini tissues on microspheroids.


Asunto(s)
Microfluídica/métodos , Organoides/citología , Bioimpresión/métodos , Humanos , Modelos Teóricos , Ingeniería de Tejidos/métodos
17.
Med Sci Monit ; 24: 2456-2464, 2018 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-29680858

RESUMEN

BACKGROUND The modification of histone acetylation and deacetylation is the most important mechanism of chromatin remodeling. These modifications are a subset of epigenetic alterations which affect tumorigenesis and progression through changes in gene expression and cell growth. Results of histone modification studies prompted us to explore the therapeutic and prognostic significance of histone deacetylase 3 (HDAC3) expression in patients with breast cancer. MATERIAL AND METHODS Immunohistochemical (IHC) staining was used to detect HDAC3 expression in a tissue microarray (TMA) that included 145 patients diagnosed with invasive ductal breast carcinoma. IHC scoring was used to evaluate the staining intensity and the proportion of positive cells. RESULTS HDAC3 expression was significantly correlated with estrogen receptor (ER)-negative expression (P=0.036) and progesterone receptor (PR)-negative expression (P=0.024). Additionally, HDAC3 expression was significantly positively correlated with human epidermal growth factor 2 (HER2) overexpression (P=0.037). Our study also indicated that high expression of HDAC3 was more frequently observed in breast tumors with PT2 classification (74%) versus PT1 (50.0%) and PT3 (71.4%) (P=0.040). Furthermore, HDAC3 was correlated with clinical stage II (P=0.046). Univariate and multivariate survival analyses showed that high expression of HDAC3 was correlated with poor overall survival (OS) (P=0.029 and P=0.033, respectively) in patients without lymph node involvement. CONCLUSIONS High HDAC3 expression is closely correlated with ER-negative expression, PR-negative expression, HER2 overexpression, PT stage, and clinical stage of breast tumors. HDAC3 may be an appropriate prognostic indicator in patients with invasive ductal breast cancer.


Asunto(s)
Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Histona Desacetilasas/biosíntesis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Femenino , Histona Desacetilasas/metabolismo , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2 , Receptores de Estrógenos/metabolismo , Análisis de Matrices Tisulares
18.
Neuro Endocrinol Lett ; 39(2): 125-129, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-30183207

RESUMEN

BACKGROUND: Patients with irritable bowel syndrome (IBS) frequently present with alterations of autonomic activity, especially higher sympathetic activity. Salivary alpha-amylase (sAA) has been implicated as a non-invasive biomarker to reflect the sympathetic activity. Thus, the current study aimed to determine if alterations of sAA secretion could be addressed in IBS patients. METHODS: We recruited twenty-five IBS patients as well as twenty-four age- and sex-matched healthy controls (HCs). Basal and stimulated (by gustatory stimulation with citric acid) saliva samples were collected from each participant, with respective salivary flow rate (SFR) calculated accordingly. Western blotting (WB) was applied to determine the sAA amount by introducing human sAA protein of known quantity. Then the sAA amount ratio was calculated, as expressed by the stimulated sAA amount to basal sAA amount. RESULTS: We observed high variability of the basal and stimulated sAA amount in both groups. An apparently higher prevalence of psychiatric disorders was detected in the IBS group, which was consistent with previous studies. Interestingly, we found elevated basal sAA amount in the IBS patients relative to HCs, which implicated higher sympathetic activities in IBS population. Moreover, we observed blunted sAA response to the gustatory stimulation in the IBS patients, which might be of pathophysiological importance for IBS. CONCLUSION: This is the first attempt to associate sAA secretion with the pathophysiology of IBS. Our results suggest an autonomic dysfunction in IBS patients.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/diagnóstico , alfa-Amilasas Salivales/análisis , Adulto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/enzimología , Biomarcadores/análisis , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/enzimología , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/enzimología , Persona de Mediana Edad , Salivación/efectos de los fármacos , Estimulación Química
19.
Med Sci Monit ; 21: 769-75, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25771535

RESUMEN

BACKGROUND: Diet is the primary way cadmium (Cd) enters the body in those without occupational exposure and who do not inhabit Cd-polluted regions. Findings on the relationship between dietary Cd exposure and breast cancer (BC) risk have been inconsistent; a meta-analysis has supported this association but 2 recent cohort studies showed inconsistent results. Hence, we performed an updated meta-analysis to re-evaluate the association between dietary Cd exposure and BC risk. MATERIAL AND METHODS: We searched PubMed, Medline, and EMBASE to identify relevant studies published through September 2014. Combined relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were used to assess the association between dietary Cd exposure and BC risk. RESULTS: We identified 6 studies involving 321 315 participants and 11 978 cases. Our study suggested there was no statistically significant positive association between dietary Cd exposure and BC risk, the combined RR and corresponding 95% CI was 1.01 [0.88, 1.14]. The result was not modified by menopause status, geographic area, or study design. CONCLUSIONS: Our study did not find a statistically significant positive association between dietary Cd exposure and BC risk. It is necessary to investigate this relationship among the high-risk groups and more cohort studies based on diverse populations are needed.


Asunto(s)
Neoplasias de la Mama/etiología , Cadmio/efectos adversos , Dieta/efectos adversos , Estudios Observacionales como Asunto , Femenino , Humanos , Sesgo de Publicación , Factores de Riesgo
20.
J Adolesc Health ; 74(3): 514-522, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37952141

RESUMEN

PURPOSE: This study sought to examine whether the daily associations between ethnic/racial discrimination and stress responses served as mediators linking ethnic/racial identity (ERI), adolescent sleep health, and somatic symptoms. METHODS: Data were drawn from 279 adolescents of color (69% female; 24% African Americans; 31% Asian Americans; 41% Latinx; and 4% unknown ethnicity/race; Mage = 14.31 years, SD = 0.65). Adolescents first completed an online survey about ERI exploration and commitment; and then 14-day diaries on ethnic/racial discrimination and stress responses (i.e., rumination and problem-solving coping), and finally, a post-diary survey about sleep and somatic health over the past two weeks. This study adopts slope-as-mediator mediation modeling, a novel approach highlighting the role of daily-level experiences in developmental processes by examining the day-to-day association between two variables as an explanatory mechanism. RESULTS: The daily associations between ethnic/racial discrimination and two stress responses significantly mediated the link between ERI exploration and adolescents' subsequent sleep and somatic health. For ERI commitment, only the mediating pathway of the association between ethnic/racial discrimination and problem-solving coping was significant. DISCUSSION: Daily responses to ethnic/racial discrimination, both adaptively and maladaptively, could in part explain the association between ERI exploration and adolescent health. Active participation in cultural activities may increase adaptive responses to ethnic/racial discrimination; meanwhile, uncertainty about ERI may lead to maladaptive reactions such as rumination. For ERI commitment, only problem-solving coping with ethnic/racial discrimination mediated the links to health outcomes, an observation possibly explained by the benefits of holding a strong sense of commitment to ERI.


Asunto(s)
Estado de Salud , Racismo , Sueño , Identificación Social , Adolescente , Femenino , Humanos , Masculino , Negro o Afroamericano , Etnicidad , Asiático , Hispánicos o Latinos
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