Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55
Filtrar
1.
J Crohns Colitis ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073573

RESUMEN

BACKGROUND & AIMS: Janus kinase (JAK) inhibitors are used for treating inflammatory bowel diseases (IBD). We aimed to identify molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location and phenotype. METHODS: Colonic and ileal explants from patients with ulcerative colitis (UC), Crohn's disease (CD), and non-IBD controls (NC) were assessed for phosphorylated signal transducers and activators of transcription (p-STAT) levels and Inflammatory genes expression panel in response to ex-vivo JAK inhibitor (tofacitinib). Cytokine production by lamina propria lymphocytes in response to tofacitinib was assessed. Human intestinal organoids were used to investigate JAK inhibitors' effects on iNOS expression. RESULTS: Explants were collected from 68 patients (UC=20; CD=20; NC=28). p-STAT1\3\5 inhibition rates varied, being higher in colonic compared to ileal explants. p-STAT1\3 inhibition rates negatively correlated with CRP levels. While significant alterations in 120 of 255 inflammatory genes were observed in colonic explants, only 30 were observed in ileal NC explants. In colonic explants from UC, significant alterations were observed in 5 genes, including NOS2. JAK inhibition significantly decreased Th1\Th2\Th17-related cytokine production from lamina propria lymphocytes. Various JAK inhibitors reduced IFN-γ-induced increase in iNOS expression in organoids. CONCLUSIONS: Site-specific anti-inflammatory effect of JAK inhibition by tofacitinib was noticed, whereby the colon was more robustly affected than the ileum. Ex-vivo response to tofacitinib is individual. JAK inhibition may attenuate inflammation by decreasing iNOS expression. Ex-vivo mucosal platforms may be a valuable resource for studying personalized drug effects in patients with IBD.

2.
Eur Rev Med Pharmacol Sci ; 28(3): 1060-1065, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38375711

RESUMEN

OBJECTIVE: Asthma is characterized by airway hyperresponsiveness due to chronic inflammation in the airways. One of the main cells involved in airway inflammation is eosinophils. In the current study, a bronchial provocation test (BPT) was performed to demonstrate airway hyperresponsiveness. We investigated the relationship between BPT and blood eosinophil count and the cut-off value of blood eosinophil count. PATIENTS AND METHODS: In this study, we retrospectively evaluated the data of 246 patients who visited our immunology and allergy clinic, a tertiary reference center, with asthma symptoms between May 2017 and March 2020 and underwent BPT with methacholine for the diagnosis of asthma. The cases were grouped according to the level of BPT positivity and negativity. RESULTS: Of 246 patients, BPT was positive in 90 (36.6%) and negative in 156 (63.4%). The blood eosinophil measurement of the BPT-positive cases was found to be statistically significantly higher than that of the BPT-negative cases (135 vs. 119 cells/µl, respectively, p=0.029). When BPT is grouped according to positivity levels, there was no statistically significant difference in blood eosinophil measurements between subgroups (p=0.174). As a result of the evaluations, the cut-off point obtained for the blood eosinophil count was determined as ≥226 cells/µl. For the blood eosinophil count, for the cut-off value of ≥226 cells/µl, sensitivity was 30.0%, specificity 87.7%, positive predictive value 58.7%, and negative predictive value 68.3%. CONCLUSIONS: This study shows that BPT positivity is associated with blood eosinophil count. The cut-off value (≥226 cells/µl) determined for blood eosinophil count may be helpful when planning BPT and evaluating the diagnosis of asthma.


Asunto(s)
Asma , Hipersensibilidad Respiratoria , Humanos , Eosinófilos , Pruebas de Provocación Bronquial , Estudios Retrospectivos , Recuento de Leucocitos , Inflamación
3.
Nat Commun ; 14(1): 4403, 2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37479684

RESUMEN

The p53 tumor suppressor regulates multiple context-dependent tumor suppressive programs. Although p53 is mutated in ~90% of small cell lung cancer (SCLC) tumors, how p53 mediates tumor suppression in this context is unknown. Here, using a mouse model of SCLC in which endogenous p53 expression can be conditionally and temporally regulated, we show that SCLC tumors maintain a requirement for p53 inactivation. However, we identify tumor subtype heterogeneity between SCLC tumors such that p53 reactivation induces senescence in a subset of tumors, while in others, p53 induces necrosis. We pinpoint cyclophilins as critical determinants of a p53-induced transcriptional program that is specific to SCLC tumors and cell lines poised to undergo p53-mediated necrosis. Importantly, inhibition of cyclophilin isomerase activity, or genetic ablation of specific cyclophilin genes, suppresses p53-mediated necrosis by limiting p53 transcriptional output without impacting p53 chromatin binding. Our study demonstrates that intertumoral heterogeneity in SCLC influences the biological response to p53 restoration, describes a cyclophilin-dependent mechanism of p53-regulated cell death, and uncovers putative mechanisms for the treatment of this most-recalcitrant tumor type.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Ciclofilinas/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Proteína p53 Supresora de Tumor/genética , Necrosis/genética , Neoplasias Pulmonares/genética
4.
Commun Biol ; 6(1): 255, 2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36899051

RESUMEN

SETD2 is a tumor suppressor that is frequently inactivated in several cancer types. The mechanisms through which SETD2 inactivation promotes cancer are unclear, and whether targetable vulnerabilities exist in these tumors is unknown. Here we identify heightened mTORC1-associated gene expression programs and functionally higher levels of oxidative metabolism and protein synthesis as prominent consequences of Setd2 inactivation in KRAS-driven mouse models of lung adenocarcinoma. Blocking oxidative respiration and mTORC1 signaling abrogates the high rates of tumor cell proliferation and tumor growth specifically in SETD2-deficient tumors. Our data nominate SETD2 deficiency as a functional marker of sensitivity to clinically actionable therapeutics targeting oxidative respiration and mTORC1 signaling.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Animales , Ratones , Adenocarcinoma del Pulmón/genética , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Estrés Oxidativo , N-Metiltransferasa de Histona-Lisina/genética
5.
Kardiologiia ; 62(8): 3-10, 2022 Aug 30.
Artículo en Ruso, Inglés | MEDLINE | ID: mdl-36066981

RESUMEN

Aim      To develop an algorithm for using ultrasonic flowmetry (USF) and epicardial ultrasonic scanning (EpiUSS) for intraoperative assessment of anatomic and functional viability of conduits.Material and methods  For viability assessment of 460 coronary grafts in 150 patients who were operated at the Bakulev National Medical Research Center for Cardiovascular Surgery (2018-2021 г.), markers of graft failure were analyzed using the USF and EpiUSS data confirmed by results of graft angiography. According to RОС analysis, the Qmean and PI values indicative of the graft failure were determined. A CHAID decision tree was developed for assessing the prognostic significance of the analyzed parameters. Based on this prognostic model, an algorithm was developed for intraoperative diagnosis of anatomic and functional graft viability during coronary bypass surgery.Results The Qmean ≤20.5 ml/min values were associated with an increased relative risk (RR) of detecting graft failure (RR, 8.2; 95 % confidence interval, CI, 4.4-15.2). The developed model shows a high accuracy of predicting the graft failure (AUC = 0.906±0.03). The RR of graft failure at PI ≥2.65 was 3.3 (95 % CI, 2.17-5.08). The prognostic model for PI (AUC = 0.745±0.042) was sufficiently accurate with respect of possible graft failure. Nodes of high and low risk for graft failure were determined in the developed decision tree. The obtained model was characterized by high sensitivity and specificity (100 and 84.3 %, respectively).Conclusion      The combined use of USF and EpiUSS allows a highly accurate assessment of both morphological and functional characteristics of graft flow. The developed algorithm for the intraoperative diagnosis of anatomic and functional graft viability can be recommended for clinical use.


Asunto(s)
Algoritmos , Puente de Arteria Coronaria , Velocidad del Flujo Sanguíneo , Angiografía Coronaria , Puente de Arteria Coronaria/efectos adversos , Circulación Coronaria , Humanos , Pronóstico , Ultrasonografía , Grado de Desobstrucción Vascular
6.
Stem Cells Transl Med ; 11(10): 1052-1060, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36073721

RESUMEN

We aim to create a bank of clinical grade cord blood-derived induced pluripotent stem cell lines in order to facilitate clinical research leading to the development of new cellular therapies. Here we present a clear pathway toward the creation of such a resource, within a strong quality framework, and with the appropriate regulatory, government and ethics approvals, along with a dynamic follow-up and re-consent process of cord blood donors from the public BMDI Cord Blood Bank. Interrogation of the cord blood bank inventory and next generation sequencing was used to identify and confirm 18 donors with suitable HLA homozygous haplotypes. Regulatory challenges that may affect global acceptance of the cell lines, along with the quality standards required to operate as part of a global network, are being met by working in collaboration with bodies such as the International Stem Cell Banking Initiative (ISCBI) and the Global Alliance for iPSC Therapies (GAiT). Ethics approval was granted by an Institutional Human Research Ethics Committee, and government approval has been obtained to use banked cord blood for this purpose. New issues of whole-genome sequencing and the relevant donor safeguards and protections were considered with input from clinical genetics services, including the rights and information flow to donors, and commercialization aspects. The success of these processes has confirmed feasibility and utility of using banked cord blood to produce clinical-grade iPSC lines for potential cellular therapies.


Asunto(s)
Sangre Fetal , Células Madre Pluripotentes Inducidas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Donantes de Sangre , Bancos de Sangre , Consentimiento Informado
7.
Eur J Immunol ; 51(4): 864-878, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33616974

RESUMEN

Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that ß-glucans, major fungal cell-wall glycans, induced chemokine secretion by IEC lines in a Dectin-1- and Syk-dependent manner. Here, we show that in contrast to ß-glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL-8, CCL2, CXCL1, and GM-CSF. Commensal fungi and ß-glucans activated Syk and ERK in IEC lines. However, only ß-glucans activated p38, JNK, and the transcription factors NF-κB p65 and c-JUN, which were necessary for cytokine secretion. Furthermore, costimulation of IEC lines with ß-glucans and C. albicans yielded decreased cytokine secretion compared to stimulation with ß-glucans alone. Finally, ex vivo stimulation of human colonic mucosal explants with zymosan and C. albicans, leads to epithelial Syk and ERK phosphorylation, implying recognition of fungi and similar initial signaling pathways as in IEC lines. Lack of cytokine secretion in response to commensal fungi may reflect IECs' response to fungal glycans, other than ß-glucans, that contribute to mucosal tolerance. Skewed epithelial response to commensal fungi may impair homeostasis and contribute to intestinal inflammation.


Asunto(s)
Candida albicans/inmunología , Pared Celular/inmunología , Células Epiteliales/inmunología , Mucosa Intestinal/inmunología , beta-Glucanos/inmunología , Células CACO-2 , Candida albicans/metabolismo , Candida albicans/fisiología , Línea Celular Tumoral , Pared Celular/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Quinasas MAP Reguladas por Señal Extracelular/inmunología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células HT29 , Interacciones Huésped-Patógeno/inmunología , Humanos , Mucosa Intestinal/microbiología , Fosforilación/inmunología , Quinasa Syk/inmunología , Quinasa Syk/metabolismo , Zimosan/inmunología , Zimosan/metabolismo , beta-Glucanos/metabolismo
8.
J Public Health Res ; 9(3): 1696, 2020 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-32874961

RESUMEN

Background: We examined paradoxical and barrio advantaging effects on cancer care among socioeconomically vulnerable Hispanic people in California. Methods: We secondarily analyzed a colon cancer cohort of 3,877 non-Hispanic white (NHW) and 735 Hispanic people treated between 1995 and 2005. A third of the cohort was selected from high poverty neighborhoods. Hispanic enclaves and Mexican American (MA) barrios were neighborhoods where 40% or more of the residents were Hispanic or MA. Key analyses were restricted to high poverty neighborhoods. Results: Hispanic people were more likely to receive chemotherapy (RR=1.18), especially men in Hispanic enclaves (RR=1.33) who were also advantaged on survival (RR=1.20). A survival advantage was also suggested among MA men who resided in barrios (RR=1.80). Conclusions: The findings were supportive of Hispanic paradox and MA barrio advantage theories. They further suggested that such advantages are greater for men, perhaps due to their greater spousal and extended familial support.

9.
Materials (Basel) ; 13(3)2020 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-32033092

RESUMEN

In this review on contacts with MoS2, we consider reports on both interface chemistry and device characteristics. We show that there is considerable disagreement between reported properties, at least some of which may be explained by variability in the properties of geological MoS2. Furthermore, we highlight that while early experiments using photoemission to study the interface behavior of metal-MoS2 showed a lack of Fermi-level pinning, device measurements repeatedly confirm that the interface is indeed pinned. Here we suggest that a parallel conduction mechanism enabled by metallic defects in the MoS2 materials may explain both results. We note that processing conditions during metal depositions on MoS2 can play a critical role in the interface chemistry, with differences between high vacuum and ultra-high vacuum being particularly important for low work function metals. This can be used to engineer the interfaces by using thin metal-oxide interlayers to protect the MoS2 from reactions with the metals. We also report on the changes in the interfaces that can occur at high temperature which include enhanced reactions between Ti or Cr and MoS2, diffusion of Ag into MoS2, and delamination of Fe. What is clear is that there is a dearth of experimental work that investigates both the interface chemistry and device properties in parallel.

10.
ACS Appl Mater Interfaces ; 11(38): 35389-35393, 2019 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-31468959

RESUMEN

Thermal annealing of Ti contacts is commonly implemented in the fabrication of MoS2 devices; however, its effects on interface chemistry have not been previously reported in the literature. In this work, the thermal stability of titanium contacts deposited on geological bulk single crystals of MoS2 in ultrahigh vacuum (UHV) is investigated with X-ray photoelectron spectroscopy and scanning transmission electron microscopy (STEM). In the as-deposited condition, the reaction of Ti with MoS2 is observed resulting in a diffuse interface between the two materials that comprises metallic molybdenum and titanium sulfide compounds. Annealing Ti/MoS2 sequentially at 100, 300, and 600 °C for 30 min in UHV results in a gradual increase in the reaction products as measured by XPS. Accordingly, STEM reveals the formation of a new ordered phase and a Mo-rich layer at the interface following heating. Due to the high degree of reactivity, the Ti/MoS2 interface is not thermally stable even at a transistor operating temperature of 100 °C, while post-deposition annealing further enhances the interfacial reactions. These findings have important consequences for electrical transport properties, highlighting the importance of interface chemistry in the metal contact design and fabrication.

11.
J Public Health Res ; 8(1): 1479, 2019 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-30997359

RESUMEN

This study tested the hypothesis that socioeconomically vulnerable Canadians with diverse acute conditions or chronic diseases have health care access and survival advantages over their counterparts in the USA. A rapid systematic review retrieved 25 studies (34 independent cohorts) published between 2003 and 2018. They were synthesized with a streamlined meta-analysis. Very low-income Canadian patients were consistently and highly advantaged in terms of health care access and survival compared with their counterparts in the USA who lived in poverty and/or were uninsured or underinsured. In aggregate and controlling for specific conditions or diseases and typically 4 to 9 comorbid factors or biomarkers, Canadians' chances of receiving better health care were estimated to be 36% greater than their American counterparts (RR=1.36, 95% CI 1.35-1.37). This estimate was significantly larger than that based on general patient or non-vulnerable population comparisons (RR=1.09, 95% CI 1.08-1.10). Contrary to prevalent political rhetoric, three studies observed that Americans experience more than twice the risk of long waits for breast or colon cancer care or of dying while they wait for an organ transplant (RR=2.36, 95% CI 2.09-2.66). These findings were replicated across externally valid national studies and more internally valid, metropolitan or provincial/state comparisons. Socioeconomically vulnerable Canadians are consistently and highly advantaged on health care access and outcomes compared to their American counterparts. Less vulnerable comparisons found more modest Canadian advantages. The Affordable Care Act ought to be fully supported including the expansion of Medicaid across all states. Canada's single payer system ought to be maintained and strengthened, but not through privatization.

12.
Elife ; 82019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30666957

RESUMEN

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


Asunto(s)
Infecciones por Clostridium/microbiología , Enfermedad de Crohn/microbiología , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Adiposidad , Adulto , Anciano , Anciano de 80 o más Años , Animales , Clostridioides difficile , Femenino , Homeostasis , Humanos , Íleon/microbiología , Sistema Inmunológico , Enfermedades Inflamatorias del Intestino , Masculino , Ratones , Ratones Endogámicos C57BL , Microbiota , Persona de Mediana Edad , Membrana Mucosa/microbiología , Fenotipo , ARN Ribosómico 16S/metabolismo , Especificidad de la Especie , Adulto Joven
13.
Inflamm Bowel Dis ; 24(5): 1045-1054, 2018 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-29688474

RESUMEN

Background: A large-scale increase in microRNA (miRNA) expression was observed in patients with ulcerative colitis who underwent pouch surgery and developed inflammation of the pouch (pouchitis). In this study, we assessed miRNA expression in these patients and investigated how regulation of its expression changes in the setting of pouchitis. Methods: Autologous samples that included mucosal biopsies, peripheral blood cells, and plasma were collected from the patients. Candidate primary and mature miRNA expressions were analyzed by quantitative polymerase chain reaction. A human intestinal epithelial cell line was used to test DICER activity, and the expression of key miRNA processing factors was analyzed by Western blot. miRNA-424 and its potential target serotonin reuptake transporter (SERT) expressions were examined by quantitative reverse transcription polymerase chain reaction and Western blot in human pouch tissues and in a human intestinal epithelial cell line stimulated with inflammatory cytokines TNF-α, IL-1ß, and INF-γ. Results: Candidate miRNA expression and protein expression of DICER-1, EXPORTIN-5, and AGO-2 were increased in association with pouch inflammation. Similarly, inflammatory cytokines increased protein expression of DICER-1, EXPORTIN-5, and AGO-2 and DICER activity in the epithelial cell line. The miRNA-424 expression increased whereas SERT expression decreased in the patients' mucosa. Similarly, incubation of the epithelial cell line with inflammatory cytokines resulted in increased miRNA-424 and decreased SERT mRNA and protein expression. Conclusions: The miRNA expression and processing are augmented in the inflamed intestinal mucosa of patients with pouchitis. These alterations are accompanied by increased expression of proteins involved in miRNA processing, suggesting that pouch inflammation contributes to miRNA processing and expression.


Asunto(s)
Colitis Ulcerosa/metabolismo , Reservorios Cólicos/patología , Mucosa Intestinal/metabolismo , MicroARNs/metabolismo , Reservoritis/metabolismo , Adolescente , Adulto , Colitis Ulcerosa/patología , Colitis Ulcerosa/cirugía , Colon/patología , Citocinas/metabolismo , Células Epiteliales/metabolismo , Femenino , Humanos , Inflamación/patología , Mucosa Intestinal/patología , Intestino Delgado/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Reservoritis/patología , Proctocolectomía Restauradora/efectos adversos , Estudios Prospectivos , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Adulto Joven
14.
Nanotechnology ; 29(14): 145201, 2018 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-29372892

RESUMEN

Contact resistance (R C) is a major limiting factor in the performance of graphene devices. R C is sensitive to the quality of the interface and the composition of the contact, which are affected by the graphene transfer process and contact deposition conditions. In this work, a linear correlation is observed between the composition of Ti contacts, characterized by x-ray photoelectron spectroscopy, and the Ti/graphene contact resistance measured by the transfer length method. We find that contact composition is tunable via deposition rate and base pressure. Reactor base pressure is found to effect the resultant contact resistance. The effect of contact deposition conditions on thermal transport measured by time-domain thermoreflectance is also reported. Interfaces with higher oxide composition appear to result in a lower thermal boundary conductance. Possible origins of this thermal boundary conductance change with oxide composition are discussed.

15.
J Intellect Disabil Res ; 61(12): 1083-1093, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28990288

RESUMEN

BACKGROUND: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. METHODS: Eighty-two children participated in four study groups: WS (n = 18), 22q112.DS (n = 24), age-matched individuals with idiopathic developmental disability (IDD; n = 20) and typically developing (TD) controls (n = 20). Participants completed four socio-cognitive tests: facial emotion recognition, mental state attribution, differentiating real from apparent emotions and trait inference based on motives and actions-outcomes. RESULTS: The current findings demonstrate that children with WS were better in labelling happy faces compared with children with 22q11.2DS, partially reflecting their exaggerated social drive. In the false belief task, however, the WS and IDD groups performed poorly compared with the 22q11.2DS group, possibly due to their difficulty to interpret subtle social cues. When asked to identify the gap between real-negative vs. apparent-positive emotions, the 22q11.2DS group performed similarly to TD children but better than the WS group, possibly due to their anxious personality and their innate bias towards negatively valence cues. Finally, individuals with WS were more willing to become friends with a story character even when the character's motives were negative, reflecting their difficulty to avoid potentially harmful real-life situations. CONCLUSIONS: Overall, our multi-facet socio-cognitive battery uncovered strengths and weaknesses in social cognition that are syndrome-specific, shared among the genetic syndromes, or common to the three clinical groups compared with healthy controls. Our findings underscore the need to devise age-specific and condition-specific assessment tools and intervention programs towards improving these children's socio-cognitive deficits.


Asunto(s)
Discapacidades del Desarrollo/fisiopatología , Síndrome de DiGeorge/fisiopatología , Emociones/fisiología , Reconocimiento Facial/fisiología , Percepción Social , Teoría de la Mente/fisiología , Síndrome de Williams/fisiopatología , Adolescente , Niño , Femenino , Humanos , Masculino
16.
Bio Protoc ; 7(3): e2128, 2017 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-34458449

RESUMEN

Hydrogels are an ideal medium for the expansion of cells in three dimensions. The ability to induce cell expansion and differentiation in a controlled manner is a key goal in tissue engineering. Here we describe a detailed method for producing hydrogels from soft tissues with an emphasis on adipose tissue. In this method, soluble, extractable proteins are recovered from the tissue and stored while the remaining insoluble tissue is processed and solubilised. Once the tissue has been sufficiently solubilised, the extracted proteins are added. The resulting product is a thermosensitive hydrogel with proteins representative of the native tissue. This method addresses common issues encountered when working with some biomaterials, such as high lipid content, DNA contamination, and finding an appropriate sterilisation method. Although the focus of this article is on adipose tissue, using this method we have produced hydrogels from other soft tissues including muscle, liver, and cardiac tissue.

17.
J Tissue Eng Regen Med ; 11(4): 1230-1241, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-25950280

RESUMEN

'Off-the-shelf' tissue-engineered skin alternatives for epidermal and dermal skin layers are available; however, no such alternative for the subdermal fat layer exists. Without this well-vascularized layer, skin graft take is variable and grafts may have reduced mobility, contracture and contour defects. In this study a novel adipose-derived acellular matrix (Adipogel) was investigated for its properties to generate subdermal fat in a rat model. In a dorsal thoracic site, a 1 × 1 cm Adipogel implant was inserted within a subdermal fat layer defect. In a dorsal lumbar site, an Adipogel implant was inserted in a subfascial pocket. Contralateral control defects remained empty. At 8 weeks wound/implant sites were evaluated histologically, immunohistochemically and morphometrically. Identifiable thoracic Adipogel implants lost volume in vivo over 8 weeks. Neovascularization and adipogenesis were evident within implants and adipocyte percentage volume was 33.07 ± 6.55% (mean ± SEM). A comparison of entire cross-sections of thoracic wounds demonstrated a significant increase in total wound fat in Adipogel-implanted wounds (37.19 ± 4.48%, mean ± SEM) compared to control (16.53 ± 4.60%; p = 0.0092), indicating that some Adipogel had been completely converted to normal fat. At the lumbar site, Adipogel also lost volume, appearing flattened, although fat generation and angiogenesis occurred. At both sites macrophage infiltration was mild, whilst many infiltrating cells were PDGFRß-positive mesenchymal cells. Adipogel is adipogenic and angiogenic and is a promising candidate for subcutaneous fat regeneration; it has the potential to be a valuable adjunct to wound-healing therapy and reconstructive surgery practice. Copyright © 2015 John Wiley & Sons, Ltd.


Asunto(s)
Adipogénesis , Geles/farmacología , Procedimientos de Cirugía Plástica/métodos , Tejido Subcutáneo/cirugía , Animales , Inmunohistoquímica , Implantes Experimentales , Masculino , Perilipina-1/metabolismo , Ratas Sprague-Dawley , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Tejido Subcutáneo/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
18.
Am J Physiol Heart Circ Physiol ; 311(4): H1063-H1071, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27521419

RESUMEN

Endothelial cells (EC) respond to mechanical forces such as shear stress in a variety of ways, one of which is cytoskeletal realignment in the direction of flow. Our earlier studies implicated the extracellular matrix protein fibronectin in mechanosensory signaling to ECs in intact arterioles, via a signaling pathway dependent on the heparin-binding region of the first type III repeat of fibrillar fibronectin (FNIII1H). Here we test the hypothesis that FNIII1H is required for EC stress fiber realignment under flow. Human umbilical vein ECs (HUVECs) exposed to defined flow conditions were used as a well-characterized model of this stress fiber alignment response. Our results directly implicate FNIII1H in realignment of stress fibers in HUVECs and, importantly, show that the matricryptic heparin-binding RWRPK sequence located in FNIII1 is required for the response. Furthermore, we show that flow-mediated stress fiber realignment in ECs adhered via α5ß1-integrin-specific ligands does not occur in the absence of FHIII1H, whereas, in contrast, αvß3-integrin-mediated stress fiber realignment under flow does not require FNIII1H. Our findings thus indicate that there are two separate mechanosignaling pathways mediating the alignment of stress fibers after exposure of ECs to flow, one dependent on αvß3-integrins and one dependent on FNIII1H. This study strongly supports the conclusion that the RWRPK region of FNIII1H may have broad capability as a mechanosensory signaling site.


Asunto(s)
Células Endoteliales/metabolismo , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Mecanotransducción Celular , Estrés Mecánico , Células Endoteliales/fisiología , Heparina , Células Endoteliales de la Vena Umbilical Humana , Humanos , Integrina alfa5beta1/metabolismo , Integrina alfaVbeta3/metabolismo , Microscopía Fluorescente
19.
Transl Psychiatry ; 6: e816, 2016 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-27219342

RESUMEN

Studying early interaction is essential for understanding development and psychopathology. Automatic computational methods offer the possibility to analyse social signals and behaviours of several partners simultaneously and dynamically. Here, 20 dyads of mothers and their 13-36-month-old infants were videotaped during mother-infant interaction including 10 extremely high-risk and 10 low-risk dyads using two-dimensional (2D) and three-dimensional (3D) sensors. From 2D+3D data and 3D space reconstruction, we extracted individual parameters (quantity of movement and motion activity ratio for each partner) and dyadic parameters related to the dynamics of partners heads distance (contribution to heads distance), to the focus of mutual engagement (percentage of time spent face to face or oriented to the task) and to the dynamics of motion activity (synchrony ratio, overlap ratio, pause ratio). Features are compared with blind global rating of the interaction using the coding interactive behavior (CIB). We found that individual and dyadic parameters of 2D+3D motion features perfectly correlates with rated CIB maternal and dyadic composite scores. Support Vector Machine classification using all 2D-3D motion features classified 100% of the dyads in their group meaning that motion behaviours are sufficient to distinguish high-risk from low-risk dyads. The proposed method may present a promising, low-cost methodology that can uniquely use artificial technology to detect meaningful features of human interactions and may have several implications for studying dyadic behaviours in psychiatry. Combining both global rating scales and computerized methods may enable a continuum of time scale from a summary of entire interactions to second-by-second dynamics.


Asunto(s)
Relaciones Madre-Hijo , Grabación en Video , Adulto , Preescolar , Femenino , Humanos , Imagenología Tridimensional , Lactante , Masculino
20.
Vestn Ross Akad Med Nauk ; (3): 300-6, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-26495717

RESUMEN

OBJECTIVE: Our aim was to compare results of the percutaneous coronary intervention (PCI) with drug elutingstent (DES) and bare metal stent (BMS) in older patients with coronary heart disease (CHD) and diabetes mellitus (DM) type 2. METHODS: Patients (> 65 years) with DM type 2 were divided into two groups: the 1st group--58 patients after PCI with DES, the 2nd group--62 patients after PCI with BMS. The average follow-up period was 32.6 ± 8.0 months. The end-points of the study were death, non-fatal myocardial infarction and restenosis of the target stenosis. RESULTS: Endovascular treatment of patients older than 65 years with DM is highly effective and safe despite the complexity of coronary lesions. There are no significant differences in the rate of early (hospital) complications in two groups. Also, we did notfind differences in three-year mortality between the groups. But the incidence of myocardial infarction in the groups with DES and BMS was 9% and 18% respectively (p = 0.039). Major adverse cardiovascular events (death, myocardial infarction and restenosis of the target stenosis) frequency was also lower in the group with DES compared to BMS (36% and 61% respectively, p = 0.001). CONCLUSION: Endovascular treatment of patients older than 65 years with DM type 2 is a highly effective and safe method despite the complexity of coronary lesions. PCI with DES compared to BMS in older patients with DM is associated with improvement of medium-term results and decreases the number of cardiovascular events.


Asunto(s)
Enfermedad de la Arteria Coronaria , Reestenosis Coronaria , Diabetes Mellitus Tipo 2/complicaciones , Infarto del Miocardio , Intervención Coronaria Percutánea , Complicaciones Posoperatorias , Stents , Anciano , Anciano de 80 o más Años , Investigación sobre la Eficacia Comparativa , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/etiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Moscú/epidemiología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Evaluación de Resultado en la Atención de Salud , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Stents/efectos adversos , Stents/clasificación , Stents/estadística & datos numéricos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA