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1.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38980369

RESUMEN

Recent studies have extensively used deep learning algorithms to analyze gene expression to predict disease diagnosis, treatment effectiveness, and survival outcomes. Survival analysis studies on diseases with high mortality rates, such as cancer, are indispensable. However, deep learning models are plagued by overfitting owing to the limited sample size relative to the large number of genes. Consequently, the latest style-transfer deep generative models have been implemented to generate gene expression data. However, these models are limited in their applicability for clinical purposes because they generate only transcriptomic data. Therefore, this study proposes ctGAN, which enables the combined transformation of gene expression and survival data using a generative adversarial network (GAN). ctGAN improves survival analysis by augmenting data through style transformations between breast cancer and 11 other cancer types. We evaluated the concordance index (C-index) enhancements compared with previous models to demonstrate its superiority. Performance improvements were observed in nine of the 11 cancer types. Moreover, ctGAN outperformed previous models in seven out of the 11 cancer types, with colon adenocarcinoma (COAD) exhibiting the most significant improvement (median C-index increase of ~15.70%). Furthermore, integrating the generated COAD enhanced the log-rank p-value (0.041) compared with using only the real COAD (p-value = 0.797). Based on the data distribution, we demonstrated that the model generated highly plausible data. In clustering evaluation, ctGAN exhibited the highest performance in most cases (89.62%). These findings suggest that ctGAN can be meaningfully utilized to predict disease progression and select personalized treatments in the medical field.


Asunto(s)
Aprendizaje Profundo , Humanos , Análisis de Supervivencia , Algoritmos , Neoplasias/genética , Neoplasias/mortalidad , Perfilación de la Expresión Génica/métodos , Redes Neurales de la Computación , Biología Computacional/métodos , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Femenino , Regulación Neoplásica de la Expresión Génica
2.
Am J Transplant ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39368656

RESUMEN

Patients receiving liver transplantation in a setting of complete portal vein (PV) and superior mesenteric vein (SMV) thrombosis (Yerdel grade 4) experience lower outcomes after surgery; prognosis is independently influenced by the portal flow reconstruction technique, showing better outcomes in physiological surgical strategies. We describe a case of living donor liver transplantation in which the patient could not receive common physiological reconstructions pre-operatively due to multiple small collaterals and extensive thrombosis down to 1st branches of SMV. We performed thrombo-endo-venectomy of the portal vein and SMV first, but acute thrombosis developed recurrently even with interposition venous homograft between peri-choledochal collateral vein and proximal recipient portal vein. Immediate after surgery, intervention radiologist performed stenting insertion into 3 stenotic points. Through multidisciplinary approach, complete physiologic recanalization was obtained with normal liver function.

3.
Am J Transplant ; 24(2): 222-238, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37321453

RESUMEN

Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.


Asunto(s)
Laparoscopía , Trasplante de Hígado , Humanos , Hepatectomía/métodos , Seúl , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Hígado/cirugía , Recolección de Tejidos y Órganos/efectos adversos , Laparoscopía/métodos , Tempo Operativo , Hospitales , Complicaciones Posoperatorias/etiología
4.
Magn Reson Med ; 91(6): 2483-2497, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38342983

RESUMEN

PURPOSE: We introduced a novel reconstruction network, jointly unrolled cross-domain optimization-based spatio-temporal reconstruction network (JUST-Net), aimed at accelerating 3D multi-echo gradient-echo (mGRE) data acquisition and improving the quality of resulting myelin water imaging (MWI) maps. METHOD: An unrolled cross-domain spatio-temporal reconstruction network was designed. The main idea is to combine frequency and spatio-temporal image feature representations and to sequentially implement convolution layers in both domains. The k-space subnetwork utilizes shared information from adjacent frames, whereas the image subnetwork applies separate convolutions in both spatial and temporal dimensions. The proposed reconstruction network was evaluated for both retrospectively and prospectively accelerated acquisition. Furthermore, it was assessed in simulation studies and real-world cases with k-space corruptions to evaluate its potential for motion artifact reduction. RESULTS: The proposed JUST-Net enabled highly reproducible and accelerated 3D mGRE acquisition for whole-brain MWI, reducing the acquisition time from fully sampled 15:23 to 2:22 min within a 3-min reconstruction time. The normalized root mean squared error of the reconstructed mGRE images increased by less than 4.0%, and the correlation coefficients for MWI showed a value of over 0.68 when compared to the fully sampled reference. Additionally, the proposed method demonstrated a mitigating effect on both simulated and clinical motion-corrupted cases. CONCLUSION: The proposed JUST-Net has demonstrated the capability to achieve high acceleration factors for 3D mGRE-based MWI, which is expected to facilitate widespread clinical applications of MWI.


Asunto(s)
Vaina de Mielina , Agua , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Imagenología Tridimensional/métodos , Procesamiento de Imagen Asistido por Computador/métodos
5.
Int J Mol Sci ; 25(12)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38928239

RESUMEN

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.


Asunto(s)
Adenosina , Alopecia , Folículo Piloso , Cabello , Minoxidil , Receptores Androgénicos , Transducción de Señal , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Alopecia/patología , Humanos , Masculino , Receptores Androgénicos/metabolismo , Adenosina/metabolismo , Adenosina/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Transducción de Señal/efectos de los fármacos , Minoxidil/farmacología , Femenino , Animales , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Cabello/metabolismo
6.
Curr Issues Mol Biol ; 45(7): 5902-5913, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37504289

RESUMEN

Abnormal inactivation of the Wnt/ß-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated the stimulatory effects of escin on the canonical Wnt/ß-catenin signaling pathway in cultured human dermal papilla cells (hDPCs). Escin stimulated Wnt/ß-catenin signaling, resulting in increased ß-catenin and lymphoid enhancer-binding factor 1 (LEF1), the accumulation of nuclear ß-catenin and the enhanced expression of Wnt target genes in cultured hDPCs. Escin drastically reduced the protein level of glycogen synthase kinase (GSK)-3ß, a key regulator of the Wnt/ß-catenin signaling pathway, while the presence of the proteasome inhibitor MG-132 fully restored the GSK-3ß protein level. The treatment of secreted frizzled-related proteins (sFRPs) 1 and 2 attenuated the activity of escin in Wnt reporter assays. Our data demonstrate that escin is a natural agonist of the canonical Wnt/ß-catenin signaling pathway and downregulates GSK-3ß protein expression by facilitating the proteasomal degradation of GSK-3ß in cultured hDPCs. Our data suggest that escin likely stimulates Wnt signaling through direct interactions with frizzled receptors. This study underscores the therapeutic potential of escin for Wnt-related diseases such as androgenetic alopecia, vitiligo and canities.

7.
Genomics ; 114(2): 110298, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35134497

RESUMEN

Yeonsan Ogye (OGYE; Gallus gallus domesticus) is a rare indigenous chicken breed that inhabits the Korean Peninsula. This breed has completely black coloring, including plumage, skin, eyes, beak, and internal organs. Despite these unique morphological characteristics, the population of OGYE has declined without in-depth research into their genome research. Therefore, this study aimed to compare the whole genome of OGYE to 12 other chicken populations, including ancestral breed, commercial breeds, Chinese indigenous breeds, and Korean native chickens. We focused on revealing the selection signature of OGYE, which has occurred through environmental pressures in the Korean Peninsula. Genome-wide selection analysis has identified local adaptation traits, such as egg development, that contribute to fetal viability and innate immune response to prevent viral and microbes infection in OGYE. In particular, SPP1 (Secreted Phosphoprotein 1), HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1), and P2RX4 (Purinergic Receptor P2X 4) could have considerable involvement in egg development and RNASEL (Ribonuclease L), BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1), and TLR4 (Toll-Like Receptor 4) are crucial for the determination of the innate immune response. This study revealed the unique genetic diversity of OGYE at the genome-wide level. Furthermore, we emphasized the sustainable management of genetic resources and formulated breeding strategies for livestock on the Korean Peninsula.


Asunto(s)
Pollos , Genómica , Animales , Pollos/genética , Pollos/metabolismo , Genoma , Fenotipo , Polimorfismo de Nucleótido Simple , Selección Genética , Secuenciación Completa del Genoma
8.
Infect Immun ; 90(6): e0004122, 2022 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-35579465

RESUMEN

Secretory IgA (SIgA) is the most abundant antibody type in intestinal secretions where it contributes to safeguarding the epithelium from invasive pathogens like the Gram-negative bacterium, Salmonella enterica serovar Typhimurium (STm). For example, we recently reported that passive oral administration of the recombinant monoclonal SIgA antibody, Sal4, to mice promotes STm agglutination in the intestinal lumen and restricts bacterial invasion of Peyer's patch tissues. In this report, we sought to recapitulate Sal4-mediated protection against STm in human Enteroids and human intestinal organoids (HIOs) as models to decipher the molecular mechanisms by which antibodies function in mucosal immunity in the human gastrointestinal tract. We confirm that Enteroids and HIO-derived monolayers are permissive to STm infection, dependent on HilD, the master transcriptional regulator of the SPI-I type three secretion system (T3SS). Stimulation of M-like cells in both Enteroids and HIOs by the addition of RANKL further enhanced STm invasion. The apical addition of Sal4 mouse IgA, as well as recombinant human Sal4 dimeric IgA (dIgA) and SIgA resulted a dose-dependent reduction in bacterial invasion. Moreover, basolateral application of Sal4 dIgA to Enteroid and HIO monolayers gave rise to SIgA in the apical compartment via a pathway dependent on expression of the polymeric immunoglobulin receptor (pIgR). The resulting Sal4 SIgA was sufficient to reduce STm invasion of Enteroid and HIO epithelial cell monolayers by ~20-fold. Recombinant Sal4 IgG was also transported in the Enteroid and HIOs, but to a lesser degree and via a pathway dependent on the neonatal Fc receptor (FCGRT). The models described lay the foundation for future studies into detailed mechanisms of IgA and IgG protection against STm and other pathogens.


Asunto(s)
Inmunoglobulina A , Organoides , Animales , Humanos , Inmunoglobulina A/metabolismo , Inmunoglobulina A Secretora , Inmunoglobulina G/metabolismo , Mucosa Intestinal/metabolismo , Ratones , Organoides/metabolismo , Salmonella typhimurium , Transcitosis
9.
Proc Natl Acad Sci U S A ; 116(52): 26816-26822, 2019 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-31826954

RESUMEN

Patients with amyotrophic lateral sclerosis (ALS) often show hallmarks of type 2 diabetes mellitus (T2DM). However, the causal link between ALS and T2DM has remained a mystery. We now demonstrate that 60% of ALS patients with T2DM (ALS-T2DM) have sera that exaggerated K+-induced increases in cytosolic free Ca2+ concentration ([Ca2+]i) in mouse islet cells. The effect was attributed to the presence of pathogenic immunoglobulin Gs (IgGs) in ALS-T2DM sera. The pathogenic IgGs immunocaptured the voltage-dependent Ca2+ (CaV) channel subunit CaVα2δ1 in the plasma membrane enhancing CaV1 channel-mediated Ca2+ influx and [Ca2+]i, resulting in impaired mitochondrial function. Consequently, impairments in [Ca2+]i dynamics, insulin secretion, and cell viability occurred. These data reveal that patients with ALS-T2DM carry cytotoxic ALS-T2DM-IgG autoantibodies that serve as a causal link between ALS and T2DM by immunoattacking CaVα2δ1 subunits. Our findings may lay the foundation for a pharmacological treatment strategy for patients suffering from a combination of these diseases.

10.
Molecules ; 27(7)2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35408582

RESUMEN

In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/ß-catenin pathway by modulating the activity of Gsk3ß in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3ß was increased. Furthermore, the expression of ß-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/ß-catenin signaling through the activation of the adenosine receptor and Gsk3ß plays a critical role in transmitting the signals from the adenosine receptor to ß-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.


Asunto(s)
Adenosina , beta Catenina , Adenosina/metabolismo , Adenosina/farmacología , Alopecia/metabolismo , Células Cultivadas , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Folículo Piloso/metabolismo , Humanos , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Vía de Señalización Wnt , beta Catenina/genética , beta Catenina/metabolismo
11.
Curr Issues Mol Biol ; 43(3): 1361-1373, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34698060

RESUMEN

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; ß-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-ß1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.


Asunto(s)
Apoptosis/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Folículo Piloso/citología , Ácido Pantoténico/análogos & derivados , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Apoptosis/genética , Biomarcadores , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Senescencia Celular/genética , Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Humanos , Ácido Pantoténico/farmacología , ARN Mensajero , Complejo Vitamínico B/farmacología
12.
Nano Lett ; 20(3): 1517-1525, 2020 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-31750664

RESUMEN

Intraocular islet transplantation was investigated as a new procedure to treat diabetes. The development of this procedure requires close monitoring of the function of both eye and islet graft. We developed a soft, smart contact lens to monitor the intraocular pressure and applied this for noninvasive monitoring in association with the intraocular islet transplantation in diabetes. A strain sensor inside the lens can detect detailed changes in intraocular pressure by focusing the strain only in the desired, selective area of the contact lens. In addition, this smart contact lens can transmit the real-time value of the intraocular pressure wirelessly using an antenna. The wireless measurement of intraocular pressure that was obtained using this contact lens had a high correlation with the intraocular pressure measured by a rebound tonometer, thereby proving the good accuracy of the contact lens sensor. In the initial period, a slight elevation of intraocular pressure was observed, but the pressure returned to normal in the initial period after the transplantation. This type of monitoring will provide important information on potential changes in the intraocular pressure associated with the transplantation procedure, and it enables appropriate clinical safety steps to be taken, if needed.


Asunto(s)
Cámara Anterior , Lentes de Contacto Hidrofílicos , Presión Intraocular , Trasplante de Islotes Pancreáticos , Animales , Cámara Anterior/fisiopatología , Cámara Anterior/cirugía , Monitoreo Fisiológico , Ratas , Ratas Endogámicas Lew
13.
Int J Mol Sci ; 22(11)2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34070360

RESUMEN

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/ß-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFß) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/ß-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.


Asunto(s)
Adenosina/farmacología , Desoxiadenosinas/farmacología , Fibroblastos/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2B/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Línea Celular , Fibroblastos/patología , Humanos , Piel/lesiones , Piel/metabolismo , Piel/patología , Cicatrización de Heridas/efectos de los fármacos , beta Catenina/metabolismo
14.
FASEB J ; 33(10): 10668-10679, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31268747

RESUMEN

PLC-ß exerts biologic influences through GPCR. GPCRs are involved in regulating glucose-stimulated insulin secretion (GSIS). Previous studies have suggested that PLC-ßs might play an important role in pancreatic ß cells. However, because of a lack of the specific inhibitors of PLC-ß isozymes and appropriate genetic models, the in vivo function of specific PLC-ß isozymes in pancreatic ß cells and their physiologic relevance in the regulation of insulin secretion have not been studied so far. The present study showed that PLC-ß1 was crucial for ß-cell function by generation of each PLC-ß conditional knockout mouse. Mice lacking PLC-ß1 in ß cells exhibited a marked defect in GSIS, leading to glucose intolerance. In ex vivo studies, the secreted insulin level and Ca2+ response in Plcb1f/f; pancreas/duodenum homeobox protein 1 (Pdx1)-Cre recombinase-estrogen receptor T2 (CreERt2) islets was lower than those in the Plcb1f/f islets under the high-glucose condition. PLC-ß1 led to potentiate insulin secretion via stimulation of particular Gq-protein-coupled receptors. Plcb1f/f; Pdx1-CreERt2 mice fed a high-fat diet developed more severe glucose intolerance because of a defect in insulin secretion. The present study identified PLC-ß1 as an important molecule that regulates ß cell insulin secretion and can be considered a candidate for therapeutic intervention in diabetes mellitus.-Hwang, H.-J., Yang, Y. R., Kim, H. Y., Choi, Y., Park, K.-S., Lee, H., Ma, J. S., Yamamoto, M., Kim, J., Chae, Y. C., Choi, J. H., Cocco, L., Berggren, P.-O., Jang, H.-J., Suh, P.-G. Phospholipase Cß1 potentiates glucose-stimulated insulin secretion.


Asunto(s)
Glucosa/metabolismo , Secreción de Insulina/fisiología , Fosfolipasa C beta/metabolismo , Animales , Línea Celular , Dieta Alta en Grasa/efectos adversos , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Intolerancia a la Glucosa/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Técnicas In Vitro , Secreción de Insulina/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Isoenzimas/deficiencia , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosfolipasa C beta/deficiencia , Fosfolipasa C beta/genética , Receptores Acoplados a Proteínas G/metabolismo , Transactivadores/genética , Transactivadores/metabolismo
15.
Curr Hypertens Rep ; 22(7): 45, 2020 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-32591971

RESUMEN

PURPOSE OF REVIEW: Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR). RECENT FINDINGS: We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR, 0.356; 95% CI, 0.236-0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR, 2.114; 95% CI, 2.004-2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1 mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype. Our findings suggest that dietary sodium intake may be causally associated with hypertension risk.


Asunto(s)
Hipertensión , Sodio en la Dieta , Adulto , Estudios de Cohortes , Quinasa 4 del Receptor Acoplado a Proteína-G , Estudio de Asociación del Genoma Completo , Humanos , Hipertensión/genética , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Cloruro de Sodio Dietético/efectos adversos , Sodio en la Dieta/efectos adversos
16.
Molecules ; 25(17)2020 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-32887384

RESUMEN

The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors-such as bFGF, KGF, PDGF-AA, and VEGF-were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway.


Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Cabello/crecimiento & desarrollo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Sistema de Señalización de MAP Quinasas , Quercetina/análogos & derivados , Apoptosis/efectos de los fármacos , Butadienos/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dermis/citología , Metabolismo Energético/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Cabello/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Nitrilos/farmacología , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Quercetina/química , Quercetina/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo
17.
Biol Pharm Bull ; 42(10): 1665-1673, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31582654

RESUMEN

Houttuynia cordata (HC) is a traditional oriental herbal medicinal plant widely used as a component of complex prescriptions in Asia for alopecia treatment. The effect of HC on hair growth and its underlying mechanism, however, have not been demonstrated or clarified. In this study, we investigated the hair growth promoting effect of HC in cultured human dermal papilla cells (hDPCs). HC extract was found to stimulate the proliferation of hDPCs and this stimulation might be in part a consequence of activated cellular energy metabolism, because treatment of HC extract increased the generation of nicotinamide adenine dinucleotide (NADH) and ATP through increasing the mitochondrial membrane potential (ΔΨ). In the context of cell cycle, HC extract increased the expression of CDK4 and decreased the expression of CCNA2 and CCNB1, implying that HC extract might induce G1 phase progression of DPCs which resulted in enhanced proliferation. HC extract increased the expression of Bcl2 essential for maintaining hair follicle anagen stage and cell survival. On the contrary, the expression of p16 and p21 was down-regulated by HC extract. In addition, HC extract enhanced the secretion of platelet-derived growth factor (PDGF)-aa and vascular endothelial growth factor (VEGF) and induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Furthermore, HC extract prolonged anagen stage in organ cultured human hair follicles. Our data strongly suggest that HC extract could support hair growth by stimulating proliferation of DPCs and elongating anagen stage, resulted from enhanced cellular energy metabolism and modulation of gene expression related to cell cycle, apoptosis, and growth factors.


Asunto(s)
Folículo Piloso/citología , Cabello/efectos de los fármacos , Extractos Vegetales/farmacología , Saururaceae , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Cabello/crecimiento & desarrollo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
18.
Arthroscopy ; 35(3): 809-815, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30733031

RESUMEN

PURPOSE: To evaluate the prevalence and location of paralabral cysts and the correlation between the type of femoroacetabular impingement (FAI) and acetabular labral tears, as well as the location of the paralabral cysts. METHODS: Patients who received a diagnosis of FAI syndrome using plain radiography, magnetic resonance imaging or magnetic resonance arthrography, or computed tomographic arthrography from 2010 to 2015 were included in this study. The exclusion criteria were patients with arthritis (Tönnis grade 2 or greater) or dysplasia. We identified paralabral cysts and their location, size, configuration. Correlations between the type of FAI and labral tears and paralabral cysts were analyzed using the χ-square test. RESULTS: Among 506 patients with FAI, paralabral cysts were found in 51 patients (55 hips) and were located anterosuperiorly in 40% of cases, posterosuperiorly in 36%, anteroinferiorly in 17%, and posteroinferiorly in 8%. We identified multilocular cysts in 60% of hips and unilocular cysts in 40%. Labral tears were radiographically found in 44 of 55 hips with paralabral cysts (80%); they were located anterosuperiorly in 59% and posterosuperiorly in 41%. Although paralabral cysts were found in the anteroinferior and posteroinferior areas, acetabular labral tears were not identified in the anteroinferior and posteroinferior areas. Classification of the type of FAI showed cam type in 14 of 55 hips (25.5%), pincer type in 16 (29%), mixed type in 7 (13%), labral tears in 15 (27%), and normal findings in 3 (5.5%). No correlation was found between the type of FAI and labral tears (P = .739) or the location of paralabral cysts (P = .228). CONCLUSIONS: Paralabral cysts in patients with FAI most commonly are found in the anterosuperior area and are of the multilocular type. Although paralabral cysts in the anterosuperior and posterosuperior portions are related to labral tears, those in the anteroinferior and posteroinferior portions are not. LEVEL OF EVIDENCE: Level IV, diagnostic case series.


Asunto(s)
Acetábulo , Quistes/diagnóstico , Pinzamiento Femoroacetabular/patología , Acetábulo/lesiones , Acetábulo/patología , Adulto , Anciano , Artrografía/métodos , Cartílago Articular/patología , Femenino , Pinzamiento Femoroacetabular/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
19.
Arthroscopy ; 34(7): 2096-2101, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29685837

RESUMEN

PURPOSE: The purpose of this study was to compare the clinical outcomes, including the visual analog pain score, University of California Los Angeles activity, modified Harris hip score, and radiologic outcomes after hip arthroscopy in male patients whose symptoms developed during military services with those in a matched-pair control group of active young, nonmilitary patients at a minimum postoperative follow-up of 2 years. METHODS: From September 2009 to December 2014, 28 male patients with mechanical symptoms that developed during military service underwent hip arthroscopic surgery. The control group included 28 professional male athletes who were matched with gender, Tönnis grade 0 or 1, crossover percentage, and labral procedure. At the minimum 2-year follow-up, radiographic and clinical outcomes were assessed using serial radiography. Statistical analysis was performed to confirm the differences between the preoperative and postoperative outcome measures. RESULTS: Most common arthroscopic procedures in the study and control groups were femoroplasty (64.4% vs 53.6%) and labral repair (64.3% vs 53.6%). All improvements in both groups were statistically significant at the last postoperative follow-up (P < .001). In the study group, 89.3% of soldiers were able to return to their preoperative military branch. Although radiologic and clinical outcomes in both groups were not significantly different, hospitalization time in soldiers was significantly longer than that in the control group (79.4 ± 27.0 vs 4.0 ± 1.3 days, P < .001). Time of return to their preoperative military branch in the study group was similar to sports activity in the control group (5.9 ± 4.3 vs 6.3 ± 3.7 months, P = .258). CONCLUSIONS: Male patients with symptoms that developed during military services achieved similar levels of benefit from hip arthroscopy as those in the control group of active young patients. Although hospitalization time in the military population was significantly longer than that in the control group, time to return to activity was similar in both groups. LEVEL OF EVIDENCE: Level III, comparative trial.


Asunto(s)
Artroscopía/métodos , Pinzamiento Femoroacetabular/cirugía , Articulación de la Cadera/cirugía , Personal Militar , Enfermedades Profesionales/cirugía , Acetabuloplastia/métodos , Adolescente , Adulto , Atletas , Estudios de Casos y Controles , Pinzamiento Femoroacetabular/diagnóstico por imagen , Estudios de Seguimiento , Articulación de la Cadera/diagnóstico por imagen , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Análisis por Apareamiento , Enfermedades Profesionales/diagnóstico por imagen , Evaluación de Resultado en la Atención de Salud , Radiografía , Traumatismos de los Tendones/diagnóstico por imagen , Traumatismos de los Tendones/cirugía , Adulto Joven
20.
Mol Cell Proteomics ; 14(4): 882-92, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25616869

RESUMEN

Elevated levels of the free fatty acid palmitate are found in the plasma of obese patients and induce insulin resistance. Skeletal muscle secretes myokines as extracellular signaling mediators in response to pathophysiological conditions. Here, we identified and characterized the skeletal muscle secretome in response to palmitate-induced insulin resistance. Using a quantitative proteomic approach, we identified 36 secretory proteins modulated by palmitate-induced insulin resistance. Bioinformatics analysis revealed that palmitate-induced insulin resistance induced cellular stress and modulated secretory events. We found that the decrease in the level of annexin A1, a secretory protein, depended on palmitate, and that annexin A1 and its receptor, formyl peptide receptor 2 agonist, played a protective role in the palmitate-induced insulin resistance of L6 myotubes through PKC-θ modulation. In mice fed with a high-fat diet, treatment with the formyl peptide receptor 2 agonist improved systemic insulin sensitivity. Thus, we identified myokine candidates modulated by palmitate-induced insulin resistance and found that the annexin A1- formyl peptide receptor 2 pathway mediated the insulin resistance of skeletal muscle, as well as systemic insulin sensitivity.


Asunto(s)
Anexina A1/metabolismo , Resistencia a la Insulina , Fibras Musculares Esqueléticas/metabolismo , Palmitatos/farmacología , Proteómica/métodos , Receptores de Formil Péptido/agonistas , Animales , Anexina A1/agonistas , Línea Celular , Biología Computacional , Medios de Cultivo Condicionados/farmacología , Dieta Alta en Grasa , Insulina/farmacología , Masculino , Ratones Endogámicos C57BL , Fibras Musculares Esqueléticas/efectos de los fármacos , Oligopéptidos/farmacología , Ratas , Receptores de Formil Péptido/metabolismo
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