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1.
Mol Cell ; 82(7): 1297-1312.e8, 2022 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-35219381

RESUMEN

Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.


Asunto(s)
Endodesoxirribonucleasas , Neoplasias , Péptidos , Poli ADP Ribosilación , ARN Largo no Codificante , Reparación del ADN , Endodesoxirribonucleasas/metabolismo , Humanos , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Péptidos/farmacología , Poli Adenosina Difosfato Ribosa/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
2.
J Neurosci ; 43(48): 8231-8242, 2023 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-37751999

RESUMEN

Dopamine is a key neurotransmitter in the signaling cascade controlling ocular refractive development, but the exact role and site of action of dopamine D1 receptors (D1Rs) involved in myopia remains unclear. Here, we determine whether retinal D1Rs exclusively mediate the effects of endogenous dopamine and systemically delivered D1R agonist or antagonist in the mouse form deprivation myopia (FDM) model. Male C57BL/6 mice subjected to unilateral FDM or unobstructed vision were divided into the following four groups: one noninjected and three groups that received intraperitoneal injections of a vehicle, D1R agonist SKF38393 (18 and 59 nmol/g), or D1R antagonist SCH39166 (0.1 and 1 nmol/g). The effects of these drugs on FDM were further assessed in Drd1-knock-out (Drd1-KO), retina-specific conditional Drd1-KO (Drd1-CKO) mice, and corresponding wild-type littermates. In the visually unobstructed group, neither SKF38393 nor SCH39166 affected normal refractive development, whereas myopia development was attenuated by SKF38393 and enhanced by SCH39166 injections. In Drd1-KO or Drd1-CKO mice, however, these drugs had no effect on FDM development, suggesting that activation of retinal D1Rs is pertinent to myopia suppression by the D1R agonist. Interestingly, the development of myopia was unchanged by either Drd1-KO or Drd1-CKO, and neither SKF38393 nor SCH39166 injections, nor Drd1-KO, affected the retinal or vitreal dopamine and the dopamine metabolite DOPAC levels. Effects on axial length were less marked than effects on refraction. Therefore, activation of D1Rs, specifically retinal D1Rs, inhibits myopia development in mice. These results also suggest that multiple dopamine D1R mechanisms play roles in emmetropization and myopia development.SIGNIFICANCE STATEMENT While dopamine is recognized as a "stop" signal that inhibits myopia development (myopization), the location of the dopamine D1 receptors (D1Rs) that mediate this action remains to be addressed. Answers to this key question are critical for understanding how dopaminergic systems regulate ocular growth and refraction. We report here the results of our study showing that D1Rs are essential for controlling ocular growth and myopia development in mice, and for identifying the retina as the site of action for dopaminergic control via D1Rs. These findings highlight the importance of intrinsic retinal dopaminergic mechanisms for the regulation of ocular growth and suggest specific avenues for exploring the retinal mechanisms involved in the dopaminergic control of emmetropization and myopization.


Asunto(s)
Dopamina , Miopía , Masculino , Ratones , Animales , Dopamina/metabolismo , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Ratones Endogámicos C57BL , Miopía/genética , Miopía/metabolismo , Retina/metabolismo , Receptores de Dopamina D1/metabolismo
3.
BMC Genomics ; 24(1): 23, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36647013

RESUMEN

BACKGROUND: It is inevitable to change the function or expression of genes during the environmental adaption of species. Both the giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to Carnivora and have developed similar adaptations to the same dietary switch to bamboos at the morphological and genomic levels. However, the genetic adaptation at the gene expression level is unclear. Therefore, we aimed to examine the gene expression patterns of giant and red panda convergent specialized bamboo-diets. We examined differences in liver and pancreas transcriptomes between the two panda species and other non-herbivorous species. RESULTS: The clustering and PCA plots suggested that the specialized bamboo diet may drive similar expression shifts in these two species of pandas. Therefore, we focused on shared liver and pancreas DEGs (differentially expressed genes) in the giant and red panda relative to other non-herbivorous species. Genetic convergence occurred at multiple levels spanning carbohydrate metabolism, lipid metabolism, and lysine degradation. The shared adaptive convergence DEGs in both organs probably be an evolutionary response to the high carbohydrate, low lipid and lysine bamboo diet. Convergent expression of those nutrient metabolism-related genes in both pandas was an intricate process and subjected to multi-level regulation, including DNA methylation and transcription factor. A large number of lysine degradation and lipid metabolism related genes were hypermethylated in promoter regions in the red panda. Most genes related to carbohydrate metabolism had reduced DNA methylation with increased mRNA expression in giant pandas. Unlike the red panda, the core gene of the lysine degradation pathway (AASS) doesn't exhibit hypermethylation modification in the giant panda, and dual-luciferase reporter assay showed that transcription factor, NR3C1, functions as a transcriptional activator in AASS transcription through the binding to AASS promoter region. CONCLUSIONS: Our results revealed the adaptive expressions and regulations of the metabolism-related genes responding to the unique nutrients in bamboo food and provided data accumulation and research hints for the future revelation of complex mechanism of two pandas underlying convergent adaptation to a specialized bamboo diet.


Asunto(s)
Ailuridae , Dieta , Ursidae , Animales , Dieta/veterinaria , Expresión Génica , Lisina/metabolismo , Ursidae/genética , Ursidae/metabolismo , Ailuridae/genética , Ailuridae/metabolismo
4.
Cancer Sci ; 114(5): 1882-1897, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36445120

RESUMEN

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/ß-catenin pathway, but it is highly expressed in colon cancer and can promote colon cancer cell proliferation. miRNAs are involved in the occurrence and progression of many tumors. However, miRNAs that can regulate NKD1 and the mechanisms by which NKD1 regulates tumor progression remain ambiguous. This research aims to reveal the potential regulatory network of NKD1 in colon cancer. miRNA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed by bioinformatics to screen for potential miRNAs targeting NKD1. Let-7b-5p was found to inhibit proliferation, migration, and invasion of colon cancer cells targeting NKD1. Further studies suggested that let-7b-5p can modulate Wnt signaling activity, and the nuclear accumulation of ß-catenin was significantly restrained by let-7b-5p through targeting NKD1. Moreover, NKD1 could prohibit the expression of the APC protein. Further studies manifested that NKD1 bound to APC and promoted the ubiquitination degradation of APC through restraining the expression of the deubiquitinating enzyme USP15 and blocking the combination between USP15 and APC. Functionally, NKD1 enhanced the proliferation and migration of colon cancer cells by inhibiting APC expression. This research revealed a novel mechanism by which the let-7b-5p-NKD1-APC-ß-catenin signaling pathway inhibited colon cancer cell progression.


Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon , Proteínas de Unión al Calcio , Neoplasias del Colon , MicroARNs , Vía de Señalización Wnt , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proteínas de Unión al Calcio/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Proteína de la Poliposis Adenomatosa del Colon/metabolismo
5.
Curr Microbiol ; 80(9): 298, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37490157

RESUMEN

The foliar disease, which is the primary complex disease of Pseudostellaria heterophylla, can be caused by multiple co-infecting pathogens, resulting in a significant reduction in yield. However, there is a lack of research on the relationship between co-infection of various pathogens and the response of resistance-related genes in P. heterophylla. Through the use of 18S rDNA sequencing and pathogenicity testing, it has been determined that Fusarium oxysporum, Alternaria alternata, Arcopilus aureus, Botrytis cinerea, Nemania diffusa, Whalleya microplaca, and Cladosporium cladosporioides are co-infecting pathogens responsible for foliar diseases in P. heterophylla. Furthermore, the qRT-PCR analysis revealed that F. oxysporum, A. alternata, B. cinerea, A. aureus, N. diffusa, Schizophyllum commune, C. cladosporioides, and Coprinellus xanthothrix upregulated ten, two, three, four, seven, thirteen, five, one, and six resistance-related genes, respectively. These findings suggest that a total of 22 resistance-related genes were implicated in the response to diverse fungi, and the magnitude and frequency of induction of resistance-related genes varied considerably among the different fungi. The aforementioned gene associated with resistance was found to be implicated in the response to multiple fungi, including PhPRP1, PhBDRN15, PhBDRN11, and PhBDRN3, which were found to be involved in the resistance response to nine, five, four, and four fungi, respectively. The findings indicate that the PhPRP1, PhBDRN15, PhBDRN11, and PhBDRN3 genes exhibit a broad-spectrum resistance to various fungi. Furthermore, the avirulence fungi C. xanthothrix, which is known to affect P. heterophylla, was found to prime a wide range of resistance responses in P. heterophylla, thereby enhancing its disease resistance. This study provided insight into the management strategies for foliar diseases of P. heterophylla and new genetic materials for disease-resistant breeding.


Asunto(s)
Coinfección , Humanos , ADN Ribosómico , Resistencia a la Enfermedad
6.
Genomics ; 114(3): 110342, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35306168

RESUMEN

Giant pandas are unique within Carnivora with a strict bamboo diet. Here, the epigenomic profiles of giant panda liver and pancreas tissues collected from three important feeding stages were investigated using BS-seq. Few differences in DNA methylation profiles were exhibited between no feeding and suckling groups in both tissues. However, we observed a tendency toward a global loss of DNA methylation in the gene-body and promoter region of metabolism-related genes from newborn to adult. Correlation analysis revealed a significant negative correlation between the changes in methylation levels within gene promoters and gene expression. The majority of genes related to nutrition metabolism had lost DNA methylation with increased mRNA expression in adult giant pandas. The few galactose metabolism and unsaturated fatty acid metabolism related genes that were hypomethylated and highly-expressed at early stages of giant panda development may meet the nutritional requirement of this species' highly altricial neonates.


Asunto(s)
Ursidae , Animales , Humanos , Recién Nacido , Ursidae/genética , Ursidae/metabolismo , Metilación de ADN , Epigenómica , Hígado/metabolismo , Páncreas/metabolismo
7.
Sensors (Basel) ; 23(21)2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37960629

RESUMEN

Haze seriously affects the visual quality of road inspection images and contaminates the discrimination of key road objects, which thus hinders the execution of road inspection work. The basic assumptions of the classical dark-channel prior are not suitable for road images containing light-colored lane lines and vehicles, while typical deep dehazing networks lack physical model interpretability, and they focus on global dehazing effects, neglecting the preservation of object features. For this reason, this paper proposes a Dark-Channel Soft-Constrained and Object-Perception-Enhanced Deep Dehazing Network (DCSC-OPE-Net) for the information recovery of road inspection images. The network is divided into two modules: a dark-channel soft-constrained dehazing module and a near-view object-perception-enhanced module. Unlike the traditional dark-channel algorithms that impose strong constraints on dark pixels, a dark-channel soft-constrained loss function is constructed to ensure that the features of light-colored vehicles and lane lines are effectively maintained. To avoid resolution loss due to patch-based dark-channel processing for image dehazing, a resolution enhancement module is used to strengthen the contrast of the dehazed image. To autonomously perceive and enhance key road features to support road inspection, edge enhancement loss combined with a transmission map is embedded into the network to autonomously discover near-view objects and enhance their key features. The experiments utilize public datasets and real road inspection datasets to validate the performance of the proposed DCSC-OPE-Net compared with typical networks using dehazing evaluation metrics and road object recognition metrics. The experimental results demonstrate that the proposed DCSC-OPE-Net can obtain the best dehazing performance, with an NIQE score of 4.5 and a BRISQUE score of 18.67, and obtain the best road object recognition results (i.e., 83.67%) among the comparison methods.

8.
Mol Genet Genomics ; 297(1): 227-239, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34985592

RESUMEN

The giant panda (Ailuropoda melanoleuca) is a global flagship species for biodiversity conservation. As the time for captive giant pandas to be released into the wild matures, wildness training is provided to allow adaptation to their natural environment. It is assumed that changes in the immune system would be integral in this adaptation from captive to wild, where many more pathogens would be encountered in their natural habitats. Therefore, this study aims to determine the expression changes of immune-related genes and their potential as immunoassay markers for adaptation monitoring in wildness training giant pandas, and then to understand the adaptation strategy of wildness training giant pandas to the wild environment, thereby improving the success rate of panda reintroduction. We obtained 300 differentially expressed genes (DEGs) by RNA-seq, with 239 up-regulated and 61 down-regulated DEGs in wildness training giant pandas compared to captive pandas. Functional enrichment analysis indicated that up-regulated DEGs were enriched in several immune-related terms and pathways. There were 21 immune-related DEGs, in which most of them were up-regulated in wildness training giant pandas, including several critical innate and cellular immune genes. IL1R2 was the most significantly up-regulated gene and is a signature of homeostasis within the immune system. In the protein-protein interaction (PPI) analysis, CXCL8, CXCL10, and CCL5 were identified as the hub immune genes. Our results suggested that wildness training giant pandas have stronger innate and cellular immunity than captive giant pandas, and we proposed that a gene set of CXCL8, CXCL10, CCL5, CD3D, NFKBIA, TBX21, IL12RB2, and IL1R2 may serve as potential immunoassay markers to monitor and assess the immune status of wildness training giant pandas. Our study offers the first insight into immune alterations of wildness training giant pandas, paving the way for monitoring and evaluating the immune status of giant pandas when reintroducing them into the wild.


Asunto(s)
Adaptación Fisiológica/genética , Adaptación Fisiológica/inmunología , Ursidae , Vida Silvestre , Animales , Células Sanguíneas/química , Células Sanguíneas/metabolismo , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/genética , Perfilación de la Expresión Génica , Sistema Inmunológico/metabolismo , Sistema Inmunológico/fisiología , Condicionamiento Físico Animal/fisiología , Transcriptoma/genética , Transcriptoma/inmunología , Ursidae/sangre , Ursidae/genética , Ursidae/inmunología
9.
J Chem Phys ; 156(19): 194305, 2022 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-35597629

RESUMEN

Steady-state and time-resolved infrared (IR) studies of cyclotetramethylene tetranitramine (HMX) were carried out, using the asymmetric nitro-stretch as probe, to investigate its solution structures and vibrational energy transfer processes in pure dimethyl sulfoxide (DMSO) and in a DMSO/water mixture. A linear IR spectrum in the nitro-stretching mode region shows two major bands and one minor band in DMSO but changes to the two major bands mainly picture when adding water as an antisolvent of HMX, suggesting a transition from well-solvated and less perfect ß-conformation to a less-solvated and close-to-perfect ß-conformation. The latter bears a similar asymmetric nitro-stretch vibration profile to the ß-polymorph in the crystal form. Density functional theory computations of the nitro-stretching vibrations suggest that HMX in DMSO may be in a NO2 group rotated ß-conformation. Two-dimensional IR cross-peak intensity reveals intramolecular energy transfer between the axial and equatorial nitro-groups in the ß-HMX on the ps time scale, which is slightly faster in the mixed solvent case. The importance of water as an antisolvent in influencing the equilibrium solvation structure, as well as the vibrational and orientational relaxation dynamics of HMX, is discussed.


Asunto(s)
Dimetilsulfóxido , Vibración , Azocinas , Dimetilsulfóxido/química , Solventes/química , Agua/química
10.
J Cardiothorac Vasc Anesth ; 36(7): 1962-1966, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34593311

RESUMEN

OBJECTIVE: This study aimed to compare the effects of nasal high-frequency oscillatory ventilation (NHFOV) and noninvasive positive-pressure ventilation (NIPPV) as the initial postextubation therapies on preventing extubation failure (EF) in high-risk infants younger than three months after congenital heart surgery (CHS). DESIGN: This was a single-center, randomized, unblinded clinical trial. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: Between January 2020 and January 2021, a total of 150 infants underwent CHS in the authors' hospital. INTERVENTIONS: Infants younger than three months with a high risk for extubation failure who were ready for extubation were randomized to either an NHFOV therapy group or an NIPPV therapy group, and received the corresponding noninvasive mechanical ventilation to prevent EF. MEASUREMENTS: Primary outcomes were reintubation, long-term noninvasive ventilation (NIV) support (more than 72 hours), and the time in NIV therapy. The secondary outcomes were adverse events, including mild-moderate hypercapnia, severe hypercapnia, severe hypoxemia, treatment intolerance, signs of discomfort, unbearable dyspnea, inability to clear secretions, emesis, and aspiration. MAIN RESULTS: Of 92 infants, 45 received NHFOV therapy, and 47 received NIPPV therapy after extubation. There were no significant differences between the NHFOV and the NIPPV therapy groups in the incidences of reintubation, long-term NIV support, and total time under NIV therapy. No significant difference was found of the severe hypercapnia between the two groups, but NHFOV treatment significantly decreased the rate of mild-moderate hypercapnia (p < 0.05). Other outcomes were similar in the two groups. CONCLUSIONS: Among infants younger than three months after CHS who had undergone extubation, NIPPV therapy and NHFOV therapy were the equivalent NIV strategies for preventing extubation failure, and NHFOV therapy was more effective in avoiding mild-moderate hypercapnia.


Asunto(s)
Cardiopatías Congénitas , Ventilación no Invasiva , Extubación Traqueal , Cardiopatías Congénitas/cirugía , Humanos , Hipercapnia/etiología , Hipercapnia/prevención & control , Lactante , Recién Nacido , Recien Nacido Prematuro , Respiración con Presión Positiva/efectos adversos , Respiración Artificial
11.
J Cardiothorac Vasc Anesth ; 36(8 Pt A): 2368-2375, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34753654

RESUMEN

OBJECTIVES: Congenital heart disease (CHD) after cardiopulmonary bypass can cause systemic inflammation, and its degree is closely related to the incidence of acute respiratory distress syndrome (ARDS). The purpose of this study was to determine the effectiveness of high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG) in reducing systemic inflammation in infants with ARDS after cardiopulmonary bypass for congenital heart surgery. DESIGN: A randomized controlled trial. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: A total of 58 infants with ARDS after congenital heart surgery were eligible and were randomized to the HFOV (n = 29) or the HFOV-VG (n = 29) between January 2020 and January 2021. INTERVENTIONS: Tracheal aspirate samples for the measurement of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were obtained on days one, two, and three of HFOV or HFOV-VG ventilation. MEASUREMENTS AND MAIN RESULTS: The authors found a significantly increasing trend in the HFOV group mean values of IL-6, IL-8, and TNF-α (p < 0.05 on days two and three v day one), and IL-6, IL-8, and TNF-α levels were significantly higher on day three in the HFOV group versus the HFOV+VG group (p < 0.05). In addition, the incidences of hypocapnia and hypercapnia in infants supported with HFOV-VG were significantly lower (p < 0.05). Furthermore, the postoperative mechanical ventilation duration in the HFOV-VG group also was shorter than that in the HFOV group (p < 0.05). CONCLUSION: Compared with HFOV alone, HFOV-VG reduced proinflammatory systemic reactions after congenital cardiac surgery, decreased the incidences of hypercapnia and hypocapnia, and shortened the postoperative mechanical ventilation duration.


Asunto(s)
Ventilación de Alta Frecuencia , Síndrome de Dificultad Respiratoria del Recién Nacido , Síndrome de Dificultad Respiratoria , Humanos , Hipercapnia , Hipocapnia , Lactante , Recién Nacido , Recien Nacido Prematuro , Inflamación/etiología , Interleucina-6 , Interleucina-8 , Pulmón , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Factor de Necrosis Tumoral alfa
12.
Heart Surg Forum ; 24(2): E249-E255, 2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33798054

RESUMEN

OBJECTIVE: This study aimed to evaluate the application of synchronized nasal intermittent positive pressure ventilation (SNIPPV) in the respiratory weaning of infants after congenital heart surgery. METHODS: We retrospectively analyzed the clinical data of 63 infants who were extubated from mechanical ventilation after congenital heart surgery between January 2020 and September 2020. The data, including demographics, anatomic diagnosis, radiology and laboratory test results, and perioperative variables were recorded. RESULTS: The extubation failure rate within 48 h after extubation was significantly lower in the SNIPPV group than in the nasal continuous positive airway pressure (NCPAP) group. The PaO2 level and PaO2/FiO2 ratio within 48 h after extubation were higher in the SNIPPV group than in the NCPAP group (P < .05). Meanwhile, the PaCO2 level within 48 h was significantly lower in the SNIPPV group (P < .05). Compared with the NCPAP group, the median duration of postoperative noninvasive support and the duration from extubation to hospital discharge were shorter in the SNIPPV group; the total hospital cost was lower in the SNIPPV group. No significant differences were observed between the two groups concerning VAP, pneumothorax, feeding intolerance, sepsis, mortality, and other complications (P > .05). CONCLUSION: SNIPPV was shown to be superior to NCPAP in avoiding reintubation after congenital heart surgery in infants and significantly improved oxygenation and reduced PaCO2 retention after extubation. Further studies are needed to confirm the efficacy and safety of SNIPPV as a routine weaning strategy.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Presión de las Vías Aéreas Positiva Contínua/métodos , Cardiopatías Congénitas/cirugía , Ventilación con Presión Positiva Intermitente/métodos , Desconexión del Ventilador/métodos , Extubación Traqueal/métodos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Retrospectivos
13.
J Cell Mol Med ; 23(4): 3032-3039, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30697920

RESUMEN

OBJECTIVE: This study aimed to investigate the effects of transforming growth factor ß1 (TGF ß1) and hepatocyte growth factor (HGF) on the expression of connective tissue growth factor (CTGF) in human atrial fibroblasts, and to explore the relationship of these factors in atrial fibrosis and atrial anatomical remodelling (AAR) of patients with atrial fibrillation (AF). METHODS: Fresh right auricular appendix tissue of 20 patients with rheumatic heart disease undergoing valve replacement surgery was collected during surgeries, 10 patients had sinus rhythm(SR), and 10 patients had chronic atrial fibrillation (CAF). Atrial fibroblasts were then cultured from the tissues with differential attachment technique and treated with either TGFß1 (10 ng/mL) or HGF (100 ng/mL). CTGF mRNA levels were measured by RT-PCR, and CTGF protein content was determined using immunofluorescence and Western blotting assays. RESULTS: CAF group had higher left atrial diameters (LADs) and higher CTGF mRNA expression in atrial fibroblasts compared with SR group. The CTGF protein content in CAF group was higher than that of SR group and positively correlated with LAD and AF duration. After CAF group was treated with TGFß1, CTGF mRNA and protein expression were significantly down-regulated, whereas when treated with HGF, expression was up-regulated compared with SR group. CONCLUSIONS: Increased CTGF expression was associated with enlarged LAD, atrial fibrosis and AAR in patients with AF. TGFß1 and HGF regulate CTGF expression in human atrial fibroblasts with up-regulation of mRNA and down-regulation of protein, therefore, either promote or inhibit atrial fibrosis, which could be related to the incidence and persistence of AF.


Asunto(s)
Remodelación Atrial , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Fibroblastos/patología , Fibrosis/etiología , Factor de Crecimiento de Hepatocito/metabolismo , Cardiopatía Reumática/complicaciones , Factor de Crecimiento Transformador beta1/metabolismo , Adulto , Fibrilación Atrial/etiología , Fibrilación Atrial/metabolismo , Fibrilación Atrial/patología , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo/genética , Femenino , Fibroblastos/metabolismo , Fibrosis/metabolismo , Fibrosis/patología , Factor de Crecimiento de Hepatocito/genética , Humanos , Masculino , Cardiopatía Reumática/metabolismo , Cardiopatía Reumática/patología , Factor de Crecimiento Transformador beta1/genética
14.
Am J Med Genet A ; 179(7): 1126-1138, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31058441

RESUMEN

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development.


Asunto(s)
Anomalías Craneofaciales/genética , Enanismo/genética , Oído/anomalías , Cardiopatías Congénitas/genética , Discapacidad Intelectual/genética , Enfermedades Pulmonares/genética , Mutación Missense , Cuello/anomalías , Obesidad/genética , Tórax/anomalías , Factores de Elongación Transcripcional/genética , Adolescente , Secuencia de Aminoácidos , Niño , Preescolar , Anomalías Craneofaciales/diagnóstico , Anomalías Craneofaciales/patología , Análisis Mutacional de ADN , Síndrome de Cornelia de Lange , Diagnóstico Diferencial , Enanismo/diagnóstico , Enanismo/patología , Oído/patología , Facies , Femenino , Expresión Génica , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/patología , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/patología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/patología , Masculino , Cuello/patología , Obesidad/diagnóstico , Obesidad/patología , Fenotipo , Síndrome , Tórax/patología , Adulto Joven
15.
Microb Pathog ; 115: 280-286, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29294370

RESUMEN

A recent study has described the normal vaginal bacterial community in giant pandas, but there is a lack of knowledge of the fungal community residing in the vagina of giant pandas. In order to comprehensively understand the vaginal fungal microbial diversity and abundance in giant pandas, high throughput sequencing was used to analyse the ITS1 region, based on thirteen samples taken from the pandas' vaginas, which were grouped by sampling points and age. The results showed that the most abundant phyla were Basidiomycota (73.37%), followed by Ascomycota (20.04%), Zygomycota (5.23%), Glomeromycota (0.014%) and Chytridiomycota (0.006%). At the genus level, Guehomyces (37.92%) was the most abundant, followed by Cladosporium (9.072%), Trichosporon (6.2%) and Mucor (4.97%). Furthermore, Candida only accounted for a low percentage of the vaginal fungal community. With the saturation of rarefaction curves and fungal diversity indices, the samples from Dujiangyan and Chungking Safari Park (DC group) showed a higher fungal species richness and diversity than other living environments. Shannon diversity indices showed significant difference between group WL (Wolong nature reserve) and DC (P < .05). Additionally, a higher diversity was found in ten to fifteen years old (Group 2) than other groups. Group 2 and Group 3 displayed significant differences in the diversities of their vaginal fungal communities (P < .05). These data that has been collected from this research will be helpful for further study to improve the reproductive status of giant pandas.


Asunto(s)
Hongos/clasificación , Hongos/genética , Micobioma/genética , Vagina/microbiología , Envejecimiento , Animales , Biodiversidad , ADN Intergénico/genética , Femenino , Hongos/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Ursidae
17.
J Phys Chem A ; 121(13): 2565-2571, 2017 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-28319388

RESUMEN

The femtosecond time-resolved multiplex coherent anti-Stokes Raman scattering (CARS) technique has been performed to investigate intramolecular vibrational redistribution (IVR) through vibrational couplings in 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) molecules. In the multiplex CARS experiment, the supercontinuum (SC) was used as broad-band Stokes light to coherently and collectively excite multiple vibrational modes, and quantum beats arising from vibrational couplings among these modes were observed. The IVR of RDX is visualized by a topological graph of these vibrational couplings, and with analysis of the topological graph, two vibrational modes, both of which are assigned to ring bending, are confirmed to have coupling interactions with most of the other vibrational modes and are considered to have a tendency of energy transfer with these vibrational modes. We suggest that the mode at 466 cm-1 is a portal of energy transfer from outside to inside of the RDX molecule and the mode at 672 cm-1 is an important transit point of energy transfer in the IVR.

18.
Eur J Gynaecol Oncol ; 36(5): 610-4, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26513895

RESUMEN

The purpose of this study was to evaluate the value of CT and MRI in aggressive angiomyxoma (AAM) of the pelvis. A series of four cases from three institutions are reviewed. Among the four cases, three were initially misdiagnosed, and local recurrence necessitated reoperation or angiographic embolization. The fourth case, with accurate preoperative diagnosis, was followed with no recurrence. CT and MR imaging demonstrated a well-defined mass, which displaced adjacent structures. Attenuation of the mass was less than that of muscle on unenhanced CT, and a swirling or layering internal architecture was found using both enhanced CT and TI-weighted MR imaging. In one patient, a layering internal architecture was seen on unenhanced CT images. MRI demonstrated the relation of the tumor to the pelvic floor better than CT. The authors concluded that both CT and MRI show the characteristic imaging pattern and trans-diaphragmatic extent of these tumors, and the diagnosis should be considered in any young woman presenting with a well-defined mass arising from the pelvis or perineum.


Asunto(s)
Mixoma/patología , Neoplasias Pélvicas/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mixoma/diagnóstico , Neoplasias Pélvicas/diagnóstico , Tomografía Computarizada por Rayos X
19.
Molecules ; 21(1): E8, 2015 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-26729072

RESUMEN

Seven metabolites of 2',3',5'-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine (WS070117) were synthesized by deacetylation, hydrolysis, cyclization, sulfonylation and glycosylation reactions, respectively. All these compounds, which could be useful as material standards for metabolic research, were characterized by NMR and HPLC-MS (ESI) analyses.


Asunto(s)
Adenosina/análogos & derivados , Adenosina/química , Ciclización , Glicosilación , Hidrólisis , Estructura Molecular
20.
Mol Genet Genomics ; 289(6): 1237-40, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24994558

RESUMEN

Treacher Collins syndrome (TCS) is the most common and well-known craniofacial disorder caused by mutations in the genes involved in pre-rRNA transcription, which include the TCOF1 gene. This study explored the role of TCOF1 mutations in Chinese patients with TCS. Mutational analysis of the TCOF1 gene was performed in three patients using polymerase chain reaction and direct sequencing. Among these three patients, two additional TCOF1 variations, a novel 18 bp deletion and a novel 1 bp insertion mutation, were found in patient 1, together with a novel nonsense mutation (p.Ser476X) and a previously reported 4 bp deletion (c.1872_1875delTGAG) in other patients. Pedigree analysis allowed for prediction of the character of the mutation, which was either pathological or not. The 18 bp deletion of six amino acids, Ser-Asp-Ser-Glu-Glu-Glu (798*803), which was located in the CKII phosphorylation site of treacle, seemed relatively benign for TCS. By contrast, another novel mutation of c.1072_1073insC (p.Gln358ProfsX23) was a frameshift mutation and expected to result in a premature stop codon. This study provides insights into the functional domain of treacle and illustrates the importance of clinical and family TCS screening for the interpretation of novel sequence alterations.


Asunto(s)
Disostosis Mandibulofacial/genética , Mutación , Proteínas Nucleares/genética , Fosfoproteínas/genética , Adolescente , China , Codón sin Sentido , Humanos , Recién Nacido , Disostosis Mandibulofacial/diagnóstico , Mutagénesis Insercional
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