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1.
Proc Natl Acad Sci U S A ; 120(20): e2300860120, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37155855

RESUMEN

Photonic gauge potentials, including scalar and vector ones, play fundamental roles in emulating photonic topological effects and for enabling intriguing light transport dynamics. While previous studies mainly focus on manipulating light propagation in uniformly distributed gauge potentials, here we create a series of gauge-potential interfaces with different orientations in a nonuniform discrete-time quantum walk and demonstrate various reconfigurable temporal-refraction effects. We show that for a lattice-site interface with the potential step along the lattice direction, the scalar potentials can yield total internal reflection (TIR) or Klein tunneling, while vector potentials manifest direction-invariant refractions. We also reveal the existence of penetration depth for the temporal TIR by demonstrating frustrated TIR with a double lattice-site interface structure. By contrast, for an interface emerging in the time-evolution direction, the scalar potentials have no effect on the packet propagation, while the vector potentials can enable birefringence, through which we further create a "temporal superlens" to achieve time-reversal operations. Finally, we experimentally demonstrate electric and magnetic Aharonov-Bohm effects using combined lattice-site and evolution-step interfaces of either scalar or vector potential. Our work initiates the creation of artificial heterointerfaces in synthetic time dimension by employing nonuniformly and reconfigurable distributed gauge potentials. This paradigm may find applications in optical pulse reshaping, fiber-optic communications, and quantum simulations.

2.
BMC Bioinformatics ; 25(1): 317, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354334

RESUMEN

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) technology has emerged as a crucial tool for studying cellular heterogeneity. However, dropouts are inherent to the sequencing process, known as dropout events, posing challenges in downstream analysis and interpretation. Imputing dropout data becomes a critical concern in scRNA-seq data analysis. Present imputation methods predominantly rely on statistical or machine learning approaches, often overlooking inter-sample correlations. RESULTS: To address this limitation, We introduced SAE-Impute, a new computational method for imputing single-cell data by combining subspace regression and auto-encoders for enhancing the accuracy and reliability of the imputation process. Specifically, SAE-Impute assesses sample correlations via subspace regression, predicts potential dropout values, and then leverages these predictions within an autoencoder framework for interpolation. To validate the performance of SAE-Impute, we systematically conducted experiments on both simulated and real scRNA-seq datasets. These results highlight that SAE-Impute effectively reduces false negative signals in single-cell data and enhances the retrieval of dropout values, gene-gene and cell-cell correlations. Finally, We also conducted several downstream analyses on the imputed single-cell RNA sequencing (scRNA-seq) data, including the identification of differential gene expression, cell clustering and visualization, and cell trajectory construction. CONCLUSIONS: These results once again demonstrate that SAE-Impute is able to effectively reduce the droupouts in single-cell dataset, thereby improving the functional interpretability of the data.


Asunto(s)
Análisis de Secuencia de ARN , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , Biología Computacional/métodos , Algoritmos , Humanos , Aprendizaje Automático , Programas Informáticos
3.
Apoptosis ; 29(5-6): 816-834, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38281279

RESUMEN

Doxorubicin (DOX) is an anthracycline antibiotic used as an antitumor treatment. However, its clinical application is limited due to severe side effects such as cardiotoxicity. In recent years, numerous studies have demonstrated that cellular aging has become a therapeutic target for DOX-induced cardiomyopathy. However, the underlying mechanism and specific molecular targets of DOX-induced cardiomyocyte aging remain unclear. Poly (ADP-ribose) polymerase (PARP) is a family of protein post-translational modification enzymes in eukaryotic cells, including 18 members. PARP-1, the most well-studied member of this family, has become a potential molecular target for the prevention and treatment of various cardiovascular diseases, such as DOX cardiomyopathy and heart failure. PARP-1 and PARP-2 share 69% homology in the catalytic regions. However, they do not entirely overlap in function. The role of PARP-2 in cardiovascular diseases, especially in DOX-induced cardiomyocyte aging, is less studied. In this study, we found for the first time that down-regulation of PARP-2 can inhibit DOX-induced cellular aging in cardiomyocytes. On the contrary, overexpression of PARP-2 can aggravate DOX-induced cardiomyocyte aging and injury. Further research showed that PARP-2 inhibited the expression and activity of SIRT1, which in turn was involved in the development of DOX-induced cardiomyocyte aging and injury. Our findings provide a preliminary experimental basis for establishing PARP-2 as a new target for preventing and treating DOX cardiomyopathy and related drug development.


Asunto(s)
Senescencia Celular , Doxorrubicina , Miocitos Cardíacos , Poli(ADP-Ribosa) Polimerasas , Sirtuina 1 , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Sirtuina 1/metabolismo , Sirtuina 1/genética , Animales , Senescencia Celular/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/genética , Ratas , Cardiotoxicidad/patología , Cardiotoxicidad/metabolismo , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Apoptosis/efectos de los fármacos , Ratas Sprague-Dawley , Antibióticos Antineoplásicos/toxicidad , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/farmacología , Cardiomiopatías/inducido químicamente , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Cardiomiopatías/genética , Humanos
4.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34718405

RESUMEN

The tremendous progress of single-cell sequencing technology has given researchers the opportunity to study cell development and differentiation processes at single-cell resolution. Assay of Transposase-Accessible Chromatin by deep sequencing (ATAC-seq) was proposed for genome-wide analysis of chromatin accessibility. Due to technical limitations or other reasons, dropout events are almost a common occurrence for extremely sparse single-cell ATAC-seq data, leading to confusion in downstream analysis (such as clustering). Although considerable progress has been made in the estimation of scRNA-seq data, there is currently no specific method for the inference of dropout events in single-cell ATAC-seq data. In this paper, we select several state-of-the-art scRNA-seq imputation methods (including MAGIC, SAVER, scImpute, deepImpute, PRIME, bayNorm and knn-smoothing) in recent years to infer dropout peaks in scATAC-seq data, and perform a systematic evaluation of these methods through several downstream analyses. Specifically, we benchmarked these methods in terms of correlation with meta-cell, clustering, subpopulations distance analysis, imputation performance for corruption datasets, identification of TF motifs and computation time. The experimental results indicated that most of the imputed peaks increased the correlation with the reference meta-cell, while the performance of different methods on different datasets varied greatly in different downstream analyses, thus should be used with caution. In general, MAGIC performed better than the other methods most consistently across all assessments. Our source code is freely available at https://github.com/yueyueliu/scATAC-master.


Asunto(s)
Análisis de la Célula Individual , Programas Informáticos , Análisis por Conglomerados , Análisis de Secuencia de ARN , Secuenciación del Exoma
5.
Phys Rev Lett ; 133(8): 083802, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39241724

RESUMEN

Experimental demonstration of tunable temporal Goos-Hänchen shift (GHS) in synthetic discrete-time heterolattices with scalar and vector gauge potentials is reported. By using Heaviside-function modulation in two fiber loops, we create a sharp gauge-potential interface and observe temporal GHS for total internal reflection (TIR), which manifests as a time delay rather than a spatial shift. The TIR occurs as the incident mode falls into the band gap of transmitted region with band shifting by scalar and vector potential. We find that both scalar and vector potential codetermine GHS by controlling the decay (imaginary part) and oscillation (real part) of a penetrated evanescent wave, in stark contrast to traditional spatial GHS only determined by the decay factor. We also observe diverging characteristics of GHS at band-gap edges where evanescent-to-propagating wave transition occurs. GHS for frustrated total internal reflection (FTIR) by a finite-width evanescent barrier is also demonstrated, which shows saturation properties to the single-interface TIR case under infinite-width limit. Finally, we develop an accumulation measurement method using multiple TIRs to improve the precision for measuring even tinier GHS. The study initiates precise measurement of temporal GHS for discrete-time reflections, which may feature potential applications in precise time-delay control and measurement.

6.
BMC Geriatr ; 24(1): 462, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802742

RESUMEN

BACKGROUND: The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality. RESULTS: Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P < 0.001), lower rates of intraoperative transfusion (10.4% vs. 19.0%, P = 0.029), more lymph node harvest (11.0 vs. 10.0, P = 0.014) and shorter postoperative length of stay (LOS) (13.0 vs. 16.0 days, P = 0.013). There were no significant differences in serious complications, reoperation, 90-day readmission and mortality rates (all P > 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM. CONCLUSIONS: It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Puntaje de Propensión , Humanos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/tendencias , Anciano , Masculino , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Laparoscopía/tendencias , Estudios Retrospectivos , Neoplasias Pancreáticas/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Anciano de 80 o más Años , Factores de Tiempo , Tiempo de Internación/tendencias
7.
Arch Gynecol Obstet ; 310(2): 855-861, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38280055

RESUMEN

OBJECTIVE: This study aims to assess the feasibility and effectiveness of color doppler flow imaging (CDFI) technology and the Slow Flow HD imaging technique in identifying fetal pulmonary veins (PVs) in the first trimester (11-13 + 6 weeks), and further explore the factors affecting fetal pulmonary vein identification in early pregnancy. METHODS: Echocardiography and scanning of PVs were performed in 240 normal singleton fetuses in early pregnancy by using CDFI and slow flow HD techniques, to compare the ability of two methods to identify the PVs. Slow Flow HD technology was used to further investigate the difference of PVs identification at different gestational ages [group I (11-11 + 6 weeks), group II (12-12 + 6 weeks), group III (13-13 + 6 weeks)] and with different maternal body mass indices (BMI) (≥ 25 and < 25). In 31 cases of 240 fetuses, transvaginal ultrasonography was added due to maternal habitus or significant retroversion of the uterus, and the difference in PVs identification between transabdominal and transvaginal examination was analyzed. RESULTS: Successful PVs identification rates via CDFI and Slow Flow HD were 32.0% and 88.3%, respectively (p < 0.05). The identification rate of at least one and two pulmonary veins in Slow Flow HD was 88.3% and 76.2%, and all four pulmonary veins in 11.6% (p < 0.05). The identification rate of group I, II and III were 76.4%, 88.9% and 96.0%, respectively. The identification rate was 45.1% in the transabdominal ultrasound group and 83.8% in the transvaginal ultrasound group. The identification rate was 62.5% in the BMI ≥ 25 group and 94.7% in the BMI < 25 group (p < 0.05). CONCLUSIONS: Slow Flow HD can detect PVs in early pregnancy more often than using CDFI. Slow Flow HD is a feasible and effective imaging technique for evaluating PVs in early pregnancy.


Asunto(s)
Estudios de Factibilidad , Primer Trimestre del Embarazo , Venas Pulmonares , Ultrasonografía Doppler en Color , Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , Adulto , Ultrasonografía Prenatal/métodos , Venas Pulmonares/diagnóstico por imagen , Edad Gestacional , Índice de Masa Corporal
8.
J Asian Nat Prod Res ; 25(7): 674-682, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36250229

RESUMEN

Two new polyketides, pholiotones B and C (1 and 2), and four known compounds, trichodermatide D (3), vermistatin (4), dehydroaltenuene A (5) and terpestacin (6) were isolated from the crude extract of Pholiota sp. Their structures were identified by NMR and MS spectroscopic data. The absolute configurations of compounds 1 and 2 were elucidated by modified Mosher's method, electronic circular dichroism (ECD) calculations and 13C NMR calculations as well as DP4+ probability analyses. All the compounds were evaluated for their antifungal and cytotoxicity.


Asunto(s)
Pholiota , Policétidos , Estructura Molecular , Policétidos/química , Espectroscopía de Resonancia Magnética , Antifúngicos/química
9.
Int J Mol Sci ; 24(8)2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37108410

RESUMEN

Studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in regulating virus infection, host immune response, and other biological processes. Although some lncRNAs have been reported to be involved in antiviral immunity, many lncRNAs have unknown functions in interactions between the host and various viruses, especially influenza A virus (IAV). Herein, we demonstrate that the expression of lncRNA LINC02574 can be induced by IAV infection. Treatment with viral genomic RNA, poly (I:C), or interferons (IFNs) significantly stimulated LINC02574 expression, while RIG-I knockdown and IFNAR1 knockout significantly decreased LINC02574 expression after viral infection or IFN treatment. In addition, inhibition of LINC02574 expression in A549 cells enhanced IAV replication, while overexpression of LINC02574 inhibited viral production. Interestingly, knockdown of LINC02574 attenuated the expression of type I and type III IFNs and multiple ISGs, as well as the activation of STAT1 triggered by IAV infection. Moreover, LINC02574 deficiency impaired the expression of RIG-I, TLR3, and MDA5, and decreased the phosphorylation level of IRF3. In conclusion, the RIG-I-dependent interferon signaling pathway can induce LINC02574 expression. Moreover, the data reveal that LINC02574 inhibits IAV replication by positively regulating the innate immune response.


Asunto(s)
Virus de la Influenza A , Gripe Humana , ARN Largo no Codificante , Virosis , Humanos , Virus de la Influenza A/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Inmunidad Innata/genética , Interferones , Replicación Viral/genética
10.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36834504

RESUMEN

Transgenic expression of Cre recombinase driven by a specific promoter is normally used to conditionally knockout a gene in a tissue- or cell-type-specific manner. In αMHC-Cre transgenic mouse model, expression of Cre recombinase is controlled by the myocardial-specific α-myosin heavy chain (αMHC) promoter, which is commonly used to edit myocardial-specific genes. Toxic effects of Cre expression have been reported, including intro-chromosome rearrangements, micronuclei formation and other forms of DNA damage, and cardiomyopathy was observed in cardiac-specific Cre transgenic mice. However, mechanisms associated with Cardiotoxicity of Cre remain poorly understood. In our study, our data unveiled that αMHC-Cre mice developed arrhythmias and died after six months progressively, and none of them survived more than one year. Histopathological examination showed that αMHC-Cre mice had aberrant proliferation of tumor-like tissue in the atrial chamber extended from and vacuolation of ventricular myocytes. Furthermore, the αMHC-Cre mice developed severe cardiac interstitial and perivascular fibrosis, accompanied by significant increase of expression levels of MMP-2 and MMP-9 in the cardiac atrium and ventricular. Moreover, cardiac-specific expression of Cre led to disintegration of the intercalated disc, along with altered proteins expression of the disc and calcium-handling abnormality. Comprehensively, we identified that the ferroptosis signaling pathway is involved in heart failure caused by cardiac-specific expression of Cre, on which oxidative stress results in cytoplasmic vacuole accumulation of lipid peroxidation on the myocardial cell membrane. Taken together, these results revealed that cardiac-specific expression of Cre recombinase can lead to atrial mesenchymal tumor-like growth in the mice, which causes cardiac dysfunction, including cardiac fibrosis, reduction of the intercalated disc and cardiomyocytes ferroptosis at the age older than six months in mice. Our study suggests that αMHC-Cre mouse models are effective in young mice, but not in old mice. Researchers need to be particularly careful when using αMHC-Cre mouse model to interpret those phenotypic impacts of gene responses. As the Cre-associated cardiac pathology matched mostly to that of the patients, the model could also be employed for investigating age-related cardiac dysfunction.


Asunto(s)
Fibrilación Atrial , Cardiomiopatías , Ferroptosis , Ratones , Animales , Miocitos Cardíacos/metabolismo , Fibrilación Atrial/metabolismo , Cardiomiopatías/metabolismo , Ratones Transgénicos , Fibrosis , Ratones Noqueados
11.
Molecules ; 28(19)2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37836827

RESUMEN

Peptides have demonstrated their efficacy as catalysts in asymmetric aldol reactions. But the constraints inherent in chemical synthesis have imposed limitations on the viability of long-chain peptide catalysts. A noticeable dearth of tools has impeded the swift and effective screening of peptide catalysts using biological methods. To address this, we introduce a straightforward bioprocess for the screening of peptide catalysts for asymmetric aldol reactions. We synthesized several peptides through this method and obtained a 15-amino acid peptide. This peptide exhibited asymmetric aldol catalytic activity, achieving 77% ee in DMSO solvent and 63% ee with over an 80.8% yield in DMSO mixed with a pH 9.0 buffer solution. The successful application of our innovative approach not only represents an advancement but also paves the way for currently unexplored research avenues.


Asunto(s)
Dimetilsulfóxido , Péptidos , Péptidos/química , Aldehídos/química , Solventes/química , Catálisis , Estereoisomerismo
12.
Molecules ; 28(3)2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36770588

RESUMEN

Chiral amines are essential components for many pharmaceuticals and agrochemicals. However, the difficulty in obtaining enantiomerically pure amines limits their application. In this study, hollow amorphous ZIF-90 (HamZIF-90) materials were prepared by template engraving, and chemical-enzyme coupling catalysts (HamZIF-90@Pd@CALB) were constructed for the chiral resolution of 1-phenylethylamine. Different from conventional materials, HamZIF-90 had tunable hollow structures by altering its central node zinc ion concentrations, and the embedded hydrogel template gave it more pore structures, which facilitated the loading of enzyme molecules and Pd nanoparticles (NPs). The establishment of the coupling catalysts shortened the mass transfer distance of the reactant molecules between the metal nanoparticles and the enzyme catalyst in the dynamic kinetic resolution (DKR) reaction, resulting in 98% conversion of 1-phenylethylamine and 93% selectivity of Sel.R-amide. The proposal of this idea provided a good idea for future tailor-made MOFs loaded with chemical and enzyme coupled catalyst.

13.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-36361587

RESUMEN

Liver hepatocellular carcinoma (LIHC) remains a global health challenge with poor prognosis and high mortality. FKBP1A was first discovered as a receptor for the immunosuppressant drug FK506 in immune cells and is critical for various tumors and cancers. However, the relationships between FKBP1A expression, cellular distribution, tumor immunity, and prognosis in LIHC remain unclear. Here, we investigated the expression level of FKBP1A and its prognostic value in LIHC via multiple datasets including ONCOMINE, TIMER, GEPIA, UALCAN, HCCDB, Kaplan-Meier plotter, LinkedOmics, and STRING. Human liver tissue microarray was employed to analyze the characteristics of FKBP1A protein including the expression level and pathological alteration in cellular distribution. FKBP1A expression was significantly higher in LIHC and correlated with tumor stage, grade and metastasis. The expression level of the FKBP1A protein was also increased in LIHC patients along with its accumulation in endoplasmic reticulum (ER). High FKBP1A expression was correlated with a poor survival rate in LIHC patients. The analysis of gene co-expression and the regulatory pathway network suggested that FKBP1A is mainly involved in protein synthesis, metabolism and the immune-related pathway. FKBP1A expression had a significantly positive association with the infiltration of hematopoietic immune cells including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Moreover, M2 macrophage infiltration was especially associated with a poor survival prognosis in LIHC. Furthermore, FKBP1A expression was significantly positively correlated with the expression of markers of M2 macrophages and immune checkpoint proteins such as PD-L1, CTLA-4, LAG3 and HAVCR2. Our study demonstrated that FKBP1A could be a potential prognostic target involved in tumor immune cell infiltration in LIHC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Pronóstico , Neoplasias Hepáticas/patología , Linfocitos T CD8-positivos/patología , Biomarcadores de Tumor , Perfilación de la Expresión Génica , Proteínas de Unión a Tacrolimus/genética
14.
BMC Musculoskelet Disord ; 21(1): 215, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32264852

RESUMEN

BACKGROUND: Our aim was to investigate the clinical efficacy and complications of antibiotic treatment regimens for patients with bone infection. METHODS: We retrospectively analysed patients with bone infection admitted to our hospital between March 2013 and October 2018. After surgical debridement was performed, the patients were divided into three groups: IV group (intravenous antibiotics for 2 weeks); oral group (intravenous antibiotics for 2 weeks followed by oral antibiotics for 4 weeks); and rifampicin group (intravenous antibiotics for 2 weeks followed by oral antibiotics plus rifampicin for 4 weeks). The infection control rate and complications were compared among the three groups. RESULTS: A total of 902 patients were enrolled. The infection sites included 509 tibias, 228 femurs, 32 humeri, 23 radii and ulnae, 40 calcanei, and 47 miscellaneous sites, as well as 23 multiple-site infections. After at least 6 months of follow-up, 148 (16.4%) patients had an infection recurrence. The recurrence rate of the IV group was 17.9%, which was not significantly higher than the recurrence rates of the oral group (10.1%) and rifampicin group (10.5%), P = 0.051. The incidence of abnormal alanine aminotransferase (ALT) levels in the IV group was 15.1%, which was lower than that in the oral group (18.0%) and rifampicin group (27.4%), P = 0.026. The rates of proteinuria in the three groups were 3.2, 4.5, and 9.3%, respectively, P = 0.020. CONCLUSIONS: After debridement of bone infection, short-term antibiotic treatment regimens might offer similar rates of infection eradication while avoiding the risk of renal and hepatic damage associated with prolonged antibiotic use. THE LEVEL OF CLINICAL RELEVANCE: Stage III.


Asunto(s)
Antibacterianos/uso terapéutico , Desbridamiento , Fracturas Óseas/complicaciones , Infecciones/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibacterianos/administración & dosificación , Niño , Preescolar , Femenino , Fracturas Óseas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
15.
Biochem Genet ; 58(1): 16-39, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31115714

RESUMEN

The identification of the cancer driver genes is essential for personalized therapy. The mutation frequency of most driver genes is in the middle (2-20%) or even lower range, which makes it difficult to find the driver genes with low-frequency mutations. Other forms of genomic aberrations, such as copy number variations (CNVs) and epigenetic changes, may also reflect cancer progression. In this work, a method for identifying the potential cancer driver genes (iPDG) based on molecular data integration is proposed. DNA copy number variation, somatic mutation, and gene expression data of matched cancer samples are integrated. In combination with the method of iKEEG, the "key genes" of cancer are identified, and the change in their expression levels is used for auxiliary evaluation of whether the mutated genes are potential drivers. For a mutated gene, the concept of mutational effect is defined, which takes into account the effects of copy number variation, mutation gene itself, and its neighbor genes. The method mainly includes two steps: the first step is data preprocessing. First, DNA copy number variation and somatic mutation data are integrated. Then, the integrated data are mapped to a given interaction network, and the diffusion kernel is used to form the mutation effect matrix. The second step is to obtain the key genes by using the iKGGE method, and construct the connection matrix by means of the gene expression data of the key genes and mutation impact matrix of the mutated genes. Experiments on TCGA breast cancer and Glioblastoma multiforme datasets demonstrate that iPDG is effective not only to identify the known cancer driver genes but also to discover the rare potential driver genes. When measured by functional enrichment analysis, we find that these genes are clearly associated with these two types of cancers.


Asunto(s)
Neoplasias de la Mama/genética , Genómica/métodos , Glioblastoma/genética , Oncogenes/genética , Variaciones en el Número de Copia de ADN , Conjuntos de Datos como Asunto , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos
16.
Environ Toxicol ; 35(6): 707-713, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32023008

RESUMEN

Excessive intake of high fat diet (HFD) and associated obese conditions are critical contributors of cardiac diseases. In this study, an active metabolite andrographolide from Andrographis paniculata was found to ameliorate HFD-induced cardiac apoptosis. C57/BL6 mouse were grouped as control (n = 9), obese (n = 8), low dose (25 mg/kg/d) andrographolide treatment (n = 9), and high dose (50 mg/kg/d) andrographolide treatment (n = 9). The control group was provided with standard laboratory chow and the other groups were fed with HFD. Andrographolide was administered through oral gavage for 1 week. Histopathological analysis showed increase in apoptotic nuclei and considerable cardiac-damages in the obese group signifying cardiac remodeling effects. Further, Western blot results showed increase in pro-apoptotic proteins and decrease in the proteins of IGF-1R-survival signaling. However, feeding of andrographolide significantly reduced the cardiac effects of HFD. The results strongly suggest that andrographolide supplementation can be used for prevention and treatment of cardiovascular disease in obese patients.


Asunto(s)
Apoptosis/efectos de los fármacos , Fármacos Cardiovasculares/farmacología , Dieta Alta en Grasa/efectos adversos , Diterpenos/farmacología , Corazón/efectos de los fármacos , Obesidad/patología , Andrographis/química , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Fármacos Cardiovasculares/aislamiento & purificación , Diterpenos/aislamiento & purificación , Masculino , Ratones , Ratones Obesos , Miocardio/metabolismo , Miocardio/patología , Obesidad/metabolismo , Obesidad/fisiopatología , Transducción de Señal
17.
Asia Pac J Clin Nutr ; 29(1): 161-165, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32229455

RESUMEN

BACKGROUND AND OBJECTIVES: A previous pilot study revealed stunted children and obese adults in urbanized settled Tibetan communities. A survey with a representative population in selected communities was conducted to test the preliminary findings. METHODS AND STUDY DESIGN: A cross-sectional study on the nutritional status involving 504 children (244 boys and 260 girls, 5-16 y) and 927 adults (422 men and 505 women, 18-90 y) was conducted in communities, with anthropometric parameters measured. The z-scores for height-for-age (HAZ) and BMI-for-age (BAZ) in children were calculated according to WHO 2007 reference. RESULTS: The children showed a double burden of both under- and over-nutrition. The prevalence of under-nutrition in children was high - stunting (HAZ <-2) 10.7%, underweight (BAZ <-2) 9.5%, combined prevalence of stunting and underweight 19.4%. The rate of over-nutrition was also alarming - obesity 12.7% (BAZ >2). The mean value of HAZ (- 0.45±1.41) was lower than, whereas that of BAZ (0.05±1.76) was comparable to, the WHO reference. No significant differences were found in under- or over-nutrition between genders. Specifically, 8.9% of children demonstrated both short stature (HAZ <-1) and overweight (BAZ >1). By contrast, community adults showed almost a one-way direction tilted towards over-nutrition - overweight 61.4% (BMI ≥24 kg/m2), obesity 30.1% (BMI ≥28 kg/m2), and central obesity 62.0% (waist circumference, men ≥85 cm, women ≥80 cm). Women were marginally more likely to be obese than men (p=0.061). CONCLUSIONS: The co-existence of under- and over-nutrition in the community may have reflected the suboptimal early life nutrition and the obesogenic environment afterwards. Potential determinants need to be explored for future interventions.


Asunto(s)
Trastornos Nutricionales/epidemiología , Estado Nutricional/etnología , Urbanización , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antropometría , Niño , Preescolar , China/etnología , Estudios Transversales , Femenino , Trastornos del Crecimiento/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Prevalencia , Delgadez/epidemiología , Tibet/epidemiología , Adulto Joven
18.
Molecules ; 25(8)2020 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-32316267

RESUMEN

Characterization of the structure and pharmacological activity of Berberis dasystachya Maxim., a traditional Tibetan medicinal and edible fruit, has not yet been reported. In this study, central composite design (CCD) combined with response surface methodology (RSM) was applied to optimize the extraction conditions of B. dasystachya oil (BDSO) using the supercritical carbon dioxide (SC-CO2) extraction method, and the results were compared with those obtained by the petroleum ether extraction (PEE) method. The chemical characteristics of BDSO were analyzed, and its antioxidant activity and in vitro cellular viability were studied by DPPH, ABTS, reducing power assay, and MTT assay. The results showed that the maximum yield of 12.54 ± 0.56 g/100 g was obtained at the optimal extraction conditions, which were: pressure, 25.00 MPa; temperature 59.03 °C; and CO2 flow rate, 2.25 SL/min. The Gas chromatography (GC) analysis results showed that BDSO extracted by the SC-CO2 method had higher contents of unsaturated fatty acids (85.62%) and polyunsaturated fatty acids (57.90%) than that extracted by the PEE method. The gas chromatography used in conjunction with ion mobility spectrometry (GC-IMS) results showed that the main volatile compounds in BDSO were aldehydes and esters. BDSO also exhibited antioxidant ability in a dose-dependent manner. Moreover, normal and cancer cells incubated with BDSO had survival rates of more than 85%, which indicates that BDSO is not cytotoxic. Based on these results, the BDSO extracted by the SC-CO2 method could potentially be used in other applications, e.g., those that involve using berries of B. dasystachya.


Asunto(s)
Antioxidantes/análisis , Berberis/química , Aceites de Plantas/análisis , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Cromatografía con Fluido Supercrítico , Aceites de Plantas/farmacología , Semillas/química
19.
Bioorg Med Chem Lett ; 29(2): 244-247, 2019 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-30501963

RESUMEN

A series of our previously described BH3 peptide mimetics derived from Bim-BH3 domain core region were found to exhibit weak to potent PTP1B binding affinity and inhibitory activities via target-based drug screening. Among these compounds, a 12-aa Bim-BH3 core sequence peptide conjugated to palmitic acid (SM-6) displayed good PTP1B binding affinity (KD = 8.38 nmol/L), inhibitory activity (IC50 = 1.20 µmol/L) and selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Furthermore, SM-6 promoted HepG2 cell glucose uptake and inhibited the expression of PTP1B, indicating that SM-6 could improve the insulin resistance effect in the insulin-resistant HepG2 cell model. These results may indicate a new direction for the application of BH3 peptide mimetics and promising PTP1B peptide inhibitors could be designed and developed based on SM-6.


Asunto(s)
Ácido Palmítico/farmacología , Péptidos/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Células Hep G2 , Humanos , Estructura Molecular , Ácido Palmítico/química , Péptidos/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Relación Estructura-Actividad
20.
Opt Express ; 26(15): 19235-19246, 2018 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-30114182

RESUMEN

We investigate the discrete temporal Talbot effect in a synthetic mesh lattice by employing two coupled fiber loops with different lengths. The lattice consists of the round-trip number and time delay of pulse trains propagating in the fiber loops. The Talbot effect occurs only as the incident pulse train in one loop has a temporal period that is 1, 2, or 4 folds of time interval corresponding to the length difference of the two loops. By varying the splitting ratio of coupler connecting the two loops, the lattice band structure can be engineered and so do the Talbot distance, which can be further tuned by imposing an initial linear phase distribution on the incident pulse train. In addition, the incident periods for Talbot effect can also be fractional fold by using time multiplexing. The study may find applications in temporal cloaking, passive amplifying, and pulse repetition rate multiplication.

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