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1.
Biochem Cell Biol ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917487

RESUMEN

In atherosclerosis, DNA methylation plays a key regulatory role in the expression of related genes. However, the molecular mechanisms of these processes in human umbilical vein endothelial cells (HUVECs) are unclear. Here, using high-throughput sequencing from the Infinium HumanMethylation450 assay, we manifested that the cg19564375 methylation of miR-520e promoter region in the peripheral blood of acute coronary syndrome (ACS) patients was higher than that of healthy controls. As shown by RQ-MSP, the upstream DNA methylation level of the miR-520e promoter region was considerably increased in ACS patients. miR-520e was markedly downregulated in ACS patients compared with healthy controls. In the oxidized low-density lipoprotein (ox-LDL)-induced HUVECs injury model, DNA methylation of the upstream region of miR-520e was significantly increased. With increasing concentrations of the methylase inhibitor 5-Aza, miR-520e expression was upregulated. The silence of methyltransferase DNMT1, rather than DNMT3a or DNMT3b, abolished the influence of miR-520e expression by ox-LDL treatment in HUVECs. A dual luciferase reporter assay revealed that miR-520e regulated the TGFBR2 3'-untranslated region region. After silencing TGFBR2, the promoting effect of miR-520e inhibitor on cell proliferation and migration may be attenuated. In conclusion, the expression of miR-520e is modified by its promoter region DNA methylation, and miR-520e and its promoter region DNA methylation may be potential biomarkers in atherosclerosis.

2.
BMC Plant Biol ; 24(1): 762, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39123107

RESUMEN

BACKGROUND: Dendrobium Sw. represents one of the most expansive genera within the Orchidaceae family, renowned for its species' high medicinal and ornamental value. In higher plants, the ankyrin (ANK) repeat protein family is characterized by a unique ANK repeat domain, integral to a plethora of biological functions and biochemical activities. The ANK gene family plays a pivotal role in various plant physiological processes, including stress responses, hormone signaling, and growth. Hence, investigating the ANK gene family and identifying disease-resistance genes in Dendrobium is of paramount importance. RESULTS: This research identified 78 ANK genes in Dendrobium officinale Kimura et Migo, 77 in Dendrobium nobile Lindl., and 58 in Dendrobium chrysotoxum Lindl. Subsequently, we conducted comprehensive bioinformatics analyses on these ANK gene families, encompassing gene classification, chromosomal localization, phylogenetic relationships, gene structure and motif characterization, cis-acting regulatory element identification, collinearity assessment, protein-protein interaction network construction, and gene expression profiling. Concurrently, three DoANK genes (DoANK14, DoANK19, and DoANK47) in D. officinale were discerned to indirectly activate the NPR1 transcription factor in the ETI system via SA, thereby modulating the expression of the antibacterial PR gene. Hormonal treatments with GA3 and ABA revealed that 17 and 8 genes were significantly up-regulated, while 4 and 8 genes were significantly down-regulated, respectively. DoANK32 was found to localize to the ArfGAP gene in the endocytosis pathway, impacting vesicle transport and the polar movement of auxin. CONCLUSION: Our findings provide a robust framework for the taxonomic classification, evolutionary analysis, and functional prediction of Dendrobium ANK genes. The three highlighted ANK genes (DoANK14, DoANK19, and DoANK47) from D. officinale may prove valuable in disease resistance and stress response research. DoANK32 is implicated in the morphogenesis and development of D. officinale through its role in vesicular transport and auxin polarity, with subcellular localization studies confirming its presence in the nucleus and cell membrane. ANK genes displaying significant expression changes in response to hormonal treatments could play a crucial role in the hormonal response of D. officinale, potentially inhibiting its growth and development through the modulation of plant hormones such as GA3 and ABA.


Asunto(s)
Ácido Abscísico , Dendrobium , Giberelinas , Reguladores del Crecimiento de las Plantas , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Repetición de Anquirina/genética , Dendrobium/genética , Dendrobium/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Genoma de Planta , Giberelinas/farmacología , Giberelinas/metabolismo , Familia de Multigenes , Filogenia , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Nanotechnology ; 35(36)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38749414

RESUMEN

Multi-photon reduction (MPR) based on femtosecond laser makes rapid prototyping and molding in micro-nano scale feasible, but is limited in material selectivity due to lack of the understanding of the reaction mechanism in MPR process. In this paper, additively manufacturing of complex silver-based patterns through MPR is demonstrated. The effects of laser parameters, including laser pulse energies and scanning speeds, on the structural and chemical characteristics of the printed structures are systematically investigated. The results show that the geometric size of printed cubes deviates from the designed size further by increasing laser pulse energy or decreasing scanning speed. The reaction mechanism of MPR is revealed by studying the elemental composition and chemical structures of printed cubes. The evolution of Raman spectra upon the laser processing parameters suggests that the MPR process mainly includes two processes: reduction and decomposition. In the MPR process, silver ions are reduced and grow into particles by accepting the electrons from ethonal molecules; meanwhile carboxyl groups in polyvinylpyrrolidone are decomposed and form amorphous carbon that is attached on the surface of silver particles. The conductivity of silver wires fabricated by MPR reaches 2 × 105S m-1and stays relatively constant as varying their cross section area, suggesting excellent electrical conduction. The understanding of the MPR process would accelerate the development of MPR technology and the implementation of MPR in micro-electromechanical systems could therefore be envisioned.

4.
Bioorg Med Chem ; 100: 117633, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38342078

RESUMEN

The methionine adenosyltransferase MAT2A catalyzes the synthesis ofthe methyl donor S-adenosylmethionine (SAM) and thereby regulates critical aspects of metabolism and transcription. Aberrant MAT2A function can lead to metabolic and transcriptional reprogramming of cancer cells, and MAT2A has been shown to promote survival of MTAP-deficient tumors, a genetic alteration that occurs in âˆ¼ 13 % of all tumors. Thus, MAT2A holds great promise as a novel anticancer target. Here, we report a novel series of MAT2A inhibitors generated by a fragment growing approach from AZ-28, a low-molecular weight MAT2A inhibitor with promising pre-clinical properties. X-ray co-crystal structure revealed that compound 7 fully occupies the allosteric pocket of MAT2A as a single molecule mimicking MAT2B. By introducing additional backbone interactions and rigidifying the requisite linker extensions, we generated compound 8, which exhibited single digit nanomolar enzymatic and sub-micromolar cellular inhibitory potency for MAT2A.


Asunto(s)
Metionina Adenosiltransferasa , Neoplasias , Humanos , Sitio Alostérico , Metionina Adenosiltransferasa/antagonistas & inhibidores , Metionina Adenosiltransferasa/metabolismo , Mutación , S-Adenosilmetionina/metabolismo
5.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39273685

RESUMEN

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus ♀ × E. tukula ♂), abbreviated as EFT, exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in EFT compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance-regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Multi-omics results highlighted the role of lipid metabolism, particularly "Fatty acid synthesis", "EPA biosynthesis", and "Signaling lipids", in EFT heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of EFT was greater than that of maternal E. fuscoguttatus (8.46% vs. 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in EFT. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4 were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in EFT, taking a significant step towards the molecular basis of heterosis.


Asunto(s)
Metilación de ADN , Vigor Híbrido , Metabolismo de los Lípidos , Vigor Híbrido/genética , Animales , Metabolismo de los Lípidos/genética , Transcriptoma , Femenino , Masculino , Epigénesis Genética , Lubina/genética , Lubina/metabolismo , Lubina/crecimiento & desarrollo , Perfilación de la Expresión Génica
6.
Entropy (Basel) ; 26(1)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38248198

RESUMEN

The extremely harsh environment of the high temperature plasma imposes strict requirements on the construction materials of the first wall in a fusion reactor. In this work, a refractory alloy system, WTaVTiZrx, with low activation and high entropy, was theoretically designed based on semi-empirical formula and produced using a laser cladding method. The effects of Zr proportions on the metallographic microstructure, phase composition, and alloy chemistry of a high-entropy alloy cladding layer were investigated using a metallographic microscope, XRD (X-ray diffraction), SEM (scanning electron microscope), and EDS (energy dispersive spectrometer), respectively. The high-entropy alloys have a single-phase BCC structure, and the cladding layers exhibit a typical dendritic microstructure feature. The evolution of microstructure and mechanical properties of the high-entropy alloys, with respect to annealing temperature, was studied to reveal the performance stability of the alloy at a high temperature. The microstructure of the annealed samples at 900 °C for 5-10 h did not show significant changes compared to the as-cast samples, and the microhardness increased to 988.52 HV, which was higher than that of the as-cast samples (725.08 HV). When annealed at 1100 °C for 5 h, the microstructure remained unchanged, and the microhardness increased. However, after annealing for 10 h, black substances appeared in the microstructure, and the microhardness decreased, but it was still higher than the matrix. When annealed at 1200 °C for 5-10 h, the microhardness did not increase significantly compared to the as-cast samples, and after annealing for 10 h, the microhardness was even lower than that of the as-cast samples. The phase of the high entropy alloy did not change significantly after high-temperature annealing, indicating good phase stability at high temperatures. After annealing for 10 h, the microhardness was lower than that of the as-cast samples. The phase of the high entropy alloy remained unchanged after high-temperature annealing, demonstrating good phase stability at high temperatures.

7.
J Hepatol ; 79(3): 605-617, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37217020

RESUMEN

BACKGROUND & AIMS: Disturbed hepatic metabolism frequently results in excessive lipid accumulation in the adipose tissue. However, the specific role of the liver-adipose axis in maintaining lipid homeostasis, as well as the underlying mechanism, has not yet been fully elucidated. In this study, we investigated the role of hepatic glucuronyl C5-epimerase (Glce) in the progression of obesity. METHODS: We determined the association between the expression of hepatic Glce and body mass index (BMI) in obese patients. Obesity models were established in hepatic Glce-knockout and wild-type mice fed a high-fat diet (HFD) to understand the effect of Glce on obesity development. The role of Glce in the progression of disrupted hepatokine secretion was examined via secretome analysis. RESULTS: Hepatic Glce expression was inversely correlated with BMI in obese patients. Moreover, Glce level was found to be decreased in the liver of a HFD murine model. Hepatic Glce deficiency led to impaired thermogenesis in adipose tissue and exacerbated HFD-induced obesity. Interestingly, decreased level of growth differentiation factor 15 (GDF15) was observed in the culture medium of Glce-knockout mouse hepatocytes. Treatment with recombinant GDF15 obstructed obesity progression derived from the absence of hepatic Glce, similar to the effect of Glce or its inactive mutant overexpressed both in vitro and in vivo. Furthermore, liver Glce deficiency led to diminished production and increased degradation of mature GDF15, resulting in reduced hepatic GDF15 secretion. CONCLUSIONS: Hepatic Glce deficiency facilitated obesity development, and decreased Glce expression further reduced hepatic secretion of GDF15, thereby perturbing lipid homeostasis in vivo. Therefore, the novel Glce-GDF15 axis plays an important role in maintaining energy balance and may act as a potential target for combating obesity. IMPACT AND IMPLICATIONS: Evidence suggests that GDF15 plays a key role in hepatic metabolism; however, the molecular mechanism for regulating its expression and secretion is largely unknown. Our work observes that hepatic Glce, as a key Golgi-localised epimerase, may work on the maturation and post-translational regulation of GDF15. Hepatic Glce deficiency reduces the production of mature GDF15 protein and facilitates its ubiquitination, resulting in the aggravation of obesity development. This study sheds light on the new function and mechanism of the Glce-GDF15 axis in lipid metabolism and provides a potential therapeutic target against obesity.


Asunto(s)
Factor 15 de Diferenciación de Crecimiento , Obesidad , Animales , Ratones , Dieta Alta en Grasa , Factor 15 de Diferenciación de Crecimiento/metabolismo , Lípidos , Hígado/metabolismo , Obesidad/metabolismo , Racemasas y Epimerasas/metabolismo
8.
BMC Plant Biol ; 23(1): 586, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37993773

RESUMEN

BACKGROUND: Mitochondrial genomes are essential for deciphering the unique evolutionary history of seed plants. However, the rules of their extreme variation in genomic size, multi-chromosomal structure, and foreign sequences remain unresolved in most plant lineages, which further hindered the application of mitogenomes in phylogenetic analyses. RESULTS: Here, we took Dendrobium (Orchidaceae) which shows the great divergence of morphology and difficulty in species taxonomy as the study focus. We first de novo assembled two complete mitogenomes of Dendrobium wilsonii and Dendrobium henanense that were 763,005 bp and 807,551 bp long with multichromosomal structures. To understand the evolution of Dendrobium mitogenomes, we compared them with those of four other orchid species. The results showed great variations of repetitive and chloroplast-derived sequences in Dendrobium mitogenomes. Moreover, the intergenic content of Dendrobium mitogenomes has undergone expansion during evolution. We also newly sequenced mitogenomes of 26 Dendrobium species and reconstructed phylogenetic relationships of Dendrobium based on genomic mitochondrial and plastid data. The results indicated that the existence of chloroplast-derived sequences made the mitochondrial phylogeny display partial characteristics of the plastid phylogeny. Additionally, the mitochondrial phylogeny provided new insights into the phylogenetic relationships of Dendrobium species. CONCLUSIONS: Our study revealed the evolution of Dendrobium mitogenomes and the potential of mitogenomes in deciphering phylogenetic relationships at low taxonomic levels.


Asunto(s)
Dendrobium , Genoma Mitocondrial , Orchidaceae , Filogenia , Orchidaceae/genética , Dendrobium/genética , Genoma Mitocondrial/genética , Genómica/métodos , Secuencia de Bases
9.
BMC Plant Biol ; 23(1): 189, 2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37038109

RESUMEN

Dendrobium orchids have multiple photosynthetic pathways, which can be used as a model system for studying the evolution of crassulacean acid metabolism (CAM). In this study, based on the results of the net photosynthetic rates (Pn), we classified Dendrobium species into three photosynthetic pathways, then employed and compared their chloroplast genomes. The Dendrobium chloroplast genomes have typical quartile structures, ranging from 150,841-153,038 bp. The apparent differences in GC content, sequence variability, and IR junctions of SSC/IRB junctions (JSBs) were measured within chloroplast genomes among different photosynthetic pathways. The phylogenetic analysis has revealed multiple independent CAM origins among the selected Dendrobium species. After counting insertions and deletions (InDels), we found that the occurrence rates and distribution densities among different photosynthetic pathways were inconsistent. Moreover, the evolution patterns of chloroplast genes in Dendrobium among three photosynthetic pathways were also diversified. Considering the diversified genome structure variations and the evolution patterns of protein-coding genes among Dendrobium species, we proposed that the evolution of the chloroplast genomes was disproportional among different photosynthetic pathways. Furthermore, climatic correlation revealed that temperature and precipitation have influenced the distribution among different photosynthetic pathways and promoted the foundation of CAM pathway in Dendrobium orchids. Based on our study, we provided not only new insights into the CAM evolution of Dendrobium but also provided beneficial genetic data resources for the further systematical study of Dendrobium.


Asunto(s)
Dendrobium , Genoma del Cloroplasto , Filogenia , Dendrobium/genética , Cambio Climático , Cloroplastos/genética , Evolución Molecular
10.
Crit Rev Biotechnol ; 43(3): 384-392, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35430946

RESUMEN

Lipids are widely distributed in various tissues of an organism, mainly in plant storage organs (e.g., fruits, seeds, etc.). Lipids are vital biological substances that are involved in: signal transduction, membrane biogenesis, energy storage, and the formation of transmembrane fat-soluble substances. Some lipids and related lipid derivatives could be changed in their: content, location, or physiological activity by the external environment, such as biotic or abiotic stresses. Lipid phosphate phosphatases (LPPs) play important roles in regulating intermediary lipid metabolism and cellular signal response. LPPs can dephosphorylate lipid phosphates containing phosphate monolipid bonds such as: phosphatidic acid, lysophosphatidic acid (LPA), and diacylglycerol pyrophosphate, etc. These processes can change the contents of some important lipid signal mediation such as diacylglycerol and LPA, affecting lipid signal transmission. Here, we summarize the research progress of LPPs in plants, emphasizing the structural and biochemical characteristics of LPPs and their role in spatio-temporal regulation. In the future, more in-depth studies are required to boost our understanding of the key role of plant LPPs and lipid metabolism in: signal regulation, stress tolerance pathway, and plant growth and development.


Asunto(s)
Fosfatidato Fosfatasa , Transducción de Señal , Fosfatidato Fosfatasa/química , Fosfatidato Fosfatasa/metabolismo , Transducción de Señal/fisiología , Ácidos Fosfatidicos , Fosfatos , Metabolismo de los Lípidos
11.
Nucleic Acids Res ; 49(D1): D1170-D1178, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33104791

RESUMEN

One of the most prominent topics in drug discovery is efficient exploration of the vast drug-like chemical space to find synthesizable and novel chemical structures with desired biological properties. To address this challenge, we created the DrugSpaceX (https://drugspacex.simm.ac.cn/) database based on expert-defined transformations of approved drug molecules. The current version of DrugSpaceX contains >100 million transformed chemical products for virtual screening, with outstanding characteristics in terms of structural novelty, diversity and large three-dimensional chemical space coverage. To illustrate its practical application in drug discovery, we used a case study of discoidin domain receptor 1 (DDR1), a kinase target implicated in fibrosis and other diseases, to show DrugSpaceX performing a quick search of initial hit compounds. Additionally, for ligand identification and optimization purposes, DrugSpaceX also provides several subsets for download, including a 10% diversity subset, an extended drug-like subset, a drug-like subset, a lead-like subset, and a fragment-like subset. In addition to chemical properties and transformation instructions, DrugSpaceX can locate the position of transformation, which will enable medicinal chemists to easily integrate strategy planning and protection design.


Asunto(s)
Bases de Datos de Compuestos Químicos , Bases de Datos Farmacéuticas , Descubrimiento de Drogas/métodos , Drogas en Investigación/farmacología , Medicamentos bajo Prescripción/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Receptor con Dominio Discoidina 1/antagonistas & inhibidores , Receptor con Dominio Discoidina 1/química , Receptor con Dominio Discoidina 1/metabolismo , Diseño de Fármacos , Drogas en Investigación/química , Fibrosis/tratamiento farmacológico , Humanos , Internet , Ligandos , Medicamentos bajo Prescripción/química , Bibliotecas de Moléculas Pequeñas/química , Programas Informáticos
12.
BMC Plant Biol ; 22(1): 201, 2022 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-35439926

RESUMEN

BACKGROUND: Because chloroplast (cp) genome has more conserved structures than nuclear genome and mitochondrial genome, it is a useful tool in estimating the phylogenetic relationships of plants. With a series of researches for cp genomes, there have been comprehensive understandings about the cp genome features. The genus Bulbophyllum widely distributed in Asia, South America, Australia and other places. Therefore, it is an excellent type genus for studying the effects of geographic isolation. RESULTS: In this study, the cp genomes of nine Bulbophyllum orchids were newly sequenced and assembled using the next-generation sequencing technology. Based on 19 Asian (AN) and eight South American (SA) Bulbophyllum orchids, the cp genome features of AN clade and SA clade were compared. Comparative analysis showed that there were considerable differences in overall cp genome features between two clades in three aspects, including basic cp genome features, SSC/IRB junctions (JSBs) and mutational hotspots. The phylogenetic analysis and divergence time estimation results showed that the AN clade has diverged from the SA clade in the late Oligocene (21.50-30.12 mya). After estimating the occurrence rates of the insertions and deletions (InDels), we found that the change trends of cp genome structures between two clades were different under geographic isolation. Finally, we compared selective pressures on cp genes and found that long-term geographic isolation made AN and SA Bulbophyllum cp genes evolved variably. CONCLUSION: The results revealed that the overall structural characteristics of Bulbophyllum cp genomes diverged during the long-term geographic isolation, and the crassulacean acid metabolism (CAM) pathway may play an important role in the Bulbophyllum species evolution.


Asunto(s)
Genoma del Cloroplasto , Orchidaceae , Asia , Australia , Genoma del Cloroplasto/genética , Orchidaceae/genética , Filogenia
13.
BMC Plant Biol ; 22(1): 529, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36376794

RESUMEN

BACKGROUND: Dendrobium officinale Kimura et Migo, which contains rich polysaccharides, flavonoids and alkaloids, is a Traditional Chinese Medicine (TCM) with important economic benefits, while various pathogens have brought huge losses to its industrialization. NBS gene family is the largest class of plant disease resistance (R) genes, proteins of which are widely distributed in the upstream and downstream of the plant immune systems and are responsible for receiving infection signals and regulating gene expression respectively. It is of great significance for the subsequent disease resistance breeding of D. officinale to identify NBS genes by using the newly published high-quality chromosome-level D. officinale genome. RESULTS: In this study, a total of 655 NBS genes were uncovered from the genomes of D. officinale, D. nobile, D. chrysotoxum, V. planifolia, A. shenzhenica, P. equestris and A. thaliana. The phylogenetic results of CNL-type protein sequences showed that orchid NBS-LRR genes have significantly degenerated on branches a and b. The Dendrobium NBS gene homology analysis showed that the Dendrobium NBS genes have two obvious characteristics: type changing and NB-ARC domain degeneration. Because the NBS-LRR genes have both NB-ARC and LRR domains, 22 D. officinale NBS-LRR genes were used for subsequent analyses, such as gene structures, conserved motifs, cis-elements and functional annotation analyses. All these results suggested that D. officinale NBS-LRR genes take part in the ETI system, plant hormone signal transduction pathway and Ras signaling pathway. Finally, there were 1,677 DEGs identified from the salicylic acid (SA) treatment transcriptome data of D. officinale. Among them, six NBS-LRR genes (Dof013264, Dof020566, Dof019188, Dof019191, Dof020138 and Dof020707) were significantly up-regulated. However, only Dof020138 was closely related to other pathways from the results of WGCNA, such as pathogen identification pathways, MAPK signaling pathways, plant hormone signal transduction pathways, biosynthetic pathways and energy metabolism pathways. CONCLUSION: Our results revealed that the NBS gene degenerations are common in the genus Dendrobium, which is the main reason for the diversity of NBS genes, and the NBS-LRR genes generally take part in D. officinale ETI system and signal transduction pathways. In addition, the D. officinale NBS-LRR gene Dof020138, which may have an important breeding value, is indirectly activated by SA in the ETI system.


Asunto(s)
Dendrobium , Ácido Salicílico , Ácido Salicílico/farmacología , Ácido Salicílico/metabolismo , Dendrobium/genética , Dendrobium/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Resistencia a la Enfermedad/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Fitomejoramiento , Transcriptoma
14.
Bioinformatics ; 37(18): 2930-2937, 2021 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-33739367

RESUMEN

MOTIVATION: Breast cancer is one of the leading causes of cancer deaths among women worldwide. It is necessary to develop new breast cancer drugs because of the shortcomings of existing therapies. The traditional discovery process is time-consuming and expensive. Repositioning of clinically approved drugs has emerged as a novel approach for breast cancer therapy. However, serendipitous or experiential repurposing cannot be used as a routine method. RESULTS: In this study, we proposed a graph neural network model GraphRepur based on GraphSAGE for drug repurposing against breast cancer. GraphRepur integrated two major classes of computational methods, drug network-based and drug signature-based. The differentially expressed genes of disease, drug-exposure gene expression data and the drug-drug links information were collected. By extracting the drug signatures and topological structure information contained in the drug relationships, GraphRepur can predict new drugs for breast cancer, outperforming previous state-of-the-art approaches and some classic machine learning methods. The high-ranked drugs have indeed been reported as new uses for breast cancer treatment recently. AVAILABILITYAND IMPLEMENTATION: The source code of our model and datasets are available at: https://github.com/cckamy/GraphRepur and https://figshare.com/articles/software/GraphRepur_Breast_Cancer_Drug_Repurposing/14220050. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Reposicionamiento de Medicamentos/métodos , Programas Informáticos , Redes Neurales de la Computación , Aprendizaje Automático
15.
BMC Endocr Disord ; 22(1): 131, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35578222

RESUMEN

BACKGROUND: Obesity is a risk factor for metabolic diseases and often influences hormone change. Lipoprotein (a) (Lp(a)) is associated with various metabolic diseases, but there are few studies on the relationship between Lp(a) and hormones in obese patients. This study investigated the the relationship between Lp(a) and hormones in Chinese overweight/obese people. METHODS: A total of 410 overweight/obese patients (Body mass index (BMI) ≥ 25 kg/m2) were included and underwent sociodemographic data investigations and relevant clinical examinations. Lp(a) was analyzed by colorimetric enzymatic assays and hormone was measured with chemiluminescence immunoassay method. According to Lp(a) levels, they were categorized into 3 groups: the lower Lp(a) group (Lp(a) levels < 30 mg/dl), the moderate Lp(a) group (Lp(a) levels between 30 mg/dl and 120 mg/dl) and the higher Lp(a) group (Lp(a) levels > 120 mg/dl). The differences of hormone levels among the three groups were compared and the relationship between Lp(a) and hormones was analyzed by Spearman's rank correlation. RESULTS: The higher Lp(a) group had significantly lower testosterone (TES) levels compared with the lower and moderate Lp(a) groups in the case of gender, age and BMI matching. Lp(a) concentration was negatively correlated with TES levels in all participants and the negative association between Lp(a) and TES levels was also observed when the analysis was stratified by gender. Additionally, the TES was statistically related with Lp(a) levels in the multiple linear regression model (95% confidence interval: - 0.451 to - 0.079). CONCLUSIONS: TES levels was negatively associated with Lp(a) levels in Chinese overweight/obese patients.


Asunto(s)
Enfermedades Metabólicas , Sobrepeso , Índice de Masa Corporal , China/epidemiología , Hormonas , Humanos , Lipoproteína(a) , Obesidad/complicaciones , Obesidad/metabolismo , Sobrepeso/complicaciones
16.
BMC Endocr Disord ; 22(1): 304, 2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36476346

RESUMEN

BACKGROUND: Meteorin-like (Metrnl) is a newly discovered adipomyokine that regulates systemic energy homeostasis. Both thyroid hormones and Metrnl increase energy expenditure and induce browning of adipose tissue. Thus, the aim of this study was to investigate serum Metrnl levels in hyperthyroid patients and the association of serum Metrnl levels with hyperthyroidism. METHODS: The study included 88 patients with newly diagnosed untreated overt hyperthyroidism and 100 age- and sex- matched healthy controls. Serum Metrnl levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum Metrnl levels were significantly elevated in patients with hyperthyroidism compared with controls. Linear regression analyses indicated that serum Metrnl levels were independently associated with FT3 (ß = 0.324, P = 0.001), FT4 (ß = 0.293, P = 0.001), and TSH (ß = -0.234, P = 0.006) after full adjustment. Additionally, further logistic regression analyses revealed that the highest Metrnl tertile was significantly associated with hyperthyroidism compared with the lowest tertile (P for trend < 0.001). The relationship remained significant even after adjusting for potential confounders. Meanwhile, each one-unit increase in circulating Metrnl was independently associated with hyperthyroidism (OR 1.021, 95%CI 1.007-1.036, P < 0.01). CONCLUSION: Serum Metrnl levels were elevated in patients with hyperthyroidism and were independently associated with hyperthyroidism.

17.
BMC Cardiovasc Disord ; 22(1): 372, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35965341

RESUMEN

BACKGROUND: The atherogenic index of plasma (AIP) is a predictor for cardiovascular diseases (CVD), while hyperuricemia is an independent risk factor for a variety of CVD. Apolipoprotein AI has been found to be a protective factor for CVD. However, the role of APO AI in the association between plasma uric acid and AIP among healthy Chinese people needs to be further explored. AIMS: To evaluate the relationship between blood uric acid and AIP level in healthy Chinese people. To evaluate the relationship between blood uric acid and Apolipoprotein AI in healthy Chinese people. METHOD: A total of 3501 normal and healthy subjects who had physical examinations were divided into the hyperuricemia (HUA) group and the normouricemia (NUA) group. RESULT: The AIP of HUA group was significantly higher than that of NUA group [0.17±0.30 vs. -0.08±0.29]. Apo AI (1.33 ± 0.21 vs. 1.47 ± 0.26 g/l) and HDL-c (1.12 ± 0.27 vs. 1.36 ± 0.33 mmol/l) were significantly lower in the HUA group than in the NUA group. LDL-C (2.81 ± 0.77 vs. 2.69 ± 0.73 mmol/l), Apo B (0.96 ± 0.20 vs. 0.89 ± 0.20 g/l), FBG (5.48 ± 0.48 vs. 5.36 ± 0.48 mmol/l) and HOMA-IR [2.75 (1.92-3.91) vs. 2.18 (1.50-3.12)] was significantly higher in HAU group than the NUA group. Increases in plasma UA were associated with increases in AIP (ß = 0.307, p < 0.01) and decreases in Apo AI (ß = - 0.236, p < 0.01). CONCLUSION: Hyperuricemia is an independent risk factor for high AIP level. Inhibition of Apolipoprotein AI may be one of the mechanisms of UA which is involved in the progression of cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares , Hiperuricemia , Apolipoproteína A-I , China/epidemiología , Estudios Transversales , Humanos , Hiperuricemia/diagnóstico , Ácido Úrico
18.
Entropy (Basel) ; 24(9)2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36141160

RESUMEN

Community detection in semantic social networks is a crucial issue in online social network analysis, and has received extensive attention from researchers in various fields. Different conventional methods discover semantic communities based merely on users' preferences towards global topics, ignoring the influence of topics themselves and the impact of topic propagation in community detection. To better cope with such situations, we propose a Gaming-based Topic Influence Percolation model (GTIP) for semantic overlapping community detection. In our approach, community formation is modeled as a seed expansion process. The seeds are individuals holding high influence topics and the expansion is modeled as a modified percolation process. We use the concept of payoff in game theory to decide whether to allow neighbors to accept the passed topics, which is more in line with the real social environment. We compare GTIP with four traditional (GN, FN, LFM, COPRA) and seven representative (CUT, TURCM, LCTA, ACQ, DEEP, BTLSC, SCE) semantic community detection methods. The results show that our method is closer to ground truth in synthetic networks and has a higher semantic modularity in real networks.

19.
Entropy (Basel) ; 24(8)2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-36010804

RESUMEN

The semantic social network is a complex system composed of nodes, links, and documents. Traditional semantic social network community detection algorithms only analyze network data from a single view, and there is no effective representation of semantic features at diverse levels of granularity. This paper proposes a multi-view integration method for community detection in semantic social network. We develop a data feature matrix based on node similarity and extract semantic features from the views of word frequency, keyword, and topic, respectively. To maximize the mutual information of each view, we use the robustness of L21-norm and F-norm to construct an adaptive loss function. On this foundation, we construct an optimization expression to generate the unified graph matrix and output the community structure with multiple views. Experiments on real social networks and benchmark datasets reveal that in semantic information analysis, multi-view is considerably better than single-view, and the performance of multi-view community detection outperforms traditional methods and multi-view clustering algorithms.

20.
BMC Genomics ; 22(1): 548, 2021 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-34273948

RESUMEN

BACKGROUND: Lipid phosphate phosphatases (LPP) are critical for regulating the production and degradation of phosphatidic acid (PA), an essential signaling molecule under stress conditions. Thus far, the LPP family genes have not been reported in rapeseed (Brassica napus L.). RESULTS: In this study, a genome-wide analysis was carried out to identify LPP family genes in rapeseed that respond to different stress conditions. Eleven BnLPPs genes were identified in the rapeseed genome. Based on phylogenetic and synteny analysis, BnLPPs were classified into four groups (Group I-Group IV). Gene structure and conserved motif analysis showed that similar intron/exon and motifs patterns occur in the same group. By evaluating cis-elements in the promoters, we recognized six hormone- and seven stress-responsive elements. Further, six putative miRNAs were identified targeting three BnLPP genes. Gene ontology analysis disclosed that BnLPP genes were closely associated with phosphatase/hydrolase activity, membrane parts, phosphorus metabolic process, and dephosphorylation. The qRT-PCR based expression profiles of BnLPP genes varied in different tissues/organs. Likewise, several gene expression were significantly up-regulated under NaCl, PEG, cold, ABA, GA, IAA, and KT treatments. CONCLUSIONS: This is the first report to describe the comprehensive genome-wide analysis of the rapeseed LPP gene family. We identified different phytohormones and abiotic stress-associated genes that could help in enlightening the plant tolerance against phytohormones and abiotic stresses. The findings unlocked new gaps for the functional verification of the BnLPP gene family during stresses, leading to rapeseed improvement.


Asunto(s)
Brassica napus , Brassica napus/genética , Brassica napus/metabolismo , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Fosfolipasas , Fosfolípidos , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética
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