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2.
Energy Fuels ; 38(11): 10370-10380, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38863683

RESUMEN

Green hydrogen from water electrolysis is a key driver for energy and industrial decarbonization. The prediction of the future green hydrogen cost reduction is required for investment and policy-making purposes but is complicated due to a lack of data, incomplete accounting for costs, and difficulty justifying trend predictions. A new AI-assisted data-driven prediction model is developed for an in-depth analysis of the current and future levelized costs of green hydrogen, driven by both progressive and disruptive innovations. The model uses natural language processing to gather data and generate trends for the technological development of key aspects of electrolyzer technology. Through an uncertainty analysis, green hydrogen costs have been shown to likely reach the key target of <$2.5 kg-1 by 2030 via progressive innovations, and beyond this point, disruptive technological developments are required to affect significantly further decease cost. Additionally, the global distribution of green hydrogen costs has been calculated. This work creates a comprehensive analysis of the levelized cost of green hydrogen, including the important balance of plant components, both now and as electrolyzer technology develops, and offers a likely prediction for how the costs will develop over time.

3.
Biomed Pharmacother ; 175: 116747, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38744217

RESUMEN

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.


Asunto(s)
Histonas , Esquizofrenia , Esquizofrenia/metabolismo , Esquizofrenia/genética , Humanos , Histonas/metabolismo , Animales , Epigénesis Genética , Procesamiento Proteico-Postraduccional , Acetilación , Metilación , Fosforilación , Ensamble y Desensamble de Cromatina
4.
Sci Adv ; 9(32): eadh1181, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37556543

RESUMEN

Mg-ion batteries offer a safe, low-cost, and high-energy density alternative to current Li-ion batteries. However, nonaqueous Mg-ion batteries struggle with poor ionic conductivity, while aqueous batteries face a narrow electrochemical window. Our group previously developed a water-in-salt battery with an operating voltage above 2 V yet still lower than its nonaqueous counterpart because of the dominance of proton over Mg-ion insertion in the cathode. We designed a quasi-solid-state magnesium-ion battery (QSMB) that confines the hydrogen bond network for true multivalent metal ion storage. The QSMB demonstrates an energy density of 264 W·hour kg-1, nearly five times higher than aqueous Mg-ion batteries and a voltage plateau (2.6 to 2.0 V), outperforming other Mg-ion batteries. In addition, it retains 90% of its capacity after 900 cycles at subzero temperatures (-22°C). The QSMB leverages the advantages of aqueous and nonaqueous systems, offering an innovative approach to designing high-performing Mg-ion batteries and other multivalent metal ion batteries.

5.
Small Methods ; 7(3): e2201537, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36609816

RESUMEN

Next-generation ultrahigh power density proton exchange membrane fuel cells rely not only on high-performance membrane electrode assembly (MEA) but also on an optimal cell structure. To this end, this work comprehensively investigates the cell performance under various structures, and it is revealed that there is unexploited performance improvement in structure design because its positive effect enhancing gas supply is often inhibited by worse proton/electron conduction. Utilizing fine channel/rib or the porous flow field is feasible to eliminate the gas diffusion layer (GDL) and hence increase the power density significantly due to the decrease of cell thickness and gas/electron transfer resistances. The cell structure combining fine channel/rib, GDL elimination and double-cell structure is believed to increase the power density from 4.4 to 6.52 kW L-1 with the existing MEA, showing nearly equal importance with the new MEA development in achieving the target of 9.0 kW L-1 .

6.
Bioresour Technol ; 369: 128479, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36513305

RESUMEN

This article reports a safe, low-cost, and industrially applicable magnetite supported on activated carbon catalyst that can be magnetically retrieved from the solid and reused multiple times without the need of a regeneration step. The FeOx/C catalyst improved the bio-oil yield by 19.7 ± 0.96 % when compared to the uncatalysed reaction at 320 °C for the HTL of draff (brewer's spent grains). The use of homogeneous Na2CO3 base as a catalyst and co-catalyst, improved carbon extraction into the aqueous phase. The exceptional catalytic activity can be attributed to the Fe3O4 phase which can produce in-situ H2 that improves the biomass decomposition and oil property with an energy recovery of ∼84 %. The FeOx/C catalyst was separated using magnetic retrieval and maintained its catalytic activity even up to 5 reaction cycles showing potential as a cheap catalyst for HTL reactions and can be scaled-up for industrial applications.


Asunto(s)
Biocombustibles , Aceites de Plantas , Temperatura , Biomasa , Agua
7.
J Oncol ; 2022: 8394816, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36471887

RESUMEN

Peptidyl arginine deiminase 1 (PADI1) catalyzes protein citrullination and has a role in regulating immune responses. The tumor immune microenvironment has been reported to be important in colorectal cancer (CRC), which was correlated with the ability of CRC patients to benefit from immunotherapy. However, there is a lack of molecular markers for matching CRC immunotherapy. Previously, single-gene risk models have only considered the effect of individual genes on intrinsic tumor properties, ignoring the role of genes and their co-expressed genes as a whole. In this study, we analyzed the differential expression of PADI1 in colorectal cancer (CRC). We found that PADI1 was highly expressed in CRC. Subgroup survival analysis revealed a prognostic survival difference for PADI1 in CRC patients aged less than 65 years, male, T stage, N0, M0, and stage I-II (p < 0.05). In addition, we analyzed the functions and signaling pathways associated with PADI1 in CRC and found that it was highly enriched in several immune-related functions and pathways. Then, a set of PADI1 co-expressed genes (PCGs) risk-prognosis scores was developed with PADI1 as the core, which could accurately predict the prognosis of CRC (p < 0.05). PCGs risk score can be an independent prognostic factor for CRC. A new set of Norman plot models were developed for clinical characteristics with age, sex, and TNM stage, which can accurately predict CRC 1, 3, and 5 years survival, and calibration curves and decision curve analysis (DCA) validated the accuracy of the models. The risk score assessed the immune microenvironment of CRC and found that the immune score was higher in the low-risk group, and CD4+ T cells, helper T cells, and eosinophils were more infiltrated in the low-risk group (p < 0.05). Immunotherapy efficacy was better in the low-risk group (p < 0.05). The underlying mechanism may be that the high-risk group of PCGs was enriched in some pathways that promote immune escape and immune dysfunction. In conclusion, PCGs may better predict CRC prognosis and immunotherapeutic response.

9.
BMC Cardiovasc Disord ; 22(1): 378, 2022 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-35987992

RESUMEN

BACKGROUND: Insulin resistance is one of the major mechanisms for cardiovascular events. Estimated glucose disposal rate(eGDR) has been demonstrated as a simple, accurate, and cost-effective estimator of insulin resistance. Our study aims to evaluate the correlation between eGDR and the prevalent IHD and assess the incremental value of eGDR for identifying prevalent IHD in the rural general population. METHODS: Our study enrolled 10,895 participants from a cross-sectional survey of a metabolic management program. The survey was conducted in the rural areas of southeastern China between October 2019 and April 2020. eGDR = 21.158 - (0.09 * waist circumference) - (3.407 * hypertension) - (0.551 * HbA1c). RESULTS: The prevalence of IHD was 4.20%. After adjusting for demographic, anthropometric, laboratory, and medical history covariates, each SD increase of eGDR brought a 25.9% risk reduction for prevalent IHD. After dividing eGDR into groups, the top group had a 58.9% risk reduction than the bottom group. Furthermore, smooth curve fitting demonstrated that the correlation between eGDR and prevalent IHD was linear in the whole range of eGDR. Additionally, AUC suggested that eGDR could significantly improve the identification of prevalent IHD by adding it to cardiovascular risk factors (0.703 vs. 0.711, P for comparison = 0.041). Finally, the category-free net reclassification index and integrated discrimination index also implicated the improvement from eGDR to identify prevalent IHD. CONCLUSION: Our data demonstrated a significant, negative, and linear correlation between eGDR and prevalent IHD. Our findings could suggest the potential usefulness of eGDR to improve the identification of prevalent IHD in the rural general population.


Asunto(s)
Diabetes Mellitus Tipo 1 , Resistencia a la Insulina , Isquemia Miocárdica , Glucemia/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 1/epidemiología , Humanos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiología , Factores de Riesgo
10.
Ann Hum Biol ; 49(3-4): 204-209, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35815603

RESUMEN

BACKGROUND: Xibe is the fifth largest minority population of Liaoning province. Predominately they live in Liaoning province (69.52%), followed by Xinjiang (18.06%), Heilongjiang (3.99%), Jilin (1.63%) and Inner Mongolia provinces (1.57%). AIM: To provide an updated and precise population database on an extended set of Y STRs not available before and explore the forensic characteristics of 26 Y chromosomal STRs. SUBJECTS & METHODS: In this study, we genotyped 406 unrelated Xibe male individuals from Liaoning province using Goldeneye® 26Y System kit and calculated the forensic parameters of these 26 Y STRs loci. RESULTS: All haplotypes generated for 406 Xibe samples using Goldeneye® 26Y kit were unique with a discrimination capacity (DC) of 1. On restricting the haplotypes to the Y-filer® set of 17 Y-STRs, we observed 392 haplotypes. Among them 93.53% (380) were unique with a DC of 0.9655 and haplotype diversity (HD) of 0.9998, showing high discrimination power of the extended set of markers in this population. Allelic frequencies ranged from 0.0024 to 0.7684 across 26 Y STRs loci. DYS385 showed the highest gene diversity (0.9691) among all markers. CONCLUSION: According to pairwise RST genetic distances among Xibe populations from China, the Liaoning Xibe population showed the closest genetic distance (0.0035) followed by Xinjiang Xibe population (0.0218). Multidimensional scaling (MDS) analysis among Xibe and 29 other Chinese populations showed that local populations such as Manchu from Liaoning and Han from Beijing had a close affinity while Tibetans from Aba, China, were most distant from Xibe populations. Moreover, 12 individuals showed a null allele at DYS448 in Xibe population samples. We submitted Y-STRs data in the Y-Chromosome Haplotype Reference Database (YHRD) for future forensic and other usage.


Asunto(s)
Cromosomas Humanos Y , Etnicidad , China , Cromosomas Humanos Y/genética , Etnicidad/genética , Frecuencia de los Genes , Genética de Población , Haplotipos , Humanos , Masculino , Repeticiones de Microsatélite
11.
Inorg Chem ; 61(23): 8854-8860, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35642338

RESUMEN

We present here the coordination self-assembly of a new heteroleptic (bpyPd)4L1L22 coordination complex (1) from one novel pyridinium-functionalized bis-2,4,6-tris(pyridin-3-yl)-1,3,5-triazine (bis-3-TPT, L1) macrocyclic ligand, two separate 3-TPT (L2) ligands, and four cis-blocking bpyPd(NO3)2 (bpy = 2,2'-bipyridine). While homoleptic self-assemblies with either L1 or L2 gave dynamic mixtures of products, a single thermodynamic heteroleptic complex was obtained driven by the shape complementarity of building blocks. Moreover, the redox-active nature of the heteroleptic assembly facilitates the highly efficient catalytic aerobic photo-oxidation of aromatic secondary alcohols under mild conditions.

13.
Gene ; 808: 145973, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34592350

RESUMEN

INTRODUCTION: Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5' regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression. MATERIALS AND METHODS: Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors. RESULTS: In SK-N-SH and U87 cell lines, regions from -337 to -159 bp, -704 to -556 bp inhibited gene expression, while -556 to -337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment -1703 to + 188 bp was significantly increased compared to adjacent fragments -1539 to + 188 bp and -1843 to + 188 bp. The protein expressions of fragments -2162 to + 188 bp and -2025 to + 188 bp, -1539 to + 188 bp and -1215 to + 188 bp, -1215 to + 188 bp and -1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the -337 to -159, -556 to -337, and -704 to -556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments. CONCLUSIONS: Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases.


Asunto(s)
Regiones no Traducidas 5'/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Línea Celular Tumoral , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Genes Reporteros , Células HEK293 , Humanos , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Transcripción Genética/genética , Activación Transcripcional/genética
14.
J Healthc Eng ; 2021: 3922611, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34917304

RESUMEN

Objective: To explore risk factors for death from cardiomyopathy and the effectiveness of health information management (HIM). Methods: A total of 80 patients with cardiomyopathy admitted in ICU of our hospital (January 2016-January 2020) were selected as study subjects, and the clinical data of the patients were retrospectively analyzed. The patients were divided into the survival group (n = 72) and the death group (n = 14) according to the treatment outcome. Then, according to the management mode, the survival group was further equally divided into the conventional group and the HIM group to investigate the influence of risk factors on prognosis of patients with cardiomyopathy and the effectiveness of HIM. Results: No significant difference was found in baseline body mass, myocardial enzymes, troponin, infection factors, history of heart disease, and gender between the survival group and the death group (P > 0.05). Compared with the survival group, the patients of the death group were older (P < 0.05), LVEF of the death group was obviously lower (P < 0.05), and the scores of APACHE II and SOFA of the death group were obviously higher (P < 0.05). Further logistic regression analysis of the univariate factors influencing the risk of death from cardiomyopathy led to the conclusion that LVEF was an independent risk factor for death in patients with cardiomyopathy. LVEF below 24.69% examined by echocardiography had a high predictive value, with a sensitivity of 98.6% and a specificity of 78.6%. No obvious difference was found in general data between the conventional group and the HIM group (P > 0.05). Compared with the conventional group, the disease remission rate, complication rate, awareness rate of health knowledge, ICU length of stay, and scores of self-management efficacy of the HIM group were obviously better (P < 0.05). No significant difference was found in 5-year mean survival rate between the conventional group and the HIM group (P > 0.05). Conclusion: Older age, lower LVEF, and higher scores of APACHE II and SOFA are all risk factors for death from cardiomyopathy. Lower LVEF is an independent risk factor, and LVEF below 24.69% is an important indicator of increased risk of death. Moreover, HIM can effectively improve short-term treatment efficacy but has little effect on the long-term survival rate.


Asunto(s)
Cardiomiopatías , Gestión de la Información en Salud , Anciano , Humanos , Estudios Retrospectivos , Factores de Riesgo
15.
Nature ; 595(7867): 361-369, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34262215

RESUMEN

With the rapid growth and development of proton-exchange membrane fuel cell (PEMFC) technology, there has been increasing demand for clean and sustainable global energy applications. Of the many device-level and infrastructure challenges that need to be overcome before wide commercialization can be realized, one of the most critical ones is increasing the PEMFC power density, and ambitious goals have been proposed globally. For example, the short- and long-term power density goals of Japan's New Energy and Industrial Technology Development Organization are 6 kilowatts per litre by 2030 and 9 kilowatts per litre by 2040, respectively. To this end, here we propose technical development directions for next-generation high-power-density PEMFCs. We present the latest ideas for improvements in the membrane electrode assembly and its components with regard to water and thermal management and materials. These concepts are expected to be implemented in next-generation PEMFCs to achieve high power density.

16.
Gene ; 779: 145494, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33588036

RESUMEN

Microalgae, one of the most important classes of biomass producers, can produce exopolysaccharides similar to bacteria. The exopolysaccharide from Chlorella (CEPS) displays remarkable anticancer activity the mechanism of which remains to be elucidated. In this study, we analyzed the inhibitory effect of CEPS on the growth of HeLa cells. The results showed that CEPS inhibited the proliferation, decreased the viability, and changed the morphology of HeLa cells. Transcriptome analysis showed that 1894 genes were differentially expressed in the CEPS-treated group compared with the control group, including 1076 genes that were upregulated and 818 genes that were downregulated. The results of gene function enrichment analysis showed that the differentially expressed genes (DEGs) were significantly enriched in apoptosis and tumor-related biological processes and participated in several cancer and apoptosisrelated signaling pathways, including the MAPK signaling pathway, TNF signaling pathway, and the PI3K-Akt signaling pathway. The protein-protein interaction network identified 13 DEGs including PTPN11, RSAD2, ISG15, IFIT1, MX2, IFIT2, OASL, OAS1, JUN, OAS2, XAF1, ISG20, and IRF9 as hub genes. Our results suggest that CEPS is a promising therapeutic drug for the follow-up interventional therapy of cancer.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Chlorella/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Polisacáridos/farmacología , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Perfilación de la Expresión Génica/métodos , Células HeLa , Humanos , Fosfatidilinositol 3-Quinasas/genética , Polisacáridos/administración & dosificación , Polisacáridos/química , Mapas de Interacción de Proteínas/efectos de los fármacos , Mapas de Interacción de Proteínas/genética , Células Vero
17.
J Am Chem Soc ; 143(4): 2016-2024, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33471998

RESUMEN

Stimuli-responsive structural transformations between discrete coordination supramolecular architectures not only are essential to construct smart functional materials but also provide a versatile molecular-level platform to mimic the biological transformation process. We report here the controlled self-assembly of three topologically unprecedented conjoined twin-cages, i.e., one stapled interlocked Pd12L6 cage (2) and two helically isomeric Pd6L3 cages (3 and 4) made from the same cis-blocked palladium corners and a new bis-bidentate ligand (1). While cage 2 features three mechanically coupled cavities, cages 3 and 4 are topologically isomeric helicate-based twin-cages based on the same metal/ligand stoichiometry. Sole formation of cage 2 or a dynamic mixture of cages 3 and 4 can be controlled by changing the solvents employed during the self-assembly. Structural conversions between cages 3 and 4 can be triggered by changes in both temperature/solvent and induced-fit guest encapsulations. Well-controlled interconversion between such topologically complex superstructures may lay a solid foundation for achieving a variety of functions within a switchable system.

18.
Front Genet ; 12: 760760, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34976009

RESUMEN

The Xinjiang Uyghur Autonomous Region of China (XUARC) harbors almost 50 ethnic groups including the Uyghur (UGR: 45.84%), Han (HAN: 40.48%), Kazakh (KZK: 6.50%), Hui (HUI: 4.51%), Kyrgyz (KGZ: 0.86%), Mongol (MGL: 0.81%), Manchu (MCH: 0.11%), and Uzbek (UZK: 0.066%), which make it one of the most colorful regions with abundant cultural and genetic diversities. In our previous study, we established allelic frequency databases for 14 autosomal short tandem repeats (STRs) for four minority populations from XUARC (MCH, KGZ, MGL, and UZK) using the AmpFlSTR® Identifiler PCR Amplification Kit. In this study, we genotyped 2,121 samples using the GoldenEye™ 20A Kit (Beijing PeopleSpot Inc., Beijing, China) amplifying 19 autosomal STR loci for four major ethnic groups (UGR, HAN, KZK, and HUI). These groups make up 97.33% of the total XUARC population. The total number of alleles for all the 19 STRs in these populations ranged from 232 (HAN) to 224 (KZK). We did not observe any departures from the Hardy-Weinberg equilibrium (HWE) in these populations after sequential Bonferroni correction. We did find minimal departure from linkage equilibrium (LE) for a small number of pairwise combinations of loci. The match probabilities for the different populations ranged from 1 in 1.66 × 1023 (HAN) to 6.05 × 1024 (HUI), the combined power of exclusion ranged from 0.999 999 988 (HUI) to 0.999 999 993 (UGR), and the combined power of discrimination ranged from 0.999 999 999 999 999 999 999 983 (HAN) to 0.999 999 999 999 999 999 999 997 (UGR). Genetic distances, principal component analysis (PCA), STRUCTURE analysis, and the phylogenetic tree showed that genetic affinity among studied populations is consistent with linguistic, ethnic, and geographical classifications.

19.
BMC Psychiatry ; 20(1): 499, 2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-33036580

RESUMEN

BACKGROUND: The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. METHODS: Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. RESULTS: Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from - 1587 to - 1371 bp (TSS, + 1), - 1149 to - 894 bp, - 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions - 603 to - 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. CONCLUSIONS: HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions - 1587 to - 1371 bp, - 1149 to - 894 bp, - 603 to - 316 bp, - 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.


Asunto(s)
Estudio de Asociación del Genoma Completo , Trastornos Mentales , Células HEK293 , Haplotipos , Humanos , Trastornos Mentales/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple/genética , Receptor de Serotonina 5-HT1B/genética , Receptores de Serotonina/genética
20.
Mol Cell Probes ; 54: 101653, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32866662

RESUMEN

Ischemic heart disease is a proverbial and common cardiovascular disease, and constitutes a leading cause of disability and mortality globally. Myocardial ischemic/reperfusion (MI/R) injury is a highly orchestrated phenomenon that involves the excessive activation of high mobility group box 1 (HMGB1) signaling. In the present study, we sought to investigate the function of miR-708 in MI/R injury due to the predicted binding to HMGB1. Intriguingly, down-regulation of miR-708 and up-regulation of HMGB1 were observed in MI/R rat model and H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. Dual luciferase reporter assays substantiated that HMGB1 was a direct target of miR-708. Moreover, miR-708 overexpression suppressed the mRNA and protein expression of HMGB1. Noticeably, elevation of miR-708 antagonized H/R-induced inhibition in cell viability; whilst, increased cell apoptosis evoked by H/R was restrained after miR-708 up-regulation. Simultaneously, miR-708 elevation suppressed H/R exposure-increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) generation, but elevated the activity of anti-oxidative stress superoxide dismutase (SOD). Additionally, H/R-increased production of pro-inflammatory cytokine TNF-α and IL-6 was offset following miR-708 overexpression. Moreover, enhancement of miR-708 inhibited H/R-evoked activation of the HMGB1-TLR4-NF-κB pathway by inhibiting the protein levels of HMGB1, TLR4 and p-p65 NF-κB. Specially, restoring this pathway offset the protective effects of miR-708 on H/R-induced cardiomyocyte injury. Together, these data indicate that miR-708 may protect against H/R-induced cardiomyocyte damage by directing targeting HMGB1 signaling, implying a promising therapeutic agent against ischemic heart disease including myocardial infarction.


Asunto(s)
Cardiotónicos/metabolismo , Proteína HMGB1/metabolismo , Hipoxia/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Oxígeno/metabolismo , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Animales , Secuencia de Bases , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Masculino , MicroARNs/genética , Miocitos Cardíacos/patología , FN-kappa B/metabolismo , Estrés Oxidativo , Ratas Sprague-Dawley , Regulación hacia Arriba/genética
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