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1.
Sci Total Environ ; 935: 173392, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38788952

RESUMEN

Although silicate fertilizer has been recently recognized for its ability to suppress methane (CH4) emissions in paddy fields, the effects of its consecutive application during the rice farming period are still a subject of debate. Moreover, while it was known that silicate fertilizer can mitigate CH4 emissions through several electron acceptors, the effect of additional application of electron acceptors have not been extensively studied. This study evaluated the effect of silicate fertilizer with varying concentrations of iron slag on CH4 emissions and rice yield over the 3 years rice farming period. Seasonal CH4 fluxes exhibited a significant decrease with the application of silicate fertilizer, with the treatment containing 2.5 % iron slag showing the maximum reduction of 35 % in 2020. Additionally, in 2021 and 2022, the application of silicate fertilizer with 2.5 % iron slag resulted in a decrease of total seasonal CH4 emission by 22 % and 23 %, respectively. Rice grain yield exhibited a significant increase with the inclusion of iron slag in the silicate fertilizer, which resulted in a 37 % and 16 % higher yield compared to no-silicate fertilization and no­iron slag silicate fertilization, respectively. Therefore, iron slag-based silicate fertilizer could be a beneficial soil amendment to mitigate CH4 emissions in rice paddy fields and improve rice productivity without negative effects on the atmospheric and soil ecosystem.


Asunto(s)
Agricultura , Fertilizantes , Hierro , Metano , Oryza , Silicatos , Metano/análisis , Agricultura/métodos , Contaminantes Atmosféricos/análisis
2.
Foods ; 13(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38731729

RESUMEN

Natural scaffolds have been the cornerstone of tissue engineering for decades, providing ideal environments for cell growth within extracellular matrices. Previous studies have favored animal-derived materials, including collagen, gelatin, and laminin, owing to their superior effects in promoting cell attachment, proliferation, and differentiation compared to non-animal scaffolds, and used immortalized cell lines. However, for cultured meat production, non-animal-derived scaffolds with edible cells are preferred. Our study represents the first research to describe plant-derived, film-type scaffolds to overcome limitations associated with previously reported thick, gel-type scaffolds completely devoid of animal-derived materials. This approach has been employed to address the difficulties of fostering bovine muscle cell survival, migration, and differentiation in three-dimensional co-cultures. Primary bovine myoblasts from Bos Taurus Coreanae were harvested and seeded on alginate (Algi) or corn-derived alginate (AlgiC) scaffolds. Scaffold functionalities, including biocompatibility and the promotion of cell proliferation and differentiation, were evaluated using cell viability assays, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction. Our results reveal a statistically significant 71.7% decrease in production time using film-type scaffolds relative to that for gel-type scaffolds, which can be maintained for up to 7 days. Film-type scaffolds enhanced initial cell attachment owing to their flatness and thinness relative to gel-type scaffolds. Algi and AlgiC film-type scaffolds both demonstrated low cytotoxicity over seven days of cell culture. Our findings indicated that PAX7 expression increased 16.5-fold in alginate scaffolds and 22.8-fold in AlgiC from day 1 to day 3. Moreover, at the differentiation stage on day 7, MHC expression was elevated 41.8-fold (Algi) and 32.7-fold (AlgiC), providing initial confirmation of the differentiation potential of bovine muscle cells. These findings suggest that both Algi and AlgiC film scaffolds are advantageous for cultured meat production.

3.
Biochem Biophys Res Commun ; 709: 149828, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38537596

RESUMEN

Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively. Analyses using dual luciferase assay and decoy RNAs that could block RNA-RNA interactions indicated that LINC00346 improves phosphatase and tensin homolog (PTEN) expression by sponging miR-25-3p. Subsequently, PTEN suppresses phosphoinositide-3 kinase (PI3K)-mediated conversion of phosphatidylinositol-4,5-bisphosphate (PIP2) into phosphatidylinositol-3,4,5-trisphosphate (PIP3) as well as consequent activation of protein kinase B (AKT) and NF-κB. Interestingly, database analysis revealed that the expression levels of LINC00346 and PTEN were simultaneously decreased in breast cancer tissues. Further analyses conducted using a breast cancer cell line, MDA-MB-231, confirmed the functional relationship among LINC00346, miR-25-3p, and PTEN in LPS-induced activation of NF-κB. These results indicate that miR-25-3p-sponging activity of LINC00346 affects the balance between PTEN and PI3K as well as the downstream activation of AKT/NF-κB pathway in inflammatory conditions.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Femenino , Humanos , Lipopolisacáridos/farmacología , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositoles , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo
4.
Sci Rep ; 14(1): 5692, 2024 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-38453974

RESUMEN

Current agricultural practices are increasingly favoring the biochar application to sequester carbon, enhance crop growth, and mitigate various environmental pollutants resulting from nitrogen (N) loss. However, since biochar's characteristics can vary depending on pyrolysis conditions, it is essential to determine the optimal standard, as they can have different effects on soil health. In this study, we categorized rice husk biochars basis on their pH levels and investigated the role of each rice husk biochar in reducing ammonia (NH3) emissions and promoting the growth of Chinese cabbage in urea-fertilized fields. The findings of this study revealed that the variation in pyrolysis conditions of rice husk biochars and N rates affected both the NH3 emissions and crop growth. The neutral (pH 7.10) biochar exhibited effective NH3 volatilization reduction, attributed to its high surface area (6.49 m2 g-1), outperforming the acidic (pH 6.10) and basic (pH 11.01) biochars, particularly under high N rates (640 kg N ha-1). Chinese cabbage yield was highest, reaching 4.00 kg plant-1, with the basic biochar application with high N rates. Therefore, the neutral rice husk biochar effectively mitigate the NH3 emissions from urea-treated fields, while the agronomic performance of Chinese cabbage enhanced in all biochar amendments.


Asunto(s)
Oryza , Suelo , Amoníaco/análisis , Urea , Temperatura , Pirólisis , Carbón Orgánico
5.
J Biomol Struct Dyn ; 42(5): 2603-2615, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37139544

RESUMEN

AIM2 and IFI16 are the most studied members of AIM2-like receptors (ALRs) in humans and share a common N-Terminal PYD domain and C-terminal HIN domain. The HIN domain binds to dsDNA in response to the invasion of bacterial and viral DNA, and the PYD domain directs apoptosis-associated speck-like protein via protein-protein interactions. Hence, activation of AIM2 and IFI16 is crucial for protection against pathogenic assaults, and any genetic variation in these inflammasomes can dysregulate the human immune system. In this study, different computational tools were used to identify the most deleterious and disease-causing non-synonymous single nucleotide polymorphisms (nsSNPs) in AIM2 and IFI16 proteins. Molecular dynamic simulation was performed for the top damaging nsSNPs to study single amino acid substitution-induced structural alterations in AIM2 and IFI16. The observed results suggest that the variants G13V, C304R, G266R, and G266D for AIM2, and G13E and C356F are deleterious and affect structural integrity. We hope that the suggested deleterious nsSNPs and structural dynamics of AIM2 and IFI16 variants will guide future research to better understand the function of these variants with large-scale studies and may assist in fresher therapeutics focusing on these polymorphisms.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Proteínas de Unión al ADN , Inflamasomas , Humanos , ADN Viral , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Inflamasomas/genética , Inflamasomas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Polimorfismo de Nucleótido Simple , Simulación por Computador
6.
Ecotoxicol Environ Saf ; 269: 115820, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38103469

RESUMEN

Perfluorooctanesulfonate (PFOS) is a ubiquitous environmental pollutant associated with increasing health concerns and environmental hazards. Toxicological analyses of PFOS exposure are hampered by large interspecies variations and limited studies on the mechanistic details of PFOS-induced toxicity. We investigated the effects of PFOS exposure on Xenopus laevis embryos based on the reported developmental effects in zebrafish. X. laevis was selected to further our understanding of interspecies variation in response to PFOS, and we built upon previous studies by including transcriptomics and an assessment of ciliogenic effects. Midblastula-stage X. laevis embryos were exposed to PFOS using the frog embryo teratogenesis assay Xenopus (FETAX). Results showed teratogenic effects of PFOS in a time- and dose-dependent manner. The morphological abnormalities of skeleton deformities, a small head, and a miscoiled gut were associated with changes in gene expression evidenced by whole-mount in situ hybridization and transcriptomics. The transcriptomic profile of PFOS-exposed embryos indicated the perturbation in the expression of genes associated with cell death, and downregulation in adenosine triphosphate (ATP) biosynthesis. Moreover, we observed the effects of PFOS exposure on cilia development as a reduction in the number of multiciliated cells and changes in the directionality and velocity of the cilia-driven flow. Collectively, these data broaden the molecular understanding of PFOS-induced developmental effects, whereby ciliary dysfunction and disrupted ATP synthesis are implicated as the probable modes of action of embryotoxicity. Furthermore, our findings present a new challenge to understand the links between PFOS-induced developmental toxicity and vital biological processes.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Perfilación de la Expresión Génica , Pez Cebra , Animales , Xenopus laevis/genética , Adenosina Trifosfato , Embrión no Mamífero , Teratógenos/toxicidad
7.
Dev Reprod ; 27(1): 9-24, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38075439

RESUMEN

The advancement in high-throughput sequencing (HTS) technology has revolutionized the field of biology, including genomics, epigenomics, transcriptomics, and metagenomics. This technology has become a crucial tool in many areas of research, allowing scientists to generate vast amounts of genetic data at a much faster pace than traditional methods. With this increased speed and scale of data generation, researchers can now address critical questions and gain new insights into the inner workings of living organisms, as well as the underlying causes of various diseases. Although the first HTS technology have been introduced about two decades ago, it can still be challenging for those new to the field to understand and use effectively. This review aims to provide a comprehensive overview of commonly used HTS technologies these days and their applications in terms of genome sequencing, transcriptome, DNA methylation, DNA-protein interaction, chromatin accessibility, three-dimensional genome organization, and microbiome.

8.
Anim Cells Syst (Seoul) ; 27(1): 180-186, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37674816

RESUMEN

Traditionally, the p-value is the criterion for the cutoff threshold to determine significant markers in genome-wide association studies (GWASs). Choosing the best subset of markers for the best linear unbiased prediction (BLUP) for improved prediction ability (PA) has become an interesting issue. However, when dealing with many traits having the same marker information, the p-values' themselves cannot be used as an obvious solution for having a confidence in GWAS and BLUP. We thus suggest a genomic estimated breeding value-assisted reduction method of the single nucleotide polymorphism (SNP) set (GARS) to address these difficulties. GARS is a BLUP-based SNP set decision presentation. The samples were Landrace pigs and the traits used were back fat thickness (BF) and daily weight gain (DWG). The prediction abilities (PAs) for BF and DWG for the entire SNP set were 0.8 and 0.8, respectively. By using the correlation between genomic estimated breeding values (GEBVs) and phenotypic values, selecting the cutoff threshold in GWAS and the best SNP subsets in BLUP was plausible as defined by GARS method. 6,000 SNPs in BF and 4,000 SNPs in DWG were considered as adequate thresholds. Gene Ontology (GO) analysis using the GARS results of the BF indicated neuron projection development as the notable GO term, whereas for the DWG, the main GO terms were nervous system development and cell adhesion.

9.
Sci Total Environ ; 902: 166174, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37562609

RESUMEN

Climate change, driven by increased greenhouse gas emissions, is a pressing environmental issue worldwide. Flooded rice paddy soils are a predominant source of methane (CH4) emissions, accounting for approximately 11 % of global emissions. Factors such as rice (Oryza sativa L.) cultivar, transplanting date, water management, and soil characteristics significantly influence these emissions. This study aimed to evaluate the CH4 emissions from rice paddies in relation to the cultivar and transplanting date. The experiment included two rice cultivars (an early-maturing cultivar, Unkwang, and a medium-late-maturing cultivar, Samkwang) and four transplanting dates (Times 1-4). In the present study, CH4 emissions were higher with earlier transplanting dates and decreased significantly with delayed transplanting. Weather conditions, such as cumulative mean air temperature, cumulative soil temperature, and total sunshine hours, were positively correlated with total CH4 emissions. The recommended regional transplanting date (Time 3) resulted in the highest rice grain yields for both cultivars. However, the earlier transplanting dates (Time 1 and Time 2) were more effective in improving plant growth characteristics such as rice straw weight, root biomass weight, and chlorophyll content. A significant positive correlation was observed between the root biomass weight of the rice and CH4 emissions in both cultivars, implying that an increase in root biomass weight led to an increase in CH4 emissions. Consequently, adhering to the advised regional transplanting dates is the most sensible approach for transplanting rice seedlings. This ensured lower CH4 emissions without compromising rice productivity or quality for both cultivars. Further research should focus on identifying the most appropriate rice-transplanting dates and management practices to effectively reduce CH4 emissions without compromising rice production.


Asunto(s)
Gases de Efecto Invernadero , Oryza , Agricultura/métodos , Metano/análisis , Suelo , Gases de Efecto Invernadero/análisis , Óxido Nitroso
10.
PLoS One ; 18(4): e0283364, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37023008

RESUMEN

Estrogen-related receptor gamma (ERRγ), the latest member of the ERR family, does not have any known reported natural ligands. Although the crystal structures of the apo, agonist-bound, and inverse agonist-bound ligand-binding domain (LBD) of ERRγ have been solved previously, their dynamic behavior has not been studied. Hence, to explore the intrinsic dynamics of the apo and ligand-bound forms of ERRγ, we applied long-range molecular dynamics (MD) simulations to the crystal structures of the apo and ligand-bound forms of the LBD of ERRγ. Using the MD trajectories, we performed hydrogen bond and binding free energy analysis, which suggested that the agonist displayed more hydrogen bonds with ERRγ than the inverse agonist 4-OHT. However, the binding energy of 4-OHT was higher than that of the agonist GSK4716, indicating that hydrophobic interactions are crucial for the binding of the inverse agonist. From principal component analysis, we observed that the AF-2 helix conformation at the C-terminal domain was similar to the initial structures during simulations, indicating that the AF-2 helix conformation is crucial with respect to the agonist or inverse agonist for further functional activity of ERRγ. In addition, we performed residue network analysis to understand intramolecular signal transduction within the protein. The betweenness centrality suggested that few of the amino acids are important for residue signal transduction in apo and ligand-bound forms. The results from this study may assist in designing better therapeutic compounds against ERRγ associated diseases.


Asunto(s)
Agonismo Inverso de Drogas , Simulación de Dinámica Molecular , Ligandos , Furilfuramida , Receptores de Estrógenos/metabolismo
11.
Comput Struct Biotechnol J ; 21: 1843-1850, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36915383

RESUMEN

The budding yeast Saccharomyces cerevisiae is a well-characterized and popular model system for investigating histone modifications and the inheritance of chromatin states. The data obtained from this model organism have provided essential and critical information for understanding the complexity of epigenetic interactions and regulation in eukaryotes. Recent advances in biotechnology have facilitated the detection and quantitation of protein post-translational modification (PTM), including acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, and acylation, and led to the identification of several novel modification sites in histones. Determining the cellular function of these new histone markers is essential for understanding epigenetic mechanisms and their impact on various biological processes. In this review, we describe recent advances and current views on histone modifications and their effects on chromatin dynamics in S. cerevisiae.

12.
Biomater Sci ; 10(24): 7117-7132, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36350285

RESUMEN

Triple-negative breast cancer (TNBC) is characterized by rapid tumor growth and resistance to cancer therapy, and has a poor prognosis. Accumulating data have revealed that cancer metabolism relies on both the Warburg effect and oxidative phosphorylation (OXPHOS), which are strongly related to the high proliferation and chemoresistance of cancer cells. Phototherapy is considered as a non-invasive method to precisely control drug activity with reduced side effects. Herein, our group introduced an Abraxane-like nanoplatform, named LCIR NPs, which significantly eradicates cancer cells via synergism between metabolic reprogramming and phototherapy effects. Endowed with mitochondria-targeting residues, the nanoparticles efficiently inhibited mitochondrial complexes I and IV as well as hexokinase II, leading to the depletion of intracellular ATP. Consequently, the photodynamic and photothermal effect triggered by NIR irradiation was enhanced due to the alleviation of hypoxia and the thermoresistance mechanism that rely on mitochondrial metabolism. In vivo experiments showed that the tumor size of mice that received the combination treatment was only 50.7 mm3, which was 21 times smaller than that of the untreated group and was much lower than those of other single treatments after 21 days. Additionally, almost no systemic undesired toxicity was detected during the observation period. We believe that the concept of LCIR as presented here offers a potential platform to overcome the resistance to conventional therapies by the incorporation with the energy metabolism inhibition approach.


Asunto(s)
Albúminas , Neoplasias , Animales , Ratones
13.
J Korean Assoc Oral Maxillofac Surg ; 48(5): 303-308, 2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36316189

RESUMEN

Objectives: Selection of treatment methods for mandibular condylar fractures remains controversial. In this study, we investigated treatment methods for condylar fractures to determine the indications for open or closed reduction. Patients and. Methods: Patients >12 years of age treated for mandibular condylar fractures with a follow-up period of ≥3 months were included in this study. The medical records of enrolled patients were reviewed for sex, age, fracture site, treatment method (open or closed reconstruction), postoperative intermaxillary fixation period, operation time, and complications. Radiological analysis of fracture fragment displacement and changes in ramal height difference was performed using computed tomography and panoramic radiography. Results: A total of 198 patients was investigated, 48.0% (n=95) of whom underwent closed reduction and 52.0% (n=103) underwent open reduction. There was no significant correlation between reduction method and patient sex, age, or follow-up period. No statistically significant difference between the incidence of complications and treatment method was observed. None of the patients underwent open reduction of condylar head fracture. Binary logistic regression analysis showed that open reduction was significantly more frequent in patients with subcondylar fracture compared to in those with a fracture in the condylar head area. There was no statistically significant correlation between the groups and fracture fragment displacement. However, there was a significant difference between the treatment groups in amount of change in ramal height difference between the fractured and the nonfractured sides during treatment. Conclusion: No significant clinical differences were found between the open and closed reduction methods in patients with mandibular condylar fractures. According to fracture site, closed reduction was preferred for condyle head fractures. There was no significant relationship between fracture fragment displacement and treatment method.

14.
Nanomaterials (Basel) ; 12(4)2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-35215047

RESUMEN

Charge transport layers have been found to be crucial for high-performance perovskite solar cells (PSCs). SnO2 has been extensively investigated as an alternative material for the traditional TiO2 electron transport layer (ETL). The challenges facing the successful application of SnO2 ETLs are degradation during the high-temperature process and voltage loss due to the lower conduction band. To achieve highly efficient PSCs using a SnO2 ETL, low-temperature-processed mesoporous TiO2 (LT m-TiO2) was combined with compact SnO2 to construct a bilayer ETL. The use of LT m-TiO2 can prevent the degradation of SnO2 as well as enlarge the interfacial contacts between the light-absorbing layer and the ETL. SnO2/TiO2 bilayer-based PSCs showed much higher power conversion efficiency than single SnO2 ETL-based PSCs.

15.
Sci Adv ; 8(3): eabl6406, 2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35061536

RESUMEN

Layer-release techniques for producing freestanding III-V epitaxial layers have been actively developed for heterointegration of single-crystalline compound semiconductors with Si platforms. However, for the release of target epitaxial layers from III-V heterostructures, it is required to embed a mechanically or chemically weak sacrificial buffer beneath the target layers. This requirement severely limits the scope of processable materials and their epi-structures and makes the growth and layer-release process complicated. Here, we report that epitaxial layers in commonly used III-V heterostructures can be precisely released with an atomic-scale surface flatness via a buffer-free separation technique. This result shows that heteroepitaxial interfaces of a normal lattice-matched III-V heterostructure can be mechanically separated without a sacrificial buffer and the target interface for separation can be selectively determined by adjusting process conditions. This technique of selective release of epitaxial layers in III-V heterostructures will provide high fabrication flexibility in compound semiconductor technology.

16.
Nanomaterials (Basel) ; 12(2)2022 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-35055225

RESUMEN

The electrical properties of polycrystalline graphene grown by chemical vapor deposition (CVD) are determined by grain-related parameters-average grain size, single-crystalline grain sheet resistance, and grain boundary (GB) resistivity. However, extracting these parameters still remains challenging because of the difficulty in observing graphene GBs and decoupling the grain sheet resistance and GB resistivity. In this work, we developed an electrical characterization method that can extract the average grain size, single-crystalline grain sheet resistance, and GB resistivity simultaneously. We observed that the material property, graphene sheet resistance, could depend on the device dimension and developed an analytical resistance model based on the cumulative distribution function of the gamma distribution, explaining the effect of the GB density and distribution in the graphene channel. We applied this model to CVD-grown monolayer graphene by characterizing transmission-line model patterns and simultaneously extracted the average grain size (~5.95 µm), single-crystalline grain sheet resistance (~321 Ω/sq), and GB resistivity (~18.16 kΩ-µm) of the CVD-graphene layer. The extracted values agreed well with those obtained from scanning electron microscopy images of ultraviolet/ozone-treated GBs and the electrical characterization of graphene devices with sub-micrometer channel lengths.

17.
J Bus Ethics ; 179(1): 25-42, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33551526

RESUMEN

The concept of people's memory maintains the finiteness of time and capacity. However, with the advancement in technology, the amount of storage memory a person can use has increased dramatically. Given that digital traces can hardly be erased or forgotten, individuals have begun to express their desire to be forgotten in the digital world, and governments and academia are considering methods to fulfill such wishes. Capturing the difficulties in terms of a cultural lag between technological advancements and regulations on individuals' data privacy needs, we identify six motives for individuals wishing to be forgotten online and investigate its expected effects on online content generation through a qualitative content analysis of 222 responses from open-ended surveys in Korea. Our findings provide implications for the literature on individual privacy and the right to be forgotten employing the cultural lag, as well as, elaborate further on the relationship between being forgotten online and the legitimacy of such requests of individuals. Additionally, implications for data providers, data controllers/processors, and governments to address this lag and build a balanced system of personal information are provided.

18.
Sci Adv ; 7(51): eabj9111, 2021 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-34910517

RESUMEN

Cellular aging is characterized by disruption of the nuclear lamina and its associated heterochromatin. How these structural changes within the nucleus contribute to age-related degeneration of the organism is unclear. Genes lacking CpG islands (CGI− genes) generally associate with heterochromatin when they are inactive. Here, we show that the expression of these genes is globally activated in aged cells and tissues. This CGI− gene misexpression is a common feature of normal and pathological aging in mice and humans. We report evidence that CGI− gene up-regulation is directly responsible for age-related physiological deterioration, notably for increased secretion of inflammatory mediators.

19.
Mater Today Bio ; 12: 100164, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34877519

RESUMEN

Depletion of tumor extracellular matrix (ECM) is viewed as a promising approach to enhance the antitumor efficacy of chemotherapeutic-loaded nanoparticles. Hyaluronidase (HAase) destroys hyaluronic acid-based tumor ECM, but it is active solely at acidic pHs of around 5.0 and is much less active at physiological pH. Herein, we report the development of our novel UV-light-reactive proton-generating and hyaluronidase-loaded albumin nanoparticles (o-NBA/HAase-HSA-NPs). The method to prepare the nanoparticles was based on pH-jump chemistry using o-nitrobenzaldehyde (o-NBA) in an attempt to address the clinical limitation of HAase. When in suspension/PEG-hydrogel and irradiated with UV light, the prepared o-NBA/HAase-HSA-NPs clearly reduced the pH of the surrounding medium to as low as 5.0 by producing protons and were better able to break down HA-based tumor cell spheroids (AsPC-1) and HA-hydrogel/microgels, presumably due to the enhanced HA activity at a more optimal pH. Moreover, when formulated as an intratumor-injectable PEG hydrogel, the o-NBA/HAase-HSA-NPs displayed significantly enhanced tumor suppression when combined with intravenous paclitaxel-loaded HSA-NPs (PTX-HSA-NPs) in AsPC-1 tumor-bearing mice: The tumor volume in mice administered UV-activated o-NBA/HAase-HSA-NPs and PTX-HSA-NPs was 198.2 â€‹± â€‹30.0 â€‹mm3, whereas those administered PBS or non-UV-activated o-NBA/HAase-HSA-NPs and PTX-HSA-NPs had tumor volumes of 1230.2 â€‹± â€‹256.2 and 295.4 â€‹± â€‹17.1 â€‹mm3, respectively. These results clearly demonstrated that when administered with paclitaxel NPs, our photoreactive o-NBA/HAase-HSA-NPs were able to reduce pH and degrade HA-based ECM, and thereby significantly suppress tumor growth. Consequently, we propose our o-NBA/HAase-HSA-NPs may be a prototype for development of future nanoparticle-based HA-ECM-depleting tumor-ablating agents.

20.
Nucleic Acids Res ; 49(5): 2583-2597, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33621342

RESUMEN

Recent genomic data analyses have revealed important underlying logics in eukaryotic gene regulation, such as CpG islands (CGIs)-dependent dual-mode gene regulation. In mammals, genes lacking CGIs at their promoters are generally regulated by interconversion between euchromatin and heterochromatin, while genes associated with CGIs constitutively remain as euchromatin. Whether a similar mode of gene regulation exists in non-mammalian species has been unknown. Here, through comparative epigenomic analyses, we demonstrate that the dual-mode gene regulation program is common in various eukaryotes, even in the species lacking CGIs. In cases of vertebrates or plants, we find that genes associated with high methylation level promoters are inactivated by forming heterochromatin and expressed in a context-dependent manner. In contrast, the genes with low methylation level promoters are broadly expressed and remain as euchromatin even when repressed by Polycomb proteins. Furthermore, we show that invertebrate animals lacking DNA methylation, such as fruit flies and nematodes, also have divergence in gene types: some genes are regulated by Polycomb proteins, while others are regulated by heterochromatin formation. Altogether, our study establishes gene type divergence and the resulting dual-mode gene regulation as fundamental features shared in a broad range of higher eukaryotic species.


Asunto(s)
Regulación de la Expresión Génica , Animales , Caenorhabditis elegans/genética , Islas de CpG , Metilación de ADN , Drosophila melanogaster/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Regiones Promotoras Genéticas , Transcripción Genética , Vertebrados/genética
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