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Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with expression changes of multiple genes critical for islet function in IUGR islets. ChIP-Seq analysis showed that IUGR-induced histone mark changes were enriched at critical transcription factor binding motifs, such as C/EBPs, Ets1, Bcl6, Thrb, Ebf1, Sox9, and Mitf. These transcription factors were also identified as top upstream regulators in our previously published transcriptome study. In addition, our ChIP-seq data revealed more than 1000 potential bivalent genes as identified by enrichment of both H3K4me3 and H3K27me3. The poised state of many potential bivalent genes was altered by IUGR, particularly Acod1, Fgf21, Serpina11, Cdh16, Lrrc27, and Lrrc66, key islet genes. Collectively, our findings suggest alterations of histone modification in key transcription factors and genes that may contribute to long-term gene dysregulation and an abnormal islet phenotype in IUGR rats.This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.Plant-based pathogenic microbes hinder the yield and quality of food production. Plant diseases have caused an increase in food costs due to crop destruction. There is a need to develop novel methods that can target and mitigate pathogenic microbes. PF-02341066 manufacturer This study focuses on investigating the effects of luteolin tetraphosphate derived silver nanoparticles (LTP-AgNPs) and gold nanoparticles (LTP-AuNPs) as a therapeutic agent on the growth and expression of plant-based bacteria and fungi. In this study, the silver and gold nanoparticles were synthesized at room temperature using luteolin tetraphosphate (LTP) as the reducing and capping agents. The synthesis of LTP-AgNPs and LTP-AuNP was characterized by Transmission Electron Microscopy (TEM) and size distribution. The TEM images of both LTP-AgNPs and LTP-AuNPs showed different sizes and shapes (spherical, quasi-spherical, and cuboidal). The antimicrobial test was conducted using fungi Aspergillus nidulans, Trichaptum biforme, Penicillium italicum, Fusarium oxysporum, and Colletotrichum gloeosporioides, while the class of bacteria employed include Pseudomonas aeruginosa, Aeromonas hydrophila, Escherichia coli, and Citrobacter freundii as Gram (-) bacteria, and Listeria monocytogenes and Staphylococcus epidermidis as Gram (+) bacterium. The antifungal study demonstrated the selective size and shape-dependent capabilities in which smaller sized spherical (9 nm) and quasi-spherical (21 nm) AgNPs exhibited 100% inhibition of the tested fungi and bacteria. The LTP-AgNPs exhibited a higher antimicrobial activity than LTP-AuNPs. We have demonstrated that smaller sized AgNPs showed excellent inhibition of A. nidulans growth compared to the larger size nanoparticles. These results suggest that LTP-AuNP and LTP-AgNPs could be used to address the detection and remediation of pathogenic fungi, respectively.Previous studies have confirmed the anti-melanogenic effect of the aerial part of Pueraria lobata, however, due to its inherent color, P. lobata has limited commercial use. In this study, an extract (GALM-DC) of the aerial part of P. lobata having improved color by the use of activated carbon was obtained. Furthermore, the active compound neobavaisoflavone (NBI) was identified from GALM-DC. The effect of NBI on melanogenesis, tyrosinase activity, α-glucosidase activity, and mechanism of action in melanocytes was investigated. Tyrosinase activity, melanin contents and the expression of melanin-related genes and proteins were determined in B16F10 cells. NBI reduced melanin synthesis and tyrosinase activity. Furthermore, NBI treatment reduced the mRNA and protein expression levels of MITF, TRP-1, and tyrosinase. NBI also works by phosphorylating and activating proteins that inhibit melanogenesis, such as GSK3β and ERK. Specific inhibitors of Akt/GSK-3β (LY294002) and MEK/ERK (PD98059) signaling prevented the inhibition of melanogenesis by NBI. NBI inhibited melanin production through the regulation of MEK/ERK and Akt/GSK-3β signaling pathways in α-MSH-stimulated B16F10 cells. NBI suppresses tyrosinase activity and melanogenesis through inhibition of α-glucosidase activity. Besides, NBI significantly reduced melanogenesis in a reconstructed human 3D skin model. In conclusion, these results suggest that NBI has potential as a skin-whitening agent for hyperpigmentation.
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