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Development of an evidence-based CPGs for pediatric appendicitis requires attention to a finite number of key decision points and content areas. Existing literature demonstrates improved patient outcomes with CPG implementation.

Development of an evidence-based CPGs for pediatric appendicitis requires attention to a finite number of key decision points and content areas. Existing literature demonstrates improved patient outcomes with CPG implementation.Retinoic acid (RA) therapy has been utilized as maintenance therapy for high-risk neuroblastoma, but over half of patients treated with RA relapse. Neuroblastoma stem cell-like cancer cells (SCLCCs) are a subpopulation of cells characterized by the expression of the cell surface marker CD133 and are hypothesized to contribute to drug resistance and disease relapse. A novel rexinoid compound, 9-cis-UAB30 (UAB30), was developed having the same anti-tumor effects as RA but a more favorable toxicity profile. In the current study, we investigated the efficacy of UAB30 in neuroblastoma patient-derived xenografts (PDX). Two PDXs, COA3 and COA6, were utilized and alterations in the malignant phenotype were assessed following treatment with RA or UAB30. UAB30 significantly decreased proliferation, viability, and motility of both PDXs. UAB30 induced cell-cycle arrest as demonstrated by the significant increase in percentage of cells in G1 (COA6 33.7 ± 0.7 vs. 43.3 ± 0.7%, control vs. UAB30) and decrease in percentage of cells in S phase (COA6 44.7 ± 1.2 vs. 38.6 ± 1%, control vs. UAB30). UAB30 led to differentiation of PDX cells, as evidenced by the increase in neurite outgrowth and mRNA abundance of differentiation markers. CD133 expression was decreased by 40% in COA6 cells after UAB30. The ability to form tumorspheres and mRNA abundance of known stemness markers were also significantly decreased following treatment with UAB30, further indicating decreased cancer cell stemness. These results provide evidence that UAB30 decreased tumorigenicity and cancer cell stemness in neuroblastoma PDXs, warranting further exploration as therapy for high-risk neuroblastoma.Keratin 8 (K8) expressed at the surface of cancer cells, referred as externalized K8 (eK8), has been observed in a variety of carcinoma cell lines. K8 has been previously reported to be expressed in poorly differentiated head and neck squamous cell carcinoma (HNSCC); however, its role during the invasive phase of upper aerodigestive tract tumorigenesis is unknown. Cohorts of HNSCC tumors for protein and mRNA expression and panel of cell lines were used for investigation. K8 was found to be externalized in a majority of HNSCC cell lines. Among the two main K8 protein isoforms only the 54 kDa was found to be present at the plasma membrane of HNSCC cells. The plasminogen-induced invasion of HNSCC cells was inhibited by the anti-eK8 D-A10 antagonist monoclonal antibody. Overexpression of K8 mRNA and protein were both correlated with tumor aggressive features and poor outcome. The effect of eK8 neutralization on invasion, its presence exclusively in cancer cells and the association of K8 expression with aggressive features and poor clinical outcome in HNSCC unravel eK8 as key player in invasion and a promising therapeutic target in HNSCC.Carotenoids are a group of natural tetraterpenoid pigments with essential roles in a variety of physiological processes of plants. check details Although carotenoid biosynthesis has been well characterized, the genetic basis of the pathway, especially in crop plants, is largely unknown. In this study, we characterized a new albino maize mutant called albino1 (alb1), which was obtained from a Mutator mutagenized population. The alb1 mutant showed defective chloroplast development and declined photosynthetic pigments, leading to a seedling-lethal phenotype. Genetic and molecular analyses indicated that ALB1 encoded a putative ζ-carotene desaturase (ZDS) involved in carotenoid biosynthesis. Measurement of carotenoids revealed that several major carotenoid compounds downstream of the ZDS were significantly reduced in alb1 mutant, indicating that ALB1 is a functional ZDS. Further transcriptome analysis revealed that several groups of nuclear genes involved in photosynthesis, such as light-harvesting complex, pigment metabolism, and chloroplast function, were significantly down-regulated in alb1 compared with wide type. Interestingly, expression of some maize plastid-localized nuclear genes, including POR, CAO, Lhcb, and RbcS, was substantially reduced in alb1 plants. Furthermore, treatment of the inhibitor fluridone significantly rescued gene transcripts of these nucleus-encoded genes in alb1 mutant, which supported the retrograde signaling of ζ-carotene/phytofluene derived molecules. These results suggested that ALB1/ZDS might function as a regulator to coordinate nuclear photosynthetic gene expression in plastid-to-nucleus retrograde signaling during development of maize plants. Together, these results have demonstrated that ALB1/ZDS is essential for carotenoids biosynthesis and plays crucial roles in chloroplast biogenesis and development in maize.Graphene, which is a unique 2D nanomaterials has received widespread attention for photothermal therapy (PTT) application. Here, we have designed the nanocomposite using polydopamine (PDA) functionalized reduced graphene oxide (rGO) nanosheets and bimetallic AuPd nanoparticles (NPs). The bimetallic AuPd nanoparticles decorated PDA functionalized rGO (AuPd-rGO/PDA) nanocomposite is synthesized by simple chemical reduction technique resulting in an average size of AuPd bimetallic nanostructure of 4.18 nm. The photothermal activity of the AuPd-rGO/PDA nanocomposite is explored under the irradiation of near infrared (NIR) laser sources of wavelength 915 nm. The temperature rises nearly 51 ± 3 °C within 3 min of irradiation NIR laser light resulting in the ablation of MDAMB-231 cancer cells up to concentration of 25 μg mL-1 of AuPd-rGO/PDA nanocomposite. This high performance of the ablation of cancer cells by photothermal therapy technique was facilitated using a low concentration of the nanocomposite by the synergistic effects of the bimetallic AuPd as well as rGO and PDA functionalization.

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