Background: The aim of this study was to analyze and compare melanoma gene expression profiles in TCGA database through the application of different genes to explore the pathogenesis of melanoma. Furthermore, we confirmed the extent of the role of KYNU in melanoma and whether it can be a potential target for the diagnosis and treatment of melanoma. Methods: The gene expression profiles of melanoma samples were downloaded from TCGA database, and matrix files were synthesized to screen differential genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis and GCDA broad institute were used to analyze common gene locus mutations and expression changes in melanoma, as well as methylation. In addition, the expression patterns of KYNU in melanoma were quantified by immunohistochemistry, Western blotting, qRT-PCR, software such as GEO DataSets and the Human Protein Atlas, and meta-analysis of skin diseases. KYNU was overexpressed in keratinocytes (HaCaT and HEKα) and melanoma cells (A375 and H1205-lu). CFDA-SE, Annexin V–PI double staining, and PI single staining were used to investigate the mechanism of KYNU in melanoma and its effects on melanoma proliferation, apoptosis, invasion, and migration. Results: The main signaling pathways involved in melanoma were EGF/EGFR–RAS–BRAF–MEK–ERK–CyclinD1/CDK4, Ras–PI3K–PTEN–PKB/AKT, and p14/p16 (CDKN2A)–MDM2–p53–p21–cyclinD1/CDK4/6–Rb/E2F. Moreover, MITF, KIT, CDH1. NRAS, AKT1, EGFR, TP53, KIT, and CDK4 were elevated in melanoma, whereas PTEN, cAMP, and BCL2 were reduced in melanoma. The copy number of tumor-promoting genes increased, while the copy number of tumor suppressor genes decreased. Changes in the copy number of the above tumor genes enriched in chromosomes were found through SNP gene mutations. The genes whose expression was negatively regulated by DNA methylation in melanoma included KRT18, CDK2, JAK3, BCL2, MITF, MET, CXCL10, EGF, SOX10, SOCS3, and KIT. The mutation rate of KYNU was high according to TCGA database. The KYNU level was decreased in melanoma. Overexpression of KYNU can promote changes in apoptotic BCL-2, metabolic KYN, 3-HAA, invasion and migration MMP9, E-cadherin, and other related proteins in melanoma. Fluorescence staining and flow analysis showed that a slower proliferation rate led to a stronger fluorescence intensity. In melanoma tumor cells with a low expression of KYNU, overexpression of KYNU could promote tumor cell apoptosis. IL-10 induced immunoregulatory changes in melanoma. The expression of MMP9 and AMPK decreased in A375, but the change in BCL-2 was not obvious. The expression of BCL-2 decreased significantly in H1205-lu. A375 showed cell-cycle arrest, indicating that IL-10 could slow down the cell cycle of melanoma. Conclusions: These results provide insights into the pathologic mechanisms of melanoma target genes and KYNU as a biomarker and potential therapeutic factor for melanoma.
Numerous therapeutic anti-tumor strategies have been developed in recent decades. However, their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors. Autophagy plays a key role in tumorigenesis and tumor treatment, in which the overproduction of reactive oxygen species (ROS) is recognized as the direct cause of protective autophagy. Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy. Among them, hydroxychloroquine is the most commonly used autophagy inhibitor in clinics, but it is severely limited by its high therapeutic dose, significant toxicity, poor reversal efficacy, and nonspecific action. Herein, we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria (PN-CeO 2 ) nanozymes as autophagy inhibitor. The antineoplastic effects of PN-CeO 2 were mediated by its high reductive activity for intratumoral ROS degradation, thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma. Further investigation highlighted PN-CeO 2 as a safe and efficient anti-tumor autophagy inhibitor. Overall, this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases. Electronic Supplementary Material Supplementary material (cellular uptake of PN-CeO 2 , effects of PN-CeO 2 on several common malignant tumor models, viability of HaCaT cells treated with PN-CeO 2 at different concentrations, time-dependent body-weight curves of SCL-1 tumor-bearing nude mice, the biodistribution of Ce element in main tissues and tumors after injection of PN-CeO 2 , measurement of Ce element concentration in urine and feces samples, H&E-stained images of main organs, and measurement of liver and kidney function in mice after different treatment) is available in the online version of this article at 10.1007/s12274-022-5139-z.
Cities in China are on the frontline of low-carbon transition which requires monitoring city-level emissions with low-latency to support timely climate actions. Most existing CO2 emission inventories lag reality by more than one year and only provide annual totals. To improve the timeliness and temporal resolution of city-level emission inventories, we present Carbon Monitor Cities-China (CMCC), a near-real-time dataset of daily CO2 emissions from fossil fuel and cement production for 48 major high-emission cities in China. This dataset provides territory-based emission estimates from 2020-01-01 to 2021-12-31 for five sectors: power generation, residential (buildings and services), industry, ground transportation, and aviation. CMCC is developed based on an innovative framework that integrates bottom-up inventory construction and daily emission estimates from sectoral activities and models. Annual emissions show reasonable agreement with other datasets, and uncertainty ranges are estimated for each city and sector. CMCC provides valuable daily emission estimates that enable low-latency mitigation monitoring for cities in China.
Background: Skin basal cell carcinoma (BCC) is the most common skin cancer with an increasing incidence rate worldwide. XB130 is a novel adaptor protein for intracellular signal transduction and it participates in cell proliferation, cell survival, cell migration and cell apoptosis. Studies have demonstrated that XB130 is involved in cancer initiation and progression; however, its expression and role in BCC have not been investigated. Methods: Immunohistochemistry was carried out to detect the expression of XB130 at protein level in skin samples obtained from patients with skin basal cell carcinoma (n=40) and healthy donors (n=35). Results: In our study, we found that the staining of XB130 was mostly observed in cytoplasm. In normal skin tissues, XB130 was expressed almost in the whole layer of the epidermis. And the expression of XB130 in BCC was significantly down-regulated compared to normal skin. Conclusions: The study suggested that XB130 is involved in the pathogenesis of BCC and it may serve as a therapeutic target of BCC. Keywords: XB130; skin basal cell carcinoma;
Electronic Health Record (EHR) is a foundation for any intelligent diagnose and medical data analytics. In our previous research, we discovered that the existing EHR in clinic mainly manually created by physicians are seriously fraud. They are too sample, containing serious mistakes and far from accurate. It causes great difficulties for any intelligent diagnose and medical data analyses. This paper reports our efforts in an attempt to automatic and semi-automatic EHR creation. We have adopted an advance AI techniques in voice recognition and text mining in order to build a prototype of "doctor's assistant", which can record conversations between a doctor and a patient, then the recorded voice file is further converted into a text file. With text mining techniques, the key symptom described by a patient is abstracted and converted into structured data. EHR will be generated automatically for doctors' approval. This will greatly reduce doctors' workload and increase the accuracy and quality of EHR.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.