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Stokholm posted an update 8 months, 3 weeks ago
Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.Acute myeloid leukemia (AML) is the most frequently diagnosed acute leukemia, and its incidence increases with age. Although the etiology of AML remains unknown, exposure to genotoxic agents or some prior hematologic disorders could lead to the development of this condition. The pathogenesis of AML involves the development of malignant transformation of hematopoietic stem cells that undergo successive genomic alterations, ultimately giving rise to a full-blown disease. From the disease biology perspective, AML is considered to be extremely complex with significant genetic, epigenetic, and phenotypic variations. Molecular and cytogenetic alterations in AML include mutations in those subsets of genes that are involved in normal cell proliferation, maturation and survival, thus posing significant challenge to targeting these pathways without attendant toxicity. In addition, multiple malignant cells co-exist in the majority of AML patients. Individual subclones are characterized by unique genetic and epigenetic abnormalities, which contribute to the differences in their response to treatment. As a result, despite a dramatic progress in our understanding of the pathobiology of AML, not much has changed in therapeutic approaches to treat AML in the past four decades. Dose and regimen modifications with improved supportive care have contributed to improved outcomes by reducing toxicity-related side effects. Several drug candidates are currently being developed, including targeted small-molecule inhibitors, cytotoxic chemotherapies, monoclonal antibodies and epigenetic drugs. This review summarizes the current state of affairs in the pathobiological and therapeutic aspects of AML.Horizontal gene transfer (HGT) refers to the movement of genetic material between distinct species by means other than sexual reproduction. HGT has contributed tremendously to the genome plasticity and adaptive evolution of prokaryotes and certain unicellular eukaryotes. The evolution of green plants from chlorophyte algae to angiosperms and from water to land represents a process of adaptation to diverse environments, which has been facilitated by acquisition of genetic material from other organisms. Selleckchem Clofarabine In this article, we review the occurrence of HGT in major lineages of green plants, including chlorophyte and charophyte green algae, bryophytes, lycophytes, ferns, and seed plants. In addition, we discuss the significance of horizontally acquired genes in the adaptive innovations of green plants and their potential applications to crop breeding and improvement.Organic photochromic compounds are attracting great interest as photoswitchable components of various bioconjugates for using in photopharmacology, targeted drug delivery and bio-imaging. Here we report on the synthesis of two novel molecular hybrids of indoline spiropyrans and alpha-lipoic acid via an esterification reaction. Preliminary photochemical studies revealed photochromic activity of 5-methoxy-substituted spirocompounds in their acetonitrile solutions. Both hybrid spiropyrans along with their parent substances in the hybrids were tested for the short-term cytotoxicity on HeLa cell cultures. The results of cytotoxicity studies showed unpredictable biocompatibility of the hybrids in comparison with the parent hydroxyl-substituted spiropyrans and α-lipoic acid, especially at the relatively high concentration of 2 mM. Using flow cytometry, we demonstrated that the both hybrids induced antioxidant response in the model cells. After the 24 h treatment, the hybrids administered at lower (500 µM) concentration caused suppressed cytosolic ROS and/or induced cellular thiols. At higher concentration, one of the hybrids demonstrated properties qualitatively similar to alpha-lipoic acid, yet far more strong. Together, flow cytometry results suggested that both hybrids of spiropyrans possess emergent biochemical and signaling antioxidant properties, exceeding those of alpha-lipoic acid.IRAK4 is a key mediator of innate immunity. There is a high interest in identifying novel IRAK4 inhibitors for the treatment of inflammatory autoimmune diseases. We describe here a highly potent and selective IRAK4 inhibitor (HS271) that exhibited superior enzymatic and cellular activities, as well as excellent pharmacokinetic properties. HS271 displayed robust in vivo anti-inflammatory efficacy as evaluated in rat models of LPS induced TNFα production and collagen-induced arthritis.