Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing. Methods: Whole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}. Results: Mutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes—identified across 10 genome sequencing studies—in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC. Conclusion: Our results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients

DNA repair and neurological disease: From molecular understanding to the development of diagnostics and model organisms

In both replicating and non-replicating cells, the maintenance of genomic stability is of utmost importance. Dividing cells can repair DNA damage during cell division, tolerate the damage by employing potentially mutagenic DNA polymerases or die via apoptosis. However, the options for accurate DNA repair are more limited in non-replicating neuronal cells. If DNA damage is left unresolved, neuronal cells die resulting in neurodegenerative disorders. A number of pathogenic variants of DNA repair proteins have been linked to multiple neurological diseases. The current challenge is to harness our knowledge of fundamental properties of DNA repair to improve diagnosis, prognosis and treatment of such debilitating disorders. In this perspective, we will focus on recent efforts in identifying novel DNA repair biomarkers for the diagnosis of neurological disorders and their use in monitoring the patient response to therapy. These efforts are greatly facilitated by the development of model organisms, which will also be summarised

Tailoring the Oxygen Reduction Activity of Hemoglobin through Immobilization within Microporous Organic Polymer–Graphene Composite

A facile one-pot, bottom-up approach to construct composite materials of graphene and a pyrimidine-based porous-organic polymer (PyPOP), as host for immobilizing human hemoglobin (Hb) biofunctional molecules, is reported. The graphene was selected because of its excellent electrical conductivity, while the PyPOP was utilized because of its pronounced permanent microporosity and chemical functionality. This approach enabled enclathration of the hemoglobin within the microporous composite through a ship-in-a-bottle process, where the composite of the PyPOP@G was constructed from its molecular precursors, under mild reaction conditions. The composite-enclathrated Fe-protoporphyrin-IX demonstrated electrocatalytic activity toward oxygen reduction, as a functional metallocomplex, yet with a distinct microenvironment provided by the globin protein. This approach delineates a pathway for platform microporous functional solids, where fine-tuning of functionality is facilitated by judicious choice of the active host molecules or complexes, targeting specific application

Pt Immobilization within a Tailored Porous-Organic Polymer–Graphene Composite: Opportunities in the Hydrogen Evolving Reaction

A facile, postsynthetic treatment of a designed composite of pyrimidine-based porous-organic polymer and graphene (PyPOP@G) with ionic Pt, and the subsequent uniform electrodeposition of Pt metallic within the pores, led to the formation of a composite material (PyPOP-Pt@G). The pyrimidine porous-organic polymer (PyPOP) was selected because of the abundant Lewis-base binding sites within its backbone, to be combined with graphene to produce the PyPOP@G composite that was shown to uptake Pt ions simply upon brief incubation in H₂PtCl₆ solution in acetonitrile. The XPS analysis of PyPOP@G sample impregnated with Pt ions confirmed the presence of Pt­(II/IV) species and did not show any signs of metallic nanoparticles, as further confirmed by transmission electron microscopy. Immediately upon electrochemical reduction of the Pt­(II/IV), metallic Pt (most likely atomistic Pt) was observed. This approach stands out, as compared to Pt monolayer deposition techniques atop metal foams, or a recently reported atomic layer deposition (ALD), as a way of depositing submonolayer coverage of precious catalysts within the 1–10 nm pores found in microporous solids. The prepared catalyst platform demonstrated large current density (100 mA/cm²) at 122 mV applied overpotential for the hydrogen evolution reaction (HER), with measured Faradaic efficiency of 97(±1)%. Its mass activity (1.13 A/mg_Pt) surpasses that of commercial Pt/C (∼0.38 A/mg_Pt) at the overpotential of 100 mV. High durability has been assessed by cyclic and linear sweep voltammetry, as well as controlled potential electrolysis techniques. The Tafel plot for the catalyst demonstrated a slope of ∼37 mV/decade, indicating a Heyrovsky-type rate-limiting step in the observed HER