https://www.cell.com/trends/cell-biology/pdf/S0962-8924(18)30020-5.pdf

Hallmarks of Cellular Senescence.

The discovery of regulated cell death processes has enabled advances in cancer treatment. In the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been implicated in the development and therapeutic responses of various types of tumours. Experimental reagents (such as erastin and RSL3), approved drugs (for example, sorafenib, sulfasalazine, statins and artemisinin), ionizing radiation and cytokines (such as IFNγ and TGFβ1) can induce ferroptosis and suppress tumour growth. However, ferroptotic damage can trigger inflammation-associated immunosuppression in the tumour microenvironment, thus favouring tumour growth. The extent to which ferroptosis affects tumour biology is unclear, although several studies have found important correlations between mutations in cancer-relevant genes (for example, RAS and TP53), in genes encoding proteins involved in stress response pathways (such as NFE2L2 signalling, autophagy and hypoxia) and the epithelial-to-mesenchymal transition, and responses to treatments that activate ferroptosis. Herein, we present the key molecular mechanisms of ferroptosis, describe the crosstalk between ferroptosis and tumour-associated signalling pathways, and discuss the potential applications of ferroptosis in the context of systemic therapy, radiotherapy and immunotherapy. Ferroptosis is an iron-dependent form of regulated cell death driven by excessive lipid peroxidation. Pharmacological agents, ionizing radiation and cytokines can induce ferroptosis and thus suppress tumour growth, but ferroptosis can also trigger inflammation-associated immunosuppression. The authors describe the key molecular mechanisms of ferroptosis, including crosstalk with tumour-associated signalling pathways, and discuss potential therapeutic applications of ferroptosis.

Broadening horizons: the role of ferroptosis in cancer.

Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a large family of RNA-binding proteins (RBPs) that contribute to multiple aspects of nucleic acid metabolism including alternative splicing, mRNA stabilization, and transcriptional and translational regulation Many hnRNPs share general features, but differ in domain composition and functional properties This review will discuss the current knowledge about the different hnRNP family members, focusing on their structural and functional divergence Additionally, we will highlight their involvement in neurodegenerative diseases and cancer, and the potential to develop RNA-based therapies

/pdf/the-hnrnp-family-insights-into-their-role-in-health-and-1sabmin86x.pdf

The hnRNP family: insights into their role in health and disease

The past 15 years have seen an explosion in our understanding of how cells replicate damaged DNA and how this can lead to mutagenesis. The Y-family DNA polymerases lie at the heart of this process, which is commonly known as translesion synthesis. This family of polymerases has unique features that enable them to synthesize DNA past damaged bases. However, as they exhibit low fidelity when copying undamaged DNA, it is essential that they are only called into play when they are absolutely required. Several layers of regulation ensure that this is achieved.

Y-family DNA polymerases and their role in tolerance of cellular DNA damage

The porcine epidemic diarrhea virus (PEDV), belonging to the α-coronavirus, is the causative agent of porcine epidemic diarrhea (PED). Presently, protection from the existing PEDV vaccine is not effective. Therefore, anti-PEDV compounds should be studied. Berbamine (BBM), Fangchinoline (FAN), and (+)-Fangchinoline (+FAN), are types of bis-benzylisoquinoline alkaloids that are extracted from natural medicinal plants. These bis-benzylisoquinoline alkaloids have various biological activities, including antiviral, anticancer, and anti-inflammatory properties. In this study, we found that BBM, FAN, and +FAN suppressed PEDV activity with a 50% inhibitory concentration of 9.00 µM, 3.54 µM, and 4.68 µM, respectively. Furthermore, these alkaloids can decrease the PEDV-N protein levels and virus titers in vitro. The time-of-addition assay results showed that these alkaloids mainly inhibit PEDV entry. We also found that the inhibitory effects of BBM, FAN, and +FAN on PEDV rely on decreasing the activity of Cathepsin L (CTSL) and Cathepsin B (CTSB) by suppressing lysosome acidification. Taken together, these results indicated that BBM, FAN, and +FAN were effective anti-PEDV natural products that prevented PEDV entry and may be considered novel antiviral drugs.

/pdf/bis-benzylisoquinoline-alkaloids-inhibit-porcine-epidemic-1tzsca21.pdf

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

Bovine gammaherpesvirus 4 (BoHV-4) is a common virus detected in bovine with respiratory disease worldwide. In this study, we identified and characterized a novel BoHV-4 strain, referred as HB-ZJK, in vaginal swabs collected from cattle in China, 2022. The long unique region (LUR) of HB-ZJK is 10,9811 bp in length. It shares 99.17% to 99.38% nucleotide identity to five BoHV-4 strains available in GenBank and the highest similarity was seen with BoHV-4V. test (JN133502.1) strain (99.38%). Mutations, insertions or deletions were observed mainly in HB-ZJK gB (ORF8), TK (ORF21), gH (ORF22), MCP (ORF25), PK (ORF36), gM (ORF39), and gL (ORF47) genes compared to its genomic coordinates. Phylogenetic analyses of gB and TK genes showed that HB-ZJK clustered with China 512 (2019), B6010 (2009), and J4034 (2009) strains, demonstrating that the isolated HB-ZJK belongs to genotype 1. This is the first report that has revealed a comprehensive genome profile of BoHV-4 strain in China. This study will provide foundation for epidemiological investigations of BoHV-4 and contribute to the molecular and pathogenic studies of BoHV-4. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986666

Characterization and phylogenetic analysis of bovine gammaherpesvirus 4 isolated in China, 2022

Influenza A viruses (IAVs) rely on viral ribonucleoprotein (vRNP) complexes to control transcription and replication. Each vRNP consists of one viral genomic RNA segment associated with multiple nucleoproteins (NP) and a trimeric IAV RNA polymerase complex. Previous studies showed that post‐translational modifications of vRNP components, such as NP, by host factors would in turn affect the IAV life cycle or modulate host anti‐viral response. In this study, we found host E3 ubiquitin ligase Pirh2 interacted with NP and mediated short‐chain ubiquitination of NP at lysine 351, which suppressed NP‐PB2 interaction and vRNP formation. In addition, we showed that knockdown of Pirh2 promoted IAV replication, whereas overexpression of Pirh2 inhibited IAV replication. However, Pirh2‐ΔRING lacking E3 ligase activity failed to inhibit IAV infection. Moreover, we showed that Pirh2 had no effect on the replication of a rescued virus, WSN‐K351R, carrying lysine‐to‐arginine substitution at residue 351. Interestingly, by analyzing human and avian IAVs from 2011 to 2020 in influenza research databases, we found that 99.18% of 26 977 human IAVs encode lysine, but 95.3% of 9956 avian IAVs encode arginine at residue 351 of NP protein. Consistently, knockdown of Pirh2 failed to promote propagation of two avian‐like influenza viruses, H9N2‐W1 and H9N2‐C1, which naturally encode arginine at residue 351 of NP. Taken together, we demonstrated that Pirh2 is a host factor restricting IAV infection by modulating short‐chain ubiquitination of NP. Meanwhile, it is noteworthy that residue 351 of NP targeted by Pirh2 may associate with the evasion of human anti‐viral response against avian‐like influenza viruses.

Yong Sam Jung

Papers

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

Characterization and phylogenetic analysis of bovine gammaherpesvirus 4 isolated in China, 2022

Pirh2 restricts influenza A virus replication by modulating short‐chain ubiquitination of its nucleoprotein