Pértille et al. Epigenetic Biomarkers of Long-Term Stress most stringent p-value (P ≤ 0.0005), we found 7 and 4 DMRs between treatments in the BR and SW populations, respectively. This study is the first approximation to identify epigenetic biomarkers of long-term exposure to stress in different lineages of production animals.

Anticancer medicines by affecting the process of spermatogenesis and damage to germ cells, leading to infertility. Cyclophosphamide (CP) as an alkylating agent and with antineoplastic activity is used for treatment of a variety of malignant tumours (Brannigan, 2007).Phosphoramide mustard and acrolein are two main active metabolites of CP, the first of which has a therapeutic role and the second has toxic effects such as apoptosis, and necrosis in normal tissues (Gu et al., 2017). Despite the high clinical applications of CP, its treatment is associated with adverse effects such as testicular toxicity and infertility. Oligospermia, azoospermia, disruption of the spermatogenesis cycle in testicular tissue are observed in patients receiving CP (Oliveira et al., 2020). In our previous study, we showed that CP led to increased oxidative stress, decreased testosterone, damage to sperm parameters, increased Caspase-3 activity (as an apoptosis biomarker) and changes in testicular tissue structure (Hamzeh et al., 2019). Chronic administration CP at low doses in males leads to increased mortality, induction of teratogenesis, abnormalities, infertility and impaired growth of their offspring

Summary Heterologous expression of a biosynthesis gene cluster from Amycolatopsis sp. resulted in the discovery of two unique class IV lasso peptides, felipeptins A1 and A2. A mixture of felipeptins stimulated proliferation of cancer cells, while having no such effect on the normal cells. Detailed investigation revealed, that pre-treatment of cancer cells with a mixture of felipeptins resulted in downregulation of the tumor suppressor Rb, making the cancer cells to proliferate faster. Pre-treatment with felipeptins made cancer cells considerably more sensitive to the anticancer agent doxorubicin and re-sensitized doxorubicin-resistant cells to this drug. Structural characterization and binding experiments showed an interaction between felipeptins resulting in complex formation, which explains their synergistic effect. This discovery may open an alternative avenue in cancer treatment, helping to eliminate quiescent cells that often lead to cancer relapse.

The results of this study suggest that mutations in mitochondrial tRNA genes might lead to deficiencies in translational process of critical proteins of the respiratory chain and potentially lead to BrS in Iranian subjects. (Cardiol J 2018; 25, 1: 113-119).

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Background p53 mutants contribute to the chronic inflammatory tumour microenvironment (TME). In this study, we address the mechanism of how p53 mutants lead to chronic inflammation in tumours and how to transform it to restore cancer immune surveillance. Methods Our analysis of RNA-seq data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project revealed that mutant p53 (mtp53) cancers correlated with chronic inflammation. We used cell-based assays and a mouse model to discover a novel gain of function of mtp53 and the effect of the mtp53 reactivating compound APR-246 on the anti-tumour immune response. Results We found that tumour samples from patients with breast carcinoma carrying mtp53 showed elevated Interferon (IFN) signalling, Tumour Inflammation Signature (TIS) score and infiltration of CD8+ T cells compared to wild type p53 (wtp53) tumours. We showed that the expression of IFN and immune checkpoints were elevated in tumour cells in a mtp53-dependent manner, suggesting a novel gain of function. Restoration of wt function to mtp53 by APR-246 induced the expression of endogenous retroviruses, IFN signalling and repressed immune checkpoints. Moreover, APR-246 promoted CD4+ T cells infiltration and IFN signalling and prevented CD8+ T cells exhaustion within the TME in vivo. Conclusions Breast carcinomas with mtp53 displayed enhanced inflammation. APR-246 boosted the interferon response or represses immune checkpoints in p53 mutant tumour cells, and restores cancer immune surveillance in vivo.