Current Molecular Medicine - Volume 22, Issue 1, 2022

Leukaemia is the most common malignant tumor in childhood and can be cured by chemotherapy. Infection is an important cause of treatment-related death and treatment failure in childhood leukaemia. Recent studies have shown that the correlation between the occurrence of leukaemia infection and the intestinal flora has attracted more and more attention. Intestinal flora can affect the body's physiological defense and immune function. When intestinal microflora disorder occurs, metabolites/microorganisms related to intestinal flora alterations and even likely the associated morphofunctional alteration of the epithelial barrier may be promising diagnostic biomarkers for the early diagnosis of leukaemia infection. This review will focus on the interaction between leukaemia infection and intestinal flora, and the influence of intestinal flora in the occurrence and development of leukaemia infection.

Epigenetic modifications refer to reversible changes in gene expression. Epigenetic changes include DNA methylation, histone modification, and non-coding RNAs that are collectively called epigenome. Various epigenetic effects account for the main impacts of environment and lifestyle on multifactorial diseases, such as cancers. The environmental impacts on cancers act as double-edged swords. While some of them are involved in cancer development, some others contribute to preventing it. In this review article, the keywords "cancer", "epigenetic", "lifestyle", "carcinogen", " cancer inhibitors” and related words were searched to finding a link between environmental factors and epigenetic mechanisms influencing cancer in ISI, PUBMED, SCOPUS, and Google Scholar databases. Based on the literature, environmental factors that are effective in cancer development or cancer prevention will be divided into physical, chemical, biological, and lifestyle types in this review. Different types of epigenetic mechanisms known for each of these agents will be addressed. Unregulated changes in epigenome play roles in tumorigenicity and cancer development. The action mechanism and genes targeted which are related to the signaling pathway for epigenetic alterations determine whether environmental agents are carcinogenic or prevent cancer. Having knowledge about the effective factors and related mechanisms such as epigenetic on cancer can help to prevent and improve cancer treatment.

Prostate cancer (PCa) represents to be the most common tumor in male and one of the most relevant causes of death in the Western countries. Androgen deprivation therapy (ADT) constitutes a widely used approach in advanced PCa. When PCa progresses in spite of ADT and castrate levels of testosterone, the severe clinical condition termed as metastatic castration-resistant prostate cancer (mCRPC) takes place. The only approach to mCRPC has been represented by chemotherapy with taxanes for many years. Nevertheless, recently introduced treatments such as 2nd generation antiandrogens (i.e., enzalutamide and abiraterone), cell immunotherapy with sipuleucel-T or targeted alpha therapy with 223Ra-dichloride, have dramatically changed mCRPC prognosis. These novel therapies call for an unmet need for imaging biomarkers suitable for patients’ pre-treatment stratification and response assessment. In this scenario, nuclear medicine can provide several metabolic and molecular probes for investigating pathological processes at a cellular and sub-cellular level. The aim of this paper is to review the most relevant findings of the literature published to date on this topic, giving particular emphasis on the pros and cons of each tracer and also covering future prospects for defining personalized therapeutic approaches.

The aging process deteriorates organs' function at different levels, causing its progressive decline to resist stress, damage, and disease. In addition to alterations in metabolic control and gene expression, the rate of aging has been connected with the generation of high amounts of Reactive Oxygen Species (ROS). The essential perspective in free radical biology is that reactive oxygen species (ROS) and free radicals are toxic, mostly cause direct biological damage to targets, and are thus a major cause of oxidative stress. Different enzymatic and non-enzymatic compounds in the cells have roles in neutralizing this toxicity. Oxidative damage in aging is mostly high in particular molecular targets, such as mitochondrial DNA and aconitase, and oxidative stress in mitochondria can cause tissue aging across intrinsic apoptosis. Mitochondria's function and morphology are impaired through aging, following a decrease in the membrane potential by an increase in peroxide generation and size of the organelles. Telomeres may be the significant trigger of replicative senescence. Oxidative stress accelerates telomere loss, whereas antioxidants slow it down. Oxidative stress is a crucial modulator of telomere shortening, and that telomere-driven replicative senescence is mainly a stress response. The age-linked mitochondrial DNA mutation and protein dysfunction aggregate in some organs like the brain and skeletal muscle, thus contributing considerably to these post-mitotic tissues' aging. The aging process is mostly due to accumulated damage done by harmful species in some macromolecules such proteins, DNA, and lipids. The degradation of non-functional, oxidized proteins is a crucial part of the antioxidant defenses of cells, in which the clearance of these proteins occurs through autophagy in the cells, which is known as mitophagy for mitochondria.

The proteins of coronavirus are classified as non-structural, structural, and accessory. There are 16 non-structural viral proteins besides their precursors (1a and 1ab polyproteins). The non-structural proteins are named nsp1 to nsp16, and they act as enzymes, coenzymes, and binding proteins to facilitate the replication, transcription, and translation of the virus. The structural proteins are bound to the RNA in the nucleocapsid (N- protein) or to the lipid bilayer membrane of the viral envelope. The lipid bilayer proteins include the membrane protein (M), an envelope protein (E), and spike protein (S). Besides their role as structural proteins, they are essential for the host cells' binding and invasion. The SARS-CoV-2 contains six accessory proteins which participate in the viral replication, assembly and virus-host interactions. The SARS-CoV-2 accessory proteins are orf3a, orf6, orf7a, orf7b, orf8, and orf10. The functions of the SARS-CoV-2 are not well known, while the functions of their corresponding proteins in SARS-CoV are either well known or poorly studied. Recently, the Oxford University and Astrazeneca, Pfizer and BioNTech have made SARS-CoV-2 vaccines by targeting the spike protein gene. The US Food and Drug Administration (FDA) and the health authorities of the United Kingdom have approved and started conducting vaccinations using the Pfizer and BioNTech mRNA vaccine. Also, The FDA of the USA has approved the use of two monoclonal antibodies produced by Regeneron pharmaceuticals to target the spike protein for treating COVID-19. The SARS-CoV-2 proteins can be used for the diagnosis, as drug targets and in vaccination trials for COVID-19. In future COVID-19 research, more efforts should be made to elaborate the functions and structure of the SARS-CoV- 2 proteins so as to use them as targets for COVID-19 drugs and vaccines. Special attention should be paid to extensive research on the SARS-CoV-2 nsp3, orf8, and orf10.

Intorductuion: Increased cell-free DNA (cfDNA) is observed in many diseases such as cancer, myocardial infarction, and autoimmune diseases. It has the ability to alter the receptor cell phenotype, triggering events related to malignant transformation. Aims: Our study aims at assessing the use of cell-free plasma DNA in the diagnosis of metastatic and non-metastatic prostate cancer. Methods: The study included 180 subjects who were classified into four groups: Group I (GI) included 50 perfect health subjects as the control group, Group II (GII) included 40 patients with prostatitis, group III (GIII) included 40 patients with benign prostatic hyperplasia (BPH) and Group IV (GIV) included 50 patients with pre-operative prostate cancer (PC). Evaluation of the plasma level of circulating cell-free DNA by real-time PCR and measurement of total PSA (tPSA) and free to total PSA percent (f/tPSA%) were carried out for all groups. Results: Our study revealed that the level of tPSA was significantly higher in prostate cancer patients, while levels of f/t PSA were found to be significantly lower. The level of cfDNA was significantly higher in prostate cancer patients (399.9±88.6ng/ul) when compared to that of group I (12.1±1.5ng/ul) (p<0.01), group II (14.7±2.4 ng/ul) (p<0.01), and group III (26.6±45.6 ng/ul) (p<0.01) respectively. Conclusion: There was a statistically significant difference in yields of cfDNA between metastatic and non-metastatic groups (P=0.03) with a higher level in the metastatic group.

Background: Head and neck cancer (HNC) develops due to a number of risk factors, including infection of Human Papillomavirus (HPV). The genetic predisposition also plays an important role in deregulating different signaling pathways including the NF-KB pathway. Certain polymorphisms are reported to affect the NF-kB pathway genes. Objectives: The present research was conducted to study the association of HPV with NF-KB1 (p50) gene polymorphisms in HNC patients of the Pakistani population. Methods: Genomic DNA from HNC tumors samples was extracted using the Exgene SV DNA extraction Kit. Allele-specific PCR and direct sequencing were done for analysis of NF-ΚB1 SNPs 94ins/del (rs28362491), rs1598858 and rs4648068. Results: The genotypes AGrs1598858, AGrs4648068 and GGrs4648068 were associated with significantly increased risk of head and neck cancer in studied population. Furthermore the HNC cases with genotypes AGrs1598858 and GGrs4648068 displayed growing risk of HPV related cancers. Promotor region SNP 94ins/del (rs28362491) was not detected in studied population. Tobacco use, lymph nodes involvement and poorly differentiated tumors were positively associated with HPV induced cancers. Conclusion: It is the first comprehensive study from Pakistan, to evaluate the polymorphic variants of NF-ΚB1. Genotypes AGrs4648068, GGrs4648068, and AGrs1598858 of NF-ΚB1 gene are associated with increased risk of head and neck cancers in the studied HPV infected Pakistani population. It can be concluded that HPV infection, involvement of lymph nodes and tobacco use can act synergetic and add up in modulating HPV induced HNC with intronic SNPs of NF-ΚB1 gene in Pakistani population.