Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting

Cell Death-Associated Molecular-Pattern Molecules: Inflammatory Signaling and Control

Apoptosis, necroptosis, and pyroptosis are different cellular death programs characterized in organs and tissues as consequence of microbes infection, cell stress, injury, and chemotherapeutics exposure. Dying and death cells release a variety of self-proteins and bioactive chemicals originated from cytosol, nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are named cell death-associated molecular-pattern (CDAMP), damage-associated molecular-pattern (DAMP) molecules, and alarmins. Some of them cooperate or act as important initial or delayed inflammatory mediators upon binding to diverse membrane and cytosolic receptors coupled to signaling pathways for the activation of the inflammasome platforms and NF-κB multiprotein complexes. Current studies show that the nonprotein thiols and thiol-regulating enzymes as well as highly diffusible prooxidant reactive oxygen and nitrogen species released together in extracellular inflammatory milieu play essential role in controlling pro- and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here, we provide an overview of these emerging concepts and mechanisms of triggering and maintenance of tissue inflammation under massive death of cells

Malaria diagnosis from pooled blood samples: comparative analysis of real-time PCR, nested PCR and immunoassay as a platform for the molecular and serological diagnosis of malaria on a large-scale

Malaria diagnoses has traditionally been made using thick blood smears, but more sensitive and faster techniques are required to process large numbers of samples in clinical and epidemiological studies and in blood donor screening. Here, we evaluated molecular and serological tools to build a screening platform for pooled samples aimed at reducing both the time and the cost of these diagnoses. Positive and negative samples were analysed in individual and pooled experiments using real-time polymerase chain reaction (PCR), nested PCR and an immunochromatographic test. For the individual tests, 46/49 samples were positive by real-time PCR, 46/49 were positive by nested PCR and 32/46 were positive by immunochromatographic test. For the assays performed using pooled samples, 13/15 samples were positive by real-time PCR and nested PCR and 11/15 were positive by immunochromatographic test. These molecular methods demonstrated sensitivity and specificity for both the individual and pooled samples. Due to the advantages of the real-time PCR, such as the fast processing and the closed system, this method should be indicated as the first choice for use in large-scale diagnosis and the nested PCR should be used for species differentiation. However, additional field isolates should be tested to confirm the results achieved using cultured parasites and the serological test should only be adopted as a complementary method for malaria diagnosis