Topic Review
GADD45A
The growth arrest and DNA damage-inducible 45 alpha (GADD45A) gene encodes a 165 aa protein localized in the nucleus, whose level is highest in the G1 phase of the cell cycle, with a substantial reduction in S. The involvement of GADD45A in the cell cycle regulation and interaction with other proteins underline its function in the cellular DNA damage response and maintaining genomic stability, which, in turn, determines its high potential in cancer transformation. The protective role of GADD45A in DNA damage-induced tumorigenesis is the main biological function of this protein, but exact mechanism of it is not known. Emerging evidence suggests that GADD45A may be important in breast cancer and several molecular pathways were reported to underline this importance, including Ras, mitogen-activated protein kinase 8 (MAPK8), JNK (c-Jun N-terminal kinase) and p38. GADD45A may play a tumor-suppressor role by induction of senescence and apoptosis in cancer cells. However, it was also shown that GADD45A may promote tumorigenesis via the GSK3 β (glycogen synthase kinase 3 beta)/β-catenin signaling. Therefore, GADD45A may function as either a tumor promotor or suppressor, depending on the kind of oncogenic stress, and these two functions are mediated by different signaling pathways.
  • 695
  • 01 Nov 2020
Topic Review
Molecular Mechanisms of Homologous Recombination
Homologous recombination (HR) is a fundamental evolutionarily conserved process that plays prime role(s) in genome stability maintenance through DNA repair and through the protection and resumption of arrested replication forks. HR promotes the exchange between homologous DNA sequences resulting in a novel combination of the genetic material. Therefore, HR is essential in genome stability maintenance but also plays an important role in genome diversity; such as in the case of meiosis. Many HR genes are deregulated in cancer cells. Notably, the breast cancer genes BRCA1 and BRCA2, two important HR players, are the most frequently mutated genes in familial breast and ovarian cancer. 
  • 668
  • 28 Apr 2021
Topic Review
Mitochondrial DNA
Increasing evidence implicates mitochondrial dysfunction in the etiology of Parkinson’s disease (PD). Mitochondrial DNA (mtDNA) mutations represent a possible cause and this mechanism might be shared with the aging process and with other age-related neurodegenerative disorders such as Alzheimer’s disease (AD). We have recently proposed a computerized method for mutated mtDNA characterization able to discriminate between AD and aging. Dealing with mtDNA mutation-based profiling of neurodegenerative disease(s), peripheral blood mtDNA sequences from late-onset PD patients and age-matched controls were analyzed and compared to the revised Cambridge Reference Sequence (rCRS). The chaos game representation (CGR) method, modified to visualize heteroplasmic mutations, was used to display fractal properties of mtDNA sequences and fractal lacunarity analysis was applied to quantitatively characterize PD based on mtDNA mutations. Parameter β, from the hyperbola model function of our lacunarity method, was statistically different between PD and control groups when comparing mtDNA sequence frames corresponding to GenBank np 5713-9713. Our original method, based on CGR and lacunarity analysis, represents a useful tool to analyze mtDNA mutations. Lacunarity parameter β is able to characterize individual mutation profile of mitochondrial genome and could represent a promising index to discriminate between PD and aging.
  • 663
  • 29 Oct 2020
Topic Review
Ferroptosis in Liver Diseases
Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and redox imbalance. Ferroptosis shows specific biological and morphological features when compared to the other cell death patterns. The loss of lipid peroxide repair activity by glutathione peroxidase 4 (GPX4), the presence of redox-active iron and the oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are considered as distinct fingerprints of ferroptosis. Several pathways, including amino acid and iron metabolism, ferritinophagy, cell adhesion, p53, Keap1/Nrf2 and phospholipid biosynthesis, can modify susceptibility to ferroptosis. Through the decades, various diseases, including acute kidney injury; cancer; ischemia-reperfusion injury; and cardiovascular, neurodegenerative and hepatic disorders, have been associated with ferroptosis. Here, we provide a short overview of the main biological and biochemical mechanisms of ferroptosis. The contribution of ferroptosis to the spectrum of liver diseases, acute or chronic is also reported. Finally, we discuss the use of ferroptosis as a therapeutic approach against hepatocellular carcinoma, the most common form of primary liver cancer.
  • 651
  • 21 Jul 2020
Topic Review
Breast Cancer Pathology and Biomarkers
This contribution describes breast pathology and breast cancer incidence and mortality statistics. The contribution also discusses the clinical performance of already approved breast cancer biomarkers and their performance is compared to novel discovered breast cancer biomarkers.
  • 593
  • 28 Jul 2020
Topic Review
TNF
TNF is a gene that plays an essential role in the body, it affects both immune response and inflammation. The gene encodes a protein called tumour necrosis factor alpha (TNFα) [1].
  • 581
  • 05 Nov 2020
Topic Review
NRF2
Nuclear factor erythroid 2‐related factor 2 (NRF2) is a transcription factor that regulates the cellular defense against toxic and oxidative insults through the expression of genes involved in oxidative stress response and drug detoxification. NRF2 activation renders cells resistant to chemical carcinogens and inflammatory challenges. In addition to antioxidant responses, NRF2 is involved in other cellular processes, including metabolism and inflammation, and its functions are beyond the originally envisioned. NRF2 activity is tightly regulated through a complex transcriptional and post-translational network that enables it to orchestrate the cell’s response and adaptation to various pathological stressors for the homeostasis maintenance. Elevated or decreased NRF2 activity by pharmacological and genetic manipulations of NRF2 activation is associated with many metabolism- or inflammation-related diseases. Emerging evidence shows that NRF2 lies at the center of a complex regulatory network and establishes NRF2 as a truly pleiotropic transcription factor. Here we summarize the complex regulatory network of NRF2 activity and its roles in metabolic reprogramming, unfolded protein response, proteostatsis, autophagy, mitochondrial biogenesis, inflammation, and immunity.
  • 555
  • 17 Jul 2020
Topic Review
Maple Syrup Urine Disease
       Maple Syrup Urine Disease (MSUD) is caused by a deficiency of branched-chain α-ketoacid dehydrogenase (BCKD). It is a metabolic disorder characterized by increased levels of branched-chain amino acids (BCAAs) and their respective branched-chain α-ketoacids (BCKAs) [1]. 
  • 547
  • 26 Oct 2020
Topic Review
Mabry Syndrome
Mabry syndrome is a condition characterized by intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia), and other signs and symptoms.
  • 512
  • 23 Dec 2020
Topic Review
Action Myoclonus–Renal Failure Syndrome
Action myoclonus–renal failure (AMRF) syndrome causes episodes of involuntary muscle jerking or twitching (myoclonus) and, often, kidney (renal) disease. Although the condition name refers to kidney disease, not everyone with the condition has problems with kidney function.
  • 490
  • 23 Dec 2020
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