Topic Review
Structure and Architecture of BRCT Domains
The human BRCT domain was first resolved from the crystal structure of the N-terminal BRCT of the X-ray repair cross-complementing protein 1 (XRCC1), determined by X-ray crystallography to a 3.2 Å resolution. Its tertiary structure features a central core of four-stranded parallel β-sheet (β1, β2, β3, and β4) flanked by two α-helices (α1 and α3) on the C-terminal end, a single α-helix (α2) on the N-terminal end, and two surface loops connecting β1 with α1 and α2 with β3 (the overall structure being β1-α1-β2-β3-α2-β4-α3). BRCT domains have been identified in a wide group of living organisms (from bacteria, parasites to mammals) and viruses. As mentioned above, those domains take part in a variety of important cell processes including DDR and cell cycle control. In addition, a few of these protein modules have been shown to be involved in pathologies such as cancer or infectious diseases including leishmaniasis. Therefore, significant efforts have been made towards finding compounds able to specifically inhibit the functions of these protein domains.
  • 348
  • 24 Jul 2023
Topic Review
Applications of Azanucleoside Analogs as DNA Demethylating Agents
Azanucleosides, such as 5-azacytidine and decitabine, are DNA demethylating agents used in the treatment of acute myeloid leukemia and myelodysplastic syndromes.
  • 217
  • 23 Jul 2023
Topic Review
Non-Alcoholic Steatohepatitis and Organokines
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. 
  • 418
  • 23 Jul 2023
Topic Review
Autophagy in Spinocerebellar Ataxia Type 3
Machado–Joseph disease (MJD) or spinocerebellar ataxia 3 (SCA3) is a rare, inherited, monogenic, neurodegenerative disease, and the most common SCA worldwide. MJD/SCA3 causative mutation is an abnormal expansion of the triplet CAG at exon 10 within the ATXN3 gene. The gene encodes for ataxin-3, which is a deubiquitinating protein that is also involved in transcriptional regulation. In normal conditions, the ataxin-3 protein polyglutamine stretch has between 13 and 49 glutamines. MJD/SCA3 patients display several signals and symptoms in which the most prominent is ataxia.
  • 279
  • 21 Jul 2023
Topic Review
Fascin-1 in Cancer Cell Metastasis
As metastasis is responsible for most cancer-related deaths, understanding the cellular and molecular events that lead to cancer cell migration and invasion will certainly provide insights into novel anti-metastatic therapeutic targets. Fascin-1 is an actin-bundling protein fundamental to all physiological or pathological processes that require cell migration. It is responsible for cross-linking actin microfilaments during the formation of actin-rich cellular structures at the leading edge of migrating cells such as filopodia, lamellipodia and invadopodia. While most epithelial tissues express low levels of Fascin-1, it is dramatically elevated in the majority of cancers and its expression has been associated with more aggressive disease and decreased overall survival. Hence, it has been proposed as a potential anti-cancer target.
  • 218
  • 21 Jul 2023
Topic Review
Regulation of Bone
During evolution, the development of bone was critical for many species to thrive and function in the boundary conditions of Earth. Furthermore, bone also became a storehouse for calcium that could be mobilized for reproductive purposes in mammals and other species. The critical nature of bone for both function and reproductive needs during evolution in the context of the boundary conditions of Earth has led to complex regulatory mechanisms that require integration for optimization of this tissue across the lifespan. Three important regulatory variables include mechanical loading, sex hormones, and innervation/neuroregulation. The importance of mechanical loading has been the target of much research as bone appears to subscribe to the “use it or lose it” paradigm. Furthermore, because of the importance of post-menopausal osteoporosis in the risk for fractures and loss of function, this aspect of bone regulation has also focused research on sex differences in bone regulation. 
  • 326
  • 21 Jul 2023
Topic Review
Antiparasitic and Immunomodulatory Activity of AMPs and CPPs
In 2020, the WHO established the road map for neglected tropical diseases 2021–2030, which aims to control and eradicate 20 diseases, including leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions, such as those caused by Trypanosoma cruzi and Leishmania spp. infections. 
  • 296
  • 21 Jul 2023
Topic Review
Fungi in Freshwaters
Deprivation of protection for aquatic hyphomycetes is disturbing because they are key players in freshwater ecosystems across the globe. The knowledge of biodiversity of aquatic hyphomycetes and freshwater ecosystems were enriched. 
  • 260
  • 21 Jul 2023
Topic Review
Clinical Applications of Polypodium leucotomos (Fernblock®) in Oncodermatology
Exposure to sun radiation leads to higher risk of sunburn, pigmentation, immunosuppression, photoaging and skin cancer. In addition to ultraviolet radiation (UVR), recent research indicates that infrared radiation (IR) and visible light (VIS) can play an important role in the pathogenesis of some of these processes. Detrimental effects associated with sun exposure are well known, but new studies have shown that DNA damage continues to occur long after exposure to solar radiation has ended. Regarding photoprotection strategies, natural substances are emerging for topical and oral photoprotection. In this sense, Fernblock®, a standardized aqueous extract of the fern Polypodium Leucotomos (PLE), has been widely administered both topically and orally with a strong safety profile. Thus, this extract has been used extensively in clinical practice, including as a complement to photodynamic therapy (PDT) for treating actinic keratoses (AKs) and field cancerization.
  • 433
  • 21 Jul 2023
Topic Review
General Properties of Genes Encoding Histone Variants
All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability to use only the right and necessary genes involved in specific functions depends on the structural organization of the nuclear chromatin, which in turn depends on the epigenetic history of each cell, which is stored in the form of a collection of DNA and protein modifications. Among these modifications, DNA methylation and many kinds of post-translational modifications of histones play a key role in organizing the complex indexing of usable genes.
  • 383
  • 21 Jul 2023
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