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Topic Review
Polycomb Complexes in Plasma Cells
Polycomb group (PcG) proteins are epigenetic regulators involved in cell fate and carcinogenesis. The emerging roles of PcG in PC differentiation and myelomagenesis position them as potential therapeutic targets in multiple myeloma (MM), a cancer that emerges from plasma cells. Plasma cells (PC) are the main effectors of adaptive immunity, responsible for producing antibodies to defend the body against pathogens. They are the result of a complex highly regulated cell differentiation process, taking place in several anatomical locations and involving unique genetic events. Pathologically, PC can undergo tumorigenesis and cause a group of diseases known as plasma cell dyscrasias, including multiple MM, a severe disease with poor prognosis characterized by the accumulation of malignant PC within the bone marrow, and high clinical and molecular heterogeneity. MM patients frequently develop resistance to treatment, leading to relapse.  Below, the roles of PcG proteins in normal and malignant plasma cells and their therapeutic implications are presented.
  • 720
  • 24 Nov 2020
Topic Review
Gene annotation for 'Flaviviridae' genomes
Responding to the ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and Zika, demands a greater understanding of how these viruses emerge and spread. Updated phylogenies are central to this understanding. Most cladograms of Flaviviridae focus on specific lineages and ignore outgroups, thus hampering the efficacy of the analysis to test ingroup monophyly and relationships. This is due to the lack of annotated Flaviviridae genomes, which has gene content variation among genera. This variation makes analysis without partitioning difficult. Therefore, we developed an annotation pipeline for the genera of Flaviviridae (Flavirirus, Hepacivirus, Pegivirus, and Pestivirus), named “Fast Loci Annotation of Viruses” (FLAVi: flavi-web.com), that combines ab initio and homology-based strategies. FLAVi recovered 100% of the genes in Flavivirus and Hepacivirus genomes. In Pegivirus and Pestivirus, annotation efficiency was 100% except for one partition each. There were no false positives. The combined phylogenetic analysis of multiple genes made possible by annotation has clear impacts over the tree topology compared to phylogenies that we inferred without outgroups or data partitioning. The final tree is largely congruent with previous hypotheses and adds evidence supporting the close phylogenetic relationship between dengue and Zika.
  • 720
  • 27 Oct 2020
Topic Review
Polymerase-1 (PARP)-1 and Cancer
One of the critical functions of PARP-1 is the response to DNA damage, which plays a pivotal role in DNA repair in cancers. PARP-1 also has widespread functions that are essential for the survival and growth of cancer cells. It regulates oxidative stress in mitochondria through the regulation of superoxide and oxidation. PARP-1 is in charge of regulating mitosis, which is a crucial role in tumorigenesis and remodels histones and chromatin enzymes related to transcriptional regulation, causing alterations in epigenetic markers and chromatin structure. Given the significance of these processes, it can be understood that these processes in cancer cells are at the frontline of the pathogenetic changes required for cancer cell survival, and these contributions can result in malignant transformation. 
  • 720
  • 28 Apr 2021
Topic Review
Biogenic Volatile Organic Compounds
Upon pathogen attack, plants very quickly undergo rather complex physico-chemical changes, such as the production of new chemicals or alterations in membrane and cell wall properties, to reduce disease damages. An underestimated threat is represented by root parasitic nematodes. In Vitis vinifera L., the nematode Xiphinema index is the unique vector of Grapevine fanleaf virus, responsible for fanleaf degeneration, one of the most widespread and economically damaging diseases worldwide. The aim of this study was to investigate changes in the emission of biogenic volatile organic compounds (BVOCs) in grapevines attacked by X. index. BVOCs play a role in plant defensive mechanisms and are synthetized in response to biotic damages. In our study, the BVOC profile was altered by the nematode feeding process. We found a decrease in β-ocimene and limonene monoterpene emissions, as well as an increase in α-farnesene and α-bergamotene sesquiterpene emissions in nematode-treated plants. Moreover, we evaluated the PR1 gene expression. The transcript level of PR1 gene was higher in the nematode-wounded roots, while in the leaf tissues it showed a lower expression compared to control grapevines.
  • 719
  • 15 Jul 2020
Topic Review
Posttranscriptional Defects of Selenoenzymes
Methylmercury (MeHg) is a well-known neurotoxicant that causes severe intoxication in humans. Research progress has pointed out the importance of oxidative stress in the pathogenesis of MeHg toxicity. MeHg-induced intracellular relative selenium deficiency due to the greater affinity of MeHg for selenohydryl groups and selenides leads to failure in the recoding of a UGA codon for selenocysteine and results in the degradation of antioxidant selenoenzyme mRNA by nonsense-mediated mRNA decay. The defect of antioxidant selenoenzyme replenishment exacerbates MeHg-mediated oxidative stress. 
  • 719
  • 09 Nov 2020
Topic Review
CRISPR-Cas9 Genome Editing in GBM
Glioblastoma multiforme (GBM) is an aggressive malignancy of the brain and spinal cord with a poor life expectancy. The low survivability of GBM patients can be attributed, in part, to its heterogeneity and the presence of multiple genetic alterations causing rapid tumor growth and resistance to conventional therapy. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) nuclease 9 (CRISPR-Cas9) system is a cost-effective and reliable gene editing technology, which is widely used in cancer research. It leads to novel discoveries of various oncogenes that regulate autophagy, angiogenesis, and invasion and play important role in pathogenesis of various malignancies, including GBM.
  • 719
  • 23 Sep 2021
Topic Review
Rejuvenate Aging Cells and Tissues
Rejuvenate aging cells and tissues is strategies to delay and potentially even reverse the aging process.
  • 719
  • 26 May 2021
Topic Review
Phytochemicals and Gastrointestinal Cancer Progression
Gastrointestinal (GI) cancer is a prevailing global health disease with a high incidence rate which varies by region. It is a huge economic burden on health care providers. GI cancer affects different organs in the body such as the gastric organs, colon, esophagus, intestine, and pancreas. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in fruits, grains, and vegetables. Consumption of phytochemicals may protect against chronic diseases like cardiovascular disease, neurodegenerative disease, and cancer. Multiple studies have assessed the chemoprotective effect of selected phytochemicals in GI cancer, offering support to their potential towards reducing the pathogenesis of the disease.The aim of this review is to summarize the current knowledge addressing the anti-cancerous effects of selected dietary phytochemicals on GI cancer and their molecular activities on selected mechanisms, i.e., nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), detoxification enzymes, adenosine monophosphate activated protein kinase (AMPK), wingless-related integration site/-catenin (wingless-related integration site (Wnt)-catenin, cell apoptosis, phosphoinositide 3-kinases (PI3K)/ protein kinase B AKT/ mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK). Overall, phytochemicals improve cancer prognosis through the downregulation of -catenin phosphorylation, therefore enhancing apoptosis, and upregulation of the AMPK pathway, which supports cellular homeostasis. Nevertheless, more studies are needed to provide a better understanding of the mechanism of cancer treatment using phytochemicals and possible side effects associated with this approach.
  • 719
  • 10 Jun 2021
Topic Review
HMGB1 in Chemotherapy-Induced Peripheral Neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines.
  • 718
  • 15 Apr 2021
Topic Review
Bacterial Enhancement of Microalgal Metabolites
Microalgae are photosynthetic microorganisms with a high potential to produce a wide variety of industrial-interest metabolites such as proteins, lipids, carbohydrates, and pigments. 
  • 718
  • 20 Apr 2021
Topic Review
Acridine-Based Antimalarials
Malaria is among the deadliest infectious diseases in the world caused by Plasmodium parasites.
  • 718
  • 19 Mar 2021
Topic Review
Rumex Species
Today, more than ever, the search for non-trivial sources of biologically active substances is critical. Plants of the genus Rumex are noteworthy. Plants of this genus stand out for a number of advantages from the dominant plant core of meadow phytocenoses of the temperate climatic zone: a short growing season, an intensive increase in biomass, and undemanding growth conditions. In addition, this plant genus is known as a super-producer of secondary phenolic compounds.
  • 717
  • 02 Mar 2022
Topic Review
PPAR Ligands in Viral Infections
Peroxisome Proliferator-Activated Receptors (PPARs), belonging to the nuclear receptor superfamily, are transcription factors playing well-established roles in several metabolic pathways in the organism, including lipid and glucose metabolism, energetic homeostasis, cell differentiation and proliferation. Since their discovery, a body of knowledge has been collected on them, and the three receptor subtypes (PPARα, PPARγ, PPARβ/δ) have attracted a great deal of efforts by medicinal chemists to identify novel drugs targeting the metabolism. PPAR agonists, antagonists, and modulators represent important pharmacological tools to induce beneficial therapeutic effects in metabolic disorders, such as metabolic syndrome, obesity, diabetes, and others.
  • 717
  • 30 Jan 2022
Topic Review
Talazoparib and Niraparib
Niraparib (MK-4827) inhibits PARP1 and PARP2. It was approved by the U.S. Food and Drug Administration (FDA) in March 2017 indicated for the therapy of adult patients with ovarian, fallopian tube and peritoneal neoplasms. Talazoparib (BMN 673) is a potent and selective inhibitor of PARP1 and PARP2 used at lower concentrations than previous generations of PARP inhibitors. The FDA approved Talazoparib in October 2018 for patients with germline BRCA-mutated, HER2-negative breast cancer. Poly (ADP-ribose) polymerases (PARP) play an essential role in different cellular processes, including several pathways of DNA repair. PARP inhibitors (PARPi) are able to impair DNA damage repair by non-homologous end joining (NHEJ). This effect depends on the cell´s ability to compensate for the inhibition of PARP-mediated pathways by other repair pathways. PARPi especially induce cell death in cancer cells with a lack of PARP-independent DNA repair pathways.
  • 716
  • 25 Jun 2021
Topic Review
Bacterial Toxins and Immunomodulation
The idea that bacterial toxins are not only killers but also execute more sophisticated roles during bacteria–host interactions by acting as negotiators has been highlighted in the past decades. Depending on the toxin, its cellular target and mode of action, the final regulatory outcome can be different. Focused on two families of bacterial toxins: genotoxins and pore-forming toxins, which have different modes of action but share the ability to modulate the host’s immune responses, independently of their capacity to directly kill immune cells. 
  • 716
  • 05 Aug 2021
Topic Review
ACE2 Signaling Pathway and Processing during COVID-19 Infection
ACE2 (angiotensin-converting enzyme) can be described as an enzyme, a transporter, and through its role as a receptor.
  • 716
  • 13 Jan 2023
Topic Review
Synthetic Oleanolic Acid Derivatives
Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid) is a pentacyclic triterpenoid, widely occurring in the plant kingdom, which includes edible and medicinal plants. The richest source of oleanolic acid (OA) are the leaves of the olive plant. Common culinary spices such as garden thyme and clove plants, as well as fruits, are also sources of OA.
  • 715
  • 22 Sep 2021
Topic Review
HuR and Hepatobiliary Cancers
HuR owns the post-transcriptional control of a large number of RNAs, enabling the protein to play pivotal roles that are dictated by the molecular functions of the transcripts. HuR targets, chiefly, include many mRNAs encoding proteins involved in cell proliferation, senescence, apoptosis, differentiation, stress, and immune responses. In turn, HuR was found to be involved not only in physiological processes (e.g., adipogenesis and muscle differentiation) but also in disease (primarily, cancer and inflammation). 
  • 715
  • 24 Jun 2022
Topic Review
Glycosaminoglycans in Cancer Therapy
The tumor microenvironment (TME) is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded by the components of the extracellular matrix (ECM). Glycosaminoglycans (GAGs), natural biomacromolecules, essential ECM, and cell membrane components are extensively altered in cancer tissues. During disease progression, the GAG fine structure changes in a manner associated with disease evolution. Thus, changes in the GAG sulfation pattern are immediately correlated to malignant transformation. Their molecular weight, distribution, composition, and fine modifications, including sulfation, exhibit distinct alterations during cancer development. GAGs and GAG-based molecules, due to their unique properties, are suggested as promising effectors for anticancer therapy. Considering their participation in tumorigenesis, their utilization in drug development has been the focus of both industry and academic research efforts. These efforts have been developing in two main directions; (i) utilizing GAGs as targets of therapeutic strategies and (ii) employing GAGs specificity and excellent physicochemical properties for targeted delivery of cancer therapeutics.
  • 715
  • 24 Mar 2021
Topic Review
Circadian Rhythms and Glioblastomas
Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells.
  • 714
  • 15 Aug 2021
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