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Topic Review
Crohn’s Disease Complication
Crohn’s Disease (CD) is a chronic inflammatory disorder in which up to 50% of patients develop fistula within 20 years after the initial diagnosis, and half of these patients suffer perianal fistulizing disease. The etiopathogenesis of CD-related perianal fistula is still unclear, and its phenotypical and molecular characteristics are even more indefinite. A better understanding would be crucial to develop targeted and more effective therapeutic strategies.
  • 715
  • 06 Dec 2021
Topic Review
ENPP2 Methylation in Health and Cancer
Autotaxin (ATX) encoded by Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) is a key enzyme in Lysophosphatidic Acid (LPA) synthesis implicated in cancer. Although its aberrant expression has been reported, ENPP2 methylation profiles in health and malignancy are not described. We examined in silico the methylation of ENPP2 analyzing publicly available methylome datasets, to identify Differentially Methylated CpGs (DMCs) which were then correlated with expression at gene and isoform levels. Significance indication was set to be FDR corrected p-value < 0.05. Healthy tissues presented methylation in all gene body CGs and lower levels in Promoter Associated (PA) regions, whereas in the majority of the tumors examined (HCC, melanoma, CRC, LC and PC) the methylation pattern was reversed. DMCs identified in the promoter were located in sites recognized by multiple transcription factors, suggesting involvement in gene expression. Alterations in methylation were correlated to an aggressive phenotype in cancer cell lines. In prostate and lung adenocarcinomas, increased methylation of PA CGs was correlated to decreased ENPP2 mRNA expression and to poor prognosis parameters. Collectively, our results corroborate that methylation is an active level of ATX expression regulation in cancer. Our study provides an extended description of the methylation status of ENPP2 in health and cancer and points out specific DMCs of value as prognostic biomarkers. 
  • 714
  • 11 Nov 2021
Topic Review
Oncoproteomics Technologies
Proteomics continues to forge significant strides in the discovery of essential biological processes, uncovering valuable information on the identity, global protein abundance, protein modifications, proteoform levels, and signal transduction pathways. Cancer is a complicated and heterogeneous disease, and the onset and progression involve multiple dysregulated proteoforms and their downstream signaling pathways. These are modulated by various factors such as molecular, genetic, tissue, cellular, ethnic/racial, socioeconomic status, environmental, and demographic differences that vary with time. The knowledge of cancer has improved the treatment and clinical management; however, the survival rates have not increased significantly, and cancer remains a major cause of mortality. Oncoproteomics studies help to develop and validate proteomics technologies for routine application in clinical laboratories for (1) diagnostic and prognostic categorization of cancer, (2) real-time monitoring of treatment, (3) assessing drug efficacy and toxicity, (4) therapeutic modulations based on the changes with prognosis and drug resistance, and (5) personalized medication. Investigation of tumor-specific proteomic profiles in conjunction with healthy controls provides crucial information in mechanistic studies on tumorigenesis, metastasis, and drug resistance. 
  • 713
  • 01 Mar 2023
Topic Review
Neurobiology of Maternal Behavior in Nonhuman Mammals
Survival of the mammal offspring depends on the correct expression of maternal behaviors, particularly during the early postnatal period. Newborns must be a powerful source of incentive sensory stimulation to the dam, and in return, they must be capable of responding either actively or passively to such stimuli, expressing acceptance and motivation to invest energy and time and willingness to risk their physical safety. Hence, the capacity to express maternal behavior depends on the sensitivity to respond to the right stimuli under certain physiological, ontogenic, or cognitive conditions. Accordingly, to understand the neurobiology of this behavior, it must be considered that neural systems are involved in acceptance, social recognition, motivation, and fear/rejection. 
  • 711
  • 06 Jan 2023
Topic Review
Long Non-Coding RNAs at the GWAS Risk Loci
Long non-coding RNAs (lncRNAs) are emerging as key players in a variety of cellular processes. Deregulation of the lncRNAs has been implicated in prostate and breast cancers. Recently, germline genetic variations associated with cancer risk have been correlated with lncRNA expression and/or function. In addition, single nucleotide polymorphisms (SNPs) at well-characterized cancer-associated lncRNAs have been analyzed for their association with cancer risk. These SNPs may occur within the lncRNA transcripts or spanning regions that may alter the structure, function, and expression of these lncRNA molecules and contribute to cancer progression and may have potential as therapeutic targets for cancer treatment. Additionally, some of these lncRNA have a tissue-specific expression profile, suggesting them as biomarkers for specific cancers.
  • 710
  • 29 Mar 2022
Topic Review
Taste Processing from Animal Models
Taste processing is an adaptive mechanism involving complex physiological, motivational and cognitive processes. Animal models have provided relevant data about the neuroanatomical and neurobiological components of taste processing. 
  • 709
  • 30 Nov 2021
Topic Review
Targets for Therapeutic Treatment of Alzheimer’s Disease
Alzheimer's disease (AD) is an adult-onset dementia characterised by progressive neurodegeneration and widespread brain damage, leading to long-term functional and cognitive impairment and greatly reduced life expectancy. While early genetic studies uncovered several polymorphisms associated with AD, more recently genome-wide association analyses and massive sequencing techniques have revealed numerous novel susceptibility genes, differentially expressed genes, and disease traits. Nevertheless, the mechanisms underlying disease onset are still not fully understood and, as with other complex human diseases, the causes of low heritability are unclear. Epigenetic mechanisms, in which changes in gene expression do not depend on changes in genotype, have been postulated as key factors in understanding the development of AD and the processes that influence age-related changes and various neurological diseases. Research on specific mutations in risk genes and epigenetic markers is increasing, enabling the development of therapeutic treatments that target the neuropathological changes associated with AD and, in many cases, are expected to reverse at least some of the cognitive impairment associated with the disease. The application of effective therapies therefore requires a growing understanding of the genetic risk factors and underlying epigenetic mechanisms involved in AD. 
  • 707
  • 23 Dec 2021
Topic Review
Rapha-Myr®:Antitumor Agent in Human Astrocytoma
We utilized Rapha Myr®, a novel blend of broccoli seed extract (Brassica Oleracea s.e., Sulforaphane glucosinolate titer 11%) plus active myrosinase, to treat the human astrocytoma cell line (1321N1). Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.
  • 706
  • 28 Apr 2021
Topic Review
Interaction of Antibiotic Mixing and Temperature
Use of antibiotics for the treatment and prevention of bacterial infections in humans, agri- and aquaculture as well as livestock rearing leads to antibiotic pollution of fresh water and these antibiotics have an impact on free-living bacteria. While we know which antibiotics are most common in natural environments such as rivers and streams, there is considerable uncertainty regarding antibiotics’ interactions with one another and the effect of abiotic factors such as temperature. 
  • 706
  • 27 Dec 2021
Topic Review
European Eel
The European eel (Anguilla anguilla) is a migratory, catadromous fish species, consisting of a single stock, distributed throughout the European continent as well as in the Mediterranean basin, which reproduces in the Atlantic Ocean and for which the panmixia hypothesis is currently accepted. 
  • 706
  • 03 Apr 2023
Topic Review
Insect Antimicrobial Peptides
Insects are the organisms from which the greatest amount of peptides are isolated. A single insect produces a mixture of 15–20 peptides, the concentration of which in the hemolymph increases rapidly during infection. Their presence in the hemolymph enables the body’s systemic response to infection, while peptides synthesized in epithelial cells participate in local reactions involving the gates of infection. With over a million described species, insects make up the largest class of organisms in the world. Insects show adaptability to repeated changes and resistance to a wide range of pathogens. The mechanism of resistance developed by insects is associated with an immune system based solely on the innate immune response, which allows for a quick and broad response to attacking organisms. Insect antimicrobial peptides (AMPs) have been increasingly used in pharmacy as well as in agriculture. With a growing number of identified peptides that can inhibit human pathogens, insect AMPs are of great interest for biomedical applications. Insect AMPs represent a highly promising alternative to overcome medical problems associated with antibiotic resistance.
  • 706
  • 05 Jul 2023
Topic Review
Perivascular Adipose Tissue-Derived Extracellular Vesicle Exosomes
Perivascular adipose tissue (PVAT)-derived extracellular vesicles (EVs) with small exosome(s) (PVAT-dEVexos) from the descending aorta are capable of entering capillaries and systemic circulation. These PVAT-dEVexos are delivered to the central nervous system (CNS) in preclinical, obese, insulin and leptin resistant, diabetic, db/db mouse models and humans with T2DM. Once within the CNS, these exosomes are capable of traversing the blood–brain barrier and the blood-cerebrospinal fluid barrier resulting in activation of the neuroglia microglia cell(s) (aMGCs) and the formation of reactive astrocytes (rACs). The chronic peripheral inflammation in the PVAT via crown-like structures consists of activated macrophages and mast cells, which harbor peripheral adipokines, cytokines, and chemokines (pCC) in addition to the EV exosomes. 
  • 705
  • 14 Nov 2022
Topic Review
Non-Coding RNA in Non-Alcoholic Fatty Liver Disease
Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, mRNA stabilization and translation, and the regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. 
  • 705
  • 23 Feb 2024
Topic Review
ATGs Involved in Plant Immunity and NPR1 Metabolism
Autophagy is an important pathway of degrading excess and abnormal proteins and organelles through their engulfment into autophagosomes that subsequently fuse with the vacuole. Autophagy-related genes (ATGs) are essential for the formation of autophagosomes. To date, about 35 ATGs have been identified in Arabidopsis, which are involved in the occurrence and regulation of autophagy. Among these, 17 proteins are related to resistance against plant pathogens. The transcription coactivator non-expressor of pathogenesis-related genes 1 (NPR1) is involved in innate immunity and acquired resistance in plants, which regulates most salicylic acid (SA)-responsive genes.
  • 704
  • 29 Nov 2021
Topic Review
Epigenetic Mechanisms in Hematologic Aging and Premalignant Conditions
Hematopoietic stem cells (HSCs) are essential for maintaining overall health by continuously generating blood cells throughout an individual’s lifespan. However, as individuals age, the hematopoietic system undergoes significant functional decline, rendering them more susceptible to age-related diseases. Growing research evidence has highlighted the critical role of epigenetic regulation in this age-associated decline. 
  • 703
  • 19 Jan 2024
Topic Review
Quercetin Induse Aggrephagy
Tartary buckwheat is used as an ingredient in flour and tea, as well as in traditional Chinese medicine for its antioxidant effects. Here, we found that an ethanol extract of tartary buckwheat (TBE) potently induced autophagy flux in HeLa cells by suppressing mTORC1 activity, as revealed by dephosphorylation of the mTORC1 substrates Ulk1, S6K, and 4EBP, as well as by the nuclear translocation of transcriptional factor EB. In addition to non-selective bulk autophagy, TBE also induced aggrephagy, which is defined as autophagy against aggregated proteins. Quercetin is a flavonol found at high levels in TBE. 
  • 702
  • 24 Aug 2021
Topic Review
Allograft Inflammatory Factor-1 in Metazoans
Allograft inflammatory factor-1 (AIF-1) is a calcium-binding scaffold/adaptor protein often associated with inflammatory diseases. Originally cloned from active macrophages in humans and rats, this gene has also been identified in other vertebrates and in several invertebrate species. Among metazoans, AIF-1 protein sequences remain relatively highly conserved. Generally, the highest expression levels of AIF-1 are observed in immunocytes, suggesting that it plays a key role in immunity. In mammals, the expression of AIF-1 has been reported in different cell types such as activated macrophages, microglial cells, and dendritic cells. Its main immunomodulatory role during the inflammatory response has been highlighted. Among invertebrates, AIF-1 is involved in innate immunity, being in many cases upregulated in response to biotic and physical challenges. AIF-1 transcripts result ubiquitously expressed in all examined tissues from invertebrates, suggesting its participation in a variety of biological processes, but its role remains largely unknown. 
  • 701
  • 17 May 2021
Topic Review
Bacteria-Mediated Modulatory Strategies for Colorectal Cancer Treatment
Colorectal cancer (CRC) is one of the most common tumors worldwide, with a higher rate of distant metastases than other malignancies and with regular occurrence of drug resistance. Therefore, scientists are forced to further develop novel and innovative therapeutic treatment strategies, whereby it has been discovered microorganisms, albeit linked to CRC pathogenesis, are able to act as highly selective CRC treatment agents. Consequently, researchers are increasingly focusing on bacteriotherapy as a novel therapeutic strategy with less or no side effects compared to standard cancer treatment methods. With multiple successful trials making use of various bacteria-associated mechanisms, bacteriotherapy in cancer treatment is on its way to become a promising tool in CRC targeting therapy.
  • 701
  • 25 Apr 2022
Topic Review
Nanomedicine for Targeted Endothelium Treatments
The term nanomedicine indicates a specific targeted treatment, which can enhance the delivery of targeted drugs and their bioavailability, as well as reduce the associated toxicity or side-effects and costs, using nanoparticles (NPs). Thus, they constitute specialized carriers with the potential to facilitate the delivery of drugs and efficient molecular targets into desired tissues, such as the endothelium.
  • 701
  • 15 Jul 2022
Topic Review
Metformin and Breast Cancer
Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast cancer, in an individual. In this regard, metformin (1, 1-dimethylbiguanide), well known as ‘Glucophage’ among diabetics, was reported to be cancer preventive while also being a potent anti-proliferative and anti-cancer agent. While meta-analysis studies reported a lower risk and incidence of breast cancer among diabetic individuals on a metformin treatment regimen, several in vitro, pre-clinical, and clinical studies reported the efficacy of using metformin individually as an anti-cancer/anti-tumor agent or in combination with chemotherapeutic drugs or radiation in the treatment of different forms of breast cancer. 
  • 700
  • 26 Jul 2021
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