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Topic Review
CYP3A in Health and Disease
CYP3A is an enzyme subfamily in the cytochrome P450 (CYP) superfamily and includes isoforms CYP3A4, CYP3A5, CYP3A7, and CYP3A43. CYP3A enzymes are indiscriminate toward substrates and are unique in that these enzymes metabolize both endogenous compounds and diverse xenobiotics. Constitutive regulation of CYP3A4 transcription, both positive and negative, is mediated by hepatocyte nuclear factor 4α (HNF4α) and other hepatic transcription factors. CYP3A4 expression is modulated by various mechanisms involving nuclear receptors, hormones, xenobiotics, and signaling molecules. CYP3A4 is regulated by a large number of xenobiotics, including many drugs, endogenous compounds, and many hormones, such as triiodothyronine, dexamethasone, and growth hormone. Xenobiotic- and endobiotic-mediated CYP3A4 induction is indirect and entails activation of such ligand-dependent nuclear receptors as PXR, CAR, VDR, glucocorticoid receptor (GR) α, estrogen receptor (ER) α, bile acid receptor (farnesoid X receptor; FXR), oxysterol receptor (liver X receptor; LXR), and peroxisome proliferator-activated receptor alpha (PPARα) as well as by binding to the three major cis-acting modules: CLEM4, distal XREM, and prPXRE.
  • 839
  • 14 Nov 2022
Topic Review
Epigenomic Dysregulation in Schizophrenia
       Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have been implicated in disease development and neuropathology, such as maternal immune infection, obstetric complications, childhood trauma and cannabis exposure. It is postulated that epigenetic factors, as well as regulatory non-coding RNAs, mediate the effects of these environmental stressors. In this review, we explore the most well-known epigenetic marks, including DNA methylation and histone modification, along with emerging RNA mediators of epigenomic state, including miRNAs and lncRNAs, and discuss their collective potential for involvement in the pathophysiology of schizophrenia implicated through the postmortem analysis of brain tissue. Given that peripheral tissues, such as blood, saliva, and olfactory epithelium have the same genetic composition and are exposed to many of the same environmental exposures, we also examine some studies supporting the application of peripheral tissues for epigenomic biomarker discovery in schizophrenia. Finally, we provide some perspective on how these biomarkers may be utilised to capture a signature of past events that informs future treatment.
  • 838
  • 27 Aug 2020
Topic Review
Ovarian Cancer Peritoneal Metastasis: Exosomes and Mesothelial-to-Mesenchymal Transition
Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.
  • 838
  • 11 Nov 2021
Topic Review
Mechanisms of α-Syn Aggregation In Vitro
The aggregation of proteins into amyloid fibers is linked to more than forty still incurable cellular and neurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy, Alzheimer’s disease and type 2 diabetes, among others. The process of amyloid formation is a main feature of cell degeneration and disease pathogenesis. Despite being methodologically challenging, a complete understanding of the molecular mechanism of aggregation, especially in the early stages, is essential to find new biological targets for innovative therapies. Here, chemical and biophysical methodologies that provided insights on Alpha-synuclein aggregation that would help to investigate other less-known aggregation-prone peptides and proteins were presented.
  • 838
  • 03 Jan 2023
Topic Review
Flavonoids in Cardiovascular Diseases
Flavonoids are metabolites of plants and fungus. Flavonoid research has been paid special attention to in recent times after the observation of their beneficial effects on the cardiovascular system. These favorable effects are exerted by flavonoids mainly due to their antioxidant properties, which result from the ability to decrease the oxidation of low-density lipoproteins, thus improving the lipid profiles. The other positive effect exerted on the cardiovascular system is the ability of flavonoids to produce vasodilation and regulate the apoptotic processes in the endothelium. Researchers suggested that these effects, including their anti-inflammatory function, are consequences of flavonoids’ potent antioxidant properties, but recent studies have shown multiple signaling pathways linked to them, thus suggesting that there are more mechanisms involved in the beneficial effect of the flavonoids on the human body. This review aims to present the latest data on the classification of these substances, their main mechanisms of action in the human body, and the beneficial effects on the physiological and pathological status of the cardiovascular system. 
  • 837
  • 10 Oct 2020
Topic Review
DNA Manipulation and Single-Molecule Imaging
DNA replication, repair, and recombination in the cell play a significant role in the regulation of the inheritance, maintenance, and transfer of genetic information. To elucidate the biomolecular mechanism in the cell, some molecular models of DNA replication, repair, and recombination have been proposed. These biological studies have been conducted using bulk assays, such as gel electrophoresis. Because in bulk assays, several millions of biomolecules are subjected to analysis, the results of the biological analysis only reveal the average behavior of a large number of biomolecules. Therefore, revealing the elementary biological processes of a protein acting on DNA (e.g., the binding of protein to DNA, DNA synthesis, the pause of DNA synthesis, and the release of protein from DNA) is difficult. Single-molecule imaging allows the analysis of the dynamic behaviors of individual biomolecules that are hidden during bulk experiments. Thus, the methods for single-molecule imaging have provided new insights into almost all of the aspects of the elementary processes of DNA replication, repair, and recombination. However, in an aqueous solution, DNA molecules are in a randomly coiled state. Thus, the manipulation of the physical form of the single DNA molecules is important. 
  • 837
  • 01 Apr 2021
Topic Review
MicroRNA-21 in Cancer
MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in regulating gene expression at a posttranscriptional level. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers, such as glioblastoma, pancreatic adenocarcinoma, non-small cell lung cancer, and many others. MiR-21 targets many vital components in a wide range of cancers and acts on various cellular processes ranging from cancer stemness to cell death. Expression of miR-21 is elevated within cancer tissues and circulating miR-21 is readily detectable in biofluids, making it valuable as a cancer biomarker with significant potential for use in diagnosis and prognosis.
  • 837
  • 21 Sep 2022
Topic Review
Recombinant Anticancer Peptides
Cationic peptides have high aptitudes to interact with cancer cells, especially multidrug resistance (MDR) cells. This interaction occurs due to the more negative charge of the membrane of cancer cells compared to normal cells. Recent studies have shown the application of cationic peptides in cancer therapy minimized the side effects of chemotherapy on normal cells. The main limitation of developing the cationic peptides for practical applications is the high cost of automated chemical production. For that reason, it is important to develop a cost-effective method for the production of mass quantities of biologically active peptides.
  • 836
  • 29 Oct 2020
Topic Review
Klotho
Klotho was initially introduced as an antiaging molecule. Klotho deficiency significantly reduces lifespan, and its overexpression extends it and protects against various pathological phenotypes, especially renal disease. It was shown to regulate phosphate and calcium metabolism, protect against oxidative stress, downregulate apoptosis, and have antiinflammatory and antifibrotic properties.
  • 836
  • 05 Mar 2021
Topic Review
ZMYND8
Zinc finger myeloid, nervy, and deformed epidermal autoregulatory factor 1-type containing 8 (Zinc finger MYND-type containing 8, ZMYND8) is a transcription factor, a histone H3-interacting protein, and a putative chromatin reader/effector that plays an essential role in regulating transcription during normal cellular growth. Mutations and altered expression of ZMYND8 are associated with the development and progression of cancer. Increased expression of ZMYND8 is linked to breast, prostate, colorectal, and cervical cancers. It exerts pro-oncogenic effects in breast and prostate cancers, and it promotes angiogenesis in zebrafish, as well as in breast and prostate cancers. In contrast, downregulation of ZMYND8 is also reported in breast, prostate, and nasopharyngeal cancers. ZMYND8 acts as a tumor suppressor in breast and prostate cancers, and it inhibits tumor growth by promoting differentiation; inhibiting proliferation, cell-cycle progression, invasiveness, and metastasis; and maintaining the epithelial phenotype in various types of cancers. These data together suggest that ZMYND8 is important in tumorigenesis; however, the existing data are contradictory. More studies are necessary to clarify the exact role of ZMYND8 in tumorigenesis. In the future, regulation of expression/activity of ZMYND8 and/or its binding partners may become useful in treating cancer.
  • 836
  • 10 Mar 2021
Topic Review
Age-Related Lysosomal Dysfunctions
Aging is a process associated with the detriment of normal physiological functions, which leads to the manifestation of diverse diseases such as cardiovascular and neurodegenerative diseases, joint degenerative diseases, and metabolic diseases such as diabetes, among others. Lysosomes are heterogeneous organelles enclosed by a lipid bilayer and filled with hydrolytic enzymes. The lysosomes are traditionally described as the subcellular structures where the degradation of other organelles and macromolecules takes place, a fundamental process for maintaining cellular proteostasis. There are several degradation processes in which the lysosomes are involved. If the substrate reaching the lysosomes comes from the extracellular environment, the degradation process is called endocytosis. If the material to be digested comes from the cell itself, the process is classified as autophagy. The lysosomes are also involved in plasma membrane repair through a mechanism called lysosomal exocytosis.  During aging, damage in cellular organelles disbalances the cellular homeostatic processes. Lysosomal dysfunction is emerging as an important factor that could regulate the production of inflammatory molecules, metabolic cellular state, or mitochondrial function. Thus, lysosomal alkalinization, amino acid storage, iron disturbances and lipofuscin accummulation are characteristic features of the lysosome during aging. 
  • 836
  • 30 Jul 2022
Topic Review
Peptide Hormones and Adipose Tissue
Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue.
  • 836
  • 06 Jun 2021
Topic Review
Dermatan Sulfate in Tissue Development
The crucial roles of dermatan sulfate (DS) have been demonstrated in tissue development of the cutis, blood vessels, and bone through construction of the extracellular matrix and cell signaling. DS classically exerts physiological functions via interaction with collagens, growth factors, and heparin cofactor-II.
  • 835
  • 14 Jul 2022
Topic Review
Bioluminescence Imaging
Bioluminescence imaging (BLI) is based on the catalytic activity of luciferase enzymes, which oxidize the substrate called luciferin to generate an excited-state molecule that emits bioluminescence.
  • 834
  • 12 Oct 2020
Topic Review
Bioactivities and Chemical Analysis of Ailanthus altissima(Mill.) Swingle
Many species of the so-called exotic plants coexist with native species in a balanced way, but others thrive very quickly and escape human control, becoming harmful—these are called invasive alien species. In addition to overcoming geographic barriers, these species can defeat biotic and abiotic barriers, maintaining stable populations. Ailanthus altissima is no exception; it is disseminated worldwide and is considered high risk due to its easy propagation and resistance to external environmental factors. Currently, it has no particular use other than ornamental, even though it is used to treat epilepsy, diarrhea, asthma, ophthalmic diseases, and seborrhoea in Chinese medicine. Considering its rich composition in alkaloids, terpenoids, sterols, and flavonoids, doubtlessly, its use in medicine or other fields can be maximised.
  • 834
  • 17 Dec 2021
Topic Review
Targeting Tyrosine Kinases in ccRCC
Clear cell renal cell carcinoma (ccRCC) is the seventh most frequently diagnosed tumor in adults in Europe and represents approximately 2.5% of cancer deaths. Currently, there are multiple therapeutic drugs available for advanced disease, including therapies against VEGFR with successful results in patients´ survival. Other tyrosine kinases’ pathways, including PDGFR, Axl or MET have emerged as key signaling pathways involved in RCC biology. 
  • 834
  • 08 Jun 2021
Topic Review
Oxidative-Stress Modulators in Hematological Malignancies
Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies.
  • 833
  • 17 Jan 2021
Topic Review
Bile Salt Hydrolases
Bile salt hydrolase (BSH; EC 3.5.1.24) is an enzyme produced by the intestinal microbiota that catalyzes the hydrolysis of amide bonds in conjugated BAs, resulting in the release of free amino acids. These enzymes belong to the N-terminal nucleophilic (Ntn) hydrolase superfamily and share a similar αββα-core structure to an N-terminal catalytic cysteine residue. This residue is critical to the catalysis mechanism and acts both as a nucleophile and a proton donor. The N-terminal amino group serves as the proton acceptor and activates the nucleophilic thiol group of the cysteine side chain. Besides the cysteine residue, other amino acids conserved in most BSHs are also relevant to the catalytic reaction, including Arg18, Asp21, Asn82, Asn175, and Arg228.
  • 831
  • 27 May 2021
Topic Review
Human Amnion-Derived Stem Cells
Human amnion-derived stem cells (hADSCs) are referred as the cells of possessing the abilities of self-renew and differentiation, which are isolated from human amnion and include human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs).
  • 830
  • 28 Sep 2021
Topic Review
Potential Biochemical Properties and Genetics of C-Reactive Protein
C-Reactive Protein (CRP) is supposed to be an accredited benchmark for physicians, to reveal or rule out inflammation, and multifarious scientific endeavors have been made so as to detect the direct pleiotropic functions of this protein. The use of CRP as the most important and critical immunochemical marker of several medical conditions, including infections such as sepsis, physiological organ diseases, various autoimmune disorders, malignancies and other health conditions, has become widely popular.
  • 830
  • 14 Nov 2023
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