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Topic Review
Modulation of the Nrf2 pathways
The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that acts through antioxidant-responsive elements (ARE) in the promoter region of deoxyribonucleic acid (DNA) and it transcriptionally promotes the expression of Phase 2 metabolism/antioxidant enzymes, such as glutathione S-transferase (GST), nicotinamide adenine dinucleotide (phosphate)  (NAD(P)H) quinone oxidoreductase-1 (NQO-1), and heme oxygenase-1 (HO-1).  The Nrf2-mediated pathway is now recognized to occupy a central position in cell defense mechanisms. Here, we discuss the historical discovery of Nrf2 and the regulatory mechanism of the Nrf2-mediated pathway, focusing on the interacting proteins and post-translational modifications. 
  • 2.3K
  • 05 Sep 2020
Topic Review
Exercise and Cartilage Regeneration Therapy
In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-β.
  • 2.3K
  • 28 Jan 2021
Topic Review
High-density lipoprotein in skin diseases
From an evolutionary perspective, lipoproteins are not only lipid transporters, but they also have important functions in many aspects of immunity. High-density lipoprotein (HDL) particles are the most abundant lipoproteins and the most heterogeneous in terms of their composition, structure, and biological functions. Despite strong evidence that HDL potently influences the activity of several immune cells, the role of HDL in skin diseases is poorly understood. Alterations in HDL-cholesterol levels have been observed in atopic dermatitis (eczema), psoriasis, urticaria, and angioedema. HDL-associated apolipoprotein (apo) A-I, apoA-IV, and apoC-III, and lyso-phosphatidylcholines potently suppress immune cell effector responses. Interestingly, recent studies provided evidence that skin diseases significantly affect HDL composition, metabolism, and function, which, in turn, could have a significant impact on disease progression, but may also affect the risk of cardiovascular disease and infections. Interestingly, not only a loss in function, but also, sometimes, a gain in function of certain HDL properties is observed.
  • 2.3K
  • 15 Dec 2020
Topic Review
Ferritin
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. Plasma ferritin is also an indirect marker of the total amount of iron stored in the body; hence, serum ferritin is used as a diagnostic test for iron-deficiency anemia. Aggregated ferritin transforms into a toxic form of iron called hemosiderin. Ferritin is a globular protein complex consisting of 24 protein subunits forming a hollow nanocage with multiple metal–protein interactions. Ferritin that is not combined with iron is called apoferritin.
  • 2.3K
  • 14 Oct 2022
Topic Review
GPCRs Regulate DNA Integrity
G protein-coupled receptors (GPCRs) and their associated signaling proteins represent one of the most diverse cellular signaling systems involved in both physiological and pathophysiological processes. Aging represents perhaps the most complex biological process in humans and involves a progressive degradation of systemic integrity and physiological resilience. This is in part mediated by age-related aberrations in energy metabolism, mitochondrial function, protein folding and sorting, inflammatory activity, signal transduction fidelity and genomic stability. An increased rate of unrepaired DNA damage is considered to be one of the key ‘hallmarks’ of aging. Over the last two decades our appreciation of the complexity of GPCR signaling systems has expanded their functional signaling repertoire. One such example of this is the incipient role of GPCRs and GPCR-interacting proteins in DNA damage and repair (DDR) mechanisms. Emerging data now suggest that GPCRs could function as stress sensors for intracellular damage such as oxidative stress. Given this role of GPCRs in the DNA damage response process, coupled to the effective history of drug targeting of these receptors, this suggests that one important future activity of GPCR therapeutics is the rational control of DNA damage repair systems.
  • 2.3K
  • 30 Apr 2021
Topic Review
Intracellular Organelles
Viruses have evolved different strategies to hijack subcellular organelles during their life cycle to produce robust infectious progeny. Successful viral reproduction requires the precise assembly of progeny virions from viral genomes, structural proteins, and membrane components. Such spatial and temporal separation of assembly reactions depends on accurate coordination among intracellular compartmentalization in multiple organelles. Virus trigger the rearrangement and morphology remodeling of intracellular organelles, including the quality control of intracellular organelles, the hijacking of the modified organelle membranes, morphology remodeling for viral replication, and degradation of intracellular organelles by virus-triggered selective autophagy.
  • 2.3K
  • 27 Oct 2020
Topic Review
CRISPR Therapeutics
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) genome editing system has been the focus of intense research in the last decade due to its superior ability to desirably target and edit DNA sequences. The applicability of the CRISPR-Cas system to in vivo genome editing has acquired substantial credit for a future in vivo gene-based therapeutic. Challenges such as targeting the wrong tissue, undesirable genetic mutations, or immunogenic responses, need to be tackled before CRISPR-Cas systems can be translated for clinical use. Hence, there is an evident gap in the field for a strategy to enhance the specificity of delivery of CRISPR-Cas gene editing systems for in vivo applications. Current approaches using viral vectors do not address these main challenges and, therefore, strategies to develop non-viral delivery systems are being explored. Peptide-based systems represent an attractive approach to developing gene-based therapeutics due to their specificity of targeting, scale-up potential, lack of an immunogenic response and resistance to proteolysis. In this review, we discuss the most recent efforts towards novel non-viral delivery systems, focusing on strategies and mechanisms of peptide-based delivery systems, that can specifically deliver CRISPR components to different cell types for therapeutic and research purposes.
  • 2.3K
  • 12 Oct 2020
Topic Review
Molecular Aspects of Thyroid Calcification
In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots ≤ 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications > 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.
  • 2.3K
  • 02 Dec 2020
Topic Review
UV Radiation in DNA Damage and Repair
Prolonged exposure to ultraviolet radiation on human skin can lead to mutations in DNA, photoaging, suppression of the immune system, and other damage up to skin cancer (melanoma, basal cell, and squamous cell carcinoma).
  • 2.3K
  • 27 Dec 2021
Topic Review
Adaptive Response to Environmental Stress
Exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposures; this adapative situation is referred as ‘hormesis’. Environmental, physical and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair- and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions studies as examplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposures doses to environmental stressors, having benefit for the maintenance of healthy status.
  • 2.2K
  • 26 Oct 2020
Topic Review
Trans-Fatty Acids
Naturally occurring (fatty acids) FAs usually have the cis-configuration. Nevertheless, under certain conditions (e.g. partial catalytic hydrogenation or enzymatic hydrogenation), a double bond in FAs may change from a cis (Z) to a trans (E) configuration (geometric isomerization) and/or move to other positions in the carbon chain (positional isomerization). TFAs mediate increase of LDL levels and decrease of HDL levels in blood, which may lead to health consequences (e.g. cardiovascular diseases), even if this association is unclear considering the small proportion (about 10%) of cholesterol participating in atherosclerosis, re-questioning the interest of statins in this context. However, awareness is strongly suggested about industrial hydrogenation  and   subsequently possible  excessive consumption of deleterious TFAs.
  • 2.2K
  • 28 Dec 2020
Topic Review
Niacin
Niacin (also known as “vitamin B3” or “vitamin PP”) includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
  • 2.2K
  • 17 Feb 2022
Topic Review
Natural Compounds and Autophagy Modulation
Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancies. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects.
  • 2.2K
  • 30 Nov 2020
Topic Review
Marine bromophenols, synthesis, biological effects
The first two marine BPs were isolated from the red algae Rhodomela larix.  Bromophenol´s (BPs) have been isolated from red, brown and green algea, ascadians, mussels, marine proteobacteria and sponges.  BPs are common marine secondary metabolites. BPs have been found to have many beneficial health properties. The synthetic efforts have been concentrated on making more of isolated compounds, but also on improving the structures to obtain better biological effects.  In that respect, it is of course useful to analyze the effects of already known compounds.  It seems like the number of hydroxyl groups is an important factor and so is conjugation for anti-oxidant and anti-radical activity.  Conjugation can be caused by nitro, acetyl or aldehyde groups preferentially in para-position to the OH-group.  On the other hand, bromination does not always seem to be a determining factor.  
  • 2.2K
  • 27 Sep 2020
Topic Review
Organelle-Targeted Fluorescent Probes
Fluorescent chemical probes have been extensively used to study biochemical events within live cells. The advent of super-resolution imaging techniques and the availability of a wide variety of fluorescent probes enable effective subcellular tracking of transient metabolites and signaling molecules that are involved in important physiological processes. Probes targeting specific organelles such as mitochondria and lysosomes have been used routinely to monitor organelle functions and have become invaluable tools for the investigation of disease-relevant pathways. These probes efficiently target subcellular organelles; however, considering the complexity and diversity of biochemical processes inside the cells, probes that are not only specific to target organelles but also tailored to applications are highly desirable. 
  • 2.2K
  • 18 Jan 2021
Topic Review
Antioxidant Properties of Ascorbic Acid
Ascorbic acid, commonly known as vitamin C, is one of the basic and best-known compounds necessary for the proper functioning of the human body. Ascorbic acid, as a one of the basic exogenous vitamins, occurs in the body in the form of ascorbate, known for its strong antioxidant and anti-inflammatory properties.
  • 2.2K
  • 18 Oct 2022
Topic Review
Whey Proteins and Its Derivatives
Milk whey proteins are one of the most valued constituents due to their nutritional and techno-functional attributes. Whey proteins are rich in bioactive peptides, possessing bioactive properties such as being antioxidant and antihypertensive as well as having antimicrobial activities, which, when ingested, confers several health benefits. These peptides have the potential to be used as an active food ingredient in the production of functional foods. In addition to their bioactivities, whey proteins are known to possess enhanced functional attributes that allow them to be utilized in broad applications, such as an encapsulating agent or carrier materials to entrap bioactive compounds, emulsification, and in edible and active packaging.
  • 2.1K
  • 11 Dec 2020
Topic Review
Implication of P38 MAPK in drugs of abuse and stress
p38 mitogen-activated protein kinases (MAPKs) are key signaling molecules in cellular responses to external stresses and regulation of pro-inflammatory cytokines. Some studies have suggested that p38 MAPK in the region of the nucleus accumbens is involved in abnormal behavioral responses induced by drugs of abuse. In this entry, we recapitulate the role of the p38 MAPK in the rewarding effects of drugs of abuse. We also summarize the implication of p38 MAPK in stress, anxiety, and depression. We opine that p38 MAPK activation is more closely associated to stress-induced aversive responses rather than drug effects per se, in particular cocaine. p38 MAPK is only involved in cocaine reward, predominantly when promoted by stress. Downstream substrates of p38 that may contribute to the p38 MAPK associated-behavioral responses are proposed. Finally, we suggest p38 MAPK inhibitors as possible therapeutic interventions against stress-related disorders by potentially increasing resilience against stress and addiction relapse induced by adverse experiences.
  • 2.1K
  • 15 Jul 2020
Topic Review
P62
P62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional protein, p62 falls into the category of those factors that can exert opposite roles in the cells. Chronic p62 accumulation was found in many types of tumors as well as in stress granules present in different forms of neurodegenerative diseases. However, the protein seems to have a Janus behaviour since it may also serve protective functions against tumorigenesis or neurodegeneration. 
  • 2.1K
  • 04 Aug 2020
Topic Review
Role of Granulosa and Theca Cells in PCOS
Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive and there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors.
  • 2.1K
  • 16 Jan 2023
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