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Topic Review
Oleanolic Acid as Modulators of Metabolic Nuclear Receptors
Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury.
  • 757
  • 25 Oct 2023
Topic Review
Bisphenol A and Obesity
Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 μg/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression.
  • 756
  • 17 Dec 2020
Topic Review
Human Cell Models of Disease
Neurological disorders, including neurodegenerative diseases, are collectively a major cause of death and disability worldwide. Altered mitochondrial function has been implicated in nearly all of these diseases. A variety of cultured cell models have been used to study these diseases including lymphocyte cells immortalized with Epstein Barr Virus. These cell models have been useful in deciphering the role of the mitochondria in these disorders.
  • 756
  • 13 May 2021
Topic Review
PPARs and Mycobacterial Infection
The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet accumulation to build the cellular environment essential for their intracellular survival. Thus, lipids are thought to be important for mycobacteria survival as well as for the invasion, parasitization, and proliferation within host cells. However, their physiological roles have not been fully elucidated. Recent studies have revealed that mycobacteria modulate the peroxisome proliferator-activated receptor (PPAR) signaling and utilize host-derived triacylglycerol (TAG) and cholesterol as both nutrient sources and evasion from the host immune system.
  • 756
  • 30 Jul 2021
Topic Review
Circadian Clock Gene Polymorphisms and Metabolic Syndrome
Metabolic syndrome is a cluster of cardio-metabolic risk factors and comorbidities, including central obesity, hypertension, hyperglycemia, and dyslipidemia. In addition, different studies have shown that the disturbances in circadian rhythm are connected with components of metabolic syndrome. Circadian rhythm is the central regulator of every aspect of human health and metabolism, and metabolic homeostasis is essential in regulating energy metabolism, especially in adipose tissue. 
  • 756
  • 10 Jan 2022
Topic Review
SHED-Dependent Oncogenic Signaling of the PEAK3 Pseudo-Kinase
The human kinome is composed of about 50 pseudo-kinases with unclear function, because they are predicted to be catalytically inactive; however, they are shown to play an important role in cancer, similar to active kinases. Understanding how these pseudo-kinases promote tumor formation despite their catalytic inactivity is a great challenge, which may lead to innovative anti-cancer therapies. The PEAK1 and 2 pseudo-kinases have emerged as important components of the protein tyrosine kinase pathway implicated in cancer progression. They can signal using a scaffolding mechanism via a conserved split helical dimerization (SHED) module.
  • 755
  • 11 Jan 2022
Topic Review
Monoclonal Antibodies: Structure and Function
Monoclonal antibodies are among the most effective tools for detecting tumor-associated antigens. The U.S. Food and Drug Administration (FDA) has approved more than 36 therapeutic antibodies for developing novel alternative therapies that have significant success rates in fighting cancer. 
  • 755
  • 29 Jun 2023
Topic Review
Voltage-Gated Calcium Channels for the Treatment of Pain
The voltage-gated calcium channels (VGCCs) are classified in low- (T-type or Cav3) or high-voltage activation (L or Cav1, N, P/Q, and R-type or Cav2). They can be further subclassified by structural similarities (channel-forming α1-subunit) where L-(Cav1.1, Cav1.2, Cav1.3, and Cav1.4), P/Q-(Cav2.1), N-(Cav2.2), and R-(Cav2.3) channels form heteromultimers (along with auxiliary β-, α2δ, and γ-subunits) and T-type (Cav3.1, Cav3.2, and Cav3.3) channels, which are α1-subunit monomers. Pain perception is a sensory and emotionally unpleasant experience; moreover, it represents a huge personal, medical, and economic burden that pharmacotherapy targeting brain pathways is now being researched for and developed in the medical field. Obviously, acute pain does not carry the load of chronic pain that is conceived as a disease on its own and as secondary to an underlying disease (like a symptom). Chronic pain is related to neuronal adaptations and is high risk for psychological distress and sleep deprivation, among other consequences impairing the quality of life. 
  • 755
  • 08 Jun 2023
Topic Review
Metabolic Diseases and Exercise Effects on Platelets
Chronic disorders are strongly linked to cardiovascular (CV) diseases, and it is unanimously accepted that regular exercise training is a key tool to improving CV risk factors, including diabetes, dyslipidemia, and obesity. Increased oxidative stress due to an imbalance between reactive oxygen species production and their scavenging by endogenous antioxidant capacity is the common ground among these metabolic disorders, and each of them affects platelet function. Habitual physical exercise triggers important mechanisms related to the exercise benefits for health improvement and protects against CV events. Platelets play an important role in many physiological and pathophysiological processes, including the development of arterial thrombosis, and physical (in)activity has been shown to interfere with platelet function. Although data reported by studies carried out on this topic show discrepancies, knowledge on platelet function affected by exercise mainly depends on the type of applied exercise intensity and whether acute or habitual, strenuous or moderate, thus suggesting that physical activity and exercise intensity may interfere with platelet function differently. 
  • 754
  • 30 Aug 2023
Topic Review
Biosynthesis of Caffeic Acid Phenethyl Ester
Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders.
  • 754
  • 14 Aug 2023
Topic Review
Metabolism and Epigenetic-Modification in MDSCs
       Myeloid-derived suppressor cells (MDSCs) are major immunosuppressive cells in the tumor microenvironment (TME). During the differentiation and development of MDSCs from myeloid progenitor cells, their functions are also affected by a series of regulatory factors in the TME, such as metabolic reprogramming, epigenetic modification, and cell signaling pathways. And there is a crosstalk between these regulatory factors. In cancer, there are important bidirectional regulatory mechanisms between metabolic remodeling and epigenome. Most chromatin modifying enzymes require cell metabolic intermediates as substrates or cofactors. In turn, epigenetic modifications regulate cell metabolism and function to some extent. The regulation between   metabolism and epigenetic modification of MDSCs can be achieved through signaling pathways related to AMPK and HIF-1α,etc.
  • 753
  • 30 Oct 2020
Topic Review
Ferritins of Sponges
Ferritins comprise a conservative family of proteins found in all species and play an essential role in resistance to redox stress, immune response, and cell differentiation. Sponges (Porifera) are the oldest Metazoa that show unique plasticity and regenerative potential. 
  • 753
  • 26 Aug 2021
Topic Review
Clinical Significance of Angiogenesis Regulating lncRNAs in Cancer
In many cancers the current staging has limitations in terms of determining prognosis. Biomarkers are critical in completing clinical staging and improving the prediction of lymph node metastasis as well as in determining cancer prognosis. Several long noncoding ribonucleic acids (lncRNAs) are over-expressed in various cancer cell lines, as well as in preclinical cancer models and patients. These lncRNAs have been explored for possible clinical application as biomarkers and as targets for therapeutic intervention.
  • 753
  • 01 Aug 2022
Topic Review
Epigenetics in Neurodegenerative Disorders
Neurodegenerative disorders (NDDs) are major health issues in Western countries. Despite significant efforts, no effective therapeutics for NDDs exist. Several drugs that target epigenetic mechanisms (epidrugs) have been recently developed for the treatment of NDDs, and several of these are currently being tested in clinical trials.
  • 753
  • 23 Feb 2023
Topic Review
Structural Characterization of Allergens
Allergens are substances that cause abnormal immune responses and can originate from various sources. IgE-mediated allergies are one of the most common and severe types of allergies, affecting more than 20% of the population in Western countries. Allergens can be subdivided into a limited number of families based on their structure, but this does not necessarily indicate the origin or the route of administration of the allergen, nor is the molecular basis of allergenicity clearly understood. 
  • 752
  • 19 Jan 2024
Topic Review
Chromatin Remodeler MORC2 in Cancer
A newly discovered chromatin remodeler, MORC2, is a Microrchidia (MORC) family member. MORC2 acts as a chromatin remodeler by binding to the DNA and changing chromatin conformation using its ATPase domain. MORC2 is highly expressed in a variety of human cancers. It controls diverse signaling pathways essential for cancer development through its target genes and interacting partners.
  • 750
  • 18 Oct 2023
Topic Review
Contribution of Long Non-Coding RNAs in Cancer Development
Long non-coding RNA (lncRNA) is a type of RNA molecule that show striking resemblance to mRNA in terms of synthesis and structure but lacks protein coding capacity. High-throughput RNA-sequencing technologies revealed that they are present in tens of thousands, outnumbering the protein coding genes. Functional investigations reveal that they show highly tissue-, cell type-, and developmental-specific expression and regulate biological processes that control differentiation and development. More importantly, recent evidence suggests that lncRNA are highly dysregulated in cancers and play a crucial role in cancer development and progression through regulating oncogenic and tumor suppressor pathways, cellular metabolism, and the immune response and tumor microenvironment.
  • 750
  • 24 Oct 2022
Topic Review
Genome-Folding Mechanisms in the Tree Domains of Life
Comparative structural/molecular biology by single-molecule analyses combined with single-cell dissection, mass spectroscopy, and biochemical reconstitution have been powerful tools for elucidating the mechanisms underlying genome DNA folding. All genomes in the three domains of life undergo stepwise folding from DNA to 30–40 nm fibers. Major protein players are histone (Eukarya and Archaea), Alba (Archaea), and HU (Bacteria) for fundamental structural units of the genome. In Euryarchaeota, a major archaeal phylum, either histone or HTa (the bacterial HU homolog) were found to wrap DNA. This finding divides archaea into two groups: those that use DNA-wrapping as the fundamental step in genome folding and those that do not. Archaeal transcription factor-like protein TrmBL2 has been suggested to be involved in genome folding and repression of horizontally acquired genes, similar to bacterial H-NS protein. Evolutionarily divergent SMC proteins contribute to the establishment of higher-order structures. Recent results are presented, including the use of Hi-C technology to reveal that archaeal SMC proteins are involved in higher-order genome folding, and the use of single-molecule tracking to reveal the detailed functions of bacterial and eukaryotic SMC proteins. Here, we highlight the similarities and differences in the DNA-folding mechanisms in the three domains of life. 
  • 749
  • 28 Dec 2021
Topic Review
Benzodiazepine Modulation of GABAA Receptors
Benzodiazepines (BZDs) are a class of widely prescribed psychotropic drugs that target GABAA receptors (GABAARs) to tune inhibitory synaptic signaling throughout the central nervous system. Despite knowing their molecular target, the researchers still do not fully understand the mechanism of modulation at the level of the channel protein. Nonetheless, functional studies, together with cryo-EM structures of GABAA(α1)2(βX)2(γ2)1 receptors in complex with BZDs, provide a wealth of information to aid in addressing this gap in knowledge. 
  • 749
  • 15 Dec 2022
Topic Review
Molecular Mechanisms Involved in Systemic Sclerosis-Related Lung Fibrosis
Systemic sclerosis (SSc), or scleroderma, is an autoimmune connective tissue disease with one of the highest mortality rates among the rheumatic diseases. Fibrosis is recognized to be a defining feature of SSc, affecting the skin and multiple visceral organs. As a result, SSc is considered the prototypic fibrosing disease. 
  • 749
  • 21 Feb 2023
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