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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. 
  • 716
  • 08 Jun 2023
Topic Review
Nociceptor–Macrophage Interactions in Apical Periodontitis
Periradicular tissues have a rich supply of peripheral afferent neurons, also known as nociceptive neurons, originating from the trigeminal nerve. While their primary function is to relay pain signals to the brain, these are known to be involved in modulating innate and adaptive immunity by initiating neurogenic inflammation (NI).
  • 714
  • 15 Sep 2023
Topic Review
FGF23 in Diabetes
The incidence of Type 2 diabetes mellitus (T2DM) results from a combination of genetic, environmental, and behavioral risk-factors that include sedentary lifestyle and diet. Related to diet, small elevations in the levels of Pi in blood also constitute a risk factor for the appearance of prediabetes situations, particularly, impaired glucose tolerance and IR, as well as for the development of T2DM. Pi serum range is maintained by diverse hormones that regulate the intestinal uptake, its mobilization from bone, and the renal excretion. Importantly, the pathophysiological repercussions of Pi imbalances also involve to these regulatory factors. Disbalances in phosphataemic regulatory-factors traditionally related to an increase in morbidity are the decrease in calcitriol (the active form of vitamin D) and the increase in parathyroid hormone (PTH) levels. Fibroblast growth factor 23 (FGF23) is considered the main regulator of phosphorus and vitamin D metabolism. FGF23 is secreted from bones, especially by osteoblasts and osteocytes, after phosphate intake and acts primarily on the kidneys to inhibit phosphate reabsorption in urine. FGF23 also inhibits calcitriol renal synthesis and the secretion of PTH in the parathyroid glands.
  • 713
  • 28 Jun 2021
Topic Review
Cellular Functions of Liver Kinase B1
The liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11) and Par-4 in C. elegans, has been identified as a master kinase of AMPKs and AMPK-related kinases. LKB1 plays a crucial role in cell growth, metabolism, polarity, and tumor suppression.
  • 713
  • 12 Oct 2022
Topic Review
Myosins
The eukaryotic cell cytoskeleton is a complex and dynamic network that shapes the cell and that is composed of various cellular proteins, among which the superfamily of actin-based motors proteins, the myosins. Myosins play a key role in many cellular processes such as cell migration, adhesion, intracellular trafficking and internalization processes, making them ideal targets for pathogenic bacteria that used them to hijack cellular pathways and colonize their human host. 
  • 712
  • 19 Jan 2021
Topic Review
Ocular Therapeutics and Molecular Delivery Strategies
Photodynamic therapy (PDT) involves activation of a photosensitizer by photon irradiation that generates reactive oxygen species (ROS) that selectively occlude CNV in the target ocular segment. It has found extensive applications in exudative AMD treatment before the rise of anti-VEGF therapy. Visudyne® is a liposomal formulation of a hydrophobic photosensitizer, Verteporfin that was approved for nAMD administration by the US FDA in 2000.
  • 712
  • 17 Nov 2021
Topic Review
KLK4T2
The human kallikrein-related peptidase 4 (KLK4) and the transcribed pseudogene KLKP1 are reported to be highly expressed in the prostate. When trying to clone transcripts of KLKP1, authors partly failed. Instead, they identified an androgen-regulated transcript, KLK4T2, which appeared to be a splice variant of KLK4 that also contained exons of KLKP1. Expression analysis of KLK4, KLK4T2, and KLKP1 transcripts in prostate cancer cell lines showed high levels of KLKP1 transcripts in the nucleus and in unfractionated cell extract, whereas it was almost completely absent in the cytoplasmatic fraction. This was in contrast to KLK4 and KLK4T2, which displayed high to moderate levels in the cytoplasm. In patient cohorts we found significantly higher expression of both KLK4T2 and KLK4 in benign prostatic hyperplasia compared to both primary prostate cancer and bone metastasis. Analysis of tissue panels demonstrated the highest expression of KLK4T2 in the prostate, but in contrast to the classical KLK4, relatively high levels were also found in placenta. So far, the function of KLK4T2 is still to be explored, but the structure of the translation product indicated that it generates a 17.4 kDa intracellular protein with possible regulatory function.
  • 712
  • 23 Dec 2021
Topic Review
MicroRNAs in Bladder Carcinomas
Bladder cancer (BLCA) is the most malignant disease of the urinary tract with variable metastatic potential. Categorized as muscle invasive (MIBC) or non-invasive (NMIBC), BLCA is the fifth most common cancer worldwide, resulting in substantial morbidity and mortality of affected individuals.
  • 711
  • 26 May 2021
Topic Review
Immunometabolism and Epithelial–Mesenchymal Transition
Epithelial–mesenchymal transition (EMT) and metabolic reprogramming in cancer cells are the key hallmarks of tumor metastasis. Since the relationship between the two has been well studied, researchers have gained increasing interest in the interplay of cancer cell EMT and immune metabolic changes. Whether the mutual influences between them could provide novel explanations for immune surveillance during metastasis is worth understanding.
  • 711
  • 23 Sep 2021
Topic Review
Oestradiol Regulation of Lipid Metabolism in Gynaecological Cancers
Cancer cells undergo metabolic reprogramming to support cell proliferation, growth, and dissemination, a trait now considered a hallmark of cancer. Alterations in lipid metabolism, and specifically, the uptake and synthesis of fatty acids (FAs), constitute one well-documented aspect of this reprogramming. Fatty acids (FAs) are carboxylic acids, consisting of hydrocarbon chains with varying degrees of length, branching and saturation. They act as primary building blocks for lipid species, such as phospholipids, sphingolipids and triglycerides, all of which participate in a wide array of biological processes. In addition to these roles, FAs are also well established as having a critical role in altering gene transcription by regulating the activity of FA-sensitive transcription factors, particularly sterol-regulatory element-binding protein (SREBP) and peroxisome proliferator-activated receptors (PPARs). More recently, dysregulated FA metabolism has been reported and studied in many cancer types, including gynaecological cancers. FA metabolism supports tumorigenesis and cancer progression through a range of processes, including membrane biosynthesis, energy storage and production, and generation of signalling intermediates. Female sex hormones, specifically oestradiol, play a crucial role in regulating FA metabolism and are also implicated in promoting the risk of gynaecological cancers. The increased risk for these cancers and their pathogenesis has been epidemiologically linked to abnormally high levels of serum oestradiol. Emerging evidence indicates aberrant FA metabolism is postulated to be mediated by the action of oestradiol, either directly via their classical, oestrogen receptor (ER)-mediated pathways, or indirectly through the insulin-like growth factor I (IGFI) receptors (IGIFR), with the levels of serum oestradiol and the IGFIR pathway both dysregulated, not only in gynaecological cancers but also in obesity.  However, the mechanisms linking oestradiol to the dysregulation of FA metabolism in these cancer types are still underexplored.
  • 711
  • 12 May 2022
Topic Review
Lipids in SARS-CoV-2 Infection
Being major components of cellular and viral membranes, lipids are undoubtedly involved in viral infections. Membrane/lipid rafts, i.e., cholesterol-rich subdomains of plasma membranes, are crucial elements for membrane fusion and endocytosis.
  • 710
  • 02 Jun 2021
Topic Review
Molecular Techniques Most often Used in Omic
Techniques used in omics have proven to be useful in studying dietary supplements. Techniques used in omics have proven to be useful in studying dietary supplements. In nutrigenomic research, it is necessary to precisely determine the influence of the tested substances on biological processes in the organism at the following levels: transcriptome, genome, proteome, and metabolome. Advanced, high-throughput techniques that generate a massive amount of data must be used to obtain a holistic view of a given subject. 
  • 709
  • 14 Feb 2023
Topic Review
Amyloid Fragmentation and Disaggregation in Yeast and Animals
Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been discovered in fungi. The propagation of fungal prion amyloids requires the chaperone Hsp104, though in excess it can eliminate some prions. Even though Hsp104 acts to disassemble prion fibrils, at normal levels it fragments them into multiple smaller pieces, which ensures prion propagation and accelerates prion conversion. Animals lack Hsp104, but disaggregation is performed by the same complement of chaperones that assist Hsp104 in yeast—Hsp40, Hsp70, and Hsp110. Exogenous Hsp104 can efficiently cooperate with these chaperones in animals and promotes disaggregation, especially of large amyloid aggregates, which indicates its potential as a treatment for amyloid diseases. However, despite the significant effects, Hsp104 and its potentiated variants may be insufficient to fully dissolve amyloid.
  • 708
  • 20 Jan 2022
Topic Review
Polymeric Micelles in Cancer Immunotherapy
Cancer immunotherapies have generated some miracles in the clinic by orchestrating our immune system to combat cancer cells. However, the safety and efficacy concerns of the systemic delivery of these immunostimulatory agents has limited their application. Nanomedicine-based delivery strategies (e.g., liposomes, polymeric nanoparticles, silico, etc.) play an essential role in improving cancer immunotherapies, either by enhancing the anti-tumor immune response, or reducing their systemic adverse effects. The versatility of working with biocompatible polymers helps these polymeric nanoparticles stand out as a key carrier to improve bioavailability and achieve specific delivery at the site of action. 
  • 707
  • 11 May 2021
Topic Review
Nitric Oxide Synthases Inhibitor T1023
A nitric oxide synthase (NOS) inhibitor, compound T1023 induce transient hypoxia and prevent acute radiation syndrome (ARS) in mice. Significant efficacy and safety in radioprotective doses (1/5–1/4 LD10) can prove its ability to prevent complications of tumor radiation therapy (RT).
  • 707
  • 26 Oct 2021
Topic Review
Pleiotropic Signaling by Reactive Oxygen Species
The excessive generation of reactive oxygen species (ROS) plays a pivotal role in the pathogenesis of diseases. ROS are central to cellular redox regulation and act as second messengers to activate redox-sensitive signals. Studies have revealed that certain sources of ROS can be beneficial or harmful to human health. Considering the essential and pleiotropic roles of ROS in basic physiological functions, future therapeutics should be designed to modulate the redox state. Dietary phytochemicals, microbiota, and metabolites derived from them can be expected to be developed as drugs to prevent or treat disorders in the tumor microenvironment.
  • 707
  • 18 May 2023
Topic Review
DispHScan
DispHScan is a web tool designed to predict protein disorder as a function of pH for multiple sequences. This new functionality offers the possibility to conduct pH-dependent disorder analysis at the proteome-wide level that might reveal new insights into the physiological and pathological role of the solution pH in the conformational plasticity of IDPs and assist scientists and industries in identifying optimal pH conditions for proteins of interest. DispHScan is freely available for academic users at: http://disphscan.ppmclab.com/
  • 706
  • 15 Nov 2021
Topic Review
miRNAs in Cancer Treatment
MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process.
  • 706
  • 07 Jul 2023
Topic Review
Highly Expressible Bacteriorhodopsin (HEBR)
Highly expressible bacteriorhodopsin (HEBR) is a light-triggered protein (optogenetic protein) that have seven transmembrane regions with retinal bound as their chromophore to sense light. HEBR has controllable photochemical properties and regulates activity on the proton pumping. Our study indicates that the HEBR protein may inhibit cell proliferation and cell cycle progression of lung cancer cells, reduce their migration activity, and suppress some stem-ness-related genes. These findings also suggest the potential of HEBR protein to regulate the growth and migration of tumor cells, which may offer the possibility for an anticancer drug.
  • 705
  • 29 Mar 2022
Topic Review
Proteasome Allostery
Allostery fundamentally describes coordination and communication between distinct sites of a multipart and multifunctional protein, or riboprotein. The proteasome rivals the ribosome in size, compositional complexity, multiplicity of active sites and substrate interactions and its importance in the cellular economy. For both, the cellular consequences of its misregulation are grave. Like the ribosome, proteasomes must coordinate multiple active sites and undergo large scale conformational realignments that optimally position its components for enzymatic processing and to move substrates. The expectation that proteasomes utilize allostery is supported by two types of experimental data. The first consists of regulators that are substrates or their components. The second consists of RPs that exhibit cooperative binding to the pair of CP sites where they dock.
  • 705
  • 14 Jun 2022
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