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Topic Review
G Protein Coupled Receptor 158
G-protein-coupled receptors (GPCRs) remain one of the most successful targets for therapeutic drugs approved by the US Food and Drug Administration (FDA). Many novel orphan GPCRs have been identified by human genome sequencing and considered as putative targets for refractory diseases. Of note, a series of studies have been carried out involving GPCR 158 (or GPR158) since its identification in 2005, predominantly focusing on the characterization of its roles in the progression of cancer and mental illness. However, advances towards an in-depth understanding of the biological mechanism(s) involved for clinical application of GPR158 are lacking.
  • 742
  • 28 Apr 2022
Topic Review
Polyphenoloxidase (PPO)
Fresh-cut produce are quite popular among consumers due to their eating ease, high quality and functional content. However, some of the processing steps taking place during minimal processing (such as cutting, peeling, draining, etc.) might speed up decay, e.g., microbial growth, dehydration or browning. When it comes to the latter, polyphenol oxidase (PPO) plays an important role, being the center of many works focused on the understanding of its reaction mechanism and the application of conservative techniques. The aim of this review study was to compare recent research about the effect of PPO on minimally processed fruits and vegetables, trying to understand the way it acts, the measurement of its activity and current treatments, such as modified atmosphere packaging, washing treatments or edible coatings, among others. In conclusion, the combination of conservation techniques (that is, hurdle technology) is vital to guarantee global quality in minimally processed fruits and vegetables, including synergistic effects which will allow the use of mild treatment conditions to decrease PPO activity. However, further research is required to clearly understand PPO inhibition in trendy techniques such as irradiation. 
  • 741
  • 10 Sep 2021
Topic Review
Polyphenols Nano Formulations
Polyphenols are phytochemical with potent antioxidant and antiinflammatory activities which are tremendously of important to fight premature aging, infections, cancers and other related chronic inflammatory diseases. Nanoencapsulation of these natural and functional biocompounds is useful to increase the bioavailability and efficiency of polyphenols, which can be further used as adjuvant therapeutics.
  • 739
  • 26 Nov 2020
Topic Review
Signal Transduction by VIP and PACAP Receptors
Homeostasis of the human immune system is regulated by many cellular components, including two neuropeptides, VIP and PACAP, primary stimuli for three class B G protein-coupled receptors, VPAC1, VPAC2, and PAC1. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) regulate intestinal motility and secretion and influence the functioning of the endocrine and immune systems. Inhibition of VIP and PACAP receptors is an emerging concept for new pharmacotherapies for chronic inflammation and cancer, while activation of their receptors provides neuroprotection. Major molecular switches of VPAC1, VPAC2, and PAC1 may act as triggers for receptor activation and compare them with similar non-covalent interactions changing upon activation that were observed for other GPCRs. Interhelical interactions in VIP and PACAP receptors that are important for agonist binding and/or activation provide a molecular basis for the design of novel selective drugs demonstrating anti-inflammatory, anti-cancer, and neuroprotective effects. As to the genetic variants of VIP, PACAP, and their receptors on signalling mediated by endogenous agonists, this sequence diversity resulting from gene splicing has a significant impact on agonist selectivity and potency as well as on the signalling properties of VIP and PACAP receptors. 
  • 739
  • 28 Mar 2022
Topic Review
Cannabis and Cannabinoids for Treatment of Cancer
Cancer is a disease which affects approximately 40% of people in their lifetime. Chemotherapy, the primary choice for treatment of cancer, is often ineffective or/and presents itself with many debilitating side effects, including loss of appetite, nausea, insomnia, and anxiety. Components of cannabis extracts, including cannabinoids and terpenes, may present an alternative for controlling side effects and may be used for tumor shrinkage together with chemodrugs. Cannabinoids act on so called endocannabinoid system (ECS) that operates in human body to maintain homeostasis. ECS promotes healthy development of tissues and regulates many processes in our organism and when disbalanced may lead to disease, including cancer. 
  • 739
  • 25 Oct 2022
Topic Review
Amyloid-β Proteins and Pericytes
This review provides an updated overview of the interaction between Aβ proteins with pericytes, one the most significant and often forgotten cellular components of the BBB and the inner blood retinal barrier (IBRB).
  • 738
  • 24 May 2020
Topic Review
YAP-TEAD Interaction Disruptors
This a entry that comprehensively covers the modalities that act as disruptors of the YAP-TEAD interaction. The transcriptional co-activator YAP (Yes-associated protein) by pairing with the transcription factor TEAD (TEA domain) orchestrates the expression of several oncogenic transcriptional programs. These programs are seen in a proportion of all solid tumors. Therefore, the disruption of YAP-TEAD interaction is proposed as an attractive option to target cancers.
  • 738
  • 11 Jan 2021
Topic Review
Sphingolipids in Central Nervous System
Bioactive lipids are a newly defined class of lipids that are actively involved in the regulation of a variety of cellular events. As the name indicates, these molecular factors are subjected to action at the arrival of a specific stimulus and undergo subsequent transitions to cope up with the insult. Among these bioactive lipids, sphingolipids have emerged as distinctive mediators of various cellular processes, ranging from cell growth and proliferation to cellular apoptosis, executing immune responses to regulating inflammation. Recent studies have made it clear that sphingolipids, their metabolic intermediates (ceramide, sphingosine-1-phosphate, and N-acetyl sphingosine), and enzyme systems (cyclooxygenases, sphingosine kinases, and sphingomyelinase) harbor diverse yet interconnected signaling pathways in the central nervous system (CNS), orchestrate CNS physiological processes, and participate in a plethora of neuroinflammatory and neurodegenerative disorders.
  • 738
  • 05 Aug 2021
Topic Review
Abscisic Acid (ABA)
Abscisic acid (ABA) is a significant regulator of numerous flexible traits of plant developmental improvements, including embryo maturation, germination, seed dormancy, floral initiation, and root growth.
  • 738
  • 25 Aug 2021
Topic Review
m1A RNA Modification in Gene Expression Regulation
N1-methyladenosine (m1A) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of m1A RNA modification in gene regulation and biological processes.
  • 738
  • 01 Jun 2022
Topic Review
Treatments of Hyperuricemia
Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis.
  • 737
  • 01 Sep 2021
Topic Review
FHL2
Four and a half LIM domains 2 (FHL2) was originally described as ‘Down-regulated in Rhabdomyosarcoma LIM protein’ (DRAL) and is composed of LIM domains that are named after their initial discovery in the proteins Lin11, Isl-1 and Mec-3. FHL2 consists of four and a half LIM domains, each composed of two zinc fingers, except the first ‘half’ LIM-domain which has only one. While the structure of the four and a half LIM domains had been uncovered previously using Nuclear Magnetic Resonance (NMR) spectroscopy, the complete FHL2 protein structure is unknown; however, it has recently been predicted using the protein structure neural network AlphaFold.
  • 737
  • 19 Oct 2021
Topic Review
RAB11-Mediated Trafficking and Human Cancers
RAB11 isoforms function as membrane organizers connecting the transport of cargoes towards the plasma membrane with the assembly of autophagic precursors and the generation of cellular protrusions. These processes dramatically impact normal cell physiology and their alteration significantly affects the survival, progression and metastatization as well as the accumulation of toxic materials of cancer cells. 
  • 736
  • 28 Jan 2021
Topic Review
Amsacrine
Amsacrine, an anticancer drug first synthesised in 1970 by Professor Cain and colleagues, showed excellent preclinical activity and underwent clinical trial in 1978 under the auspices of the US National Cancer Institute, showing activity against acute lymphoblastic leukaemia.
  • 736
  • 25 Feb 2021
Topic Review
PARP Inhibitor-Induced Synthetic Lethality
The advanced development of synthetic lethality has opened the doors for specific anti-cancer medications of personalized medicine and efficient therapies against cancers. One of the most popular approaches being investigated is targeting DNA repair pathways as the implementation of the poly-ADP ribose polymerase 1 (PARP) inhibitor (PARPi) into individual or combinational therapeutic schemes. Such treatment has been effectively employed against homologous recombination-defective solid tumors as well as hematopoietic malignancies. In the most common aspect of precision medicine, PARPi triggers synthetic lethality in cancer cells harboring BRCA1/2 mutations/deficiencies. 
  • 736
  • 05 Dec 2022
Topic Review
Polymorphism in α-Synuclein
The synucleinopathies exhibit differences in their clinical and pathological representations, reminiscent of prion disorders. Emerging evidence suggests that α-Syn self-assembles and polymerizes into conformationally diverse polymorphs in vitro and in vivo, similar to prions. These α-Syn polymorphs arising from the same precursor protein may exhibit strain-specific biochemical properties and the ability to induce distinct pathological phenotypes upon their inoculation in animal models.
  • 735
  • 20 Oct 2021
Topic Review
Dystroglycanopathy
Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan. At least 18 causative genes of dystroglycanopathy have been identified, and its clinical symptoms are diverse, ranging from severe congenital to adult-onset limb-girdle types. 
  • 735
  • 12 Jan 2022
Topic Review
Didymo
Didymosphenia geminata diatoms, or Didymo, was first found to be an invasive species that could have negative impacts on the environment due to the aggressive growth of its polysaccharide-based stalks.
  • 735
  • 08 Nov 2021
Topic Review
Extracellular Vesicles in Tumour Microenvironment
The tumour microenvironment (TME) contains cells of different origin, including cancer, immune, endothelial, and stromal cells. In the last decades extracellular vesicles (EV) released by these cells have gained attention as drivers of the TME diversity and tumour behaviour. In the TME, EV can switch tumour growth, immune-escape and metastatic spread or exert anti-tumour activity depending on their cell of origin and cargo. Moreover, since potentially detectable in different biological fluids, EV have been proposed as diagnostic and therapeutic, or “theragnostic” tools. Specifically, EV cargo has been considered a tumour “fingerprint”, and differentially expressed proteins and genetic materials proposed as potential targets for anti-cancer based therapies. Approaches using engineered EV or EV as naturally delivery system for “therapeutics” have been explored in preclinical models and their effectiveness, in targeting the TME, proven in primary and metastatic tumours. More recently, CAR-T cells and CAR EV combo platform have been proposed to improve the CAR-based anti-cancer approach. Likewise, their potential application for immune cell targeting has provide significant insights to move towards anti-cancer immunotherapeutic approaches. On these bases, a number of clinical trials aimed to deeply explore EV clinical application as anti-tumour based approach or “theragnostics” are on-going. Should validated as diagnostic/prognostic/anti-cancer tools the still open questions would be hopefully addressed and their clinical application would become the on-coming challenge against cancer. However, to move towards EV clinical application several hurdles including potency tests, scalability and full characterization in agreement with the regulatory agency should be solved.
  • 734
  • 09 Nov 2020
Topic Review
Extracellular Heat Shock Proteins
Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses.
  • 734
  • 20 Apr 2022
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