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Topic Review
The Virtuous Galleria mellonella as Scientific Model
The first research on the insect Galleria mellonella was published 85 years ago, and the larva is now widely used as a model to study infections caused by bacterial and fungal pathogens, for screening new antimicrobials, to study the adjacent immune response in co-infections or in host-pathogen interaction, as well as in a toxicity model. The immune system of the G. mellonella model shows remarkable similarities with mammals. Furthermore, results from G. mellonella correlate positively with mammalian models and with other invertebrate models. Unlike other invertebrate models, G. mellonella can withstand temperatures of 37 °C, and its handling and experimental procedures are simpler. Despite having some disadvantages, G. mellonella is a virtuous in vivo model to be used in preclinical studies, as an intermediate model between in vitro and mammalian in vivo studies, and is a great example on how to apply the bioethics principle of the 3Rs (Replacement, Reduction, and Refinement) in animal experimentation. 
  • 533
  • 13 Mar 2023
Topic Review
The Viral Agents of BRDC
Bovine respiratory disease complex (BRDC) is a multifactorial disease of cattle which presents as bacterial and viral pneumonia. The causative agents of BRDC work in synergy to suppress the host immune response and increase the colonisation of the lower respiratory tracts by pathogenic bacteria. Environmental stress and/or viral infection predispose cattle to secondary bacterial infections via suppression of key innate and adaptive immune mechanisms. This allows bacteria to descend the respiratory tract unchallenged. BRDC is the costliest disease among feedlot cattle, and whilst vaccines exist for individual pathogens, there is still a lack of evidence for the efficacy of these vaccines and uncertainty surrounding the optimum timing of delivery. 
  • 677
  • 14 Apr 2021
Topic Review
The VBNC State in Beneficial Bacteria
Bacteria in the viable but non-culturable (VBNC) state exhibit a remarkable phenomenon: they are unable to grow and form colonies on conventional culture media, yet they remain alive and able to restart their metabolic activity. Cells in this status typically display reduced levels of metabolic activity and undergo significant metabolic alterations, such as reductions in nutrient transport and respiration rates and macromolecular synthesis, and form resistance structures similar to spores. However, a feature that distinguishes the VNBC state is the continuous gene expression within these cells.
  • 346
  • 08 Jan 2024
Topic Review
The Vaccine against Human Cytomegalovirus
Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines—e.g., live-attenuated, chimeric, viral-based—and non-living ones—subunit, RNA-based, virus-like particles, plasmid-based DNA—have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV’s capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development.
  • 540
  • 07 Jun 2021
Topic Review
The V-ATPase a3 Subunit
This entry focuses on one of the 16 proteins composing the V-ATPase complex responsible for resorbing bone: the a3 subunit. The rationale for focusing on this biomolecule is that mutations in this one protein account for over 50% of osteopetrosis cases, highlighting its critical role in bone physiology. Despite its essential role in bone remodeling and its involvement in bone diseases, little is known about the way in which this subunit is targeted and regulated within osteoclasts. To this end, this review is broadened to include the three other mammalian paralogues (a1, a2 and a4) and the two yeast orthologs (Vph1p and Stv1p). By examining the literature on all of the paralogues/orthologs of the V-ATPase a subunit, we hope to provide insight into the molecular mechanisms and future research directions specific to a3. This review starts with an overview on bone, highlighting the role of V-ATPases in osteoclastic bone resorption. We then cover V-ATPases in other location/functions, highlighting the roles which the four mammalian a subunit paralogues might play in differential targeting and/or regulation. Author review the ways in which the energy of ATP hydrolysis is converted into proton translocation, and go in depth into the diverse role of the a subunit, not only in proton translocation but also in lipid binding, cell signaling and human diseases. Finally, the therapeutic implication of targeting a3 specifically for bone diseases and cancer is discussed, with concluding remarks on future directions.
  • 438
  • 21 Jul 2021
Topic Review
The Urokinase Receptor in Targeted Cancer Therapy
The urokinase-type plasminogen activator receptor (uPAR) has now firmly established itself as a versatile molecular target holding promise for the treatment of aggressive malignancies. The copious abundance of uPAR in virtually all human cancerous tissues versus their healthy counterparts has fostered a gradual shift in the therapeutic landscape targeting this receptor from function inhibition to cytotoxic approaches to selectively eradicate the uPAR-expressing cells by delivering a targeted cytotoxic insult.  
  • 498
  • 29 Mar 2022
Topic Review
The Urinary Microbiome
The recent discovery of the urinary microbiome bolstered the notion that microbes might play a role in bladder cancer. Although microbial involvement in bladder neoplastic transformation and metastatic progression, except schistosomiasis, has not been established, accumulating research suggests that dysbiosis of the urinary microbiome can produce a chronically inflammatory urothelial microenvironment and lead to bladder cancer.
  • 394
  • 30 Sep 2022
Topic Review
The uPA/uPAR System in Fibrosis Progression
Urokinase plasminogen activator (uPA) is a single-chain serine protease that can cleave and activate Plg into plasmin by binding to urokinase plasminogen activator receptor (uPAR). uPA is secreted as a single-chain glycosylated zymogen called pro-uPA, and pro-uPA is activated by several proteinases, such as kallikrein, stromelysin, and plasmin. uPAR is a glycosyl-phosphatidyl-inositol anchored (GPI) membrane protein that consists of three domains: D1 (residues 1–92), D2 (residues 93–191) and D3 (residues 192–283). uPAR is cleaved between the D1 and D2 domains (linker region) and the GPI-anchor domain by several proteases, such as uPA, plasmin, MMPs, and GPI-specific phospholipase D, and then forms soluble uPAR (suPAR; full length D1-D3, D2D3, and D1).
  • 701
  • 01 Feb 2023
Topic Review
The Unfolded Protein Response in Cystic Fibrosis
The UPR is responsible for the activation of degradation genes of the ERAD, the increased expression of chaperons and limits the global protein synthesis in cells. It limits the expression of the p.Phe508del-CFTR itself, by the activation of ATF6. Therefore, the hypothesis that it is likely triggered but becomes obvious when other events happen, including infection and/or inflammation, that also contribute the UPR triggering.
  • 382
  • 26 Nov 2021
Topic Review
The Ubiquitin Proteasome System and Mitochondrial Homeostasis
Mitochondria abundance and activity are fundamental elements underlying the dynamic adaptation of cells to stress conditions. The shape and number of mitochondria are tightly controlled by key biological processes, such as fusion and fission (also known as mitochondrial dynamics) and mitophagy that operate in an interconnected and dynamic way to sustain cellular health and metabolic needs.
  • 387
  • 13 Jan 2023
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