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Topic Review
AhR in the Hallmarks of Brain Aging
AhR, a member of the basic helix-loop-helix (bHLH)-PAS superfamily, performs various functions within the brain. It is an ancient protein that possesses shared functions and structures across various species in the evolutionary tree. It is widely distributed in various regions of the brain, such as the hippocampus, the cortex, and the hypothalamus, and its expression changes during the course of brain development.
  • 775
  • 20 Oct 2021
Topic Review
Immune Checkpoint Agents
Immune checkpoint inhibitors represent a promising treatment choice in many kind of tumours, including hepatocellular carcinoma (HCC). In this review, we provide an overview of the role of these new agents in the management of HCC according to the Barcelona staging system, alongside with a critical evaluation of the current status and future directions. Several clinical trials are focusing on the use of immunotherapy in HCC, alone or in combinations with antiangiogenetic agents as well as local treatment. However, the majority of those trials are still ongoing and, until now, only a few combinations were approved in the clinical practice from the regulatory authorities. Additionally, decisions about the choice of the right sequence of treatments in HCC patients in the light of the “continuum of care” principles, is still hard. In fact, it requires careful consideration in a multidisciplinary context in order to ensure a tailored treatment for each patient. 
  • 775
  • 09 Nov 2020
Topic Review
Multidrug Resistance
Multidrug resistance (MDR) transporters belonging to either the ATP-Binding Cassette (ABC) or Major Facilitator Superfamily (MFS) groups are major determinants of clinical drug resistance in fungi. The overproduction of these proteins enables the extrusion of incoming drugs at rates that prevent lethal effects. The promiscuity of these proteins is intriguing because they export a wide range of structurally unrelated molecules. Research in the last two decades has used multiple approaches to dissect the molecular basis of the polyspecificity of multidrug transporters. With large numbers of drug transporters potentially involved in clinical drug resistance in pathogenic yeasts, this review focuses on the drug transporters of the important pathogen Candida albicans. This organism harbors many such proteins, several of which have been shown to actively export antifungal drugs. Of these, the ABC protein CaCdr1 and the MFS protein CaMdr1 are the two most prominent and have thus been subjected to intense site-directed mutagenesis and suppressor genetics-based analysis. Numerous results point to a common theme underlying the strategy of promiscuity adopted by both CaCdr1 and CaMdr1. 
  • 774
  • 03 Feb 2021
Topic Review
Normal Tension Glaucoma
Glaucoma is a neurodegenerative disease of the eye, which involves degeneration of retinal ganglion cells (RGCs): the output neurons of the retina to the brain, which with their axons comprise the optic nerve. Glaucoma is usually associated with elevated intraocular pressure (IOP), but there is a subtype of glaucoma, termed normal tension glaucoma, that presents with normal IOP.
  • 774
  • 12 Feb 2021
Topic Review
Vitamin D and Glomerulonephritis
Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeo-stasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease (CKD) patients, Vitamin D function is im-paired; the renal hydrolyzation of its inactive form by the action of 1α-hydroxylase declines at the same pace of reduced nephron mass. Moreover, Vitamin D major carrier, the D-binding pro-tein (DBP), is less represented due to Nephrotic Syndrome (NS), proteinuria, and the alteration of the cubilin–megalin–amnionless receptor complex in the renal proximal tubule. In Glomeru-lonephritis (GN), Vitamin D supplementation demonstrated to significantly reduce proteinuria and to slow kidney disease progression. It also has potent antiproliferative and immunomodu-lating functions, contributing to the inhibitions of kidney inflammation. Vitamin D preserves the structural integrity of the slit diaphragm guaranteeing protective effects on podocytes. Acti-vated Vitamin D has been demonstrated to potentiate the antiproteinuric effect of RAAS inhibi-tors in IgA nephropathy and Lupus Nephritis, enforcing its role in the treatment of glomerulo-nephritis: calcitriol treatment, through Vitamin D receptor (VDR) action, can regulate the hepa-ranase promoter activity and modulate the urokinase receptor (uPAR), guaranteeing podocyte preservation. It also controls the podocyte distribution by modulating mRNA synthesis and protein expression of nephrin and podocin. Maxalcalcitol is another promising alternative: it has about 1/600 affinity to vitamin D binding protein (DBP), compared to Calcitriol, overcoming the risk of hypercalcemia, hyperphosphatemia and calcifications, and it circulates principally in un-bound form with easier availability for target tissues. Doxercalciferol, as well as paricalcitol, showed a lower incidence of hypercalcemia and hypercalciuria than Calcitriol. Paricalcitol demonstrated a significant role in suppressing RAAS genes expression: it significantly decreases angiotensinogen, renin, renin receptors, and vascular endothelial growth factor (VEGF) mRNA levels, thus reducing proteinuria and renal damage.
  • 774
  • 11 Oct 2021
Topic Review
Sideroflexins/SLC56 Family
Sideroflexins (SLC56 family) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes.
  • 774
  • 26 Feb 2021
Topic Review
Three-Dimensional In Vitro Cell Culture Models
Despite tremendous advancements in technologies and resources, drug discovery still remains a tedious and expensive process. Though most cells are cultured using 2D monolayer cultures, due to lack of specificity, biochemical incompatibility, and cell-to-cell/matrix communications, they often lag behind in the race of modern drug discovery. There exists compelling evidence that 3D cell culture models are quite promising and advantageous in mimicking in vivo conditions. It is anticipated that these 3D cell culture methods will bridge the translation of data from 2D cell culture to animal models. Although 3D technologies have been adopted widely these days, they still have certain challenges associated with them, such as the maintenance of a micro-tissue environment similar to in vivo models and a lack of reproducibility. However, newer 3D cell culture models are able to bypass these issues to a maximum extent.
  • 774
  • 10 Aug 2022
Topic Review
Glutathione in the Brain
Glutathione (GSH) is the most abundant non-protein thiol, and plays crucial roles in the antioxidant defense system and the maintenance of redox homeostasis in neurons.
  • 774
  • 13 May 2021
Topic Review
Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients
Neuroblastoma is the most common extracranial solid tumor of childhood, with a median age at diagnosis of 17 months. Its incidence is 10.2 cases per million children aged <15 years. Neuroblastoma arises in tissues of the sympathetic nervous system, mostly in the adrenal medulla or paraspinal ganglia. It appears as a mass in the abdomen, pelvis, neck, or chest, with about half of the patients having metastatic disease at diagnosis. The presence of metastatic diseases over the age of 12 or 18 months and aggressive biological features (e.g., MYCN oncogene amplification) define high-risk neuroblastoma. The prognosis for such patients is poor, with a long-term survival rate of only 40%.
  • 774
  • 07 Jan 2022
Topic Review
Antimicrobial Essential Oils
Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of multidrug-resistant strains of bacteria, fungi, viruses, and parasites.
  • 773
  • 27 Jan 2022
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