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Topic Review
TRIM22. A Multitasking Antiviral Factor
Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors.
  • 915
  • 29 Jul 2021
Topic Review
Precision Medicine in Rare Diseases
The own patient-derived cells can be used to perform personalized pharmacological screening in genetic rare diseases. For precision medicine to be successful at the therapeutic level, in addition of the information provide from genomics, pharmacogenomics, metabolomics and proteomics, our proposal argues that it is also necessary to know the cellular response, and therefore the behavior of particular mutations in vitro, to various therapeutic options. Precision medicine relies on the assumption that different mutations and marked inter-individual genetic variation can contribute significantly to drug response. The goal of personalized medicine is to maximize the probability of therapeutic efficacy for an individual patient.
  • 914
  • 23 Nov 2020
Topic Review
AKR1B10 in Physiology and Pathophysiology
AKR1B10 is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the aldo-keto reductase (AKR) 1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α. The enzyme is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. In contrast, AKR1B10 expression is low in other tissues, where the enzyme is upregulated in cancers, as well as in non-alcoholic fatty liver disease and several skin diseases. In addition, the enzyme’s expression is elevated in cancer cells resistant to clinical anti-cancer drugs. Thus, growing evidence supports AKR1B10 as a potential target for diagnosing and treating these diseases. Herein, we reviewed the literature on the roles of AKR1B10 in a healthy gastrointestinal tract, the development and progression of cancers and acquired chemoresistance, in addition to its gene regulation, functions, and inhibitors.
  • 914
  • 24 Jun 2021
Topic Review Video
Photodynamic Therapy for Prostate Cancer
Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therapy, and chemotherapy, are associated with significant side effects and limitations. Photodynamic therapy (PDT) is a promising alternative that has the potential to provide a minimally invasive and highly targeted approach to treating prostate cancer. PDT involves the use of photosensitizers (PSs) that are activated by light to produce reactive oxygen species (ROS), which can induce tumor cell death. 
  • 914
  • 03 Sep 2023
Topic Review
Inhibition of Replication Fork Formation and Progression
Over 1.2 million deaths are attributed to multi-drug-resistant (MDR) bacteria each year. Persistence of MDR bacteria is primarily due to the molecular mechanisms that permit fast replication and rapid evolution. As many pathogens continue to build resistance genes, current antibiotic treatments are being rendered useless and the pool of reliable treatments for many MDR-associated diseases is thus shrinking at an alarming rate. In the development of novel antibiotics, DNA replication initiation and the primosome are still largely underexplored targets.
  • 913
  • 05 Jun 2023
Topic Review
mtUPR for the Treatment of Mitochondrial Diseases
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich’s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. 
  • 912
  • 19 Dec 2023
Topic Review
ATRX/DAXX and ALT
ATRX is named for its causal role in ATR-X syndrome (α-thalassemia with mental impairment, X-linked), an X-linked disorder characterized by developmental delays, urogenital abnormalities, distinctive craniofacial features, and α-thalassemia caused by insufficient α-globin expression. Because of the central role of decreased α-globin mRNA expression in the ATR-X phenotype, research on ATRX initially focused on its potential as a transcriptional regulator. In fact, ATRX in concert with DAXX play wide-ranging roles in maintaining chromatin and reckoning with problematic DNA repeat sequences, with downstream effects on gene expression that have critical impacts in development. Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of Telomeres or ALT. The ALT process is linked to mutations in the ATRX/DAXX/H3.3 histone chaperone complex. This complex is responsible for depositing non-replicative histone variant H3.3 at pericentric and telomeric heterochromatin but has also been found to have roles in ameliorating replication in repeat sequences and in promoting DNA repair.
  • 911
  • 17 Apr 2023
Topic Review
Drosophila Melanogaster Research
Parkinson’s disease (PD) is a complex neurodegenerative disorder that is currently incurable. As a consequence of an incomplete understanding of the etiology of the disease, therapeutic strategies mainly focus on symptomatic treatment. Even though the majority of PD cases remain idiopathic (~90%), several genes have been identified to be causative for PD, facilitating the generation of animal models that are a good alternative to study disease pathways and to increase our understanding of the underlying mechanisms of PD. Drosophila melanogaster has proven to be an excellent model in these studies.
  • 910
  • 23 Mar 2021
Topic Review
STxB in Mucosal Vaccination
One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells. 
  • 910
  • 25 Mar 2022
Topic Review
Microgravity Effects on the Matrisome
Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the “gravisensors” in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity.
  • 910
  • 11 Apr 2022
Topic Review
MSCs - Gene Delivery Tool
To clearly define MSCs, and develop universal criteria for such cell population, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) proposed a set of standards for pre-clinical research studies. The minimal criteria of MSCs as determined by the ISCT are the following ones: The MSCs population must be plastic-adherent when maintained in tissue culture vessels under standard culture conditions.
  • 909
  • 25 Jun 2021
Topic Review
GPR15 in Vascular Tissue
GPR15 as a member of the Class A (rhodopsin) orphan G protein-coupled receptor (GPCR) family  has been recently deorphanized by identification of two endogenous receptor-activating ligands in human. Interestingly, in vascular tissue they interact apparently with different cell types. While one ligand triggers a cytoprotective effect on endothelial cells from the luminal site of vessels, the other ligand is rather responsible for the homing of GPR15-expressing lymphocytes into the colon. Thus, in addition to the role of GPR15 as a co-receptor for the human immunodeficiency virus (HIV) or to the expansion of GPR15-expressing lymphocytes in blood by chronic smoking this review will summarize findings to the role of GPR15 for vascular tissue based on new described receptor-ligand interactions.
  • 909
  • 21 Oct 2021
Topic Review
Impact of Endoplasmic Reticulum Stress for Type-1-Diabetes
Type-1-diabetes (T1D) is a multifactorial disorder with a global incidence of about 8.4 million individuals in 2021. It is primarily classified as an autoimmune disorder, where the pancreatic β-cells are unable to secrete sufficient insulin. This leads to elevated blood glucose levels (hyperglycemia). The development of T1D is an intricate interplay between various risk factors, such as genetic, environmental, and cellular elements. Here, the focus is on cellular elements such as ER stress leading to defects in insulin secretion and β-cell destruction.
  • 909
  • 03 Nov 2022
Topic Review
Therapeutic Potential of Apoptotic MSCs or MSC-Derived ApoBDs
Mesenchymal stem cells (MSCs) have shown promising therapeutic effects both in preclinical studies (in animal models of a wide range of diseases) and in clinical trials. However, the efficacy of MSC-based therapy is not always predictable. Moreover, despite the large number of studies, the mechanisms underlying the regenerative potential of MSCs are not fully elucidated. It has been reliably established that transplanted MSCs can undergo rapid apoptosis and clearance from the recipient’s body, still exhibiting therapeutic effects, especially those associated with their immunosuppressive/immunomodulating properties. The mechanisms underlying these effects can be mediated by the efferocytosis of apoptotic MSCs by host phagocytic cells.
  • 909
  • 18 Nov 2022
Topic Review
Transient Nuclear Envelope Rupture during Metastasis
Metastasis is the process that allows the seeding of tumor cells in a new organ. The migration and invasion of cancer cells involves the pulling, pushing, and squeezing of cells through narrow spaces and pores. Tumor cells need to cross several physical barriers, such as layers of basement membranes as well as the endothelium wall during the way in and out of the blood stream, to reach the new organ.
  • 907
  • 10 Feb 2022
Topic Review
Epithelial Stem Cell Innovation
The field of epithelial stem cell development has been irrevocably shaped by the work of American scientist Howard Green, whose breakthroughs in stem cell culture methods translated to therapeutic practice.
  • 907
  • 20 Mar 2023
Topic Review
Tissue Renin-Angiotensin System
Tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1–7/MasReceptor axis.
  • 906
  • 09 Apr 2021
Topic Review
Transthyretin: Osteoarticular and Cardiovascular Diseases
Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor.
  • 906
  • 16 Nov 2021
Topic Review
VAV Proteins
The VAV GEF family has been traditionally linked to protumorigenic actions in cancer. This idea was reinforced by the use of both cancer cell lines and mouse models demonstrating the proactive role of VAV proteins in the development of different types of tumors, such as skin and breast cancer. However, given the presence of structural domains that facilitate the interaction with a large number of protein partners and the particular features of some of the VAV-dependent pathways, it is conceivable that VAV proteins might antagonize cell transformation in certain in vivo contexts.
  • 904
  • 27 Oct 2021
Topic Review
Drug Repositioning of PD-1/PD-L1 Checkpoint
Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have considerably improved the treatment of some cancers, but novel drugs, new combinations, and treatment modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option to elicit antitumor immunity against cancer consists of using approved and marketed drugs known for their capacity to modulate the expression and functioning of the PD-1/PD-L1 checkpoint. Specifically, the repositioning of the approved drugs liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole/flubendazole, and a few other modulators of the PD-1/PD-L1 checkpoint (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their capacity to bind to PD-L1 or to repress its expression and function offer novel perspectives for combination with PD-1 targeted biotherapeutics. These known and affordable drugs could be useful to improve the therapy of cancer.
  • 904
  • 22 Jul 2022
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