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Topic Review
High Triglycerides and Cognitive Impairment
The rise of life expectancy contributes to the burden of the aging-dependent decline of physical and mental functions. One of the most common and challenging neuropsychological condition is cognitive impairment (CI), defined as the decrease of intellectual functions ranging from mild forms of forgetfulness to severe and debilitating dementia. The burden of cognitive disorders is huge and still growing, however the etiology and the degree of cognitive impairment vary considerably. Neurodegenerative and vascular mechanisms were most frequently assessed in patients with dementia. The possible involvement of triglycerides levels in cognitive function through putative mechanisms such as brain blood barrier dysfunction or amyloid metabolism imbalance, but not all research in the field found this association.
  • 864
  • 05 Jul 2021
Topic Review
Oxidative Stress, ROS, and Antioxidants with Diabetes Mellitus
The Greek physician, Aretaios, coined the term “diabetes” in the 1st Century A.D. “Mellitus” arose from the observation that the urine exhibits a sweetness due to its elevated glucose levels. Diabetes mellitus (DM) accounted for 6.7 million deaths globally in 2021 with expenditures of USD 966 billion. Mortality is predicted to rise nearly 10-fold by 2030. Oxidative stress, an imbalance between the generation and removal of reactive oxygen species (ROS), is implicated in the pathophysiology of diabetes. Whereas ROS are generated in euglycemic, natural insulin-regulated glucose metabolism, levels are regulated by factors that regulate cellular respiration, e.g., the availability of NAD-linked substrates, succinate, and oxygen; and antioxidant enzymes that maintain the cellular redox balance. Only about 1–2% of total oxygen consumption results in the formation of superoxide anion and hydrogen peroxide under normal reduced conditions. 
  • 863
  • 21 Nov 2022
Topic Review
Magnetic-Based Three-Dimensional Cell Culture Technology
Cell-based assays, conducted on monolayer (2D) cultured cells, are an unquestionably valuable tool for biomedical research. However, three-dimensional (3D) cell culture models have gained relevance due to the advantages of better mimicking the microenvironment and tissue microarchitecture in vivo. Magnetic-based 3D (m3D) cell culture systems can be used for this purpose. These systems are based on exposing magnetized cells to magnetic fields by levitation, bioprinting, or ring formation to promote cell aggregation into 3D structures.
  • 862
  • 03 Nov 2022
Topic Review
Antiviral Agents Targeting Viral Polymerases
Viral DNA and RNA polymerases are two kinds of very important enzymes that synthesize the genetic materials of the virus itself, and they have become extremely favorable targets for the development of antiviral drugs because of their relatively conserved characteristics. There are many similarities in the structure and function of different viral polymerases, so inhibitors designed for a certain viral polymerase have acted as effective universal inhibitors on other types of viruses.
  • 862
  • 14 Nov 2022
Topic Review
Immunomodulatory Activity of Antimicrobial Peptides
Antimicrobial peptides (AMPs) in humans are represented by three main families: defensins, cathelicidins, histatins. Defensins, depending on the type of disulfide bond arrangement, are divided into alpha- and beta-defensins. Alpha- and beta-defensins are constitutively produced by neutrophils, lymphocytes, and epithelial cells of the skin and mucous membranes.
  • 861
  • 18 Mar 2022
Topic Review
Multifunctional Plant Virus Nanoparticles
Breast cancer treatment using plant-virus-based nanoparticles (PVNPs) has achieved considerable success in preclinical studies. PVNP-based breast cancer therapies include non-targeted and targeted nanoplatforms for delivery of anticancer therapeutic chemo and immune agents and cancer vaccines for activation of local and systemic antitumor immunity. Interestingly, PVNP platforms combined with other tumor immunotherapeutic options and other modalities of oncotherapy can improve tumor efficacy treatment.
  • 859
  • 20 Sep 2022
Topic Review
Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas
Diagnosing cutaneous melanoma is usually straightforward based on these malignancies’ histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. 
  • 859
  • 15 Jun 2023
Topic Review
Oligonucleotide-Based Therapies
The global burden of chronic kidney disease (CKD) is increasing every year and represents a great cost for public healthcare systems, as the majority of these diseases are progressive. Therefore, there is an urgent need to develop new therapies. Oligonucleotide-based drugs are emerging as novel and promising alternatives to traditional drugs. Their expansion corresponds with new knowledge regarding the molecular basis underlying CKD, and they are already showing encouraging preclinical results, with two candidates being evaluated in clinical trials. However, despite recent technological advances, efficient kidney delivery remains challenging, and the presence of off-targets and sideeffects precludes development and translation to the clinic.
  • 858
  • 31 Mar 2021
Topic Review
Repurposing Anticancer Drugs against COVID-19
The pandemic of the coronavirus disease 2019 (COVID-19) represents an unprecedented challenge to identify effective drugs for prevention and treatment. Due to the similarity of cancer-induced inflammation, immune dysfunction, and coagulopathy to COVID-19, anticancer drugs, such as Interferon, Pembrolizumab or Bicalutamide, are already being tested in clinical trials for repurposing, alone or in combination.
  • 858
  • 15 Jun 2021
Topic Review
RAD52 in Genome Maintenance
The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.
  • 858
  • 14 Sep 2021
Topic Review
B Cells in Autoinflammatory Disorders
Whereas autoimmune diseases are mediated primarily by T and B cells, auto-inflammatory syndromes (AIFS) involve natural killer cells, macrophages, mast cells, dendritic cells, different granulocyte subsets and complement components. In contrast to autoimmune diseases, the immune response of patients with AIFS is not associated with a breakdown of immune tolerance to self-antigens.
  • 858
  • 13 Jan 2023
Topic Review
Dystrophinopathy Diagnosis and Therapy
Dystrophinopathies are x-linked muscular disorders that emerge from mutations in the Dystrophin gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoid therapy. Appropriate choice of steroids and regimen is crucial. Creatine kinase (CK) has a 71% potential of detecting female carriers that are increased by multiplex ligation-dependent probe amplification (MLPA) or dystrophin study in biopsy. Clinical neurologists need to relate to patients and families of patients with neurocognitive problems since mental retardation might be part of Duchenne's picture.
  • 858
  • 11 Sep 2023
Topic Review
Immune Control of Avian Influenza Virus Infection
The avian influenza A virus (AIV) is naturally prevalent in aquatic birds, infecting different avian species and transmitting from birds to humans. Both AIVs, the H5N1 and H7N9 viruses, have the potential to infect humans, causing an acute influenza disease syndrome in humans, and are a possible pandemic threat. AIV H5N1 is highly pathogenic, whereas AIV H7N9 has comparatively low pathogenicity.
  • 857
  • 18 Apr 2023
Topic Review
Dementia Care in Italy, Hungary
According to the World Health Organization (WHO), dementia is one of the more serious challenges of the future . Most countries have a variety of policies, institutions and financial aids implemented to ease the burden on families carrying out the bulk of care work for their relatives with dementia. However, due to the COVID-19 outbreak, some of these support systems have become much more difficult (or even impossible) to access or utilize, an effect mediated by the mandatory stringency measures adopted by governments during the first wave of the pandemic to mitigate its impact on the population. Both Italy and Hungary belong to clusters of countries showing challenges concerning the degree of resilience. However, Italy is part of a cluster having weak resilience in informal care and moderate resilience in formal care provision, while Hungary belongs to a cluster with weak resilience in both formal and informal care (i.e., with a higher share of older adults reporting difficulties in receiving formal care—i.e., home care—and a quite low share receiving informal care from people outside their home, being the supply of both types of care provision dramatically decreased compared to the pre-pandemic period).
  • 856
  • 09 Jul 2021
Topic Review
SZR-104
By being an antagonist of glutamate and other receptors, kynurenic acid serves as an endogenous neuroprotectant in several pathologies of the brain. Unfortunately, systemic administration of kynurenic acid is hindered by its low permeability through the blood–brain barrier. One possibility to overcome this problem is to use analogues with similar biological activity as kynurenic acid, but with an increased permeability through the blood–brain barrier. We synthesized six novel aminoalkylated amide derivatives of kynurenic acid, among which SZR-104 (N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-hydroxyquinoline-2-carboxamide) proved to have the highest permeability through an in vitro blood–brain barrier model. In addition, permeability of SZR-104 was significantly higher than that of kynurenic acid, xanthurenic acid and 39B, a quinolone derivative/xanthurenic acid analogue.
  • 854
  • 07 Apr 2021
Topic Review
Zinc-Alpha2-Glycoprotein (AZGP1) and Fibrotic Kidney Disease
Chronic Kidney Disease (CKD) is a condition characterized by a gradual loss of kidney function over time. It is typically accompanied by progressive fibrosis of the tubulointerstitial compartment.
  • 854
  • 26 Jan 2022
Topic Review
Challenges Encountered in NAFLD Animal Models
As a term, non-alcoholic fatty liver disease (NAFLD) was proposed to describe the histopathological fatty changes in hepatocytes in which alcohol consumption is not involved as the etiological inducer. Non-alcoholic fatty liver disease (NAFLD) embraces several forms of liver disorders involving fat disposition in hepatocytes ranging from simple steatosis to the severe stage, namely, non-alcoholic steatohepatitis (NASH). However, no reproducible experimental animal model displays the full spectrum of pathophysiological, histological, molecular, and clinical features associated with human NAFLD/NASH progression.
  • 850
  • 09 Feb 2022
Topic Review
CD147/Basigin in Malignant Tumors and T-Cell-Mediated Immunological Disorders
CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MTC-1 and MCT-4 export the lactic acid that is converted from pyruvate in glycolysis to maintain the intracellular pH level and a stable metabolic state. Under physiological conditions, cellular energy production is induced by mitochondrial oxidative phosphorylation. Glycolysis usually occurs under anaerobic conditions, whereas cancer cells depend on glycolysis under aerobic conditions. T cells also require glycolysis for differentiation, proliferation, and activation. Human malignant melanoma cells expressed higher levels of MCT-1 and MCT-4, co-localized with CD147 on the plasma membrane, and showed an increased glycolysis rate compared to normal human melanocytes. CD147 silencing by siRNA abrogated MCT-1 and MCT-4 membrane expression and disrupted glycolysis, inhibiting cancer cell activity. Furthermore, CD147 is involved in psoriasis. MCT-1 was absent on CD4+ T cells in CD147-deficient mice. The naïve CD4+ T cells from CD147-deficient mice exhibited a low capacity to differentiate into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in the CD147-deficient mice than in the wild-type mice. Overall, CD147/Basigin is involved in the development of malignant tumors and T-cell-mediated immunological disorders via glycolysis regulation.
  • 849
  • 26 Dec 2023
Topic Review
Microbiome-Brain-Gut Axis in the Pathogenesis of Depressive Disorder
The brain and gut, through the microbiota, can influence each other’s functions via neuroendocrine, neuroimmune and sensory-neural molecular pathways. Moreover, both hypothalamic-pituitary-adrenal (HPA) axis and gut peptides might be involved in this communication system.
  • 848
  • 18 May 2022
Topic Review
PD-1/PD-L1 Inhibitors in Ovarian Cancer
Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a high number of intra tumor infiltrating lymphocytes (TILs). Therefore, immunomodulation is considered to have an important role in cancer treatment, and immune checkpoint inhibitors may be useful for restoring T cell-mediated antitumor immunity. PD-1 is a 50–55 kDa, 288 aa transmembrane glycoprotein that lacks the membrane-proximal cysteine residue required for homodimerization that is present in the structure of the other members of the CD28 family, thus rendering PD-1 monomeric, both in solution and on cell surface. The cytoplasmic domain presents two tyrosine residues, with the membrane-proximal one constituting an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the second one constituting an immunoreceptor tyrosine-based switch motif (ITSM).
  • 848
  • 25 Sep 2023
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