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Topic Review
Approaches to Identify Functional SNPs in mRNA 3′UTRs
The complementary interaction of microRNAs (miRNAs) with their binding sites in the 3′untranslated regions (3′UTRs) of target gene mRNAs represses translation, playing a leading role in gene expression control. MiRNA recognition elements (MREs) in the 3′UTRs of genes often contain single nucleotide polymorphisms (SNPs), which can change the binding affinity for target miRNAs leading to dysregulated gene expression. Accumulated data suggest that these SNPs can be associated with various human pathologies (cancer, diabetes, neuropsychiatric disorders, and cardiovascular diseases) by disturbing the interaction of miRNAs with their MREs located in mRNA 3′UTRs. Numerous data show the role of SNPs in 3′UTR MREs in individual drug susceptibility and drug resistance mechanisms. This work brief the data on such SNPs focusing on the most rigorously proven cases. Some SNPs belong to conventional genes from the drug-metabolizing system (in particular, the genes coding for cytochromes P450 (CYP 450), phase II enzymes (SULT1A1 and UGT1A), and ABCB3 transporter and their expression regulators (PXR and GATA4)). Other examples of SNPs are related to the genes involved in DNA repair, RNA editing, and specific drug metabolisms. The gene-by-gene studies and genome-wide approaches utilized or potentially utilizable to detect the MRE SNPs associated with individual response to drugs discussed.
  • 511
  • 24 Nov 2022
Topic Review
Asthma and Obesity
Asthma is a common chronic airway disease characterized by variable airflow limitation resulting from the combination of airway narrowing, airway hypersensitivity, airway wall thickening, and increased mucus hypersecretion. Airway narrowing results from both chronic inflammation and airway remodeling. Asthma is a heterogeneous disease with several distinct clinical presentations (phenotypes) and complex pathophysiological mechanisms (endotypes). Obesity is the consequence of an excessive body fat accumulation due to an imbalance of energy intake and energy expenditure. Diagnosis of obesity is usually established by assessing the body mass index (BMI) ≥ 30 kg/m2.
  • 510
  • 22 Feb 2021
Topic Review
Pharmacogenetics in Chronic Kidney Disease
Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. Pharmacogenetics could fill this gap.
  • 510
  • 28 Jul 2021
Topic Review
New Therapeutical Approaches for COVID-19
The pandemic of coronavirus disease (COVID-19) stimulated an unprecedented international collaborative effort for rapid diagnosis, epidemiologic surveillance, clinical management, prevention, and treatment. Since the beginning of the COVID-19 pandemic, treatment of the SARS-CoV-2 infection was a real challenge. An overview of the viral structure and life cycle of SARS-CoV-2 is given and future therapeutical options are discussed.
  • 509
  • 08 Jun 2022
Topic Review
Anti-Angiogenic Drugs
Angiogenesis can be revisited as a complex biological process with numerous compensatory pathways that can be activated, challenging the discovery of predictive biomarkers, since the cancer microenvironment and the complex milieu are difficult to classify and several actors are simultaneously shaping the key pro-angiogenic ecosystem. Bevacizumab represents the archetypic example of the various mechanisms of action, which may differ between cancer types and chemotherapy, unveiling the multifaceted functions in driving regression of existing tumor vasculature, halting new vessel growth, shaping the anti-permeability of surviving vasculature, and priming vessel normalization and co-option. Unfortunately, a poor correlation between response and survival exists, and the effects are mainly limited to PFS, and from a clinical trials standpoint, cross-over events at progression make identification of response criteria and biomarkers difficult.
  • 508
  • 29 Nov 2021
Topic Review
NO in Viral Infections
Nitric oxide is a ubiquitous signaling radical that influences critical body functions. Its importance in the cardiovascular system and the innate immune response to bacterial and viral infections has been extensively investigated. The overproduction of NO is an early component of viral infections, including those affecting the respiratory tract. The production of high levels of NO is due to the overexpression of NO biosynthesis by inducible NO synthase (iNOS), which is involved in viral clearance. The development of NO-based antiviral therapies, particularly gaseous NO inhalation and NO-donors, has proven to be an excellent antiviral therapeutic strategy. 
  • 507
  • 20 Apr 2022
Topic Review
Oral Administration for Small Extracellular Vesicles Delivery
Small extracellular vesicles (sEVs) have burst into biomedicine as a natural therapeutic alternative for different diseases. Considered nanocarriers of biological origin, various studies have demonstrated the feasibility of their systemic administration, even with repeated doses. sEVs can resist the degradative conditions of the gastrointestinal tract after oral administration, accumulating regionally in the intestine, where they are absorbed for systemic biodistribution. 
  • 506
  • 14 Mar 2023
Topic Review
Inhibiting Angiogenesis by Anti-Cancer Saponins
Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis.
  • 508
  • 24 Mar 2023
Topic Review
Subcellular Localization of Membrane-Type-1 Matrix Metalloproteinase
Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Membrane-type-1 matrix metalloproteinase (MT1-MMP), a transmembrane protein, is first known to localize to the cell membrane.
  • 505
  • 15 Sep 2022
Topic Review
Aqueous Prostaglandin Eye Drop Formulations
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the long-term treatment of open-angle glaucoma, prostaglandin analogues (PGAs) are the first-line treatment and are available as marketed eye drop formulations for intraocular pressure (IOP) reduction by increasing the trabecular and uveoscleral outflow. PGAs have low aqueous solubility and are very unstable (i.e., hydrolysis) in aqueous solutions, which may hamper their ocular bioavailability and decrease their chemical stability. Additionally, treatment with PGA in conventional eye drops is associated with adverse effects, such as conjunctival hyperemia and trichiasis. It has been a very challenging for formulation scientists to develop stable aqueous eye drop formulations that increase the PGAs’ solubility and enhance their therapeutic efficacy while simultaneously lowering their ocular side effects.
  • 505
  • 28 Oct 2022
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