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Topic Review
Endolysins
Endolysins are phage-encoded enzymes utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application.
  • 895
  • 24 Mar 2021
Topic Review
Hydroxycinnamic Acids and Skin Damages/Disorders
Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high generation of harmful free radicals, or an impairment in the immune response regulation, which can profoundly change the skin tissue’ repair process, vulnerability, and functionality. Moreover, diabetes diffusion, antibiotic resistance, and abuse of aggressive soaps and disinfectants following the COVID-19 emergency could be causes for the future spreading of skin disorders. In the last years, hydroxycinnamic acids and derivatives have been investigated and applied in several research fields for their anti-oxidant, anti-inflammatory, and anti-bacterial activities.
  • 893
  • 06 Jul 2021
Topic Review
Oximes
Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-stroke activities. Many oximes are kinase inhibitors and have been shown to inhibit over 40 different kinases, including AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase (CDK), serine/threonine kinases glycogen synthase kinase 3 α/β (GSK-3α/β), Aurora A, B-Raf, Chk1, death-associated protein-kinase-related 2 (DRAK2), phosphorylase kinase (PhK), serum and glucocorticoid-regulated kinase (SGK), Janus tyrosine kinase (JAK), and multiple receptor and non-receptor tyrosine kinases. Some oximes are inhibitors of lipoxygenase 5, human neutrophil elastase, and proteinase 3. The oxime group contains two H-bond acceptors (nitrogen and oxygen atoms) and one H-bond donor (OH group), versus only one H-bond acceptor present in carbonyl groups. This feature, together with the high polarity of oxime groups, may lead to a significantly different mode of interaction with receptor binding sites compared to corresponding carbonyl compounds, despite small changes in the total size and shape of the compound. In addition, oximes can generate nitric oxide.
  • 893
  • 03 Jun 2021
Topic Review
Atorvastatin
Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia.
  • 888
  • 01 Jun 2021
Topic Review
Vitamin E in Neuro-Nutrition
Vitamin E was first discovered by the American endocrinologist and anatomist Herbert. M. Evans, together with his assistant Katherine S. Bishop. The isolated substance, later termed vitamin E, describes a group of compounds consisting of four tocopherol (TP)- and four tocotrienol (TT)-derivatives.
  • 888
  • 27 Oct 2021
Topic Review
Mechanisms of Resistance to Gemcitabine
Gemcitabine is still the standard-of-care chemotherapeutic drug for pancreatic ductal adenocarcinoma (PDAC). However, the response rate is quite low. There are multiple mechanisms and participants in gemcitabine resistance.
  • 887
  • 01 Jun 2022
Topic Review
Eucalyptus globulus Leaves in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects.
  • 884
  • 17 Aug 2022
Topic Review
β-Lactamase Inhibitors
The inhibitors of β-lactamases (BLI) have gained a prominent role in the safeguard of beta-lactams. In the last years, new β-lactam–BLI combinations have been registered or are still under clinical evaluation, demonstrating their effectiveness to treat complicated infections. It is also noteworthy that the pharmacokinetics of BLIs partly matches that of β-lactams companions, meaning that some clinical situations, as well as renal impairment and renal replacement therapies, may alter the disposition of both drugs. Common pharmacokinetic characteristics, linear pharmacokinetics across a wide range of doses, and known pharmacokinetic/pharmacodynamic parameters may guide modifications of dosing regimens for both β-lactams and BLIs. However, comorbidities (i.e., burns, diabetes, cancer) and severe changes in individual pathological conditions (i.e., acute renal impairment, sepsis) could make dose adaptation difficult, because the impact of those factors on BLI pharmacokinetics is partly known. Therapeutic drug monitoring protocols may overcome those issues and offer strategies to personalize drug doses in the intensive care setting. Further prospective clinical trials are warranted to improve the use of BLIs and their β-lactam companions in severe and complicated infections. 
  • 884
  • 11 Jul 2021
Topic Review
Aryl Hydrocarbon Receptor
The aryl hydrocarbon receptor (AhR) was first identified as the intracellular protein that 14 bound and mediated the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and 15 dioxin-like compounds (DLCs). Subsequent studies show that the AhR plays an important role in 16 maintaining cellular homeostasis and in pathophysiology and there is increasing evidence that the 17 AhR is a important drug target. The AhR binds structurally diverse compounds including 18 pharmaceuticals, phytochemicals, endogenous biochemicals some of which may serve as 19 endogenous ligands. Classification of DLCs and non-DLCs based on their persistence (metabolism), 20 toxicities, binding to wild-type/mutant AhR and structural similarities have been reported. This 21 review provides data suggesting that ligands for the AhR are selective AhR modulators (SAhRMs) 22 which exhibit tissue/cell-specific AhR agonist and antagonist activities and their functional diversity 23 is similar to selective receptor modulators that target steroid hormone and other nuclear receptors.
  • 882
  • 10 Feb 2021
Topic Review
Nutritional Interventions for COVID-19
The coronavirus infection (COVID‐19) conveys a serious threat globally to health and economy because of lack of vaccines and specific treatments. A common factor for conditions that predispose for serious progress is a low-grade inflammation, as seen e.g. in metabolic syndrome, diabetes and heart failure to which micronutrient deficiencies may contribute.  The aim of the present article is to explore the usefulness of early micronutrient intervention, with focus on zinc, selenium and vitamin D, to relieve escalation of COVID-19.  Methods: We have conducted an online search for articles published in the period 2010-2020 on zinc, selenium and vitamin D and corona and related virus infections.  Results: There were a few studies providing direct evidence on association between zinc, selenium and vitamin D and COVID-19.  Adequate supply of zinc, selenium, and vitamin D, is essential for resistance to other viral infections, immune function and reduced inflammation. Hence, it is suggested that nutrition intervention securing an adequate status might protect against SARS-CoV2, and  mitigate the course of COVID‐19.  Conclusion: We recommend initiation of adequate supplementation in high risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority as regards this nutritive adjuvant therapy, which should be started prior to administration of specific and supportive medical measures. 
  • 878
  • 24 Aug 2020
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