Topic Review
Ivermectin as Broad-Spectrum Host-Directed Antiviral
The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received attention in the last eight years due to its exciting potential as an antiviral. It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus 1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. Excitingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Phase III human clinical trials have been completed for DENV, with >60 trials currently in progress worldwide for SARS-CoV-2.
  • 6101
  • 30 Sep 2020
Topic Review
Immunoformulation for COVID-19
The number of patients infected with the SARS-CoV-2 is still growing worldwide, with no current vaccine or medicinal treatment up to this date. Here we describe the cases of four COVID-19 patients that used a combination of therapeutic/nutraceutical agents for improvement of their symptoms. The ingredients were: immune transfer factor (oligo- and polypeptides fractions from porcine spleen, ultrafiltered at <10 kDa; Imuno TF®), anti-inflammatory natural blend (Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis; Miodesin®), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax®). The four showed improvement in general symptoms after using the combination proposed here. The cases presented here are just a first hint towards its benefit (decreases time necessary for the recovery of the patients), this would be a good starting point to the further investigation of this possible add-on therapy in controlled clinical studies. Limited sample size and study design are limitations for definitive conclusions on the add-on therapy.
  • 2934
  • 05 Nov 2020
Topic Review
Physiological Effects of Marijuana
To understand the impact of marijuana on the cardiovascular system, it is imperative to understand the endocannabinoid system. The endocannabinoid system (ECS) is comprised of the endocannabinoids anandamide and 2-arachidonylglycerol (both of which are endogenous lipid mediators), their metabolic enzymes, and G-protein coupled cannabinoid receptor 1 (CB1R) plus G-protein coupled cannabinoid receptor 2 (CB2R) [24]. CB1R is the primary receptor that mediates the effects of marijuana. CB1R is present in the brain, heart, vascular smooth muscle, and peripheral nervous system [6]. Its extensive presence in the human body makes its activation wide-reaching and impacts multiple systems.
  • 2578
  • 06 Nov 2020
Topic Review
Plant-Dominant Low-Protein Diet
Plant-dominant low-protein diet (LPD), also abbreviated as "PLADO" is a patient-centered LPD of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in providing nutrition care to patients with non-dialysis-dependent chronic kidney disease (CKD). PLADO's composition and meal plans can be designed and adjusted based on individualized needs and according to the principles of precision nutrition. The goal of PLADO is to slow kidney disease progression, to avoid or delay dialysis therapy initiation, and to ensure cardiovascular health and longevity.  The ideal type of PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of the conservative and preservative management of CKD.
  • 1848
  • 05 Nov 2020
Topic Review
Applications of Nanocellulose/Nanocarbon Composites: Focus on Biotechnology and Medicine
Nanocellulose/nanocarbon composites are newly-emerging smart hybrid materials containing cellulose nanoparticles, such as nanofibrils and nanocrystals, and carbon nanoparticles, such as “classical” carbon allotropes (fullerenes, graphene, nanotubes and nanodiamonds), or other carbon nanostructures (carbon nanofibers, carbon quantum dots, activated carbon and carbon black). The nanocellulose component acts as a dispersing agent and homogeneously distribute the carbon nanoparticles in aqueous environment. Nanocellulose/nanocarbon composites can be prepared with many advantageous properties, such as high mechanical strength, flexibility, stretchability, tunable thermal and electrical conductivity, tunable optical transparency, photodynamic and photothermal activity, nanoporous character and high adsorption capacity. They are therefore promising for a wide range of industrial applications, such as energy generation, storage and conversion, water purification, food packaging, construction of fire retardants and shape memory devices. They also hold great promise for biomedical applications, such as radical scavenging, photodynamic and photothermal therapy of tumors and microbial infections, drug delivery, biosensorics, isolation of various biomolecules, electrical stimulation of damaged tissues (e.g. cardiac, neural), neural and bone tissue engineering, engineering of blood vessels and advanced wound dressing, e.g. with antimicrobial and antitumor activity. However, the potential cytotoxicity and immunogenicity of the composites and their components must also be taken into account.
  • 1749
  • 01 Nov 2020
Topic Review
Aquaporin Inhibitors
Aquaporins (AQPs) are water channel proteins that are essential to life, being expressed in all kingdoms. In humans, there are 13 AQPs, at least one of which is found in every organ system. The structural biology of the AQP family is well-established and many functions for AQPs have been reported in health and disease. AQP expression is linked to numerous pathologies including tumor metastasis, fluid dysregulation, and traumatic injury. The targeted modulation of AQPs therefore presents an opportunity to develop novel treatments for diverse conditions. Various techniques such as video microscopy, light scattering and fluorescence quenching have been used to test putative AQP inhibitors in both AQP-expressing mammalian cells and heterologous expression systems. The inherent variability within these methods has caused discrepancy and many molecules that are inhibitory in one experimental system (such as tetraethylammonium, acetazolamide, and anti-epileptic drugs) have no activity in others. Some heavy metal ions (that would not be suitable for therapeutic use) and the compound, TGN-020, have been shown to inhibit some AQPs. Clinical trials for neuromyelitis optica treatments using anti-AQP4 IgG are in progress. However, these antibodies have no effect on water transport. More research to standardize high-throughput assays is required to identify AQP modulators for which there is an urgent and unmet clinical need.
  • 1542
  • 06 Sep 2021
Topic Review
Ibrexafungerp is a first-in-class IV/oral triterpenoid antifungal agent. Similar in mechanism of action to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against Candida spp.,Aspergillus spp., dimorphic fungi Pneumocystis and other emerging yeasts and mold pathogens including azole and echinocandin-resistant isolates. It is currently in late clinical development for treatment and prevention of vulvovaginal candidiasis. Other ongoing trials include treatment of serious fungal infections, including, invasive candidiasis, Candida auris infections, invasive aspergillosis and refractory fungal disease in patients not responding to or who are intolerant to standard of care .
  • 1418
  • 17 Mar 2021
Topic Review
Self-Amplifying mRNA Vaccine
The core principle behind mRNA vaccines is to encode the antigen in the mRNA and then to deliver the transcript to the host cell cytoplasm using a non-viral delivery system, allowing antigen expression and induction of an antigen-specific immune response. Self-amplifying RNA (saRNA) is a type of mRNA that also encodes viral replicase, which enables the RNA to self-replicate upon delivery into the cell.
  • 1240
  • 13 Feb 2021
Topic Review
Health-Promoting Beverages
Tea, a beverage made from the processed leaves of the tea plant, Camellia sinensis, and herbal infusions, were primarily consumed to their pleasant taste. Nowadays, are also consumed due to the existence of nutraceutical compounds in the herbs used, such as polyphenols.
  • 1201
  • 30 Oct 2020
Topic Review
Nonparametric Limits of Agreement
The assessment of agreement in method comparison and observer variability analysis of quantitative measurements is usually done by the Bland-Altman Limits of Agreement, where the paired differences are implicitly assumed to follow a normal distribution. Whenever this assumption does not hold, the 2.5% and 97.5% percentiles are obtained by quantile estimation. In the literature, empirical quantiles have been used for this purpose. In this simulation study, we applied both sample, subsampling, and kernel quantile estimators as well as other methods for quantile estimation to sample sizes between 30 and 150 and different distributions of the paired differences. The performance of 15 estimators in generating prediction intervals was measured by their respective coverage probability for one newly generated observation. Our results indicated that sample quantile estimators based on one or two order statistics outperformed all the other estimators and can be used for deriving nonparametric Limits of Agreement. For sample sizes exceeding 80 observations, more advanced quantile estimators, such as the Harrell-Davis and estimators of Sfakianakis-Verginis type, which use all the observed differences, performed likewise well, but may be considered intuitively more appealing than simple sample quantile estimators that are based on only two observations per quantile.
  • 1172
  • 27 Oct 2020
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