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Topic Review
RBM-007
RBM-007 is an anti-FGF2 aptamer composed of 37 nucleotides, whose ribose 2′ positions are modified to resist ribonucleases, in addition to being 5′-PEGylated and 3′-conjugated with an inverted dT to confer an advantageous pharmacokinetic profile. RBM-007 binds strongly and specifically to FGF2 and does not cross-react with other FGF family proteins or heparin-binding proteins, blocking the interaction between human FGF2 and its receptors FGFR1 through FGFR4. The dissociation constant (KD) of the non-PEGylated form of RBM-007 to human FGF2 protein is 2 pM, compared to 5, 7, and 27 pM in rat, mouse, and rabbit protein, respectively, showing the high affinity of RBM-007 for different FGF2s regardless of the species difference.
  • 732
  • 08 Jul 2021
Topic Review
Bone Products Bioequivalence Study
An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μg molybdenum, 250 μg boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β-glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (T max), concentration (C max), half-life (T 1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein T max (2 hrs), C max (0.7 μM), T 1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered T max (6 hrs), C max (0.57 μM), T 1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption.
  • 732
  • 01 Nov 2020
Topic Review
Cutaneous Squamous Cell Carcinoma (CSCC)
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. Several drugs have been developed for CSCC treatment, but the disease may actually be induced by drugs as well. Molecular mechanisms underlie pharmacologically-induced CSCC, and a sound knowledge of them could help physicians better tackle this tumor. 
  • 731
  • 29 Oct 2020
Topic Review
Delivery Systems for Nucleic Acids/Proteins
Gene therapy has been used as a potential approach to address the diagnosis and treatment of genetic diseases and inherited disorders. In this line, non-viral systems have been exploited as promising alternatives for delivering therapeutic transgenes and proteins. In this entry, we explored how biological barriers are effectively overcome by non-viral systems, usually nanoparticles, to reach an efficient delivery of cargoes.
  • 731
  • 31 Mar 2021
Topic Review
Current Insights on Antifungal Therapy
The high incidence of fungal infections has become a worrisome public health issue, having been aggravated by an increase in host predisposition factors. Despite all the drugs available on the market to treat these diseases, their efficiency is questionable, and their side effects cannot be neglected. Bearing that in mind, it is of upmost importance to synthetize new and innovative carriers for these medicines not only to fight emerging fungal infections but also to avert the increase in drug-resistant strains.
  • 730
  • 29 Sep 2020
Topic Review
The Role of Saponins in the Neuropathic Pain
Neuropathic pain is a chronic pain caused by tissue injury or disease involving the somatosensory nervous system, which seriously affects the patient’s body function and quality of life. Saponins are a class of compounds with diverse structures, consisting of sapogenin and glycosyl groups. The common ones of the saccharides that make up saponins are D-glucose, D-galactose, D-xylose, L-arabinose, and L-rhamnose, etc.
  • 729
  • 18 Jul 2022
Topic Review
Therapeutic Potential of Jasmonic Acid
The main representatives of jasmonate compounds include jasmonic acid and its derivatives, mainly methyl jasmonate. Extracts from plants rich in jasmonic compounds show a broad spectrum of activity, i.e., anti-cancer, anti-inflammatory and cosmetic. Studies of the biological activity of jasmonic acid and its derivatives in mammals are based on their structural similarity to prostaglandins and the compounds can be used as natural therapeutics for inflammation. Jasmonates also constitute a potential group of anti-cancer drugs that can be used alone or in combination with other known chemotherapeutic agents.
  • 729
  • 28 Sep 2021
Topic Review
Diarylureas
The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties.
  • 729
  • 25 Jan 2021
Topic Review
Radiation-engineered nano-scale bio-hybrid polymer devices
Bio-hybrid hydrogels consist of a water-swollen hydrophilic polymer network encapsulating or conjugating single biomolecules, or larger and more complex biological constructs like whole cells. By modulating at least one dimension of the hydrogel system at the micro- or nanoscale, the activity of the biological component can be extremely upgraded with clear advantages for the development of therapeutic or diagnostic micro- and nano-devices. Gamma or e-beam irradiation of polymers allow a good control of the chemistry at the micro-/nanoscale with minimal recourse to toxic reactants and solvents. Another potential advantage is to obtain simultaneous sterilization when the absorbed doses are within the sterilization dose range.
  • 729
  • 29 Jan 2021
Topic Review
PDE2A for Mouse Liver Development
cAMP and cGMP are intracellular signaling molecules produced in response to a plethora of extracellular signals in order to coordinate cellular metabolism, proliferation, differentiation and apoptosis. Phosphodiesterases (PDEs) are the enzymes that hydrolyze cAMP and cGMP in order to end or to limit the responses to these signals. To date 11 PDE families (named PDE1 to PDE11) have been identified across each cell type expressed in a peculiar pattern. They enclose 21 genes that codify approximately 100 enzymes that form a redundant network ensuring the compensation of activity in case of alteration of activity or lack of expression of one of the members. PDE2A, a cAMP-hydrolyzing enzyme, represents the exception to this picture, as PDE2A knockout is embryonic lethal. Knockout embryos show that the lack of the enzyme has the greatest impact on the development of the heart and of the liver, which is no longer able to assume its hematopoietic role. The increase of the intracellular cAMP level and the downregulation of the anti-apoptotic gene Bcl2 might explain the loss of integrity in the PDE2A knockout liver niche that compromises the hematopoietic function and maturation.
  • 726
  • 29 Oct 2020
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