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Topic Review
Innovations in Chewable Formulations and 3D Printing
Since their introduction, chewable dosage forms have gained traction due to their ability to facilitate swallowing, especially in paediatric, geriatric and dysphagia patients. Their benefits stretch beyond human use to also include veterinary applications, improving administration and palatability in different animal species. Despite their advantages, current chewable formulations do not account for individualised dosing and palatability preferences. In light of this, three-dimensional (3D) printing, and in particular the semi-solid extrusion technology, has been suggested as a novel manufacturing method for producing customised chewable dosage forms. This advanced approach offers flexibility for selecting patient-specific doses, excipients, and organoleptic properties, which are critical for ensuring efficacy, safety and adherence to the treatment. 
  • 677
  • 07 Sep 2022
Topic Review
Metformin for Lung Cancer
Metformin is an oral biguanide which has been first-line treatment for type 2 diabetes for several years, however, research has showed that patients undergoing treatment with metformin have a decreased risk for cancer. Interestingly, the compund exhibits a considerable number of antitumor effects which could potentially improve lung cancer treatment. Nonetheless, data regarding the use of metformin as part of the therapeutic scheme for patients with lung cancer has been inconsistent to date. One of the points that the current literature fails to address is the differential effects of metformin in lean vs. obese subjects, which is well established in its use for diabetes, as well as its newly described mechanism of action which depends on redox status of the tumor cell.
  • 677
  • 04 Jul 2022
Topic Review
A Novel, Pan-PDE Inhibitor From the Group of 7,8-Disubstituted Purine-2,6-Dione Derivatives
Phosphodiesterases (PDEs) inhibitors are currently a widespread and extensively studied group of anti-inflammatory and anti-fibrotic compounds which may find use in the treatment of numerous lung diseases, including asthma and chronic obstructive pulmonary disease. Several PDE inhibitors are currently in clinical development, and some of them, e.g. roflumilast, are already recommended for clinical use. Due to numerous reports indicating that elevated intracellular adenosine 3’,5’-cyclic monophosphate (cAMP) levels may contribute to alleviation of inflammation and airway fibrosis, new and effective PDE inhibitors are constantly being sought. Recently, a group of 7,8-disubstituted purine-2,6-dione derivatives, representing novel and prominent pan-PDE inhibitors has been synthesized. Some of them were reported to modulate transient receptor potential ankyrin 1 (TRPA1) ion channels as well. Compound 145 (4-(8-butoxy-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(5-(tert-butyl)-2-hydroxyphenyl)butanamide) – a pan-PDE inhibitor and a weak TRPA1 modulator inhibited fibroblast to myofibroblasts transition (FMT) as well as MRC-5 human lung fibroblasts proliferation, migration, and contraction. The effect of this compound appeared to depend mainly on its strong PDE inhibitory properties, and not on its effects on TRPA1 modulation. The strong anti-remodelling effects of 145 required activation of the cAMP/protein kinase A/CREB pathway leading to inhibition of transforming growth factor type β1 (TGF-β1) and Smad-dependent signalling in MRC-5 cells.
  • 677
  • 09 Sep 2021
Topic Review
Cardiothoracic Surgical Critical Care Medicine
Cardiothoracic surgical critical care medicine (CT-CCM) is a medical discipline centered on the perioperative care of diverse groups of patients. With an aging demographic and an increase in burden of chronic diseases the utilization of cardiothoracic surgical critical care units is likely to escalate. Given these projections, it is important to assess the state of cardiothoracic surgical intensive care, to develop goals and objectives for the future, and to identify knowledge gaps in need of scientific inquiry.
  • 677
  • 09 Jan 2023
Topic Review
Dietary Macronutrients in Modulating Gut Microbiota
Over the past two decades a plethora of studies have identified broad-spanning associated links between the gut microbiota and systemic health and disease risk. The responses of the gut microbiota to sensitive factors are considered to be a valuable tool to exploit and develop new strategies to promote human health. Among these influential factors, dietary factors, including micro- and macro-nutrients, are the most influential in shaping and modulating the human gut microbiota.
  • 678
  • 30 Jun 2022
Topic Review
Intensive Care Unit-Acquired Weakness and Sarcopenia
Intensive care unit-acquired weakness (ICUAW) brings about skeletal muscle wasting due to critical illness and has important clinical implications, significantly impacting rehabilitation, and increasing both morbidity and mortality. ICUAW is sometimes referred to as critical illness polyneuromyopathy—being called critical illness polyneuropathy (CIP) when nerve involvement predominates, or critical illness myopathy (CIM) where muscle involvement is crucial. It manifests as muscle weakness that develops rapidly, prior to any detectable muscle wasting. 
  • 677
  • 10 Aug 2022
Topic Review
Unnatural Gallotannins
Nature has been a source of inspiration for the development of new pharmaceutically active agents. Polyphenols, including gallotannins, are widely studied as they protect cells against oxidative damage and pathogen attack. A series of new unnatural gallotannins (GTs), derived from D-lyxose, D-ribose, D-rhamnose, D-mannose, and D-fructose have been designed and synthesized i order to study the protective and antimicrobial effects of synthetic polyphenols that are structurally related to plant-derived products. Apart from spectral analysis, their antioxidant activity was evaluated. Structurally different GTs were screened in vitro for their antimicrobial properties against a spectrum of staphylococci, enterococci, and mycobacteria. Furthermore, the antibiofilm activity of GTs against S. aureus, and their ability to inhibit sortase A were inspected. Experimental data suggest that synthetic GTs could be considered as promising candidates for pharmacological, biomedical, and food industry applications.
  • 677
  • 14 Sep 2021
Topic Review
Toxin-Based Models of Parkinson’s Disease
Different neurotoxins have been shown to cause DAergic neuron degeneration with a high degree of selectivity. Some utilize the dopamine transporter to enter the neurons, others are lipophilic agents or neurotransmitter receptors' agonists that, directly or indirectly, ultimately impair the mitochondrial respiratory chain. Taking advantage of these properties, several molecules have been extensively used to obtain PD experimental models. These include 6-OHDA, MPTP (MPP+), the pesticides rotenone and paraquat, and the non-protein aminoacid L-BMAA.
  • 677
  • 29 Apr 2022
Topic Review
Hypothermic and Normothermic Perfusion in Kidney Transplantation
Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment.
  • 678
  • 03 Dec 2021
Topic Review
Lomentospora prolificans: A Neglected Fungus
Lomentospora prolificans, formerly known as Scedosporium prolificans, is a rare, highly virulent filamentous fungus that has been incriminated for numerous infections in immunocompromised as well as immunocompetent individuals. Disseminated disease is largely confined to immunocompromised patients and has a high mortality rate. Successful recovery from infection is difficult due to high rates of intrinsic resistance to antifungals. Aggressive surgical debridement wherever appropriate, and effective and timely antifungal treatment are the pillars for successful management.
  • 677
  • 05 Sep 2022
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