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Topic Review
Fucoidans and Bowel Health
Fucoidans are cell wall polysaccharides found in various species of brown seaweeds. They are fucose-containing sulfated polysaccharides (FCSPs) and comprise 5–20% of the algal dry weight. Fucoidans possess multiple bioactivities, including antioxidant, anticoagulant, antithrombotic, anti-inflammatory, antiviral, anti-lipidemic, anti-metastatic, anti-diabetic and anti-cancer effects. Dietary fucoidans provide small but constant amounts of FCSPs to the intestinal tract, which can reorganize the composition of commensal microbiota altered by FCSPs, and consequently control inflammation symptoms in the intestine. Although the bioactivities of fucoidans have been well described, there is limited evidence to implicate their effect on gut microbiota and bowel health.
  • 714
  • 27 Aug 2021
Topic Review
Nintedanib
Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families.
  • 713
  • 30 Sep 2021
Topic Review
Drug Discovery Research around Tetanus Toxin Fragment C
Tetanus caused by the tetanus toxin (TT) is a fatal illness, which despite the existence of a vaccine, led to an estimated 34,684 deaths in 2019. TT is a neurotoxin produced by Clostridium tetani, a Gram-positive pathogenic bacterium, mainly found in soil and the gastrointestinal tracts of animals. TT induces the inhibition of neurotransmitter release, leading to spastic paralysis in a four-step process. First, TT binds to specific receptors, mainly composed of lipids and gangliosides, found at the neuromuscular junction (NMJ). Another receptor is reached by TT after these first bindings: a protein receptor responsible for its internalization (second step). This double receptor binding is responsible for the high affinity between TT and nerve cells. Third, TT is then transported into the cell body via axonal retrograde transport. In the last step, the proteolytic cleavage by TT of the VAMP/synaptobrevin, a neuronal substrate, leads to the inhibition of neurotransmitter release. All of these biological properties can be distinct associated parts of the TT structure. TT is a 150.7 kDa protein composed of a 52.4 kDa light chain and a 98.3 kDa heavy chain linked by a disulfide bond.
  • 708
  • 26 Aug 2022
Topic Review
Differential Inhibitors of Aldose Reductase
Aldose reductase, classified within the aldo-keto reductase family as AKR1B1, is an NADPH dependent enzyme that catalyzes the reduction of hydrophilic as well as hydrophobic aldehydes. AKR1B1 is the first enzyme of the so-called polyol pathway that allows the conversion of glucose into sorbitol, which in turn is oxidized to fructose by sorbitol dehydrogenase. The activation of the polyol pathway in hyperglycemic conditions is generally accepted as the event that is responsible for a series of long-term complications of diabetes such as retinopathy, cataract, nephropathy and neuropathy. The role of AKR1B1 in the onset of diabetic complications has made this enzyme the target for the development of molecules capable of inhibiting its activity.
  • 707
  • 11 Apr 2022
Topic Review
Gold-based anticancer delivery systems
The structures of these gold derivatives (i.e. gold nanoparticles, gold (I)/(III) complexes and carbene-based gold complexes) were synthesized to evaluate the influence of  increased activity and/or selectivity on their pharmacological effects.
  • 707
  • 06 Apr 2021
Topic Review
Medicinal-Plant Extracts against Chikungunya Virus
The lack of specific treatment for chikungunya fever makes the need for anti-chikungunya virus agents more crucial. This study was conducted to evaluate 132 extracts obtained by sequential solvent extraction from 21 medicinal plants for cytopathic effect inhibitory activity using virus-infected Vero cells in two different sample introduction modes. Among the extracts, 42 extracts (31.8%) from 12 plants in the concurrent mode and three extracts (2.3%) from a plant in the non-concurrent mode displayed strong cytopathic effect inhibitory activity (cell viability ≥70%). Viral load quantification analysis unveiled that the extracts of Clinacanthus nutans (chloroform, ethyl acetate, and ethanol), Hydrocotyle sibthorpioides (ethanol), and Ocimum americanum (ethanol and methanol) hindered the release of viral progeny from the infected cells while the extracts of Ficus deltoidea (ethanol), Gynura bicolor (water), H. sibthorpioides (water), and O. americanum (chloroform and ethyl acetate) blocked the entry of virus into the cells. The extracts of Diodella sarmentosa (ethyl acetate), Diplazium esculentum (chloroform, ethyl acetate, and ethanol), and G. bicolor (ethanol) possessed virucidal effect and caused 5.41-log to 6.63-log reductions of viral load compared to the virus control. The results indicate that these medicinal plants are potential sources of anti-chikungunya virus agents that have varied modes of action. 
  • 706
  • 16 Aug 2021
Topic Review
Human Drug-Drug Interactions
Patients suffering from complex diseases (infectious diseases, oncology) or several conditions (co-morbidities) require combination therapies of different drugs. Combining different drugs will potentially lead to drug-drug interactions, influencing the efficacy and safety of the treatment. Development of novel drugs that are intended to be used in combination should consider drug-drug interactions as early as possible. Even with limited data, drug-drug interactions in humans can be predicted using model-informed drug discovery and development (MID3). The concept to utilize and integrate data from in vitro combination experiments combined with preclinical in vivo data on the exposure-response relationships of the drugs in combination through a computational model-informed approach, is introduced here with tuberculosis as case study.
  • 704
  • 29 May 2021
Topic Review
The Pharmaceutical Industry in 2021
2021 will be remembered for the COVID-19 pandemic. Although five vaccines have been approved by the two most important drug regulatory agencies, namely the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the pandemic has still not been brought under control. However, despite the context of a global pandemic, 2021 has been an excellent year with respect to drug approvals by the FDA. In 2021, 50 drugs have been authorized, making it the fourth-best year after 2018 (59 drugs) and 1996 and 2020 (53 each). Regarding biologics, 2021 has been the third-best year to date, with 14 approvals, and it has also witnessed the authorization of 36 small molecules.
  • 704
  • 21 Mar 2022
Topic Review
Lymphatic Route in Cardiovascular Medicine
The lymphatic network is a unidirectional and low-pressure vascular system that is responsible for the absorption of interstitial fluids, molecules, and cells from the peripheral tissue, including the skin and the intestines. Targeting the lymphatic route for drug delivery employing traditional or new technologies and drug formulations is exponentially gaining attention in the quest to avoid the hepatic first-pass effect. 
  • 704
  • 19 Aug 2021
Topic Review
The Structure and Function of Integrins
Integrins are heterodimeric transmembrane proteins that mediate adhesive connections between cells and their surroundings, including surrounding cells and the extracellular matrix (ECM). They modulate tissue mechanics and regulate intracellular signaling, including cell generation, survival, proliferation, and differentiation, and the up-regulation of integrins in tumor cells has been confirmed to be associated with tumor development, invasion, angiogenesis, metastasis, and therapeutic resistance. Thus, integrins are expected to be an effective target to improve the efficacy of tumor therapy. A variety of integrin-targeting nanodrugs have been developed to improve the distribution and penetration of drugs in tumors, thereby, improving the efficiency of clinical tumor diagnosis and treatment. 
  • 703
  • 29 Jun 2023
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