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Topic Review
Aptamers in Parasitology
Aptamers are single-stranded DNA or RNA sequences of 20-80 nucleotides that interact with different targets such as: proteins, ions, viruses, or toxins, through non-covalent interactions and their unique three-dimensional conformation. They are obtained in vitro by the systematic evolution of ligands by exponential enrichment (SELEX). Because of their ability of target recognition with high specificity and affinity, aptamers are usually compared to antibodies. However, they present many advantages that make them promising molecules for the development of new methods for the diagnosis and treatment of human diseases. In medical parasitology, aptamers also represent an attractive alternative for the implementation of new parasite detection methods, easy to apply in endemic regions. The aim of this study was to describe the current advances in the development of diagnostic tests based on aptamers in parasitology. For this, articles were selected following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with specific inclusion and exclusion criteria. The 26 resulting articles deal with the use of aptamers for the detection of six important protozoa that affect human health. This systematic review clearly demonstrates the specificity, sensitivity and selectivity of aptamers and aptasensors, that certainly will soon become standard methods in medical parasitology.
  • 603
  • 18 Jan 2021
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.
  • 4.2K
  • 06 Sep 2021
Topic Review
Aqueous Prostaglandin Eye Drop Formulations
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the long-term treatment of open-angle glaucoma, prostaglandin analogues (PGAs) are the first-line treatment and are available as marketed eye drop formulations for intraocular pressure (IOP) reduction by increasing the trabecular and uveoscleral outflow. PGAs have low aqueous solubility and are very unstable (i.e., hydrolysis) in aqueous solutions, which may hamper their ocular bioavailability and decrease their chemical stability. Additionally, treatment with PGA in conventional eye drops is associated with adverse effects, such as conjunctival hyperemia and trichiasis. It has been a very challenging for formulation scientists to develop stable aqueous eye drop formulations that increase the PGAs’ solubility and enhance their therapeutic efficacy while simultaneously lowering their ocular side effects.
  • 554
  • 28 Oct 2022
Topic Review
Aqueous Soluble Drug
The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility.
  • 1.4K
  • 20 Sep 2022
Topic Review
Arachidonic, Docosahexaenoic Acids and neurodevelopment
The long-chain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid,22:6n-3 (DHA), and arachidonic acid,20:4n-6 (ARA) are important nutrients required for fetal brain growth and development. The accumulation of DHA and ARA in the fetal brain predominantly occurs in the third trimester of a human pregnancy. The de novo synthesis of these LCPUFAs seems low in a growing fetus and placenta; the maternal intake of these fatty acids contributes a significant share for brain development.
  • 520
  • 30 Jun 2021
Topic Review
Arboviruses as a Cause of Undifferentiated Febrile Illnesses
Arthropod-borne viruses (arboviruses) are, by definition, transmitted between vertebrate hosts by biting arthropods (mosquitoes, ticks, sandflies, midges and gnats). Some arboviral infections — notably, dengue, chikungunya, Zika, Japanese encephalitis, yellow fever and West Nile viruses — pose a major public health threat worldwide. Many others are known or thought to lead to acute undifferentiated febrile illness (UFI), of which a significant proportion of cases are not diagnosed. In low-income countries, a diagnosis of UFI is extremely common due to the lack of pathology laboratory resources. Yet, even in high-income nations, which have adequate access to and quality of diagnostic tools, up to one third of pyrexias may be of unknown origin. It has been estimated that between 12-35% of hospitalized patients with UFI die from UFI-associated complications. In this context, identifying the contribution of hitherto less studied arboviruses as potential etiological agents of UFI and prioritizing the development and availability of diagnostic tests may greatly assist in reducing the global burden of UFI-related disease.
  • 1.1K
  • 22 Apr 2022
Topic Review
Arboviruses in Australia
In excess of 75 arboviruses have been identified in Australia, some of which are now well established as causative agents of debilitating diseases. These include Ross River virus, Barmah Forest virus, and Murray Valley encephalitis virus, each of which may be detected by both antibody-based recognition and molecular typing. For most of the remaining arboviruses that may be associated with pathology in humans, routine tests are not available to diagnose infection. A number of these so-called ‘neglected’ or ‘orphan’ arboviruses are considered likely to have infected humans at a regular rate for decades. Some may be associated with undifferentiated febrile illness — fever, the cause of which is not obvious — for which around half of all cases each year remain undiagnosed. Ongoing research aims to better understand the distribution, epidemiology, and transmission ecology of these mosquito-transmitted viruses that are currently unique to Australia.
  • 1.5K
  • 22 Apr 2022
Topic Review
Arbutin
Arbutin is a compound with a structure in which one molecule of D-glucose is bound to hydroquinone.
  • 1.6K
  • 18 Aug 2021
Topic Review
Arctigenin Enhances the Cytotoxic Effect
Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of STAT3 and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial Bax levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX.
  • 530
  • 30 Oct 2020
Topic Review
Arcuate Neurocircuits
Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. A growing area of research is to better understand how peripheral hormones interact with a widely distributed network of brain circuits involved in the control of energy balance. In this regard, the arcuate nucleus of the hypothalamus has emerged as an important brain region due to its ability to sense circulating hormones and to modulate neural pathways controlling food intake and energy expenditure, and blood pressure.
  • 610
  • 22 Jul 2021
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