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Topic Review
Intra-Organismal Distribution of Tetrodotoxin in Tetrodotoxin-Bearing Animals
Tetrodotoxin (TTX), one of the deadliest natural toxins, has attracted the interest of researchers from various fields for decades. This non-protein, weakly basic, heat-resistant low-molecular-weight toxin selectively blocks voltage-gated sodium channels along the muscle and nerve cells.
  • 918
  • 08 Nov 2022
Topic Review
Allosteric Drug Discovery
Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
  • 918
  • 26 Sep 2021
Topic Review
Anticancer Properties of Carnosol
Cancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signaling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumors. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signaling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2).
  • 918
  • 15 Oct 2020
Topic Review
Maedi-Visna in Dairy Sheep
Maedi-visna in sheep is a chronic viral disease with worldwide distribution causing significant monetary losses in the sheep sector. Lack of effective treatment or vaccines, knowledge gaps regarding the epizootiology of the disease (e.g. significance of vertical and horizontal transmission) and the scarcity of protocols for the early and efficient diagnosis of maedi-visna infections are the major obstacles in the implementation of universally accepted control programs. The diagnostic methods currently used are based on the detection of either antibodies or the viral genome. In general, accuracy, sensitivity and specificity of the available serological and molecular assays vary and therefore, modifications on the diagnostic protocols on an evidential basis are necessary. Therefore, the combination of diagnostic assays and the development of effective strategies for mass implementation thereof are critical targets to achieve and constitute major challenges in maedi-visna research field.
  • 918
  • 28 Oct 2020
Topic Review
Methyltransferase SETDB1
SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase that exerts important effects on epigenetic gene regulation. SETDB1 complexes (SETDB1-KRAB-KAP1, SETDB1-DNMT3A, SETDB1-PML, SETDB1-ATF7IP-MBD1) play crucial roles in the processes of histone methylation, transcriptional suppression and chromatin remodelling.
  • 917
  • 02 Aug 2021
Topic Review
Deinonychosauria
Deinonychosauria is a probable stem-bird clade of maniraptoran dinosaurs that lived from the Late Jurassic to the Late Cretaceous periods. Fossils have been found across the globe in North America, Europe, Africa, Japan , China , Mongolia, Manchuria, Madagascar , Argentina , and Antarctica, with fossilized teeth giving credence to the possibility that they inhabited Australia as well. This group of dinosaurs are known for their sickle-shaped toe claws and features in the shoulder bones.
  • 917
  • 24 Oct 2022
Topic Review
Peroxisomal Stress Response and Inter-Organelle Communication
Peroxisomes are single membrane-bound organelles found in all eukaryotic cells and organisms, from yeast to plants and mammals. They are key regulators of cellular and metabolic homeostasis. These organelles play important roles in redox metabolism, the oxidation of very-long-chain fatty acids (VLCFAs), and the biosynthesis of ether phospholipids. Given the essential role of peroxisomes in cellular homeostasis, peroxisomal dysfunction has been linked to various pathological conditions, tissue functional decline, and aging. In the past few decades, a variety of cellular signaling and metabolic changes have been reported to be associated with defective peroxisomes, suggesting that many cellular processes and functions depend on peroxisomes. Peroxisomes communicate with other subcellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum (ER), and lysosomes. These inter-organelle communications are highly linked to the key mechanisms by which cells surveil defective peroxisomes and mount adaptive responses to protect them from damages. 
  • 917
  • 15 Feb 2022
Topic Review
History of Pregnancy Test
The home pregnancy test is the most frequently performed laboratory test for self-diagnosis (home diagnostic test). It is also the first laboratory test that has been adapted for self-use at home.
  • 918
  • 11 Sep 2023
Topic Review
Ryanodine Receptor
The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation–contraction coupling. The activity of the RyR is regulated by the changes in the level of many intracellular factors, such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly.
  • 917
  • 20 Oct 2021
Topic Review
The Pathology of Parkinson’s Disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by a loss of dopaminergic neurons, leading to bradykinesia, rigidity, tremor at rest, and postural instability, as well as non-motor symptoms such as olfactory impairment, pain, autonomic dysfunction, impaired sleep, fatigue, and behavioral changes. 
  • 917
  • 23 Feb 2021
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