Interestingly, sunitinib treatment resulted in significant downregulation of angiogenesis-related genes, in line with its mechanism of action. Similar to hiPS-derived-cardiomyocytes, heart slices recapitulated the expected toxicity of doxorubicin and trastuzumab, however, slices were superior in detecting sunitinib cardiotoxicity and mechanism in the clinically relevant concentration range of 0.1-1 μM. These results indicate that heart slice culture models have the potential to become a reliable platform for testing and elucidating mechanisms of drug cardiotoxicity.Gastrointestinal (GI) cancers, leading causes of cancer-related deaths, have been serious challenging human diseases up to now. Because of high rates of mortality, late-stage diagnosis, metastasis to distant locations, and low effectiveness and adverse events of routine standard therapies, the quality of life and survival time are low in patients with GI cancers. Hence, many efforts need to be done to explore and find novel efficient treatments. Beneficial effects of melatonin have been reported in a wide variety of human diseases. Melatonin has antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. Various studies have showed the regulatory effects of melatonin on apoptotsis, autophagy and angiogenesis; these properties result in the inhibition of invasion, migration, and proliferation of GI cancer cells in vivo and in vitro. Together, this review suggests that melatonin in combination with anticancer agents may improve the efficacy of routine medicine and survival rate of patients with cancer.Mucopolysaccharidoses (MPS) represent a devastating group of lysosomal storage diseases (LSD) affecting approximately 1 in 25,000 individuals, where degradation of glycosaminoglycans (GAG) by lysosomal enzymes is impaired due to mutations causing defects in one of GAG-degrading enzymes. The most commonly used therapy for MPS is enzyme replacement therapy, consisting of application of an active form of the missing enzyme. However, supply of the missing enzyme is not enough in case of MPS types whose symptoms are expressed in central nervous system (CNS), as enzyme does not cross the blood-brain barrier. Moreover, even though enzyme replacement therapy for non-neuronopathic MPS IVA type is approved, it has a limited impact on bone abnormalities, that are one of main symptoms in the disease. Therefore, research into alternative therapeutic approaches for these types of MPS is highly desirable. One such alternative strategy is accelerated degradation of GAG by induction of autophagy. Autophagy is a process of lysosomal degradation of macromolecules that become abnormal or unnecessary for cells. One of the latest discoveries is that GAGs can also be such molecules. Potential drug should also cross blood-brain barrier and be safe in long-term therapy. It seems that one of the polyphenols, resveratrol, can meet the requirements. The mechanism of its action in autophagy stimulation is pleiotropic. Therefore, in this review, we will briefly discuss potential of resveratrol treatment for mucopolysaccharidosis through autophagy stimulation based on research in diseases with similar outcome.Conotoxins (CnTX) are bioactive peptides produced by marine molluscs belonging to Conus genus. The biochemical structure of these venomous peptides is characterized by a low number of amino acids linked with disulfide bonds formed by a high degree of post-translational modifications and glycosylation steps which increase the diversity and rate of evolution of these molecules. CnTX different isoforms are known to target ion channels and, in particular, voltage-gated sodium (Na+) channels (Nav channels). These are transmembrane proteins fundamental in excitable cells for generating the depolarization of plasma membrane potential known as action potential which propagates electrical signals in muscles and nerves for physiological functions. Disorders in Nav channel activity have been shown to induce neurological pathologies and pain states. Here, we describe the current knowledge of CnTX isoform modulation of the Nav channel activity, the mechanism of action and the potential therapeutic use of these toxins in counteracting neurological dysfunctions.Lexical perseveration, the inappropriate repetition of a previous response, is common in aphasia. Two underlying mechanisms have been proposed residual activation and incremental learning. Previous attempts to differentiate the two have relied on experimental paradigms that encourage semantically related errors and analysis techniques designed to detect perseverations over short distances, resulting in a bias towards detecting short-lag, semantically related perseverations that both mechanisms can account for. Two key predictions that differentiate these accounts remain untested only residual activation can explain short-lag, semantically unrelated perseverations, whereas only incremental learning can explain long-lag, semantically related perseverations.  https://www.selleckchem.com/products/gsk-3008348-hydrochloride.html  In this paper, we used a large set of picture naming trials and a novel analysis technique to test these key predictions in a multi-session study involving six individuals with aphasia. We found clear evidence for both mechanisms in different individuals, demonstrating that either one is sufficient to cause perseveration. Importantly, perseverations due to residual activation were associated with more severely impaired systems than those due to incremental learning, suggesting that a certain degree of structural and functional integrity was necessary for incremental learning. Finally, the results supported a key prediction of the incremental learning account by showing perseverations over longer lags than have previously been reported.Bone morphogenetic proteins (BMPs) are a highly conserved and diverse family of proteins that play essential roles in various stages of development including the formation and patterning of the central nervous system (CNS). Bioavailability and function of BMPs are regulated by input from a plethora of transcription factors and signaling pathways. Intriguingly, recent literature has uncovered novel roles for BMPs in regulating homeostatic and pathological responses in the adult CNS. Basal levels of BMP ligands and receptors are widely expressed in the adult brain and spinal cord with differential expression patterns across CNS regions, cell types and subcellular locations. Recent evidence indicates that several BMP isoforms are transiently or chronically upregulated in the aged or pathological CNS. Genetic knockout and pharmacological studies have elucidated that BMPs regulate several aspects of CNS injury and repair including cell survival and differentiation, reactive astrogliosis and glial scar formation, axon regeneration, and myelin preservation and repair.