Alzheimer's disease (AD) is a typical progressive, chronic neurodegenerative disorder with worldwide prevalence. Its clinical manifestation involves the presence of extracellular plaques and intracellular neurofibrillary tangles (NFTs). NFTs occur in brain tissues as a result of both Ab agglomeration and Tau phosphorylation. Although there is no known cure for AD, research into possible cures and treatment options continues using cell-cultures and model animals/organisms. The nuclear factor-kappa b (NF-jb) plays an active role in the progression of AD. Impairment to this signaling module triggers undesirable phenotypic changes such as neuroinflammation, activation of microglia, oxidative stress related complications, and apoptotic cell death. These imbalances further lead to homeostatic abnormalities in the brain or in initial stages of AD essentially pushing normal neurons toward the degeneration process. Interestingly, the role of NF-jb signaling associated receptor-interacting protein kinase is currently observed in apoptotic and necrotic cell death, and has been reported in brains. Conversely, the NF-jb signaling pathway has also been reported to be involved in normal brain functioning. This pathway plays a crucial role in maintaining synaptic plasticity and balancing between learning and memory. Since any impairment in the pathways associated with NF-jb signaling causes altered neuronal dynamics, neurotherapeutics using compounds including, antioxidants, bioflavonoids, and non-steroidal anti-inflammatory drugs against such abnormalities offer possibilities to rectify aberrant excitatory neuronal activity in AD. In this review, we have provided an extensive overview of the crucial role of NF-jb signaling in normal brain homeostasis. We have also thoroughly outlined several established pathomechanisms associated with NF-jb pathways in AD, along with their respective therapeutic approaches.
Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial–mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.
Introduction:: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an increased mortality rate across the globe. However, the underlying mechanism of SARS-CoV-2 altering human immune response is still elusive. The existing literature on miRNA mediated pathogenesis of RNA virus viz. Dengue virus, West Nile virus, etc. raises a suspicion that miRNA encoded by SARS-CoV-2 might facilitate virus replication and regulate the host’s gene expression at the post-transcriptional level. Methods:: We investigated this possibility via computational prediction of putative miRNAs encoded by the SARS-CoV-2 genome using a novel systematic pipeline that predicts putative mature-miRNA and their targeted genes transcripts. To trace down if viral-miRNAs targeted the genes critical to the immune pathway, we assessed whether mature miRNA transcripts exhibit effective hybridization with the 3’UTR region of human gene transcripts. Conversely, we also tried to study human miRNA-mediated viral gene regulation to get insight into the miRNA mediated offense and defense mechanism of viruses and their host organisms in toto. Results:: Our analysis led us to shortlist six putative miRNAs that target, majorly, genes related to cell proliferation/differentiation/signaling, and senescence. Nonetheless, they also target immune-related genes that directly/indirectly orchestrate immune pathways like TNF (Tumor Necrosis Factor) signaling and Chemokine signaling pathways putatively serving as the nucleus to cytokine storms. Conclusion:: Besides, these six miRNAs were found to conserved so far across 80 complete genomes of SARS-CoV-2 (NCBI Virus, last assessed 12 April 2020) including Indian strains that are also targeted by 7 human miRNAs and can, therefore, be exploited to develop MicroRNA-Attenuated Vaccines.
Abstract. Natural Language Generation (NLG) is defined as the systematic approach for producing human understandable natural language text based on nontextual data or from meaning representations. This is a significant area which empowers human-computer interaction. It has also given rise to a variety of theoretical as well as empirical approaches. This paper intends to provide a detailed overview and a classification of the state-of-the-art approaches in Natural Language Generation. The paper explores NLG architectures and tasks classed under document planning, micro-planning and surface realization modules. Additionally, this paper also identifies the gaps existing in the NLG research which require further work in order to make NLG a widely usable technology.
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