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In silico molecular docking and virtual screening of natural compounds against Tubulin-7-Aminonoscapine complex (6Y6D) for estimation of anticancer potential
No full text117-130This comprehensive study integrated in silico molecular docking and pharmacokinetic profiling to elucidate the interactions and properties of eight bioactive compounds (nimbin, azadirachtin, betasitosterol, nimbidinin, chavicol, chavibetol, curcumin, and zingiberene) from natural sources with protein 6Y6D. SwissADME and SwissTargetPrediction are used for pharmacokinetic screening, whereas, autodock vina is used for molecular docking and virtual screening. Protox3 software was used to establish each phytoconstituent's specific toxicity profile. According to the results, nimbidinin and nimbin exhibit extraordinary binding affinity without toxicity and have the potential to be further screened as lead compounds. Azadirachtin, on the other hand, exhibits the highest binding affinity with a moderate toxicity profile. Furthermore, zingiberene and chavicol exhibit low binding affinities. A detailed investigation reveals the binding modes and molecular interactions with different amino acids. Our findings may facilitate the development of novel drugs and provide a foundation for further experimental validation
Exploring the Intersection of AI and IPR in the Context of the Emerging Phenomenon of Deepfakes
No full text59-64The article endeavors to delve deep into the world of 'deepfakes'. Deepfakes are a product of technological advancements
in artificial intelligence (AI) which have creators and consumers of their own. However, like any other technological
invention, the phenomenon of deepfakes also presents itself as a double-edged sword. The disruptions produced by
deepfakes have become ubiquitous, transcending geographical borders, and blurring boundaries between reality and fiction.
The intersection between artificial intelligence and intellectual property rights is a crucial assessment point and merits
meticulous examination, considering its contemporary relevance. The article is an attempt to review and analyze the
disruptive nature of deepfakes, their manifestations and ramifications in the world of media and entertainment, the recipients
of the infamous technology, and their corresponding rights, including personality rights and right of publicity, potential
threats, and possible legal remedies within the framework of intellectual property law
Application of CuO nanoparticles on performance and emission characteristics of ternary blends of diesel, waste cooking oil and pumpkin seed oil biodiesel in an IC engine
No full text33-40The aim of this work is to demonstrate the effect of copper oxide (CuO) nanoparticles doped biodiesel on the
performance and emission characteristics of a compression ignition (CI) engine. The base fuel (B20) is a ternary blend of
10% waste cooking oil (WCO) biodiesel, 10% pumpkin seed oil (PSO) biodiesel, and 80% conventional diesel. The B20
blend has been doped with CuO nanoparticles at four different dosage of 20, 40, 60 and 80 ppm. The tests are conducted on
a single-cylinder diesel engine with no modifications and under standard operating conditions. WCO and PSO were
identified for this work due to their good economic viability, and the oils are converted into biodiesel through the
transesterification process. The performance parameters, such as brake thermal efficiency (BTE) and brake specific fuel
consumption (BSFC) under different load conditions are evaluated. The emission characteristics of carbon monoxide (CO),
hydrocarbons (HC), and oxides of nitrogen (NOx) are also considered for this study. From the results, it is found that the use
of a ternary blend with CuO for an IC engine gives higher BTE with reduced BSFC. It is also perceived that the emission of
CO and HC from the engine can be controlled with the addition of CuO nanoparticles
Synthesis of a redox-active pyrene-FLFL-dopamine amphiphile and investigation of their self-assembly at different pH leading to microfibrous formation
No full text98-105N-(1-((1-((3,4-Dihydroxyphenethyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4-(pyren-1-yl)butanamide (Py-FL-FL-DP) has been synthesised using the traditional amide coupling reactions of 1-pyrene butyric acid, boc-l-phenyl alanine, l-phenyl alanine methyl ester and dopamine. Py-FL-FL-DP shows a pH dependant aggregation between pH 4 and 10 which can be monitored spectroscopically, resulting in a reversible quinone/hydroquinone oxidation – reduction transformation of the dopamine moiety. The photoexcitation of Py-FL-FL-DP at λex 345 nm at higher pH preferentially results in aggregation induced emission (AIE) photorelaxation mechanism in comparison to thermal relaxation or intramolecular charge transfer (ICT). SEM micrographs show the formation of fibrillar nanostructure with increasing pH specially at pH 10. The CD experiment offers deeper insights into the chirality that developed in the nanofiber self-assemblies at pH levels 7 to 10, which is attributed to the twisted conformations of the pyrene moieties within the self-assembled structure. The unique pH-dependent self-assembly and redox behavior of Py-FL-FL-DP, particularly its reversible optical and structural changes in response to pH variations, make it a promising candidate for real-time pH monitoring in biomedical applications, such as intracellular imaging and the design of controlled drug delivery systems targeting pH-sensitive environments
CRISPR/Cas9 mediated next generation gene therapy in chronic myeloid leukemia
No full text52-65Present study, we aimed to manipulate the BCR::ABL1 fusion gene, which is responsible for the etiopathogenesis of Chronic myeloid leukemia (CML), in vitro. Mechanism of this molecular pathogenesis is based on encoding the BCR::ABL1p210 oncoprotein with excessive and irregular tyrosine kinase activity and eventually causes the CML phenotype. On the other hand, patients developing drug resistance or the side effects of bone marrow transplantation on mortality and morbidity strengthened our hypothesis that CRISPR/Cas9 could be an advance in preclinical studies in this research. Cytogenetic and molecular genetic characterization of K562 cells has been performed. Intronic sequences were detected by sequencing in the translocation of the BCR::ABL1 fusion gene. Genome editing in CML cells was done by transfection of lipofectamine and electroporation. The efficiency of CRISPR/Cas9 on the BCR::ABL1p210 was analyzed by qRT-PCR. Gene expression of the BCR::ABL1p210 fusion before and after CRISPR/Cas9 manipulation, which changed during the culture time, was compared logarithmic over the transcript values in the molecular response. We recorded that BCR::ABL1p210 manipulation showed an approximately 100-fold decrease in expression as (+1 log) before (-1 log) after CRISPR/Cas9 manipulation. Thus, the BCR::ABL1p210 fusion gene expression was significantly decreased by mediated CRISPR/Cas9 manipulation. As a result, the effect of the CRISPR/Cas9 genome editing was revealed via the knockdown of the BCR::ABL1p210 in our study. Thus, CRISPR/Cas9 can target the BCR::ABL1p210 fusion gene due to the interference effect
Aspergillus niger acidogenic metabolism: A biased view from the C and N interface
No full text321-330Aspergillus niger is the major citric acid producer and this has matured into an industrial process through fermentation.
Despite a century of research to elucidate the underlying mechanisms of acidogenesis, clear and definitive answers have
eluded us. The voluminous literature ranges from fungal physiology to genomics. Much of it focuses on carbon
stoichiometry between glucose and citric acid and has overlooked the extant close interactions between the fungal carbon
and nitrogen metabolism. Because the regulation at the carbon-nitrogen interface is important, several approaches were
taken to discern the role of A. niger nitrogen metabolism in acidogenesis. An enhanced GABA shunt operates while the
carbon flux exits TCA cycle at citrate. The NADP-glutamate dehydrogenase bridges TCA cycle and GABA shunt. The
allosteric response of this enzyme to 2-oxoglutarate could control the carbon flux at the interface of carbon-nitrogen
metabolism. While Mn[II] limitation favours citric acid production, arginase (metalloenzyme with bound Mn[II]) does not
directly affect the fungal citrate overflow. The acidogenic growth appears to mimic nitrogen starvation and is associated
with an extended autophagic state of A. niger. The atg strains are compromised in citrate overflow thereby directly
implicating autophagy in the process. Autophagy-associated movement of relevant enzymes during fermentation suggests
that the entire citrate synthesis machinery could be operating insidethe fungal vacuole
Advances in myogenic differentiation: Role of stem cells, RNA-binding proteins, Molecular pathways, and Detection techniques
No full text301-320The demand for effective muscle regeneration therapies has grown with the prevalence of muscle-degenerative conditions like muscular dystrophies which lack curative treatments. Although stem cells, including induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs), have great promise for muscle regeneration, their therapeutic application is constrained in the absence of a thorough comprehension of myogenic differentiation mechanisms. A complicated network of molecular pathways, including Wnt, Notch, and Hedgehog, controls the myogenic differentiation process of the muscle progenitors. Various transcription regulators, including MyoD1, Pax 3 and 7, Myf5, and Mrf4, and the Cis-regulatory sites near the promoters, orchestrate the intricate mechanisms of gene regulation for differentiation. Activation of the signaling cascades conveys the message of muscle tissue-specific gene expression via regulating the genes at the transcriptional, epigenetic, post-transcriptional, and translational stages. Muscle-specific DNA methylation, histone acetylation and deacetylation, histone methylation, etc., and their regulators also play crucial roles in the chromatin accessibility of myogenic gene expression. In addition, The RNA-binding protein families, especially the MBNL-family, hnRNP-family, and the CELF-family, which modulate RNA-splicing, mRNA stability, and translation, are also major players in this process. Misregulation of these regulatory factors may cause muscle pathogenesis in patients. Metabolic alterations in glycolysis and OXPHOS due to changes in energy demand are crucial regulatory steps of myogenic differentiation of stem cells. Changes in mitochondrial biogenesis and metabolic pathways meet the shifting energy needs while controlling the levels of reactive oxygen species affecting the fate of the stem cells. In this review article, we discussed the advances made in the recent past of all the above aspects of myogenic differentiation of stem cells along with cutting-edge technologies, including real-time imaging, metabolic imaging, gene editing tools, and organoid cultures to study the dynamic changes at the cellular and subcellular levels during muscle differentiation
