Search results for: P. N. Guru

Authors: Jayashree And Gajjam

Abstract:

Intellectual humility (IH) is defined as a virtuous mean between intellectual arrogance and intellectual self-diffidence by the ‘Doxastic Account of IH’ studied, researched and developed by western scholars not earlier than 2015 at the University of Edinburgh. Ancient Indian philosophical texts or the Upanisads written in the Sanskrit language during the later Vedic period (circa 600-300 BCE) have long addressed the virtue of being humble in several stories and narratives. The current research paper questions and revisits these character traits in an Indian context following an experimental method. Based on the subjective reports of more than 400 Indian teenagers and adults, it argues that while a few traits of IH (such as trustworthiness, respectfulness, intelligence, politeness, etc.) are panhuman and pancultural, a few are not. Some attributes of IH (such as proper pride, open-mindedness, awareness of own strength, etc.) may be taken for arrogance by the Indian population, while other qualities of Intellectual Diffidence such as agreeableness, surrendering can be regarded as the characteristic of IH. The paper then gives the reasoning for this discrepancy that can be traced back to the ancient Indian (Upaniṣadic) teachings that are still prevalent in many Indian families and still anchor their views on IH. The name Upanisad itself means ‘sitting down near’ (to the Guru to gain the Supreme knowledge of the Self and the Universe and setting to rest ignorance) which is equivalent to the three traits among the BIG SEVEN characterized as IH by the western scholars viz. ‘being a good listener’, ‘curious to learn’, and ‘respect to other’s opinion’. The story of Satyakama Jabala (Chandogya Upanisad 4.4-8) who seeks the truth for several years even from the bull, the fire, the swan and waterfowl, suggests nothing but the ‘need for cognition’ or ‘desire for knowledge’. Nachiketa (Katha Upanisad), a boy with a pure mind and heart, follows his father’s words and offers himself to Yama (the God of Death) where after waiting for Yama for three days and nights, he seeks the knowledge of the mysteries of life and death. Although the main aim of these Upaniṣadic stories is to give the knowledge of life and death, the Supreme reality which can be identical with traits such as ‘curious to learn’, one cannot deny that they have a lot more to offer than mere information about true knowledge e.g., ‘politeness’, ‘good listener’, ‘awareness of own limitations’, etc. The possible future scope of this research includes (1) finding other socio-cultural factors that affect the ideas on IH such as age, gender, caste, type of education, highest qualification, place of residence and source of income, etc. which may be predominant in current Indian society despite our great teachings of the Upaniṣads, and (2) to devise different measures to impart IH in Indian children, teenagers, and younger adults for the harmonious future. The current experimental research can be considered as the first step towards these goals.

Keywords: ethics and virtue epistemology, Indian philosophy, intellectual humility, upaniṣadic texts in ancient India

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

Procedia PDF Downloads 65