p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

Funding Information: Funding: This work was supported by the Foundation for Science and Technology (FCT), through funds from the State Budget, and by the European Regional Development Fund through the “Pro-grama Operacional Regional do Centro (Centro 2020)—Sistema de Apoio à Investigação Científica e Tecnológica—Programas Integrados de IC&DT” (Project Centro-01-0145-FEDER-000019—C4—Centro de Competências em Cloud Computing) and the project ref: UIDB/00709/2020. This work was also supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. D. Gomes also acknowledges the doctoral fellowship from FCT (ref: 2020.06792.BD). This work was also supported by the Ramalingaswami Fellowship (BT/RLF/Re-entry/64/2017), Department of Biotechnology, Govt. of India (V.K.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6’s oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs.publishersversionpublishe

Bio-chemical amelioration effects on physico-chemical dynamics of sodic soils under rice (Oryza sativa) –wheat (Triticum aestivum) cropping system

The effect of dhaincha (Sesbania aculeata) as first crop on physico-chemical dynamics and productivity of “B” class sodic soils was assessed on farmer’s field under rice-wheat cropping system to generate the knowledge of sodic soil management for increasing the soil and crop productivity for sustainable crop production in sodic soil environment. The experiment was laid out in randomized block design at ten sites having six treatment combinations of different doses of gypsum and green manuring with sesbania under two cropping sequences, i e sesbania-rice (Oryza sativa L.) -wheat (Triticum aestivum L.) and rice-wheat. Cultivation of sesbania with gypsum significantly decreased the surface soil pH from 9.3 to 8.6 and increased the hydraulic conductivity from 0.3 × 10-3 to 3.7 × 10-3 cm/hr and buildup of soil organic matter by increasing organic carbon content from 0.20 % to 0.22 % through growing of sesbania. Sesbania green manure also increased the available water content in the soil system, which enhanced soil moisture availability for longer period. As a result, rice crop yield increased by 16.2 % in sesbania-rice- wheat cropping system in comparison to rice–wheat cropping sequence because of synergistic effect of sesbania with gypsum. Consequently, residual effect of sesbania green manuring alone and in combination with gypsum significantly enhanced the wheat grain yield by 42.5 % and 72.5 % and 80% in T4, T5 and T6 treatments respectively during first year in sesbania–rice-wheat cropping sequence as compared to control. In consecutive second year, rice and wheat grain yields further enhanced by 8.1 % and 2.71% respectively, under sesbania –rice -wheat than that of rice –wheat cropping sequence. Under sesbania- rice- wheat and rice-wheat-sesbania cropping sequence, rice and wheat grain yield were similar. Hence, inclusion of Sesbania aculeata as green manure either before or after rice-wheat cropping sequence is equally better to improve the soil physical dynamics and crop productivity of ‘B’ class sodic soils in Indo-Gangetic region of Uttar Pradesh

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Not AvailableThe effect of dhaincha (Sesbania aculeata) as first crop on physico-chemical dynamics and productivity of “B” class sodic soils was assessed on farmer’s field under rice wheat cropping system to generate the knowledge of sodic soil management for increasing the soil and crop productivity for sustainable crop production in sodic soil environment. The experiment was laid out in randomized block design at ten sites having six treatment combinations of different doses of gypsum and green manuring with sesbania under two cropping sequences, i e sesbania-rice (Oryza sativa L.) -wheat (Triticum aestivum L.) and rice-wheat. Cultivation of sesbania with gypsum significantly decreased the surface soil pH from 9.3 to 8.6 and increased the hydraulic conductivity from 0.3 × 10-3 to 3.7 × 10-3 cm/hr and buildup of soil organic matter by increasing organic carbon content from 0.20 % to 0.22 % through growing of sesbania. Sesbania green manure also increased the available water content in the soil system, which enhanced soil moisture availability for longer period. As a result, rice crop yield increased by 16.2 % in sesbania-rice- wheat cropping system in comparison to rice–wheat cropping sequence because of synergistic effect of sesbania with gypsum. Consequently, residual effect of sesbania green manuring alone and in combination with gypsum significantly enhanced the wheat grain yield by 42.5 % and 72.5 % and 80% in T4, T5 and T6 treatments respectively during first year in sesbania–rice-wheat cropping sequence as compared to control. In consecutive second year, rice and wheat grain yields further enhanced by 8.1 % and 2.71% respectively, under sesbania –rice -wheat than that of rice –wheat cropping sequence. Under sesbania rice- wheat and rice-wheat-sesbania cropping sequence, rice and wheat grain yield were similar. Hence, inclusion of Sesbania aculeata as green manure either before or after rice wheat cropping sequence is equally better to improve the soil physical dynamics and crop productivity of ‘B’ class sodic soils in Indo-Gangetic region of Uttar Pradesh.Not Availabl