Evaluation of binding mode between anticancer drug etoposide and human serum albumin by numerous spectrometric techniques and molecular docking

Etoposide (EPD) is a chemotherapy drug served to treat numerous cancers, and human serum albumin (HSA) functioning as transportation of variant small compounds (exogenous and endogenous). Its binding interaction was studied computationally (molecular docking) and spectrometrically by FT-IR, UV-vis, fluorescence (emission, 3D and synchronous) and CD with pH 7.40 at 292, 300 and 308 K temperatures. The obtained results were imparted that HSA bounded by EPD via static process, ultimately the formation of EPD-HSA complex with strong binding constant (10(5)) through vander Waals and hydrogen bonds. EPD can induce the differing in secondary structure, conformation and microenvironments of HSA upon binding; polarity around Trp increased and its distance to EPD was also analysed. Displacement estimations and molecular docking have demonstrated that EPD notably binds to site III (IB) of HSA. Influence of Co2+, Na+, Fe2+, Zn2+ and Ca2+ ions on EPD-HSA system was examined

Cancer impacts microRNA expression, release and function in cardiac and skeletal muscle

Circulating microRNAs are emerging as important biomarkers of various diseases including cancer. Intriguingly, circulating levels of several microRNAs are lower in cancer patients compared with healthy individuals. In this study, we tested the hypothesis that a circulating microRNA might serve as a surrogate of the effects of cancer on microRNA expression or release in distant organs. Here we report that circulating levels of the muscle-enriched miR-486 is lower in breast cancer patients compared with healthy individuals, and that this difference is replicated faithfully in MMTV-PyMT and MMTV-Her2 transgenic mouse models of breast cancer. In tumor-bearing mice, levels of miR-486 were relatively reduced in muscle, where there was elevated expression of the miR-486 target genes PTEN and FOXO1A and dampened signaling through the PI3K/AKT pathway. Skeletal muscle expressed lower levels of the transcription factor MyoD which controls miR-486 expression. Conditioned media (CM) obtained from MMTV-PyMT and MMTV-Her2/Neu tumor cells cultured in vitro was sufficient to elicit reduced levels of miR-486 and increased PTEN and FOXO1A expression in C2C12 murine myoblasts. Cytokine analysis implicated TNFα and four additional cytokines as mediators of miR-486 expression in CM-treated cells. Since miR-486 is a potent modulator of PI3K/AKT signaling and the muscle-enriched transcription factor network in cardiac/skeletal muscle, our findings implicated TNFα-dependent miRNA circuitry in muscle differentiation and survival pathways in cancer

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Dynamics of Rationality and Irrationality in The Painter of Signs

R. K. Narayan occupies a significant place in the Indian literary scene. He remains one of the most read, cherished, and appreciated novelist and is an integral part of the University curriculum. The Painter of Signs (1976) is a well-known novel by R.K. Narayan. The text provides a beautiful scope to unearth the intricate dynamics of rationality and irrationality distinction that in fact provides much content for the plot of the novel. The present paper makes an attempt to explore the dynamics of the conceptual framework of rationality and irrationality distinction through a scrutiny of certain instances taking place within the space of the novel.&nbsp; The paper also tries to illustrate that the criticism made by the main protagonists, Raman and Daisy using the conceptual framework of rationality and irrationality are targeted towards ritual practices prevalent in Indian society. Thereby, the paper attempts to build a background to make intelligible the comments and attitude of the main characters towards the incidents taking place around them. At the same time, the paper explores the way in which the novel thus provides a significant space to examine the interplay and dynamics of the framework of rationality and irrationality and how it can impact one’s experience of life

A diversified spectrometric and molecular docking technique to biophysical study of interaction between bovine serum albumin and sodium salt of risedronic acid, a bisphosphonate for skeletal disorders

The binding interaction between bovine serum albumin (BSA) and sodium salt of risedronic acid (RSN) was studied by using the FT-IR (Fourier transform infrared), UV-Vis (ultraviolet–visible), fluorescence (emission and synchronous), CD (circular dichroism) spectrometric, and computational (molecular docking) techniques at 289, 297, and 305 K temperatures with physiological buffer of pH 7.40. The conformational and secondary structural changes observed for BSA from CD spectra and by curve fitting procedure were applied to Fourier self-deconvolution in FT-IR spectra. The formation of a BSA-RSN complex was confirmed from UV-Vis spectroscopy. The static type of quenching shown for RSN to BSA was verified from Stern–Volmer and modified Stern–Volmer equations. The binding constant of order 105 was obtained to be confirming that there exists a strong binding interaction between BSA and RSN. Synchronous fluorescence shows that the microenvironment of tryptophan was altered, not tyrosine of BSA; in addition to this, the distance between tryptophan of BSA and RSN was found out from Forster’s theory of nonradiation energy transfer. The interaction between BSA and RSN mainly occurred as a result of hydrogen bonds and van der Waals forces, the process is exothermic and spontaneous, and it was achieved through van ’t Hoff equation. This interaction was affected by the presence of biologically active Fe2+, Ni2+, Ca2+, Mg2+, and Cd2+ ions and was also studied. The subdomain IIIA of BSA involved with RSN interaction was authenticated from molecular docking analysis

Combined Multispectroscopic and Molecular Docking Assessments to the Effect of an Anticonvulsant, Oxcarbazepine on Human Serum Albumin Conformation and its Binding Properties

Elimination and distribution of drugs are affected by human serum albumin (HSA) interaction. In children and adults, specific types of seizures are controlled by oxcarbazepine (OXZ) alone or in combination with other medications. However, the OXZ interaction with HSA was probed through 3D fluorescence, emission fluorescence, UV-Vis spectroscopy, and molecular docking. OXZ statically quenched the HSA fluorescence spontaneously and exothermically. Thermodynamic parameters revealed the involvement of hydrogen bonds together with van der Waals forces. Molecular docking inspections confirmed that OXZ is bound to site I of HSA. Strong binding with OXZ (of K-b order 10(5) L/mol) reduced the secondary, micro-environmental, and conformational structures of HSA, suggesting that it unfolds. Thus, the assessment of such conformational details of OXZ-HSA binding is pivotal in surveying the efficacy of OXZ as a therapeutic operator and interpreting its pharmacokinetic properties

Detailed investigation of effects of Zn2+, Fe2+ and Cu2+ metal ions on the binding interaction between eletriptan hydrochloride an anti-migraine headache drug and bovine serum albumin by various spectrometric techniques and molecular docking studies

Bovine serum albumin acts as storage and a transport of endogenous and exogenous compounds with protein in the blood. Eletriptan hydrochloride is an anti-migraine headache drug and binding of this drug to albumin is necessary in pharmacokinetic and pharmacodynamics. Many metal ions are present in blood plasma, therefore, the study on the effects of metal ions on the interaction between drugs and plasma proteins are essential. In this study, the effects of metal ions Zn2+, Fe2+ and Cu2+ on the interaction between bovine serum albumin (BSA) and eletriptan hydrochloride (ELT) were investigated by employing emission fluorescence, synchronous fluorescence, ultraviolet–visible (UV–Vis) absorption, Fourier transform infrared (FT-IR) spectroscopic and molecular docking studies at physiological buffer conditions (pH7.4). Results show that static quenching, spontaneous process, hydrogen bonds and vander Waals interactions and the values of Ka, n,Kb, R0,r and thermodynamic parameters were obtained at different temperatures; then the binding sites for ELT in BSA present in sub-domains IIA, IIIA and IB. The entire outcome indicates that the metal ions decrease the binding efficacy of ELT on BSA. The study of binding phenomena is important in providing basic information on the pharmacological actions, biotransformation and bio-distribution, and this would be useful in pharmaceutical industry, life sciences and clinical medicine

Mainstream Media’s framing of #metoo campaign in India

The #metoo campaign became a worldwide phenomenon, through the tweet was made against the Hollywood producer Harvey Weinstein by the actress Alyssa Milano on October 15, 2017. In India the campaign took off on October 7, 2018, when the actress Tanushree Dutta made serious allegations against the actor Nana Patekar, narrating her experiences while she was working with him in a film in 2008. The impact of the awareness created by #metoo campaign was such that well known personalities including the Union minister M J Akbar had to step down when the sexual harassment charges were leveled against them.In the backdrop of all these incidents, the study analyses the role of India media in framing of #metoo movements in India. The research paper analyses Indian news media’s coverage of this social media movement. The study focuses on the analyses of 40 news articles in two major national dailies in India.La campaña #metoo se convirtió en un fenómeno mundial, a través del tweet hecho contra el productor de Hollywood Harvey Weinstein por la actriz Alyssa Milano el 15 de octubre de 2017. En India, la campaña despegó el 7 de octubre de 2018, cuando la actriz Tanushree Dutta hizo serias acusaciones contra el actor Nana Patekar, narrando sus experiencias mientras trabajaba con él en una película en 2008. El impacto de la conciencia creada por la campaña #metoo fue tal que personalidades conocidas como el entonces ministro de la Unión MJ Akbar tuvieron que renunciar cuando los cargos de acoso sexual fueron en su contra. En el contexto de todos los incidentes, el estudio analiza el papel de los principales medios de comunicación indios en el marco de los movimientos #metoo en la India. El trabajo de investigación analiza la cobertura de los medios de comunicación de la India de este movimiento de redes sociales. El estudio se centra en el análisis de 26 artículos de noticias en dos diarios nacionales importantes en la India