Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins

Mitoxantrone is a potent antitumor drug, widely used in the treatment of various cancers. In the present study, we have investigated and compared the affinity of anticancer drug, mitoxantrone, to EDTA-soluble chromatin (SE-chromatin), DNA and histones employing UV/Vis, fluorescence, CD spectroscopy, gel electrophoresis and equilibrium dialysis techniques. The results showed that the interaction of mitoxantrone with SE-chromatin proceeds into compaction/aggregation as revealed by reduction in the absorbencies at 608 and 260 nm (hypochromicity) and disappearance of both histones and DNA on the gels. Mitoxantrone interacts strongly with histone proteins in solution making structural changes in the molecule as shown by CD and fluorescence analysis. The binding isotherms demonstrate a positive cooperative binding pattern for the chromatin- mitoxantrone interaction. It is suggested higher binding affinity of mitoxantrone to chromatin compared to DNA implying that the histone proteins may play an important role in the chromatin- mitoxantrone interaction process

Investigating the changes in chemical quality characteristics of Ardestan plain underground water resources during 1995-2019

Objectives: Considering the importance of underground water sources, continuous evaluation of their quality should be considered to prevent chemical pollution. Therefore, the purpose of this research is to investigate the changes in the chemical quality of water in the Qanats (aqueducts) and wells of Ardestan Plain during the years 1995 to 2019.Methods: This research was conducted retrospectively in 2021 based on the data collected by Ardestan Department of Natural Resources during the period of 1995-2019. Data were analyzed by SPSS software, version 2016 and compared to Iranian drinking water quality standards.Results: Data showed that Total Dissolved Solids (TDS) and the Total Hardness of well water were increased 367.3, 168.8 respectively. These parameters were increased by 188.1 and 90 mg L-1 for Qanat water, respectively. And other water quality parameters were increased including magnesium, calcium, sulfate, bicarbonate, chloride and Electrical Conductivity (EC).  The trend of TDS and TH showed that in the all of the well water exceeded from the drinking water standard especially in 2019.Conclusion: Paying attention to the process of chemical changes of water in the Ardestan plain reminds us that in the future, water sources will be at risk of damage, especially in the low-altitude parts of the plain

A COMPARISON OF NALBUPHINE AND PENTAZOCINE IN CONTROLLING POSTOPERATIVE PAIN IN DOGS

Surgical success in most cases is governed by the quality of post-operative pain management. In Pakistan, most veterinary surgeons face a dire predicament as they fail astutely in this regard. Owing to the controlled dispensing of potent narcotics and their potential misuse, an imperative need for effective post-operative analgesic management of pain exists in dogs. 32 dogs were randomly divided into two groups. Group A was injected Nalbuphine @ 0.5 mg/kg post-operatively while Group B was injected Pentazocine @ 3mg/kg. Subjective and objective analysis of pain was conducted by unbiased observers. Vital signs (Temperature, pulse, respiration) were analyzed along with supplementation of hepatic and renal function tests. Objective and subjective analysis of both groups yielded results in the favor of pentazocine. In group A, temperature, pulse and respiration averaged 101.86±0.58oF, 83.46±2.75 per minute and 19.26±2.14 per minute respectively. Group 2 demonstrated temperature, pulse and respiration averages of 102.31±0.40oF, 83.41±2.74 per minute and 19.54±2.14 per minute respectively. Values of hepatic and renal function were also observed to be significantly higher in Nalbuphine treated group. All the results indicate that pentazocine is not only a significantly better analgesic but also has lower hepatotoxic and renal toxic effects

Human Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 in Children

The novel coronavirus, known as 2019-nCoV or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an epidemic with high mortality and morbidity since December 2019, in Wuhan, China. The infection has now been transmitted to more than 210 countries worldwide and caused more than 200,000 deaths. Similar to other coronaviruses such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), SARS-CoV-2 appears to less commonly affect pediatrics and to cause less severe disease along with fewer symptoms compared to adults. Available data suggest that the pediatric population is just as likely as adults to become infected with SARS-CoV-2. However, they may be asymptotic or have milder symptoms than adults; they can be potential carriers of the disease. This article reviews the present understanding of SARS-CoV-2 infection in the pediatric age group in comparison with MERS-CoV and SARS-CoV. (c) 2020 Elsevier Inc. All rights reserved

Whole-genome informed circulating tumor DNA analysis by multiplex digital PCR for disease monitoring in B-cell lymphomas: a proof-of-concept study

IntroductionAnalyzing liquid biopsies for tumor-specific aberrations can facilitate detection of measurable residual disease (MRD) during treatment and at follow-up. In this study, we assessed the clinical potential of using whole-genome sequencing (WGS) of lymphomas at diagnosis to identify patient-specific structural (SVs) and single nucleotide variants (SNVs) to enable longitudinal, multi-targeted droplet digital PCR analysis (ddPCR) of cell-free DNA (cfDNA).MethodsIn 9 patients with B-cell lymphoma (diffuse large B-cell lymphoma and follicular lymphoma), comprehensive genomic profiling at diagnosis was performed by 30X WGS of paired tumor and normal specimens. Patient-specific multiplex ddPCR (m-ddPCR) assays were designed for simultaneous detection of multiple SNVs, indels and/or SVs, with a detection sensitivity of 0.0025% for SV assays and 0.02% for SNVs/indel assays. M-ddPCR was applied to analyze cfDNA isolated from serially collected plasma at clinically critical timepoints during primary and/or relapse treatment and at follow-up.ResultsA total of 164 SNVs/indels were identified by WGS including 30 variants known to be functionally relevant in lymphoma pathogenesis. The most frequently mutated genes included KMT2D, PIM1, SOCS1 and BCL2. WGS analysis further identified recurrent SVs including t(14;18)(q32;q21) (IGH::BCL2), and t(6;14)(p25;q32) (IGH::IRF4). Plasma analysis at diagnosis showed positive circulating tumor DNA (ctDNA) levels in 88% of patients and the ctDNA burden correlated with baseline clinical parameters (LDH and sedimentation rate, p-value <0.01). While clearance of ctDNA levels after primary treatment cycle 1 was observed in 3/6 patients, all patients analyzed at final evaluation of primary treatment showed negative ctDNA, hence correlating with PET-CT imaging. One patient with positive ctDNA at interim also displayed detectable ctDNA (average variant allele frequency (VAF) 6.9%) in the follow-up plasma sample collected 2 years after final evaluation of primary treatment and 25 weeks before clinical manifestation of relapse.ConclusionIn summary, we demonstrate that multi-targeted cfDNA analysis, using a combination of SNVs/indels and SVs candidates identified by WGS analysis, provides a sensitive tool for MRD monitoring and can detect lymphoma relapse earlier than clinical manifestation

ُScience and Culture: a Look at the Most Important Cultural Analysis in Sociology of Science and Technology

Formerly most sociologists of science and technology did little to research in the formal literature of the Sociology of Culture and may even were resistant to cultural analysis. The sociologists of culture have also written little analysis on the process of knowledge and technology production. This is contrary to the basic characteristic of the new sociology of knowledge and science that is emphasis on culture and cultural analysis in science and technology studies. In this article, we trace and analyze how sociologists of science and technology have performed cultural analysis. More recent moves to extend studies of science and technology "outward" beyond formal scientific settings have created new possibilities for the sociology of culture. They have also attracted more attention to the place of culture in knowledge and technology studies. Of these recent attempts are the studies on materialistic culture, scientific citizenship, macro - epistemic (culture in knowledge society), and finally civic epistemologies

Knowledge as a Cultural Product: From the Sociology of Scientific Knowledge to the Cultural Studies of Science

The main characteristic (feature) of the sociology of knowledge and science is its emphasis on the culture and cultural analysis within the scientific and technological research. This study concerns with the study of two research fields in which new sociologists of science and technology have presented their cultural analysis. These two fields include: sociology of scientific knowledge and cultural studies of science.Sociology of scientific knowledge is the first school of thought which makes the content of scientific knowledge inclined to and compliant with the cultural and sociological analysis. In SSK, the main presupposition is that “the scientific knowledge is totally arbitrary.” Accordingly, the design and evaluation of scientific theories and claims are the consequence of social interests and cultural inclinations (trends), in a way that the scientific theories become a tool for the justification, legitimating, encouragement and contentment.At the early 1990s, with the rise of crisis (chaos) within the explanations of sociology of scientific knowledge and a flood of criticism against it, the whole subjectivity of the field came to a standstill (reached an impasse) and the initiatives in scientific research were replaced by different theoretical orientations like cultural studies. In contrast to the sociology of scientific knowledge, the cultural studies of science concerns with the rejection of “explanation” and, instead, focuses on the “meaning” and “understanding”. In other words, it has come back to an old dispute between explanatory and hermeneutic approaches and those  which pursue the regulative (legalistic) comprehensiveness along the more positivistic lines.This emerging field emphasizes the issue that the uncertainty, instability, ambiguity (vagueness) and difference must be given a more important role in sciences. Cultural studies of science gave rise to a change from the sociology of scientific knowledge to a new culturalism