Comprehensive Analysis of Chemical Structures That Have Been Tested as CFTR Activating Substances in a Publicly Available Database CandActCFTR

Background: Cystic fibrosis (CF) is a genetic disease caused by mutations in CFTR, which encodes a chloride and bicarbonate transporter expressed in exocrine epithelia throughout the body. Recently, some therapeutics became available that directly target dysfunctional CFTR, yet research for more effective substances is ongoing. The database CandActCFTR aims to provide detailed and comprehensive information on candidate therapeutics for the activation of CFTR-mediated ion conductance aiding systems-biology approaches to identify substances that will synergistically activate CFTR-mediated ion conductance based on published data.Results: Until 10/2020, we derived data from 108 publications on 3,109 CFTR-relevant substances via the literature database PubMed and further 666 substances via ChEMBL; only 19 substances were shared between these sources. One hundred and forty-five molecules do not have a corresponding entry in PubChem or ChemSpider, which indicates that there currently is no single comprehensive database on chemical substances in the public domain. Apart from basic data on all compounds, we have visualized the chemical space derived from their chemical descriptors via a principal component analysis annotated for CFTR-relevant biological categories. Our online query tools enable the search for most similar compounds and provide the relevant annotations in a structured way. The integration of the KNIME software environment in the back-end facilitates a fast and user-friendly maintenance of the provided data sets and a quick extension with new functionalities, e.g., new analysis routines. CandActBase automatically integrates information from other online sources, such as synonyms from PubChem and provides links to other resources like ChEMBL or the source publications.Conclusion: CandActCFTR aims to establish a database model of candidate cystic fibrosis therapeutics for the activation of CFTR-mediated ion conductance to merge data from publicly available sources. Using CandActBase, our strategy to represent data from several internet resources in a merged and organized form can also be applied to other use cases. For substances tested as CFTR activating compounds, the search function allows users to check if a specific compound or a closely related substance was already tested in the CF field. The acquired information on tested substances will assist in the identification of the most promising candidates for future therapeutics.

Transcriptome and Biochemical Analysis Jointly Reveal the Effects of Bacillus cereus AR156 on Postharvest Strawberry Gray Mold and Fruit Quality

Postharvest strawberry is susceptible to gray mold disease caused by Botrytis cinerea, which seriously damage the storage capacity of fruits. Biological control has been implicated as an effective and safe method to suppress plant disease. The aim of this study is to evaluate the postharvest disease control ability of Bacillus cereus AR156 and explore the response of strawberry fruit to this biocontrol microorganism. Bacillus cereus AR156 treatment significantly suppressed gray mold disease and postponed the strawberry senescence during storage. The bacterium pretreatment remarkably enhanced the reactive oxygen-scavenging and defense-related activities of enzymes. The promotion on the expression of the encoding-genes was confirmed by quantitative real-time PCR (qRT-PCR) that significantly increased the expression of the marker genes of salicylic acid (SA) signaling pathway, such as PR1, PR2, and PR5, instead of that of the jasmonic acid (JA)/ethylene (ET) pathway, which was also shown. Moreover, through transcriptome profiling, about 6,781 differentially expressed genes (DEGS) in strawberry upon AR156 treatment were identified. The gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that AR156 altered the transcription of numerous transcription factors and genes involved in the SA-related plant disease resistance, metabolism, and biosynthesis of benzoxazinoids and flavonoids. This study offered a non-antagonistic Bacillus as a method for postharvest strawberry storage and disease control, and further revealed that the biocontrol effects were arisen from the induction of host responses on the transcription level and subsequent resistance-related substance accumulation.

Knowledge and Attitude Regarding Ill Effects of Substance Use Among School Going Children, Golaghat

Adolescent starts with early healthy teens and ends up with the many unhealthy issues if not taken care of One of the high risk health issues of adolescence is related to substance use. It is a decade ago worldwide problem where India too has fallen into this viscous cycle. It has not only affected the health of adolescence but has also affected the future of the entire nation. Objectives: The study aimed to find out knowledge and attitude on ill effects of substance use among school going children. Material and Methods: The study adopted cross sectional descriptive design. The study was conducted in three School of Golaghat, Assam for a period of 2 weeks among 265 school going children who were selected using purposive sampling technique after taking the consent. Tool knowledge questionnaire related Substance Use and Attitude scale related Substance Use was used. Results: It was found that 94% of the school going children was having high knowledge level on the ill effects of substance use and their attitude varies towards the substance use. There was no significant association found between knowledge score and selected socio demographic variable. Conclusion: It was found that even after having sufficient knowledge and negative attitude towards the substance use, many adolescent are trapped in this phenomena. It may be because of lack of assertiveness and weaken coping ability of the adolescence. Keywords: Knowledge, Attitude, Substance use, School Going Children.

Application of RP-HPLC for the Estimation of Allopurinol and Its Related Substances in Bulk and Tablet Dosage Form

Aims: The main aim of the present study was to develop and validate a simple and cost- effective method for the estimation of allopurinol and its related substances by using RP-HPLC. Study Design: Estimation of Allopurinol and its related substance in bulk and tablet dosage forms by RP-HPLC. Place and Duration of Study: Chalapathi Drug Testing Laboratory, Chalapathi Institute of Pharmaceutical Sciences, Chalapathi Nagar, Lam, Guntur-522034 between October 2020 to January 2021. Methodology: Method development was carried out by using Schimadzu, Prominence-i series LC 3D-Plus autosampler embedded with lab solutions software, equipped with PDA detector using YMC column (150 mm X 4.6 mm, 3 μm) and 0.1M Ammonium acetate buffer as a mobile phase in the ratio of 100% at a flow rate of 1.0 ml/min at a wavelength of 255nm. The developed method was validated according to ICH guidelines. Results: The linearity was observed in the range of 20-100 µg/ml with a regression (R2) value of 0.999. Developed method was specific with no interactions and accurate with 100.11% for allopurinol and 99.54% for its related substance. The limit of detection for allopurinol was 2 µg/ml and for related substance was 0.0.1 µg/ml. The limit of quantification for allopurinol was 6 µg/ml and for related substance was 0.03 µg/ml respectively. The percentage relative standard deviation was found to be NMT 2 which indicates that the proposed method was precise and robust. Conclusion: The developed method was simple, precise and accurate and can be successfully employed for the estimation of allopurinol in bulk and tablet dosage form.

The Insurgence of Tramadol Abuse among the Most Active Population in Jirapa Municipality: A Study to Assess the Magnitude of the Abuse and Its Contributory Factors

Background. Tramadol has gained popularity among the drugs of the most active population especially the respondents in Ghana abuse especially farmers who nicknamed as “farm and buy cow.” It has recently become a public health concern, and stakeholders are worried about tramadol abuse and its implications on health in the Upper West Region. The study sought to measure the prevalence of tramadol/related substance abuse and the associated factors. Methods. A community-based analytic cross-sectional study involving 420 respondents was conducted. The participants were selected using a multistage sampling technique. Semistructured questionnaire was used to generate the data. Results. About 77.6% of the respondents abuse tramadol while 83.9% of the participants take at least one other related substance or drug. Participants with history of any substance abuse were 5 times more likely to abuse tramadol [ AOR = 5.15 ; 95% CI (1.501-17.656); p = 0.009 ], compared to respondents with no history of any substance abuse. Respondents who take tramadol to enhance sex were 4 times more likely to abuse tramadol [ AOR = 3.776 ; 95% CI (1.352-10.545); p = 0.011 ]. Formal sector employment was protective against tramadol abuse [ AOR = 0.100 ; 95% CI (0.017-0.595); p = 0.011 ] compared to self-employment and the unemployed. In addition, use of nonopioid prescription drugs for posttraumatic/pain management reduced the risk of tramadol abuse [ AOR = 0.237 ; 95% CI (0088-0.640); p = 0.004 ] compared to the posttraumatic/pain management dependence on prescription of only opioid like tramadol. Conclusion. An infantile municipality like Jirapa is challenged with high level of tramadol and related substance which has serious repercussion on the health system in the Jirapa district. It is important that measures are taken by the stakeholders to stop tramadol and related substance and mitigate the impact of drug abuse in the district.