Pharmacological basis for the medicinal use of polyherbal formulation and its ingredients in cardiovascular disorders using rodents

A compound herbal formulation (POL4) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL4 and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL4 and its ingredients in hypertension

An approach to map geography mark-up language data to resource description framework schema

GML serves as premier modeling language used to represent data of geographic information related to geography locations. However, a problem of GML is its ability to integrate with a variety of geographical and GPS applications. Since, GML saves data in coordinates and in topology for the purpose to integrate data with variety of applications on semantic web, data be mapped to Resource Description Framework (RDF) and Resource Description Framework Schema (RDFS). An approach of mapping GML metadata to RDFS is presented in this paper. This study focuses on the methodology to convert GML data in semantics to represent in extended and enriched form such as RDFS as representation in RDF is not sufficient over semantic web. Firstly, we have GML script from case study and parse it using GML parser and get XML file. XML file parse using Java and get text file to extract GML features and then get a graph form of these features. After that we designed methodology of prototype tool to map GML features to RDFS. Tool performed features by features mapping and extracted results are represented in the tabular form of mapping GML metadata to RDFS. © 2020, Springer Nature Singapore Pte Ltd.E

Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn.

Background The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses. Methods The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms. Results In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction. Conclusion These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders

TAT-peptide conjugated repurposing drug against SARS-CoV-2 main protease (3CLpro): potential therapeutic intervention to combat COVID-19

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide (WHO, 11 September, 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CL^{pro}). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide^{47–57} (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CL^{pro} to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future

Factors affecting Pakistani young adults’ intentions to uptake COVID‐19 vaccination: an extension of the theory of planned behavior

Introduction: Aside from personal beliefs, young adults’ intention to uptake the COVID-19 vaccine can be influenced by their fear of COVID-19 and perceived infectability of COVID-19. The present study incorporated fear of COVID-19 and perceived infectability with the theory of planned behavior (TPB) to form an expanded TPB to analyze factors affecting Pakistani young adults’ intentions to uptake the COVID-vaccine in Pakistan. Methods: A cross-sectional study was conducted and recruited participants from Pakistani social media users. The proposed extended TPB model was examined by using structural equation modeling. Results: A total of 1034 individuals replied to the survey. The three factors of the original theory of planned behavior and the fear of COVID-19 were positively related to their intention to uptake COVID-19 vaccination (r = 0.25-0.66). Moreover, the perceived infectability positively influenced the three theories of planned behavioral factors and the fear of COVID-19 (r = 0.27-0.60), also affecting the participants’ intentions to uptake COVID-19 vaccination. Conclusions: Perceived infectability was positively related to the participants’ intentions to uptake COVID-19 vaccination, and perceived behavioral control was the strongest mediator. More evidence-based information concerning treatments and COVID-19 vaccination are needed to encourage individuals to uptake the vaccine

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora

<p>Abstract</p> <p>Background</p> <p><it>Fumaria parviflora </it>Linn. (<it>Fumariaceae</it>), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders.</p> <p>Methods</p> <p>The <it>in-vivo </it>prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system.</p> <p>Results</p> <p>The aqueous-methanol extract of <it>Fumaria parviflora </it>(Fp.Cr), which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the <it>in-vivo </it>in mice at 30 and 100 mg/kg. In the <it>in-vitro </it>studies, Fp.Cr (0.01-1 mg/ml) caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive). This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse.</p> <p>Conclusions</p> <p>This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders such as, indigestion and constipation. This study also suggests using different species to know better picture of pharmacological profile of the test material.</p

Fear of COVID-19 and workplace phobia among Pakistani doctors: a survey study

Background: The novel coronavirus disease-2019 (COVID-19) has seriously affected the lives of millions of people across the world. It has also heavily burdened healthcare professionals and the virus poses serious risks for their personal and professional lives. Therefore, the present study examined the associations between fear of COVID-19 and workplace phobia among doctors in Pakistan during the COVID-19 pandemic. Methods: An online survey was conducted among 421 doctors in Pakistan between April 10 and May 25, 2020. The Workplace Phobia Scale (WPS) and the Fear of COVID-19 Scale (FCV-19S) were the main psychometric instruments used in this study. Results: There was a significant positive relationship between fear of COVID-19 and workplace panic anxiety and workplace avoidance behavior. Significantly higher fear of COVID-19 was found among (i) females compared to males, (ii) doctors with 5 years or less of work experience compared to those with more than 5 years, and (iii) postgraduate trainees compared with other ranks. Two groups (doctors who were above 30 years old and postgraduate trainees) were found to have higher levels of workplace phobia compared to their counterparts. Doctors with severe levels of fear of COVID-19 had significantly higher levels of workplace panic anxiety and workplace avoidance behavior. Conclusions: Fear of COVID-19 was significantly associated with workplace phobia which may negatively affect doctors’ performance. Therefore, important steps are needed to protect doctors’ health by providing sufficient resources to allay their fears and anxieties which consequently help them in carrying out their frontline duties in response to the COVID-19 pandemic