1,293 research outputs found
Transformational changes and sustainability : from the perspective of identity, trust, commitment, and withdrawal
Drawing upon the psychology of sustainability, effective organizations can create a sense of belongingness for people, and successfully facilitate growth and development activities for both individuals as well as the organization itself. Extending the recommendations of Zappala, Toscano, and Licciardello, the current study considers a range of variables. The role of overall justice judgements and change favorableness are taken as predictors of affective commitment to change and exit-based withdrawal. The relationship is mediated by organizational identification and moderated by trust in organization. Overall, the results support the hypothesized relationships. Specifically, findings showed that both change favorableness and overall justice judgements are positively related to affective commitment to change and negatively related to exit-based withdrawal. Organizational identification mediates the relationships between overall justice judgements−affective commitment to change, change favorableness−affective commitment to change, and change favorableness−exit-based withdrawal, whilst trust in organizations moderated the direct relationship between overall justice judgements−affective commitment to change, and change favorableness−exit-based withdrawal. Furthermore, the indirect effect of trust in organizations positively moderated the relationship of overall justice judgements and change favorableness with affective commitment to change, and at the same time, it negatively moderated the relationship between change favorableness and exit-based withdrawal via organizational identification. Crucially, for practitioners, this brings trust of employees as a key factor that should be managed to ensure sustainable change. Both trust and identity appear important in improving commitment and lowering the exit-based withdrawal behavior of employees. Future recommendations, implications, and limitations are discussed
Evaluation of Antihypertensive Effect of Aqueous Methanol Extract of Caralluma tuberculata N.E.Br in Sprauge Dawley Rats
Purpose: To evaluate the phytochemical profile and antihypertensive effect of Caralluma tuberculata N.E.Br (AMECT).Methods: The antihypertensive effect of the aqueous methanol extract of (AMECT) was evaluated in both normotensive and hypertensive rats. In normotensive rats, various doses (100, 300 and 500 mg/kg body weight, p.o.) were administered at 0, 1, 3 and 6 hr intervals. Anti-hypertensive activity of the crude extract was investigated in three experimental hypertensive models, viz, egg-fed diet, glucose-induced and cadmium-induced hypertensive rats. Cardiovascular parameters, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) were measured by tail cuff method using non-invasive blood pressure apparatus (NIBP) attached. AMECT was also investigated for its phytochemical profile.Results: The results indicate that AMECT produced a dose-dependent, significant (p < 0.05) decrease in SBP, DBP, MBP, and HR (p < 0.01) of normotensive rats, when compared to control groups, at all test doses. The 500 mg/kg dose produced a highly significant effect (mm Hg, p < 0.001) in SBP (85.9 ± 7.2), DBP (71.86 ± 12.1), MBP (75.1 ± 11.7) and HR (238.08 ± 8.3 beats/min), in comparison to 100 and 300 mg/kg doses; therefore, 500 mg/kg was selected for antihypertensive test in egg-fed, glucose-induced and cadmium-treated hypertensive rats. Significant (p < 0.05) antihypertensive and negative chronotropic effects were observed in hypertensive models compared to their respective normal controls. Phytochemical analysis revealed the presence of tannins, alkaloids, phenolic compounds, cardiac glycosides and flavonoids.Conclusion: The findings indicate that Caralluma tuberculata possesses significant anti-hypentensive activity in rats.Keywords: Phytochemical profile, Antihypertensive, Cardiovascular, Caralluma tuberculata N.E.Br, Blood pressur
Antihypertensive Activity of Aqueous-Methanol Extract of Berberis Orthobotrys Bien Ex Aitch in Rats
Purpose: To investigate the hypotensive potential of Berberis orthobotrys Bien Ex Aitch (Family: Berberidaceae) in both normotensive and hypertensive rats.Methods: Aqueous-methanol (70:30) extract of Berberis orthobotrys at doses of 25, 50, 75 and 100 mg/kg was evaluated for its effect on blood pressure and heart rate using non-invasive blood pressure measuring apparatus. After initial screening, 100 mg/kg dose that produced a maximum effect was selected for the antihypertensive study. Median lethal dose (LD50) and sub-chronic toxicity of the extract were also determined. Various biochemical parameters and organ weight were measured usingstandard procedures.Results: The extract produced a significant (p < 0.01) decrease in systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and heart rate of normotensive rats at all test doses with maximum effect at 100 mg/kg. Similarly, a significant antihypertensive and negative chronotropic effect was observed in both hypertensive models. LD50 of the extract was 200 mg/kg in mice. The extract also exhibited a reduction (p < 0.05) in serum alanine transaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), triglycerides and low density lipoprotein (LDL) levels while a significant (p < 0.05) increase in high density lipoproteins (HDL) level was observed.Conclusion: It seems that the aqueous-methanol extract of Berberis orthobotrys possesses active compounds which may be responsible for the antihypertensive and negative chronotropic effects in rats.Keywords: Berberis orthobotrys, Antihypertensive, Egg feed diet, Blood lipid
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
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
Towards High Capacity Li-ion Batteries Based on Silicon-Graphene Composite Anodes and Sub-micron V-doped LiFePO4 Cathodes
Lithium iron phosphate, LiFePO4 (LFP) has demonstrated promising performance as a cathode material in lithium ion batteries (LIBs), by overcoming the rate performance issues from limited electronic conductivity. Nano-sized vanadium-doped LFP (V-LFP) was synthesized using a continuous hydrothermal process using supercritical water as a reagent. The atomic % of dopant determined the particle shape. 5 at. % gave mixed plate and rod-like morphology, showing optimal electrochemical performance and good rate properties vs. Li. Specific capacities of >160 mAh g−1 were achieved. In order to increase the capacity of a full cell, V-LFP was cycled against an inexpensive micron-sized metallurgical grade Si-containing anode. This electrode was capable of reversible capacities of approximately 2000 mAh g−1 for over 150 cycles vs. Li, with improved performance resulting from the incorporation of few layer graphene (FLG) to enhance conductivity, tensile behaviour and thus, the composite stability. The cathode material synthesis and electrode formulation are scalable, inexpensive and are suitable for the fabrication of larger format cells suited to grid and transport applications
Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities
Background
Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods
To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results
Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion
The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO
A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication
Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome
Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin
In the context of recently emerged novel influenza strains through reassortment, avian influenza subtypes such as H5N1, H7N7, H7N2, H7N3 and H9N2 pose a constant threat in terms of their adaptation to the human host. Among these subtypes, it was recently demonstrated that mutations in H5 and H9 hemagglutinin (HA) in the context of lab-generated reassorted viruses conferred aerosol transmissibility in ferrets (a property shared by human adapted viruses). We previously demonstrated that the quantitative binding affinity of HA to α2→6 sialylated glycans (human receptors) is one of the important factors governing human adaptation of HA. Although the H7 subtype has infected humans causing varied clinical outcomes from mild conjunctivitis to severe respiratory illnesses, it is not clear where the HA of these subtypes stand in regard to human adaptation since its binding affinity to glycan receptors has not yet been quantified. In this study, we have quantitatively characterized the glycan receptor-binding specificity of HAs from representative strains of Eurasian (H7N7) and North American (H7N2) lineages that have caused human infection. Furthermore, we have demonstrated for the first time that two specific mutations; Gln226→Leu and Gly228→Ser in glycan receptor-binding site of H7 HA substantially increase its binding affinity to human receptor. Our findings contribute to a framework for monitoring the evolution of H7 HA to be able to adapt to human host.National Institutes of Health (U.S.) (GM R37 GM057073-13)Singapore-MIT Alliance for Research and Technolog
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