BanLec, a banana lectin, is a potent inhibitor of Middle East respiratory syndrome coronavirus in in vitro assays

Poster Abstract Session - Viral Infections: Treatment and Prevention: no. 1159BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause human infections with multiple clusters two years after the onset of the epidemic. Though mild cases have been recognized, the infection is severe in those with co-morbidities and >30% of patients die from the infection. Our recent structure-based development of a fusion inhibitor is one of the few treatment options for MERS and it led us to hypothesize that other existing antivirals that block cellular entry may also be active against MERS-CoV. BanLec is a jacalin-related banana lectin that has potent anti-HIV activity through binding to glycosylated viral envelope proteins and blocking cellular entry. We assessed the anti-MER-CoV activity of BanLec in cell culture assays. METHODS: The anti-MERS-CoV activity of BanLec was assessed by cytopathic effect (CPE) inhibition, viral yield reduction, and plaque reduction (PRA) assays in Vero, Calu-3, and/or HK2 cells. The cytotoxicity of BanLec was also assessed. RESULTS: The CC50 of BanLec was >10 nM in Vero and Calu-3 cells. CPE was completely absent in Vero and HK2 cells infected with MERS-CoV on 3 dpi with 30.00 nM of BanLec. In Calu-3 cells, CPE was completely absent at 90.00 nM of the drug. The EC50 of BanLec ranged from 3.99-4.82 nM (Table 1). The mean viral loads reduced by 7.13, 3.40, and 3.63 log10 copies/ml in Vero, Calu-3, and HK2 cells respectively (Fig. 1A to C). The highest percentage of plaque reduction at a concentration of >10 nM of BanLec were 100% and 59.5% in Vero cells and HK2 cells respectively (Fig. 2A & B). CONCLUSION: BanLec exhibits potent in vitro anti-MERS-CoV activity. The detailed mechanism and in vivo correlation of its antiviral activity should be further tested in animal models. The potential advantages of using BanLec for MERS include its high stability and the prospect of using it as a topical treatment or prophylaxis for exposed patients. (Table see attachment)BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause human infections with multiple clusters two years after the onset of the epidemic. Though mild cases have been recognized, the infection is severe in those with co-morbidities and >30% of patients die from the infection. Our recent structure-based development of a fusion inhibitor is one of the few treatment options for MERS and it led us to hypothesize that other existing antivirals that block cellular entry may also be active against MERS-CoV. BanLec is a jacalin-related banana lectin that has potent anti-HIV activity through binding to glycosylated viral envelope proteins and blocking cellular entry. We assessed the anti-MER-CoV activity of BanLec in cell culture assays. METHODS: The anti-MERS-CoV activity of BanLec was assessed by cytopathic effect (CPE) inhibition, viral yield reduction, and plaque reduction (PRA) assays in Vero, Calu-3, and/or HK2 cells. The cytotoxicity of BanLec was also assessed. RESULTS: The CC50 of BanLec was >10 nM in Vero and Calu-3 cells. CPE was completely absent in Vero and HK2 cells infected with MERS-CoV on 3 dpi with 30.00 nM of BanLec. In Calu-3 cells, CPE was completely absent at 90.00 nM of the drug. The EC50 of BanLec ranged from 3.99-4.82 nM (Table 1). The mean viral loads reduced by 7.13, 3.40, and 3.63 log10 copies/ml in Vero, Calu-3, and HK2 cells respectively (Fig. 1A to C). The highest percentage of plaque reduction at a concentration of >10 nM of BanLec were 100% and 59.5% in Vero cells and HK2 cells respectively (Fig. 2A & B). CONCLUSION: BanLec exhibits potent in vitro anti-MERS-CoV activity. The detailed mechanism and in vivo correlation of its antiviral activity should be further tested in animal models. The potential advantages of using BanLec for MERS include its high stability and the prospect of using it as a topical treatment or prophylaxis for exposed patients

Evolution in inter-firm governance along the transport biofuel value chain in maritime Silk Road countries

We investigate how value chain governance can evolve in the transport biofuel sector beyond logistics and operations optimization, drawing on cases of eighteen manufacturers in four Belt and Road countries. We find that key motivations for vertical integration include control of strategic factors such as security of supply and gaining access to the retail market, subject to inter-institutional and intra-organizational barriers. We contribute to a theory of governance mode selection by suggesting plural governance mode offers a key strategic choice under institutional constraints. In BRI countries, plural mode could be less disruptive when integrating value chains.ESRC-Cambridge Commonwealth Trust-Dorothy Hodgkin Postgraduate Awar

Application of the One-Minute Preceptor Technique by Novice Teachers in the Gross Anatomy Laboratory

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May I have your consent? Informed consent in clinical trials- feasibility in emergency situations

Clinical researchers in acute emergency settings are commonly faced with the difficulty of satisfying the conventional ethical requirement of obtaining informed consent, whilst ensuring a representative group of patients is recruited into studies. We discuss our own experience in addressing institutional ethical requirements to obtain informed consent in a multi-centre trial, recruiting highly agitated patients in the emergency setting in Melbourne, Australia. We suggest that, through the application of existing ethical and legal frameworks and pre-emptive communication with the key stakeholders in ethics committees, hospital insurers and legal representatives, a balance can be struck between ethical and legal requirements on the one hand, and the integrity of the research question, on the other.published_or_final_versio

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

Effects of ferroelectric-poling-induced strain on the quantum correction to low-temperature resistivity of manganite thin films

Author name used in this publication: H. L. W. ChanAuthor name used in this publication: H. S. Luo2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data

\ua9 2024 The Authors. Background: Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer\u27s perspective to inform early resource planning in Hong Kong. Methods: We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources. Findings: With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US$309.0 million and US$58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849–57,896 active prevalent cases would cost more than US$322.3 million and US$60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31–54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages. Interpretation: A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios. Funding: Research Impact Fund from the University Grants Committee, Research Grants Council with matching fund from the Hong Kong Association of Pharmaceutical Industry (R7007-22)

Individualised Transcranial Magnetic Stimulation Targeting of the Left Dorsolateral Prefrontal Cortex for Enhancing Cognition: A Randomised Controlled Trial

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual’s performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour–Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS’s cognitive enhancing effects

Suppression of low-density lipoprotein oxidation, vascular smooth muscle cell proliferation and migration by a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis is a major cause of death in developed world. Atherosclerosis is characterized by low-density lipoprotein deposition in the arterial wall which ultimately begets the formation of lesions. Rupture of lesions finally leads to clinical events such as heart attack and stroke. Atherosclerosis is a complication associated with diabetes. In patients with diabetes, the risk of atherosclerosis is three to five folds greater than in non-diabetics. Our previous study showed that a herbal extract of <it>Radix Astragali, Radix Codonopsis </it>and <it>Cortex Lycii</it>, namely SR10, could improve glucose homeostasis both <it>in vitro </it>and <it>in vivo</it>. In this study, we want to further investigate the efficacy of SR10 in treating atherosclerosis.</p> <p>Method</p> <p>The inhibitory effect of SR10 on low-density lipoprotein oxidation was investigated using free radical-induced erythrocyte hemolysis model and copper ion-induced low-density lipoprotein oxidation model. Since vascular smooth muscle cell proliferation and migration are important processes in atherogenesis, we also examined the effect of SR10 in inhibiting these events.</p> <p>Results</p> <p>Our results showed that SR10 inhibited erythrocyte hemolysis with IC₅₀value at 0.25 mg/ml and significantly prolonged low-density lipoprotein oxidation <it>in vitro</it>. SR10 attenuated platelet derived growth factor-BB-induced vascular smooth muscle cell proliferation by promoting cell cycle arrest at G₀/G₁phase as well as inhibiting vascular smooth muscle cell migration.</p> <p>Conclusion</p> <p>The potential application of SR10 in treating atherosclerosis has been implied in this study. Animal model will be needed to further verify the efficacy of SR10 in future.</p