Biomolecular and Biomedical Science Research Collection

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Now showing 1 - 5 of 234
  • Publication
    The Role of Nano-systems in the Delivery of Glucose-lowering Drugs for the Pre-emption and Treatment of Diabetes-associated Atherosclerosis
    (American Physiological Society, 2024-03-19) ; ; ;
    Diabetes is one of the most prevalent diseases worldwide. In recent decades, type-2 diabetes has become increasingly common, particularly in younger individuals. Diabetes leads to many vascular complications, including atherosclerosis. Atherosclerosis is a cardiovascular disease characterized by lipid-rich plaques within the vasculature. Plaques develop over time, restricting blood flow; and can therefore be the underlying cause of major adverse cardiovascular events, including myocardial infarction and stroke. Diabetes and atherosclerosis are intrinsically linked. Diabetes is a metabolic syndrome which accelerates atherosclerosis and increases the risk of developing other co-morbidities, such as Diabetes-associated Atherosclerosis (DAA). Gold-standard anti-diabetic medications focus on attenuating hyperglycemia. Though recent evidence suggests that glucose-lowering drugs may have broader applications, beyond diabetes-management. This review mainly evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1 RA), such as Liraglutide and Semaglutide in DAA. These drugs mimic gut hormones (incretins), which inhibit glucagon secretion whilst stimulating insulin secretion, thus improving insulin sensitivity. This facilitates delayed gastric emptying and increased patient satiety; hence they are also indicated for the treatment of obesity. GLP-1 RAs have significant cardioprotective effects, including decreasing low-density lipoprotein (LDL)-cholesterol and triglycerides levels. Liraglutide and Semaglutide have specifically been shown to decrease cardiovascular risk. Liraglutide has displayed a myriad of anti-atherosclerotic properties, with the potential to induce plaque regression. This review aims to address how glucose-lowering medications can be applied to treat diseases other than diabetes. We specifically focus on how nanomedicines can be used for the site-specific delivery of anti-diabetic medicines for the treatment of diabetes-associated atherosclerosis.
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  • Publication
    Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis
    Rationale Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways. Objectives To investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF. Methods EVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs. Results A significantly higher level of EVs were released from CFBE41o- (p<0.0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p<0.001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p<0.001-0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls. Conclusion This study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF.
      18Scopus© Citations 18
  • Publication
    Neuroprotective Nanoparticles Targeting the Retina: A Polymeric Platform for Ocular Drug Delivery Applications
    Neuroprotective drug delivery to the posterior segment of the eye represents a major challenge to counteract vision loss. This work focuses on the development of a polymer-based nanocarrier, specifically designed for targeting the posterior eye. Polyacrylamide nanoparticles (ANPs) were synthesised and characterised, and their high binding efficiency was exploited to gain both ocular targeting and neuroprotective capabilities, through conjugation with peanut agglutinin (ANP:PNA) and neurotrophin nerve growth factor (ANP:PNA:NGF). The neuroprotective activity of ANP:PNA:NGF was assessed in an oxidative stress-induced retinal degeneration model using the teleost zebrafish. Upon nanoformulation, NGF improved the visual function of zebrafish larvae after the intravitreal injection of hydrogen peroxide, accompanied by a reduction in the number of apoptotic cells in the retina. Additionally, ANP:PNA:NGF counteracted the impairment of visual behaviour in zebrafish larvae exposed to cigarette smoke extract (CSE). Collectively, these data suggest that our polymeric drug delivery system represents a promising strategy for implementing targeted treatment against retinal degeneration.
      96Scopus© Citations 3
  • Publication
    Novel zebrafish patient-derived tumor xenograft methodology for evaluating efficacy of immune-stimulating BCG therapy in urinary bladder cancer
    Background: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. Methods: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. Results: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. Conclusions: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.
      55Scopus© Citations 3
  • Publication
    Simultaneous removal of malachite green and hexavalent chromium by Cunninghamella elegans biofilm in a semi-continuous system
    The present study was conducted to evaluate the potential of the fungus Cunninghamella elegans for simultaneous decolourisation of a triphenylmethane dye malachite green (MG) and hexavalent chromium [Cr(VI)] in the same media. This fungus can degrade MG through its reduction into leucomalachite green and then demethylation followed by oxidative cleavage. Along with MG degradation, C. elegans biofilm could effectively and repeatedly remove Cr(VI) from the liquid cultures even in the presence of high concentrations (40 g L−1) of NaCl and various other metal ions. C. elegans biofilm was also found to adsorb different dyes (reactive black-5, acid orange 7, direct red 81 and brilliant blue G) concurrently with Cr(VI). Based on its potential for simultaneous removal of dyes and Cr(VI) as well as reusability, C. elegans biofilm is envisaged as an efficient bioresource to devise strategies for treatment of wastewaters loaded with multiple pollutants.
      47Scopus© Citations 37