School of Allied Health Sciences

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A structure-based virtual high-throughput screening, molecular docking, molecular dynamics and MM/PBSA study identified novel putative drug-like dual inhibitors of trypanosomal cruzain and rhodesain cysteine proteases
(Springer, 2023-01-08) Bhambra, Avninder S.; Eurtivong, Chatchakorn; Zimmer, Collin; Schirmeister, Tanja; Butkinaree, Chutikarn; Saruengkhanphasit, Rungroj; Niwetmarin, Worawat; Ruchirawat, Somsak
Virtual screening a collection of ~ 25,000 ChemBridge molecule collection identified two nitrogenous heterocyclic molecules, 12 and 15, with potential dual inhibitory properties against trypanosomal cruzain and rhodesain cysteine proteases. Similarity search in DrugBank found the two virtual hits with novel chemical structures with unreported anti-trypanosomal activities. Investigations into the binding mechanism by molecular dynamics simulations for 100 ns revealed the molecules were able to occupy the binding sites and stabilise the protease complexes. Binding affinities calculated using the MM/PBSA method for the last 20 ns showed that the virtual hits have comparable binding affinities to other known inhibitors from literature suggesting both molecules as promising scaffolds with dual cruzain and rhodesain inhibition properties, i.e. 12 has predicted ΔGbind values of − 38.1 and − 38.2 kcal/mol to cruzain and rhodesain, respectively, and 15 has predicted ΔGbind values of − 34.4 and − 25.8 kcal/mol to rhodesain. Per residue binding free energy decomposition studies and visual inspection at 100 ns snapshots revealed hydrogen bonding and non-polar attractions with important amino acid residues that contributed to the ΔGbind values. The interactions are similar to those previously reported in the literature. The overall ADMET predictions for the two molecules were favourable for drug development with acceptable pharmacokinetic profiles and adequate oral bioavailability.
Open Access
Albumin is an integrative protein of blood plasma and beyond.
(MDPI, 2024-11-25) Belinskaia, D. A.; Jenkins, R. O.; Goncharov, N. V.
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Assessing the Toxicity of Functionalised Porous Silica Nanoparticles.
(Wiley, 2022) Singh, Neenu; Patel, Trisha R. Y.; Girija, U. V.; Ahmad, Z.
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Curriculum design
(Taylor and Francis, 2024-05-31) Bhambra, Avninder S.
A curriculum is a key academic document, setting out the programme structure and content, also the rationale and vision for a course. It informs stakeholders and assures them a course is fit for purpose as well as demonstrates the level of quality required in the higher education sector. When considering curriculum design for biomedical science, designers must understand the needs of the profession and how to effectively educate those wishing to pursue a career as a Biomedical Scientist. However, not every student has this career aspiration in mind so each programme should be able to prepare students for diverse career paths. Such variation, combined with the already complex nature of the discipline, adds to the challenge of delivering a suitable curriculum which also considers professional development, as well as transferable and practical skills.
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DMU E-PARASITOLOGY: A TOOL TO TEACH CELL AND PARASITE CULTURE
(Oxford University Press, 2019) Pena-Fernandez, A; Hurtado, C.; Singh, Neena; Anjum, U.; Evans, M. D.
Open Access
Dystrophin Dp71 is essential for the development and function of macrophages
(bioRxiv, 2025-04-25) Chira, Natalia; Swatler, Julian; Manousopoulou, Antigoni; Rumney, Robin; Hajto, Jacek; Oksiejuk, Aleksandra; Baquero, Diana Garay; Rog, Justyna; White, Cory; Hinz, Stefan; Alnassar, Nancy; Young, Chirstopher N. J.; Arkle, Steven; Korostynski, Michal; Kozlowska, Ewa; Byrne, D.; Gorecki, Dariusz C.
Mutations in the DMD gene, encoding dystrophins, cause progressive muscle degeneration with severe sterile inflammation. While macrophages predominate amongst muscle-infiltrating cells, being central to both damage and regeneration, they were not known to express dystrophin. Yet, we recently demonstrated Dp71 dystrophin expression correlating with tumour infiltrating macrophages. Here we report physiological, developmentally regulated expression of Dp71 in human and mouse hematopoietic stem cells, which decreases with cell maturation into bone marrow macrophages (BMM). Proteomics with molecular and functional analyses in mouse dystrophin-null BMM and peritoneal macrophages reveal that absence of dystrophin disturbs their development. Alterations in over 300 proteins mapped to pathways and networks relating to reduced migration and phagocytosis and increased NLRP3 inflammasome functions. These defects are Dp71-dependent and not caused by the dystrophic environment, since Dmdmdx mouse macrophages, which express Dp71, are not affected. Thus, we identify an important new role for the DMD gene. Altered Dp71 expression in tumour microenvironment cells and in dystrophin-null patients should be investigated to understand the commonalities between DMD and tumours, and potentially identify new treatments.
Open Access
Evaluation of the plastid and nuclear DNA barcodes in genus Ocimum towards quality assurance in herbal industry
(Elsevier, 2024-12-27) Amit Kumar; Vereena Rodrigues; Akanksha Saxena; Priyanka Mishra; Ashutosh K. Shukla; Ajit Kumar Shasany; Nazar, Nazia; Sgamma, Tiziana; Slater, A.; Velusamy Sundaresan
Rationale Species of the genus Ocimum are of immense value and are in high demand in trade which leads to unscrupulous adulteration of both crude drugs as well as formulations. Traditional method-based authentication is difficult in case of incomplete or damaged samples and in dried herbal bulk material. High degree of morphological similarity, issues of polyploidy, and the possibility of inter- and intraspecific hybridization have plagued the Ocimum market. Hence, there is an immediate need for developing DNA barcodes for fast and accurate identification of the species. Objective In this study, three plastid regions (matK, rbcL, and trnH-psbA) and two nuclear regions (ITS and ITS2) have been evaluated for their performance as DNA barcodes to check the delineation of Ocimum species. Materials and Methods Five widely accepted markers were assessed for their efficiency using methods like Nearest genetic distance, Wilcoxon test, Best Match (BM), and Neighbor-Joining (NJ) tree methods. Conclusion Our study suggests that discrimination rate amongst single barcodes is the highest for trnH-psbA with the NJ analysis (92 %). By combining two or more barcodes, no significant changes were observed. A reliable and commercially viable DNA barcoding system has been developed for accurate species identification of various Ocimum species. The varied approaches used in the investigation had different species identification potential. The identification success rates of plastid DNA and nuclear DNA barcodes were comparable using pairwise genetic distance (PWG-distance), BM, and NJ methods. Despite having high inter-specific and the lowest intra-specific genetic distance, trnH-psbA failed to discriminate Ocimum species having hybrid origin, indicating the need to develop more suitable barcode loci in future.
Open Access
How do care workers learn to care for people with dementia living in care homes? A model of informal learning
(Emerald, 2024-08-28) Latham, Isabelle; Brooker, Dawn; de Vries, Kay
Purpose – This paper describes a model of “Learning to care” derived from a study exploring how care workers in care homes learn to care for people living with dementia. The “Learning to care” model is primarily informal in nature in which influences such as formalised training and organisational culture impact care outcomes indirectly rather than directly. Design/methodology/approach – This study used a focused, critical ethnographic approach in two care homes in England resulting in 63 h of observation of care of people living with advanced dementia, 15 semistructured interviews and 90 in-situ ethnographic interviews with care staff. Findings – The findings reveal a three-level model of learning to care. At the level of day-to-day interactions is a mechanism for learning that is wholly informal and follows the maxim “What Works is What Matters”. Workers draw on resources and information within this process derived from their personal experiences, resident influences and care home cultural knowledge. Cultural knowledge is created through a worker’s interactions with colleagues and the training they receive, meaning that these organisational level influences affect care practice only indirectly via the “WhatWorks is WhatMatters” mechanism. Originality/value – This study makes an original contribution by explaining the nature of day-to-day informal learning processes as experienced by care workers and those living with dementia in care homes. In particular, it illuminates the specific mechanisms by which organisational culture has an effect on care practice and the limitations of formal training in influencing such practice.
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In vitro detection of cancer cells using a novel fluorescent choline derivative
(Springer Nature, 2024-11-20) Caprifico, Anna; Vaghi, Luca; Spearman, Peter; Calabrese, Gianpiero; Papagni, Antonio
Introduction The treatment of preinvasive lesions is more effective than treating invasive disease, hence detecting cancer at its early stages is crucial. However, currently, available screening methods show various limitations in terms of sensitivity, specificity, and practicality, thus novel markers complementing traditional cyto/histopathological assessments are needed. Alteration in choline metabolism is a hallmark of many malignancies, including cervical and breast cancers. Choline radiotracers are widely used for imaging purposes, even though many risks are associated with their radioactivity. Therefore, this work aimed to synthesise and characterise a non-radioactive choline tracer based on a fluorinated acridine scaffold (CFA) for the in vitro detection of cervical and breast cancer cells by fluorescence imaging. Methods CFA was fully characterised and tested for its cytotoxicity on breast (MCF-7), cervical (HeLa), glioblastoma (U-87 MG) and hepatoblastoma (HepG2) cancer cell lines and in normal cell lines (epithelial, HEK-293 and human dermal fibroblasts, HDFs). The cellular uptake of CFA was investigated by a confocal microscope and its accumulation was quantified over time. The specificity of CFA over mesenchymal origin cells (HDFs), as a model of cancer-associated fibroblasts was investigated by fluorescence microscopy. Results CFA was toxic at much higher concentrations (HeLa IC50 = 200 ± 18 µM and MCF-7 IC50 = 105 ± 3 µM) than needed for its detection in cancer cells (5 µM). CFA was not toxic in the other cell lines tested. The intensity of CFA in breast and cervical cancer cells was not significantly different at any time point, yet it was greater than HepG2 and U-87 MG (p ≤ 0.01 and p ≤ 0.0001, respectively) after 24 h incubation. A very weak signal intensity was recorded in HEK-293 and HDFs (p ≤ 0.001 and p ≤ 0.0001, respectively). A selective ability of CFA to accumulate in HeLa and MCF-7 was recorded upon co-culture with fibroblasts. Conclusions The results showed that CFA preferentially accumulated in cancer cells rather than in normal cells. These findings suggest that CFA may be a potential diagnostic probe for discriminating healthy tissues from malignant tissues due to its specific and highly sensitive features; CFA may also represent a useful tool for in vitro/ex vivo investigations of choline metabolism in patients with cervical and breast cancers.
Open Access
Integrating DNA Barcoding Within an OrthogonalApproach for Herbal Product Authentication:A Narrative Review
(Wiley, 2024-11-12) Nazar, Nazia; Saxena, Akanksha; Sebastian, Anu; Slater, Adrian; Sundaresan, Velusamy; Sgamma, Tiziana
Introduction: Existing methods for morphological, organoleptic, and chemical authentication may not adequately ensure the accurate identification of plant species or guarantee safety. Herbal raw material authentication remains a major challenge in herbal medicine. Over the past decade, DNA barcoding, combined with an orthogonal approach integrating various testing methods for quality assurance, has emerged as a new trend in plant authentication. Objective: The review evaluates DNA barcoding and common alternative testing in plant-related sectors to enhance quality assurance and accurate authentication. Method: Studies were selected based on their relevance to the identification, quality assurance, and safety of herbal products. Inclusion criteria were peer-reviewed articles, systematic reviews, and relevant case studies from the last two decades focused on DNA barcoding, identification methods, and their applications. Exclusion criteria involved studies lacking empirical data, those not peer-reviewed, or those unrelated to the main focus. This ensured the inclusion of high-quality, pertinent sources while excluding less relevant studies. Results: An orthogonal approach refers to the use of multiple, independent methods that provide complementary information for more accurate plant identification and quality assurance. This reduces false positives or negatives by confirming results through different techniques, combining DNA barcoding with morphological analysis or chemical profiling. It enhances confidence in results, particularly in cases of potential adulteration or misidentification of plant materials. Conclusion: This study highlights the persistent challenges in assuring the quality, purity, and safety of plant materials. Additionally, it stresses the importance of incorporating DNA-based authentication alongside traditional methods, to enhance plant material identification.
Open Access
Long-term study on the applicability of virtual resources for teaching and learning molecular techniques.
(Editorial Aula Magna. McGraw-Hill Interamericana de España S.L., 2024-04-09) Peña-Fernández, A.; Sgamma, Tiziana; Evans, M. D.; Peña, M. A.
Since 2018, we have been updating and testing the effectiveness of two open-access virtual laboratories to teach molecular techniques using a blended approach to our second-year Clinical Science students enrolled in the shared module of Molecular Gene- tics and Genomics at De Montfort University (DMU, England). Briefly, students were asked to complete all the different exercises and calculations to prepare a master mix for PCR analysis and to produce gels for electrophoresis. In the physical laboratory practicals (two 3-hour long sessions), students were asked to directly perform the tasks in small groups, with little instructions/demonstration. Specific feedback was collected in 2020/21 and 22/23, following high levels of learning (93,6 %) reported in the introduction of our blended activity in 2018/19. Thus, 78,9 %, 100 % and 79 %, 100 % indicated that they learnt how to perform PCR and gel electrophoresis, respectively for each question/cohort. Moreover, responders highlighted that they learnt strategies to trouble-shooting a PCR assay, suggesting that the specific virtual laboratory units would be successful to train students how to run this molecular technique in a laboratory (as this aspect was only taught through the website resources). However, a high pro- portion of students indicated that these resources could not substitute the physical practicals in the laboratory (36,9 %, 66,6 %). The virtual laboratory resources on molecular biology available could enhance the teaching/learning of these highly specific laboratory techniques.
Open Access
Modulation of albumin esterase activity by warfarin and diazepam.
(MDPI, 2024-10-27) Belinskaia, D. A.; Batalova, A. A.; Voronina, P. A.; Shmurak, V. I.; Vovk, M. A.; Polyanichko, A. M.; Sych, T. S.; Samodurova, K. V.; Antonova, V. K.; Volkova, A. A.; Gerda, B. A.; Jenkins, R. O.; Goncharov, N. V.
Data are accumulating on the hydrolytic activity of serum albumin towards esters and organophosphates. Previously, with the help of the technology of proton nuclear magnetic resonance (1H NMR) spectroscopy, we observed the yield of acetate in the solution of bovine serum albumin and p-nitrophenyl acetate (NPA). Thus, we showed that albumin possesses true esterase activity towards NPA. Then, using the methods of molecular docking and molecular dynamics, we established site Sudlow I as the catalytic center of true esterase activity of albumin. In the present work, to expand our understanding of the molecular mechanisms of albumin pseudoesterase and true esterase activity, we investigated—in experiments in vitro and in silico—the interaction of anticoagulant warfarin (WRF, specific ligand of site Sudlow I) and benzodiazepine diazepam (DIA, specific ligand of site Sudlow II) with albumins of different species, and determined how the binding of WRF and DIA affects the hydrolysis of NPA by albumin. It was found that the characteristics of the binding modes of WRF in site Sudlow I and DIA in site Sudlow II of human (HSA), bovine (BSA), and rat (RSA) albumins have species differences, which are more pronounced for site Sudlow I compared to site Sudlow II, and less pronounced between HSA and RSA compared to BSA. WRF competitively inhibits true esterase activity of site Sudlow I towards NPA and does not affect the functioning of site Sudlow II. Diazepam can slow down true esterase activity of site Sudlow I in noncompetitive manner. It was concluded that site Sudlow I is more receptive to allosteric modulation compared to site Sudlow II.
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Novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives and their antitrypanosomal activities against T.brucei
(Elsevier, 2024-06-05) Bhambra, Avninder S.; Taylor, Annie; Hering, Moritz; Elsegood, Mark R. J.; Teat, Simon J.; Weaver, George W.; Arroo, R. R. J.; Kaiser, Marcel; Maeser, Pascal
Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 µM against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the <1 µM range. We have demonstrated that substituted 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidines present promising antitrypanosomal hit molecules with potential for further preclinical development.
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Phenolic Metabolites Protocatechuic Acid and Vanillic Acid Improve Nitric Oxide Bioavailability via the Akt-eNOS Pathway in Response to TNF-α Induced Oxidative Stress and Inflammation in Endothelial Cells
(MDPI, 2024-11-11) Festa, Joseph; Hussain, Aamir; Al-Hareth, Zakia; Bailey, Stephen J.; Singh, Harprit; Da Boit, Mariasole
Background/Objectives: Reduced nitric oxide (NO) bioavailability secondary to excess-superoxide-driven oxidative stress is central to endothelial dysfunction. Previous studies suggest that phenolic metabolites may improve NO bioavailability, yet limited research is available in response to an inflammatory mediator. Therefore, we assessed the effects of cyanidin-3-glucoside (C3G) and its phenolic metabolites protocatechuic acid (PCA) and vanillic acid (VA) on NO bioavailability in a TNF-α induced inflammatory environment. Methods: Primary human umbilical vein endothelial cells (HUVECs) were supplemented with either C3G, PCA, or VA at 1 μM for 24 h before being stimulated with TNF-α 20 ng/mL for an additional 24 h. Measurements included cell viability, apoptosis, reactive oxygen species (ROS), nitrite concentrations, and endothelial nitric oxide synthase (eNOS) and Akt at the mRNA and protein level. Results: Phenolic metabolites did not increase the eNOS expression or nitrite levels in the unstimulated environment; rather, the metabolites mediated NO bioavailability in response to TNF-α induced oxidative stress, with increased viability, eNOS mRNA, phosphorylation, and nitrite levels. Conclusions: Phenolic metabolites, in the presence of TNF-α, can improve NO bioavailability at physiologically relevant concentrations via the Akt-eNOS pathway. This demonstrates that the induction of inflammation is a prerequisite for phenolic metabolites to promote protective properties in endothelial cells by activating the Akt-eNOS pathway.
Open Access
Research ethics training, challenges, and suggested improvements across Europe: Radiography research ethics standards for Europe (RRESFE).
(Elsevier, 2022-08-05) Bockhold, S.; McNulty, J.; Abdurakman, E.; Bezzina, P.; Drey, N.; England, A.; Flinton, D.; Khine, R.; McEntee, M.; Mekiš, N.; Precht, H.; Rainford, L.; Sá Dos Reis, C.; Santos, A.; Syrgiamiotis, V.; Willis, S.; Woodley, J.; Beardmore, C.; Harris, R.; O'Regan, T.; Malamateniou, C.
The Radiography Research Ethics Standards for Europe (RRESFE) project aimed to provide a cross-sectional view of the current state of radiography research ethics across Europe. This included investigating education and training in research ethics, and identifying the key challenges and potential improvements associated with using existing research ethics frameworks.
Open Access
Testing Green Tea Extract and Ammonium Salts as Stimulants of Physical Performance in a Forced Swimming Rat Experimental Model
(MDPI, 2024-09-24) Korf, E. A.; Novozhilov, A. V.; Mindukshev, I. V.; Glotov, A. S.; Kudryavtsev, I. V.; Baidyuk, E. V.; Dobrylko, I. A.; Voitenko, N. G.; Voronina, P. A.; Habeeb, S.; Ghanem, A.; Osinovskaya, N. S.; SEREBRYAKOVA, M. K.; Krivorotov, D. V.; Jenkins, R. O.; Goncharov, N. V.
The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination with GTE as stimulants of physical performance in a forced swimming rat experimental model. The determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry of blood plasma; biochemistry of erythrocytes; hematology; immunology; gene expression of slow- and fast-twitch muscles (m. soleus, SOL, and m. extensor digitorum longus, EDL, respectively); and morphometric indicators of slow- and fast-twitch muscles. Regarding the negative control (intact animals), the maximum number of changes in all blocks of indicators was recorded in the GTE + ACR group, whose animals showed the maximum functional result and minimum lactate values on the last day of the experiment. Next, in terms of the number of changes, were the groups ACR, ACL, GTE + ACL, GTE and NaCl (positive control). In general, the number of identified adaptive changes was proportional to the functional state of the animals of the corresponding groups, in terms of the duration of the swimming load in the last four days of the experiment. However, not only the total number but also the qualitative composition of the identified changes is of interest. The results of a comparative analysis suggest that, in the model of forced swimming we developed, GTE promotes restoration of the body and moderate mobilization of the immune system, while small doses of ammonium salts, especially ammonium carbonate, contribute to an increase in physical performance, which is associated with satisfactory restoration of skeletal muscles and the entire body. The combined use of GTE with ammonium salts does not give a clearly positive effect.
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The Cytotoxic Potential of Mesoporous Silica Loaded Anticancer Drug on 3D Model of HCT116 Colon Cancer Cell Line
(Wiley, 2022-08-19) Otele, Ibemusu Michael; Ahmad, Z.; Sayed, Elshaimaa; Ruparelia, K. C.; Singh, Neenu
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Toxicological Assessment of Porous Silica Nanoparticles: Cytotoxicity, Genotoxicity and Immunogenicity
(Elsevier, 2024-09-01) Patel, Trisha; Venkatraman Girija, U.; Ahmad, Z.; Singh, Neenu
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Toxicological assessment of porous silica nanoparticles: Cytotoxicity, genotoxicity, immunogenicity.
(Oxford University Press, 2024-09-27) Trisha, Patel; Ahmad, Z.; Venkatraman Girija, U.; Sahota, T. S.; Singh, Neenu

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