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Dr Tarsem Sahota

Job: Post Doctoral Fellow

Faculty: Health and Life Sciences

School/department: Leicester School of Pharmacy

Address: De Montfort University, The Gateway, Leicester, LE1 9BH.

T: +44 (0)116 250 6972 / +44(0)116 250 6220

E: ssahota@dmu.ac.uk

W: https://www.dmu.ac.uk/hls

 

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Personal profile

  • Development of artificial pancreas
  • Delivery of insulin by self regulation
  • Structure and behaviour of insulin in solution
  • Polymerisation and covalent structures of proteins and polysaccharides, e.g. lectins and glucose polymers
  • In vivo studies
  • Development of a triggered dermatological formulation for the treatment of psoriasis
  • Physiological parameters for exercise in diabetes.

Research group affiliations

  • Department of Diabetes and Endocrinology, University Hospitals of Leicester NHS Trust
  • National Physical Laboratory
  • IOCT, De Montfort University
  • Renfrew Group, Leicester

Publications and outputs

  • Unraveling the Atomistic Mechanism of Electrostatic Lateral Association of Peptide 𝜷-Sheet Structures and Its Role in Nanofiber Growth and Hydrogelation
    dc.title: Unraveling the Atomistic Mechanism of Electrostatic Lateral Association of Peptide 𝜷-Sheet Structures and Its Role in Nanofiber Growth and Hydrogelation dc.contributor.author: Soliman, M.; Khedr, A.; Sahota, T. S.; Armitage, Rachel; Allan, Raymond N.; Laird, Katie; Allcock, N.; Ghuloum, F. I.; Amer, M. H.; Alazragi, R.; Edwards-Gayle, C. J. C.; Wychowaniec, Jacek K.; Vargiu, A. V.; Elsawy, M. dc.description.abstract: Guiding molecular assembly of peptides into rationally engineered nanostructures remains a major hurdle against the development of functional peptide-based nanomaterials. Various non-covalent interactions come into play to drive the formation and stabilization of these assemblies, of which electrostatic interactions are key. Here, the atomistic mechanisms by which electrostatic interactions contribute toward controlling self-assembly and lateral association of ultrashort β-sheet forming peptides are deciphered. Our results show that this is governed by charge distribution and ionic complementarity, both affecting the interaction patterns between charged residues: terminal, core, and/or terminal-to-core attraction/repulsion. Controlling electrostatic interactions enabled fine-tuning nanofiber morphology for the 16 examined peptides, resulting into versatile nanostructures ranging from extended thin fibrils and thick bundles to twisted helical "braids" and short pseudocrystalline nanosheets. This in turn affected the physical appearance and viscoelasticity of the formed materials, varying from turbid colloidal dispersions and viscous solutions to soft and stiff self-supportive hydrogels, as revealed from oscillatory rheology. Atomistic mechanisms of electrostatic interaction patterns were confirmed by molecular dynamic simulations, validating molecular and nanoscopic characterization of the developed materials. In essence, detailed mechanisms of electrostatic interactions emphasizing the impact of charge distribution and ionic complementarity on selfassembly, nanostructure formation, and hydrogelation are reported. dc.description: open access article
  • P13-21 Toxicological assessment of porous silica nanoparticles: cytotoxicity, genotoxicity and immunogenicity
    dc.title: P13-21 Toxicological assessment of porous silica nanoparticles: cytotoxicity, genotoxicity and immunogenicity dc.contributor.author: Patel, Trisha; Ahmad, Z.; Venkatraman Girija, U.; Sahota, T. S.; Singh, Neenu
  • Toxicological assessment of porous silica nanoparticles: Cytotoxicity, genotoxicity, immunogenicity.
    dc.title: Toxicological assessment of porous silica nanoparticles: Cytotoxicity, genotoxicity, immunogenicity. dc.contributor.author: Trisha, Patel; Ahmad, Z.; Venkatraman Girija, U.; Sahota, T. S.; Singh, Neenu
  • Breakfast portion sizes: visual cues and consumption
    dc.title: Breakfast portion sizes: visual cues and consumption dc.contributor.author: Kwiecien, Kinga; Santos-Merx, Lourdes; Sahota, T. S.; Da Boit, Mariasole
  • Elderberry extract improves molecular markers of endothelial dysfunction linked to atherosclerosis
    dc.title: Elderberry extract improves molecular markers of endothelial dysfunction linked to atherosclerosis dc.contributor.author: Festa, Joseph; Hussain, Aamir; Hackney, Amon; Desai, Unmesh; Sahota, T. S.; Singh, Harprit; Da Boit, Mariasole dc.description.abstract: Endothelial dysfunction (ED), secondary to diminished nitric oxide (NO) production and oxidative stress, is an early subclinical marker of atherosclerosis. Reduced NO bioavailability enhances the adhesion of monocytes to endothelial cells and promotes atherosclerosis. Elderberry extract (EB) is known to contain high levels of anthocyanins which could exert vascular protective effects. Specifically, we investigated the functional capacity of EB on various markers of ED. Human umbilical vein endothelial cells (HUVEC) were pretreated with EB 50 μg/mL and stimulated with TNF-α 10 ng/mL. Cell viability, apoptosis, oxidative stress; eNOS, Akt, Nrf2, NOX-4, and NF-κB at the protein level were measured. A co-culture model was used to determine whether EB could prevent the adhesion of monocytes (THP-1) to HUVECs. Moreover, the expression of adhesion molecules and pro-inflammatory cytokines were also measured. It was demonstrated that EB prevented TNF-α induced apoptosis and reactive oxygen species production in HUVECs. Additionally, EB upregulated Akt and eNOS activity, and Nrf2 expression in response to TNF-α, whereas it decreased NOX-4 expression and NF-κB activity. EB prevented the adhesion of monocytes to HUVECs, as well as reduced IL-6 and MCP-1 levels, which was associated with inhibition of VCAM-1 expression. Our results demonstrate that EB upregulates key cellular markers of endothelial function and ameliorates markers of ED. EB could be used as a potential nutritional aid for preventing atherosclerosis progression. dc.description: open access article
  • Synthesis and Identification of Biologically Active Mono-Labelled FITC-Insulin Conjugate
    dc.title: Synthesis and Identification of Biologically Active Mono-Labelled FITC-Insulin Conjugate dc.contributor.author: Sahota, T. S.; Vu, Tam; Taylor, M. Joan; Singh, Harprit; Bottrill, Andrew; Bilmoria, Jay dc.description.abstract: Fluorescently labelling proteins such as insulin have wide ranging applications in a pharmaceutical research and drug delivery. Human insulin (Actrapid®) was labelled with fluorescein isothiocyanate (FITC) and the synthesised conjugate identified using reverse phase high performance liquid chromatography (RP-HPLC) on a C18 column and a gradient method with mobile phase A containing 0.1% trifluoroacetic acid (TFA) in Millipore water and mobile phase B containing 90% Acetonitrile, 10% Millipore water and 0.1% TFA. Syntheses were carried out at varying reaction times between 4 and 20 h. Mono-labelled FITC-insulin conjugate was successfully synthesised with labelling at the B1 position on the insulin chain using a molar ratio of 2:1 (FITC:insulin) at a reaction time of 18 h and confirmed by electrospray mass spectroscopy. Reactions were studied across a pH range of 7–9.8 and the quantities switch from mono-labelled to di-labelled FITC-insulin conjugates at a reaction time of 2 h (2:1 molar ratio) at pH > 8. The conjugates isolated from the studies had biological activities in comparison to native insulin of 99.5% monoB1, 78% monoA1, 51% diA1B1 and 0.06% triA1B1B29 in HUVEC cells by examining AKT phosphorylation levels. MonoB1 FITC-insulin conjugate was also compared to native insulin by examining cell surface GLUT4 in C2C12 skeletal muscle cells. No significant difference in the cellular response was observed for monoB1 produced in-house compared to native insulin. Therefore mono-labelled FITC-insulin at the B1 position showed similar biological activity as native insulin and can potentially be used for future biomedical applications. dc.description: The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • The impact of moderate combination exercise on HbA1c, IL-6, and TNF in type 2 diabetic and non-diabetic subjects: an interventional non-randomized clinical trial
    dc.title: The impact of moderate combination exercise on HbA1c, IL-6, and TNF in type 2 diabetic and non-diabetic subjects: an interventional non-randomized clinical trial dc.contributor.author: Sahota, T. S.; Taylor, M. Joan; Alsubaie, Nawal; Alharbi, Bandar dc.description.abstract: Introduction: The main causes of worldwide increase in prevalence of type 2 diabetes are the daily consumption of excessive number of calories and sedentary lifestyle. Diabetes is usually accompanied by hypertension, lipid disorders and obesity that are considered as risk factors for developing diabetes. This study is designed to assess the benefit of a combined exercise programme (cardio “aerobic” and resistance) on HbA1c and the inflammatory markers (IL-6, and TNF) in type 2 diabetic (T2D) and non-diabetic (ND) subjects. Materials and methods: This is an interventional non randomized clinical trial conducted from 2016 to 2019 at exercise physiology laboratory at De Montfort University (DMU). Our target volunteers are T2D (HbA1c > 6.4), and ND (HbA1c < 5.8) with age group from 18-60 years old who are fit and able to do exercise. No restriction on weight. HbA1c, weight, BMI, waist and lung capacity were measured at baseline and at the 12th exercise session. In each exercise session the participant performed a combined exercise program consists of 30 min of resistance exercise followed by 20 min moderate cycling to be done twice a week for 6 weeks. Results: We enrolled 17 T2D intervention group 4 female and 13 male and 8 ND control group 5 female and 3 male. In both groups there was a significant reduction in HbA1c level after 6 weeks (P= 0.000). In T2D there were a significant weight reduction that decreased from (92.0± 4.3) to (90.0±4.5), (P< 0.001), BMI reduction that decreased from (30.8± 1.0) to (30.2± 0.9), (P< 0.001). In ND, the changes in weight reduction and BMI level were not significant. In T2D the changes in IL-6 level were only significant after the last exercise session. It was increased from 1.79±0.4 to 3.88±1.9 pg/ml (P=0.002), while it was not significant in ND group. In T2D and ND subjects, the changes in TNF level were insignificant. Conclusion: Development of combination exercise programs as a non-pharmacological intervention for diabetic and non-diabetic population are essential to decrease the prevalence of diabetes worldwide. In addition to conduction of public awareness events for proper implementation. dc.description: open access article
  • Immunological Biomarkers for Diabetes Management
    dc.title: Immunological Biomarkers for Diabetes Management dc.contributor.author: Furmonaviciene, Ruta; Saiful, Shubo; Gunawardena, T.G.; Hill, Andrew; Chauhan, Krishan; Desai, Unmesh; Sahota, T. S.; Taylor, M. Joan; Alsubaie, Naval dc.description.abstract: Globally there are 422 million known cases of people affected with diabetes according to the world health organisation (1). It is estimated that 46% of people with diabetes worldwide are undiagnosed (2). Monitoring diabetes and improving life style for such patients is also a big challenge for current healthcare. To address this global health issue, we have investigated immunological serum and salivary biomarkers for diabetes using molecular arrays, namely cytokine and growth factor kit I from Randox Laboratories Ltd, London, UK.
  • WP: Learning about Diabetes in the Lab
    dc.title: WP: Learning about Diabetes in the Lab dc.contributor.author: Furmonaviciene, Ruta; Ioannou, Marilena; Sahota, T. S.; Laing, Cerri; Taylor, Joan dc.description.abstract: See poster file attached.
  • Glucose lowering strategies with insulin
    dc.title: Glucose lowering strategies with insulin dc.contributor.author: Taylor, M. Joan; Sahota, T. S.; Chauhan, Krishan P dc.description.abstract: People with type 1 diabetes must use insulin and a large fraction of those with type 2 condition also do so. Many therefore struggle with the unpredictable balancing of insulin dose with calorie intake and utility. A healthy pancreas makes meticulous adjustment on a continuous basis that present therapeutic insulin administration cannot match. However, much progress has been made to make it simpler to inject both background and fast-acting boost insulins with a view to better mimicking normal pancreatic output. The present fast insulins are reviewed with accent on the primary amino acid structures of the biosynthetic types that diffuse more quickly than regular insulin that associates in hexamers. This makes boost doses kinetically and clinically more effective, allowing people to inject better estimated boost and corrective doses. Formulation advances are discussed for their present and potential contributions. The newer slow-acting insulins are also described and compared, their advantage also being kinetic with a lower likelihood of inducing overnight hypoglycaemia when used optimally. Finally, the appreciation of the advantages of alternative routes of administration such as oral and peritoneal are included in this review because of the possibility of altering the hepatic to peripheral ratio, the reasons for which are more effective but less obesogenic insulin activity. The logistics of oral insulin are summarised in terms of the risks to the insulin structure, the facilitation of paracellular uptake at the apical surface and the paradoxically advantageous hepatic first pass. Other non-invasive routes are also included in the review. dc.description: open access journal

Click here for a full listing of Tarsem Sahota's publications and outputs.

Key research outputs

Taylor, M. J., S. Tanna, et al. (2008). "UV Cross-Linked Dextran Methacrylate - Concanavalin A Methacrylamide Gel Materials for Self-Regulated Insulin Delivery." Drug Dev Ind Pharm 34(1): 73-82.

Taylor M J, Tanna, S., Sahota, T. S. et al “Glucose-sensitive gel rheology of dextran-concanavalin A mixtures suitable for self-regulating insulin delivery” Pharmaceutical Development and Technology 15(1):80-8, 2010.

Taylor M J, Sahota, T. S. “In vivo study of a polymeric glucose sensitive insulin delivery system using a rat model” Journal of Pharmaceutical Sciences, 9, 10, 4215-4227 2010.

S., Sahota, Sawicka,  Taylor M J, Tanna, , T. S. “Effect of varying molecular weight of dextran on acrylic derivatised dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery” Drug Development and Industrial Pharmacy, 2011, Mar;37(3):351-8.

Research interests/expertise

  • Insulin physico-chemistry
  • Diabetes control
  • Drug delivery
  • Rheometry (viscosity of gels and sols)
  • Engineering and design of devices for drug delivery
  • Physiological parameters for exercise in diabetes.

Conference attendance

Posters
Taylor, M. & Sahota, T. Glucose-sensitive insulin delivery in vivo - an artificial pancreas? (Poster) 3rd International Conference on Advanced Treatments and Technologies (ATTD) Basel Feb 2010

Sahota T.S. & Taylor M.J. Competitive displacement of blue dextran by cibacron blue in dextran albumin gels? (Poster) Intern. Symp. Control. Rel. Bioact. Mater, Controlled Release Society, Inc. Portland, Oregon 2010

Sahota T.S. & Taylor M.J. Closed Loop Delivery in the Pig (accepted poster) Controlled Release Society Annual Symposium, Quebec, Canada 2012

Consultancy work

  • Polymer synthesis
  • Rheology
  • HPLC
  • Pressure measurements
  • Diabetes
  • Focus groups and survey design
  • GPC

Externally funded research grants information

Co-Investigator on the following grants:

  • NEAT funding (£278k)
  • HFCE matched funding (25k)
  • Edith Murphy Foundation 2008 (£50k)
  • Edith Murphy Foundation 2011 (£200k)
  • Lachesis (£5k)