Do T2DM and Hyperglycaemia Affect the Expression Levels of the Regulating Enzymes of Cellular O-GlcNAcylation in Human Saphenous Vein Smooth Muscle Cells?

Protein O-GlcNAcylation, a dynamic and reversible glucose-dependent post-translational modification of serine and threonine residues on target proteins, has been proposed to promote vascular smooth muscle cell proliferation and migration events implicated in vein graft failure (VGF). Therefore, targeting the enzymes (glutamine fructose-6P amidotransferase (GFAT), O-GlcNAc transferase (OGT), and O-GlcNAcase (OGA)) that regulate cellular O-GlcNAcylation could offer therapeutic options to reduce neointimal hyperplasia and venous stenosis responsible for VGF. However, it is unclear how type 2 diabetes mellitus (T2DM) and hyperglycaemia affect the expression of these enzymes in human saphenous vein smooth muscle cells (HSVSMCs), a key cell type involved in the vascular dysfunction responsible for saphenous VGF. Therefore, our aim was to assess whether T2DM and hyperglycaemia affect GFAT, OGT, and OGA expression levels in HSVSMCs in vitro. Expression levels of GFAT, OGT, and OGA were determined in low-passage HSVSMCs from T2DM and non-T2DM patients, and in HSVSMCs treated for 48 h with hyperglycaemic (10 mM and 25 mM) glucose concentrations, by quantitative immunoblotting. Expression levels of OGT, OGA, and GFAT were not significantly different in HSVSMC lysates from T2DM patients versus non-T2DM controls. In addition, treatment with high glucose concentrations (10 mM and 25 mM) had no significant effect on the protein levels of these enzymes in HSVSMC lysates. From our findings, T2DM and hyperglycaemia do not significantly impact the expression levels of the O-GlcNAcylation-regulating enzymes OGT, OGA, and GFAT in HSVSMCs. This study provides a foundation for future studies to assess the role of O-GlcNAcylation on VGF in T2DM

Defining the miRnome of Saphenous Vein Smooth Muscle Cells from Patients with Type 2 Diabetes Mellitus

Citation: Hussain, A.; Asare-Amankwah, Y.; Qureshi, S.; Thornton, M.J.; Palmer, T.M.; Bolanle, I.O.; Wood, I.C.; Turner, N.A.; Porter, K.E.; Tedder, A.; et al. Defining the miRnome of Saphenous Vein Smooth Muscle Cells from Patients with Type 2 Diabetes Mellitus. Diabetology 2024, 5, 178-189. https://doi. Abstract: Type 2 diabetes mellitus (T2DM) patients suffer premature development of cardiovascular disease and commonly require cardiac revascularization using the autologous saphenous vein (SV). Smooth muscle cells (SMCs) are the principal cell type within the vascular wall and are dysfunctional in T2DM SV-SMCs, yet the mechanisms underpinning this are incompletely understood. The purpose of this study was to interrogate differential microRNA (miRNA) expression in SV-SMCs to enhance our understanding of T2DM SV-SMC phenotypic change. miRNA expression in primary human SV-SMCs from T2DM and non-diabetic (ND) donors was determined using an array (n = 6 each of ND and T2DM SV-SMCs). Differentially expressed miRNAs were ranked, and functional annotation of the 30 most differentially expressed miRNAs using DAVID and KEGG analysis revealed pathways related to SMC phenotype, including proliferation, migration, cytokine production and cell signaling. After selecting miRNAs known to be involved in SMC phenotypic regulation, miR-17, miR-29b-2, miR-31, miR-130b and miR-491 were further validated using qRT-PCR (n = 5 each of ND and T2DM SV-SMC), with miR-29b-2 subsequently being removed from further investigation. Potential mRNA targets were identified using mirDIP. Predicted target analysis highlighted likely dysregulation in transcription, epigenetic regulation, cell survival, intracellular signaling and cytoskeletal regulation, all of which are known to be dysfunctional in T2DM SV-SMCs. In conclusion, this paper identified four miRNAs that are dysregulated in T2DM SV-SMCs and are implicated in functional changes in the behavior of these cells. This provides a step forward in our understanding of the molecular and epigenetic regulation of vascular dysfunction in T2DM

Effective information provision to rural dwellers in the era of economic recession in Nigeria: lessons from Osun State Public Library and NLA

Rural dwellers in Nigeria make up the larger proportion of the people whose information needs are not sufficiently met even though they contribute meaningfully to national development. The failure of the Nigerian public libraries to effectively perform its roles as a local gate way to knowledge and the layman’s university has adversely affected effective information provision to the citizens, especially those at the grass root resulting in adverse poverty in the land. The paper thus examines effective information provision to rural dwellers as a panacea for economic recession and poverty alleviation in Nigeria. This opinion paper employ secondary sources of information gathering and a practical approach to poverty alleviation in some rural communities in Osun State by the Osun State Nigerian Library Association. The write up discussed factors which made the attainment of the lofty aims and objectives of the UNESCO Manifesto unrealizable by public libraries in Nigeria. This in turn has resulted in acute poverty, ignorance, illiteracy and lack of access to basic needs such as water, food, education, healthcare, sanitation, security etc. among the rural dwellers. As recommended, public librarians should create a clear vision of their values in their capacity to provide effective quality services to rural dwellers through awareness campaign, orientation of rural dwellers on the use of alternatives means of lively hood, mobile library services, provision of community services by the NLA, increased budgetary allocation and provision of social and economic amenities for the rural dwellers.Keywords: Effective Information Provision, Rural Dwellers, Economic Recession, Poverty alleviation, Public Librarie

Evaluation of the neuropharmacologic potentials of methanol leaf extract of Cnidoscolus aconitifolius in mice

Background and Aim: Despite the plethora of drugs currently available, neurodegenerative diseases are leading cause of morbidity and mortality globally. Hence, there is a need for the development of more alternatives that are safe, efficient, and effective. In Nigeria, the leaves of Cnidoscolus aconitifolius are used ethnomedicinally for the management of central nervous system related disorders such as convulsion and anxiety. In this study, we evaluated some neuropharmacological effects of the methanol leaf extract of C. aconitifolius (CAE) in mice. Methods: Different groups of mice (n = 5) were administered 100, 200 and 400 mg/kg of CAE and then evaluated for sedative-hypnotic, anxiolytic, antidepressant, anticonvulsant, and muscle relaxant properties using standard protocols. Results: The onset of sleep was significantly reduced (P < 0.001), and sleep duration was significantly (P < 0.01) prolonged at doses of 200 and 400 mg/kg. All doses of the extract significantly (P < 0.05) reduced the number of head dips in hole-board test. In elevated plus maze test, the dose of 400 mg/kg increased (P < 0.05) the number of open arm entries without altering the time spent in the open arms of the maze. At 400 mg/kg, there was a significant (P < 0.05) reduction in the duration of immobility in forced swimming test. Doses of 200 and 400 mg/kg of the extract reduced (P < 0.05) the duration of immobility in the tail suspension test. The extract did not exhibit any anticonvulsant effect either in chemically induced or electrically induced models, and there was no significant alteration in motor coordination in extract-treated mice. Conclusion: Our results showed that CAE possesses sedative-hypnotic and antidepressant properties but lack anticonvulsant, anxiolytic and muscle relaxant actions in mice