Biology subjects

Bello, S. O.

Publications and source records attributed to Bello, S. O..

4 recordsLinked to original sources

bioRxiv2025

Mechanical unloading coupled with coronary reperfusion reduces fibrosis and stimulates cardiomyocyte proliferation after myocardial infarction

IntroductionPercutaneous left ventricular assist devices (pLVADs) have become essential tools during coronary reperfusion in high risk PCI. Significant reduction in infarct propagation is observed when mechanical unloading is coupled with reperfusion, but little is known of the effect this reduction in wall stress and extracellular matrix with pLVADs have on the hearts regenerative capacity. ObjectiveThis study investigates the effect coronary reperfusion coupled with mechanical unloading has on myocardial fibrosis, and the impact these changes in extracellular matrix have on the hearts regenerative potential. MethodsMI was induced by coronary artery ligation in Lewis rats. Hearts underwent permanent coronary ligation (AMI) or were reperfused after 90 minutes (AMI/R). In each group, hearts were either loaded (AMI-L or AMI/R-L) or unloaded (AMI-U or AMI/R-U). In the unloaded subgroup, the infarcted hearts were explanted after 90 minutes and transplanted into the abdomen of healthy recipients via heterotopic abdominal heart-lung transplantation. The recipients heart acted as control. Hearts were analysed on day 7. Results30 hearts were studied. In the permanent ligation group, fibrosis increased in both the loaded and unloaded hearts with no significant rise in cardiomyocyte proliferation. After coronary reperfusion, there was a decrease in fibrosis with mechanical unloading and cardiomyocyte proliferation rose significantly (AMI/R-L vs AMI/R-U p= 0.0001). Cardiomyocyte proliferative rate in the loaded and unloaded hearts was 0.6%, and 3.7% respectively after permanent ligation, and 0.5%, and 10.4% respectively after coronary reperfusion. ConclusionThese data show that coronary reperfusion coupled with mechanical unloading reduces myocardial fibrosis and upregulates cardiomyocyte proliferation after myocardial infarction. TRANSLATIONAL PERSPECTIVEThis study demonstrates that the adult hearts intrinsic regenerative capacity is significantly augmented when coronary reperfusion is coupled with mechanical unloading after MI in an animal model. This finding has significant translational implications for myocardial self- repair and recovery especially in ischaemic cardiomyopathy. The investigation of cardiomyocyte proliferative response should be included in current ongoing trials such as the PROTECT IV, RECOVER IV, and IMPACT trials, all currently investigating clinical outcomes when mechanical unloading is coupled with coronary reperfusion after MI.

physiology↗

bioRxiv2023

SERODIAGNOSIS OF SALMONELLA INFECTION: USING A LOGISTIC REGRESSION MODEL.

Salmonella infection remains a major global health problem and worsened by lack of appropriate diagnostic tools to aid early detection and teatment, particularly in low-income nations. Salmonella typhi is the most common causative agent of typhoid fever and the prevalence of this illness has been on the increase specifically in areas of poor personal hygiene and sanitation. This study was carried out to further improve the diagnosis of salmonella infection, through a mathematical regression model. An analysis was performed using the logistic regression approach and the predictability of the model was done by extracting fifteen (15) typhoid observations from the obtained samples; for the model to predict their status. The model was able to accurately predict 66.7% of the observations. This study showed an increased prevalence in typhoid fever including a significant correlation between typhoid fever and other parameters. The global burden of this illness can be minimized by proper vaccination, and prompt but appropriate diagnosis and treatment.Further studies and test-meaasures also needs to be carried out to improve diagnosis and treatment regimen.

microbiology↗

bioRxiv2022

Erythromycin, Retapamulin, Pyridoxine, Folic acid, and Ivermectin dose-dependently inhibit cytopathic effect, Papain-like Protease, and MPRO of SARS-CoV-2

We previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 M, 4.23 M, 9.29 M, 3.19 M and 84.31 M respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50 of 0.94 M, 0.88 M, 1.14 M, 1.07 M, 1.51 M respectively and the main protease(MPRO) with IC50 of 1.35 M, 1.25 M, 7.36 M, 1.15 M and 2.44 M respectively. The IC50 for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

pharmacology and toxicology↗

bioRxiv2022

Innovative, rapid, high throughput method for drug repurposing in a pandemic - a case study of SARS-CoV-2 and COVID-19

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use; either because of demonstrated lack of clinical efficacy in trials, inappropriate dose requirements and probably use of inappropriate pre-clinical laboratory surrogates of effectiveness. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods that highlight inhibition of viral induced cytopathic effect (CPE) as a laboratory surrogate of effectiveness. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms. FundingTETFund Covid-19 Special Intervention Research grant(grant number TETFund/DR&D/CE/ SI/COVID-19/UDUS/VOL 1)

pharmacology and toxicology↗