Publications by authors named "S Yahaya"

21 Publications

Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside.

Infect Genet Evol 2021 May 28;93:104944. Epub 2021 May 28.

Centre for Drug Research, Universiti Sains Malaysia, USM, 11800 Pulau Pinang, Malaysia. Electronic address:

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (M, PL, 3CL), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.
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May 2021

Twenty-Four-Month Outcomes of Drug-Coated Balloon in Diabetic Patients in the BIOLUX P-III Registry: A Subgroup Analysis.

Ann Vasc Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Diagnostic and Interventional Radiology, Klinikum Rosenheim, Rosenheim, Germany.

Objectives: This study aims to assess the use of drug-coated balloon (DCB) in a large patient population under real-world conditions and, specifically, analyse the impact of diabetes mellitus on long term outcomes following DCB utilisation.

Methods: BIOLUX P-III is a prospective, international, multicentre, registry that was conducted at 41 centres. The present study is a 24-month subgroup analysis of patients with diabetes mellitus having infrainguinal lesions treated with the Passeo-18 Lux DCB. The primary endpoints were freedom from major adverse events (MAEs) within 6 months of intervention and freedom from clinically driven target lesion revascularisation (CD-TLR) within 12 months of intervention.

Results: Of the 882 patients in the registry, 418 had diabetes (516 lesions). Most diabetics had concomitant hypertension (88.8%) and hyperlipidaemia (70.3%). Insulin dependence was observed in 48.8% of diabetics. Moreover, smoking (62.2%) and chronic renal insufficiency (41.9%) were also found to be common in this cohort. Chronic limb threatening ischemia (Rutherford class ≥4) was present in 53.1% of all patients. 22.9% of lesions were infrapopliteal, while 22.5% of lesions were treated for in-stent restenosis. The mean target lesion length was 85.6 ± 73.2 mm, and 79.4% of lesions were calcified (of which 17.9% were heavily calcified). Overall, device success was 99.7%. Freedom from MAEs was 90.5% (95% confidence interval (95% CI): 87.2-93.0) at 6 months, 85.4% (95% CI: 81.5-88.6) at 12 months and 80% (95% CI: 75.5-83.8) at 24 months. Freedom from CD-TLR was 95.9% (95% CI: 93.8-97.4), 91.6% (95% CI: 88.7-93.8), and 87.1% (95% CI: 83.5-89.9) at 6, 12, and 24 months, respectively. All-cause mortality at 24 months in diabetics was 16.0% (95% CI: 12.6-20.2), and major target limb amputation was 6.1% (95% CI: 4.1-8.9), which was significantly higher than in non-diabetics (8.4% (95% CI: 6.0-11.6), P = 0.0005 and 1.2% (95% CI: 0.5-2.9), P <0.0001, respectively). At 24 months, 82.0% of patients had improved by ≥1 Rutherford class.

Conclusion: Treatment of a real-world diabetic patient population with the Passeo-18 Lux DCB resulted in high efficacy and low complication rates, despite the fact that diabetic patients usually suffer from a multitude of concomitant comorbidities.

Clinical Trial Registration: NCT02276313.
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April 2021

Calcitriol Supplementation Ameliorates Microvascular Endothelial Dysfunction in Vitamin D-Deficient Diabetic Rats by Upregulating the Vascular eNOS Protein Expression and Reducing Oxidative Stress.

Oxid Med Cell Longev 2021 2;2021:3109294. Epub 2021 Feb 2.

Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia.

Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 g/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.
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February 2021

COVID-19 in children: a case series from Nigeria.

Pan Afr Med J 2020 28;35(Suppl 2):53. Epub 2020 May 28.

Department of Community Medicine Amadu Bello University, Zaria, Nigeria.

Introduction: The global spread of COVID-19 remains unabated in the past few months with a rise in the number of available literature on the novel virus. There are very few paediatric studies and are mainly from developed countries with a paucity of information on the clinical manifestation of COVID-19 disease in African children, including Nigeria.

Methods: We described the clinical presentation, laboratory findings, treatment and outcome in a group of five Nigerian children managed at a COVID-19 isolation and treatment centre in Nigeria.

Results: We managed a total of five children with an age range of 3 months to 8 years in the last four weeks (16th April to 15th May 2020). Three of the five children were males. All the children had close contact with family members that tested positive for COVID-19. Out of the five children, one had moderate disease, three had mild symptomatic disease, and one was asymptomatic. Two out of the five children had lymphocytosis. Out of the four children who had chest radiograph, two had features of pneumonia.

Conclusion: COVID-19 is not uncommon in Nigerian children, and all had a confirmed family member with COVID-19. Besides, contrary to leucopaenia with lymphopaenia observed in the adult's population, we found lymphocytosis in this cohort and about 50.0% had pneumonic changes on chest radiograph.
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March 2021

Sex differences in patients undergoing transcatheter aortic valve replacement in Asia.

Open Heart 2021 01;8(1)

Department of Cardiology, Sichuan University West China Hospital, Chengdu, China.

Objectives: Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.

Methods: Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.

Results: Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.

Conclusions: Asian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
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January 2021