Association between human leukocyte antigen alleles and COVID-19 disease severity.

Background: the human leukocyte antigen (HLA) loci have been widely characterized to be associated with viral infectious diseases. Several studies including various ethnic groups and populations suggested associations between certain HLA alleles and SARS-CoV-2 infection. Despite the numerous associations identified, the role of HLA polymorphisms in determining the individual response to SARS-CoV-2 infection is controversial among different Saudi populations.

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia.

Congenital disorders of glycosylation (CDG) are a group of more than 100 rare genetic disorders characterized by impaired glycosylation of proteins and lipids. The clinical presentation of CDG varies tremendously, from single-organ to multi-organ involvement and from prenatal death to a normal adult phenotype. In this case study, we report a large consanguineous family with multiple children suffering from cerebral palsy, seizure, developmental and epileptic encephalopathy, and global developmental delay.

Tween 80-Based Self-Assembled Mixed Micelles Boost Valsartan Transdermal Delivery.

Valsartan (Val) is an important antihypertensive medication with poor absorption and low oral bioavailability. These constraints are due to its poor solubility and dissolution rate. The purpose of this study was to optimize a mixed micelle system for the transdermal delivery of Val in order to improve its therapeutic performance by providing prolonged uniform drug levels while minimizing drug side effects.

Variants Can Associate with Non-Syndromic Congenital Heart Disease without Aortopathy.

Background: Congenital heart diseases (CHD) are the most common congenital malformations in newborns and remain the leading cause of mortality among infants under one year old. Molecular diagnosis is crucial to evaluate the recurrence risk and to address future prenatal diagnosis. Here, we describe two families with various forms of inherited non-syndromic CHD and the genetic work-up and resultant findings.

Reply to Zandi, M.; Soltani, S. Comment on "Alfassam et al. Development of a Colorimetric Tool for SARS-CoV-2 and Other Respiratory Viruses Detection Using Sialic Acid Fabricated Gold Nanoparticles. 2021, , 502".

When COVID-19 was first announced back in 2019, there were vast number of attempts to halt the progression of the SARS-CoV-2 virus once and for all [...

Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes.

Despite the enormous economic and societal burden of chronic kidney disease (CKD), its pathogenesis remains elusive, impeding specific diagnosis and targeted therapy. Herein, we sought to elucidate the genetic causes of end-stage renal disease (ESRD) and identify genetic variants associated with CKD and related traits in Saudi kidney disease patients. We applied a genetic testing approach using a targeted next-generation sequencing gene panel including 102 genes causative or associated with CKD.

Fast-Dissolving Nifedipine and Atorvastatin Calcium Electrospun Nanofibers as a Potential Buccal Delivery System.

Geriatric patients are more likely to suffer from multiple chronic diseases that require using several drugs, which are commonly ingested. However, to enhance geriatric patients' convenience, the electrospun nanofiber system was previously proven to be a successful alternative for the existing oral dosage forms, i.e.

Consanguinity and Congenital Heart Disease Susceptibility: Insights into Rare Genetic Variations in Saudi Arabia.

Congenital heart disease (CHD) encompasses a wide range of structural defects of the heart and, in many cases, the factors that predispose an individual to disease are not well understood, highlighting the remarkable complexity of CHD etiology. Evidence of familial aggregation of CHD has been demonstrated in different communities and for different cardiac lesions. Consanguinity, particularly among first cousins, is an added risk factor for these families, particularly in societies where it is considered a common cultural practice, as confirmed in previous studies conducted in Saudi Arabia and other countries.

The Role of the Disrupted Podosome Adaptor Protein (SH3PXD2B) in Frank-Ter Haar Syndrome.

Frank-Ter Haar syndrome (FTHS), sometimes referred to as Ter Haar syndrome, is a rare hereditary disorder that manifests in skeletal, cardiac, and ocular anomalies, including hypertelorism, glaucoma, prominent eyes, and facial abnormalities. In this study, we performed whole-exome sequencing (WES) to identify the genetic component responsible for the phenotype of the index patient, a male infant born to a consanguineous family from Saudi Arabia. The analysis revealed a homozygous missense variant, c.

Correlation between ABO Blood Group Phenotype and the Risk of COVID-19 Infection and Severity of Disease in a Saudi Arabian Cohort.

Background: Disease severity among patients infected with SARS-CoV-2 varies remarkably. Preliminary studies reported that the ABO blood group system confers differential viral susceptibility and disease severity caused by SARS-CoV-2. Thus, differences in ABO blood group phenotypes may partly explain the observed heterogeneity in COVID-19 severity patterns, and could help identify individuals at increased risk.

Association of KIR gene polymorphisms with COVID-19 disease.

Background: Natural killer (NK) cells play an essential role against viruses. NK cells express killer cell immunoglobulin-like receptors (KIRs) which regulate their activity and function. The polymorphisms in KIR haplotypes confer differential viral susceptibility and disease severity caused by infections.

Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks.

Novel Autosomal Recessive Splice-Altering Variant in Is Associated with Congenital Heart Disease.

Congenital heart defects (CHDs) are the most common types of birth defects, and global incidence of CHDs is on the rise. Despite the prevalence of CHDs, the genetic determinants of the defects are still in the process of being identified. Herein, we report a consanguineous Saudi family with three CHD affected daughters.

Development of Epirubicin-Loaded Biocompatible Polymer PLA-PEG-PLA Nanoparticles: Synthesis, Characterization, Stability, and In Vitro Anticancerous Assessment.

Unlabelled: Epirubicin (EPI) is an anti-cancerous chemotherapeutic drug that is an effective epimer of doxorubicin with less cardiotoxicity. Although EPI has fewer side effects than its analog, doxorubicin, this study aims to develop EPI nanoparticles as an improved formula of the conventional treatment of EPI in its free form.

Methods: In this study, EPI-loaded polymeric nanoparticles (EPI-NPs) were prepared by the double emulsion method using a biocompatible poly (lactide) poly (ethylene glycol) poly(lactide) (PLA-PEG-PLA) polymer.

Development of a Colorimetric Tool for SARS-CoV-2 and Other Respiratory Viruses Detection Using Sialic Acid Fabricated Gold Nanoparticles.

Sialic acid that presents on the surface of lung epithelial cells is considered as one of the main binding targets for many respiratory viruses, including influenza and the current coronavirus (SARS-CoV-2) through the viral surface protein hemagglutinin. Gold nanoparticles (Au NPs) are extensively used in the diagnostic field owing to a phenomenon known as 'surface plasmonic resonance' in which the scattered light is absorbed by these NPs and can be detected via UV-Vis spectrophotometry. Consequently, sialic acid conjugated Au NPs (SA-Au NPs) were utilized for their plasmonic effect against SARS-CoV-2, influenza B virus, and Middle-East respiratory syndrome-related coronavirus (MERS) in patients' swab samples.

Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality.

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.

A cell-based drug delivery platform for treating central nervous system inflammation.

Mesenchymal stem cells (MSCs) are promising candidates for the development of cell-based drug delivery systems for autoimmune inflammatory diseases, such as multiple sclerosis (MS). Here, we investigated the effect of Ro-31-8425, an ATP-competitive kinase inhibitor, on the therapeutic properties of MSCs. Upon a simple pretreatment procedure, MSCs spontaneously took up and then gradually released significant amounts of Ro-31-8425.

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks.

Novel Self-Assembled Polycaprolactone-Lipid Hybrid Nanoparticles Enhance the Antibacterial Activity of Ciprofloxacin.

Ciprofloxacin (CIP), a widely used antibiotic, is a poor biopharmaceutical resulting in low bioavailability. We optimized a CIP polymer-lipid hybrid nanoparticle (CIP-PLN) delivery system to enhance its biopharmaceutical attributes and the overall therapeutic performance. CIP-PLN formulations were prepared by a direct emulsification-solvent-evaporation method.

Optimized Polyethylene Glycolylated Polymer-Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment.

Purpose: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer-lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy.

Methods: ANS loaded PEGylated polymer-lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios.

Role of sphingolipid metabolism in neurodegeneration.

Sphingolipids are a class of lipids highly enriched in the central nervous system (CNS), which shows great diversity and complexity, and has been implicated in CNS development and function. Alterations in sphingolipid metabolism have been described in multiple diseases, including those affecting the central nervous system (CNS). In this review, we discuss the role of sphingolipid metabolism in neurodegeneration, evaluating its direct roles in neuron development and health, and also in the induction of neurotoxic activities in CNS-resident astrocytes and microglia in the context of neurologic diseases such as multiple sclerosis and Alzheimer's disease.

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype.

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity.

PDCD6IP, encoding a regulator of the ESCRT complex, is mutated in microcephaly.

Primary microcephaly (PM) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci identified to date. We report a consanguineous family with PM, intellectual disability and short stature. Using whole exome sequencing, we identified a homozygous frameshift variant in programmed cell death 6 interacting protein (PDCD6IP, c.

A Novel Homozygous Non-sense Mutation in the Catalytic Domain of MTHFR Causes Severe 5,10-Methylenetetrahydrofolate Reductase Deficiency.

Severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is a heterogeneous metabolic disorder inherited in an autosomal recessive manner. Pathogenic mutations in gene have been associated with severe MTHFR deficiency. The clinical presentation of MTHFR deficiency is highly variable and associated with several neurological anomalies.