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Introduction: Lithium disilicate glass-ceramic (LDC) restorations exhibit microorganism infiltration, recurrent caries, pulpal lesions, periodontal inflammation, and cement exposure to the oral environment over time. All these factors lead to restoration failure. This systematic review aimed to investigate the clinical outcomes of LDC full-coverage crowns (FCC) in permanent teeth compared with those of other full-coverage restoration materials., Materials & Methods: Search strategies were developed for four databases: Web of Science, OVID, PubMed, and Scopus. Data extraction and quality appraisals were performed by two independent reviewers. Data on the presence of caries, post-operative sensitivity, and periodontal changes were extracted from the included clinical studies. In addition to the outcome measures, data on the sample size, study groups, method of restoration fabrication, type of impression, and type of abutment were recorded., Results: We retrieved 3989 records for the title and abstract screening. Of these, 19 clinical studies met the inclusion criteria. The overall quality of the included studies indicates a low risk of bias. Most studies reported no pulpal involvement, recurrent caries, or post-operative sensitivity and presented a favorable periodontal response after the cementation of LDC-FCC during different follow-up periods., Conclusion: Based on the endodontic and periodontic clinical responses of natural tooth abutments and their supporting periodontium, LDC-FCC can be considered a clinically successful restorative option., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Helicobacter pylori ( H. pylori ) has been identified as a group-1 definite carcinogen. As of yet, there is no available vaccine for this microorganism. Our study aimed to identify antigenic peptides in H. pylori using an in silico proteomic approach, and to evaluate their effectiveness as potential vaccine candidates. Four different peptide sequences were prioritized using the reverse vaccinology, namely, CagA 1 , CagA 2 , VacA, and SabA. Peptides emulsified with Freunde's adjuvant were used to immunize BALB/C mice. Subcutaneously immunized mice were challenged by oral administration of H. pylori. IgG, IgA, IL4, and IL17 were detected in mice sera. Histopathology of the dissected stomach of vaccinated and control mice were assessed using H&E stain. IgG was significantly higher in mice vaccinated with SabA. IL-4 was significantly increased in CagA 1 , CagA 2 , VacA, and SabA vaccinated mice compared to the adjuvant group. Additionally, histopathological examination of gastric tissue showed a protective effect in the vaccinated groups compared to adjuvant and PBS groups. Our findings indicate a promising effect of the tested epitopes, particularly the SabA antigen, to induce an immune response against H. pylori ., Competing Interests: The authors declare no conflicts of interest.

Background: Molecular diagnosis of early onset inflammatory bowel disease (IBD) is very important for adopting suitable treatment strategies. Owing to the sparse data available, this study aims to identify the molecular basis of early onset IBD in Arab patients., Methods: A consanguineous Arab family with monozygotic twins presenting early onset IBD was screened by whole exome sequencing (WES). The variants functional characterization was performed by a series of computational biology methods. The IBD variants were further screened in in-house whole exome data of 100 Saudi cohorts ensure their rare prevalence in the population., Results: Genetic screening has identified the digenic autosomal recessive mode of inheritance of ITGAV (G58V) and FN1 (G313V) variants in IBD twins with early onset IBD. Findings from pathogenicity predictions, stability and molecular dynamics have confirmed the deleterious nature of both variants on structural features of the corresponding proteins. Functional biology data suggested that both genes show abundant expression in gastrointestinal tract and immune organs, involved in immune cell restriction, regulation of different immune related pathways. Data from knockout mouse models for ITGAV gene has revealed that the dysregulated expression of this gene impacts intestinal immune homeostasis. The defective ITGAV and FN1 involved in integrin pathway, are likely to induce intestinal inflammation by disturbing immune homeostasis., Conclusions: Our findings provide novel insights into the molecular etiology of pediatric onset IBD and may likely pave way in developing genomic medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Numan, Jan, Al-Saud, Rashidi, Alrayes, Alsufyani, Mujalli, Shaik, Mosli, Elango, Saadah and Banaganapalli.)

Myocardial infarction (MI) is the most prevalent coronary heart disease caused by the complex molecular interactions between multiple genes and environment. Here, we aim to identify potential biomarkers for the disease development and for prognosis of MI. We have used gene expression dataset (GSE66360) generated from 51 healthy controls and 49 patients experiencing acute MI and analyzed the differentially expressed genes (DEGs), protein-protein interactions (PPI), gene network-clusters to annotate the candidate pathways relevant to MI pathogenesis. Bioinformatic analysis revealed 810 DEGs. Their functional annotations have captured several MI targeting biological processes and pathways like immune response, inflammation and platelets degranulation. PPI network identify seventeen hub and bottleneck genes, whose involvement in MI was further confirmed by DisGeNET database. OpenTarget Platform reveal unique bottleneck genes as potential target for MI. Our findings identify several potential biomarkers associated with early stage MI providing a new insight into molecular mechanism underlying the disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Familial hypercholesterolemia (FH) is a lipid disorder caused by pathogenic mutations in LDLRAP1 gene. The present study has aimed to deepen our understanding about the pathogenicity predictions of FH causative genetic mutations, as well as their relationship to phenotype changes in LDLRAP1 protein, by utilizing multidirectional computational analysis., Methods: FH linked LDLRAP1 mutations were mined from databases, and the prediction ability of several pathogenicity classifiers against these clinical variants, was assessed through different statistical measures. Furthermore, these mutations were 3D modelled in protein structures to assess their impact on protein phenotype changes., Results: Our findings suggest that Polyphen-2, when compared with SIFT, M-CAP and CADD tools, can make better pathogenicity predictions for FH causative LDLRAP1 mutations. Through, 3D simulation and superimposition analysis of LDLRAP1 protein structures, it was found that missense mutations do not create any gross changes in the protein structure, although they could induce subtle structural changes at the level of amino acid residues. Near native molecular dynamic analysis revealed that missense mutations could induce variable degrees of fluctuation differences guiding the protein flexibility. Stability analysis showed that most missense mutations shifts the free energy equilibrium and hence they destabilize the protein. Molecular docking analysis demonstrates the molecular shifts in hydrogen and ionic bonds and Van der waals bonding properties, which further cause differences in the binding energy of LDLR-LDLRAP1 proteins., Conclusions: The diverse computational approaches used in the present study may provide a new dimension for exploring the structure-function relationship of the novel and deleterious LDLRAP1 mutations linked to FH., (© 2020 John Wiley & Sons, Ltd.)

Celiac disease (CD) is a gastrointestinal disorder whose genetic basis is not fully understood. Therefore, we studied a Saudi family with two CD affected siblings to discover the causal genetic defect. Through whole exome sequencing (WES), we identified that both siblings have inherited an extremely rare and deleterious CPED1 genetic variant (c.241 A > G; p.Thr81Ala) segregating as autosomal recessive mutation, suggesting its putative causal role in the CD. Saudi population specific minor allele frequency (MAF) analysis has confirmed its extremely rare prevalence in homozygous condition (MAF is 0.0004). The Sanger sequencing analysis confirmed the absence of this homozygous variant in 100 sporadic Saudi CD cases. Genotype-Tissue Expression (GTEx) data has revealed that CPED1 is abundantly expressed in gastrointestinal mucosa. By using a combination of systems biology approaches like protein 3D modeling, stability analysis and nucleotide sequence conservation analysis, we have further established that this variant is deleterious to the structural and functional aspects of CPED1 protein. To the best of our knowledge, this variant has not been previously reported in CD or any other gastrointestinal disease. The cell culture and animal model studies could provide further insight into the exact role of CPED1 p.Thr81Ala variant in the pathophysiology of CD. In conclusion, by using WES and systems biology analysis, present study for the first-time reports CPED1 as a potential causative gene for CD in a Saudi family with potential implications to both disease diagnosis and genetic counseling., (© 2020 The Author(s).)