Haitham Alkadi

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia, generating circulating glycated albumin (GA). The development and progression of liver cancer, and more specifically hepatocellular carcinoma (HCC), are increased in patients with T2D. To facilitate early diagnosis and appropriate therapeutic strategies, we sought to identify novel HCC biomarkers in these patients by investigating the biological impact of GA on HepG2 and metastatic HuH7 HCC cell lines. After treatment with various concentrations (25–200 µg/mL) of methylglyoxal-derived GA, cell viability, migration, and invasion were assessed, respectively, by CellTiter-Glo ^® , scratch assay, and Matrigel™-coated Transwell™ inserts. The expression of signaling and oncology-related proteins was monitored using Western blot and protein array analyses. GA significantly and dose-dependently modulated cell viability, wound healing, and oncogenic p-ERK according to a bell-shaped curve, compared to untreated cells, the control. At 100 µg/mL, GA significantly stimulated cell invasion and augmented ribosomal protein S6 phosphorylation, EpCAM, and galectin-3 expression in metastatic HuH7 cells, mainly to a lesser extent in HepG2 cells. TCGA database analysis revealed, unlike EpCAM, a positive correlation between the high expression levels of genes encoding pS6 kinase and galectin-3, and liver cancer patients’ high BMI, advanced stages of HCC, metastatic status, and poor overall survival. By immunohistochemical staining, only galectin-3 was detected significantly in HCC tissues from T2D Saudi patients compared to their non-diabetic counterparts. A larger cohort is needed to evaluate galectin-3 expression as a potential biomarker and its prognostic values in T2D patients with HCC.

MERS is a respiratory disease caused by MERS‐CoV. Multiple outbreaks have been reported, and the virus co‐circulates with SARS‐CoV‐2. The long‐term (> 6 years) cellular and humoral immune responses to MERS‐CoV and their potential cross‐reactivity to SARS‐CoV‐2 and its variants are unknown. We comprehensively investigated long‐lasting MERS‐CoV‐specific cellular and humoral immunity, and its cross‐reactivity against SARS‐CoV‐2 and its variants, in individuals recovered from MERS‐CoV infection 1–10 years prior. Two cohorts of MERS‐CoV survivors (31 unvaccinated, 38 COVID‐19 vaccinated) were assessed for MERS‐CoV IgG, memory CD4⁺/CD8⁺ T cells, and neutralizing antibodies against MERS‐CoV and SARS‐CoV‐2 variants. MERS‐CoV IgG levels and T cell responses were higher in the 1–5 vs 6–10 year postinfection groups. Vaccinated MERS‐CoV survivors had significantly elevated MERS‐CoV IgG and neutralization compared to unvaccinated. Both groups demonstrated cross‐reactive neutralization of SARS‐CoV‐2 variants. MERS‐CoV survivors vaccinated against SARS‐CoV‐2 had higher anti‐MERS IgG, cellular immunity, and neutralization than unvaccinated survivors. MERS‐CoV immune responses can persist for a decade. COVID‐19 vaccination boosted humoral and cellular immunity in MERS‐CoV survivors, suggesting the benefits of vaccination for this population. These findings have implications for pan‐coronavirus vaccine development.

The annual seasonal influenza vaccination is the most effective way of preventing influenza illness and hospitalization. However, the effectiveness of influenza vaccines has always been controversial. Therefore, we investigated the ability of the quadrivalent influenza vaccine to induce effective protection. Here we report strain-specific influenza vaccine effectiveness (VE) against laboratory-confirmed influenza cases during the 2019/2020 season, characterized by the co-circulation of four different influenza strains. During 2019–2020, 778 influenza-like illness (ILI) samples were collected from 302 (39%) vaccinated ILI patients and 476 (61%) unvaccinated ILI patients in Riyadh, Saudi Arabia. VE was found to be 28% and 22% for influenza A and B, respectively. VE for preventing A(H3N2) and A(H1N1)pdm09 illness was 37.4% (95% CI: 43.7–54.3) and 39.2% (95% CI: 21.1–28.9), respectively. The VE for preventing influenza B Victoria lineage illness was 71.7% (95% CI: −0.9–3), while the VE for the Yamagata lineage could not be estimated due to the limited number of positive cases. The overall vaccine effectiveness was moderately low at 39.7%. Phylogenetic analysis revealed that most of the Flu A genotypes in our dataset clustered together, indicating their close genetic relatedness. In the post-COVID-19 pandemic, flu B-positive cases have reached three-quarters of the total number of influenza-positive cases, indicating a nationwide flu B surge. The reasons for this phenomenon, if related to the quadrivalent flu VE, need to be explored. Annual monitoring and genetic characterization of circulating influenza viruses are important to support Influenza surveillance systems and to improve influenza vaccine effectiveness.

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.