Mohammad A. Alanazi

Stroke is a health problem all over the world. It is a primary cause of disability and ranked number two death cause. In kingdom of Saudi Arabia KSA, the prevalence of stroke in the KSA estimated to be more than 40 per 100 thousand in 2021. The incidence of stroke is increasing in KSA. The risk factors for stroke are grouped into modifiable and nonmodifiable. The modifiable risk factors include diabetes, hyperlipidemia physical inactivity, and diet, whereas the nonmodifiable include sex, age, and race/ethnicity. Decreasing the modifiable risk factors reduces the burden of stroke in population. The long noncoding RNAs (LncRNAs) ANRIL is suggested as a biomarker and treatment target for stroke. The Transcription factor 7-like 2 (TCF7L2) has crucial roles in biological and pathological processes such as inflammation, metabolism, and atherosclerosis. In this study, we examined the associations of ANRIL rs1333045 C>T, CYP2C19*17 (C806T, rs12248560C>T, and TCF7L2 rs12255372 G>T with stroke in 100 stroke cases and 100 matched healthy controls from Tabuk population using the amplification refractory mutation system PCR (ARMS-PCR). Results indicated that the T allele of the ANRIL rs1333048 C>T was associated with stroke with Odd ratio (OR) = 1.73, P value-0.0067. Likewise, the GT genotype and the T allele of the TCF7L2 rs12255372 G>T were associated with stroke with OR = 2.14, P value = 0.01, and 1.9, P value = 0.004, respectively. In addition, the CT genotype and T allele of the CYP2C19*17 (rs12248560) C>T were also associated stroke with OR = 2, P value = 0.02 and OR = 2.3, P value = 0.002, respectively. We conclude that ANRIL rs1333045 C>T, CYP2C19*17 (C806T, rs12248560C>T, and TCF7L2 rs12255372 G>T are potential loci for susceptibility to stroke. This will assist in treatment and/or prevention of cerebrovascular disease.

The global impact of COVID-19 was staggering, with millions of cases and related mortality reported worldwide. Genetic variations play a significant role in determining an individual’s susceptibility to SARS-CoV-2 infection and progress to severe disease. This pilot study provides an experimental approach using WES to identify certain rare and novel genetic variants that might affect an individual’s susceptibility to the risk of SARS-CoV-2 infection, offering an initial exploration of these genetic variants. In the study cohort with 16 patients, the mortality rate was higher in male patients due to severe disease. There was a substantial burden of comorbidity, including hypertension, ischemic heart disease, and T2DM, conditions which independently increase the risk of adverse outcomes in COVID-19 patients. A total of 4478 variants were identified, distributed across 322 genes within the cohort. The majority of these variants were missense substitutions along with frameshift variants, inframe insertions/deletions (indels), and nonsense variants. The variants were further categorized by types to include single-nucleotide polymorphisms (SNPs), deletions (DEL), and insertions (INS). The gene with the highest number of variants was HLA-DRB1, followed by HLA-B, ABO, HPS4, and SP110 displaying both common polymorphisms and rare variants. Moreover, the HLA-B gene exhibited the highest number of rare candidate variants, followed by AK2, IRF7, KMT2D, TAP1, and HLA-DRB1. Several genes harbored multiple novel variants, including TAP1, AK2, G6PC3, HLA-B, IL12RB2, and ITGB2. The frequencies of the identified variants were found to be either zero or extremely low (below 1% threshold) in the Middle Eastern or in the overall combined population, suggesting that these are indeed rare and do not represent common indigenous polymorphisms. Functional enrichment analysis of the constructed protein–protein interaction network in our preliminary findings revealed that the identified genes are primarily enriched in pathways associated with immune deficiency and DNA repair. This initial exploration of genetic variants in COVID-19 susceptibility provides a foundation for future large-scale studies.

Green seaweed (Ulva sp.) is frequently used as a food component and nutraceutical agent because of its high polysaccharide and natural fiber content in Asian countries. This study investigates both metabolomic profiling of Ulva sp. and the neuroprotective efficacy of its ethanol extract and its underlying mechanisms in a rotenone‐induced rat model of neurodegeneration, mimicking Parkinson's disease (PD) in humans. Metabolomic profiling of Ulva sp. extract was done using liquid chromatography high resolution electrospray ionization mass spectrometry and led to the identification of 22 compounds belonging to different chemical classes.Catenin Beta Additionally, this study demonstrated the neuroprotective properties against rotenone‐induced PD, which was achieved through the suppression of elevated levels of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 together with the inhibition of reactive oxygen species (ROS) generation, apoptosis, inflammatory mediators, and the phosphoinositide 3‐kinases/serine/threonine protein kinase (PI3K/AKT) pathway. Using a protein–protein interaction network, AKT1, GAPDH, TNF‐α, IL‐6, caspase 3, signal transducer and activator of transcription 3, Catenin Beta 1, epidermal growth factor receptor, B‐cell lymphoma ‐2, and HSP90AA1 were identified as the top 10 most significant genes. Finally, molecular docking results showed that compounds 1, 3, and 7 might possess a promising anti‐parkinsonism effect by binding to active sites of selected hub genes. Therefore, it is hypothesized that the Ulva sp. extract has the potential to be further developed as a potential therapeutic agent for the treatment of PD.

The genus Hertia , which belongs to the Asteraceae family, is a flowering genus with 12 species found in Africa, North and South.

Nutritional deficits in one’s diet have been established as the key risk factor for T2DM in recent years. Nutritional therapy has been demonstrated to be useful in treating T2DM. The current study was carried out to assess the nutritional composition of bovine (12 months), chicken (4 months), sheep (13 months), and goat (9 months) femur bone extracts, as well as their potential therapeutic effects on T2DM regression in a Wistar albino rat model (500 mg/kg b.wt.). The proximate composition of the different extracts, their fatty acid composition, their amino acids, and their mineral contents were identified. In vivo data indicated considerably improved T2DM rats, as seen by lower serum levels of TL, TG, TC, ALT, AST, ALP, bilirubin, creatinine, urea, IL-6, TNF-α, sICAM-1, sVCAM-1, and MDA. Low levels of HDL-C, GSH, and total proteins were restored during this study. Histological investigations of liver and pancreatic tissue revealed that the distribution of collagen fibers was nearly normal. The bovine extract, on the other hand, was the most active, followed by the sheep, goat, and finally chicken extract. This research could result in the creation of a simple, noninvasive, low-cost, and reliable method for T2DM control, paving the way for potential early therapeutic applications in T2DM control.

Tamarindus indica Linn (tamarind, F. Leguminosae) is one of the most widely consumed edible fruits in the world. Phytochemical investigation of tamarind pulp n-butanol fraction yielded one new (+)-pinitol glycoside compound 1 (25% w/w), and 1D, 2D NMR, and HRESIMS investigation were used to confirm the new compound’s structure. (+)-Pinitol glycoside showed anti-Alzheimer potential that was confirmed in prophylactic and treatment groups by decreasing time for the T-maze test; decreased TAO, brain and serum AChE, MDA, tau protein levels, and β amyloid peptide protein levels; and increasing GPX, SOD levels, and in vivo regression of the neurodegenerative features of Alzheimer’s dementia in an aluminum-intoxicated rat model. The reported molecular targets for human Alzheimer’s disease were then used in a network pharmacology investigation to examine their complex interactions and identify the key targets in the disease pathogenesis. An in silico-based analysis (molecular docking, binding free energy calculation (ΔG_Binding), and molecular dynamics simulation) was performed to identify the potential targets for compound 1. The findings of this study may lead to the development of dietary supplements for the treatment of Alzheimer’s disease.

Impaired skin wound healing is still a major challenge, especially with immunocompromised patients who express delayed healing and are susceptible to infections. Injection of rat-derived bone marrow mesenchymal stem cells (BMMSCs) via the tail vein accelerates cutaneous wound healing via their paracrine activity. The present work aimed to investigate the combined wound-healing potential of BMMSCs and Halimeda macroloba algae extract in immunocompromised rats. High-resolution liquid chromatography-mass spectrometry (HR-LC-MS) investigation of the extract revealed the presence of variant phytochemicals, mostly phenolics, and terpenoids, known for their angiogenic, collagen-stimulating, anti-inflammatory, and antioxidant properties. The BMMSCs were isolated and characterized for CD markers, where they showed a positive expression of CD90 by 98.21% and CD105 by 97.1%. Twelve days after inducing immunocompromise (40 mg/kg hydrocortisone daily), a circular excision was created in the dorsal skin of rats and the treatments were continued for 16 days. The studied groups were sampled on days 4, 8, 12, and 16 after wounding. The gross/histopathological results revealed that the wound closure (99%), thickness, density of new epidermis and dermis, and skin elasticity in the healed wounds were considerably higher in the BMMSCs/Halimeda group than the control group (p < 0.05). RT-PCR gene expression analysis revealed that the BMMSCs/Halimeda extract combination had perfectly attenuated oxidative stress, proinflammatory cytokines, and NF-_KB activation at day 16 of wounding. The combination holds promise for regenerative medicine, representing a revolutionary step in the wound healing of immunocompromised patients, with still a need for safety assessments and further clinical trials.

Human β-defensin (HBD), a member of the antimicrobial peptides, is essential for respiratory epithelial cells’ microbial defense, and is affected by cigarette smoking (CS). Its expression is upregulated by stimulation from microbes or inflammation. Genetic polymorphisms in the HBD-1 gene have been implicated in the development of various smoking-related diseases, including chronic obstructive pulmonary disease and asthma. Thus, we sought to analyze possible associations between HBD-1 single-nucleotide polymorphism (SNP) in HBD-1 gene and CS in ethnic Saudi Arabian subjects. Variants rs1047031 (C/T), rs1799946 (C/T), rs2738047 (C/T), and rs11362 (C/T) were investigated by genotyping 575 blood specimens from males and females, smokers/non-smokers: 288/287. The CT and CT+TT genotypes of rs1799946 presented an ~5-fold increased correlation with CS among the female smokers, compared with the female controls (OR = 5.473, P = 0.02003; and OR = 5.211, P = 0.02028, respectively), an observation similar to rs11362 SNP in female smokers, but with protective effects in TT genotype, compared with the CC reference allele (OR = 0.143, P = 0.04368). In shisha smokers, the heterozygous CT and the CT/TT genotype of rs2738047 polymorphism showed the same results with ~3-fold increased correlation with CS (OR = 2.788; P = 0.03448), compared with the cigarette smokers category. No significant association was shown in genotypic distributions and allelic frequencies of rs1047031. Further investigations, including large study samples, are required to investigate the effects of shisha on human beta-defensin expression and protein levels.

Using a monoclonal antibody that specifically recognizes thymine glycol (Tg) in DNA, we measured the kinetics of the removal of Tg from the genomes of wild‐type and repair gene mutant strains of Escherichia coli treated with hydrogen peroxide. Tg is rapidly and efficiently removed from the total genomes of repair‐proficient cells in vivo and the removal of Tg is completely dependent on the nth gene that encodes the endonuclease III glycosylase. Hence, it appears that little redundancy in the repair of Tg occurs in vivo, at least under the conditions used here. Moreover, previous studies have found that nth mutants are not sensitive to killing by hydrogen peroxide but xth mutant strains (deficient in the major AP endonuclease, exonuclease III) are sensitive. We find that cell death correlates with the persistence of single‐strand breaks rather than the persistence of Tg. We attempted to measure transcription‐coupled removal of Tg in the lactose operon using the Tg‐specific monoclonal antibody in an immunoprecipitation approach but were not successful in achieving reproducible results. Furthermore, the analysis of transcription‐coupled repair in the lactose operon is complicated by potent inhibition of β‐galactosidase expression by hydrogen peroxide.