Influence of matrix metalloproteinase 9 variant rs17576 on ischemic stroke risk and severity in acute coronary syndrome.

BACKGROUND: Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. METHODS: A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. RESULTS: Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). CONCLUSION: We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

Lactoferrin: Antimicrobial impacts, genomic guardian, therapeutic uses and clinical significance for humans and animals.

Lactoferrin (LF) is a protein found in several bodily fluids, such as milk. This protein has a diverse range of functions and is evolutionarily conserved. Lactoferrin is a multifunction protein with distinct biological abilities affecting mammals' immune structures. Reports indicated that the daily uptake of LF from dairy products is unsatisfactory in detecting further health-promoting abilities. Research has shown that it protects against infection, mitigates cellular senescence, and improves nutritional quality. Additionally, LF is being studied as a potential treatment for various diseases and conditions, including gastrointestinal issues and infections. Studies have also demonstrated its effectiveness against various viruses and bacteria. In this article, we'll look closer at the structure of LF and its various biological activities, including its antimicrobial, anti-viral, anti-cancer, anti-osteoporotic, detoxifying, and immunomodulatory properties. More specifically, the protective effect of LF against oxidative DNA damage was also clarified through its ability to abolish DNA damaging issues without interfacing with host genetic material. Fortification with LF protects mitochondria dysfunction syndromes via sustaining redox status and biogenesis and suppressing apoptosis and autophagy singling. Additionally, we'll examine the potential benefits of lactoferrin and provide an overview of recent clinical trials conducted to examine its use in laboratory and living models.

Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma.

BACKGROUND: The PSMB8 and PSMB9 immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in PSMB9 and PSMB8. We determined any associations between these SNPs and susceptibility to UBC in the Saudi community. METHODS: Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the PSMB9 rs17587 G>A and PSMB8 rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model. RESULTS: The PSMB9 rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21, P < 0.0001). In contrast, the PSMB8 rs2071543 SNP showed no association with UBC risk (OR = 1.13, P = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1; P = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4; P = 0.0026) models. Genotypic distribution of the PSMB8 rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (P > 0.05). CONCLUSION: These results suggest a potential role for PSMB9 as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.

In Vitro Anticancer and Antibacterial Activities of the Essential Oil of Forsskal's Basil Growing in Extreme Environmental Conditions.

Many species belonging to the genus Ocimum are used for aromatic, medicinal, and cosmetic purposes. The essential oil (OFEO) obtained by hydrodistillation of the flowering aerial parts of Forsskal's Basil "Ocimum forskolei Benth" growing in extreme environmental conditions in Mecca Region, Saudi Arabia was analyzed by GC-MS. The main constituents were phenylpropanoids (methyl eugenol 55.65% and eugenol 11.66%), monoterpene (linalool 9.75%), and sesquiterpenes (germacrene D 3.72% and ß-caryophyllene 2.57%). The OFEO was tested against MCF7, HT29, and HCT116 cancer cells and compared with normal fibroblast cells (MRC5). The MTT assay showed that HCT116 was more sensitive to OFEO (IC50 5.34 µg/mL), which reduced the number of HCT116 colonies at 6 µg/mL, while causing complete colony death at 12 and 24 µg/mL. Western Blotting and qRT-PCR were used to evaluate the level change of different proteins with respect to GAPDH. OFEO upregulated the apoptotic protein (caspase 3), and downregulated the cell proliferation proteins (AKT and pAKT), cell cycle arrest (PCNA, Cyclin D1), and the anti-apoptotic Bcl2 proteins. OFEO was also tested against reference strains of Gram-negative and Gram-positive bacteria including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus by using the well-diffusion and assessing their MICs, which ranged from 250 to 500 µg/mL.

Associations of Clinical Factors and Blood Groups With the Severity of COVID-19 Infection in Makkah City, Saudi Arabia.

Context: The possible associations between the different blood groups and clinical factors with COVID-19 infection among patients in Makkah city. Objective: To investigate the relationship between ABO blood groups and COVID-19 infection in patients who were tested positive and to elucidate the most common ABO blood groups with a higher infectivity of COVID-19 and disease association. Materials and Methods: This was an observational cross-sectional study that included COVID-19 patients diagnosed with PCR and who were hospitalized in Al-Noor Specialist Hospital (Makkah) during the period between March to November 2020. The ABO and Rhesus blood groups alongside the clinical characteristics were determined and retrieved from medical records and HESN of the Ministry of Health of the Kingdom of Saudi Arabia (KSA). Results: The overall confirmed COVID-19 cases included in this study were 1,583 patients who underwent positive PCR testing between March and November 2020. The frequencies of blood groups were as follows: group O+ (37%), group A+ (29.2%), group B+ (22.6%), group AB+ (5.1%), group O- (2.8%), group B- (1.8%), group A- (1.1%), and group AB- (0.4%). However, no significant correlations were observed for ABO groups and Rh types with the severity of COVID-19 illness. Conversely, signs and symptoms of respiratory distress syndrome (RDS), pneumonia, and respiratory failure symptoms, alongside a history of diabetes mellitus, hypertension, chronic kidney diseases, and congestive heart failure significantly increased the risk of death from COVID-19 infection. Moreover, the rates of fever, cough, and asthma were markedly lower in the deceased group compared with the recovered group of patients. Conclusion: The association between the different blood groups with the prevalence and mortality of COVID-19 among infected patients has yet to be elucidated as we found no significant differences in the observed versus expected distribution of ABO phenotypes among the included cases. The prevalence of RDS, pneumonia, and respiratory failure was found higher among hospitalized COVID-19 patients in the deceased group. However, other factors such as fever, cough, and asthma appeared to be more significantly lower than in the recovered group.

Risk of Colorectal Carcinoma May Predispose to the Genetic Variants of the GST, CYP450, and TP53 Genes Among Nonsmokers in the Saudi Community.

PURPOSE: Colorectal carcinoma (CRC) represents a considerable public health burden in Saudi Arabia. Several candidate genes and genetic variants have been associated with morbidity and mortality among patients with CRC. We explored whether allelic variants of the GSTM1, GSTT1, CYP450 (rs4646903 and rs1048943), and TP53 (rs1042522) genes predisposed nonsmoking Saudi individuals to increased risk for CRC. PATIENTS AND METHODS: DNA from buccal cells of 158 participants (80 with CRC and 78 healthy controls) were analyzed for five SNPs using conventional PCR and TaqMan genotyping assays. The SNPStats software was utilized to choose the best interactive inheritance mode for selected SNPs (https://www.snpstats.net). RESULTS: The mean age of diagnosis was 62.4±13.5 years (range, 40-83 years), with those aged 71-80 years and those aged 40-50 years accounting for the most diagnoses (35.7% and 28.6% of diagnosis, respectively). The GSTM1 and TP53 rs1042522 SNPs were associated with CRC (OR= 3.7; P< 0.0001, and OR= 1.6; P= 0.033, respectively). A plausible contribution to CRC was observed for the GSTM1 and TP53 rs1042522 SNPs (x 2 Yates= 14.7; P= 0.00013, and x 2 Yates= 11.2; P= 0.0008, respectively), while the GSTT1 null variant did not affect risk. Heterozygosity in the CYP450 (rs4646903 and rs1048943 SNPs) was associated with a significant risk for CRC. The GSTM1/GSTT1 and CYP450 rs4646903/rs1048943 SNP pairs were in linkage disequilibrium, and the associations were statistically significant (P= 0.01 and P= 4.6x10‒7, respectively). CONCLUSION: The GSTM1 and TP53 rs1042522 variants can increase the development of CRC in Saudi nonsmokers. Even the presence of one copy of a variant allele in the CYP1A1 gene can predispose CRC risk. Additional studies should also examine other SNP combinations with lifestyle factors that may help prevent, rather than facilitate, colorectal tumorigenesis.

Variations in TAP1 and PSMB9 Genes Involved in Antigen Processing and Presentation Increase the Risk of Vitiligo in the Saudi Community.

BACKGROUND: The antigen processing 1 (TAP1) and proteasome 20S subunit beta 9 (PSMB9) genes are associated with strong susceptibility to many autoimmune diseases. Here, we explored whether TAP1/PSMB9 genetic variants, individually or combined, affected susceptibility to the complex, autoimmune-based skin disorder vitiligo. METHODS: Samples of genomic DNA from buccal cells of 172 patients with vitiligo and 129 healthy controls were analyzed using TaqMan™ genotyping assays for the TAP1 rs1135216 (A>G) and PSMB9 rs17587 (A>G) single nucleotide polymorphisms (SNPs). SNPStats software (https://www.snpstats.net) was utilized to choose the best interactive inheritance mode for selected SNPs. RESULTS: The genotype frequencies for the TAP1 rs1135216 and PSMB9 rs17587 SNPs were in Hardy-Weinberg equilibrium for cases (P= 0.11 and P= 0.10, respectively) but not for controls (P< 0.05). The TAP1 rs1135216 (D637G) and PSMB9 rs17587 (R60H) SNPs increased the risk of vitiligo four-fold and two-fold, respectively (odds ratio [OR]= 4.6; 95% confidence interval [CI], 3.2-6.5; P< 0.0001 and OR= 2.2; 95% CI, 1.5-3.1; P< 0.0001). The recessive model (G/G-D/G versus D/D) and the codominant model (R/R versus R/H) were the best models of inheritance for the rs113526 and rs17587 SNPs, respectively (OR= 16.4; 95% CI, 2.0-138; P= 0.0006 and OR= 1.7; 95% CI, 0.3-1.8; P= 0.013). Vulgaris, focal vulgaris, and acryl/acrofacial were the most common vitiligo subtypes in our sample (51%, 21%, and 19%, respectively). Heterozygous rs113526 (637D/G) and rs17587 (60R/H) were the most common genotypes in most vitiligo subtypes. The heterozygous 637D/G genotype and the 637G variant allele were significantly more common in patients with active disease than in patients with stable disease (P= 0.000052 and P= 0.0063, respectively). CONCLUSION: Our findings suggest a crucial role for TAP1 rs1135216 and PSMB9 rs17587 in the risk and progression of vitiligo in the Saudi community. Genomic analyses are needed to identify more candidate genes and more genetic variants associated with vitiligo.