Association of Polymorphisms in PD-1 and LAG-3 Genes with Acute Myeloid Leukemia.

Background and objectives: Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of immature myeloid cells. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are essential for controlling anti-tumor immune responses. This study aims to explore the correlation between specific genetic variations (SNPs) in the PDCD1 (rs2227981) and LAG3 (rs12313899) genes and the likelihood of developing AML in the Saudi population. Material and methods: total of 98 Saudi AML patients and 131 healthy controls were genotyped for the PDCD1 rs2227981 and LAG3 rs12313899 polymorphisms using TaqMan genotyping assays. A logistic regression analysis was conducted to evaluate the relationship between the SNPs and AML risk using several genetic models. Results: The results revealed a significant association between the PDCD1 rs2227981 polymorphism and increased AML risk. In AML patients, the frequency of the G allele was considerably greater than in healthy controls (OR = 1.93, 95% CI: 1.31-2.81, p = 0.00080). The GG and AG genotypes were associated with a very high risk of developing AML (p < 0.0001). In contrast, no significant association was observed between the LAG3 rs12313899 polymorphism and AML risk in the studied population. In silico analysis of gene expression profiles from public databases suggested the potential impact of PDCD1 expression levels on the overall survival of AML patients. Conclusions: This study provides evidence for the association of the PDCD1 rs2227981 polymorphism with an increased risk for AML in the Saudi population.

Rs10204525 Polymorphism of the Programmed Death (PD-1) Gene Is Associated with Increased Risk in a Saudi Arabian Population with Colorectal Cancer.

Checkpoint programmed death-1 (PD-1) has been identified as an immunosuppressive molecule implicated in the immune evasion of transformed cells. It is highly expressed in tumor cells in order to evade host immunosurveillance. In this study, we aimed to assess the association between single nucleotide polymorphisms (SNP) of PD-1 and the risk of colorectal cancer (CRC) in the Saudi population. For this case-control study, the TaqMan assay method was used for genotyping three SNPs in the PD-1 gene in 100 CRC patients and 100 healthy controls. Associations were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for multiple inheritance models (codominant, dominant, recessive, over-dominant, and log-additive). Moreover, PD-1 gene expression levels were evaluated using quantitative real-time PCR in colon cancer tissue and adjacent colon tissues. We found that the PD-1 rs10204525 A allele was associated with an increased risk of developing CRC (OR = 2.35; p = 0.00657). In addition, the PD-1 rs10204525 AA homozygote genotype was associated with a high risk of developing CRC in the codominant (OR = 21.65; p = 0.0014), recessive (OR = 10.97; p = 0.0015), and additive (OR = 1.98; p = 0.012) models. A weak protective effect was found for the rs2227981 GG genotype (OR = 2.52; p = 0.034), and no significant association was found between the rs2227982 and CRC. Haplotype analysis showed that the rs10204525, rs2227981, rs2227982 A-A-G haplotype was associated with a significantly increased risk of CRC (OR = 6.79; p =0.031).

Targeting HER-2 over expressed breast cancer cells with 2-cyclohexyl-N-[(Z)-(substituted phenyl/furan-2-yl/thiophene-2-yl)methylidene]hydrazinecarbothioamide.

Cyclohexyl thiosemicarbazone derivatives (C1-14) were synthesized, characterized and evaluated against HER-2 over expressed breast cancer cells. The synthesized compounds were screened in vitro against four breast cancer cell lines; SKBr-3, MCF-7, MDA-MB-468 and MDA-MB-231. All the compounds showed activity against HER-2 over expressed SKBr-3 cells with (IC50 = 25.6 ± 0.07 µM-61.6 ± 0.4 µM). The most active compounds inhibit ALDH⁺ breast cancer stem cells more effectively than the cancer stem cells specific agent Salinomycin. Immunohistochemistry staining also confirmed that these compounds inhibit the expression of HER-2 on SKBr-3 cells. Compound C2 significantly inhibited the cell migration and cell adhesion of breast cancer cell lines. Compound C2 was found to most active compound of this series targeting HER-2 over expressed breast cancer cells.

Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (-658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between -658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population.

A cross-sectional study factors associated with resilience among medical staff in radiology departments during COVID-19, Riyadh, Kingdom of Saudi Arabia.

OBJECTIVES: This study aims to assess the level of resilience of medical workers in radiology departments in Riyadh, Kingdom of Saudi Arabia, during the COVID-19 outbreak and to explore associated factors. SETTING: Medical staff, including nurses, technicians, radiology specialists and physicians, working in radiology departments at government hospitals in Riyadh, Saudi Arabia during the COVID-19 outbreak. DESIGN: A cross-sectional study. PARTICIPANTS: The study was conducted among 375 medical workers in radiology departments in Riyadh, Kingdom of Saudi Arabia. The data collection took place from 15 February 2022 to 31 March 2022. RESULTS: The total resilience score was 29.37±6.760 and the scores of each dimension showed that the higher mean score was observed in the domain of 'flexibility', while the lowest was observed in 'maintaining attention under stress'. Pearson's correlation analysis showed that there was a significant negative correlation between resilience and perceived stress (r=-0.498, p<0.001). Finally, based on multiple linear regression analysis, factors affecting resilience among participants are the availability of psychological hotline (available, B=2.604, p<0.050), knowledge of COVID-19 protective measures (part of understanding, B=-5.283, p<0.001), availability of adequate protective materials (partial shortage, B=-2.237, p<0.050), stress (B=-0.837, p<0.001) and education (postgraduate, B=-1.812, p<0.050). CONCLUSIONS: This study sheds light on the level of resilience and the factors that contribute to resilience in radiology medical staff. Moderate levels of resilience call for health administrators to focus on developing strategies that can effectively help cope with workplace adversities.

Awareness of basic life support and cardiopulmonary resuscitation among female secondary school students in government schools in Riyadh city, KSA.

BACKGROUND AND OBJECTIVE: Basic life support (BLS) and cardiopulmonary resuscitation (CPR) are urgently required and must be performed when cardiac arrest occurs. These lifesaving procedures must be learned by healthcare professionals. In developed countries, members of the public, academics, and students learn how to carry out these emergency procedures. Knowledge of these simple procedures determines successful outcome. This study was conducted to determine the level of awareness of BLS and CPR among female secondary students at governmental schools in Riyadh city, Saudi Arabia (SA). METHODS: This cross-sectional study was conducted in five governmental secondary schools in Riyadh city, SA, between June 2015 and June 2016. Total of 1224 female students were selected randomly, and data were collected using a self-reported structured questionnaire. RESULTS: A total of 1170 participants completed the questionnaire. Most of the participants (81.5%) were Saudis. More than 50% of the students (54.8%) did not have information about BLS, and 82.6% felt their knowledge about BLS was insufficient. Only 10.8% of the participants had taken a BLS course, and only 38.5% believe BLS courses should be mandatory. CONCLUSION: The level of awareness regarding BLS among female secondary school students in governmental schools in Riyadh was found to be insufficient. The introduction of BLS and CPR courses in the curriculum of governmental secondary schools in Riyadh city is highly recommended.

Hypoglycemia in Type 2 Diabetes Mellitus patients: A review article.

Hypoglycemia is an essential issue for diabetic patients and considered a limiting factor in the glycemic management. Heterogeneity of the diseases in Type 2 Diabetes Mellitus can affect the frequency of hypoglycemia, especially when the patient has cardiovascular diseases. There are several factors that lead to hypoglycemia including sulfonylurea therapy, insulin therapy, delaying or missing a meal, physical exercise, or alcohol consumption. Long-term studies reported that repeated hypoglycemia could increase the risk of cardiovascular diseases. During Ramadan fasting, diabetic patients have high incidence of hypoglycemia. Therefore, focused education about hypoglycemia in routine life of diabetic patients and during fasting in Ramadan is important to reduce the complications.