Abdulrahman Algarni

Poly(ADP-ribose) polymerase 9 (PARP9) is an interferon-inducible PARP family member implicated in tumor cell survival, immune signalling, and poor prognosis, suggesting potential value as a biomarker and therapeutic target in cancer. Its expression pattern and clinical relevance in acute myeloid leukaemia (AML) is unclear. We investigated the expression of PARP9 in AML patient samples. We analysed transcriptomic data from TCGA-LAML, GTEx, Human Protein Atlas, DepMap, and BloodSpot to characterise PARP9 expression across cancers, hematopoietic hierarchies, and AML subgroups. Cross-cancer analysis showed significantly higher PARP9 expression in AML compared with most non-hematologic malignancies (p < 0.001). Within hematopoietic lineages, PARP9 expression was significantly high in megakaryocyte–erythroid progenitors (p < 0.05), B cells (p < 0.001), polymorphonuclear cells (p < 0.001), and monocytes (p < 0.001), with the highest expression in polymorphonuclear cells. AML samples exhibited ~ 2.4-fold higher expression of PARP9 when compared to normal tissues (p < 0.001). PARP9 high expression was found to be associated with specific FAB subtypes M0, M1, M2, M4 and M5 and in patients exhibiting intermediate and adverse cytogenetic risk profiles (p < 0.05). Additionally, patients with high PARP9 expression showed significantly poor overall survival outcomes (log-rank p = 0.035; HR 1.49, 95% CI 1.03–2.16), although PARP9 was not independently prognostic after adjustment for age and cytogenetic risk in multivariable Cox regression. Furthermore, the differential expression analysis identified 457 upregulated and 1141 downregulated genes associated with high PARP9 expression, which in silico analysis linked to immune and cancer-related pathways, including PD‑1/PD‑L1 signalling, NOD-like receptor signalling, cytokine–cytokine receptor interaction, and hematopoietic lineage. Overall, PARP9 was consistently highly expressed in AML and associated with adverse-risk categories, distinct transcriptional pathways, and poor survival outcomes, highlighting its potential as a biomarker warranting further study to validate its role in AML.

As per the Global Cancer Observatory, the WHO Eastern Mediterranean region (which includes the Arabic countries) ranks highest for age-standardized mortality rate at 4 per 100,000, thus indicating a probable role of genetic associations. Identifying the genes associated with leukemia in the Arab population is crucial for effective preventive and treatment strategies. This scoping review aimed to determine the nature and extent of research available on the genes associated with the major types of leukemia among the Arab population. As per the scoping review guidelines, a comprehensive search was conducted in PUBMED and Google Scholar for articles published before 01/10/2023 and focused on leukemia-related genes among the Arab population. In total 119 studies, focusing on genes associated with leukemia met the inclusion criteria. On reviewing these studies, 27 genes were found to be associated with ALL, 33 genes with AML, seven genes with CLL, and 14 genes with CML. The majority of these genes were associated with an increased risk for the disease. Notably, the 119 studies covered only nine out of the 22 Arab countries, with 56 studies carried out in Egypt, exhibiting an imbalance in the regional distribution of the research landscape. Thus, indicating the inadequacy of research on leukemia genetics in the Arab region in comparison to the Western studies. This finding highlights the need for extensive research in the Middle Eastern region to gain geographically heterogeneous genetic information about the Arab population. In conclusion, this scoping study highlights the genes associated with the major types of leukemia among the Arab population and also indicates the need for comprehensive and regionally balanced research on leukemia genetics in Middle Eastern countries. Addressing this gap is essential to provide robust genetic data that can be used for targeted interventions to improve leukemia outcomes in the Middle East. Increased research efforts in all Middle Eastern countries will contribute to a greater understanding of genetic predisposition and help develop effective prevention strategies and treatments tailored to this population.

Introduction: This study investigated the impact of flipped learning versus traditional instruction on medical students’ academic performance and self-efficacy in a haematology course, and examined gender differences. Flipped learning is an instructional approach where students review pre-recorded lecture content at home, and active learning occurs in the classroom. Self-efficacy refers to students’ beliefs in their ability to succeed and accomplish learning goals. Methods: A quasi-experimental study was conducted with 86 third-year Saudi medical students (46 males, 40 females) in a 10-week haematology course. Students were assigned to flipped learning group (n = 41) or traditional lecture group (n = 45). Both groups completed pre- and post-intervention academic tests and self-efficacy surveys. Data were analyzed using descriptive statistics and t-tests. Results: The flipped learning group showed an increase in academic scores (p <.05) and self-efficacy scores (p <.05) compared to the traditional group, but between group differences were not statistically significant. Female students in the flipped learning group showed the greatest increase in academic scores and self-efficacy. Most students perceived flipped learning positively for enhancing learning and preparation for class. Conclusion: Flipped learning promoted self-efficacy compared to traditional lectures in medical students. Gender-specific benefits were observed, highlighting the need to design instruction to meet diverse student needs.

Background: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). Objective: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). Materials and methods: This case–control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed. Results: The study found that women with DVT had significantly lower levels of PC and PS compared with controls (P < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS. Conclusion: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Chronic lymphocytic leukemia (CLL) is an incurable neoplasm of B-lymphocytes, which accounts for about one-third of all leukemias. Ocimum sanctum, an herbaceous perennial, is considered as one of the important sources of drugs for the treatment of various diseases, including cancers and autoimmune diseases. The present study was designed to screen various phytochemicals of O. sanctum for discovering their potential to inhibit Bruton’s tyrosine kinase (BTK), a well-known drug target of CLL. Various phytochemicals of O. sanctum were screened for their potential to inhibit BTK using several in silico protocols. First, the molecular docking approach was used to calculate the docking scores of the selected phytochemicals. Then, the selected top-ranked phytochemicals were screened for their physicochemical characteristics using ADME analysis. Finally, the stability of the selected compounds in their corresponding docking complexes with BTK was analysed using molecular dynamics simulations. Primarily, our observations revealed that, out of the 46 phytochemicals of O. sanctum, six compounds possessed significantly better docking scores (ranging from −9.2 kcal/mol to −10 kcal/mol). Their docking scores were comparable to those of the control inhibitors, acalabrutinib (−10.3 kcal/mol), and ibrutinib (−11.3 kcal/mol). However, after ADME analysis of these top-ranked six compounds, only three compounds (Molludistin, Rosmarinic acid, and Vitexin) possessed drug likeliness characteristics. During the MD analysis, the three compounds Molludistin, Rosmarinic acid, and Vitexin were found to remain stable in the binding pocket in their corresponding docking complexes with BTK. Therefore, among the 46 phytochemicals of O. sanctum tested in this study, the three compounds, Molludistin, Rosmarinic acid, and Vitexin are the best inhibitors of BTK. However, these findings need to be confirmed by biological experiments in the laboratory.

Purpose: Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10) rs1800896 polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and validate whether this SNP is a risk factor for adult ALL. Patients and Methods: This case–control study was based on a subset of newly diagnosed 154 adult patients with ALL recruited from the Radiation and Isotope Center in Khartoum (RICK) and 154 healthy controls from the same geographical area. Genomic DNA was used for the genotyping of rs1800896 polymorphism through allele-specific polymerase chain reaction (PCR) assays. Results: The genotypic frequencies of rs1800896 showed a statistically significant association of AG and AA genotypes with adult ALL (p< 0.001). Combined genotypes AG+GG vs AA also showed a positive association of rs1800896 with adult ALL (OR=4.89). The allelic frequencies of G and A did not show any significant difference in adult patients with ALL compared with the control group. AG rs1800896 genotype showed an increased risk of B and T ALL (OR=2.51 and 4.70, respectively). Age at diagnosis, gender, and immunophenotype (B vs T ALL) did not exhibit any association of rs1800896 with ALL in this patient group. Conclusion: rs1800896 polymorphism is associated with an increased risk of ALL in adult patients irrespective of the age at diagnosis, gender, and immunophenotype of ALL.

TNF–α influences lymphomagenesis by upregulating proinflammatory and antiapoptotic pathways. In this study, we evaluated the frequency of TNF–α rs1800629 (–308 G>A) polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and its correlation with age at diagnosis, gender and subtype of ALL. In this case control study, a total of 330 individuals were recruited, including 165 newly diagnosed adult patients with ALL, from the Radiation and Isotope Center in Khartoum (RICK) and 165 healthy normal controls. TNF–α rs1800629 polymorphism was tested through allele-specific polymerase chain reaction (PCR) assay. The frequency of the rs1800629 GA genotype was high (70.9% vs. 60%, OR = 1.84) in the patient group as compared to healthy controls, whereas GG and AA genotypes did not exhibit any statistically significant difference between controls and patients. Based on subtype, GG and GA rs1800629 genotypes showed increased risk of B-ALL (OR 0.46 and 2.12, respectively), whereas rs1800629 GG, GA and AA genotypes did not show any disease association with T-ALL (p > 0.05). Age at diagnosis and gender did not exhibit any association of rs1800629 with ALL in the patient group. In conclusion, rs1800629 is associated with high risk of adult B-ALL, with an insignificant effect of age at diagnosis and gender.

Colorectal cancer remains one of the leading prevalent cancers in the world and is the fourth most common cause of death from cancer. Unfortunately, the currently utilized chemotherapies fail in selectively targeting cancer cells and cause harm to healthy cells, which results in profound side effects. Researchers are focused on developing anti-cancer targeted medications, which is essential to making them safer, more effective, and more selective and to maximizing their therapeutic benefits. Milk-derived extracellular vesicles (EVs) from camels and cows have attracted much attention as a natural substitute product that effectively suppresses a wide range of tumor cells. This review sheds light on the biogenesis, methods of isolation, characterization, and molecular composition of milk EVs as well as the therapeutic potentials of milk EVs on colorectal cancer.

A library of 1,4-dihydropyridine-based 1,2,3-triazol derivatives has been designed, synthesized, and evaluated their cytotoxic potential on colorectal adenocarcinoma (Caco-2) cell lines. All compounds were characterized and identified based on their ¹H and ¹³C NMR (Nuclear Magnetic Resonance) spectroscopic data. Furthermore, molecular docking of best anticancer hits with target proteins (protein kinase CK2α, tankyrase1, and tankyrase2) has been performed. Our results implicated that most of these compounds have significant antiproliferative activity with IC₅₀ values between 0.63 ± 0.05 and 5.68 ± 0.14 µM. Moreover, the mechanism of action of most active compounds 13ab′ and 13ad′ suggested that they induce cell death through apoptosis in the late apoptotic phase as well as dead phase, and they could promote cell cycle arrest at the G2/M phase. Furthermore, the molecular docking study illustrated that 13ad′ possesses better binding interaction with the catalytic residues of target proteins involved in cell proliferation and antiapoptotic pathways. Based on our in vitro and in silico study, 13ad′ was found to be a highly effective anti-cancerous compound. The present data indicate that dihydropyridine-linked 1,2,3-triazole conjugates can be generated as potent anticancer agents.