The Prevalence of Transfusion-Transmitted Diseases Among Blood Donors in the Central Blood Bank in Makkah, Saudi Arabia.

Background This study aimed to analyze the health and demographic characteristics of blood donors in Makkah, Saudi Arabia, and assess the prevalence and correlation of two markers related to hepatitis B infection: hepatitis B virus surface antigen (HBsAg) and anti-hepatitis B virus surface antibody (HBsAb). Materials and methods The study used a retrospective design and collected data from the Central Blood Bank in Makkah, Saudi Arabia, in 2022. The sample size was 7,875 blood donors. The study used various methods, such as serological testing, nucleic acid testing (NAT), and statistical analysis. The data were analyzed using Pearson correlation to examine the relationships between different variables. Results The predominant age group was 29-39 years, accounting for 46.9% of the total donors. In terms of blood types, O+ve was the most common, representing 40.3% of the donors. The investigation into infectious markers revealed overall low levels of reactivity among donors. For HBsAg, a marker of active hepatitis B infection, only 0.36% of the units were reactive. Conversely, the anti-HBsAb, which indicates immunity to hepatitis B, was reactive in 6.83% of the units. The correlation analysis illuminated some critical relationships. The total number of units tested had a statistically significant, albeit weak, positive relationship with HBsAg reactivity, shown by a Pearson correlation coefficient of 0.030 and a p-value of 0.008. Conversely, the total number of units tested and anti-HBsAb reactivity showed a moderate negative correlation, with a Pearson correlation coefficient of -0.437 and a p-value of less than 0.001. However, no significant correlation was identified between HBsAg and anti-HBsAb reactivity, indicating that active infection and immunity status might not be directly linked. Conclusion This extensive study provides in-depth insights into the sociodemographic characteristics of blood donors and the prevalence of key infectious markers within this population. It underlines the imperative of rigorous screening of blood units, particularly given the low immunity levels to hepatitis B identified. Also, the study showed the importance of screening blood units and vaccinating people against hepatitis B. It also suggested the need for more research on blood safety and infection-immunity relationships.

Diverse pharmacological potential of pyridazine analogs against various diseases.

Pyridazinone analogs possess diverse types of pharmacological activities, such as anticancer, antimicrobial, anticonvulsant, analgesic, anti-inflammatory, antioxidant, antihypertensive, antisecretory, antiulcer, and other useful pharmacological activities. They also possess cyclooxygenase (COX) inhibitors, dipeptidyl peptidase inhibitors, phosphodiesterase inhibitors, glutamate transporter activators, adenosine receptor antagonists, serotonin receptors antagonists, lipooxygenase, cholinesterase, vasodilator, and anesthetics. Pyridazine rings are the essential structure for some marketed drugs, such as pimobendan, levosimendan as a cardiotonic drug, and emorfozan as an analgesic and anti-inflammatory (Non-steroidal anti-inflammatory drug) agent. So, researchers all over the world have paid attention to synthesizing various pyridazinone compounds mainly due to the ease of design and synthesis of different analogs and variables in the pharmacological responses. This review article focuses on the pharmacological activities of different pyridazine analogs.

Phenotypical evaluation of lymphocytes and monocytes in patients with type 2 diabetes mellitus in Saudi Arabia.

OBJECTIVES: To evaluate the levels of total lymphocytes, B-lymphocytes (CD19+), T-lymphocytes (CD3+), natural killer (NK) cells (CD3-/CD56+), and monocyte subsets in type 2 diabetes mellitus (T2DM) patients in Saudi Arabia. In addition, this study aimed to evaluate whether B- and T-lymphocyte subsets are frequently altered in patients with T2DM. METHODS: A case-control study included 95 participants recruited in the study: 62 patients with T2DM and 33 healthy individuals. All the patients were admitted to the Diabetic Centre in Taif, Saudi Arabia. Blood samples were collected between April and August 2022. The hemoglobin A1c (HbA1c) level was evaluated in all patients. Flow cytometry was used to measure the expression of B-lymphocyte, T-lymphocyte, NK cells, and monocyte markers. The unpaired t-test was carried out to evaluate the differences in these markers between T2DM patients and healthy individuals. RESULTS: Patients with T2DM were associated with a lower percentage of total lymphocytes, higher percentage of B-lymphocytes, naive, and memory B subsets. In addition, patients with T2DM showed lower percentage of total T-lymphocytes (CD3+) and CD4 T-cells, but higher CD8 T-cell expression. Also, the NK-cell level was reduced in patients with T2DM, and the levels of monocyte subsets were altered. CONCLUSION: These data suggested that levels of lymphocytes and monocytes are impaired in T2DM patients, and this might be associated with the higher risk of infections observed in these patients.

Identification of human immunodeficiency virus -1 E protein-targeting lead compounds by pharmacophore based screening.

OBJECTIVES: To identify potential compounds by seeking the knowledge of molecular interactions between human immunodeficiency virus (HIV) glycoprotein (gp) 120 protein and anti-HIV drug (BMS-488043). METHODS: This study is a computational structure-based drug design study, carried out at University of Taif, Saudi Arabia and African Genome Centre (AGC), Mohammed VI Polytechnic University, Benguerir, Morocco from January 2021 to March 2022. Initially, using the docked structure of gp120 with BMS-488043, a structure-based pharmacophore model was created. The generated model was utilized for virtual screening of the ZINC and ChemBridge database in order to identify hit compounds. To further assess the time-dependent stability of the selected complexes, computer simulation was performed. RESULTS: From pharmacophore-based screening, 356 hits were obtained from both the database. The docking studies of the retrieved hit compounds reveal that all the compounds fit into the binding site of gp120. However, based on the significant interactions with the crucial residues and docking scores four compounds were suggested as potential hits. MD simulation of ChemBridge14695864 and ZINC06893293 in complex with gp120 suggested that both compounds significantly stabilized the receptor. CONCLUSION: These findings could aid in the design of effective drugs against HIV by inhibiting the interaction between gp120 and CD4.

Detection of erythroid progenitors and erythrocytopathies in patients with severe COVID-19 disease.

OBJECTIVES: To assess the effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on erythropoiesis and red blood cells (RBC) surface markers by evaluating erythroid progenitor cells (CD [cluster of differentiation]71+/CD235a+) and RBC surface markers (CD235a and CD36), together with various hematological parameters. METHODS: This case-control study includes 47 participants recruited in the study: 30 patients with coronavirus disease 2019 (COVID-19) and 17 healthy individuals. The COVID-19 patients were recruited from the intensive care unit (ICU) of various hospitals in Makkah, Saudi Arabia. Blood samples were collected during July and September 2021. Red blood cells indices were measured using a CBC analyzer. The expression of CD235a, CD71, and CD36 was obtained using flow cytometry technique. The unpaired t-test was conducted to evaluate the differences in these markers in COVID-19 patients and healthy individuals. RESULTS: The data showed that more than half of the COVID-19 patients were anemic (64%). Expansion of erythroid progenitors (CD71+/CD235a+) was detected in the COVID-19 patients. Analysis of the expression of RBC surface markers, such as CD235a and CD36, showed that SARS-CoV-2 was associated with significantly higher expression of these markers in COVID-19 patients. CONCLUSION: Severe acute respiratory syndrome coronavirus-2 promoted the expansion of erythroid progenitors in the peripheral blood of COVID-19 patients. In addition, the expression of RBC surface markers was higher in COVID-19 patients. The expansion of erythroid progenitors and alteration of RBC surface markers can contribute to erythrocytopathies observed in severe COVID-19 patients and can therefore be used as prognostic factors.

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia.

Cyclophosphamide (CP) is a mutagen that is used in cancer chemotherapy, due to its genotoxicity and as an immunosuppressive agent. Thalidomide (TH) is another cancer chemotherapeutic drug. In this study, the cytogenotoxicity and hypoxia modulatory activities of two phthalimide analogs of TH have been evaluated with/without CP. Both analogs have increased CP-stimulated chromosomal aberrations than those induced by TH, including gaps, breaks/fragments, deletions, multiple aberrations, and tetraploidy. The analogs have elevated the cytotoxic effect of CP by inhibiting the mitotic activity, in which analog 2 showed higher mitosis inhibition. CP has induced binucleated and polynucleated bone marrow cells (BMCs), while micronuclei (MN) are absent. TH and analogs have elevated the CP-stimulated binucleated BMCs, while only analogs have increased the CP-induced polynucleated BMCs and inhibited the mononucleated BMCs. MN-BMCs were shown together with mononucleated, binucleated, and polynucleated cells in the CP group. Both analogs have elevated mononucleated and polynucleated MN-BMCs, whereas in presence of CP, TH and analogs have enhanced mononucleated and binucleated MN-BMCs. The analogs significantly induce DNA fragmentation in a comet assay, where analog 1 is the strongest inducer. The treatment of mice with CP has resulted in a high hypoxia status as indicated by high pimonidazole adducts and high HIF-1α and HIF-2α concentrations in lymphocytes. Analogs/CP-treated mice showed low pimonidazole adducts. Both analogs have inhibited HIF-1α concentration but not HIF-2α. Taken together, the study findings suggest that both analogs have a higher potential to induce CP-genotoxicity than TH and that both analogs inhibit CP-hypoxia via the HIF-1α-dependent mechanism, in which analog 1 is a more potent anti-hypoxic agent than analog 2. Analog 1 is suggested as an adjacent CP-complementary agent to induce CP-genotoxicity and to inhibit CP-associated hypoxia.

Anti-hypoxic Effect of Polysaccharide Extract of Brown Seaweed Sargassum dentifolium in Tongue Squamous Cell Carcinoma.

Sargassum dentifolium, (Turner) C. Agarth, 1820, is an edible brown alga collected from red seashores, Egypt. Oral tongue squamous cell carcinoma (OTSCC) is an aggressive malignancy. Hypoxia leads to chemotherapeutic resistance. This work aimed to explore the anti-hypoxia effect of water-soluble polysaccharide fractions of S. dentifolium (SD1-SD3) in CAL-27 OTSCC cells. Cell cytotoxicity assay (MTT); cell death mode (DNA staining); total hypoxia (pimonidazole), HIF-1α (ELISA and immunocytochemistry), HIF-1ß (ELISA), and hsa-miRNA-21-5p and hsa-miRNA-210-3p (qRT-PCR) were investigated. SD1 and SD2 showed a cytotoxic effect due to apoptosis. SD2 and SD3 decreased total cell hypoxia, inhibited miR-210 (p < 0.001 and p < 0.01), miR-21 (p < 0.01 and p < 0.05), and HIF-1α (p < 0.01 and p < 0.05), respectively. However, only SD3 suppressed HIF-1ß (p < 0.05). In conclusion, SD2 showed a potential anti-hypoxia effect through amelioration of HIF-1α regulators, which may help in decreasing hypoxia-induced therapeutic resistance.

The Antidiabetic Effects and Modes of Action of the Balanites aegyptiaca Fruit and Seed Aqueous Extracts in NA/STZ-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic metabolic disorder that threatens human health. Medicinal plants have been a source of wide varieties of pharmacologically active constituents and used extensively as crude extracts or as pure compounds for treating various disease conditions. Thus, the aim of this study is to assess the anti-hyperglycemic and anti-hyperlipidemic effects and the modes of action of the aqueous extracts of the fruits and seeds of Balanites aegyptiaca (B. aegyptiaca) in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Gas chromatography-mass spectrometry analysis indicated that 3,4,6-tri-O-methyl-d-glucose and 9,12-octadecadienoic acid (Z,Z)- were the major components of the B. aegyptiaca fruit and seed extracts, respectively. A single intraperitoneal injection of STZ (60 mg/kg body weight (b.w.)) 15 min after intraperitoneal NA injection (60 mg/kg b.w.) was administered to induce type 2 DM. After induction was established, the diabetic rats were treated with the B. aegyptiaca fruit and seed aqueous extracts (200 mg/kg b.w./day) via oral gavage for 4 weeks. As a result of the treatments with the B. aegyptiaca fruit and seed extracts, the treated diabetic-treated rats exhibited a significant improvement in the deleterious effects on oral glucose tolerance; serum insulin, and C-peptide levels; liver glycogen content; liver glucose-6-phosphatase and glycogen phosphorylase activities; serum lipid profile; serum free fatty acid level; liver lipid peroxidation; glutathione content and anti-oxidant enzyme (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) activities; and the mRNA expression of the adipose tissue expression of the insulin receptor ß-subunit. Moreover, the treatment with fruit and seed extracts also produced a remarkable improvement of the pancreatic islet architecture and integrity and increased the islet size and islet cell number. In conclusion, the B. aegyptiaca fruit and seed aqueous extracts exhibit potential anti-hyperglycemic and anti-hyperlipidemic effects, which may be mediated by increasing the serum insulin levels, decreasing insulin resistance, and enhancing the anti-oxidant defense system in diabetic rats.

Angelica archangelica and Ginkgo biloba Extracts Recover Functional Blood Hemoglobin Derivatives in Rabbits Exposed to High Altitude.

BACKGROUND: Shortage of oxygen is a common condition for residents of high-altitude (HA) areas. In mammals, hemoglobin (Hb) has four derivatives: oxyhemoglobin (Hb-O2), carboxyhemoglobin (Hb-CO), sulfhemoglobin (Hb-S), and methemoglobin (Met-Hb). In HA areas, aberrant physiological performance of blood hemoglobin is well-established. OBJECTIVES: The study aimed to investigate the influence of 30 days of HA residence on rabbits' total Hb, Hb derivatives, Hb autooxidation rate, and antioxidant enzymes in comparison to low-altitude control rabbits. Further, the study aimed to investigate the effect of antioxidant-rich Angelica archangelica and/or Ginkgo biloba extracts on the same parameters in HA-resident rabbits. METHODS: Rabbits subjected to 30 days of HA residence were compared to low-altitude control rabbits. HA-residence rabbits were then orally administered 0.11 g/kg b.wt. of Angelica archangelica and/or Ginkgo biloba extract for 14 days. Hb derivatives and Hb autooxidation rate were measured spectrophotometrically. Antioxidant enzymes were estimated using specialized kits. RESULTS: Compared to low-altitude rabbits, 30-day HA-residence rabbits showed a noticeable increase (p<0.05) in Hb-O2 and Hb-CO concentration. In addition, Met-Hb concentration, autooxidation rate of Hb molecules, and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) exhibited a remarkable increase in HA-residence rabbits (p<0.01), reflective of rapid ROS generation. In HA-residence rabbits, both individual and combined treatment with antioxidant-rich extracts for 14 days resulted in recovery to near-normal functional levels of Hb-O2 and Met-Hb, Hb autooxidation rate, and activities of SOD and GPx, while only combined treatment led to Hb-O2 recovery. CONCLUSION: The findings suggest that functional Hb levels may be recovered by oral administration of A. archangelica, G. biloba, or combined treatments. In conclusion, oxidative stress due to living in HA areas may be avoided by supplementation with natural antioxidants.

Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/ß-catenin, and PI3K/Akt/mTOR signaling pathways.

Hepatocellular carcinoma (HCC) has been identified as one of the most deadly malignancies with limited therapeutic efficacy worldwide. However, understanding the molecular mechanisms of crosstalk between signaling pathways in HCC and predicting cancer cell responses to targeted therapeutic interventions remain to be challenge. Thus, in this study, we aimed to evaluate the anticancerous efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally-induced HCC in rats. In vitro investigations were also performed and the anticancer effects against HCC cell lines (HepG2 and Huh7) were confirmed. Wistar rats were given diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4) and were orally treated with STE (200 mg/kg body weight (bw)), Sm (150 mg/kg bw), and Sb (5 mg/kg bw) every other day from the 1st or 16th week to the 25th week of DEN/AAF/CCl4 injection. Treatment with STE, Sm, and Sb inhibited the growth of cancerous lesions in DEN/AAF/CCl4-treated rats. This inhibition was associated with inhibition of Ki-67 expression and repression of HGF/cMet, Wnt/ß-catenin, and PI3K/Akt/mTOR signaling pathways. STE, Sm, and Sb improved liver function biomarkers and tumor markers (AFP, CEA, and CA19.9) and increased total protein and albumin levels in serum. STE, Sm, and Sb treatment was also noted to reduce the hepatic production of lipid peroxides, increase hepatic glutathione content, and induce the activities of hepatic antioxidant enzymes in DEN/AAF/CCl4-treated rats. These results indicate that STE, Sm, and Sb exert anti-HCC effects through multiple pathways, including suppression of Ki-67 expression and HGF/cMet, Wnt/ß-catenin, and PI3K/Akt/mTOR pathways and enhancement of antioxidant defense mechanisms.

In vitro and in vivo Antibacterial effect of Commiphora gileadensis Methanolic Extract against Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVE: Commiphora gileadensis is a plant in the Burseraceae family that grows in the western area of Saudi Arabia. Traditionally, it is used in the treatment of some superficial infections. MATERIALS AND METHODS: The methanolic extract of Commiphora gileadensis isolated from its leaves and branches. The in vitro study was conducted to determine the effect of this extract on Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa using an agar diffusion and Minimum inhibitory concentration (MIC) methods. The in vivo study was conducted through two different methods. The first method, 20 male Balb c-1 mice were used for the determination of Commiphora gileadensis methanolic extract toxicity (LD50). In the second method, 40 male mice were used and were put into four groups. The first and second groups were injected subcutaneously with 108 CFU of MRSA 1 mL-1, while the third and fourth groups were injected with 108 CFU of Pseudomonas aeruginosa 1 mL-1. The comparison between groups was done by using a t-test (p<0.05). RESULTS: The methanolic extract of Commiphora gileadensis had a greater sensitivity zone on MRSA and Pseudomonas aeruginosa, 7 and 3 mm respectively. The MIC of the extract was 1/8 and 1/2 for MRSA and Pseudomonas aeruginosa respectively. The in vivo study showed that the extract was non-toxic, it also showed that the extract decreased the mortality of mice induced by MRSA injection significantly (p<0.05) While insignificantly with Pseudomonas aeruginosa. CONCLUSION: The total Commiphora gileadensis methanolic extract had an antibacterial effect on MRSA and Pseudomonas aeruginosa. This extract was non-toxic for the mice.

Association Between Random Glucose Level and Leukocytes Count in Female Cancer Patients.

Leukocytosis is common among patients suffering from cancer when leukocytes count exceeds 11,000 cells per mm3. This is a usual immune response toward infection and foreign elements. This leads to the release of inflammatory mediators at the targeted site. Studies have found leukocytes count increase in diabetes mellitus patients. Random glucose level indicates the patient is at risk of developing diabetes mellitus. In this study, the association between random glucose level and leukocytes count in female cancer patients is evaluated. About 210 cancer patients included in this study and the results have indicated a positive association between high glucose level and high leukocyte count. This indicates poor prognosis of the patients as high glucose levels increase tumor cell proliferation and high leukocytes count can induce inflammation leading to the progression of cancer and increase mortality rate.

Association of toll-like receptors 2, 4, 9 and 10 genes polymorphisms and Helicobacter pylori-related gastric diseases in Saudi patients.

Purpose: Helicobacter pylori is one of the most prevalent human pathogens worldwide. However, the outcomes of H. pylori infection are markedly variable from asymptomatic mild lesion to malignant transformation. Many factors are suggested to influence these infection outcomes, including host immunity and genetic susceptibility. Toll-like receptors (TLRs) can recognise different microbial components and play an essential role in the mucosal immune response against H. pylori infection. Materials and Methods: The association between the common single nucleotide polymorphisms (SNPs) in the genes of TLR2, 4, 9 and 10 and H. pylori-related gastric diseases were investigated by molecular methods after the confirmation of H. pylori infection. The study included 210 patients in three groups; chronic gastritis (n = 90), peptic ulcer disease (PUD) (n = 75) and gastric carcinoma (n = 45). Results: The results showed a significant association between TLR4 SNPs (rs 4986790 and rs 4986791) and the presence of H. pylori infection, especially in chronic gastritis patient group. Furthermore, TLR9-rs352140 TT genotype was more prevalent among chronic gastritis patient group. TLR10-rs 10004195 TT genotype was found to be less prevalent among H. pylori-related chronic gastritis and PUD and was suspected to have a protective effect. TLR2 SNPs (rs3804099 and rs3804100) showed no significant statistical difference between H. pylori-infected patients and the controls. Conclusion: TLR genes polymorphisms may play a role in H. pylori infection susceptibility and may influence its outcomes; however, the ethnic and other factors may modify this effect.

Generating homogenous cortical preplate and deep-layer neurons using a combination of 2D and 3D differentiation cultures.

Embryonic stem cells (ESCs) can be used to derive different neural subtypes. Current differentiation protocols generate heterogeneous neural subtypes rather than a specific neuronal population. Here, we present a protocol to derive separate two-deep layer cortical neurons from mouse ESCs (mESCs). mESCs were differentiated into mature Tbr1 or Ctip2-positive neurons using a monolayer-based culture for neural induction and neurosphere-based culture for neural proliferation and expansion. The differentiation protocol relies on SMAD inhibition for neural induction and the use of FGF2 and EGF for proliferation and it is relatively short as mature neurons are generated between differentiation days 12-16. Compared with the monolayer-based differentiation method, mESCs can be directed to generate specific deep-layer cortical neurons rather than heterogeneous cortical neurons that are generated using the monolayer differentiation culture. The early analysis of progenitors using flow cytometry, immunocytochemistry, and qRT-PCR showed high neuralization efficiency. The immunocytochemistry and flow cytometry analyses on differentiation days 12 and 16 showed cultures enriched in Tbr1- and Ctip2-positive neurons, respectively. Conversely, the monolayer differentiation culture derived a mixture of Tbr1 and Ctip2 mature neurons. Our findings suggested that implementing a neurosphere-based culture enabled directing neural progenitors to adopt a specific cortical identity. The generated progenitors and neurons can be used for neural-development investigation, drug testing, disease modelling, and examining novel cellular replacement therapy strategies.

Awareness of human papillomavirus infection complications, cervical cancer, and vaccine among the Saudi population. A cross-sectional survey.

OBJECTIVES: To determine human papillomavirus (HPV) infection, cervical cancer, and vaccine awareness among the Saudi population. METHODS: This cross-sectional study of a convenience sample comprising 1033 participants (males and females) from different parts of Kingdom of Saudi Arabia was conducted between August 2018 and January 2019 using a web-based questionnaire. This self-administrated questionnaire was distributed to all participants. Collected data included age groups, cervical cancer, Papanicolaou (Pap) smear, and HPV vaccine awareness. RESULTS: The response rate was 95%. Approximately 50% of the participants were 15-22 years old, less than 3% were more than 46 years old, and less than 10% had heard of HPV. Awareness and previous knowledge of the Pap smear as a screening tool was variable with male (5.9%) and female (27.9%) participants, having knowledge of the test. There were no statistically significant differences (p more than 0.05) between males and females in their knowledge of HPV's role in cervical and penile cancers, the HPV vaccine availability in the hospital, its role in cervical cancer prevention, and suggestions that this vaccine should be provided to married and non-married women. CONCLUSION: There is a lack of knowledge and misinformation regarding cervical cancer, Pap smears, HPV, and HPV association with cervical cancer. These data can be used as a basis to formulate effective population awareness programs.