Zingiberene exerts chemopreventive activity against 7,12-dimethylbenz(a)anthracene-induced breast cancer in Sprague-Dawley rats.

Breast cancer is the primary cause of cancer-related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12-dimethylbenz(a)anthracene (DMBA)-stimulated mammary carcinogenesis in rats and MDA-MB-231 cells. Breast cancer was induced in the Female Sprague-Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor-α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA-MB-231 cells. Zingiberene substantially modulated the DMBA-stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA-stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA-MB-231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA-stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent.

The Frequencies of ABO and Rh Phenotypes among Male Blood Donors in Northwestern Saudi Arabia.

BACKGROUND: Transfusion-dependent patients in Saudi Arabia are numerous because of the existence of life-threatening inherited diseases such as sickle cell anemia and thalassemia. Thus, analysis of the frequencies of the ABO and rhesus (Rh) phenotypes is vital. This study sought to evaluate the frequencies of the ABO and Rh phenotypes among male blood donors in Hail region. METHODS: One hundred and twenty-six (126) blood samples were collected from male donors living in Hail region and were screened for ABO and Rh phenotypes. The collected data were statistically analyzed using GraphPad Prism (version 9.3.1). RESULTS: Among 126 blood donors, 43.6% were classified into the O blood group. Additionally, Rh antigen e was predominantly detected in this study (99.2%). A total of 103 blood donors exhibited D antigen, whereas 23 were negative for D antigen. The DCe/dce (R1r) phenotype was observed in 29.1% of RhD positive donors, while 73.9% of RhD negative blood donors expressed the dce/dce (rr) phenotype. CONCLUSIONS: The O phenotype and e antigen were most frequently observed in male blood donors from Hail province. RhD positive samples took advantage of total blood donor samples over RhD negative samples. CcDee (R1r) phenotype was commonly identified in the RhD positive population, whereas ccddee (rr) phenotype was consis¬tently detected in the RhD negative male donors.

Isolation, Characterization and Anticancer Activity of Two Bioactive Compounds from Arisaema flavum (Forssk.) Schott.

Medicinal plants play important role in the public health sector worldwide. Natural products from medicinal plants are sources of unlimited opportunities for new drug leads because of their unique chemical diversity. Researchers have focused on exploring herbal products as potential sources for the treatment of cancer, cardiac and infectious diseases. Arisaema flavum (Forssk.) is an important medicinal plant found in the northwest Himalayan regions of Pakistan. It is a poisonous plant and is used as a remedy against snake bites and scorpion stings. In this study, two bioactive compounds were isolated from Arisaema flavum (Forssk.) and their anticancer activity was evaluated against human breast cancer cell line MCF-7 using an MTT assay. The crude extract of Arisaema flavum (Forssk.) was subjected to fractionation using different organic solvents in increasing order of polarity. The fraction indicating maximum activity was then taken for isolation of bioactive compounds using various chromatographic and spectroscopic techniques such as column chromatography, thin-layer chromatography (TLC), gas chromatography−mass spectrometry (GC-MS), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Crude extract of Arisaema flavum (Forssk.), as well as various fractions extracted in different solvents such as n-hexane, chloroform and ethyl acetate, were tested against human breast cancer cell line MCF-7 using an MTT assay. The crude extract exhibited significant dose-dependent anticancer activity with a maximum activity of 78.6% at 500 µg/mL concentration. Two compounds, hexadecanoic acid ethyl ester with molecular formula C18H36O7 and molar mass 284 and 5-Oxo-19 propyl-docosanoic acid methyl ester with molecular formula C26H50O3 and molecular mass 410, were isolated from chloroform fraction. These compounds were tested against the MCF-7cell line for cytotoxic activity and exhibited a significant (p < 0.00l) decrease in cell numbers for MCF-7 cells with IC50 of 25 µM after 48 h of treatment. Results indicated that Arisaema flavum (Forssk.) possesses compounds with cytotoxic activity that can further be exploited to develop anticancer formulations.

Familial pseudohyperkalemia in blood donors: a novel mutation with implications for transfusion practice.

BACKGROUND: Familial pseudohyperkalemia (FP) is a dominantly inherited condition in which red blood cells (RBCs) have an increased cold-induced permeability to monovalent cations. Potassium leaks into the supernatant of all stored blood with time, but FP RBCs leak potassium more rapidly. We investigated two unrelated blood donors whose RBC donations demonstrated unexpectedly high potassium after 5 and 6 days' storage. We matched the observed pattern of RBC cation leak to a previously recognized family with FP (FP-Cardiff) and investigated the likely cause with targeted DNA analysis. STUDY DESIGN AND METHODS: Cation leakage from the donor RBCs and from standard donor units was measured. DNA analysis of donors and family members with FP-Cardiff was performed. Allele frequencies were obtained from human variation databases. RESULTS: Both implicated donors were found to have increased cold-induced potassium leak identical in pattern to affected members of the family with FP-Cardiff. We found a heterozygous substitution Arg723Gln in the ATP-binding cassette, Subfamily B, Member 6 protein that segregated with FP in the Cardiff family and was also present in both blood donors. Arg723Gln is listed in human variation databases with an allele frequency of approximately 1:1000. CONCLUSIONS: We describe a novel FP mutation that may affect 1:500 European blood donors and causes rapid loss of potassium from stored RBCs. This finding has implications for neonates and infants receiving large-volume RBC transfusions. Genomic screening of donors could be used to identify donors with this mutation and potentially improve the quality and safety of donor units.

Transplacental Transfer of SARS-CoV-2 Receptor-Binding Domain IgG Antibodies from Mothers to Neonates in a Cohort of Pakistani Unvaccinated Mothers.

The presence of COVID-19 antibodies in the maternal circulation is assumed to be protective for newborns against SARS-CoV-2 infection. We investigated whether maternal COVID-19 antibodies crossed the transplacental barrier and whether there was any difference in the hematological parameters of neonates born to mothers who recovered from COVID-19 during pregnancy. The cross-sectional study was conducted at the Saidu Group of Teaching Hospitals, located in Swat, Khyber Pakhtunkhwa. After obtaining written informed consent, 115 healthy, unvaccinated mother-neonate dyads were included. A clinical history of COVID-19-like illness, laboratory-confirmed diagnosis, and contact history were obtained. Serum samples from mothers and neonates were tested for SARS-CoV-2 anti-receptor-binding domain (anti-RBD) IgG antibodies. Hematological parameters were assessed with complete blood counts (CBC) and peripheral blood smear examinations. The study population consisted of 115 mothers, with a mean age of 29.44 ± 5.75 years, and most women (68/115 (59.1%)) were between 26 and 35 years of age. Of these mothers, 88/115 (76.5 percent) tested positive for SARS-CoV-2 anti-RBD IgG antibodies, as did 83/115 (72.2 percent) neonatal cord blood samples. The mean levels of SARS-CoV-2 IgG antibodies in maternal and neonatal blood were 19.86 ± 13.82 (IU/mL) and 16.16 ± 12.90 (IU/mL), respectively, indicating that maternal antibodies efficiently crossed the transplacental barrier with an antibody transfer ratio of 0.83. The study found no significant difference in complete blood count (CBC) parameters between seropositive and seronegative mothers, nor between neonates born to seropositive and seronegative mothers.

Genotyping of Dombrock blood group system in blood donors from Saudi Arabia: A single-center study.

OBJECTIVES: To establish the frequency of Dombrock (DO) blood group genotypes in Western Saudi Arabians and to compare the findings with other populations in the 1000 genomes database. METHODS: This cross-sectional study was carried out between December 2018 and February 2019. A total of 440 blood samples in ethylenediaminetetraacetic acid tubes were collected from unrelated Saudi Arabian blood donors from Jeddah, Saudi Arabia. Deoxyribonucleic acid was extracted, followed by an allele-specific polymerase chain reaction for DO*01 and DO*02 alleles (c.793A>G, rs11276). The allele and genotype frequencies were counted and compared to those in other populations using the Chi-squared test with Bonferroni adjustments. RESULTS: The DO allele frequencies for blood donors from western Saudi Arabia were 0.432 for DO*01 and 0.568 for DO*02. The DO genotype frequencies were 0.182 for DO*01/01, 0.318 for DO*02/02, and 0.5 for DO*01/02. The DO genotype frequencies were similar to Europeans, Americans, and South Asians but significantly different from the genotype frequencies of Africans and East Asians reported in the 1000 genomes database. CONCLUSION: Dombrock genotype frequencies in the Western Saudi Arabian population were different from Africans and East Asians but not from Europeans, Americans, and South Asians. This study contributes to a genotyped blood donor database and may advance transfusion safety for patients in western Saudi Arabia.

Systematic Review and Meta-Analysis of the Susceptibility of ABO Blood Groups to Venous Thromboembolism in Individuals with Factor V Leiden.

A limited number of studies investigated the association between the ABO blood groups and the incidence of venous thromboembolism in individuals with Factor V Leiden; however, discordant findings were reported. Consequently, this systematic review and meta-analysis aimed to evaluate the existing evidence on the susceptibility of the ABO blood group to venous thromboembolism in individuals with Factor V Leiden. All English-published articles on the Web of Science, Scopus, PubMed, EMBASE, and Google Scholar were comprehensively and systematically searched by the author without a time or region limit. Four studies were included in the qualitative synthesis and meta-analysis after the removal of studies that were not eligible. According to the analyses of the fixed and random effects, the point estimates of the effect size and the 95% confidence interval were 0.416 (95% CI: 0.397−0.435) and 0.392 (95% CI: 0.288−0.507), respectively. In contrast, the homogeneity test (Q value) reveals that blood group data distributions have a heterogenous structure (Q = 432.187; p-value < 0.001). The pooled event rates and the 95% CIs for the A, AB, B, and O-blood groups were 0.518 (95% CI: 0.411−0.622), 0.592 (95% CI: 0.495−0.683), 0.205 (95% CI: 0.041−0.612), and 0.283 (95% CI: 0.247−0.322), respectively. According to the findings, people with Factor V Leiden with blood group AB are more likely to develop venous thromboembolism than those with blood groups A, O, and B. The overall statistical significance of the ABO blood group's susceptibility to venous thromboembolism in individuals with Factor V Leiden was <0.001 (pooled p-value). In conclusion, the current meta-analysis provides an additional indication that blood group AB individuals with Factor V Leiden are at higher risk of developing venous thromboembolism, and blood type B is connected to a lower risk of developing venous thromboembolism.

Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity.

Background: Iron deficiency anemia (IDA) is a global health problem affecting the quality of life of more than 2 billion individuals. The current practice guidelines diagnose and monitor IDA via conventional hematological and iron biomarkers, which take several months before they are corrected under an iron-treatment plan. Reticulocyte hemoglobin equivalent (Ret-He) is used as a marker in most new hematology analyzers to assess iron incorporation into erythrocyte hemoglobin directly. This study aims to examine the efficacy of Ret-He as a marker for iron deficiency (ID) and IDA and investigate whether Ret-He is sensitive to iron therapy. Methods: Two blood samples were drawn from 182 participants for CBC and iron profile measurements. Follow-up samples were drawn from participants with a confirmed diagnosis of ID and/or IDA. Results: Ret-He levels were lower in the ID and IDA groups compared to the control (p < 0.0001), and lower in the IDA group compared to the ID group (p < 0.0001). Ret-He was correlated with ferritin at ID level (<30.0 mg/mL; r = 0.39) and severe IDA (<13.0 ng/mL; p-value < 0.01, r = 0.57). Cut-off values of <28.25 pg for ID and <21.55 pg for IDA showed a higher specificity and sensitivity (ID; AUC: 0.99, sensitivity: 92.73%, specificity: 97.87%) and (IDA; AUC: 0.94, sensitivity: 90.63%, specificity: 92.31%). Finally, Ret-He successfully reflected the iron therapy (p < 0.001) when compared to hemoglobin (Hb) (p = 0.1). Conclusions: Ret-He is a potential marker for detecting and diagnosing different stages of ID with high validity and is very sensitive in reflecting the iron incorporation in a short time.

Impact of COVID-19 on Blood Donation and Supply: A Multicenter Cross-Sectional Study from Saudi Arabia.

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic caused a major impact on blood donation process and supply globally. A lockdown management procedure was launched nationally in Saudi Arabia to manage this global health crisis. The main aim of this study was to determine the effect of COVID-19 lockdown on blood donation services and supply in different regions of Saudi Arabia. Study Design and Methods. A retrospective cross-sectional study was conducted in the blood bank centers of 5 major cities including Riyadh, Jeddah, Dammam, Hail, and Jizan in Saudi Arabia. Demographic and blood characteristics were retrieved from the first 6 months of 2019 (January-June) and compared to the same period of 2020. RESULTS: Our findings showed variation in the characteristics of blood donation and supply among the centers surveyed, as some of these centers were adversely affected, while others showed an increase in the availability of blood products during the pandemic. For example, Jeddah's center was significantly affected by COVID-19 lockdown whereas Hail's center showed a significant increase in the analyzed characteristics of blood donation services in 2020 compared to 2019. Overall, there was no major difference among the surveyed centers between 2020 and 2019, and this might be due to the effective management of blood supply and transfusion. Discussion. Although blood supply and transfusion practice was slightly affected at various degree among the surveyed centers, the whole process did not show a significant effect on the overall outcome. This is in fact due to the proper preparedness, management of blood requirements and supplies, and efficient response of the surveyed centers in Saudi Arabia.

Consumption of Food Components of the Mediterranean Diet Decreases the Risk of Breast Cancer in the Makkah Region, Saudi Arabia: A Case-Control Study.

Background: Breast cancer is one of the leading causes of death worldwide, it affects both men and women. In Saudi Arabia, breast cancer has been the most prevalent type of cancer in women, for the past few years. Dietary habits and cultural beliefs vary according to region, and further studies are required to demonstrate the relationship between these dietary habits and cultural beliefs and the risk of developing breast cancer. This study is aimed to discover the relationship between preventive dietary factors of the Mediterranean diet and rates of breast cancer among postmenopausal women in the Makkah region of Saudi Arabia. Methods: A case-control study was conducted in King Abdulla Medical City Hospital, Makkah, Saudi Arabia and included 432 Saudi female participants: 218 in the control group and 214 breast cancer patients. All participants were postmenopausal, around the same age, and all were ethnically Arab Saudis. Data were obtained using a self-administered validated questionnaire. Results: Study results showed that a diet that includes 1-2 servings of legumes weekly, 1-5 servings of fish weekly, 1-5 servings of dairy products daily, 3-5 servings of fruits and vegetables daily, and more than one cup of black tea and coffee per day significantly (p < 0.05) reduces the risk of breast cancer. Conclusion: This study demonstrates that consuming a Mediterranean diet, which includes legumes, fish, fruits and vegetables, black tea, coffee, and low intake of dairy products, works as a preventive factor against breast cancer in postmenopausal females from the Makkah region.

Corrigendum: Consumption of Food Components of the Mediterranean Diet Decreases the Risk of Breast Cancer in the Makkah Region, Saudi Arabia: A Case-Control Study.

[This corrects the article DOI: 10.3389/fnut.2022.863029.].

Enhancing the utilization of packed red blood cells stock in maternity hospitals.

OBJECTIVES: To assess and enhance the efficiency of transfusion services in maternity hospitals. METHODS: A case control study was conducted from January to December 2016. A corrective policy of replacing preoperative type and hold step with blood transfusion request (BTR) hold was used only on healthy patients undergoing elective cesarean sections (c-section). The crossmatch/transfusion (C:T) ratio and a cost comparison were the evaluating factors. Data were analyzed using an Excel spreadsheet and SPSS statistical software. RESULTS: A total of 1,200 BTRs were analyzed, comprising 659 before implementation of the corrective policy and 541 blood transfusion requests after implementation of the corrective policy. From January to March, the C:T ratio of c-sections was nearly 7 times the American Association of Blood Banks recommended limit of 2.5. Most of the blood units (94%) were damaged due to repeated booking. After implementation, the cost-e ectiveness of erythrocyte transfusion was greatly enhanced as all the ordered blood units were used and the C:T ratio was reduced to the ideal limit of one. The number of destroyed units was drastically decreased from 450 units to zero; as a result, 83% of the transfusion costs were saved. CONCLUSION: The policy enhances the cost-effectiveness of erythrocyte transfusion and laboratory testing, and saves on additional, unnecessary costs.

The involvement of cation leaks in the storage lesion of red blood cells.

Stored blood components are a critical life-saving tool provided to patients by health services worldwide. Red cells may be stored for up to 42 days, allowing for efficient blood bank inventory management, but with prolonged storage comes an unwanted side-effect known as the "storage lesion", which has been implicated in poorer patient outcomes. This lesion is comprised of a number of processes that are inter-dependent. Metabolic changes include a reduction in glycolysis and ATP production after the first week of storage. This leads to an accumulation of lactate and drop in pH. Longer term damage may be done by the consequent reduction in anti-oxidant enzymes, which contributes to protein and lipid oxidation via reactive oxygen species. The oxidative damage to the cytoskeleton and membrane is involved in increased vesiculation and loss of cation gradients across the membrane. The irreversible damage caused by extensive membrane loss via vesiculation alongside dehydration is likely to result in immediate splenic sequestration of these dense, spherocytic cells. Although often overlooked in the literature, the loss of the cation gradient in stored cells will be considered in more depth in this review as well as the possible effects it may have on other elements of the storage lesion. It has now become clear that blood donors can exhibit quite large variations in the properties of their red cells, including microvesicle production and the rate of cation leak. The implications for the quality of stored red cells from such donors is discussed.

Distal renal tubular acidosis with hereditary spherocytosis.

Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

An infant with pseudohyperkalemia, hemolysis, and seizures: cation-leaky GLUT1-deficiency syndrome due to a SLC2A1 mutation.

CONTEXT: GLUT1 (glucose transporter 1) deficiency syndrome is a well-known presentation in pediatric practice. Very rare mutations not only disable carbohydrate transport but also cause the red cell membrane to be constitutively permeant to monovalent cations, namely sodium and potassium. OBJECTIVE: The aim of this study was to describe the pediatric presentation of a patient with GLUT1 deficiency with such a cation-leaky state. SUBJECT AND METHODS: The infant presented with erratic hyperkalemia, neonatal hyperbilirubinemia, anemia, hepatic dysfunction, and microcephaly. Later, seizures occurred and developmental milestones were delayed. Magnetic resonance imaging and computerized tomography scans of the brain showed multiple abnormalities including periventricular calcification. Visual impairment was present due to the presence of both cataracts and retinal dysfunction. RESULTS: Measurements of red cell cation content showed extremely leaky red cells (causing the hemolysis) and temperature-dependent loss of potassium from red cells (explaining the hyperkalemia as pseudohyperkalemia). A trinucleotide deletion in SLC2A1, coding for the deletion of isoleucine 435 or 436 in GLUT1, was identified in the proband. CONCLUSION: This is the fourth pedigree to be described with this most unusual syndrome. The multisystem pathology probably reflects a combination of glucose transport deficiency at the blood-brain barrier (as in typical GLUT1 deficiency) and the deleterious osmotic effects of a cation-leaky membrane protein in the cells where GLUT1 is expressed, notably the red cell. We hope that this detailed description will facilitate rapid diagnosis of this disease entity.