Serum Ferritin and its Importance for SARS-CoV-2-Infected Patients.

BACKGROUND: Serum ferritin is an acute-phase protein whose level is increased in several inflammatory diseases. This review describes the structure and function of ferritin as well as its association with the prognosis of patients with COVID-19. METHODS: We searched MEDLINE/PubMed databases, Scopus, and Web of Science for prospective and review articles that examined ferritin and its association with COVID-19 severity. Based on all these articles and clinical experience, a review was constructed and full texts of the articles that were retrieved were accessed. RESULTS: All COVID-19 related studies conducted in 2020, which performed serum ferritin testing, clearly showed ferritin as a biomarker of COVID-19 severity in hospitalized patients. Ferritin levels in severe patients were significantly increased relative to those in non-severe patients (p < 0.001). Non-survivors had significantly higher ferritin levels than the survivors (p < 0.001). CONCLUSIONS: Determination of ferritin levels was specific and sensitive for early disease severity prediction in patients with COVID-19. Serum ferritin can also be used for predicting the response to COVID-19 vaccines.

Emphasizing the link between blood types in multi-ethnic disparities and COVID-19 infection in Makkah, Saudi Arabia.

OBJECTIVES: To analyze the impact and distribution of blood groups in different ethnicities and the extent of susceptibility to infection with COVID-19 in Makkah, Saudi Arabia. METHODS: A retrospective study was performed on 4,609 COVID-19 patients from five ethnic groups to assess the impact and distribution of different blood types and susceptibility to COVID-19 infection. The study was carried out between November 2020 and June 2021 in the College of Medicine, Umm Al-Qura University in collaboration with the General Directorate of Health Affairs, Makkah, Saudi Arabia. RESULTS: Blood group (A, B, and O) distributions in 2,617 COVID-19 patients with local control populations was done. Our study found that in both Saudi and non-Saudi populations, blood groups O and A were associated with higher infection rates, whereas blood group AB was associated with lower infection rates (p=0.0001). COVID-19 seems to be associated with blood groups A, B, and AB (RR=3.23, 95% CI=2.702-3.821, p=0.0001). COVID-19 risk was lower in people with O blood group (RR=0.783, 95% CI=0.733-0.836, p=0.0001). South Asians had higher odds of COVID-19 infection when compared to Saudi cases and other ethnic groups (OR=1.12, 95 % CI: 1.074-1.24, p=0.04). CONCLUSION: We emphasize that COVID-19 infection is not proportional among ethnically related blood groups. Notably, RhD-negative protect against COVID-19, whereas A and O blood types are more susceptible. Thus, when assessing COVID-19 prognosis and vaccination priority, blood groups A and O are critical.

Multiple Molecular Mechanisms to Overcome Multidrug Resistance in Cancer by Natural Secondary Metabolites.

Plant secondary metabolites (SMs) common natural occurrences and the significantly lower toxicities of many SM have led to the approaching development and use of these compounds as effective pharmaceutical agents; especially in cancer therapy. A combination of two or three of plant secondary metabolites together or of one SM with specific anticancer drugs, may synergistically decrease the doses needed, widen the chemotherapeutic window, mediate more effective cell growth inhibition, and avoid the side effects of high drug concentrations. In mixtures they can exert additive or even synergistic activities. Many SM can effectively increase the sensitivity of cancer cells to chemotherapy. In phytotherapy, secondary metabolites (SM) of medicinal plants can interact with single or multiple targets. The multi-molecular mechanisms of plant secondary metabolites to overcome multidrug resistance (MDR) are highlighted in this review. These mechanisms include interaction with membrane proteins such as P-glycoprotein (P-gp/MDR1); an ATP-binding cassette (ABC) transporter, nucleic acids (DNA, RNA), and induction of apoptosis. P-gp plays an important role in the development of MDR in cancer cells and is involved in potential chemotherapy failure. Therefore, the ingestion of dietary supplements, food or beverages containing secondary metabolites e.g., polyphenols or terpenoids may alter the bioavailability, therapeutic efficacy and safety of the drugs that are P-gp substrates.

Systematic Analysis of Spleen Tyrosine Kinase Expression and its Clinical Outcomes in Various Cancers.

BACKGROUND: Spleen tyrosine kinase (SYK) is an important enzyme in the proliferation and differentiation of all hematopoietic tissues. Its role as a cancer driver is well documented in liquid tumors; however, cumulative evidence has suggested an opposite role in other tumor types. OBJECTIVES: To systematically assess the expression of SYK, its prognostic value and epigenetic status in different cancers using bioinformatics tools. METHODS: In this bioinformatics study, Oncomine database and cBioPortal were used to study the SYK gene expression, Kaplan-Meier plotter to study its prognostic value and MethHC to assess the SYK gene methylation in various cancers. RESULTS: From 542 unique analyses of the SYK gene, it was found to be overexpressed in bladder, breast and colon cancers but downregulated in leukemia, lymphoma and myeloma. Compared with normal tissues, breast and brain tumors showed an overexpression of the SYK gene, whereas lymphoma and leukemia had lower expression. The Kaplan-Meier survival analysis revealed that SYK expression in pancreatic, gastric, liver and lung patients were correlated with better overall survival. Using cBioPortal, prostate cancer was found to have the highest SYK gene mutation frequency, and the mean expression was highest in diffuse large B-cell lymphoma, acute myeloid leukemia and thymoma. Using the MethHC database, SYK promoter hypermethylation was found to be significantly higher in breast, renal, liver, lung, pancreatic, prostatic, skin and stomach cancers compared with the normal tissue (P < 0.005). CONCLUSION: The results of this study indicate the potential use of SYK as a diagnostic and therapeutic target for different type of cancers. However, further experimental data are required to validate these results before use of SYK in clinical settings.

Mutation Frequencies in Endometrial Cancer Patients of Different Ethnicities and Tumor Grades: An Analytical Study.

BACKGROUND: Endometrial carcinoma is a predominant health problem for women worldwide. However, there is a lack of data on genetic mutation frequencies in endometrial cancer patients of different ethnicities and tumor grades. OBJECTIVE: The objective of this study is to provide data regarding mutation frequencies in endometrial cancer patients of different ethnic groups and tumor grades by analyzing large-scale cancer genomic datasets of a database. MATERIALS AND METHODS: The following databases of cBioPortal were explored for possible mutation frequency variations in endometrial cancer patients: the Uterine Corpus Endometrial Carcinoma (TCGA, PanCancer Atlas) database for ethnicity-based studies; the Uterine Corpus Endometrial Carcinoma (TCGA, Nature 2013) database for tumor grade-based study; and GDC Data Portal database for calculating survival rates using the Kaplan-Meier method. RESULTS: PTEN mutation frequency was almost identical in all ethnic groups studied (White, Black/African American, Asian, Native Hawaiian or other Pacific Islander, and American Indian or Asian Native). PIK3CA and ARID1A mutation frequencies were higher in White and Asian patients compared with other ethnicities; TP53 and FAT1 mutation frequencies were higher in Black/African Americans; and CTNNB1 and RYR2 mutation frequencies were higher Native Hawaiians or Asian Natives. TTN mutation frequency was lower in Asian patients. With regards to mutation frequencies at different tumor stages, in all genes, >50% of the mutations occurred during the first stage, except in TP53 and POLQ. In terms of prognosis in endometrial cancer considering the 10 most frequently mutated genes, PIK3CA and ARID1A mutations were correlated with good prognosis, whereas TP53 and PIK3R1 mutations were correlated with poor prognosis; mutations in all other genes did not show significant differences. CONCLUSION: This study revealed a new mutation frequency profile for different ethnicities and tumor grades in endometrial cancer patients. However, because this is a retrospective study, future prospective studies should be conducted including large sample sizes and more controlled measurements.

Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp.

Sinonasal polyps are very common benign lesions of the nasal mucosa. Most of nasal polyps (NP) are idiopathic, and the pathophysiology of this disease is still incompletely understood. Nitric oxide (NO) is a reactive molecule generated by nitric oxide synthase (NOS). NO has been identified as an important mediator in airway function and pathogenesis of several respiratory system diseases. Histological and genetical expression of iNOS was detected to evaluate the role of NO in the pathogenesis of allergic (ANP) and nonallergic nasal polyps (NANP). Forty patients with nasal polyps (20 allergic and 20 nonallergic) were identified by history, clinical examination, and investigation. NPs were obtained from the middle turbinate (MT) during concha bullosa surgery. Twenty normal MT nasal tissues were taken as the control from patients undergoing concha bullosa surgery, without any evidence of allergy or inflammation. A nasal polyp specimen from each patient was subjected for immune-histochemical study followed by histological examination to detect the expression of iNOS. RT-PCR was used to evaluate the iNOS gene expression in isolated tissues. The expression of iNOS in both epithelial and stromal layers was greater in NP than in MT tissues. The ANP group showed more iNOS expression than those of the NANP group. The relative mRNA levels of iNOS gene were significantly higher in ANP (2.5-fold) compared to the normal (1.02-fold, P < 0.001) and NANP (1.5-fold, P < 0.01) groups. NP exhibited a significantly high expression of iNOS at both histological and genetical levels. NO might be an essential factor in the life history of NP. Further studies in a larger sample size are required to explain the probable mechanisms of NO in pathogenesis of NP.

Trends in the incidence and mortality of cancer in Saudi Arabia.

OBJECTIVES: To analyze the overall trends in cancer incidence and mortality in Saudi Arabia between 1990 and 2016.   Methods: Data were retrieved through a Global Burden of Disease (GBD, 2016) database (Viz Hub) that is developed by the Institute for Health Metrics and Evaluation at the University of Washington. Results: The incidence of cancer increased around 26-fold for thyroid cancer; approximately 10-fold in breast, colon, bladder and uterine cancers; 8-fold for prostate cancer; 5-fold for renal cancer; 4-fold for pancreatic and ovarian cancer; 3.5-fold for lung cancer; 3-fold for liver cancer, and 2 folds for lymphoma, leukemia and gastric cancer. There was also an increase in the percentage of mortality due to cancer during this period. However, we noticed that the percentage of deaths due to cancer decreased after 70 years of age in Saudi Arabia population. Conclusion: The increases in the incidence of different types of cancer in the past decade could be due to the revolutionary change in socioeconomic status that has occurred in Saudi Arabia; therefore, a national plan should be established for cancer prevention, screening and therapy. Concerning mortality, the decrease in its percentage among elderly people could be due to biological factors that should be investigated in the future.