A Comprehensive Two-Decade Analysis of Lymphoma Incidence Patterns in Saudi Arabia.

Background: Lymphomas account for approximately 10% of all cancer cases among the Saudi population. Even when separated, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are in the top ten most commonly diagnosed cancers among Saudi men and women. Despite the substantial cost of HL and NHL to public health, the resources to assess their impact are insufficient. This study provides a two-decade detailed assessment of lymphoma incidence trends in the Saudi population. Methods: Analysis of the Saudi Cancer Registry (SCR) data for various incidence metrics from 2001 to 2020 was conducted. Joinpoint regression analysis was further performed to investigate temporal trends globally and by age group, gender, and administrative region. Results: HL cases grew by 174.1%, whereas NHL cases increased by only 80% for that time period. The HL overall Age-Standardized Incidence Rate (ASR) increased by 100% for both genders combined but remained unchanged for NHL. The median age at diagnosis for HL (20-30 years) and NHL (46-57 years) was lower than in many other nations. Our model identified increasing trends for HL with annual percentage changes (APCs) of 2.94% (CI: 2.2-3.7) and 3.67% (CI: 2.6-4.7) for males and females, respectively. The rise was mainly among young groups under 40. On the contrary, the NHL cohort revealed notable declining tendencies. We discovered alarming rates of HL in Saudi Arabia's APC (2.23% for males and 3.88% for females) and ASR compared to other Western countries. Overall, the majority of the patients presented with advanced-stage disease at a younger age and with slight male predominance. Conclusions: The overall incidence of lymphoma (especially HL) has been rising among Saudis. Implementation of secondary and tertiary prevention measures, as well as management of modifiable risk factors, is warranted.

Prevalence and association of hyperuricemia with liver function in Saudi Arabia: a large cross-sectional study.

BACKGROUND: Hyperuricemia is linked to an increased risk of various chronic diseases, but data on the prevalence and association of hyperuricemia with liver function in Saudi Arabia are scarce. OBJECTIVES: Evaluate the prevalence, association, and risk measures of hyperuricemia and liver function in the Saudi population. DESIGN: Retrospective, cross-sectional analysis. SETTING: Database on large portion of Saudi population. PATIENTS AND METHODS: Laboratory data, age, and gender of the studied subjects were collected from Al Borg Diagnostics. Subjects were stratified, based on their uric acid (UA) levels, into three groups: hypouricemic, normouricemic, and hyperuricemic. The association of UA with liver enzymes was examined in all three groups. MAIN OUTCOME MEASURES: Association of serum UA levels with alanine transaminase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). SAMPLE SIZE: 13 314 subjects. RESULTS: Our study showed that the prevalence of hyperuricemia in the Saudi population is 17.3% (20.3% in males and 15.1% in females). We also found a positive correlation between ALT, AST, and TB with UA levels. The risk of being hyperuricemic was significantly increased in individuals with elevated ALT, AST, and TB. Individuals with elevated ALT, AST, and total TB had a higher chance of having hyperuricemia than those with normal activity. Notably, ALT, AST, and TB had good discriminating capacity for hyperuricemia. CONCLUSIONS: Hyperuricemia is highly prevalent in the Saudi population and is associated with compromised liver function. However, further studies are needed to elucidate the mechanisms underlying these findings in large prospective cohort studies in different populations. LIMITATIONS: Lack of data on other potential confounding variables.

Bufalin reprograms erythrocyte lifespan through p38 MAPK and Rac1 GTPase.

Ample evidence indicates that bufalin (BFN), a cardiotonic steroid in Bufo toad toxin, possesses a potent anticancer activity mainly by stimulating apoptosis in cancer cells. Human red blood cells (RBCs) undergo eryptosis which contributes to a plethora of pathological conditions. No reports, however, have examined the potential toxicity of BFN to RBCs. This study aims to characterize the biochemical mechanisms governing the influence of BFN on the physiology and lifespan of RBCs. Isolated RBCs from healthy volunteers were exposed to anticancer concentrations of commercially available BFN from the skin of Bufo gargarizans (10-200 µM) for 24 h at 37 °C. Photometric assays were used to estimate hemolysis and hemolytic markers, and flow cytometry was used to detect eryptotic markers. Phosphatidylserine externalization was captured by fluorescein isothiocyante-labeled annexin V, cellular dimensions by light scatter patterns, and intracellular Ca2+ and reactive oxygen species (ROS) by fluorogenic dyes Fluo4/AM and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), respectively. BFN caused Ca2+-independent hemolysis and release of LDH, AST, CK, and K+, and increased annexin V-bound cells, cytosolic Ca2+, cell shrinkage, and ROS levels. BFN also disrupted Na+ and Mg2+ trafficking, and was sensitive to PEG 8000, sucrose, SB203580, and NSC 23766. In whole blood, BFN depleted hemoglobin stores, increased fragmented RBCs, and was selectively toxic to reticulocytes, lymphocytes, and platelets. In conclusion, BFN elicits premature RBC death, subject to regulation by p38 MAPK and Rac1 GTPase, and is detrimental to other peripheral blood cells. Altogether, these novel findings prompt cautious consideration of the toxin in anticancer therapy.

Rosmarinic Acid Elicits Calcium-Dependent and Sucrose-Sensitive Eryptosis and Hemolysis through p38 MAPK, CK1α, and PKC.

BACKGROUND: Rosmarinic acid (RA) possesses promising anticancer potential, but further development of chemotherapeutic agents is hindered by their toxicity to off-target tissue. In particular, chemotherapy-related anemia is a major obstacle in cancer therapy, which may be aggravated by hemolysis and eryptosis. This work presents a toxicity assessment of RA in human RBCs and explores associated molecular mechanisms. METHODS: RBCs isolated from healthy donors were treated with anticancer concentrations of RA (10-800 µM) for 24 h at 37 °C, and hemolysis and related markers were photometrically measured. Flow cytometry was used to detect canonical markers of eryptosis, including phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, cell size by FSC, and oxidative stress by H2DCFDA. Ions and pH were assessed by an ion-selective electrode, while B12 was detected by chemiluminescence. RESULTS: RA elicited concentration-dependent hemolysis with AST and LDH release but rescued the cells from hypotonic lysis at sub-hemolytic concentrations. RA also significantly increased annexin-V-positive cells, which was ameliorated by extracellular Ca2+ removal and isosmotic sucrose. Furthermore, a significant increase in Fluo4-positive cells and B12 content and a decrease in FSC and extracellular pH with KCl efflux were noted upon RA treatment. Hemolysis was augmented by blocking KCl efflux and was blunted by ATP, SB203580, staurosporin, D4476, isosmotic urea, and PEG 8000. CONCLUSIONS: RA stimulates Ca2+-dependent and sucrose-sensitive hemolysis and eryptosis characterized by PS exposure, Ca2+ accumulation, loss of ionic regulation, and cell shrinkage. These toxic effects were mediated through energy deprivation, p38 MAPK, protein kinase C, and casein kinase 1α.

Eriocitrin Disrupts Erythrocyte Membrane Asymmetry through Oxidative Stress and Calcium Signaling and the Activation of Casein Kinase 1α and Rac1 GTPase.

BACKGROUND: Hemolysis and eryptosis result in the premature elimination of circulating erythrocytes and thus contribute to chemotherapy-related anemia, which is extremely prevalent in cancer patients. Eriocitrin (ERN), a flavanone glycoside in citrus fruits, has shown great promise as an anticancer agent, but the potential toxicity of ERN to human erythrocytes remains unstudied. METHODS: Erythrocytes were exposed to anticancer concentrations of ERN (10-100 µM) for 24 h at 37 °C, and hemolysis and associated markers were quantified using colorimetric assays. Eryptosis was assessed by flow cytometric analysis to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ using Fluo4/AM, and oxidative stress with 2-,7-dichlorodihydrofluorescin diacetate (H2DCFDA). ERN was also tested against specific signaling inhibitors and anti-hemolytic agents. RESULTS: ERN caused significant, concentration-dependent hemolysis at 20-100 µM. ERN also significantly increased the percentage of eryptotic cells characterized by Ca2+ elevation and oxidative stress. Furthermore, the hemolytic activity of ERN was significantly ameliorated in the presence of D4476, NSC23766, isosmotic urea and sucrose, and polyethylene glycol 8000 (PEG). In whole blood, ERN significantly elevated MCV and ESR, with no appreciable effects on other peripheral blood cells. CONCLUSIONS: ERN promotes premature erythrocyte death through hemolysis and eryptosis characterized by PS externalization, Ca2+ accumulation, membrane blebbing, loss of cellular volume, and oxidative stress. These toxic effects, mediated through casein kinase 1α and Rac1 GTPase, can be ameliorated by urea, sucrose, and PEG. Altogether, these novel findings are relevant to the further development of ERN as an anticancer therapeutic.

Stimulation of Hemolysis and Eryptosis by ß-Caryophyllene Oxide.

BACKGROUND: Eryptosis stimulated by anticancer drugs can lead to anemia in patients. ß-caryophyllene oxide (CPO) is an anticancer sesquiterpene present in various plants; however, its effect on the structure and function of human red blood cells (RBCs) remains unexplored. The aim of this study was to investigate the hemolytic and eryptotic activities and underlying molecular mechanisms of CPO in human RBCs. METHODS: Cells were treated with 10-100 µM of CPO for 24 h at 37 °C, and hemolysis, LDH, AST, and AChE activities were photometrically assayed. Flow cytometry was employed to determine changes in cell volume from FSC, phosphatidylserine (PS) externalization by annexin-V-FITC, intracellular calcium by Fluo4/AM, and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). Cells were also cotreated with CPO and specific signaling inhibitors and antihemolytic agents. Furthermore, whole blood was exposed to CPO to assess its toxicity to other peripheral blood cells. RESULTS: CPO induced concentration-responsive hemolysis with LDH and AST leakage, in addition to PS exposure, cell shrinkage, Ca2+ accumulation, oxidative stress, and reduced AChE activity. The toxicity of CPO was ameliorated by D4476, staurosporin, and necrosulfonamide. ATP and PEG 8000 protected the cells from hemolysis, while urea and isotonic sucrose had opposite effects. CONCLUSIONS: CPO stimulates hemolysis and eryptosis through energy depletion, Ca2+ buildup, oxidative stress, and the signaling mediators casein kinase 1α, protein kinase C, and mixed lineage kinase domain-like pseudokinase. Development of CPO as an anticancer therapeutic must be approached with prudence to mitigate adverse effects on RBCs using eryptosis inhibitors, Ca2+ channel blockers, and antioxidants.

Comprehensive Retrospective Analysis of Colorectal Cancer Incidence Patterns in Saudi Arabia.

Colorectal cancer (CRC) is the commonest cancer in Saudi males and the third most common in Saudi females. Although CRC represents a major public health challenge, the resources to evaluate its burden are inadequate. This study aims to elucidate the magnitude of CRC incidence trends in the Saudi population by age, gender, and administrative region. Data for multiple incidence measures were analyzed from the Saudi Cancer Registry (SCR) retrospectively from 2001 to 2018. Temporal trends were further analyzed by age group, gender, administrative region, and globally using joinpoint regression analysis. The number of CRC cases climbed by 335.6% and the disease increased by 56.4% to comprise 12.2% of all cancers cases. The age-standardized incidence rate (ASR) increased by 152% overall, and the median age at diagnosis peaked at 60 and 58 years for males and females, respectively. Riyadh and the Eastern Region had the highest ASR for both genders, peaking at 21.8 and 19.2 for males and 17.4 and 16.5 for females per 100 K population. Our prediction model identified growing trends with annual percentage changes (APCs) of 4.59% in males (CI: 3.1-6.1) and 3.91% among females (CI: 2.4-5.5). Males above 75 years had the highest APC (7.9%, CI: 5.3-10.7), whereas the highest APC among females was found in the age group 70-74 (5.4%, CI: 2.8-8). Globally, APC was the highest for both genders compared to selected countries. CRC incidence is increasing alarmingly in Saudi Arabia and is projected to continue. There is a need for better screening strategies, preventative measures, and awareness-building.

Association of the HALP Score with Dyslipidemia: A Large, Nationwide Retrospective Study.

Background and Objectives: Dyslipidemia is a major risk factor for cardiovascular disease (CVD). The identification of new biomarkers that may enhance the risk assessment of lipid abnormalities is a promising approach in improving risk prediction of CVD. There is no information on the association of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score with dyslipidemia. The aim of this study was to investigate the clinical utility of the HALP score in light of dyslipidemia. Materials and Methods: A retrospective analysis of 7192 subjects was initiated to assess the association between the HALP score and disturbed lipid markers. Medians were compared by Mann-Whitney U or Kruskal-Wallis tests and the diagnostic performance and risk assessment were calculated. Results: Median HALP score among all subjects was 53.3, with varying values between males and females. Notably, median HALP was significantly elevated in all forms of dyslipidemia and among males and females irrespective of age. The odds of having elevated HALP score values were significantly higher in all lipid abnormalities. Moreover, HALP score was significantly yet weakly correlated with lipid markers, while the highest diagnostic accuracy of the HALP score was observed with an elevated ratio of total cholesterol to high-density lipoprotein (TC/HDL) (area under the curve, AUC = 0.6411, p < 0.0001). The decision curve analysis (DCA) showed that the HALP score can reliably predict the presence of dyslipidemia. Conclusions: This study demonstrates that the HALP score is a novel, cost-effective index that is associated with a disturbed lipid profile. Further investigation of the nature of this association is needed.

Tamoxifen induces eryptosis through calcium accumulation and oxidative stress.

Chemotherapy-related anemia is a major obstacle in anticancer therapy. Tamoxifen (TAM) is an antiestrogen prescribed for breast cancer patients with hemolytic potential and apoptotic properties in nucleated cells. However, the eryptotic activity of TAM has hitherto escaped the efforts of investigators. RBCs from apparently healthy volunteers were treated with 1-50 µM of TAM for 24 h at 37 °C. Hemoglobin leakage and LDH, AST, and AChE activities were photometrically determined while K+, Na+, and Mg2+ were detected by ion-selective electrode. Flow cytometry was used to identify eryptotic cells by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, sell size and morphology by FSC and SSC signals, respectively, and oxidative stress by H2DCFDA. Whole blood was also exposed to 30 µM of TAM for 24 h at 37 °C to examine the toxicity of TAM to WBCs and platelets. TAM caused Ca2+-independent, dose-responsive hemolysis accompanied by K+, LDH, and AST leakage without improving the mechanical stability of RBCs in hypotonic environments. TAM treatment also increased the proportion of cells positive for annexin-V-FITC, Fluo4, and DCF, along with diminished FSC and SSC signals and AChE activity. Notably, TAM toxicity was aggravated by sucrose but abrogated by vitamin C, PEG 8000, and urea. Moreover, TAM exhibited distinct cytotoxic profiles against leukocytes and platelets. TAM-induced eryptosis is characterized by breakdown of membrane asymmetry, inhibition of AChE activity, Ca2+ accumulation, cell shrinkage, and oxidative stress. Vitamin C, PEG 8000, and urea may hold promise to subvert the undesirable toxic effects of TAM on RBCs.

AST and ALT APRI Scores and Dysglycemia in Saudi Arabia: A Retrospective Population Study.

BACKGROUND: Hyperglycemia is a common symptom of numerous conditions, most notably diabetes mellitus and Cushing's syndrome, and the liver plays a pivotal role in the regulation of glucose metabolism. The AST-platelet ratio index (AST APRI score) and ALT-platelet ratio index (ALT APRI score) are novel parameters whose association with circulating glucose levels remains poorly studied. METHODS: Laboratory data of 14,177 subjects were retrospectively analyzed for the association between AST and ALT APRI scores and fasting blood glucose (FBG) using the Mann-Whitney U and Kruskal-Wallis tests, Spearman's rank correlation coefficient, prevalence and odds ratio (OR) and ROC curve analysis. RESULTS: AST and ALT APRI scores showed progressive increases with FBG, and the mean FBG was significantly higher in subjects with high AST (104.9 ± 0.33 to 120.8 ± 3.27, p < 0.0001) and ALT (104.7 ± 0.34 to 111.6 ± 1.30, p < 0.0001) APRI scores. However, the AST APRI score but not the ALT APRI score was affected by age and gender. Notably, both elevated AST and ALT APRI scores were more prevalent in hyperglycemic subjects irrespective of gender and were associated with FBG, albeit through mediator variables. Increased AST (OR = 2.55, 95% CI: 1.46-2.06, p < 0.0001) and ALT (OR = 1.73, 95% CI: 1.46-2.06, p < 0.0001) APRI scores carried a significantly higher risk for hyperglycemia. Importantly, the ALT APRI score was superior to that of the AST APRI score in distinguishing hyperglycemic subjects. CONCLUSIONS: The AST and ALT APRI scores are inexpensive, novel markers of FBG and may serve as supportive evidence in the diagnosis and management of hyperglycemic conditions.

A Retrospective Analysis of the Association of Neutrophil-Lymphocyte Ratio (NLR) with Anemia in the Saudi Population.

Background: The link between inflammation and anemia is well established but fluctuations in the emerging inflammatory index, neutrophil-lymphocyte ratio (NLR), in anemic subjects remain ambiguous. The purpose of this study is to address the prevailing knowledge gaps regarding the association of NLR with anemia in the Saudi population. Methods: Laboratory results of NLR, C-reactive protein (CRP), and hemoglobin for 14,261 subjects were obtained from Al Borg Diagnostics and retrospectively analyzed. Means, risk measures, and the diagnostic performance of NLR for anemia were examined in age- and gender-wise comparisons. Results: NLR was significantly elevated in anemic individuals and those with high NLR had a significantly lower Hb concentration. Moreover, elevated NLR was more prevalent in anemic subjects (PR: 1.87, 95% CI: 1.46-2.40, p < 0.0001) and carried a greater risk for the condition (OR: 1.91, 95% CI: 1.47-2.48, p < 0.0001) as did CRP. These observations demonstrated distinct age- and gender-specific patterns. However, both parameters were of no value in the diagnosis of anemia as seen from receiver operating characteristic curves. Conclusions: Altogether, these findings indicate that elevated NLR is associated with anemia, which suggests its usefulness for monitoring rather than diagnosing anemia associated with inflammation in Saudi subjects. Further examination of this association in longitudinal studies is needed.

Stimulation of Hemolysis and Eryptosis by α-Mangostin through Rac1 GTPase and Oxidative Injury in Human Red Blood Cells.

BACKGROUND: Chemotherapy-related anemia is prevalent in up to 75% of patients, which may arise due to hemolysis and eryptosis. Alpha-mangostin (α-MG) is a polyphenolic xanthonoid found in the mangosteen tree (Garcinia mangostana) whose antitumor medicinal properties are well-established. Nevertheless, the potential toxic effects of α-MG on red blood cells (RBCs) have, as of yet, not been as well studied. METHODS: RBCs were exposed to 1-40 µM of α-MG for 24 h at 37 °C. Hemolysis and related markers were measured using colorimetric assays, eryptotic cells were identified through Annexin-V-FITC, Ca2+ was detected with Fluo4/AM, and oxidative stress was assessed through H2DCFDA using flow cytometry. The toxicity of α-MG was also examined in the presence of specific signal transduction inhibitors and in whole blood. RESULTS: α-MG at 10-40 µM caused dose-dependent hemolysis with concurrent significant elevation in K+, Mg2+, and LDH leakage, but at 2.5 µM it significantly increased the osmotic resistance of cells. A significant increase was also noted in Annexin-V-binding cells, along with intracellular Ca2+, oxidative stress, and cell shrinkage. Moreover, acetylcholinesterase activity was significantly inhibited by α-MG, whose hemolytic potential was significantly ameliorated by the presence of BAPTA-AM, vitamin C, NSC23766, and isosmotic sucrose but not urea. In whole blood, α-MG significantly depleted intracellular hemoglobin stores and was selectively toxic to platelets and monocytes. CONCLUSIONS: α-MG possesses hemolytic and eryptotic activities mediated through Ca2+ signaling, Rac1 GTPase activity, and oxidative injury. Also, α-MG leads to accelerated cellular aging and specifically targets platelet and monocyte populations in a whole blood milieu.

Metabolic exhaustion and casein kinase 1α drive deguelin-induced premature red blood cell death.

1. Deguelin (DGN), a retinoid isolated from many plants, exhibits a potent anticancer activity against a wide spectrum of tumour cells. There is a dearth of evidence, however, regarding the toxicity of DGN to red blood cells (RBCs). This is relevant given the prevalent chemotherapy-associated anaemia observed in cancer patients.2. RBCs were exposed to 1-100 µM of DGN for 24 h at 37 °C. Haemolysis and related markers were photometrically measured while flow cytometry was employed to detect phosphatidylserine exposure through Annexin-V-FITC binding and light scatter properties. Additionally, cytosolic Ca2+ and reactive oxygen species were quantified using Fluo4/AM and H2DCFDA, respectively. DGN was also tested against specific signalling inhibitors in addition to vitamin C and ATP.3. DGN caused a significant increase in Annexin-V-positive cells which was accompanied by cell shrinkage without Ca2+ elevation or oxidative stress. DGN also elicited dose-responsive haemolysis which was ameliorated by preventing KCl efflux and in the presence of sucrose, D4476, and ATP. In whole blood, DGN significantly reduced the reticulocyte count and increased platelet distribution width and large cell count.4. DGN triggers premature RBC eryptosis and haemolysis through casein kinase 1α and ATP depletion, and exhibits a specific toxicity towards reticulocytes and platelets.

Association of Platelet-Monocyte Ratio with Dyslipidemia in Saudi Arabia: A Large, Population-Based Study.

BACKGROUND: Abnormal lipid metabolism predisposes to cardiovascular disease. However, dyslipidemia is often asymptomatic leading to its underdiagnosis. Therefore, it is of utmost importance to identify biomarkers that reflect an abnormal lipid profile and trigger the specific investigation of lipid metabolism. The platelet-monocyte ratio (PMR) is a severely understudied index whose association with disturbed lipid markers remains unknown. METHODS: A cross-sectional study of the association between PMR and comprehensive lipid profile including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), TC/HDL, LDL/HDL, and TG/HDL in 14,269 Saudi subjects was designed. Prevalence, risk measures, association, and the diagnostic performance (i.e., area under the curve (AUC)) were evaluated. RESULTS: Median PMR was significantly elevated in subjects with high TC (p < 0.01), TG, TC/HDL, LDL/HDL, TG/HDL, and LDL and reduced in those with low HDL (all p < 0.0001) compared to normal subjects. The increase in PMR was abolished when only males with high TC were considered. Except for TC and LDL, all other abnormal markers were significantly more prevalent when PMR was lower (higher for HDL) than a certain cutoff specific for each parameter. Moreover, the odds of having PMR readings above or below the selected cutoffs are significantly higher with all lipid abnormalities. PMR was also weakly but significantly and differentially correlated with all forms of dyslipidemia (p < 0.0001). Notably, the highest diagnostic accuracy of PMR was observed for reduced HDL (AUC = 0.608, p < 0.0001) and elevated TG/HDL (AUC = 0.596, p < 0.0001). CONCLUSIONS: PMR is a novel, inexpensive, and readily available index that is associated with all forms of dyslipidemia, suggesting its potential use in related disorders.

Shared and Distinct Gut Microbial Profiles in Saudi Women with Metabolically Healthy and Unhealthy Obesity.

BACKGROUND: Mounting evidence suggests a pivotal role for the gut microbiome in energy disequilibrium characteristic of obesity. The clinical utility of microbial profiling for the distinction between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) remains ill-defined. We aim to probe microbial composition and diversity in young adult Saudi females with MHO and MUO. This observational study included anthropometric and biochemical measurements and shotgun sequencing of stool DNA for 92 subjects. α- and ß-diversity metrics were calculated to determine the richness and variability in microbial communities, respectively. Results showed that Bacteroides and Bifidobacterium merycicum were less abundant in MUO compared to healthy and MHO groups. BMI was negatively correlated with B. adolescentis, B. longum, and Actinobacteria in MHO, while being positively correlated with Bacteroides thetaiotaomicron in both MHO and MUO. Positive correlations between waist circumference and B. merycicum and B. thetaiotaomicron were observed in MHO and MUO, respectively. Compared to MHO and MUO groups, higher α-diversity was detected in healthy individuals who also had higher ß-diversity compared to those with MHO. We conclude that modulation of the gut microbiome cohorts through prebiotics, probiotics, and fecal microbiota transplantation may be a promising preventive and therapeutic approach to obesity-associated disease.

Metagenomic Shotgun Sequencing Reveals Specific Human Gut Microbiota Associated with Insulin Resistance and Body Fat Distribution in Saudi Women.

(1) Background: Gut microbiota dysbiosis may lead to diseases such as insulin resistance and obesity. We aimed to investigate the relationship between insulin resistance, body fat distribution, and gut microbiota composition. (2) Methods: The present study included 92 Saudi women (18-25 years) with obesity (body mass index (BMI) ≥ 30 kg/m2, n = 44) and with normal weight (BMI 18.50-24.99 kg/m2, n = 48). Body composition indices, biochemical data, and stool samples were collected. The whole-genome shotgun sequencing technique was used to analyze the gut microbiota. Participants were divided into subgroups stratified by the homeostatic model assessment for insulin resistance (HOMA-IR) and other adiposity indices. (3) Results: HOMA-IR was inversely correlated with Actinobacteria (r = -0.31, p = 0.003), fasting blood glucose was inversely correlated with Bifidobacterium kashiwanohense (r = -0.22, p = 0.03), and insulin was inversely correlated with Bifidobacterium adolescentis (r = -0.22, p = 0.04). There were significant differences in α- and ß-diversities in those with high HOMA-IR and waist-hip ratio (WHR) compared to low HOMA-IR and WHR (p = 0.02, 0.03, respectively). (4) Conclusions: Our findings highlight the relationship between specific gut microbiota at different taxonomic levels and measures of glycemic control in Saudi Arabian women. Future studies are required to determine the role of the identified strains in the development of insulin resistance.

Antibacterial and Antibiofilm Activities of ß-Lapachone by Modulating the Catalase Enzyme.

BACKGROUND: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of ß-Lapachone (ß-Lap), a novel synthetic compound. METHODS: The antibacterial activity of the ß-Lap compound was examined against laboratory strains by agar well diffusion method and broth dilution assay. Growth kinetics in presence of ß-Lap on Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa (ATCC 27853) were assessed by microplate alamarBlue assay. Crystal violet blue assay was used for biofilm inhibition and biofilm eradication. P. aeruginosa catalase (KatA) complexed with ß-Lap was modeled using molecular docking approach. RESULTS: ß-Lap exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Bioinformatics analysis suggests that ß-Lap can inhibit KatA activity by interacting with catalase proximal active site and heme binding site. The activity of some commercial antibiotics was enhanced in association with ß-Lap. In addition, ß-Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains. CONCLUSION: These observations indicated that ß-Lap could be a promising antibacterial agent for the treatment and prevention of infectious diseases.

Molecular Mechanisms and Pathophysiological Significance of Eryptosis.

Despite lacking the central apoptotic machinery, senescent or damaged RBCs can undergo an unusual apoptosis-like cell death, termed eryptosis. This premature death can be caused by, or a symptom of, a wide range of diseases. However, various adverse conditions, xenobiotics, and endogenous mediators have also been recognized as triggers and inhibitors of eryptosis. Eukaryotic RBCs are unique among their cell membrane distribution of phospholipids. The change in the RBC membrane composition of the outer leaflet occurs in a variety of diseases, including sickle cell disease, renal diseases, leukemia, Parkinson's disease, and diabetes. Eryptotic erythrocytes exhibit various morphological alterations such as shrinkage, swelling, and increased granulation. Biochemical changes include cytosolic Ca2+ increase, oxidative stress, stimulation of caspases, metabolic exhaustion, and ceramide accumulation. Eryptosis is an effective mechanism for the elimination of dysfunctional erythrocytes due to senescence, infection, or injury to prevent hemolysis. Nevertheless, excessive eryptosis is associated with multiple pathologies, most notably anemia, abnormal microcirculation, and prothrombotic risk; all of which contribute to the pathogenesis of several diseases. In this review, we provide an overview of the molecular mechanisms, physiological and pathophysiological relevance of eryptosis, as well as the potential role of natural and synthetic compounds in modulating RBC survival and death.

Blood indices of omega-3 and omega-6 polyunsaturated fatty acids are altered in hyperglycemia.

Polyunsaturated fatty acids (PUFAs) may favorably influence the risk and clinical course of diabetes mellitus (DM). In particular, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) alleviate oxidative injury and insulin resistance characteristic of DM. Uncertainty still remains, however, as to the composition and proportions of blood PUFAs in relation to fasting blood glucose levels. This study, thus, aims to examine the patterns of blood PUFA indices in normoglycemic (NG) and hyperglycemic (HG) Saudi subjects. Age, gender, FA profiles, and laboratory records of 143 subjects collected from September 2014 to March 2018 were retrospectively analyzed. Means, prevalence rates, associations, risk measures, and the diagnostic accuracy of PUFAs were determined. HG subjects had significantly lower AA (0.70%, 95% CI: 0.59-0.80% vs 0.46%, 95% CI: 0.38-0.53%) and higher EPA/AA ratio (0.36, 95% CI: 0.30-0.42 vs 0.69, 95% CI: 0.61-0.77). Gender-wise comparisons revealed that ώ-6/ώ-3 ratio was the only PUFA index significantly elevated in HG males (0.36, 95% CI: 0.26-0.45 vs 5.68, 95% CI: 4.98-6.38) while both DHA (2.91%, 95% CI: 2.54-3.29% vs 3.37%, 95% CI: 3.13-3.60%) and ώ-3 index (3.1%, 95% CI: 2.70-3.49% vs 3.63%, 95% CI: 3.38-3.88%) were significantly elevated in HG females. Furthermore, reduced AA and elevated EPA/AA ratio were more prevalent in HG subjects (26.53 vs 28.72 and 30.61 vs 38.29, respectively) and exhibited the highest diagnostic accuracy for HG among all PUFA indices. Altogether, our study revealed that distinct, gender-specific blood PUFA indices are differentially regulated in HG subjects which may be valuable for DM management.