Xylitol is prothrombotic and associated with cardiovascular risk.

BACKGROUND AND AIMS: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute. METHODS: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10). RESULTS: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects. CONCLUSIONS: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.

Microhardness and Gloss of a New CAD/CAM Hybrid Material Following Accelerated Aging and Coffee Immersion.

PURPOSE: To evaluate and compare the effect of accelerated aging and coffee immersion on the microhardness and gloss of a new computer-aided design and computer-aided manufacturing (CAD/CAM) hybrid material (Crystal Ultra) to those of contemporary restorative materials. MATERIALS AND METHODS: A total of 160 specimens (12 × 14 × 1 mm ± 0.05 mm) were obtained from IPS e.max (IPS), VITA Enamic (VE), Crystal Ultra (CU), Lava Ultimate (LU), and CeraSmart (CS) high-translucency CAD/CAM blocks. The Vickers microhardness and gloss of the specimens were determined after thermocycling and coffee immersion. Data analysis was performed using SPSS (α = .05). RESULTS: IPS and CS specimens exhibited the highest (572.66 ± 11.30) and lowest (61.92 ± 3.91) microhardness, respectively. The highest gloss was observed with IPS specimens (3.31 ± 0.32), and LU specimens showed the lowest gloss (2.33 ± 0.06). A significant difference in gloss was observed between the materials at all measurement intervals (P < .01), except at T0 (P = .43). IPS specimens showed no significant changes in either group at any measurement interval. CONCLUSIONS: The microhardness and gloss of the new CU material were comparable to those of the tested contemporary hybrid restorative materials. Glass-ceramic showed superior hardness and gloss compared to hybrid restorative materials. Accelerated aging with thermocycling and staining significantly affected the microhardness and gloss of all tested CAD/CAM materials.

Angiotensin II modulates THP-1-like macrophage phenotype and inflammatory signatures via angiotensin II type 1 receptor.

Angiotensin II (Ang II) is a major component of the renin-angiotensin or renin-angiotensin-aldosterone system, which is the main element found to be involved in cardiopathology. Recently, long-term metabolomics studies have linked high levels of angiotensin plasma to inflammatory conditions such as coronary heart disease, obesity, and type 2 diabetes. Monocyte/macrophage cellular function and phenotype orchestrate the inflammatory response in various pathological conditions, most notably cardiometabolic disease. An activation of the Ang II system is usually associated with inflammation and cardiovascular disease; however, the direct effect on monocyte/macrophages has still not been well elucidated. Herein, we have evaluated the cellular effects of Ang II on THP-1-derived macrophages. Ang II stimulated the expression of markers involved in monocyte/macrophage cell differentiation (e.g., CD116), as well as adhesion, cell-cell interaction, chemotaxis, and phagocytosis (CD15, CD44, CD33, and CD49F). Yet, Ang II increased the expression of proinflammatory markers (HLA-DR, TNF-α, CD64, CD11c, and CD38) and decreased CD206 (mannose receptor), an M2 marker. Moreover, Ang II induced cytosolic calcium overload, increased reactive oxygen species, and arrested cells in the G1 phase. Most of these effects were induced via the angiotensin II type 1 receptor (AT1R). Collectively, our results provide new evidence in support of the effect of Ang II in inflammation associated with cardiometabolic diseases.

Prevalence of internalized stigma in patients with psychiatric illness in Abha, Southern Region, Saudi Arabia.

BACKGROUND: Mental stigma occurs when patients with various mental disorders are labeled by their disorders. Little is known about the burden of mental stigma on patients with mental disorders. The aim of this study was to evaluate the incidence of mental stigma on patients with psychiatric disorder in Saudi Arabia. MATERIALS AND METHODS: This cross-sectional study was conducted among previously diagnosed patients with any psychiatric disorder attending King Khalid Hospital, Abha, Saudi Arabia. The patients were interviewed with a sociodemographic questionnaire and a validated Arabic version of the Internalized Stigma of Mental Illness (ISMI-29) scale. Chi-square test and t-test were used to assess the association between various demographic characteristics and presence of stigma. RESULTS: The study included 489 patients with different psychiatric disorders. The mean age of the participants was 32.8 years and 54.6% were females. About 39% participants showed no to minimal internalized stigma, 37.4% of total sample had mild stigma, 20% had moderate stigma, and 3.7% had severe stigma. A signficantly higher proportion (71.4%) of widowed patients had stigma (P = 0.032). CONCLUSION: Self-stigma is prevalent among patients with psychiatric disorders in Abha, Saudi Arabia, but lower than the prevalence in developing countries. Marital status has a significant impact on the prevalence and severity of the self-stigma of patients. There is a need for awareness program to reduce self-stigma. Psychiatric institutions should also focus on promotion of patients' social life and increase patient's awareness of certain issues that could prevent stigma.

Effect of Gender on Postoperative Outcome and Duration of Ventilation After Coronary Artery Bypass Grafting (CABG).

INTRODUCTION: The study assessed coronary artery bypass grafting (CABG) postoperative outcomes and associated factors in Saudi male and female patients. This was a retrospective cohort of patients who underwent CABG at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, from January 2015 to December 2022.  Results: We included 392 patients, of whom 63 (16.1%) were female. Female undergoing CABG were significantly older (p=0.0001), had a significantly higher incidence of diabetes (p=0.0001), obesity (p=0.001), hypertension (p=0.001), and congestive heart failure (p=0.005), with a smaller body surface area (BSA) (p=0.0001) than male. Though renal dysfunction, previous cerebrovascular accident/transient ischemic attack (CVA/TIA), and myocardial infarction (MI), incidences were similar in both genders. Females were at significantly higher risk of mortality (p=0.0001), longer hospital stay (p=0.0001), and prolonged ventilation (p=0.0001). Preoperative renal dysfunction was the only statistically significant predictor of postoperative complications (p=0.0001). Female gender and preoperative renal dysfunction, were significant independent predictors of postoperative mortality and prolonged ventilation (p=0.005). CONCLUSION: This study's findings indicated that females have worse CABG outcomes and a higher risk of morbidities and complications. Uniquely our study showed a higher incidence of prolonged ventilation in females postoperatively.

Quantitative proteomics analysis of COVID-19 patients: Fetuin-A and tetranectin as potential modulators of innate immune responses.

Treatment of severe cases of coronavirus disease 2019 (COVID-19) is extremely important to minimize death and end-organ damage. Here we performed a proteomic analysis of plasma samples from mild, moderate and severe COVID-19 patients. Analysis revealed differentially expressed proteins and different therapeutic potential targets related to innate immune responses such as fetuin-A, tetranectin (TN) and paraoxonase-1 (PON1). Furthermore, protein changes in plasma showed dysregulation of complement and coagulation cascades in COVID-19 patients compared to healthy controls. In conclusion, our proteomics data suggested fetuin-A and TN as potential targets that might be used for diagnosis as well as signatures for a better understanding of the pathogenesis of COVID-19 disease.

Assessing the relationship between burnout syndrome and irritable bowel syndrome among medical health providers and medical students in Saudi Arabia.

Burnout syndrome, characterized by chronic unmanageable workplace stress, has been linked to lower gastrointestinal disorders, including irritable bowel syndrome. However, the relationship between burnout syndrome and irritable bowel syndrome among medical health providers and medical students in Saudi Arabia has not been fully explored. This cross-sectional correlational study was conducted in Southern Saudi Arabia from 2021 to 2022 and involved 931 medical health providers and medical students who completed an electronic questionnaire. The study assessed the presence and severity of burnout and irritable bowel syndrome and examined their relationship. Burnout syndrome was evaluated using the Maslach Burnout Inventory-Student Survey (MBI-SS), while irritable bowel syndrome criteria and severity were assessed using validated tools. The study found that 85% of medical health providers and medical students experienced high levels of burnout and irritable bowel syndrome severity, with physicians and nurses mainly affected. Occupational exhaustion was high in 44.4% of participants, while depersonalization was high in 53% of participants. Personal accomplishment was low in 73.5% of participants. Mild, moderate, and severe irritable bowel syndrome was reported in 25.6%, 23.8%, and 12% of participants, respectively. The study highlights a significant association between burnout syndrome and irritable bowel syndrome severity among medical health providers and medical students in Saudi Arabia. These findings underscore the importance of developing effective interventions to prevent and manage burnout syndrome and related health issues among healthcare professionals and medical students in the region.

The artificial sweetener erythritol and cardiovascular event risk.

Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200 ), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200 ) and European (n = 833, DRKS00020915 ) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18-2.77) and 2.21 (1.20-4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study ( NCT04731363 ), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.

The Intersection of Health Rehabilitation Services with Quality of Life in Saudi Arabia: Current Status and Future Needs.

Quality of life (QoL) is essential for maintaining a healthy, balanced lifestyle, especially among individuals with chronic diseases. Saudi Arabia (SA) launched a health sector transformation program as part of the nationwide Vision 2030 initiative to ensure the sustainable development of efficient healthcare services, aiming to improve health by increasing well-being and QoL. More investigation into the current status of health rehabilitation services provided to individuals with chronic diseases and future needs to optimize services and improve QoL is needed. This was narratively discussed by experts from different health rehabilitation services in SA. Comprehensive health rehabilitation services including orthopedic, occupational, cardiac, pulmonary, critical care, perioperative, hearing and speech, substance use disorders, and vocational rehabilitation services were addressed. Health rehabilitation services in SA, as in other countries, are suboptimal for individuals in health rehabilitation programs. To optimize the QoL of individuals with chronic diseases, health rehabilitation services should be tailored based on the unique requirements of each service and its serving patients. The shared need to improve health rehabilitation services includes the adoption of home-based and telehealth services, the integration of multi-governmental sectors, the empowerment and allocation of health rehabilitation specialists, public awareness campaigns, policy legislation and guideline development, and the implementation of a long-term follow-up system. This review is one of the first to address the intersection of health rehabilitation services and QoL in SA; urgent and holistic actions are paramount to address the pressing need to optimize SA's health rehabilitation services. The experts' recommendations in this study may be applicable to other countries' health systems, as health rehabilitation services are not well optimized globally.

Patterns of Dyslipidemia in the Anemic and Nonanemic Hypertensive Saudi Population: A Cross-Sectional Study.

Background: Risk factors of cardiovascular disease include dyslipidemia, hypertension (HTN), and anemia. Our objective is to assess the patterns of dyslipidemia in the anemic and non-anemic hypertensive Saudi population. Methods: A retrospective, cross-sectional study of the gender, blood pressure, lipid markers, and CBC parameters of 3111 subjects, which were retrieved from the database of Al-Borg Medical Laboratories over a six-year period (2014-2019), was carried out. Means were compared among study groups and the prevalence, association, and diagnostic accuracy of lipid markers for HTN were evaluated. Results: TG, LDL/HDL, and TG/HDL were significantly higher (P < 0.0001) in hypertensives. Anemia reduces TC and LDL (P < 0.0001) in both genders, and reduces all markers and increases HDL (P < 0.01) in male hypertensives. HTN was more prevalent in anemics with high TC than normal TC (38.23% vs 11.17%, P < 0.001) and in non-anemics with high TG than normal TG (56.31% vs 21.22%, P < 0.001). Furthermore, non-anemics with high TG/HDL had the highest risk for HTN (RR = 1.20, 95% CI = 1.1551-1.2473, P < 0.0001). Elevated TC (P = 0.0142), TG (P < 0.0001), TC/HDL (P < 0.0001), LDL/HDL (P < 0.0001), and TG/HDL (P < 0.0001), and low HDL (P < 0.0001) were risk factors for HTN as shown by ORs. In anemics, high TC/HDL, LDL/HDL, and TG/HDL were not. Importantly, only TG and TG/HDL had a discriminating capacity for HTN. Conclusion: The anemic state of hypertensive Saudi patients influences dyslipidemia which warrants further investigation.

Microhardness and gloss of a new CAD-CAM hybrid material following accelerated aging and coffee immersion.

PURPOSE: To evaluate and compare the effect of accelerated aging and coffee immersion on the microhardness and gloss of a new CAD/CAM hybrid material (Crystal Ultra) to those of contemporary restorative materials. MATERIALS AND METHODS: A total of 160 specimens (12 x 14 x 1 mm ± 0.05 mm) were obtained from (IPS e.max [IPS], VITA Enamic [VE], Crystal Ultra [CU], Lava Ultimate [LU], and CeraSmart [CS]) high-translucency CAD/CAM blocks. The Vickers microhardness and gloss of the specimens were determined following thermocycling and coffee immersion. Data analysis was performed using SPSS (α = .05). RESULTS: IPS and CS specimens exhibited the highest (572.66 ± 11.30) and lowest (61.92 ± 3.91) microhardness, respectively. The highest gloss was observed with IPS specimens (3.31 ± 0.32), and LU specimens showed the lowest gloss (2.33 ± 0.06). A significant difference in gloss was observed between the materials at all measurement intervals (P < .01), except at T0 (P = .43). IPS specimens showed no significant changes in either group at any measurement interval. CONCLUSION: The microhardness and gloss of the new CU material were comparable to those of the tested contemporary hybrid restorative materials. Glass-ceramic showed superior hardness and gloss compared to hybrid restorative materials. Accelerated aging by thermocycling and staining significantly affected the microhardness and gloss of all the tested CAD/CAM materials.

Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19.

Dysregulation of renin-angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity and mortality. This study sought to investigate the effect of exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cells response in recovered COVID-19 patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang II and then stimulated with a SARS-CoV-2 peptide pool. T-cell responses were measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation was measured using a phosphokinase array. Our results showed that Ang II treatment significantly increased the magnitude of SARS-CoV-2-specific T-cell response in stimulated PBMCs with a SARS-CoV-2 peptide pool. Moreover, the phosphorylation levels of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increases in the presence of Ang II. The mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of T-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed increased productions of IL-1ß and IL-6 in Ang II-stimulated PBMCs without affecting the IL-10 level. To our knowledge, this study is the first to demonstrate that Ang II exaggerates SARS-CoV-2-specific T-cells response. Therefore, during COVID-19 infection, Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection.

Awareness of medical law among health care practitioners in Saudi Arabia.

OBJECTIVES: To determine the level of awareness of medical law among healthcare practitioners and to identify factors that influence that level of awareness in Saudi Arabia. METHODS: This cross-sectional study was carried out in Riyadh, Saudi Arabia in 2020-2021 via a survey including 750 healthcare practitioners, from different specialties including all regions in Saudi Arabia. Participants included consultants, senior registrars, interns, and residents. RESULTS: Majority of enrolled healthcare practitioners had poor awareness of medical law (approximately 97%). Only 1.5% had adequate awareness of medical law, and only 1.5% had moderate awareness. Factors associated with increased medical law awareness were the age group between 25 and 34, being from the central region, and having a clinical practice for less than 10 years p-value of <0.05. CONCLUSION: Awareness of medical law among healthcare practitioners is limited in Saudi Arabia. Professional medico-legal education should be part of required competencies for undergraduate and postgraduate levels of medical education. Health care practitioners must be educated with laws and regulations of practicing health professions in the country.

Knowledge and attitude of pregnant women in the Kingdom of Saudi Arabia toward Noninvasive prenatal testing: A single center study.

BACKGROUND: Noninvasive prenatal testing (NIPT) is a screening tool for chromosomal aneuploidies. Prior knowledge of NIPT is an inherent factor in the decision-making process. We assessed the knowledge and attitude of pregnant women related to prenatal testing with a particular focus on NIPT. METHODS: A prospective cross-sectional study, using a culturally validated questionnaire, was conducted with 342 pregnant women of whom 74.9% consented for prenatal screening. Mean age and gestational weeks ± standard deviation was 31 ± 5 and 26 ± 11, respectively. RESULTS: A positive/very positive attitude was observed to ultrasound, followed by FCT, NIPT, and lastly to CVS. More than half of the participants (56.1%) had no previous knowledge of NIPT. A reaching significance association was detected between education and knowledge of NIPT. Significant association was detected between risk for aneuploidy and knowledge of NIPT. The majority (74%) indicated their willingness to perform the test. The effect and value of society on the pregnant women to make a decision regarding NIPT was negligible. CONCLUSION: The pregnant women in the current study displayed a lack of knowledge and awareness regarding prenatal screening, particularly the NIPT. We recommend that pregnant women receive adequate counseling regarding prenatal screening to increase their awareness and knowledge of prenatal testing, including NIPT.

Viridiflorol induces anti-neoplastic effects on breast, lung, and brain cancer cells through apoptosis.

All active natural molecules are not fully exploited as therapeutic agents, causing delays in the advancement of anticancer drug discovery. Viridiflorol is a natural volatile element that may work as anti-cancer compound. We tested the anticancer properties of viridiflorol at different concentrations ranging from 0.03 to 300 µM in vitro on three cancer cells including breast (MCF-7), lung (A549) and brain (Daoy). The cancer cells responses were documented after treatment using MTT and Annexin V assays. Viridiflorol showed cytotoxic effects against all tested cell lines, reducing cell viability in a concentration-dependent manner with variable IC50 values. Daoy and A549 cell lines were more sensitive to viridiflorol when compared with temozolomide and doxorubicin, respectively. Viridiflorol demonstrated the highest anticancer activity against the Daoy cells with an estimated IC50 of 0.1 µM followed by MCF-7 at 10 µM, and A549 at 30 µM. In addition, upon exposure to concentrations ranging from 30 µM to 300 µM of viridiflorol, early and late apoptotic cell death was induced in a concentration dependent manner in Daoy (55.8%-72.1%), MCF-7 (36.2%-72.7%) and A459 (35%-98.9%) cell lines, respectively. In conclusion, viridiflorol demonstrates cytotoxic and apoptotic ability in three different cancer cell lines (brain, breast and lung).

Association between maxillofacial fractures and brain injuries in trauma patients: a cross-sectional study in the Kingdom of Saudi Arabia.

Introduction: trauma is on the rise in the Kingdom of Saudi Arabia (KSA) due to rapid urbanization and motorization, posing increased risks of traumatic maxillofacial and brain injuries. Given the high morbidity and mortality associated with these injuries, this study aimed to measure the prevalence and associated factors of brain injury among head injury trauma patients. Methods: a cross-sectional study was conducted at the King Khalid hospital and Prince Sultan Centre for Healthcare in Al-Kharj City and the Al Kharj Military Industries Corporation Hospital in Al-Kharj City in the KSA. Multivariable logistic regression modelling was performed to ascertain clinical factors associated with Traumatic Brain Injury (TBI). Results: we included 109 participants aged median 25 and IQR (18-35) years 26.95 ± 14.73 years. Most participants were males (92.7%, n = 101) and 68% (n = 75) had Saudi nationality. About 47.7% (n = 52) had maxillofacial/skull fractures and 44% (n = 48) had TBI. Participants in the age group of 31-40 years experienced a greater risk of TBI than those in the age group of 10 or less years (aOR: 6.2, CI = 1.1p = 0.041). Participants with parietal bone fractures (aOR = 23.1, CI = 3.0 - 181.3, p = 0.003) and frontal bone fractures (aOR = 19.1, CI = 1.7 - 217.0, p = 0.017) were more likely to have TBI compared to those with other skull and facial fractures. Conclusion: fractures of parietal and frontal bones are associated with a higher risk of TBI in the KSA. Patients with TBI following road accidents with fractures of the frontal or parietal bones, particularly those in the 31-40 age group should therefore be treated with strong suspicion of underlying traumatic brain injury.

Induction of hemolysis and eryptosis by occupational pollutant nickel chloride is mediated through calcium influx and p38 MAP kinase signaling.

OBJECTIVES: Nickel (Ni) is an abundant environmental hazard and an occupational pollutant. Exposure to Ni compounds is prevalent in electroplating workers and in the printing industry, among others. The toxicity of Ni manifests as dermatological, gastrointestinal, respiratory, allergic, and cardiovascular symptoms. In particular, hyperbilirubinemia and reticulocytosis have been detected in intoxicated subjects; an observation possibly implicating selective red blood cell (RBC) toxicity. Herein, the interaction of nickel chloride (NiCl2) with human RBCs and associated molecular mechanisms are described. MATERIAL AND METHODS: Cells from healthy donors were incubated for 24 h at 37°C in the presence or absence of 0.5‒10 mM of NiCl2, and cytotoxicity was determined through hemoglobin leakage by colorimetry under different experimental conditions. Eryptotic markers were also identified by flow cytofluorometry using Annexin-V-FITC tagging for phosphatidylserine (PS) exposure, light scatter properties for cellular dimensions, Fluo4/AM labeling for intracellular calcium, and H2DCFDA staining for reactive oxygen species (ROS). Additionally, small molecule inhibitors were used to probe the signaling pathways involved. RESULTS: It was found that NiCl2 at 10 mM caused profound intracellular calcium overload and significant calcium-dependent hemolysis. Also, NiCl2 reduced forward scatter and increased side scatter, Annexin- positive cells, and ROS levels. Importantly, NiCl2-induced hemolysis was significantly attenuated by the exclusion of extracellular calcium, and in the presence of p38 MAP kinase (MAPK) inhibitor SB203580. CONCLUSIONS: It is concluded that NiCl2 induces p38 MAPK-dependent hemolysis, and stimulates the canonical features of premature eryptosis. This report presents the first description of the molecular mechanisms underlying the hemolytic and eryptotic potential of NiCl2 and, thus, may explain changes in hematological parameters observed in poisoning victims. Int J Occup Med Environ Health. 2022;35(1):1-11.

Erythritol modulates the polarization of macrophages: Potential role of tumor necrosis factor-α and Akt pathway.

Low-calorie sweeteners are substitutes for sugar and frequently used by patients with cardiometabolic diseases. Erythritol, a natural low-calorie sugar alcohol, was linked to cardiometabolic diseases in several recent metabolomics studies. However, the characterization of its role in disease development is lacking. Macrophage polarization orchestrates the immune response in various inflammatory conditions, most notably cardiometabolic disease. Therefore, the physiological effects of Erythritol on THP-1 macrophages were investigated. We observed an increased cellular abundance of proinflammatory M1 macrophages, characterized by CD11c, TNF-α, CD64, CD38, and HLA-DR markers and decreased anti-inflammatory M2 macrophages, characterized by mannose receptor CD206. The, Erythritol increased ROS generation, and the activation of the AKT pathway, cytosolic calcium overload, and cell cycle arrest at the G1 phase. Concomitantly, an increased population of necroptotic macrophages was observed. In conclusion, we provide evidence that Erythritol induced the proinflammatory phenotype in THP-1 macrophages and this was associated with an increased population of necroptotic macrophages. PRACTICAL APPLICATIONS: This assessment provides evidence of the effects of Erythritol on macrophages, particularly THP-1-derived macrophages. Our results support the role of Erythritol in driving the inflammation that is associated with cardiometabolic diseases and provide insights in the role of Erythritol as an inducer of necroptosis in THP-1 derived macrophages that could be associated the disease.

SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril).

A purified spike (S) glycoprotein of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) coronavirus was used to study its effects on THP-1 macrophages, peripheral blood mononuclear cells (PBMCs), and HUVEC cells. The S protein mediates the entry of SARS-CoV-2 into cells through binding to the angiotensin-converting enzyme 2 (ACE2) receptors. We measured the viability, intracellular cytokine release, oxidative stress, proinflammatory markers, and THP-1-like macrophage polarization. We observed an increase in apoptosis, ROS generation, MCP-1, and intracellular calcium expression in the THP-1 macrophages. Stimulation with the S protein polarizes the THP-1 macrophages towards proinflammatory futures with an increase in the TNFα and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 µM reduced apoptosis, ROS, and MHC-II expression induced by S protein. We analyzed the sensitivity of the HUVEC cells after the exposure to a conditioned media (CM) of THP-1 macrophages stimulated with the S protein. The CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, the direct stimulation of the HUVEC cells with the S protein, slightly increased HIF1α and MCP-1 expression, which was significantly increased by the ACE inhibitor treatment. The S protein stimulation induced ROS generation and changed the mitogenic responses of the PBMCs through the upregulation of TNFα and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 µM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 µM) exposed more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that the blood and vascular components could be activated directly through S protein systemically present in the circulation and that the activation of the local renin angiotensin system may be partially involved in this process. Graphical: Suggested pathways that might be involved at least in part in S protein inducing activation of inflammatory markers (red narrow) and angiotensin-converting enzyme inhibitor (ACEi) modulation of this process (green narrow).

The Effect of Local Renin Angiotensin System in the Common Types of Cancer.

The Renin Angiotensin System (RAS) is a hormonal system that is responsible for blood pressure hemostasis and electrolyte balance. It is implicated in cancer hallmarks because it is expressed locally in almost all of the body's tissues. In this review, current knowledge on the effect of local RAS in the common types of cancer such as breast, lung, liver, prostate and skin cancer is summarised. The mechanisms by which RAS components could increase or decrease cancer activity are also discussed. In addition to the former, this review explores how the administration of AT1R blockers and ACE inhibitors drugs intervene with cancer therapy and contribute to the outcomes of cancer.