Changes in dietary habits and eating behaviors during COVID-19 induced confinement: A study from Jordan.

Objective: This study aimed to evaluate dietary habits (DH) and eating behaviors (EB) among adults during confinement induced by COVID-19 in Jordan. Method: In this cross-sectional study, an online survey designed to assess the change in DH and EB during April and May 2020 was distributed using various social media platforms. Results: The survey was completed by a total of 1844 adult (18-72 years) participants from the public in Jordan. The results indicated an increase (42.5-61.8%) in most of the DH and EB examined in the current study in the majority of participants. Among these changes, they have increased (p < 0.05) the prevalence of fruit and vegetable, immune boosters, water, and hot beverage consumption, as well as decreased (p < 0.05) eating in restaurants and fatty food consumption, indicating a positive change. Conversely, a larger (p < 0.05) proportion of participants reported increased consumption of high-calorie food and late-night eating, indicating a risky behavior for obesity and subsequent chronic complications. Additionally, age, sex, obesity, education, income, and type of job appeared to contribute (p < 0.05) to changes in DH and EB. Overall, confinement caused by COVID-19 appears to compel adults to adopt a specific DH and EB. Although most of these changes were positive, some were negative. Conclusion: This study provides essential information for designing subpopulation recommendations and developmental programs for adults under such conditions.

Metabolic Reprogramming and Cell Adhesion in Acute Leukemia Adaptation to the CNS Niche.

Involvement of the Central Nervous System (CNS) in acute leukemia confers poor prognosis and lower overall survival. Existing CNS-directed therapies are associated with a significant risk of short- or long-term toxicities. Leukemic cells can metabolically adapt and survive in the microenvironment of the CNS. The supporting role of the CNS microenvironment in leukemia progression and dissemination has not received sufficient attention. Understanding the mechanism by which leukemic cells survive in the nutrient-poor and oxygen-deprived CNS microenvironment will lead to the development of more specific and less toxic therapies. Here, we review the current literature regarding the roles of metabolic reprogramming in leukemic cell adhesion and survival in the CNS.

The Emerging Role of Suppressors of Cytokine Signaling (SOCS) in the Development and Progression of Leukemia.

Cytokines are pleiotropic signaling molecules that execute an essential role in cell-to-cell communication through binding to cell surface receptors. Receptor binding activates intracellular signaling cascades in the target cell that bring about a wide range of cellular responses, including induction of cell proliferation, migration, differentiation, and apoptosis. The Janus kinase and transducers and activators of transcription (JAK/STAT) signaling pathways are activated upon cytokines and growth factors binding with their corresponding receptors. The SOCS family of proteins has emerged as a key regulator of cytokine signaling, and SOCS insufficiency leads to constitutive activation of JAK/STAT signaling and oncogenic transformation. Dysregulation of SOCS expression is linked to various solid tumors with invasive properties. However, the roles of SOCS in hematological malignancies, such as leukemia, are less clear. In this review, we discuss the recent advances pertaining to SOCS dysregulation in leukemia development and progression. We also highlight the roles of specific SOCS in immune cells within the tumor microenvironment and their possible involvement in anti-tumor immunity. Finally, we discuss the epigenetic, genetic, and post-transcriptional modifications of SOCS genes during tumorigenesis, with an emphasis on leukemia.

Anti-TNF-α agents Modulate SARS-CoV-2 Receptors and Increase the Risk of Infection Through Notch-1 Signaling.

Although millions of patients with underlining conditions are treated primarily with anti-TNF-α agents, little is known about the safety of this standard therapy during the coronavirus disease-2019 (COVID-19) pandemic. In this study, we investigated the effect of anti-TNF-α monoclonal antibodies on the cellular entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increasing the risk of COVID-19 development. We focused on the expression of angiotensin-converting enzyme II (ACE2), type II transmembrane serine proteases (TMPRSS2)/TNF-α converting enzyme (TACE) ratio. We also investigated the involvement of Notch-1 signaling and its downstream influence on IL-6, myeloid cell leukemia sequence-1(MCL-1) in the anti-TNF-α mode of action and increased the susceptibility to Mycobacterium avium subspecies paratuberculosis (MAP) infection. Surprisingly, anti-TNF-α downregulated ACE2 expression by 0.46-fold and increased TMPRSS2/TACE ratio by 44% in THP-1 macrophages. Treatment of macrophages with rIL-6 also downregulated ACE2 and increased TMPRSS2/TACE ratio by 54%. Interestingly, anti-TNF-α treatment upregulated Notch-1, IL-6, and MCL-1 by 1.3, 1.2, and 1.9-fold, respectively, and increased viability and burden of MAP infection in macrophages. Blocking Notch signaling doubled ACE2 expression, decreased TMPRSS2/TACE ratio by 38%, and reduced MAP viability by 56%. In a small group of patients, ACE2 level was significantly lower in the plasma from rheumatoid arthritis (RA) patients on anti-TNF-α treatment compared to healthy control. The data in this critical study demonstrated that through Notch-1/IL-6 signaling, anti-TNF-α agents decreased ACE2 expression and shedding through TMPRSS2/TACE modulation and increased the susceptibility to infection. Overall, this study warns against anti-TNF-α therapy in some patients with underlining inflammatory conditions during the COVID-19 pandemic. The findings should impact current guidelines regarding treatment decisions of patients on anti-TNF-α during the COVID-19 pandemic.

MiR-146a rs2910164 G > C polymorphism modulates Notch-1/IL-6 signaling during infection: a possible risk factor for Crohn's disease.

BACKGROUND: MiR-146a, an effector mediator, targets Notch-1 and regulates the innate and adaptive immune systems response. Recently, we reported that Notch-1 signaling plays a key role in macrophage polarization and response during infection. We employed Mycobacterium avium paratuberculosis (MAP) infection in Crohn's disease (CD) as a model to demonstrate the role of Notch-1/IL-6 signaling on MCL-1 based apoptosis and intracellular MAP infection and persistence. This study was designed to investigate the impact of polymorphisms in miR146a on the immune response and infection in our MAP-CD model. METHODS: We determined the incidence of miR-146a rs2910164 G > C in 42 blood samples from clinical CD patients and controls. We also measured the effect of rs2910164 on expression of Notch-1 and IL-6, and plasma IL-6 protein levels in our study group. Finally, we analyzed the blood samples for MAP DNA and studied any correlation with miR-146a polymorphism. Samples were analyzed for statistical significance using unpaired tow-tailed t-test, unpaired two-tailed z-score and odds ratio. P < 0.05 considered significant. RESULTS: MiR-146a rs2910164 GC was detected at a higher incidence in CD (52.6%) compared to healthy controls (21.7%) rs2910164 GC Heterozygous polymorphism upregulated Notch-1 and IL-6, by 0.9 and 1.7-fold, respectively. As expected, MAP infection was detected more in CD samples (63%) compared to healthy controls (9%). Surprisingly, MAP infection was detected at a higher rate in samples with rs2910164 GC (67%) compared to samples with normal genotype (33%). CONCLUSIONS: The data clearly associates miR-146a rs2910164 GC with an overactive immune response and increases the risk to acquire infection. The study is even more relevant now in our efforts to understand susceptibility to SARS-CoV-2 infection and the development of COVID-19. This study suggests that genetic variations among COVID-19 patients may predict who is at a higher risk of acquiring infection, developing exacerbating symptoms, and possibly death. A high scale study with more clinical samples from different disease groups is planned.

The dietary peroxidized lipid, 13-HPODE, promotes intestinal inflammation by mediating granzyme B secretion from natural killer cells.

It is well known that consumption of a high-fat diet (HFD) promotes intestinal inflammation despite little being known about causative factors. Recent evidence implicates dietary peroxidized lipids (POLs), which are typically formed from the oxidation of polyunsaturated fatty acid double bonds, as potential contributors due to their enrichment in HFDs, ability to be formed during gastrointestinal transit, and immunogenic and cytotoxic properties. 13-HPODE, the most common dietary POL, demonstrates pro-inflammatory activity in a variety of immune cells, especially Natural Killer (NK) cells whose role in mediating intestinal inflammation remains unclear. Therefore, we set out to investigate how 13-HPODE and other POLs modulate NK-cell activity in the context of intestinal inflammation. We not only found that NK cells fully decompose exogenous 13-HPODE, but that direct treatment stimulates TNF-α and MCP1 expression as well as Granzyme B (GZMB) secretion in a dose-dependent manner. Similar results were observed upon incubation of NK cells with oxidized, but not-unoxidized, low-density lipoproteins. Secretory products from 13-HPODE-treated NK cells were able to induce Caco2 intestinal cell inflammation in the same way as exogenous GZMB with greater sensitivity in undifferentiated compared to differentiated cells. Results were recapitulated in 13-HPODE-fed mice, demonstrating both spatial and temporal patterns of elevated GZMB expression that favored acute treatments in the distal intestinal epithelium. Collectively, our results suggest that that HFD-derived POLs, like 13-HPODE, potentially contribute to intestinal inflammation by stimulating the secretion of pro-inflammatory granzymes by resident NK cells, ultimately revealing a more direct role for diet in modulating gut homeostasis and the immune environment.

Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates. In this study, we propose that the peroxidized fatty acid components of HFDs could contribute to inflammation of the gut. The inflammatory nature of peroxidized linoleic acid (13-HPODE), was confirmed in vitro by analyzing pro-inflammatory gene expression in Caco-2 cells via RT-PCR and ELISA. Additionally, peroxide induced apoptosis was tested by Annexin-V fluorescent staining, while permeability was tested by FITC-dextran flux and TEER. The 13-HPODE-induced inflammation of intestinal epithelium was evaluated in vivo by analyzing pro-inflammatory cytokines under acute and chronic conditions after feeding 13-HPODE to C57BL/6J mice. Our data show that 13-HPODE significantly induced pro-inflammatory gene expression of TNF-α and MCP-1 in vitro, most notably in differentiated Caco-2 cells. Further, acute and chronic 13-HPODE treatments of mice similarly induced pro-inflammatory cytokine expression in the epithelium of both the proximal and distal small intestines, resident immune cells in Peyer's patches and peritoneal macrophages. The results of this study not only confirm the pro-inflammatory properties of peroxidized fats on the gut mucosa, but for the first time demonstrate their ability to differentially induce pro-inflammatory gene expression and influence permeability in the intestinal epithelium and mucosal cells. Collectively, our results suggest that the immunogenic properties of HFD's in the gut may be partly caused by peroxide derivatives, providing potential insight into how these diets contribute to exacerbations of IBD.

Notch-1 Signaling Modulates Macrophage Polarization and Immune Defense against Mycobacterium avium paratuberculosis Infection in Inflammatory Diseases.

Despite the extensive research on Notch signaling involvement in inflammation, its specific role in macrophage response in autoimmune disease and defense mechanisms against bacterial infection, such as Mycobacterium avium paratuberculosis (MAP), remains unknown. In this study, we investigated the molecular role of Notch-1 signaling in the macrophage response during MAP infection. In particular, we measured the in vitro effect of MAP on Notch-1 signaling and downstream influence on interleukin (IL)-6 and myeloid cell leukemia sequence-1 (MCL-1) and consequent cellular apoptosis, MAP viability, and macrophage polarization. Overall, the data show significant upregulation in Notch-1, IL-6, and MCL-1 in MAP-infected macrophages, parallel with a decrease in apoptosis and elevated pro-inflammatory response in these infected cells. On the contrary, blocking Notch signaling with γ-secretase inhibitor (DAPT) decreased MAP survival and burden, increased apoptosis, and diminished the pro-inflammatory response. In particular, the treatment of infected macrophages with DAPT shifted macrophage polarization toward M2 anti-inflammatory phenotypic response. The outcome of this study clearly demonstrates the critical role of Notch signaling in macrophage response during infection. We conclude that MAP infection in macrophages activates Notch-1 signaling and downstream influence on IL-6 which hijack MCL-1 dependent inhibition of apoptosis leading to its chronic persistence, and further inflammation. This study supports Notch-1 signaling as a therapeutic target to combat infection in autoimmune diseases such as Crohn's disease and Rheumatoid Arthritis.

The Role of Notch Signaling in Macrophages during Inflammation and Infection: Implication in Rheumatoid Arthritis?

Notch signaling coordinates numerous cellular processes and has been implicated in many pathological conditions, including rheumatoid arthritis (RA). Although the role of Notch signaling in development, maturation, differentiation, and activation of lymphocytes has been comprehensively reported, less is known about its role in myeloid cells. Certainly, limited data are available about the role of Notch signaling in macrophages during inflammation and infection. In this review, we discuss the recent advances pertaining to the role of Notch signaling in differentiation, activation, and metabolism of macrophages during inflammation and infection. We also highlight the reciprocal interplay between Notch signaling and other signaling pathways in macrophages under different inflammatory and infectious conditions including pathogenesis of RA. Finally, we discuss approaches that could consider Notch signaling as a potential therapeutic target against infection- and inflammation-driven diseases.

Proinflammatory Properties of Peroxidized Fat May Contribute to the Etiology of Crohn's Disease.

Crohn's disease (CD) is a well-known subset of inflammatory bowel disease (IBD) that results in patchy inflammation through the entire thickness of the bowel wall, with the ability to target virtually any part of the gastrointestinal tract, but most commonly affecting the area between the ileum and the cecum. While a bacterial origin of Crohn's is well speculated, it is difficult to pinpoint what drives inflammation in these subjects, particularly the flare-ups or the sudden symptomatic intensification or recurrence. This review aims at tracing the etiology of CD back to diet, particularly fried foods, a known aggravator of symptoms. Based on the reactions that frying entails, the chemical composition of the food is altered in ways that can lead to maldigestion and inflammation. Current evidence suggests a direct dietary role in the inflammation underlying CD or the flare-ups. The presented review focuses on an underresearched, yet, very applicable topic. We suggest that emphasis should be put on dietary alteration as a means of treatment for patients with CD to supplement current therapy for optimal results. With the widespread popularity of fried foods, it is important to raise awareness about the potential negative outcomes that are prevalent worldwide.

Vascular function and handgrip strength in rheumatoid arthritis patients.

OBJECTIVE: To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. METHODS: Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. RESULTS: The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = -0.3; P = 0.009) and RHVR (r = -0.3; P = 0.007). CONCLUSION: The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.

The clinical and nonclinical values of nonexercise estimation of cardiovascular endurance in young asymptomatic individuals.

Exercise testing is associated with barriers prevent using cardiovascular (CV) endurance (CVE) measure frequently. A recent nonexercise model (NM) is alleged to estimate CVE without exercise. This study examined CVE relationships, using the NM model, with measures of obesity, physical fitness (PF), blood glucose and lipid, and circulation in 188 asymptomatic young (18-40 years) adults. Estimated CVE correlated favorably with measures of PF (r = 0.4 - 0.5) including handgrip strength, distance in 6 munities walking test, and shoulder press, and leg extension strengths, obesity (r = 0.2 - 0.7) including % body fat, body water content, fat mass, muscle mass, BMI, waist and hip circumferences and waist/hip ratio, and circulation (r = 0.2 - 0.3) including blood pressures, blood flow, vascular resistance, and blood (r = 0.2 - 0.5) profile including glucose, total cholesterol, LDL-C, HDL-C, and triglycerides. Additionally, differences (P < 0.05) in examined measures were found between the high, average, and low estimated CVE groups. Obviously the majority of these measures are CV disease risk factors and metabolic syndrome components. These results enhance the NM scientific value, and thus, can be further used in clinical and nonclinical settings.

Assessment of Cardiovascular Risk Factors Among University Students: The Gender Factor.

BACKGROUND: Evidence indicates that the pathophysiological process of cardiovascular (CV) disease begins at early age, though the manifestations of the disease do not appear until middle age adulthood. Risk factors for CV disease, particularly lipoprotein profiles, are affected by physiological abnormalities, and lifestyle related issues. To evaluate prevalence of CV diseases risk factors among university students and to investigate relation between number of risk factors and body anthropometric, hematological and biochemical indices parameters. METHODS: In this cross sectional study, 348 students were randomly recruited. Blood glucose, cholesterol profile (total, HDL, and LDL cholesterol), and triglyceride were measured using standard protocols. Physical activity (PA) level was assessed using the short-form Arabic version of the International Physical Activity Questionnaires (IPAQ). RESULTS: The most commonly encountered CV disease risk factor was low levels of HDL-C, followed by physical inactivity, high levels TG, and obese BMI. When stratified by gender, females were less likely to have low HDL-C, and high TG, whereas, males were more likely to have overweight or obese BMI (P < 0.001). About 49% of the participants had at least one CV disease risk factor, where as the prevalence of having one, two and three or more CV disease risk factors were 35.7%, 9.3% and 4%, respectively. Additionally, the number of CV disease risk factors showed strong positive correlation with increases in body fat and bone percentages, glucose, total cholesterol, TG, LDL-C, BMI, and WHR (range of R2: 0.17 to 0.603). On the other hand, physical activity, percentages of body water and muscle, HDL-C showed inverse strong correlation with cardiovascular risk factors (range of R2: -0.239 to -0.412). CONCLUSIONS: Results indicate the high prevalence of CV disease risk factors among university students, and stress the need for early intervention programs to counteract these risks.

Blood pressure and circulatory relationships with physical activity level in young normotensive individuals: IPAQ validity and reliability considerations.

Physical activity (PA) reduces risk of cardiovascular diseases, including hypertension. However, the international physical activity questionnaire (IPAQ) relationships with blood pressure (BP) and flow (BF) and vascular resistance (VR) in healthy young individuals have not been studied. Therefore, BP, BF, and VR relationships with the IPAQ were evaluated in college normotensive students (18-23 yrs). Additionally, the IPAQ relationships with body fat (%BF), muscle mass (MM), body mass index (BMI), waist/hip (W/H) ratio, maximum walking distance in 6 min (6MWD), and handgrip strength (MHG) were examined to evaluate the questionnaire validity against fitness. Subsequently, the IPAQ was administered three times to examine its reliability. Walking, moderate, and total PAs correlated negatively with sysbolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (range: r = -3 to -0.5, p < 0.05). Additionally, all BP measures were greater in least physically active individuals. In a subgroup of 42 students, IPAQ sitting time correlated with BF (r = -0.3) and VR (r = 0.4). The intraclass correlation coefficient (ICC) for walking, moderate, vigorous, and total PAs and sitting time/week were, 0.97, 0.96, 0.97, 0.97, and 0.96, respectively. The males scored greater vigorous PA (p = 0.001) than the females, while moderate, walking, and total PAs were the same (p > 0.05). Additionally, vigorous PA correlated with %BF (r = -0.2), MM (r = 0.3), MHG (r = 0.3), and 6MWD (r = 0.3) and total PA correlated with MM (r = 0.2), MHG (r =0.2), and 6MWD (r = 0.3). The IPAQ association with the circulatory measures demonstrates PA importance for controlling BP and adds clinical value to the IPAQ. Additionally, the IPAQ is reliable, can discriminate between populations, and reasonably valid against health-related fitness.