Unraveling the significance of PPP1R1A gene in pancreatic ß-cell function: A study in INS-1 cells and human pancreatic islets.

BACKGROUND AND AIMS: The protein phosphatase 1 regulatory inhibitor subunit 1A (PPP1R1A) has been linked with insulin secretion and diabetes mellitus. Yet, its full significance in pancreatic ß-cell function remains unclear. This study aims to elucidate the role of the PPP1R1A gene in ß-cell biology using human pancreatic islets and rat INS-1 (832/13) cells. RESULTS: Disruption of Ppp1r1a in INS-1 cells was associated with reduced insulin secretion and impaired glucose uptake; however, cell viability, ROS, apoptosis or proliferation were intact. A significant downregulation of crucial ß-cell function genes such as Ins1, Ins2, Pcsk1, Cpe, Pdx1, Mafa, Isl1, Glut2, Snap25, Vamp2, Syt5, Cacna1a, Cacna1d and Cacnb3, was observed upon Ppp1r1a disruption. Furthermore, silencing Pdx1 in INS-1 cells altered PPP1R1A expression, indicating that PPP1R1A is a target gene for PDX1. Treatment with rosiglitazone increased Ppp1r1a expression, while metformin and insulin showed no effect. RNA-seq analysis of human islets revealed high PPP1R1A expression, with α-cells showing the highest levels compared to other endocrine cells. Muscle tissues exhibited greater PPP1R1A expression than pancreatic islets, liver, or adipose tissues. Co-expression analysis revealed significant correlations between PPP1R1A and genes associated with insulin biosynthesis, exocytosis machinery, and intracellular calcium transport. Overexpression of PPP1R1A in human islets augmented insulin secretion and upregulated protein expression of Insulin, MAFA, PDX1, and GLUT1, while silencing of PPP1R1A reduced Insulin, MAFA, and GLUT1 protein levels. CONCLUSION: This study provides valuable insights into the role of PPP1R1A in regulating ß-cell function and glucose homeostasis. PPP1R1A presents a promising opportunity for future therapeutic interventions.

Effect of camel milk on lipid profile among patients with diabetes: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

The effects of camel milk (CM) intake on lipid profile among patients with diabetes remain controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to calculate the effect size of CM intake on blood lipids among patients with type 1 (T1D) and type 2 (T2D) diabetes. We searched nine databases from inception until December 31, 2022, to identify relevant RCTs. Effect sizes for total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) were calculated and expressed using mean differences (MD) and confidence intervals (CI). Of 4,054 retrieved articles, 10 RCTs (a total of 347 participants aged 8-70 years, 60.5% male) were eligible for inclusion. The pooled results from a random-effects model showed statistically significant decreases in TC (MD - 21.69, 95% CI: 41.05, - 2.33; p = 0.03; I2=99%), TG (MD - 19.79, 95% CI: -36.16, - 3.42; p=0.02, I2=99%), and LDL (MD -11.92, CI: -20.57, -3.26; p = 0.007, I2=88%), and a significant increase in HDL (MD 10.37, 95% CI, 1.90, 18.84; p=0.02, I2=95%) in patients with diabetes supplemented with CM compared with usual care alone. Subgroup analysis revealed that only long-term interventions (> 6 months) elicited a significant reduction in TC levels and TG levels. Consumption of fresh CM by patients with diabetes resulted in significant reductions in TC, TG, and LDL levels, while showing a significant increase in HDL levels. Patients with T1D elicited a more beneficial effect in lowering TC, LDL, and TG levels and in increasing HDL levels than their corresponding partners with T2D. In conclusion, long-term consumption of CM for patients with diabetes, especially those with T1D, could be a useful adjuvant therapy to improve lipid profile alongside prescribed medications. However, the high heterogeneity in the included studies suggests that more RCTs with larger sample sizes and longer intervention durations are required to improve the robustness of the available evidence.

Reflection on Ramadan Fasting Research Related to Sustainable Development Goal 3 (Good Health and Well-Being): A Bibliometric Analysis.

There is a large body of research on Ramadan intermittent fasting (RIF) and health in Muslim communities, that can offer insights to promote the achievement of Sustainable Development Goal 3 (SDG 3), which encompasses good health and well-being. Based on recent bibliometric evidence, we hypothesized that RIF research is highly relevant to SDG 3, particularly Targets 3.1, 3.2, 3.4, and 3.5. Therefore, this bibliometric study quantified RIF literature supporting SDG 3 and associated targets over the past seven decades and explored themes and trends. All types of research articles were extracted from the Scopus database from inception to March 2022. Microsoft Excel, Biblioshiny, and VOSviewer were used to qualitatively and quantitatively examine RIF research trends supporting SDG 3 and associated targets. We identified 1729 relevant articles. The number of publications notably increased since 1986, with a dramatic increase in 2019-2020. RIF research predominantly supported Target 3.4 (reducing risk for non-communicable diseases), with research hotspots being diabetes, diabetes medications, pregnancy, physiology, metabolic diseases, and obesity and metabolism. This target was also the most commonly supported by dedicated authors and institutions publishing on RIF, whereas other SDG 3 targets were negligibly addressed in comparison. Our comprehensive bibliometric analysis of RIF literature showed growing support for SDG 3 through positive contributions to half of the SDG 3 targets, although Target 3.4 received the most attention. We also identified knowledge gaps that may shape further research directions on RIF and promote the achievement of SDG 3 in Muslim communities.

Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets.

Cardiovascular diseases (CVDs) are highly associated with both vitamin D deficiency and obesity, two prevalent health conditions worldwide. Arterial stiffness, an independent predictor of CVDs, is particularly elevated in both conditions, yet the molecular mechanisms underlying this phenomenon remain elusive, hindering effective management of CVDs in this population. We recruited 20 middle-aged Emiratis, including 9 individuals with vitamin D deficiency (Vit D level ≤20 ng) and obesity (BMI ≥30) and 11 individuals as control with Vit D level >20 ng and BMI <30. We measured arterial stiffness using pulse wave velocity (PWV) and performed whole transcriptome sequencing to identify differentially expressed genes (DEGs) and enriched pathways. We validated these findings using qRT-PCR, Western blot, and multiplex analysis. PWV was significantly higher in the vitamin D deficient and obese group relative to controls (p ≤ 0.05). The DEG analysis revealed that pathways related to interleukin 1 (IL-1), nitrogen metabolism, HIF-1 signaling, and MAPK signaling were over-activated in the vitamin D deficient and obese group. We found that HIF-1alpha, NOX-I, NOX-II, IL-1b, IL-8, IL-10, and VEGF were significantly upregulated in the vitamin D deficient and obese group (p < 0.05). Our study provides new insights into the molecular mechanisms of arterial stiffness in vitamin D deficiency and obesity, demonstrating the role of oxidative stress and inflammation in this process. Our findings suggest that these biomarkers may serve as potential therapeutic targets for early prevention of CVDs. Further studies are needed to investigate these pathways and biomarkers with larger cohort.

Changes in energy and macronutrient intakes during Ramadan fasting: a systematic review, meta-analysis, and meta-regression.

CONTEXT: Ramadan fasting (RF) is associated with various physiological and metabolic changes among fasting Muslims. However, it remains unclear whether these effects are attributable to changes in meal timing or changes in dietary energy and macronutrient intakes. Furthermore, the literature on the associations between RF, meal timing, and energy and macronutrient intakes is inconclusive. OBJECTIVES: This systematic review aimed to estimate the effect sizes of RF on energy and macronutrient intakes (carbohydrates, protein, fats, dietary fiber, and water) and determine the effect of different moderators on the examined outcomes. DATA SOURCES: The Cochrane, CINAHL, EMBASE, EBSCOhost, Google Scholar, PubMed/MEDLINE, ProQuest Medical, Scopus, ScienceDirect, and Web of Science databases were searched from inception to January 31, 2022. DATA EXTRACTION: The studies that assessed energy, carbohydrate, protein, fat, fiber, and water intakes pre- and post-fasting were extracted. DATA ANALYSIS: Of the 4776 identified studies, 85 relevant studies (n = 4594 participants aged 9-85 y) were selected. The effect sizes for the studied variables were as follows: energy (number of studies [K] = 80, n = 3343 participants; mean difference [MD]: -142.45; 95% confidence interval [CI]: -215.19, -69.71), carbohydrates (K = 75, n = 3111; MD: -23.90; 95% CI: -36.42, -11.38), protein (K = 74, n = 3108; MD: -4.21; 95% CI: -7.34, -1.07), fats (K = 73, n = 3058; MD: -2.03; 95% CI: -5.73, 1.67), fiber (K = 16, n = 1198; MD: 0.47; 95% CI: -1.44, 2.39), and water (K = 17, n = 772; MD: -350.80; 95% CI: -618.09, 83.50). Subgroup analyses showed age significantly moderated the 6 dietary outcomes, and physical activity significantly moderated water intake. There were significant reductions in energy, carbohydrate, and protein intakes during RF. CONCLUSIONS: The change in meal timing rather than quantitative dietary intake may explain various physiological and health effects associated with RF.

Ramadan intermittent fasting is associated with ameliorated inflammatory markers and improved plasma sphingolipids/ceramides in subjects with obesity: lipidomics analysis.

Intermittent fasting (IF) is associated with enormous metabolic alterations that underpin its diverse health effects. Changes in lipid metabolism, particularly ceramides, and other sphingolipids, are among the most notable of these alterations. This study investigated the lipidomic alterations associated with 29-30 days of Ramadan diurnal intermittent fasting (RIF) in metabolically healthy overweight and obese subjects. A prospective cohort of 57 overweight and obese adults (70% males, 38.4 ± 11.2 years), with an age range of 18-58 years was observed prior to and at the conclusion of Ramadan. At both time points, anthropometric, biochemical (lipid profile, glycemic, and inflammatory markers), and dietary intake measurements were taken. Using liquid chromatography-mass spectrometry, a lipidomic analysis of ceramides and other sphingolipids was conducted. Using paired sample t-tests, pre- and post-Ramadan anthropometric, biochemical, and dietary values were compared. RIF was associated with improved levels of lipid profile compartments and inflammatory markers. In addition, RIF was associated with a decrease in plasma sphingosine and sphinganine, which was accompanied by a decrease in sphingosine 1-phosphate and sphinganine 1-phosphate. In addition, RIF was associated with decreased C17, C22, and C24 sphingomyelin, but not C14, C16, C18, C20, and C24:1 sphingomyelin, as well as C20, C22, C24, and C24:1 dihydrosphingomyelin, but not C16 and C18 dihydrosphingomyelin. This study demonstrates that RIF is associated with improvements in plasma sphingosine, sphinganine sphingomyelin, and dihydrosphingomyelin lipid species, as well as improved lipid profile and inflammatory markers, which may confer short-term protection against cardiometabolic problems in patients with overweight/obesity.

Molecular pathogenicity of 1-nonadecene and L-lactic acid, unique metabolites in radicular cysts and periapical granulomas.

Recently, 1-nonadecene and L-lactic acid were identified as unique metabolites in radicular cysts and periapical granuloma, respectively. However, the biological roles of these metabolites were unknown. Therefore, we aimed to investigate the inflammatory and mesenchymal-epithelial transition (MET) effects of 1-nonadecene, and the inflammatory and collagen precipitation effects of L-lactic acid on both periodontal ligament fibroblasts (PdLFs) and peripheral blood mononuclear cells (PBMCs). PdLFs and PBMCs were treated with 1-nonadecene and L-lactic acid. Cytokines' expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). E-cadherin, N-cadherin, and macrophage polarization markers were measured using flow cytometry. The collagen, matrix metalloproteinase (MMP)-1, and released cytokines were measured using collagen assay, western blot, and Luminex assay, respectively. In PdLFs, 1-nonadecene enhances inflammation through the upregulation of some inflammatory cytokines including IL-1ß, IL-6, IL-12A, monocyte chemoattractant protein (MCP)-1, and platelet-derived growth factor (PDGF) α. 1-Nonadecene also induced MET through the upregulation of E-cadherin and the downregulation of N-cadherin in PdLFs. 1-Nonadecene polarized macrophages to a pro-inflammatory phenotype and suppressed their cytokines' release. L-lactic acid exerted a differential impact on the inflammation and proliferation markers. Intriguingly, L-lactic acid induced fibrosis-like effects by enhancing collagen synthesis, while inhibiting MMP-1 release in PdLFs. These results provide a deeper understanding of 1-nonadecene and L-lactic acid's roles in modulating the microenvironment of the periapical area. Consequently, further clinical investigation can be employed for target therapy.

SARS-CoV-2-free residual proteins mediated phenotypic and metabolic changes in peripheral blood monocytic-derived macrophages in support of viral pathogenesis.

The large-scale dissemination of coronavirus disease-2019 (COVID-19) and its serious complications have pledged the scientific research communities to uncover the pathogenesis mechanisms of its etiologic agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods of unveiling such mechanisms are rooted in understanding the viral agent's interactions with the immune system, including its ability to activate macrophages, due to their suggested role in prolonged inflammatory phases and adverse immune responses. The objective of this study is to test the effect of SARS-CoV-2-free proteins on the metabolic and immune responses of macrophages. We hypothesized that SARS-CoV-2 proteins shed during the infection cycle may dynamically induce metabolic and immunologic alterations with an inflammatory impact on the infected host cells. It is imperative to delineate such alterations in the context of macrophages to gain insight into the pathogenesis of these highly infectious viruses and their associated complications and thus, expedite the vaccine and drug therapy advent in combat of viral infections. Human monocyte-derived macrophages were treated with SARS-CoV-2-free proteins at different concentrations. The phenotypic and metabolic alterations in macrophages were investigated and the subsequent metabolic pathways were analyzed. The obtained results indicated that SARS-CoV-2-free proteins induced concentration-dependent alterations in the metabolic and phenotypic profiles of macrophages. Several metabolic pathways were enriched following treatment, including vitamin K, propanoate, and the Warburg effect. These results indicate significant adverse effects driven by residual viral proteins that may hence be considered determinants of viral pathogenesis. These findings provide important insight as to the impact of SARS-CoV-2-free residual proteins on the host cells and suggest a potential new method of management during the infection and prior to vaccination.

The Essential Role of 17-Octadecynoic Acid in the Pathogenesis of Periapical Abscesses.

INTRODUCTION: Periapical abscesses are 1 of the most frequent pathologic lesions in the alveolar bone. Recently, we have identified 17-octadecynoic acid (17-ODYA) as the highest unique metabolite in periapical abscesses. Therefore, the aim of this study was to investigate the immunologic and pathophysiological roles of this metabolite in the initiation and development of periapical abscesses. METHODS: Periodontal ligament fibroblasts and peripheral blood mononuclear cells were treated with 17-ODYA. Gene expression analysis and interleukin (IL)-8 release were determined using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Macrophage polarization and cytokine release were also determined using flow cytometry and Luminex bioassay (R&D Systems, Minneapolis, MN), respectively. RESULTS: In periodontal ligament fibroblasts, 17-ODYA caused significant (P < .0001) up-regulation of IL-1α, IL-1ß, IL-6, matrix metalloproteinase-1, and monocyte chemoattractant protein-1 at 10 µmol/L after 6 days of treatment and up-regulation of platelet-derived growth factor alpha and vascular endothelial growth factor alpha at all tested concentrations after 2 days of treatment. In peripheral blood mononuclear cells, 17-ODYA significantly increased the expression of IL-1α, IL-1ß, IL-6, matrix metalloproteinase-1, and monocyte chemoattractant protein-1 at 10 µmol/L (P < .0001) and vascular endothelial growth factor alpha and platelet-derived growth factor alpha at 1 µmol/L 17-ODYA (P < .0001). 17-ODYA polarized macrophages toward a proinflammatory phenotype (M1) and suppressed the release of pro- and anti-inflammatory cytokines. 17-ODYA significantly enhanced the release of IL-8. CONCLUSIONS: This study was the first to identify the pathologic role of 17-ODYA in the development of periapical abscesses. The results of this study are important in shedding light on the pathogenesis of periapical abscesses in relation to microbial metabolites.

Haptoglobin polymorphism modulates cardiometabolic impacts of four consecutive weeks, dawn to sunset Ramadan intermittent fasting among subjects with overweight/obesity.

AIMS: Haptoglobin (Hp) is a multifaceted marker of inflammation, and mediates the interplay between obesity, inflammation, and cardiometabolic dysfunction. However, the role of the Hp phenotype in modulating intermittent fasting (IF)-induced cardiometabolic changes remains to be elucidated. METHODS: Hp phenotype was determined for the study subjects. Cardiometabolic markers were assessed before and at the end of four consecutive weeks, dawn to sunset IF. RESULTS: A total of 114 subjects (75 males and 39 females, 38.7 ± 11.7 years, body mass index (BMI) of 30.41 ± 5.09 kg/m2) were recruited. Hp2-2 (n = 55, 48.2 %) and Hp2-1 (n = 53, 46.5 %) were the predominant phenotypes. Significant reductions were observed in serum Hp, IL-6, TNF-α, triglycerides (TG), total cholesterol (TC), LDL, BMI, and fat mass (FM), while a significant elevation was observed in serum CD163, HDL, and IL-10 at the end of the IF month for the whole population. Based on the Hp polymorphism, significant decreases in Hp, BMI, FM, TG, LDL, and TNF-α, with significant increases in HDL and CD163 levels were observed among subjects with Hp2-2 and Hp2-1 phenotypes. A more pronounced reduction in FM was reported in subjects with Hp2-2 in comparison with Hp2-1. CONCLUSION: Hp gene polymorphism modulates IF-induced changes in cardiometabolic markers. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN18205186; https://trialsearch.who.int/?TrialID=ISRCTN18205186.

Seven decades of Ramadan intermittent fasting research: Bibliometrics analysis, global trends, and future directions.

BACKGROUND AND AIMS: There is a large body of research focused on various aspects related to Ramadan intermittent fasting (RIF) and human health and disease. This study aimed to quantify the bibliometric data of RIF medical research over the past seven decades and explore these variables qualitatively via text mining analysis. METHODS: We used the Scopus search engine to identify published articles related to RIF from inception to December 31, 2021. All types of research articles were included. Scientometric and bibliometric measures were determined using Excel, Biblioshiny, and VOSviewer. This study proposed a bibliometric and text mining method to qualitatively and quantitatively recognize the RIF research trend. RESULTS: The Scopus search returned 1915 relevant articles. Most citations pertained to publications from the last two decades, and most publications were original research articles. These publications had received around 27,000 citations, and the 20 most prolific publishing journals had an average h-index of 112.25. More than one-third of all medical publications were in open-access journals. There was a 13-fold increase in medical research on RIF over the past few decades. We identified the 10 most prolific publishing countries, institutes, journals, and authors. We also identified five scientific hotspots of RIF scientific literature, which were: diabetes, metabolic health, public health, physiology, and maternity. CONCLUSION: This is the first comprehensive bibliometric analysis of medical research related to RIF. The research gaps identified will shape future research directions and foster collaborative research activities toward enhanced medical nutrition research revolving around RIF.

Ramadan Intermittent Fasting Is Associated with Changes in Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Metabolically Healthy Obese Subjects.

Background and Objectives: Dietary modification is the principal approach to the management of hyperlipidemia in adults. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma cholesterol and a target for novel lipid-lowering pharmacotherapies. This study aimed to explore how circulating levels of PCSK9 changed during Ramadan intermittent fasting in metabolically healthy obese subjects. Materials and Methods: This cross-sectional study used convenience sampling to recruit 55 overweight and obese participants (22 females and 33 males) who observed Ramadan fasting. Body weight and composition, glucoregulatory factors, serum PCSK9 concentration, dietary intake, and physical activity were assessed 1 week before and at the end of Ramadan fasting. Results: The median (interquartile range) age was 35 (22) years, and body mass index was 30.2 (5.4). We found significant (p < 0.05) increases in serum levels of PCSK9, serum insulin, insulin resistance, and leptin at the end of Ramadan compared with pre-fasting levels. Significant (p < 0.05) reductions in body weight, waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and adiponectin were also observed at the end of Ramadan. Conclusions: Observing Ramadan fasting was associated with increased PCSK9 levels in metabolically healthy obese subjects. The complex relationships between PCSK9 and insulin resistance and dysregulation of adipokine secretion in relation to dietary and lifestyle modifications during Ramadan warrant further research.

Effect of Camel Milk on Glucose Homeostasis in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The effects of camel milk (CM) intake on glycemic control in patients with diabetes are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of CM intake on glucose homeostasis parameters in patients with both types of diabetes mellitus; T1DM and T2DM. We searched Google Scholar, PubMed/MEDLINE, EBSCO host, CINAHL, ScienceDirect, Cochrane, ProQuest Medical, Web of Science, and Scopus databases from inception until the end of November 2021. Relevant RCTs were identified, and the effect size was reported as mean difference (MD) and standard deviation (SD). Parameters of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting serum insulin (FI), insulin resistance (expressed in terms of HOMA-IR), insulin dose (ID) received, serum insulin antibody (IA), and C-peptide (CP) were tested. Out of 4054 collected articles, 14 RCTs (total 663 subjects) were eligible for inclusion. The pooled results obtained using a random-effects model showed a statistically significant decrease in HbA1c levels (MD, −1.24, 95% confidence interval (CI): −2.00, −0.48, p < 0.001 heterogeneity (I2) = 94%) and ID received (MD, −16.72, 95% CI: −22.09, −11.35 p < 0.00001, I2 = 90%), with a clear tendency was shown, but non-significant, to decrease FBG (MD, −23.32, 95% CI: −47.33, 0.70, p = 0.06, I2 = 98%) in patients with diabetes who consumed CM in comparison to those on usual care. Conversely, the consumption of CM did not show significant reductions in the rest of the glucose homeostasis parameters. Subgroup analysis revealed that patients with T2DM were more beneficially affected by CM intake than those with T1DM in lowering FBG, while patients with T1DM were more beneficially affected by CM intake than those with T2DM in lowering HbA1c. Both fresh and treated (pasteurized/fermented) CM gave similar beneficial effects in lowering HbA1c. Lastly, a relatively superior effect for longer duration on shorter duration (>6 months, ≤6 months, respectively) of CM intake is found in lowering HbA1c. To conclude, long-term consumption of CM by patients with diabetes could be a useful adjuvant therapy alongside classical medications, especially in lowering the required insulin dose and HbA1c. Due to the high heterogeneity observed in the included studies, more controlled trials with a larger sample size are warranted to confirm our results and to control some confounders and interfering factors existing in the analyzed articles.

Ramadan diurnal intermittent fasting is associated with significant plasma metabolomics changes in subjects with overweight and obesity: A prospective cohort study.

Introduction: During the holy month of Ramadan, adult healthy Muslims are mandated to abstain from dawn to sunset, with free eating at night hours that may extend up to 12 h. The current work was designed to investigate the metabolomics changes incurred upon the observance of Ramadan diurnal intermittent fasting (RDIF). Methods: Twenty-five metabolically healthy participants with overweight and obesity (7 females and 18 males, with a mean age of 39.48 ± 10.0 years) were recruited for the study and were followed before and at the end of RDIF month. Dietary, anthropometric, biochemical, and physical activity assessments were performed before and at the end of the fasting month. The metabolomic assay was performed using liquid chromatography-mass spectrometry for the two-time points. Results and discussion: Metabolomics assay revealed a significant reduction in a few metabolites. The analysis revealed that 27 metabolites differed significantly (P < 0.05) between pre-and post-RDIF. Among the differentially abundant metabolites, 23 showed a decrease with fasting, these included several amino acids such as aspartame, tryptophan, phenylalanine, histidine, and other metabolites including valeric acid, and cortisol. On the other hand, only four metabolites showed increased levels after RDIF including traumatic acid, 2-pyrrolidinone, PC[18:1(9Z)/18:1(9Z)], and L-sorbose. The MetaboAnalyst® platform reported that the top enriched metabolic pathways included: (1) histidine metabolism; (2) folate biosynthesis (3) phenylalanine, tyrosine, and tryptophan biosynthesis; (4) aminoacyltRNA biosynthesis; (5) caffeine metabolism; (6) vitamin B6 metabolism; and several other pathways relating to lipid metabolisms such as arachidonic acid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In conclusion, RDIF entails significant changes in various metabolic pathways that reflect different dietary and lifestyle behaviors practiced during the fasting month.

Does four-week consecutive, dawn-to-sunset intermittent fasting during Ramadan affect cardiometabolic risk factors in healthy adults? A systematic review, meta-analysis, and meta-regression.

AIMS: This study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29-30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression. DATA SYNTHESIS: We conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18-85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K = 77, number of subjects N = 3705, Hedge's g = -0.092, 95% confidence interval (CI): -0.168, 0.016); TG (K = 74, N = 3591, Hedge's g = -0.127, 95% CI: -0.203, 0.051); HDL-C (K = 68, N = 3528, Hedge's g = 0.138, 95% CI: 0.051, 0.224); LDL-C (K = 65, N = 3354, Hedge's g = -0.115, 95% CI: -0.197, -0.034); VLDL-C (K = 13, N = 648, Hedge's g = -0.252, 95% CI: -0.431, 0.073), DBP (K = 32, N = 1716, Hedge's g = -0.255, 95% CI: -0.363, 0.147), and HR (K = 12, N = 674, Hedge's g = -0.082, 95% CI: -0.300, 0.136). Meta-regression revealed that the age of fasting people was a significant moderator of changes in both HDL-C (P = 0.02) and VLDL-C (P = 0.01). Male sex was the only significant moderator of changes in LDL-C (P = 0.055). Fasting time duration was the only significant moderator of HDL-C (P = 0.001) at the end of Ramadan. CONCLUSIONS: RDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people.

Ramadan Diurnal Intermittent Fasting Is Associated With Attenuated FTO Gene Expression in Subjects With Overweight and Obesity: A Prospective Cohort Study.

Aim and Background: A growing body of evidence supports the impact of intermittent fasting (IF) on normalizing body weight and that the interaction between body genes and environmental factors shapes human susceptibility to developing obesity. FTO gene is one of these genes with metabolic effects related to energy metabolism and body fat deposition. This research examined the changes in FTO gene expression upon Ramadan intermittent fasting (RIF) in a group of metabolically healthy subjects with overweight and obesity. Methods: Sixty-three (63) subjects were recruited, of which 57 (17 males and 40 females, mean age 38.4 ± 11.2 years) subjects with overweight and obesity (BMI = 29.89 ± 5.02 kg/m2were recruited and monitored before and at the end of Ramadan month), and 6 healthy subjects with normal BMI (21.4 ± 2.20 kg/m2) recruited only to standardize the reference for normal levels of FTO gene expression. In the two-time points, anthropometric, biochemical, and dietary assessments were undertaken, and FTO gene expression tests were performed using RNA extracted from the whole blood sample. Results: In contrast to normal BMI subjects, the relative gene expressions in overweight/obese were significantly decreased at the end of Ramadan (-32.30%, 95% CI-0.052 -0.981) in comparison with the pre-fasting state. Significant reductions were found in body weight, BMI, fat mass, body fat percent, hip circumference, LDL, IL-6, TNF-α (P<0.001), and in waist circumference (P<0.05), whilst HDL and IL-10 significantly increased (P<0.001) at the end of Ramadan in comparison with the pre-fasting levels. Binary logistic regression analysis for genetic expressions showed no significant association between high-energy intake, waist circumference, or obesity and FTO gene expression. Conclusions: RIF is associated with the downregulation of the FTO gene expression in subjects with obesity, and this may explain, at least in part, its favorable metabolic effects. Hence, RIF presumably may entail a protective impact against body weight gain and its adverse metabolic-related derangements in subjects with obesity.

Effect of diurnal intermittent fasting during Ramadan on ghrelin, leptin, melatonin, and cortisol levels among overweight and obese subjects: A prospective observational study.

BACKGROUND: Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors, and fluctuate with light and dark cycles. During the fasting month of Ramadan, a shift to nighttime eating is expected to affect circadian rhythm hormones and, subsequently, the levels of melatonin, cortisol, ghrelin, and leptin. The present study aimed to examine the effect of diurnal intermittent fasting (DIF) during Ramadan on daytime levels of ghrelin, leptin, melatonin, and cortisol hormones in a group of overweight and obese subjects, and to determine how anthropometric, dietary, and lifestyle changes during the month of Ramadan correlate with these hormonal changes. METHODS: Fifty-seven overweight and obese male (40) and female (17) subjects were enrolled in this study. Anthropometric measurements, dietary intake, sleep duration, and hormonal levels of serum ghrelin, leptin, melatonin, and salivary cortisol were assessed one week before the start of Ramadan fasting and after 28 days of fasting at fixed times of the day (11:00 am-1:00 pm). RESULTS: At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly (P<0.001) decreased, while salivary cortisol did not change compared to the levels assessed in the pre-fasting state. CONCLUSIONS: DIF during Ramadan significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones. Further studies are needed to assess DIF's impact on the circadian rhythmicity of overweight and obese fasting people.

Ramadan intermittent fasting and immunity: An important topic in the era of COVID-19.

WITH the growing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) infection, a parallel growing interest arose concerning potential preventive and adjunct therapies, dietary and lifestyle modifications, and remedies that may boost the immunity against SARS-CoV-2 infection. Furthermore, as Ramadan intermittent religious fasting that is practiced by about one and a half billion Muslims throughout the globe is coincide this year with COVID-19 pandemic, a growing debate rose concerning the expected impact of fasting during Ramadan month and the associated dietary and lifestyle behaviors on the body's immunity against the pandemic infection. Published literature was searched to find out how intermittent fasting (IF) and its model of Ramadan affect the various aspects related to the body's immunity against microbial infections. IF was found to impact immunity by changing different related elements, including oxidative stress and inflammation, metabolism, body weight, and body composition. Dietary and lifestyle modifications during Ramadan month and their impact on immunity, such as water intake and hydration status, sleep duration and timing, caloric intake and mealtime, and social and spirtual activities, were addressed. Further research is warranted to figure out how IF during ramadan affects immunity against SARS-CoV-2 infection.

Selective inhibition of Rhizopus eumelanin biosynthesis by novel natural product scaffold-based designs caused significant inhibition of fungal pathogenesis.

Melanin is a dark color pigment biosynthesized naturally in most living organisms. Fungal melanin is a major putative virulence factor of Mucorales fungi that allows intracellular persistence by inducing phagosome maturation arrest. Recently, it has been shown that the black pigments of Rhizopus delemar is of eumelanin type, that requires the involvement of tyrosinase (a copper-dependent enzyme) in its biosynthesis. Herein, we have developed a series of compounds (UOSC-1-14) to selectively target Rhizopus melanin and explored this mechanism therapeutically. The compounds were designed based on the scaffold of the natural product, cuminaldehyde, identified from plant sources and has been shown to develop non-selective inhibition of melanin production. While all synthesized compounds showed significant inhibition of Rhizopus melanin production and limited toxicity to mammalian cells, only four compounds (UOSC-1, 2, 13, and 14) were selected as promising candidates based on their selective inhibition to fungal melanin. The activity of compound UOSC-2 was comparable to the positive control kojic acid. The selected candidates showed significant inhibition of Rhizopus melanin but not human melanin by targeting the fungal tyrosinase, and with an IC50 that are 9 times lower than the reference standard, kojic acid. Furthermore, the produced white spores were phagocytized easily and cleared faster from the lungs of infected immunocompetent mice and from the human macrophages when compared with wild-type spores. Collectively, the results suggested that the newly designed derivatives, particularly UOSC-2 can serve as promising candidate to overcome persistence mechanisms of fungal melanin production and hence make them accessible to host defenses.