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This study synthesized gold nanoparticles (AuNPs) using a facile microwave-assisted chemical route and evaluated them as potential anticancer candidates against breast and colon cancer cell lines. Numerous spectral characterization tools were used to study the optical properties, structure, and morphology of the prepared AuNPs. UV-Vis spectroscopy showed a characteristic peak at 517 nm, which confirms the formation of AuNPs. The crystalline structure of NPs was studied by X-ray diffraction, and the NPs’ shape and size were calculated with Field emission transmission electron microscopy. The synthesized AuNPs were found to be uniform in size in the range of 2–6 nm. A variety of biological tests, including MTT, scratch, real time polymerase chain reaction (RT-PCR), and comet assays were adopted to assess the anticancer potential of these AuNPs in the studied cancer cell models. The findings suggested a cell-dependent cytotoxicity of AuNPs. Different cell viability of 40.3 and 66.4% were obtained for MCF-7 and HCT-116, respectively, at 5 µg/mL of AuNPs. The scratch assay showed AuNPs impede cell migration in a concentration-dependent manner in the MCF-7 cell line. On the other hand, real-time polymerase chain reaction (RT-PCR) of apoptotic (p53, Bax, and caspase-3) and anti-apoptotic (BCl-2) genes revealed upregulation and downregulation of these genes, respectively, probably leading to its cytotoxicity. At 5 µg/mL concentration of AuNPs, reactive oxygen species (ROS) production was found to be increased by 26.4 and 42.7%, respectively, in MCF-7 and HCT-116 cells. Similarly, comet assay demonstrated AuNPs induced DNA damage in the studied cancer cell lines. These findings suggest that the observed anticancer efficacy of AuNPs was driven by ROS generation. The synthesized AuNPs appeared to be a promising therapeutic against cancer cells. However, our in vitro data need to be confirmed and validated in ex vivo and in vivo models so that this NP can be further exploited for human use.

Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC50 value of 16.6 µM. Hesperidin shows a significant binding toward α-amylase with a binding constant (Ka) of the order of 104 M−1. The evaluation of thermodynamic parameters (∆H and ∆S) suggested that van der Waals force and hydrogen bonding drive seemingly specific hesperidin-α-amylase complex formation. Glycation and oxidation studies were performed using human serum albumin (HSA) as ideal protein. Hesperidin inhibited fructosamine content ≈40% at 50 µM and inhibited advanced glycation end products (AGEs) formation by 71.2% at the same concentration. Moreover, significant recovery was evident in free –SH groups and carbonyl content of HSA. Additionally, molecular docking also entrenched in vitro observations and provided an insight into the important residues (Trp58, Gln63, His101, Glu233, Asp300, and His305) at the heart of hesperidin-α-amylase interaction. This study delineates mechanistic insight of hesperidin-α-amylase interaction and provides a platform for use of hesperidin to treat AGEs directed diseases.

BACKGROUND: In addition to calcium and phosphate homeostasis in peripheral tissues; vitamin D performs a neuroprotection role in the nervous system. The neuroprotective actions of vitamin D include: increasing vitamin D receptor (VDR) expression, control glutathione synthesis and nitric oxide synthase activity and induce neurotrophins such as nerve growth factor (NGF). VDR mediates cellular actions, and biological responses of the vitamin D. OBJECTIVE: To study the effect of VDR and NGF expression levels by vitamin D3 treatment in induced oxidative stress in primary cortical neuronal cultures. METHOD: Primary neuronal cultures were set up from the cortex region of neonatal rat’s brain. They were cultured for up to 72 h in the presence of 0.25μg/ml vitamin D3. These cells were exposed to 0.5 mM H2O2 for two hours before collecting cell pellet and medium for biochemical assays. Control and H2O2 treated cells were cultured in the absence of vitamin D3 treatment. Sandwich ELISA was used to study NGF expression. Western blotting and immunofluorescence of cultured cells were used to estimate the expression of VDR. RESULTS: Vitamin D3 treatment increased more significantly (P

Lactoferrin is a heme-binding multifunctional glycoprotein known for iron transportation in the blood and also contributes to innate immunity. In this study, the interaction of theaflavin monogallate, a polyphenolic component of black tea, with camel milk lactoferrin was studied using various biophysical and computational techniques. Fluorescence quenching at different temperatures suggests that theaflavin monogallate interacted with lactoferrin by forming a non-fluorescent complex, i.e., static quenching. Theaflavin monogallate shows a significant affinity towards lactoferrin with a binding constant of ∼104–105 M−1 at different temperatures. ANS binding shows that the binding of polyphenol resulted in the burial of hydrophobic domains of lactoferrin. Moreover, thermodynamic parameters (ΔH, ΔS and ΔG) suggested that the interaction between protein and polyphenol was entropically favored and spontaneous. Circular dichroism confirmed there was no alteration in the secondary structure of lactoferrin. The energy transfer efficiency (FRET) from lactoferrin to theaflavin was found to be approximately 50%, with a distance between protein and polyphenol of 2.44 nm. Molecular docking shows that the binding energy of lactoferrin–theaflavin monogallate interaction was −9.7 kcal mol−1. Theaflavin monogallate was bound at the central cavity of lactoferrin and formed hydrogen bonds with Gln89, Tyr192, Lys301, Ser303, Gln87, and Val250 of lactoferrin. Other residues, such as Tyr82, Tyr92, and Tyr192, were involved in hydrophobic interactions. The calculation of various molecular dynamics simulations parameters indicated the formation of a stable complex between protein and polyphenol. This study delineates the binding mechanism of polyphenol with milk protein and could be helpful in milk formulations and play a key role in the food industry.

Type 2 diabetes mellitus (T2DM) outcomes were observed to be influenced by circulating trace elements' status. The differences and correlations between serum levels of chromium (Cr), manganese (Mn), nickel (Ni), and selenium (Se) in Saudi patients with and without T2DM as well as those with prediabetes (pre-DM) were examined in this retrospective cross-sectional study.Anthropometrics and fasting blood samples were collected from 119 patients with T2DM (aged 41-64 years), 95 non-T2DM (aged 27-55 years), and 80 with pre-DM (aged 35-57 years). An inductively coupled plasma-mass spectrometer was used to measure trace minerals in the blood.T2DM patients had significantly lower Mn serum concentrations than controls. There was no difference in Cr and Ni levels between groups. Serum Mn and Ni levels were lower in pre-DM subjects than controls. Serum Se concentrations were higher in pre-DM and T2DM patients than controls. In T2DM patients, serum Cr and Mn levels were inversely correlated with glucose, while Ni and Se levels were positively correlated with glucose in the T2DM group.Because of their roles in glucose metabolism, impaired trace element status may also play a role in T2DM pathogenesis. Appropriate dietary control and mineral supplementation are recommended.

Protein fibrillation is a leading cause of innumerable neurodegenerative diseases. The exact underlying mechanism associated with the formation of fibrils is yet to be known. Recently, the role of metal ions resulting into fibrillation of proteins has gained attention of the scientific community. In this piece of work, we have investigated the effect of the aluminum (Al) metal ion on the kinetics of aggregation of bovine serum albumin (BSA) protein under physiological conditions by employing several biophysical and microscopic techniques. Quenching of tryptophan fluorescence was observed along with 9 nm blue shift, demonstrating BSA becomes more hydrophobic during unfolding pathway of thermal denaturation. Moreover, ANS (8-Anilino-1-naphthalene sulfonic acid) binding shows quenching in fluorescence intensity with increasing time of incubation at 65 0C, suggesting unfolding leading to the disruption of hydrophobic patches in BSA. Besides, Thioflavin T intensity indicated a significant acceleration in BSA fibrillation at a ratio of 1:1 and 1:2 of BSA and Al (III) metal ion respectively. In addition, circular dichroism (CD) spectroscopy study revealed the transition of BSA from α-helical conformation to the β-sheet rich structure. Molecular docking analysis demonstrated significant binding affinity (-1.2 kcal/mol) of Al (III) with BSA involving Phe501, Phe506, Val575, Thr578, Gln579, Leu531 residues. Transmission electron microscopy (TEM) reaffirm augmentation of thermal-induced BSA fibril formation in the presence of Al (III) metal ions. This study highlights the metal chelating potency as the possible therapeutic target for neurological diseases.

Low levels of vitamin D have been linked with increased adiposity and diminished muscle strength. Whether it is also related to fat deposition in muscle tissues is not studied well. This study explored the associations between circulating 25-hydroxyvitamin D (25(OH)D) and fat deposition in muscle tissues of adult Arab males. A total 465 adult Saudi males were included in this cross-sectional study. Anthropometrics, body composition and muscle strength were assessed. Serum 25(OH)D was determined and quantified enzymatically. They were grouped according to vitamin D status: deficient (25(OH)D 50 nmol/l)140 (30.1%). Mean level of lean/height2, lean-arm-legs and lean-arms-legs/height2 were significantly higher in 25(OH)D deficient participants (p-values 0.03; 0.05 and 0.01 respectively). Thigh strength was significantly higher in 25(OH)D sufficient participants than their deficient counterparts (p = 0.02). In all participants, a significant correlation between 25(OH)D was observed with age and thigh-strength (p-values

The aldose reductase (AR) enzyme is considered a potential target for the management of diabetic complications. In this study, we describe the binding and enzyme kinetics of AR by naringenin, a bioflavonoid present in many dietary sources. Naringenin showed an inhibitory effect on the activity of AR with an IC50 value of 2.6 μM in an uncompetitive manner. Binding studies confirmed that the naringenin-AR complex has high spontaneous affinity (Ka = 1.94–7.88 × 104) with negative ΔG° value (−5.78 kcal mol−1). The interaction was enthalpy driven and the microenvironment of aromatic residues of AR was also altered. Various stages of protein oxidation and glycation were also measured. Naringenin inhibited fructosamine content by approximately 31.6% at 10 μM, and at the same concentration, >93% inhibition of fluorescent advanced glycation end-products (AGEs) was achieved. There was a significant recovery in free thiol groups and carbonyl content of bovine serum albumin (BSA). Furthermore, molecular docking of naringenin with AR revealed that naringenin formed two hydrogen bonds (Asn160 and Ile260), and three Pi-Pi interactions (two with Trp20 and one with His110). This study provides molecular insight of naringenin-AR interaction and mechanism of antiglycation which may be useful in the development of inhibitors for AGEs formation.

This study aimed to assess the relationship between vitamin D [25(OH)D] status and parathyroid hormone (PTH) in Saudi adults to determine the optimum 25(OH)D cut-off in the Saudi adult population. A total of 1093 apparently healthy Saudi subjects (720 women and 373 men) aged 50.7 ± 13.9 years were included in this cross-sectional study. Serum 25(OH)D, PTH, calcium and albumin levels were determined. The over-all prevalence of 25(OH)D deficiency (

Quinoline yellow (QY) is a synthetic yellow dye widely used as a coloring agent for various foodstuffs. In the current study, we have examined the role of QY on the aggregation propensity of hen egg-white lysozyme (HEWL) under physiological conditions. The dye induced conformational changes in HEWL leading to aggregate formation were identified by circular dichroism (CD), turbidity analysis, fluorescence measurement and microscopic (TEM) imaging. Molecular docking and molecular dynamics simulation studies were also employed to strengthen binding and aggregation results. Our results indicate that 25-100 µM of QY induces aggregation in HEWL, while lower QY concentrations (5 and 10 µM) does not have any effect on the aggregation propensity of HEWL. The kinetics of HEWL aggregation demonstrate nucleation independent aggregation of HEWL without lag phase. On the other hand, far UV-CD analysis illustrated the loss of α-helical structure with the increasing concentration of QY. TEM results also support the formation of aggregate structures in HEWL when exposed to QY. Molecular docking and simulation studies revealed that the HEWL-QY complex is stable as compared to individual entities. In silico analysis also illustrated that QY-induced aggregation of HEWL proceeds through the formation of hydrogen bonds, electrostatic (Pi-Anion) and Pi-Sulfur interactions. The above-mentioned results highlight the possible detrimental effect by food additive dyes, particularly in protein misfolding.

Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall −0.34, p

P-Coumaric acid (p-CA) is a plant metabolite with anti-inflammatory and antioxidant effects. Due to its therapeutic potential, p-CA has attracted much attention from the scientific community lately. Oxidative stress, amyloid formation, and impaired proteasomal degradation are hallmarks of neurodegenerative diseases like Alzheimer's (AD) and are targets for developing therapeutics against such conditions. Here, we have investigated the anti-amyloidogenic properties of p-coumaric acid on hen egg white lysozyme (HEWL). Heat, pH, and agitation (55 °C, pH 2.0, 600 rpm) stress were used to induce amyloid formation in lysozyme. The aggregates characterization was done by turbidity, Rayleigh light scattering (RLS), and thioflavin-T (ThT) assays. Moreover, ANS (1-anilino naphthalene sulphate) binding assay and circular dichroism (CD) were employed to unveil protein hydrophobicity and secondary structure perturbation, respectively. Lysozyme demonstrated increased hydrophobicity and transition of α-helix to β-sheet under aggregating conditions. Moreover, co-incubation of lysozyme with p-coumaric acid attenuates the process of amyloid in a concentration dependent manner. At 50 and 200 μM concentrations of p-coumaric acid, lysozyme retained its native-like folded structure. Cytotoxicity protection on human SK-N-SH neuroblastoma cell line was also observed using MTT assay and phase contrast microscopy. In addition, transmission electron microscopy (TEM) reaffirms the fibrillar nature of lysozyme aggregates and their attenuation by p-coumaric acid. The steady state fluorescence revealed that the mode of fluorescence quenching for the HEWL-p-coumaric acid interaction is static rather than dynamic. Moderate strength of binding in order of 10

Amyloid fibrils abnormally accumulate together in the human body under certain conditions, which can result in lethal conditions. Thus, blocking this aggregation may prevent or treat this disease. Chlorothiazide (CTZ) is a diuretic and is used to treat hypertension. Several previous studies suggest that diuretics prevent amyloid-related diseases and reduce amyloid aggregation. Thus, in this study we examine the effects of CTZ on hen egg white lysozyme (HEWL) aggregation using spectroscopic, docking, and microscopic approaches. Our results showed that under protein misfolding conditions of 55 °C, pH 2.0, and 600 rpm agitation, HEWL aggregated as evidenced by the increased turbidity and Rayleigh light scattering (RLS). Furthermore, thioflavin-T, as well as trans electron microscope (TEM) analysis confirmed the formation of amyloid structures. An anti-aggregation effect of CTZ is observed on HEWL aggregations. Circular dichroism (CD), TEM, and Thioflavin-T fluorescence show that both CTZ concentrations reduce the formation of amyloid fibrils as compared to fibrillated. The turbidity, RLS, and ANS fluorescence increase with CTZ increasing. This increase is attributed to the formation of a soluble aggregation. As evidenced by CD analysis, there was no significant difference in α-helix content and β-sheet content between at 10 µM CTZ and 100 µM. A TEM analysis of HEWL coincubated with CTZ at different concentrations validated all the above-mentioned results. The TEM results show that CTZ induces morphological changes in the typical structure of amyloid fibrils. The steady-state quenching study demonstrated that CTZ and HEWL bind spontaneously via hydrophobic interactions. HEWL–CTZ also interacts dynamically with changes in the environment surrounding tryptophan. Computational results revealed the binding of CTZ to ILE98, GLN57, ASP52, TRP108, TRP63, TRP63, ILE58, and ALA107 residues in HEWL via hydrophobic interactions and hydrogen bonds with a binding energy of −6.58 kcal mol−1. We suggest that at 10 µM and 100 μM, CTZ binds to the aggregation-prone region (APR) of HEWL and stabilizes it, thus preventing aggregation. Based on these findings, we can conclude that CTZ has antiamyloidogenic activity and can prevent fibril aggregation.

Angiogenin (ANG), a multifunctional protein known to induce blood vessel formation, is a potential biomarker for cardiovascular diseases; however, whether it is affected by vitamin D supplementation is not known. This interventional study in vitamin D-deficient Saudi adults was designed to investigate it. A total of 100 vitamin D-deficient Saudi adults aged 30–50 years were randomly selected to undergo 6-month vitamin D supplementation. Circulating levels of fasting glucose, lipids, vitamin D, apolipoproteins (AI, AII, B, CI, CII, CIII, E, and H), and ANG were measured using commercially available assays at baseline and after six months. Overall, vitamin D levels increased significantly post intervention. With this, levels of apo-CIII and apo-E significantly increased (p-values of 0.001 and 0.009, respectively) with a significant parallel decrease in apo-B (p = 0.003). ANG levels were significantly positively associated with most apolipoproteins and inversely correlated with HDL-cholesterol. Post intervention, the changes in ANG levels were positively correlated with apo-E (r = 0.32; p < 0.01 in all subjects and r = 0.40; p < 0.05 in males). Vitamin D supplementation may modestly affect ANG levels. The association observed between ANG and apo-E is worthy of further investigation since both biomarkers have been linked to neurodegenerative disorders.

Epidemiological studies suggest that the Zinc-α-2-glycoprotein (ZAG) plays significant physiological roles. In this study we investigate whether ZAG could be considered as a clinical biomarker in the diagnosis and prognosis of metabolic syndrome (MetS) in Saudi population. As such insights urgently required for management of MetS. Thus, we have determined serum levels of ZAG in patients with MetS and normal individuals. We have also assessed the correlation between ZAG and different components of MetS. In this case–control study, clinical information of 200 Saudi male and female subjects (age range 30–65) with MetS (n = 100) and healthy controls (n = 100) were extracted from the database of the Chair of Biomarkers of Chronic Disease (CBCD) in King Saud University (KSU), Riyadh, Saudi Arabia. MetS was screened according to NCEP ATP III criteria (National Cholesterol Education Program Adult Treatment Panel III). Fasting glucose and lipid profile levels were measured using Konelab. Serum TNF-α, IL- 6, CRP and ZAG levels were measured using commercially available assays. There was an age-dependent significant increase in ZAG level among MetS subjects than controls (43.8 ± 19.5 vs 48.1 ± 14.8; P = 0.04). A significant inverse correlation between ZAG and serum HDL-cholesterol (r = − 0.20, P P P P

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( OR = 1.49 , 95% CI 1.0-2.1, P = 0.03 ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048 ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

The present study aimed to determine the serum organochlorine pesticides (OCPs) levels and risk of exposure among Saudi adults. Most OCPs are considered as endocrine-disrupting chemicals, and exposure can induce adverse health effects in both humans and wildlife. Serum OCP levels have not been documented in the Saudi population. Serum OCP concentrations were quantified using gas chromatography mass spectrometry (GC-MS/MS) in 302 serum samples collected from adult Saudis. All studied OCPs were detected in all participants. High concentrations of DDT and its metabolites (DDE and DDD) were detected in both males and females, with concentrations being significantly higher in males. High concentrations of 2,4-DDE, 4,4-DDE, and gamma-HCH were detected (18.31, 16.12, and 15.15 ng g−1 lipid and 5.9, 7.1, and 8.6 ng g−1 lipid for males and females, respectively). Alpha-HCH, Beta-HCH, 2,4-DDT, and 4,4-DDT were detected at concentrations lower than 2 ng g−1. Levels of OCPs varied according to age and body mass index (BMI). Serum concentrations of OCPs significantly differed between Saudi males and females and were influenced by age and BMI. This study is the first to document serum OCP concentrations in Saudi adults from Riyadh, KSA. Monitoring programs are suggested for evaluating serum OCP concentrations in the general population to track toxicity levels and serve as an indicator of possible adverse health effects. Keywords: Organochlorine pesticides, GC-MS/MS, Public health, Saudi Arabia

Summary Objective The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus (T2DM). Methods Saudi adults with naive T2DM (n = 30; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5 × 109 cfu/g of Ecologic®Barrier (multi-strain probiotics; n = 31; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters [glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR)], lipids [triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio], inflammatory markers [tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP)] and adipocytokines [leptin, adiponectin and resistin] at baseline and after 3 and 6 months of intervention. Results Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (−3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers. Conclusion Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy. Trial registration ClinicalTrials.gov Identifier: NCT01765517 .

This study aims to investigate the association of vitamin D (VD) knowledge, behavior, and attitude with BMI status among Saudi adults. This cross-sectional online survey included a total of 774 participants (M/F: 239/535). Knowledge about the overall sources of VD was highest in OB participants in correctly identifying sunlight (95.1%; p < 0.001) while significantly more OW participants answered food (83.1%; p = 0.04) and fortified food (66.5%; p = 0.02). However, 18.9% of OB participants also wrongly identified air as a VD source and this was significantly higher than in other groups (p = 0.03). OW participants were 50% less likely to identify salmon and fish oil (odds ratio, OR 0.5 (95% Confidence interval, CI 0.4–0.7); p < 0.01) and 40% more likely to identify chicken (OR 1.4 (1.0–1.9); p < 0.05) as dietary sources of VD than controls. On the other hand, OB participants were almost three times more likely to know that sunlight exposure is the main source of VD than controls (OR 2.65 (1.2–6.0); p < 0.05). In conclusion, while VD knowledge overall was apparently high in Saudi adults regardless of BMI status, the quality of knowledge among OB and OW individuals appear inconsistent, particularly in terms of identifying the right VD sources. Public health awareness campaigns should include the correction of VD misconceptions so that high-risk populations are able to make well-informed decisions in achieving optimal VD levels.

The continuous loss of human life due to the paucity of effective drugs against different forms of cancer demands a better/noble therapeutic approach. One possible way could be the use of nanostructures-based treatment methods. In the current piece of work, we have synthesized silver nanoparticles (AgNPs) using plant (Heliotropiumbacciferum) extract using AgNO3 as starting materials. The size, shape, and structure of synthesized AgNPs were confirmed by various spectroscopy and microscopic techniques. The average size of biosynthesized AgNPs was found to be in the range of 15 nm. The anticancer potential of these AgNPs was evaluated by a battery of tests such as MTT, scratch, and comet assays in breast (MCF-7) and colorectal (HCT-116) cancer models. The toxicity of AgNPs towards cancer cells was confirmed by the expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR. The cell viability assay showed an IC50 value of 5.44 and 9.54 µg/mL for AgNPs in MCF-7 and HCT-116 cell lines respectively. We also observed cell migration inhibiting potential of AgNPs in a concentration-dependent manner in MCF-7 cell lines. A tremendous rise (150–250%) in the production of ROS was observed as a result of AgNPs treatment compared with control. Moreover, the RT-PCR results indicated the difference in expression levels of pro/antiapoptotic proteins in both cancer cells. All these results indicate that cell death observed by us is mediated by ROS production, which might have altered the cellular redox status. Collectively, we report the antimetastasis potential of biogenic synthesized AgNPs against breast and colorectal cancers. The biogenic synthesis of AgNPs seems to be a promising anticancer therapy with greater efficacy against the studied cell lines.

Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC

Widespread vitamin D deficiency (serum 25-hydroxyvitamin D 50 nmol/L) in Saudi Arabia (SA) has been documented, yet a time trend is needed to establish where the prevalence is headed. This study aims to fill this gap.This cross-sectional series (N = 7360) were conducted in the central region of SA from 2008 to 2017. Participants of all ages were taken from multiple cohorts that included the Biomarker Screening in Riyadh (2008-2010; N = 1460), the Osteoporosis Registry (2014-2017; N = 1225), Gestational Diabetes Mellitus cohort (2014-2017, N = 281), Vitamin D School Project (2011-2017; N = 3039) and Prediabetes cohort (2012-2017; N = 1355) master databases.Vitamin D deficiency in SA has a 10-year prevalence of 73.2 %. Between 2008-2017, the prevalence of vitamin D deficiency decreased from 87.1% to 64.7% for participants aged 18-40 years (p-trend0.001), and from 86.2% to 45.7% in participants aged40 years (p-trend0.001). During this period, vitamin D deficiency in females decreased from 80.1% to 69.6% (p-trend0.001), whereas in males, it decreased from 93.2% to 49.3% (p-trend0.001). Serum 25(OH)D was observed to have an overall increase of 2.2 ± 0.1 nmol/l (p 0.001) along with the seasonally adjusted annual increase of 1.3 ± 0.2 nmol/l from 2008 to 2017 (p 0.001).The decreasing trend in vitamin D deficiency in SA across all demographics suggests successful public health campaigns over time. It will be interesting to investigate further whether the general improvement in the vitamin D status at the community level also translated in lesser incidences of vitamin d-related diseases over time.

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18-22) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in -vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and -vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women.

Introduction: This study aimed to investigate the association between components of metabolic syndrome (MetS) at first trimester and development of Gestational diabetes mellitus (GDM) in 498 Saudi pregnant women.Materials and Methods: Biochemical and anthropometric parameters were determined at the first trimester and MetS components were defined. Participants were screened for GDM at follow up according to International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. The main outcome measures were development of GDM and GDM risk vs. MetS components at first trimester.Results: One hundred twenty three (24.7%) were diagnosed with GDM according to IADPSG criteria. GDM risk was significantly higher for participants with hypertriglyceridemia at 1st trimester even after adjusting for age, BMI and parity (OR: 1.82; CI: 1.1–3.7, p = 0.04). Furthermore, the odds of hyperglycemia at 1st trimester was significantly higher in GDM than in non-GDM participants even after adjustments (OR: 2.13, 95% CI: 1.1 to 4.3, p = 0.038). The receiver operating characteristic (ROC) for predicting GDM revealed an area under the curve (AUC) of 0.69 (95% CI: 0.64 to 0.74, p < 0.001) and 0.71 (95% CI: 0.65 to 0.77, p < 0.001) for first-trimester hyperglycemia and hypertriglyceridemia respectively.Conclusions: The incidence of GDM in Saudi pregnant women was strongly associated with hyperglycemia and hypertriglyceridemia at first trimester. These findings are of clinical importance, as an assessment of MetS in early pregnancy can identify women at higher risk of developing GDM.

Vitamin D supplementation may be used to lower oxidative stress. This interventional study aimed to investigate the effects of vitamin D supplementation on glutathione peroxidase 1 (GPx1) levels and other parameters in Arab adults with prediabetes. A total of 203 Saudi adults with prediabetes and vitamin D deficiency [intervention group, N = 146 (53 males and 93 females), control group, N = 57 (25 males and 32 females)] were included in this non-randomized, six-month intervention study. The intervention group received 50,000 international units (IU) cholecalciferol tablets once a week for two months, then twice a month for the next two months, followed by 1000 IU daily for the last two months. The control group received no supplementation. Serum 25(OH)D, lipid profile, glucose, C-reactive protein (CRP) and GPx1 were measured at baseline and after six months. Post-intervention, GPx1 concentrations increased significantly in the intervention group [17.3 (11.5&ndash, 59.0) vs 26.7 (11.4&ndash, 59.9) p &lt, 0.01] while no changes were observed in the control group (p = 0.15). This significant increase in 25(OH)D and GPx1 levels persisted after adjusting for age and BMI. Stratification according to sex revealed that this favourable increase in GPx1 was true only for males (p = 0.002). In all groups, baseline GPx1 was inversely correlated with low density lipoprotein (LDL)-cholesterol (r = &minus, 0.26, p &lt, 0.01) and body mass index (BMI) (r = &minus, 0.20, p &lt, 0.05), while positively correlated with age (r = 0.18, p &lt, 0.05) and systolic blood pressure (r = 0.19, p &lt, 0.05). In conclusion, vitamin D supplementation favourably enhanced GPx1 levels in adult Arabs with prediabetes, particularly in males.

Methylglyoxal (MG) is a potent glycating agent which reacts with proteins to form advanced glycation end products (AGEs). These chemically stable AGEs crosslink with proteins and could lead to amyloid formation that has the role in several diseases including Alzheimer's and Parkinson's. In this piece of work, glycation-induced conformational changes in HSA were observed with quenching of tryptophan fluorescence by 73.8% (41 nm red shift) and loss of hydrophobicity of HSA. CD spectroscopy result reaffirmed secondary structure changes in HSA. Moreover, MG-induced changes in HSA, proceeds to amyloid structure as characterized by an increase in thioflavin (ThT) fluorescence and transmission electron microscopy (TEM) images of HSA aggregates. Quercetin was found to inhibit both AGEs production and amyloid formation. Viability of MCF-7 cells was found to be increased with AGEs treatment, illustrating proliferation of cancer cells. Wound healing assay also revealed increased proliferation and migration of cells in the presence of AGEs. Additionally, molecular docking analyses were performed to demonstrate interactions involved in the stabilization of HSA-quercetin complex. The binding affinities of quercetin were found to be (

RON receptor tyrosine kinase is a transmembrane protein directly involved in suppression of inflammation and its aberrant expression linked to cancers and metastasis. Efforts to block deregulated RON signaling in tumors using small molecule kinase inhibitors or antibodies have been complicated by the presence of unknown number/types of isoforms of RON, which, despite being structurally similar, localize differently and mediate varied functions. Current study was designed to identify the splice variants of RON transcripts formed by skipping of sequences between exons 9 and 14 for better understanding of isoform specific RON signaling in cancers. PCR amplification and bi-directional sequencing of a 901 bp cDNA sequence located between exons 9 to 14 of RON from lung cancer cell lines revealed the presence of two splicing variants formed by skipping of exons 11 and 11-13. Each of these transcripts was found in more than one cell line. Expressed sequence tag (EST) database search indicated that the splicing variant lacking exons 11-13 was a novel one. Here we conclude that the splice variants of RON lacking exon 11 and exons 11-13 were detected in several lung cancer cell lines. Novel variant formed by skipping exons 11-13, the sequence of which code for transmembrane region, is predicted to code for a truncated isoform that may be secreted out. Tumors may antagonize the ligand dependent anti-inflammatory function of wild-type RON by secreting out the ligand binding isoforms.

Introduction. Nitric oxide (NOx) is an important biomolecule which interacts with other molecules including 25(OH)D to mediate various metabolic pathways. Interactions and associations of NOx with 25(OH)D have been well studied bothin vitroandin vivo, yet associations in apparently healthy adolescents have never been studied.Methods. A total of 740 (245 boys and 495 girls) apparently healthy Saudi adolescents aged 10-17 years were included in this cross-sectional study, to determine the associations of NOx with 25(OH)D and other biomarkers in Saudi adolescents. Serum NOx, 25(OH)D, and other biochemical and anthropometric parameters were measured following standard protocols and manufacturers’ guidelines.Results. NOx level was significantly higher in boys than girls (pConclusion. The significantly inverse association of NOx and 25(OH)D among apparently healthy adolescents is influenced by sex and further strengthens the extraskeletal role of 25(OH)D in maintaining endothelial homeostasis in this age group, particularly in boys. Whether vitamin D correction can influence NOx production over time among adolescents remains to be proven.

Vitamin D deficiency is rampant in the Middle East, even in children and adolescents. This study was designed to investigate the effects of different vitamin D repletion strategies commonly used on serum vitamin D levels of Saudi adolescents. Study design: A 6-month multi-center, controlled, clinical study, involving 34 schools in the central region of Riyadh, Saudi Arabia. Different strategies of vitamin D supplementation were tested (200 ml fortified milk of different brands or vitamin D tablet (1,000IU). Anthropometrics were taken and fasting blood samples withdrawn at baseline and after intervention for the quantification of serum glucose, lipid profile and 25(OH) vitamin D. A significant increase in 25(OH)D level was observed in subjects supplemented with vitamin D tablet, milk brand 2 and milk brand 4, whereas subjects supplied with fortified milk brands 1 and 3 respectively, exhibited a significant decrease in 25(OH)D levels. Analysis of covariance showed that after adjusting for baseline 25(OH)D, age, gender and BMI, the mean 25(OH)D levels of children who were taking vitamin D tablet (9.1 ± 0.8 nmol/l) and milk brand 4 were significantly higher (7.3 ± 1.1 nmol/l) than children taking milk brand 2 (1.6 ± 1.0 nmol/l). Subjects supplied with milk brands 1 and 2 exhibited a significant increase in total cholesterol level, while it dropped significantly in subjects taking milk brand 3, while no changes were observed in other groups. Different strategies in vitamin D supplementation used in this clinical study elicited varying degrees of improvement in serum 25(OH)D level. The observed outcomes were dependent on the strategy and gender in the Saudi adolescent population, with oral tablet supplementation being favored in boys.

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N = 63) and those without (N = 54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R = 0.18; p = .08) and HOMA β (R = −0.19; p = .09) as well as significant positive associations with total cholesterol (R = 0.25; p = .02), LDL-cholesterol (R = 0.25; p = .02), 25(OH)D (R = 0.22; p = .04), albumin (R = 0.30; p