Carboxymethylcellulose encapsulated fingolimod, siRNA@ZnO hybrid nanocomposite as a new anti-Alzheimer's material.

Alzheimer's disease (AD) is a fatal neurological disorder that causes cognitive and memory function to deteriorate. A critical pathogenic event that speeds up the development of AD is the interaction between dysfunctional microglia and amyloid-ß (Aß). We have developed a hybrid nanocomposite material to treat AD by normalizing the dysfunctional microglia. The material is based on carboxymethylcellulose (CMC) encapsulated fingolimod, siRNA, and zinc oxide (ZnO) with variable loading (CMC-Fi-siRNA@ZnO a-d ). The material was characterized using different techniques including FTIR, XRD, thermal analysis, SEM with EDX, and TEM micrographs. The chemical structure was confirmed by FTIR and XRD analyses, which indicated the successful integration of ZnO nanoparticles (NPs) into the polymer matrix, signifying a well-formed composite structure. The thermal stability order at 10% weight loss was CMC-Fi-siRNA@ZnO c > CMC-Fi-siRNA@ZnO b > CMC-Fi-siRNA@ZnO d > CMC-Fi-siRNA@ZnO a . The CMC-Fi-siRNA@ZnO d dramatically alleviates the priming of microglia by lowering the level of proinflammatory mediators and increasing the secretion of BDNF. This considerably improves the phagocytosis of Aß. In the cell viability test in immortalized microglia cells (IMG), the hybrid nanocomposite (NP) exhibited no significant effect on cell survival after 48 hours of incubation. The NP also decreased the cytotoxicity caused by Aß. Therefore, the CMC-hybrid NP has high potential as a drug delivery system in the development of therapeutic strategies for AD.

Analysis of MIR27A (rs11671784) Variant Association with Systemic Lupus Erythematous.

Multiple microRNAs (miRs) are associated with systemic autoimmune disease susceptibility/phenotype, including systemic lupus erythematosus (SLE). With this work, we aimed to unravel the association of the miR-27a gene (MIR27A) rs11671784G/A variant with SLE risk/severity. One-hundred sixty-three adult patients with SLE and matched controls were included. A TaqMan allelic discrimination assay was applied for MIR27A genotyping. Logistic regression models were run to test the association with SLE susceptibility/risk. Genotyping of 326 participants revealed that the heterozygote form was the most common genotype among the study cohort, accounting for 72% of the population (n = 234), while A/A and G/G represented 15% (n = 49) and 13% (n = 43), respectively. Similarly, the most prevalent genotype among cases was the A/G genotype, which was present in approximately 93.3% of cases (n = 152). In contrast, only eight and three patients had A/A and G/G genotypes, respectively. The MIR27A rs11671784 variant conferred protection against the development of SLE in several genetic models, including heterozygous (G/A vs. A/A; OR = 0.10, 95% CI = 0.05-0.23), dominant (G/A + G/G vs. AA; OR = 0.15, 95% CI = 0.07-0.34), and overdominant (G/A vs. A/A + G/G; OR = 0.07, 95% CI = 0.04-0.14) models. However, the G/G genotype was associated with increased SLE risk in the recessive model (G/G vs. A/A+ G/G; OR = 17.34, 95% CI = 5.24-57.38). Furthermore, the variant showed significant associations with musculoskeletal and mucocutaneous manifestations in the patient cohort (p = 0.035 and 0.009, respectively) and platelet and white blood cell counts (p = 0.034 and 0.049, respectively). In conclusion, the MIR27A rs11671784 variant showed a potentially significant association with SLE susceptibility/risk in the studied population. Larger-scale studies on multiethnic populations are recommended to verify the results.

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach.

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = -0.87, p < 0.001). Kaplan-Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

Glutathione S-Transferase (GSTT1 rs17856199) and Nitric Oxide Synthase (NOS2 rs2297518) Genotype Combination as Potential Oxidative Stress-Related Molecular Markers for Type 2 Diabetes Mellitus.

BACKGROUND: Deregulation of the antioxidant enzymes was implicated in pathogenesis and complications of type 2 diabetes mellitus (T2DM). The data relate the genetic variants of these enzymes to T2DM are inconsistent among various populations. PURPOSE: We aimed to explore the association of 13 genetic variants of "superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and nitric oxide synthase (NOS)" with T2DM susceptibility and the available clinical laboratory data. SUBJECTS AND METHODS: A total of 384 individuals were enrolled in this work. Different genotypes of the genes mentioned above were characterized using TaqMan OpenArray Genotyping assays on a Real-Time polymerase chain reaction system. RESULTS: After age- and sex-adjustment, among the studied 13 variants, GSTT1 rs17856199 was associated with T2DM under homozygote (OR=3.42; 95% CI:1.04-11.2, p=0.031), and recessive (OR=3.57; 95% CI: 1.11-11.4, p=0.029) comparison models. The NOS2 rs2297518*A allele was more frequent among the T2DM cohort (58.1% vs 35.4%, p<0.001) and showed a dose-response effect; being heterozygote was associated with higher odds for developing DM (OR=4.06, 95% CI=2.13-7.73, p<0.001), whereas being AA homozygote had double the risk (OR=9.06, 95% CI=3.41-24.1, p<0.001). Combined NOS2 rs2297518*A and either GSTT1 rs17856199*A or *C genotype carriers were more likely to develop T2DM. Different associations with sex, BMI, hyperglycemia, and/or hyperlipidemia were evident. The principal component analysis revealed NOS2 rs2297518*G, old age, dyslipidemia, high systolic blood pressure, and elevated HbA1c were the main classifiers of T2DM patients. CONCLUSION: The oxidative stress-related molecular markers, GSTT1 rs17856199 and NOS2 rs2297518 variants were significantly associated with T2DM risk and phenotype in the study population.

Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study.

Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic variants, including single nucleotide polymorphisms (SNPs) of the antioxidant-related genes, may impact disease risk in several populations. This preliminary study aimed to explore the association of 12 SNPs related to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) genes with obesity susceptibility in a Saudi population. A total of 384 unrelated participants, including 154 (40.1%) obese individuals, were enrolled. TaqMan OpenArray Genotyping assays were used. Six SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T; (2) SOD1 rs2234694*A; (3) SOD2 rs4880*G; (4) SOD3 rs2536512*A; (5) GPX1 rs1800668*A; (6) NOS3 rs1799983*G. Four SNPs were associated with higher obesity risk under heterozygote and dominant models for GSTM1 rs1056806 (C/T), homozygote model for SOD2 rs4880 (A/G), and homozygote and recessive models for GPX1 rs1800668 (A/G). In contrast, SOD3 rs2536512 (A/G) were less likely to be obese under heterozygote and dominant models. The CGAG, CAAA, TGGG, and CGAG combined genotypes showed a higher risk of obesity. In conclusion, the present results suggest that oxidative-stress-related genetic determinants could significantly associate with obesity risk in the study population.

Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

Aluminum chloride (AlCl3) is a neurotoxic substance, while coenzyme Q10 (CoQ10) is considered a lipid antioxidant. Herein, their effects on the molecular structure of lipids and the morphology of the hippocampus brain tissue were investigated. Three groups of Wistar albino male rats were used in this study. For four weeks, one group was kept as a control group; the second group was given AlCl3; the third group was given AlCl3/CoQ10. Fourier transform infrared (FTIR) and histopathological examinations were utilized to estimate alterations in the molecular structure of the lipids and the cell morphology, respectively. The FTIR spectra revealed considerable decreases in the CH contents and alterations in the molecular ratios of olefinic[double bond, length as m-dash]CH/νas(CH3), νas(CH2)/νas(CH3), and νas(CH2)/[νas(CH2) + νs(CH2)] in the group given AlCl3. However, no significant changes were detected in those rats given AlCl3/CoQ10. Histopathology images uncovered shrinking and dark centers in the pyramidal cells of brain tissue hippocampal cells. The diameters of the pyramidal cells were estimated to be 4.81 ± 0.55 µm, 4.04 ± 0.71 µm, and 4.63 ± 0.71 µm for the control, AlCl3, and AlCl3/CoQ10 groups, respectively. The study showed that the AlCl3 could cause a shrinking of around 16% in the hippocampus pyramidal cells; besides, CoQ10 is a powerful therapeutic antioxidant to help restore the hippocampal neurons to a regular state.

Correction: Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

[This corrects the article DOI: 10.1039/D1RA03786B.].

The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study.

Type 2 diabetes mellitus (T2DM) is a common polygenic disease with associated comorbidities. Obesity is a major risk factor for the development of T2DM. The aim of this study is to determine the allele and genotype frequency of peroxisome proliferator-activated receptor-γ (PPARγ) rs1801282, fat mass and obesity-associated protein (FTO) rs9939609, and melanocortin 4 receptor (MC4R) rs2229616 polymorphisms and their association with risk of T2DM in the western Saudi population as mediators of adiposity phenotypes. In a cross-sectional prospective study, genomic DNA from control and T2DM patients were isolated and genotyped for these single-nucleotide polymorphisms. There was a significant association of the MC4R rs2229616 variant with T2DM, but no association with T2DM was detected with PPARγ rs1801282 or FTO rs9939609. The combination of C/C for PPARγ rs1801282, A/A for FTO rs9939609, and C/C for MC4R rs2229616 increased the risk of T2DM by 1.82. The A/T genotype for FTO rs9939609 was predicted to decrease the risk of T2DM when combined with C/C for PPARγ rs1801282 and C/C for MC4R rs2229616 or C/C for PPARγ rs1801282 and C/T MC4R rs2229616. In conclusion, our study showed the risk of the assessed variants for the development of T2DM in the Saudi population.

SLC22A1 And ATM Genes Polymorphisms Are Associated With The Risk Of Type 2 Diabetes Mellitus In Western Saudi Arabia: A Case-Control Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major global health problem that is progressively affected by genetic and environmental factors. The aim of this study is to determine the influence of solute carrier family 22 member 1 (SLC22A1) rs628031 and rs461473, and ataxia telangiectasia mutated (ATM) rs11212617 polymorphisms on the risk of T2DM in Saudi Arabia by considering many parameters associated with glycemic control of T2DM, such as body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), and triglyceride. METHODS: In a case-control study, genomic DNA from controls and diabetic groups was isolated and genotyped for each single-nucleotide polymorphism. RESULTS: There were significant correlations between T2DM and both BMI and HbA1c. Significant associations between G/G and A/G genotypes of rs628031 and rs461473 variants of SLC22A1 and high levels of HbA1c were detected. Therefore, G was predicted to be the risk allele among the assessed SLC22A1 variants. A significant correlation was observed between A/A and A/C genotypes of the rs11212617 polymorphism of ATM and elevated HbA1c. Relative risk calculation confirmed A to be the risk allele in the T2DM population. CONCLUSION: Our study showed the risk of the assessed SLC22A1 and ATM variants on glycemic control parameters in diabetic patients.

Evaluation of the toxic effect of the herbicide 2, 4-D on rat hepatocytes: an FT-IR spectroscopic study.

Infrared spectroscopy is a powerful technique used to investigate molecular structures to the level of bond lengths and angles. In this study, the hepatotoxic effect of 2, 4-dichlorophenoxyacetic acid (2, 4-D) was investigated using Fourier transform infrared (FT-IR) spectroscopy. The experiment was performed on 15 male albino Wister rats (250-350 g) divided randomly into a control group (5 rats) and 2, 4-D-treated group (10 rats). The 2, 4-D-treated group received a single oral gavage LD50 dose of 639 mg/kg body weight; the rats were then killed and the livers excised 24 h after 2, 4-D administration. Spectroscopic results revealed that there was a significant reduction in protein content as well as a marked decrease in the secondary structure of protein after 2, 4-D intoxication. Moreover, looseness of membrane lipid chain packing, lipid polarity and/or significant increases in the formation of lipids with hydroperoxyl groups and carbonyl compounds were shown in the 2, 4-D LD50-treated group compared to the control group. Glycogen is dramatically decreased in rat liver after the induction of 2, 4-D. In conclusion, FTIR spectroscopy proved to be a rapid and sensitive approach to cytotoxicity diagnosis and monitoring of toxin-induced damage in biological membranes and proteins. In addition, the FTIR parameters employed in this study can be used as biophysical indicators of toxin-induced cell or membrane damage during apoptosis.

Maternal leptin, adiponectin, resistin, visfatin and tumor necrosis factor-alpha in normal and gestational diabetes.

Gestational diabetes mellitus (GDM) is a common medical complication associated with pregnancy. The present study evaluates the changes in maternal adipocytokines (leptin, adiponectin, resistin, visfatin and tumor necrosis factor-alpha; TNF-α) in pregnancy complicated with GDM compared to normal pregnancy at 2nd and 3rd trimesters. The study included total number of 142 pregnant women classified into 4 groups: normal pregnancy (n = 33) and pregnancy with GDM (n = 24) both at 2nd trimester and normal pregnancy (n = 38) and GDM (n = 47) at 3rd trimester. Both GDM groups were significantly presented with elevated body mass index, fasting blood sugar and abnormal oral glucose tolerance test compared to their matched control. Results indicated reduction in maternal serum leptin and adiponectin in GDM compared to normal pregnancy at 3rd trimester. Elevated resistin and TNF-α were evident among pregnancy complicated with GDM at both tested trimesters. On the other hand, significant elevation in maternal visfatin was noted between GDM and matched control at 2nd trimester only. Significant increase in maternal leptin and visfatin and resistin was noted by advances in gestational period in healthy pregnancy. On the other hand, reduced adiponectin and elevated visfatin mean values were noticed in GDM at 3rd compared to 2nd trimester. It could be concluded that increased insulin resistance accompanies GDM is associated with suppressed leptin and adiponectin and increased resistin and TNF-α which might suggest their involvement in the development of GDM.

Thyroid function in newly diagnosed HIV-infected patients.

BACKGROUND: A variety of HIV-related endocrine dysfunctions including adrenal, gonadal and thyroid disorders have been reported. We aimed to compare between the markers of thyroid function in newly diagnosed HIV-infected patients and healthy volunteers as a control group. The prevalence of the thyroid abnormalities in HIV-infected patients was assessed and the levels of thyroid autoantibodies were also determined. METHODS: A total of 100 newly diagnosed HIV-infected patients having a CD4 cell count of 180-350 cells/mm(3) were enrolled in the study. Same number of healthy volunteers were also included for comparison. Measurements of thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxin and free triiodothyronine levels beside thyroid autoantibodies, including antithyroglobulin (ATBG) and antithyroid peroxidase (ATPO), were carried out for all patients and volunteers. RESULTS: In total, 70% of HIV-infected patients had normal thyroid function tests when compared with control individuals, while 30% of HIV-infected patients had abnormal thyroid function. Of the 30 cases, 11 cases had abnormal TSH values, with increased TSH predominant (7% of HIV cases) than decreased TSH (4% of patients) values. Incidence of thyroid abnormalities ranging from hypothyroidism (subclinical and overt: 6% and 1%, respectively) to hyperthyroidism (2%) and nonthyroidal illness (9%) were estimated in HIV-infected patients. The values of thyroid autoantibodies were almost normal in HIV-infected patients, except the three cases presented with elevated ATBG, indicating that thyroid abnormalities were not due to elevated ATBG and ATPO. CONCLUSIONS: Thyroid hormones are of great importance and due to high prevalence of thyroid function abnormality, it is recommended that thyroid function tests should be monitored in all HIV-infected patients before starting the treatment.

Mineral content and microbiological examination of some white cheese in Jeddah, Saudi Arabia during 2008.

Different local and exported white cheese samples were collected from different markets in Jeddah during September 2008. Trace and heavy metals including Pb, Zn, Mn, Cu, Fe and Cd were analyzed using atomic absorption spectrometry. The concentration of the tested metals was in the range, Fe(++)>Zn(+++)>Mn(++)>Pb(++)>Cu(++)>Cd(++). The mean concentration of 7.63, 7.19, 0.5, 0.47, 0.16 and 0.14 µg/g was recorded for Fe, Zn, Mn, Pb, Cu and Cd, respectively. The concentration of iron ranged from 3.5 to 11.9 µg/g, zinc from 3.4 to 10.5, manganese from 0.12 to 1.0, lead from 0.14 to 1.14, and copper from 0.09 to 0.22. Yeasts and fungi were counted on Sabouraud and Potato Dextrose media and incubation was carried out at 25°C for 7 and 5 days, respectively. Yeast count and fungi count of cheese were ranged from 0.1 to 0.44CFU/g and from 0.123 to 1.11 CFU/g, respectively. Three out of 20 samples of cheese were contaminated with toxigenic fungi with 5% contamination level. Aflatoxin G1 was recorded in three samples using immunoadsorbent column chromatography with a range from 7 to 13 ppm.