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Sickle cell disease (SCD) is a genetic disorder that affects millions of individuals worldwide. Chronic anemia, hemolysis and vasculopathy are the most common symptoms that arise from hemoglobin (Hb) polymerization, which is the primary event of SCD. The above process can lead to erythrocyte sickling. Therapeutic options for SCD remain limited, and novel therapies are still being evaluated for their effectiveness in particular populations. Sphingosine-1-phosphate (SIP), a significant bioactive sphingolipid, acts as a potent signal mediator, modulating several cellular functions. The potential role of erythrocyte-SIP in enhancing SCD severity has been previously reported by multiple studies. Therefore, the present review article aimed to summarize the effects of S1P on the progression of SCD and provide strategies to modulate this process. More specifically, it focused on erythrocyte-SIP as a potential target for reducing the complications associated with SCD, thus paving the way for the development of novel therapeutic strategies for SCD.

Background Obesity is one of the main causes of morbidity and mortality worldwide. More than 120 genes have been shown to be associated with obesity related phenotypes. The aim of this study was to determine the effect of selected genetic polymorphisms in Uncoupling protein 1 ( UCP1 ) and Niemann-Pick C1 ( NPC1 ) genes in an obese population in Saudi Arabia. Methods The genotypes of rs1800592, rs10011540 and rs3811791 ( UCP1 gene) and rs1805081 and rs1805082 ( NPC1 gene) were determined in a total of 492 subjects using TaqMan chemistry by Real-time PCR. In addition, capillary sequencing assay was performed to identify two specific polymorphisms viz., rs45539933 (exon 2) and rs2270565 (exon 5) of UCP1 gene. Results A significant association of UCP1 polymorphisms rs1800592 [OR, 1.52 (1.10–2.08); p  = 0.009] was observed in the obese cohort after adjusting with age, sex and type 2 diabetes. Further BMI based stratification revealed that this association was inconsistent with both moderate and extreme obese cohort. A significant association of UCP1 polymorphisms rs3811791 was observed only in the moderate-obese cohort [OR = 2.89 (1.33–6.25); p  = 0.007] but not in the extreme-obese cohort indicating an overlying genetic complexity between moderate-obesity and extreme-obesity. The risk allele frequencies, which were higher in moderate-obese cohort, had abnormal HDL, LDL and triglyceride levels. Conclusion The rs1800592 and rs3811791 of UCP1 gene are associated with obesity in general and in the moderate-obese group in particular. The associated UCP1 polymorphisms in the moderate-obese group may regulate the impaired energy metabolism which plays a significant role in the initial stages of obesity.

Background Obesity and diabetes are two chronic metabolic diseases whose prevalence is increasing at an alarming rate globally. A close association between obesity, diabetes, and insulin resistance has been identified, and many studies have pinpointed obesity as a causal risk factor for insulin resistance. However, the mechanism underlying this association is not entirely understood. In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. Methods The samples comprised subcutaneous adipose tissues collected from three cohorts: lean non-diabetic (controls; n  = 20), obese-non-diabetic ( n  = 66), and obese-diabetic ( n  = 32). Ceramide levels were quantified using LC-MS/MS and mRNA expression level for different enzymes were estimated using real-time PCR-based RNA expression analysis. Results C16-ceramide ( P  = 0.023), C16-dihydro-ceramide ( P  < 0.005), C18-dihydro-ceramide ( P  = 0.009) and C24-ceramide ( P  = 0.040) levels were significantly increased in the obese cohort compared to the control group. However, stratification of the obese group revealed a significant increase in the C16-ceramide levels ( P  = 0.027) and mRNA over expression of the serine palmitoyl transferases enzyme subunit SPT1 ( P  < 0.005) in the obese-diabetic cohort compared to the obese-non-diabetic cohort. Conclusions The present study indicates that C16-ceramide plays a pivotal role in inducing insulin resistance. Overexpression of SPT1 in the obese-diabetic group and its positive correlation with C16-ceramide suggest that C16-ceramide was generated through the de novo pathway.

Background and Objectives: Sickle cell anemia (SCA) is a hereditary monogenic disease due to a single β-globin gene mutation that codes for the production of sickle hemoglobin. Its phenotype is modulated by fetal hemoglobin (HbF), a product of γ-globin genes. Exploring the molecules that regulate γ-globin genes at both transcriptional and translational levels, including microRNA (miRNA), might help identify alternative therapeutic targets. Materials and Methods: Using next-generation sequencing we identified pre-miRNAs and mature miRNA expression signatures associated with different HbF levels in patients homozygous for the sickle hemoglobin gene. The involvement of identified miRNAs in potential SCD-related pathways was investigated with the DIANA TOOL and miRWalk 2.0 database. Results: miR-184 were most highly upregulated in reticulocytes. miR-3609 and miR-483-5p were most highly downregulated in sickle cell anemia with high HbF. miR-370-3p that regulates LIN28A, and miR-451a which is effective in modulating α- and β- globin levels were also significantly upregulated. miRNA targeted gene pathway interaction identified BCL7A, BCL2L1, LIN28A, KLF6, GATA6, solute carrier family genes and ZNF genes associated with erythropoiesis, cell cycle regulation, glycosphingolipid biosynthesis, cAMP, cGMP-PKG, mTOR, MAPK and PI3K-AKT signaling pathways and cancer pathways. Conclusions: miRNA signatures and their target genes identified novel miRNAs that could regulate fetal hemoglobin production and might be exploited therapeutically.

Caffeic acid phenethyl ester (CAPE) is a naturally occurring polyphenolic concentrated in propolis of honeybee hives. CAPE has been shown various physiological and pharmacologic properties. The aim of the present study was to investigate the effects of CAPE on proinflammatory markers in growing rats by performing the moderate swimming test. A total number of 21 male Wistar albino rats were separated into three groups (n = 7): sedentary: negative control group; exercise: positive control group received vehicle orally and exercise + CAPE: CAPE treated group: treated with CAPE (20 mg/kg) orally 30 min before exercise, for 5 days. The animals were left free to swim in the tank, 20 minutes/day for 5 days. At 24 hours after finishing the experiment, rats were euthanised and blood was collected to analyze the level of serum interleukin IL-6 and tumor necrosis factor-α (TNF-α). Growing rats subjected to the moderate swimming test and in those treated with CAPE showed a lower level of TNF-α compared to the negative control. More interestingly, the one-way ANOVA data demonstrated a decreased level of proinflammatory IL-6 in the CAPE-treated group compared to the negative control. Results of this study indicate that short-term administration of CAPE may modulate proinflammatory cytokine profiles during moderate exercise and may serve to boost the anti-inflammatory effects of exercise. Further studies are needed to evaluate the efficacy and safety of long-term administration of CAPE as an adjective anti-inflammatory agent.

Obesity is a major health threat worldwide. It predisposes individuals to diabetes, cardiovascular complications, and cancer. Genetic and environmental factors are responsible for the increasing incidence of obesity. In this study, we investigated the genetic factors associated with obesity in young Saudi women. In this cross-sectional study, 131 young Saudi female students were recruited. Body mass index (BMI), waist-hip ratio, blood glucose, triglyceride, cholesterol, HDL, LDL, and vitamin D3 levels of the subjects were determined. Twelve SNPs of different genes that showed a correlation with obesity in different population were tested, namely GNPDA2 (rs10938397), TCF7L2 (rs10885409), FTO (rs1477196), ADIPOQ (rs1501299), MC4R (rs17782313), ABCA1 (rs1800977), FTO (rs1861868), VDR (rs2228570), VDR (rs731236), VDR (rs7975232), ADIPOQ (rs266729), and PFPK (rs6602024). Student's -test was conducted for all parameters. Pearson correlation was performed to identify the correlated variables. The frequencies of different risk alleles were determined by direct counting of the test allele divided by the total number of alleles and compared. Only two SNPs, rs1861868 of and rs7975232 of , of the twelve tested SNPs showed significant protective associations with the BMI with odds ratio 0.3886 (0.1761-0.8572); 0.0192 and odds ratio 0.4563 (0.2343-0.8888); p 0.0211, respectively. The current study showed that minor alleles, \"T\" of and \"A\" of , might be protective factors against increased BMI in young Saudi female subjects. To elucidate this association, further studies with larger sample size involving both sexes are required.

Objectives: This study aimed to determine the effects of propolis on immune mediators and tissue histopathology in rats with L-arginine-induced acute pancreatitis (AP). Methods: This study was conducted at Imam Abdulrahman Bin Faisal University, Dammam, Saudia Arabia between September and November 2017. A total of 24 male albino Wistar rats were divided into three equal groups. Group one was the negative control, group two was the positive control (L-arginine-induced AP) and group three received treatment (L-arginineinduced AP and propolis). The rats in group three were treated with 100 mg/kg propolis for seven days after AP induction. Pancreatic tissue was evaluated histologically and levels of interleukin (IL)-6, IL-22 and IL-1β and tumour necrosis factor-alpha (TNF-α) were measured. Results: Propolis reduced the quanitity of proinflammatory molecules (TNF-α, IL-1β and IL-6) in group three compared to group two, significantly increased the overall antiinflammatory effect of IL-22 (P <0.005) and reduced interstitial inflammation and neutrophil cell infiltration of the pancreatic tissues. Conclusion: Propolis may exert a therapeutic effect in AP. Further studies are required to demonstrate the mechanisms of propolis in AP

Background Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD). Methods Eight genetic variants in four genes ( SHROOM3, MYH9, SLC7A9, and CST3 ) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls. Genetic variants were tested for association with the development of CKD (eGFR < 60 ml/min/1.73m 2 ) and effects were compared with results obtained from 133,413 participants in the CKD genetics consortium. Multivariable regression was used to evaluate the role of these eight variants in improving prediction of CKD development. Results All eight variants were present in Saudi populations with minor allele frequency ranging from 16 to 46%. The risk variant in all four genes demonstrated the same direction of effect as observed in European populations. One variant, rs4821480, in MYH9 was significantly associated with increased risk of development of CKD (OR = 1.69, 95% CI 1.22–2.36, P =  0.002), but the additional variants were not statistically significant given our modest sample size. Conclusions CKD risk variants identified in European populations are present in Saudis. We did not find evidence to suggest heterogeneity of effect size compared to previously published estimates in European populations. Multivariable logistic regression analysis showed a statistically significant improvement in predicting the CKD using models with either FGF23 and vitamin D or FGF23, vitamin D level, and MYH9 genotypes (AUC = 0.93, 95% CI 0.90–0.95, P  <  0.0001).

Epidermal growth factor receptor ( ) is a commonly altered gene that is identified in various cancers, including head and neck squamous cell carcinoma (HNSCC). Therefore, is a promising molecular marker targeted by monoclonal antibodies and small molecule inhibitors targeting the tyrosine kinase (TK) domain. The objective of this study was to investigate the spectrum of mutations in exons 18, 19, 20, and 21 of the gene in HNSCC patients. This retrospective study included 47 confirmed HNSCC cases. Mutations in the TK domain, exons 18, 19, 20, and 21 of the gene, were detected by Scorpion chemistry and ARMS technologies on Rotor-Gene Q real-time polymerase chain reaction. The tumors exhibited EGFR-TK domain mutations in 57% of cases. Four cases of T790M mutations were reported for the first time among HNSCC patients. Out of the total mutations, L861Q (exon 21), exon 20 insertions and deletions of exon 19 accounted for the majority of mutations (21%, 19%, and 17%, respectively). mutation status was correlated with the higher grade ( =0.026) and advanced stage ( =0.034) of HNSCC tumors. Higher frequency of EGFR-TK domain mutations together with the presence of the T790M mutation suggests that identification of these mutations might streamline the therapy and provide a better prognosis in HNSCC cases.

Background. End-stage renal disease (ESRD) is the result of hypertensive nephrosclerosis and chronic glomerular diseases and is associated with high morbidity and mortality. There are strong heritable components in the manifestation of the disease with a genetic predisposition to renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis. Recent studies in genetics have examined modifiable risk factors that contribute to renal disease, and this has provided a deep insight into progressive kidney disease. Single-nucleotide polymorphisms at the proximity of SHROOM3, CST3, SLC7A9, and MYH9 genes have been associated with an increased risk of developing CKD and ESRD. Methods. A total of 160 CKD patients and 189 control subjects of Saudi origin participated in the study. Eight polymorphisms (SHROOM3-rs9992101, rs17319721; SLC7A9-rs4805834; MYH9-rs4821480, rs4821481, rs2032487, rs3752462; CST3-rs13038305) were genotyped using TaqMan assay, and the haplotype analysis was done using the HaploView 4.2 software. Results. Haplotype analysis revealed a novel haplotype “E6”-GTTT to be associated significantly with an increased risk for ESRD (p=0.0001) and CKD (p=0.03). Conclusion. CKD is often silent until symptomatic uremia during the advanced stages of the disease. The newly identified haplotype will help recognize patients at risk for a rapid progression of CKD to ESRD. Accurate detection and mapping of the genetic variants facilitates improved risk stratification and development of improved and targeted therapeutic management for CKD.