Investigation the role of CD24 in metastatic colorectal cancer

CD24 is a small (81 amino acids) GPI anchored protein which is involved in promoting cell motility and stemness and may be a part of the metastatic process. It is a heavily glycosylated molecule and contains numerous O-glycosylation sites together with two N-glycosylation sites. N-glycosylation is thought to be important in protein function, and therefore, the aim of this study is to (a) investigate the importance of N-glycosylation in the function of CD24, (b) identify other potentially functional sites in CD24 by deletion mapping, (c) define downstream targets of CD24, and (d) identify the extrinsic signals of which activate CD24. (a) Through site-directed mutagenesis, we changed the glycosylated residues N32 (ACC to CAA) and Q52 (AAT to CAG) in CD24. Mutating each of these sites individually, when compared to pCCD24WT (wild-type CD24), caused a partial reduction in ability to induce cell motility and cell invasion (cell motility p=0.0001 cell invasion p=0.0001) and, unexpectedly, resulted in significantly enhanced cell proliferation (p=0.0001). Mutation of both sites resulted in a near loss of motility induction and retained cell proliferation. (b) We mapped the functional sites of CD24 by deleting seven amino acid segments of the whole of the mature peptide. Apart from the N-glycosylation sites, no other functional domains were identified which altered cell motility or proliferation. (c) Previously, in our lab it has been shown that Cten is downstream motility-inducing target of CD24. We hypothesised that CD24 may signal through the Notch pathway since Notch1 has an important role in maintaining CSCs. Results showed that forced expression of CD24 upregulates Notch1 and Cten whilst knockdown of CD24 causes loss of Notch1 and Cten expression. However, forced expression of CD24 with simultaneous knockdown of Notch1 resulted in failure to induce Cten. (d) CD24 is reported to act as a ligand of P-selectin. We found that stimulating CD24 expressing cell lines induced with P-selectin induced cell motility (p=0.0011) and caused an increased in the protein expression of downstream targets of CD24. Stimulating cell lines expressing CD24 with mutant glycosylation sites resulted in a failure to induce motility or CD24 targets. We conclude, the removal of the N-glycosylation sites in CD24 resulted in a loss of cell migration and invasion, thereby suggesting the importance of these sites in mediating the migration and invasion functions of CD24. Unexpectedly, these mutations also appeared to stimulate cell proliferation, suggesting that wild type CD24 can functionally inhibit cell proliferation. Deletion mapping did not reveal any other functional sites on the mature CD24 suggesting that O-glycosylation is relatively affecting the glycosylation in the biology of CD24. Notch1 was to be an important downstream target of CD24 and a regulator of Cten. The binding of P-selectin with CD24 resulted in increased motility of CD24 which is also dependent on N-glycosylation

Use of novel oral anticoagulants for Treatment of cerebral venous sinus Thrombosis: a case series and follow up

Thrombosis of cerebral venous sinuses and/or cortical veins (CVST) is an infrequent type of stroke for which anticoagulation is considered standard of treatment. However, 40% of CVST patients have evidence of parenchymal changes like edema or haemorrhage on neuroimaging which complicates use of anticoagulation in such cases. Therefore, Novel Oral Anticoagulants (NOACs) are recently being used for treatment of CVST as they are associated with half the risk of intracerebral haemorrhage as caused by vitamin K antagonist. Case reports and case series have reported use of NOACs in CVST with good outcomes both clinically and radiologically. We report use of NOACs in five cases of CVST without any worsening or recurrence of symptoms or complication on follow up

Multiple sclerosis following bariatric surgery: A report of five cases

Multiple sclerosis (MS) is a debilitating chronic inflammatory demyelinating disease that affects the central nervous system. The underlying cause of multiple sclerosis is unknown, yet there are various predisposing factors. Currently, bariatric surgery is an increasingly common solution for obesity. It has been reported that bariatric procedures result in miscellaneous neurological complications. To the best of our knowledge, this is the first case series to report the occurrence of MS following bariatric surgery. Here we report the cases of five patients who were recruited for inclusion following neurological examination, complete cerebrospinal fluid (CSF) study, enhanced cranial as well as spinal cord magnetic resonance (MR) images. Diagnosis of multiple sclerosis was made based on McDonalds criteria (2010). All cases were diagnosed with relapsing-remitting form of multiple sclerosis (RRMS) after various types of bariatric surgeries

Relationship Between Glycated Haemoglobin and Carotid Atherosclerotic Disease Among Patients with Acute Ischaemic Stroke

Objectives: This study aimed to determine the relationship between glycaemic control and carotid atherosclerotic disease among patients with acute ischaemic stroke (AIS). Methods: This retrospective cross-sectional study took place in the Neurology Department of King Fahad Hospital of University, Khobar, Saudi Arabia, from April to October 2017. Data were collected from the medical records of 244 patients with a diagnosis of AIS confirmed by computed tomography. Doppler ultrasounds of the carotid artery were performed to determine the presence of increased carotid intima media thickness (CIMT) and plaques. Results: Significantly higher mean glycated haemoglobin (HbA1c) levels were noted in cases with high CIMT values (P = 0.002), but not in cases with carotid plaques (P = 0.360). In addition, there was a significant association between diabetes mellitus (DM) and high CIMT (P = 0.045), but not with carotid plaques (P = 0.075). Finally, while dyslipidaemia and age were independently correlated with high CIMT values (P = 0.034 and 0.050 each). Conclusion: High HbA1c levels were associated with high CIMT values, but not with carotid plaques. Therefore, HbA1c levels may be useful as an indirect marker of the initial stages of carotid artery atherosclerosis. Keywords: Glycated Hemoglobin A1c; Diabetes Mellitus; Carotid Intima-Media Thickness; Atherosclerotic Plaque; Stroke

The Effect of Socio-economic status on the Oral Hygiene of Elementary School Children in the City of Dammam, Saudi Arabia

ABSTRAC

Attitude and hesitancy of human papillomavirus vaccine among Saudi parents

Background: Human papillomavirus (HPV) is closely associated with cervical cancer. The HPV vaccine is expected to protect against two-thirds of cervical cancer cases in Saudi Arabia. Objectives: To determine the awareness and attitude regarding the HPV vaccine among Saudi parents attending family medicine clinics in Riyadh. Materials and Methods: All Saudi parents of patients of Family Medicine Pediatric Clinics, King Faisal Specialist Hospital and Research Centre (KFSH&RC), Riyadh, were invited to participate in this study between November 2019 and May 2020. A culturally sensitive and specially designed questionnaire was administered using an interview-based model. The data collected included sociodemographic information, knowledge of HPV and its vaccine, and attitudes regarding HPV acceptance. Results: A total of 296 study participants completed our questionnaire on the HPV vaccine. About 70.6% of the participants were not aware of the HPV vaccine and the majority of them either did not know or did not associate HPV as an etiology for cervical cancer (38.8 and 37.8%, respectively). Only 28.6% of the participants were aware that cervical cancer can be prevented by a vaccine and 89.5% of the study participants did not receive the HPV vaccine for themselves or their children. The employee status was significantly associated with a history of receiving the HPV vaccine (χ2 (2) = 10.607, P =0.005), while age and the level of education had a statistically significant relationship with planning on having the HPV vaccine ((χ2 (9) = 51.841, P <.001) and (χ2 (12) = 23.977, P =0.02), respectively). The level of awareness of the HPV vaccine was significantly associated with a history of having the HPV vaccine; (χ2 (1) = 38.486, P <.001) as well as with planning on having the HPV vaccine (χ2 (1) = 38.486, P <.001). Moreover, the reasons for hesitancy were a statistically significant factor for unvaccinated respondents who were not planning to have the HPV vaccine (χ2 (21) = 97.689, P <.001) while it was not significantly associated with the unvaccinated respondents who were planning to have the HPV vaccine (χ2 (9) = 6.989, P =.63). Conclusion: Our study clearly demonstrated a poor level of awareness and attitude toward the HPV vaccine among Saudi parents. A higher level of awareness of the HPV vaccine was significantly associated with planning on having the vaccine. There is a need for effective awareness programs for better HPV-related education in order to increase the acceptance of the HPV vaccine among Saudi parents

Advanced coats-like retinopathy as the initial presentation of Familial Retinal Arterial Macroaneurysms

Purpose: To describe two young Saudi brothers with bilateral progressive retinal arterial aneurysms and a subtotal exudative retinal detachment with Coats-like presentation in the older sibling as the initial presentation of Familial Retinal Arterial Macroaneurysms (FRAM). Observations: Two young Saudi brothers with a family history of consanguinity presented with the classic clinical presentation and genetic identification of FRAM. In this report, we describe the presence of prominent peripheral retinal capillary changes mimicking Coats' disease. Conclusions and importance: FRAM can present similar to bilateral Coats' disease and should be considered in the differential diagnosis of Coats-like retinopathy. The diagnosis of FRAM may have a significant implication because of the associated cardiac abnormality, such as supravalvular pulmonary stenosis, which should be evaluated by echocardiography and managed accordingly. Keywords: Familial retinal arterial macroaneurysms (FRAM), Insulin-like growth factor binding protein 7 (IGFBP7), Supravalvular pulmonic stenosis, Coats’-like retinopathy, Retinal arterial aneurysm

Comparative study of <i>Nigella</i> <i>Sativa</i> and triple therapy in eradication of <i>Helicobacter Pylori</i> in patients with non-ulcer dyspepsia

Background/Aim: A large number of diseases are ascribed to Helicobacter pylori (H. pylori), particularly chronic active gastritis, peptic ulcer disease and gastric cancer. Successful treatment of H. pylori infection with antimicrobial agents can lead to regression of H. pylori-associated disorders. Antibiotic resistance against H. pylori is increasing, and it is necessary to find new effective agents. Nigella sativa seed (NS), a commonly used herb, possesses in vitro anti-helicobacter activity. The present study was undertaken to evaluate the efficacy of NS in eradication of H. pylori infection in non-ulcer dyspeptic patients. Materials and Methods: The study was conducted on 88 adult patients attending King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, from 2007 to 2008, with dyspeptic symptoms and found positive for H. pylori infection by histopathology and urease test. Patients were randomly assigned to four groups, receiving i) triple therapy (TT) comprising of clarithromycin, amoxicillin, omeprazole [n= 23], ii) 1 g NS &#x002B; 40 mg omeprazole (OM) [n= 21], iii) 2 g NS &#x002B; OM [n= 21] or iv) 3 g NS &#x002B; OM [n= 23]. Negative H. pylori stool antigen test four weeks after end of treatment was considered as eradication. Results: H. pylori eradication was 82.6, 47.6, 66.7 and 47.8&#x0025; with TT, 1 g NS, 2 g NS and 3 g NS, respectively. Eradication rates with 2 g NS and TT were statistically not different from each other, whereas H. pylori eradication with other doses was significantly less than that with TT (P &lt; 0.05). Dyspepsia symptoms improved in all groups to a similar extent. Conclusions: N. sativa seeds possess clinically useful anti-H. pylori activity, comparable to triple therapy. Further clinical studies combining N. sativa with antibiotics are suggested