The effect of p53 on the activity of NRF2 and NDRG2 genes through apoptotic pathway in IDH-wildtype glioblastoma.

BACKGROUND: Tumor suppressor (p53) acts to integrate multiple stress signals into diverse antiproliferative responses. Its potential to transactivate or downregulate genes through apoptotic pathway in IDH-wildtype glioblastoma has never been explored. METHODS: A group of twenty patients diagnosed with IDH-wildtype glioblastoma, were tested for p53 expression and NDRG2/NRF2 genes activity through protein and gene profiling assays. The connotation between these elements has been explored. RESULTS: The mean patients' age was 64-years. All tumors were IDH-wildtype. p53 was expressed in 12 tumors and absent in 8 tumors. The activity of NDRG2 gene was downregulated in all cases. The activity of NRF2 gene was upregulated in 17 tumors and downregulated in 3 tumors. There was a significant statistical difference in PFS among tumors exhibiting different levels of p53 expression and NDRG2 gene activity [p-value= 0.025], in which 12 tumors with downregulated NDRG2 expression and positive p53 expression had earlier tumor recurrence. This statistical difference in PFS was insignificant when we compared p53 expression with NRF2 gene activity [p-value= 0.079]. CONCLUSIONS: During cell cycle arrest at G2 phase, p53 expression in IDH-wildtype glioblastoma in elderly individuals, coupled with the downregulation of NDRG2 gene activity, led to an aberrant increase in tumor cell proliferation and accelerated tumor recurrence. However, the influence of p53 on NRF2 gene activity was found to be insignificant.

Prognostic Factors Affecting Postsurgical Outcomes of Adult Patients with Intracranial Meningioma: A Retrospective Study.

OBJECTIVE: To identify the prognostic factors of surgical resection for meningioma and their relationship with patient outcomes. METHODS: This retrospective study included 53 patients (≥16 years), who underwent surgical resection for intracranial meningioma at the King Abdulaziz University Hospital from 2012 to 2022. Data regarding tumor location and size, histopathological type, chief complaint, chief complaint duration, admission date, diagnosis, operation, and discharge date were collected. These data were subjected to univariate and bivariate analyses to investigate the relationship between the postsurgical outcomes of the patients with meningioma and the variables of age at surgery, sex, length of hospitalization, chief complaint, Glasgow outcome score, World Health Organization histopathological classification, body mass index, tumor size, and nature of surgical resection. RESULTS: The mean age of our study cohort was 49.09 ± 12.64 years, with a female preponderance (75.5%) and mean body mass index of 29.31 ± 5.52 kg/m2. length of hospitalization (mean: 26.92 ± 54.88 days) demonstrated a significant (P = 0.012) impact on prognosis after surgery. In addition, convexity meningiomas (21.2%), which were observed in the maximum number of cases, and mean tumor volume (28.67 ± 48.85 mm) were significantly (P = 0.049) associated with the outcome. Most patients (78.8%) underwent total surgical resection, and histopathological examinations revealed a higher frequency of grade 1 than grade 2 tumors. CONCLUSIONS: Short duration of hospitalization and superficial location of the tumor are associated with optimal outcomes after surgical resection for patients with meningioma.

Correction: Ashraf et al. Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches. Molecules 2022, 27, 4652.

The updated affiliation information can be seen in the affiliation part of this correction [...].

The Short-Term Outcome of Seizure and Anti-epileptic Use After Cranial Surgery: A Retrospective Record Review.

Objectives The study aims to correlate craniotomies and their effect on epileptic activity and to assess the impact of prophylaxis anti-epileptic drugs (AEDs) used to prevent seizure activity after craniotomy. Method This was a mono-center retrospective review of patients undergoing craniotomy from 2010-2021 at King Abdulaziz University Hospital (KAUH), a tertiary center in Jeddah, Saudi Arabia. The patients were divided into two groups depending on preoperative anti-epileptic drug usage and the occurrence of seizures after the surgery. Out of 192, 24.6% had a seizure before the surgery, while the rest reported no seizure activity. We used descriptive statistics to categorize the study population and applied t-test and chi-square to compare different groups and outcomes. Results One-hundred-ninety-two patients were studied: 24.6% had preoperative seizure history and 82.1% were on prophylactic AEDs. The incidence of post-craniotomy seizures was 7.6% in patients with anti-epileptic prophylaxis and 2.7% in those without prophylaxis before the surgery. Almost three-quarters of the patients (72.4%) had surgery for brain tumor resection and redo-craniotomy while the rest (25.5%) were for intracranial hemorrhages (p=0.052). On multivariate analysis, the primary predictor of post-craniotomy seizures was the preoperative history of seizures. Finally, the administration of AEDs does not prevent seizure occurrence after craniotomy (p=0.153). Moreover, the type of prophylaxis and reason for the surgery played no significant role in seizure occurrence. Conclusion Post-craniotomy seizures were common, and preoperative AEDs for primary seizure prevention were not associated with a lower incidence of seizures after craniotomy.

Unravelling Binding of Human Serum Albumin with Galantamine: Spectroscopic, Calorimetric, and Computational Approaches.

Human serum albumin (HSA), an abundant plasma protein, binds to various ligands, acting as a transporter for numerous endogenous and exogenous substances. Galantamine (GAL), an alkaloid, treats cognitive decline in mild to moderate Alzheimer's disease and other memory impairments. A vital step in pharmacological profiling involves the interaction of plasma protein with the drugs, and this serves as an essential platform for pharmaceutical industry advancements. This study is carried out to understand the binding mechanism of GAL with HSA using computational and experimental approaches. Molecular docking revealed that GAL preferentially occupies Sudlow's site I, i.e., binds to subdomain IIIA. The results unveiled that GAL binding does not induce any conformational change in HSA and hence does not compromise the functionality of HSA. Molecular dynamics simulation (250 ns) deciphered the stability of the HSA-GAL complex. We performed the fluorescence binding and isothermal titration calorimetry (ITC) to analyze the actual binding of GAL with HSA. The results suggested that GAL binds to HSA with a significant binding affinity. ITC measurements also delineated thermodynamic parameters associated with the binding of GAL to HSA. Altogether, the present study deciphers the binding mechanism of GAL with HSA.

Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches.

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP's). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer's disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson's disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of -6.9 kcal/mol forming interactions with binding pocket's critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M-1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Medical students vs general public awareness regarding disc prolapse in Jeddah.

BACKGROUND: Disc herniation is a condition where tearing occurs in the outer annular layer of the intervertebral pad leading the inner gel-like material to bulge ouwards the spinal cord, due to the high load of the vertebrae. This will produce back pain and symptoms in different sites according to the level of the herniation in the vertebral column. AIM: To compare the level of awareness regarding disc herniation among the general population and medical students in Jeddah. METHODOLOGY: A descriptive cross-sectional study was conducted through an electronic questionnaire to assess the level of awareness regarding disc prolapse among the general population and medical students in Jeddah. The questionnaire was in the Arabic language, it was taken and validated by the previous study which took place in Taif. RESULTS: Our studied sample involved 1026 individuals aged between 11 and 99 years, with a mean age of 34.03 ± 13.28 years old. More than half of the respondents were female (55.4%), most of them were Saudi nationals (90.1%), and most of them have received a higher education (67.7%). Results showed that 54.1% of the general population and 77.7% of medical students reported good knowledge regarding this condition. CONCLUSION: This study revealed that the level of awareness regarding disc prolapse among the general population and medical students was poor in some respects such as: knowledge about the preventive measures, symptoms of the disease, the most common site in the spine affected by the disease, and the gold standard imaging method to diagnose this disease.