Molecular signature to predict quality of life and survival with glioblastoma using Multiview omics model.

Glioblastoma multiforme (GBM) patients show a variety of signs and symptoms that affect their quality of life (QOL) and self-dependence. Since most existing studies have examined prognostic factors based only on clinical factors, there is a need to consider the value of integrating multi-omics data including gene expression and proteomics with clinical data in identifying significant biomarkers for GBM prognosis. Our research aimed to isolate significant features that differentiate between short-term (≤ 6 months) and long-term (≥ 2 years) GBM survival, and between high Karnofsky performance scores (KPS ≥ 80) and low (KPS ≤ 60), using the iterative random forest (iRF) algorithm. Using the Cancer Genomic Atlas (TCGA) database, we identified 35 molecular features composed of 19 genes and 16 proteins. Our findings propose molecular signatures for predicting GBM prognosis and will improve clinical decisions, GBM management, and drug development.

Selenium and mercury concentrations in biological samples from patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic disease affecting multiple organs. Furthermore, viral infection depletes several trace elements and promotes complex biochemical reactions in the body. Smoking has been linked to the incidence of COVID-19 and associated mortality, and it may impact clinical effects, viral and bacterial conversion, and treatment outcomes. OBJECTIVES: To study the relationship between severe acute respiratory syndrome coronavirus type 2 and the elemental concentrations of selenium (Se) and mercury (Hg) in biological samples from smokers and nonsmokers infected with the virus and in healthy individuals. METHOD: We evaluated changes in the concentrations of essential (Se) and toxic (Hg) elements in biological samples (blood, nasal fluid, saliva, sputum, serum, and scalp hair) collected from male smokers and nonsmokers (aged 29-59 years) infected with COVID-19 and from healthy men in the same age group. The patients lived in different cities in Sindh Province, Pakistan. The Se and Hg concentrations were determined using atomic absorption spectrophotometry. RESULTS: Se concentrations in all types of biological samples from smokers and nonsmokers with COVID-19 were lower than those of healthy smokers and nonsmokers. Hg concentrations were elevated in both smokers and nonsmokers with COVID-19. CONCLUSIONS: In the current study, persons infected with COVID-19 had higher concentrations of toxic Hg, which could cause physiological disorders, and low concentrations of essential Se, which can also cause weakness. COVID-19 infection showed positive correlations with levels of mercury and selenium. Thus, additional clinical and experimental investigations are essential.

RP-HPLC Method Development, Validation, and Drug Repurposing of Sofosbuvir Pharmaceutical Dosage Form: A Multidimensional Study.

A smooth, exceptionally sensitive, correct, and extra reproducible RP-HPLC technique was developed and demonstrated to estimate Sofosbuvir (SOF) in pharmaceutical dosage formulations. This process was carried out by Agilent High-Pressure Liquid Chromatograph 1260 with GI311C Quat. Pump, Phenomenex Luna C-18 (150 mm × 4.6 mm × 5 µm) (USA), and Photodiode Array Detector (PDA) G1315D. The cell section, including acetonitrile and methanol with 80:20 v/v and solution (B) 0.1% phosphoric acid (40:60), was used for the study. However, 10 µL of the sample was injected with a drift flow of 1 mL/min. The separation occurred at a column temperature of 30 °C, and the eluents used PDA set at 260 nm. The retention time of SOF was 5 min. The calibration curve was modified linearly within the range of 0.05-0.15 mg/mL with a correlation coefficient of 0.99 and genuine linear dating among top vicinity and consciousness in the calibration curve. The detection and quantification restrictions were 0.001 and 0.003 mg/mL, respectively. SOF recovery from pharmaceutical components ranged from 98% to 99%. The percentage assay of SOF was 99%. Analytical validation parameters, such as specificity, linearity, precision, accuracy, and selectivity, were studied, and the percentage relative standard deviation (%RSD) was less than 2%. All other key parameters were observed within the desired thresholds. Hence, the proposed RP-HPLC technique was proven effective for developing SOF in bulk and pharmaceutical pill dosage forms. SOF was found to interact with SARS-COV-2 nsp12, and molecular docking results revealed its high affinity and firm binding within the active site groove of nsp12. The key interacting residues include; LYS-72, GLN-75, MET-80 ALA-99, ASN-99, TRP-100, TYR-101 with ASN-99 and TRP-100 forming hydrogen bonds. Molecular Dynamics simulation of SOF and nsp12 complex elucidated that the system was stable throughout 20ns. Therefore, this drug repurposing strategy for SOF can be used for treating COVID-19 infections by performing animal experiments and accurate clinical trials in the future.

Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.