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Glioblastoma (GBM) stands as the most common primary malignant brain tumor. Despite the best standard therapies, GBM survivors have a brief survival time, about 24 months on average. The treatment is troublesome because the cancer cells may not respond well to specific therapies as they grow within an extensive network of blood vessels. Our study aims to evaluate the impact of paclitaxel 5.3 μg/mL and topotecan 0.26 μM solely and in pairwise combination on the resultant metabolic and proteomic signatures of the U87 cell line while using the precise ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF) analytical technology. The U87 cells wear treated with DMSO, paclitaxel 5.3 μM, topotecan 0.26 μM, and their combinations. Using One-way ANOVA, we observed 14 significantly altered metabolites compared to those cells treated with DMSO. For combination treatment (paclitaxel and topotecan), 11 metabolites were significantly dysregulated. Sparse partial least squares-discriminant analysis (sPLS-DA) revealed minimal overlap, highlighting distinctions among the four groups. While for proteomics, a total of 79 proteins were significantly dysregulated among the groups. These findings can aid in identifying new biomarkers associated with the utilized drugs and creating a map for targeted therapy. EIF3F, GNB2L1, HINT2, and RPA3 were shown to be significantly upregulated in the combination group relative to the control. Moreover, ribosome, apoptosis, HIF-1 signaling, arginine and proline, glutathione, purine metabolism, apelin signaling pathway, and glycolysis were significantly altered in the combination group. Overall, this study underscores the effectiveness of multi-omics approaches in revealing the molecular mechanisms driving chemotherapy responses in cancer cells. Additionally, this work generates a comprehensive list of molecular alterations that can serve as a foundation for further investigations and inform personalized healthcare strategies to enhance patient outcomes.

COVID-19 is a highly contagious infectious disease that has posed a global threat, leading to a widespread pandemic characterized by multi-organ complications and failures. Aims: The present study was conducted to evaluate the impact of Pfizer and Sinopharm vaccines on metabolomic changes and their correlations with immune pathways. Main methods: The study used a cross-sectional design and implemented an untargeted metabolomics-based approach. Plasma samples were obtained from three groups: non-vaccinated participants, Sinopharm-vaccinated participants, and Pfizer-vaccinated participants. Comparative metabolomic analysis was conducted using TIMS-QTOF, and multiple t-tests with a 5 % false discovery rate (FDR) were performed using MetaboAnalyst software. Key findings: Out of the 105 metabolites detected, 72 showed statistically significant changes (p-value < 0.05) across the different groups. Notably, several metabolites such as neopterin, pyridoxal, and syringic acid were markedly altered in individuals vaccinated with Pfizer. Conversely, in the Sinopharm-vaccinated group, significant alterations were observed in sphinganine, neopterin, and sphingosine. These metabolites hold potential as biomarkers for evaluating vaccine efficacy. Additionally, both Pfizer and Sinopharm vaccinations were found to influence sphingolipid and histidine metabolisms compared to the control group. The Sinopharm group also displayed changes in lysine degradation relative to the control group. When comparing the enriched pathways between the Pfizer and Sinopharm-vaccinated groups, differences were observed in purine metabolism. Furthermore, alterations in tryptophan and vitamin B6 metabolism were noted when comparing the Pfizer-vaccinated group with both the control and Sinopharm-vaccinated groups. Significance: These findings highlight the importance of metabolomics in assessing vaccine effectiveness and identifying potential biomarkers for monitoring the efficacy of newly developed vaccines in a shorter timeframe.

Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures. In this study, we employed hindlimb unloading (HU) mouse model, which mimics astronauts in space and bedridden patients, to first evaluate cardiovascular and skeletal muscle function, followed by proteomics and metabolomics LC-MS/MS-based analysis using serum samples. Three weeks of unloading caused changes in the function of the cardiovascular system in c57/Bl6 mice, as seen by a decrease in mean arterial pressure and heart weight. Unloading for three weeks also changed skeletal muscle function, causing a loss in grip strength in HU mice and atrophy of skeletal muscle indicated by a reduction in muscle mass. These modifications were partially reversed by a two-week recovery period of reloading condition, emphasizing the significance of the recovery process. Proteomics analysis revealed 12 dysregulated proteins among the groups, such as phospholipid transfer protein, Carbonic anhydrase 3, Parvalbumin alpha, Major urinary protein 20 (Mup20), Thrombospondin-1, and Apolipoprotein C-IV. On the other hand, metabolomics analysis showed altered metabolites among the groups such as inosine, hypoxanthine, xanthosine, sphinganine, l-valine, 3,4-Dihydroxyphenylglycol, and l-Glutamic acid. The joint data analysis revealed that HU conditions mainly impacted pathways such as ABC transporters, complement and coagulation cascades, nitrogen metabolism, and purine metabolism. Overall, our results indicate that microgravity environment induces significant alterations in the function, proteins, and metabolites of these mice. These observations suggest the potential utilization of these proteins and metabolites as novel biomarkers for assessing and mitigating cardiovascular and skeletal muscle deconditioning associated with such conditions.

The vehicular industry is looking for continuous challenges to develop the sustainability of its manufacturing, maintenance processes, and vehicle emissions due to marketability, environmental, economic, and policy concerns. The present study focuses on the impact of these processes on the environment. In Pakistan, most of the auto-body refinishing processes are carried out in an open atmosphere. The shades of Azadirachta indica (Neem Tree) are generally used for the outdoor practice of scrapping, grinding, and painting in auto-body refinishing shops of Pakistan. Azadirachta indica leaves were selected as bio-indicator. For the present work, 26 affected sites and 10 control sites were selected from Karachi city, which is the financial hub and biggest city of Pakistan. Concentrations of different metals (Fe, Co, Cd, Cr, Cu, Mn, Mo, Ni, Pb, and Zn) were determined by atomic absorption spectrophotometer. A geographic information system (GIS) is used to present the variation in concentrations within Karachi city. The only positive correlation was observed in Pb and Mn (0.750). Principal component analysis (PCA) is applied to identify the anthropogenic effect between auto-body refinishing areas and control areas. Almost all analyzed metals show higher concentration at affected sites but Pb (87.14 mg/kg), Mn (46.47 mg/kg) and Fe (146.95 mg/kg) were leading the values, as compared to their concentration at control sites, Pb (48.83 mg/kg), Mn (15.23 mg/kg) and Fe (43.07 mg/kg). All analyzed metals are frequently present in different color pigments, whereas Pb, Mn, and Fe may also come from other sources, like the anti-knocking agent, vehicular exhaust, and scraping of car surface.