A non-targeted metabolomics comparative study on plasma of pfizer and sinopharm COVID-19 vaccinated individuals, assessed by (TIMS-QTOF) mass spectrometry.

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.

The neuroprotective effect of human primary astrocytes in multiple sclerosis: In vitro model.

Recent studies highlighted the role of astrocytes in neuroinflammatory diseases, particularly multiple sclerosis, interacting closely with other CNS components but also with the immune cells. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still unclear. In this study we develop an astrocyte in vitro model to evaluate their role in multiple sclerosis after being treated with CSF isolated from both healthy and MS diagnosed patients. Gene expression and ELISA assays reveal that several pro-inflammatory markers IL-1ß, TNF-α and IL-6, were significantly downregulated in astrocytes treated with MS-CSF. In contrast, neurotrophic survival, and growth factors, and GFAP, BDNF, GDNF and VEGF, were markedly elevated upon the same treatment. In summary, this study supports the notion of the astrocyte involvement in MS. The results reveal the neuroprotective role of astrocyte in MS pathogenicity by suppressing excessive inflammation and increasing the expression of tropic factors.

Pomegranate peel: Bioactivities as antimicrobial and cytotoxic agents.

This is a comparative study to evaluate the effectiveness of six pomegranate peel extracts (PPEs) as antibacterial and antiproliferative agents. The Six PPEs were prepared using four solvent systems and each filtrate was concentrated to a gummy material to be used in the evaluation. The well-diffusion method was used to evaluate their antimicrobial activity against bacteria typically associated with food spoilage: Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus, and three Bacillus species. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) was used to evaluate the cytotoxicity against colorectal carcinoma cells (HCT116), prostate adenocarcinoma (PC3), ovarian cancer cells (SKOV-3), and fibroblasts (MRC-5). The antioxidant evaluation was done using the 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) assay. The pH of the water-containing extracts was acidic and almost the same over 6 weeks. The six PPEs inhibited the bacterial growth in a comparable level to standard antibiotics. The effectiveness of each extract was dependent on the bacterial strain, and the Listeria showed a remarkable inhibition when exposed to the aqueous extract prepared at room temperature (RT). The aqueous (RT) and methanol PPEs had a significant antioxidant scavenging capability and a remarkable cytotoxic activity against the PC3 with half maximal inhibitory concentration (IC50) of 0.1 µg/mL. The boiled aqueous extract exhibited antiproliferative activity against HCT116 with an IC50 of 21.45 µg/mL. The effect on SKOV-3 and fibroblasts was insignificant. With the exception of butanol, the antioxidant screening shows an inverse correlation between the polarity of the extraction solvent and the IC50 exhibited by the PPEs. The variation in the effectiveness of PPEs is suggested to be due to variable soluble bioactive compounds that may interact differently with different cells, though water-containing extracts are promising antibacterial agents. The findings clearly show that pomegranate peel possessed the potential to be an eco-friendly novel source for natural compounds that can be implemented in the food industry as a natural antimicrobial and natural food additive to prevent foodborne illnesses.

Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia.

Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)2-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells. Method: The growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line. Results: Inecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI50 values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI50 values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1. Conclusion: The study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML.

Anti-Inflammatory and Antioxidant Effects of Rosmarinic Acid Trimetallic (Cu0.5Zn0.5Fe2O4) Nanoparticles.

Newly, green metallic-nanoparticles (NPs) have received scientists' interest due to their wide variable medicinal applications owned to their economical synthesis and biologically compatible nature. In this study, we used rosmarinic acid (RosA) to prepare Cu0.5Zn0.5FeO4 NPs and later encapsulated them using PEG polymer. Characterization of NPs was done using the XRD method and SEM imaging. Further, we explored the encapsulated NPs for anti-inflammatory properties by downregulating the expression of pro-inflammatory cytokines mRNA in LPS-stimulated Raw 264.7 cells. Besides, employing DPPH, NO and ABTS radical scavenging assays to examine the antioxidant activity of the synthesized Cu0.5Zn0.5FeO4 NPs. Cu0.5Zn0.5FeO4 NPs revealed moderate antioxidant activity by scavenging DPPH and nitric oxide. We demonstrated that the NPs showed high potential anti-inflammatory activity by suppressing the mRNA and protein levels of pro-inflammatory cytokines in a dose-dependent manner, in LPS-induced Raw 264.7 cells. To our best knowledge, this is the first report where RosA was found to be a suitable phyto source for the green synthesis of Cu0.5Zn0.5FeO4 NPs and their in vitro anti-inflammatory and antioxidant effects. Taken together, our findings suggest that the RosA is a green resource for the eco-friendly synthesis of Cu0.5Zn0.5FeO4/PEG NPs, which further can be employed as a novel anti-inflammatory therapeutic agent.