Benzoxazoles possess a wide range of therapeutic activities, including antimicrobial, antitumor, anti-inflammatory, and other. Using in silico and in vitro approaches, we determined the potential antitumor activity of benzoxazoles synthesized from thymoquinone in diffuse large B-cell lymphoma (DLBCL) cells. Molecular docking analysis showed strong binding affinities of benzoxazoles toward Akt and nuclear factor kappa B (NF-κB) protein targets that promote cancer cell proliferation and survival and whose expression is linked to tumorigenesis of activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL subtypes. WST-8 assay showed the highest inhibitory activity of benzoxazole derivative bearing thiophene substituent in both DLBCL models. Western blot analysis indicated the inhibitory activity of selected compounds in HBL-1 cells, with decreased p-NF-κB and p-Akt protein expression, whereas treatment of DHL-4 cells stimulated the expression of p-Akt and p-NF-κB protein levels. These data suggest distinct, cell line-dependent activities of the substances that potentially act through diverse oncogenic signaling pathways in DLBCL cells and activation of compensatory cell mechanisms that could be an important step for combinatorial treatment approaches.

The complex link between COVID‐19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID‐19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro‐inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID‐19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID‐19 and its long‐term repercussions, which is the focus of this review paper.

Diffuse large B cell lymphoma (DLBCL) is classified into Germinal Center B‐cell (GCB) and activated B‐cell (ABC) subgroups originating from different stages of lymphoid differentiation. Cell of origin dictates the behavior and therapeutic response of DLBCL. This study aimed to evaluate single and combinatorial effects of metformin and thymoquinone (TQ) in two DLBCL cell lines belonging to GCB and ABC subtypes. Metformin and TQ caused dose‐dependent responses in both ABC and GCB DLBCL subtypes. Metformin had a greater impact on the ABC subtype while TQ demonstrated more pronounced effects on the GCB subtype. Synergistic effects were observed in the DHL4 (GCB subtype) but not in the HBL1 (ABC subtype) cell line. This is the first study to compare the effects of metformin and TQ in ABC versus GCB subtype of DLBCL. It brings valuable results that could be utilized in further research aimed at reshaping treatments for subtype‐specific lymphomas.

BACKGROUND: Preclinical drug testing requires in vitro and in vivo assessments that are vital for studying drug pharmacokinetics and toxicity. Distinct factors that play an important role in drug screening, such as hydrophobicity, solubility of the substance and serum protein binding can be challenging by inducing result inconsistencies. Hence, establishing accurate methods to quantify drug concentrations in cell cultures becomes pivotal for reliable and reproducible results important for in vivo dosing predictions. OBJECTIVE: This research focuses on developing an optimized analytical approach via high-pressure liquid chromatography (HPLC) to determine thymoquinone (TQ) levels in monolayer cell cultures. METHODS: The method’s validation adheres to the International Council for Harmonisation (ICH) guideline M10, ensuring its acceptance and applicability. Using an HPLC system with a Diode Array Detector (DAD), the study fine-tuned various parameters to achieve an efficient separation of TQ. Validation covered specificity, sensitivity, matrix effects, linearity, precision, and accuracy, alongside assessing TQ stability in RPMI-1640 medium. RESULTS: The HPLC method exhibited remarkable TQ specificity, free from interfering peaks at the analyte retention. Sensitivity analysis at the lower limit of quantification (LLOQ) revealed 5.68% %CV and 98.37% % mean accuracy. Matrix effect evaluation showcased accuracy within 85–115%. Linearity spanned in the concentration range of 2–10 μ M with a correlation coefficient ( r 2 ) of 0.9993. Precision and accuracy were aligned with acceptance criteria. The proposed method was found to be greener in terms of usage of persistent, bioaccumulative, and toxic chemicals and solvents, corrosive samples, and waste production. CONCLUSION: The developed HPLC-DAD method emerges as specific, accurate, sensitive, and reliable for TQ determination in cell cultures. It ensures robust TQ quantification, enhancing precise in vitro assessments and dependable dosing predictions for in vivo studies. Further research is advocated to investigate TQ’s stability across diverse environmental conditions.

Chronic myeloid leukemia (CML) is a myeloproliferative haematological malignancy characterized by constitutive activation of BCR-ABL1 tyrosine kinase in the majority of patients. BCR-ABL1 expression activates signaling pathways involved in cell proliferation and survival. Current treatment options for CML include tyrosine kinase inhibitors (TKI) with resistance as a major issue. Various treatment options for overcoming resistance are being investigated. Among them, phytochemical curcumin could play an important role. Curcumin has been found to exhibit anti-cancerous effects in various models, including CML, through regulation of multiple molecular signaling pathways contributing to tumorigenesis. We have evaluated curcumin’s effects on imatinib-sensitive LAMA84S and K562, as well as imatinib-resistant LAMA84R cell lines. Our results indicate a significant dose-dependent decrease in cell viability and proliferation of imatinib-sensitive and imatinib-resistant cell lines after curcumin treatment. Suppression of key signaling molecules regulating metabolic and proliferative events, such as Akt, P70S6K and NF-kB, was observed. Increased expression of caspase-3 suggests the potential pro-apoptotic effect of curcumin in the imatinib-resistant CML model. Additional in silico molecular docking studies revealed binding modes and affinities of curcumin with different targets and the results are in accordance with in vitro findings. Altogether, these results indicate the potential role of curcumin in the treatment of CML.