Background: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. Methods: Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. Results: Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups. Conclusions: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

One of the worst diseases, cancer claims millions of lives each year throughout the world, necessitating the creation of novel treatments. In this study, we designed a novel series of 1,3,4-thiadiazoles through the reaction of 2-(4-methyl-2-(2-(1-phenylethylidene)hydrazineyl)thiazole-5-carbonyl)-N-phenylhydrazine-1-carbothioamide (3) with the proper hydrazonoyl halides. Using the MTT assay, the newly synthesized thiadiazoles' growth-inhibitory potential against the liver cancer cell line HepG2-1 was assessed. In comparison to the standard drug doxorubicin (IC₅₀ = 0.72 ± 0.52 µM), the results showed that two compounds, 16b and 21 (IC₅₀ = 0.69 ± 0.41 and 1.82 ± 0.94 µM, respectively) had promising anticancer activity. The structural activity relationship (SAR) was investigated. In addition, molecular docking analysis onto quinone oxidoreductase2 (NQO2) receptor (PDB: 4ZVM) was investigated against the potent compounds to examine the reliability of the in vitro results. The newly prepared thiadiazole-thiazole hybrids are therefore regarded as potent anticancer drugs.

Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.

In the current study, pyromellitimide benzoyl thiourea cross-linked chitosan (PIBTU-CS) hydrogel, was evaluated as a green biocatalyst for the efficient synthesis of novel thiazole derivatives. The PIBTU-CS hydrogel showcased key advantages, such as an expanded surface area and superior thermal stability, establishing it as a potent eco-friendly catalyst. By employing PIBTU-CS alongside ultrasonic irradiation, we successfully synthesized a series of novel thiazoles through the reaction of 2-(4-((2-carbamothioylhydrazineylidene)methyl)phenoxy)-N-(4-chlorophenyl)acetamide with a variety of hydrazonoyl halides (6a–f) and α-haloketones (8a–c or 10a,b). A comparative analysis with TEA revealed that PIBTU-CS hydrogel consistently delivered significantly higher yields. This synthetic strategy provided several benefits, including mild reaction conditions, reduced reaction times, and consistently high yields. The robustness of PIBTU-CS was further underscored by its ability to be reused multiple times without a substantial reduction in catalytic efficiency. The structures of the synthesized thiazole derivatives were meticulously characterized using a range of analytical techniques, including IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry (MS), confirming their successful formation. These results underscore the potential of PIBTU-CS hydrogel as a sustainable and recyclable catalyst for the synthesis of heterocyclic compounds. Additionally, all synthesized products were tested for their anticancer activity against HepG2-1 cells, with several new compounds exhibiting good anticancer effects.

This study aimed to synthesize new aza-acyclic nucleosides (aza-acyclovir) and evaluate the efficacy of these synthetic compounds as potential antimicrobial, anticancer, and antioxidant agents. We prepared two novel aza-acyclic nucleosides via two reactions. The first reaction involved trichloroisocyanuric acid and dibenzosulphonyl diethylamine, and the second reaction involved trichloroisocyanuric acid and diethanolamine. We then used one-dimensional nuclear magnetic resonance (NMR) spectroscopy, two-dimensional NMR spectroscopy, infrared spectroscopy, and mass spectrometry to determine the structures of the resulting compounds. In this regard, we first tested the antimicrobial activity of these compounds against various bacteria, including Bacillus cereus, B. subtilis, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa, and against fungal pathogens, including Aspergillus fumigatus, Candida tropicalis, and Alternaria solani. Next, the precise mode for the interaction between synthesized aza-acyclic nucleosides and the target protein 8HQ5 was elucidate using molecular docking analysis. Subsequently, we tested the synthesized compounds for putative anticancer activity at different concentrations (i.e., 12.5, 25, 50, 100, and 200 µg/mL) against A549 cell (Human epithelial lung carcinoma) and human umbilical vein endothelial cell (HUVEC) lines. In addition, compounds antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl-based and cupric reducing antioxidant capacity-based methods at different concentrations (i.e., 31.25, 62.5, 125, 250, and 500 µg/mL). Results revealed that both aza-acyclic nucleosides inhibited both bacterial and fungal strains, although toxicity toward bacterial strains was generally greater than toward fungal strains. We also observed that the molecular docking results were consistent with the results of in vitro antimicrobial assessments. Further, both aza-cyclic nucleosides exhibited cytotoxic effects against both the A549 cell and HUVEC lines. Despite exhibiting lower radical scavenging activity than ascorbic acid (an antioxidant compound used as a standard), Compound 1 from the novel synthetic aza-acyclic nucleosides showed a higher reduction capacity, which was dose-dependent. Overall, we report newly synthesized compounds that show promising antimicrobial, anticancer, and antioxidant effects.

This paper aimed to examine the impact of flavonoid osajin (OSJ) on liver damage induced by sepsis. A total of 30 male rats were divided into 5 groups (Sham, sepsis, OSJ 150, OSJ 300 and reference). During sepsis, elevated lipid peroxidation (LPO) level and catalase activity (CAT) and decreased glutathione (GSH) level and superoxide dismutase (SOD) activity were observed in hepatic tissues of sepsis group in comparison with Sham group. A strong interleukin-33 and caspase-3 expressions were detected in hepatic tissues of sepsis group. On the contrary, OSJ administration to OSJ 300 group showed a significant decrease (P < 0.001) in LPO level (176±2.926) and significant increase (P < 0.001) in GSH level (10.586±0.083) and SOD activity (29.152±0.094) in comparison with sepsis group (185.777±1.735, 8.246±0.124, 24.307±0.379 respectively). In addition, the consumption of OSJ reduced expressions of interleukin-33 and caspase-3 and improved histopathological integrity. In conclusions, OSJ has hepatoprotective effect against sepsis-induced liver injury. GRAPHICAL ABSTRACT