A series of 30 non-covalent imidazo[1,2-a]quinoxaline-based inhibitors of epidermal growth factor receptor (EGFR) were designed and synthesized. EGFR inhibitory assessment (against wild type) data of compounds revealed 6b, 7h, 7j, 9a and 9c as potent EGFR^WT inhibitors with IC₅₀ values of 211.22, 222.21, 193.18, 223.32 and 221.53 nM, respectively, which were comparable to erlotinib (221.03 nM), a positive control. Furthermore, compounds exhibited excellent antiproliferative activity when tested against cancer cell lines harboring EGFR^WT; A549, a non-small cell lung cancer (NSCLC), HCT-116 (colon), MDA-MB-231 (breast) and gefitinib-resistant NSCLC cell line H1975 harboring EGFR^L858R/T790M. In particular, compound 6b demonstrated significant inhibitory potential against gefitinib-resistant H1975 cells (IC₅₀ = 3.65 μM) as compared to gefitinib (IC₅₀ > 20 μM). Moreover, molecular docking disclosed the binding mode of the 6b to the domain of EGFR (wild type and mutant type), indicating the basis of inhibition. Furthermore, its effects on redox modulation, mitochondrial membrane potential, cell cycle analysis and cell death mode in A549 lung cancer cells were also reported.

Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cell... Plain language summary Osteoporosis is a common complication for people with diabetes. High glucose causes oxidative stress, and the antioxidant and anti-inflammatory properties of selenium nanopar...

Background: Several randomized controlled trials (RCTs) have shown conflicting results on cortisol levels following probiotic administration in healthy and diseased populations. Previous analyses were inconclusive due to limited studies, and evidence is lacking on how these effects vary by health status; region; therapy duration; medications, and use of single or multiple strains. Methods: In this systematic review and meta-analysis (PROSPERO [CRD42024538539]), we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, CINAHL, ProQuest, and Web of Science Preprints until 13 August 2024, for RCTs on probiotic administration, either alone or combined, across all age groups and without specific medical condition requirements. We applied random-effects meta-analysis, assessed bias using the Cochrane RoB 2 tool, and evaluated evidence certainty with GRADE. Findings: We screened 1739 records and retrieved 46 RCTs (3516 participants). Probiotics supplementation decreased cortisol levels compared to the control arm [46 RCTs; SMD: −0.45; 95% CI: −0.83; −0.07; I²: 92.5%, low certainty]. Among various subgroups; probiotics supplementation decreased the cortisol levels in the subgroups without concomitant medications [37 RCTs; SMD: −0.30; 95% CI [−0.58; −0.03], I²: 88.7%] with a single probiotic strain [30 RCTs; SMD: −0.33; 95% CI: −0.63; −0.028; I²: 88.8%], in a healthy population [35 RCTs; SMD:−0.3; 95% CI: −0.58; −0.03; I²: 88.7] and in the Asia region [21 RCTs; SMD: −0.83; 95% CI: −1.58; −0.07; I²: 95%]. Interpretation: A low level of evidence suggests probiotics might reduce cortisol levels, but more targeted studies are needed to identify variables affecting the response in specific subgroups.

Tyrosine kinase inhibitors are validated therapeutic agents against EGFR-mutated non-small cell lung cancer (NSCLC). However, the associated critical side effects of these agents are inevitable, demanding more specific and efficient targeting agents. Recently, we have developed and reported a non-covalent imidazo[1,2-a]quinoxaline-based EGFR inhibitor (6b), which showed promising inhibitory activity against the gefitinib-resistant H1975(L858R/T790M) lung cancer cell line. In the present study, we further explored the 6b compound in vivo by employing the A549-induced xenograft model in nude mice. The results indicate that the administration of the 6b compound significantly abolished the growth of the tumor in the A549 xenograft nude mice. Whereas the control mice bearing tumors displayed a declining trend in the survival curve, treatment with the 6b compound improved the survival profile of mice. Moreover, the histological examination showed the cancer cell cytotoxicity of the 6b compound was characterized by cytoplasmic destruction observed in the stained section of the tumor tissues of treated mice. The immunoblotting and qPCR results further signified that 6b inhibited EGFR in tissue samples and consequently altered the downstream pathways mediated by EGFR, leading to a reduction in cancer growth. Therefore, the in vivo findings were in corroboration with the in vitro results, suggesting that 6b possessed potential anticancer activity against EGFR-dependent lung cancer. 6b also exhibited good stability in human and mouse liver microsomes.