RESUMO
Tobacco and alcohol have been identified as health risk behaviors associated with significant unfavorable health consequences, ranking within the list of the top ten causes of mortality and disability-adjusted life years (DALY). The combustion of tobacco leads to the formation of acrylamide (ACR), which is well known for its neurotoxic effects. Similarly, alcohol consumption has also been widely recognized for its neurotoxic effects. Both substances can affect neurons and neuroglia cells through various pathways. This study sought to examine the impacts of co-administration of ACR and intermittent-access ethanol (IAE) consumption over a period of one month. The experimental group received 20 mg/kg of ACR, administered orally, along with IAE of 20% ethanol sessions lasting 24 h, three times per week. The cognitive outcomes were assessed utilizing the elevated plus maze (EPM), which was employed as a means of assessing the capability to learn and remember, the novel object recognition (NOR) test, which was employed to assess recognition memory, and the Y-maze, which was used to explore a new environment and navigate. Additionally, ELISA assays were performed to examine underlying mechanisms, including markers associated with inflammation (NF-κB, PGE2, and TNF-α), apoptosis (Bcl2, Bax, and Caspase-3), and oxidative stress (MDA, catalase, and GSH). These markers were assessed in the brain homogenate as part of the investigation. Furthermore, a histopathological study was conducted. The findings indicated that NF-κB levels increased significantly in the combination of ACR and IAE groups (ACR + IAE) compared to either the ACR-alone or IAE-alone groups. However, parallel changes were observed in TNF-α, PGE2, Bax, Bcl-2, Caspase-3, GSH, and CAT levels when comparing the ACR + IAE group to the ACR-alone group. Comparable alterations were noted between the ACR + IAE treatment and IAE-alone groups in TNF-α, Bcl-2, MDA, GSH, and CAT levels. Moreover, the histopathological analysis revealed significant changes between the ACR + IAE and the ACR- or IAE-alone groups. Regarding memory parameters assessed using tests including EPM, NOR, and Y-maze, considerable changes were observed across all treatment groups as opposed to the control. Surprisingly, there were no notable differences in the NOR and Y-maze tasks between the alone and combination treatment. Further study is necessary to explore the long-term alteration of co-administering ACR and IAE on behavior, memory, and neurotoxicity-related mechanisms, in order to elucidate their combined effects more clearly.
RESUMO
Combination of bovine serum albumin with microemulsions as constituting ingredient biopolymer has long been regarded an innovative method to address the surface functionalization and stability issues in the targeted payload deliveries, thereupon producing effectively modified microemulsions, which are superior in loading capacity, transitional and shelf-stability, as well as site-directed/site-preferred delivery, has become a favored option. The current study aimed to develop an efficient, suitable and functional microemulsion system encapsulating sesame oil (SO) as a model payload towards developing an efficient delivery platform. UV-VIS, FT-IR, and FE-SEM were used to characterize, and analyze the developed carrier. Physicochemical properties assessments of the microemulsion by dynamic light scattering size distributions, zeta-potential, and electron micrographic analyses were performed. The mechanical properties for rheological behavior were also studied. The HFF-2 cell line and hemolysis assays were conducted to ascertain the cell viability, and in vitro biocompatibility. The in vivo toxicity was determined based on a predicted median lethal dose (LD50) model, wherein the liver enzymes' functions were also tested to assess and confirm the predicted toxicity.
RESUMO
Cancer prevalence has increased at an alarming rate worldwide. Complexity, resistance mechanism and multiple compensatory survival pathways of cancer cells have abated the response of currently available cancer medications. Therefore, multi-target agents rather than single target might provide a better solution to these cancer therapy issues. In the present study, anti-PLK1 (Polo-like kinase 1) potential of the eight FDA-approved (2017) anti-cancer drugs have been explored using molecular docking approach. Out of all the tested drugs, brigatinib, niraparib and ribociclib showed better binding affinity towards the 'kinase domain' of PLK1. The Gibbs free binding energy (ΔG) and inhibition constant (K i) values for brigatinib, niraparib and ribociclib interaction with the kinase domain of PLK1 were '- 8.05 kcal/mol and 1.26 µM', '- 8.35 kcal/mol and 0.729 µM' and '- 7.29 kcal/mol and 4.52 µM', respectively. Interestingly, the docking results of these three drugs were better than the known PLK1 inhibitors (BI-2536 and rigosertib). The ΔG and K i values for BI-2536 and rigosertib interaction with the kinase domain of PLK1 were '- 6.8 kcal/mol and 10.38 µM' and '- 6.6 kcal/mol and 14.51 µM', respectively. Brigatinib, niraparib and ribociclib have been approved by FDA for the treatment of non-small cell lung cancer, ovarian/fallopian tube cancer and breast cancer, respectively. PLK1 is regarded as a potential cancer target, and it is specifically over-expressed in different types of cancer cells, including aforementioned cancers. Actually, the target enzymes for anti-cancer action of brigatinib, niraparib and ribociclib are tyrosine kinase, poly(ADP-ribose) polymerase and cyclin-dependent kinase 4/6, respectively. However, based on our outcomes, we could safely state that PLK1 might plausibly emerge as an add-on target for each of these three anti-cancer drugs. We strongly believe that this study would assist in the development of better dual-targeting cancer therapeutic agent in the near future.