This study synthesized a total of 18 new anthranilic acid hydrazones and quinazolin-4(3H)-one derivatives, evaluating their cytotoxicity against the MCF7 and HUVEC cell lines. The anticancer effects of these compounds and their interactions with estrogen receptor alpha (ER alpha) and HER2 through molecular docking and molecular dynamics simulations. Cytotoxicity assays revealed that most compounds exhibited higher selectivity for MCF7 cells compared to HUVEC cells, with compounds 12, 13, 14, 23, and 29 showing superior efficacy over the standard drug 5-fluorouracil (5-FU). Notably, compound 12 displayed the highest selectivity index (SI = 3.9) and an IC50 of 77.3 mu M against MCF7 cells. Compounds 14 and 29 also demonstrated significant selectivity indices of 3.0 and 3.5, respectively, with IC50 values of 111.4 mu M and 74.0 mu M against MCF7 cells. Molecular docking studies identified compounds 14 and 29 as strong inhibitors of ER alpha and HER2, with stable interactions and favorable binding profiles in docking and MD analyses. Furthermore, ADME analysis indicated good drug like properties for most compounds, aligning with Lipinski's rule of five, supporting their potential as orally bioavailable drugs. This research highlights compounds 14, and 29 as promising candidates for targeted breast cancer therapy via inhibition of ER alpha and HER2

Objectives: Dental bone formation involves various cellular and molecular mechanisms, and phytoestrogens such as formononetin (FORM) are promising because of their estrogenic, anti-inflammatory, and antioxidant effects. This study investigated the effect of FORM on osteoblast proliferation, differentiation, and mineralization in combination with spongiosa granulates (BO) in vitro. Materials and Methods: Human fetal osteoblast cells (hFOB1.19) were treated with increasing concentrations of FORM (1, 10, and 100 µg/mL), BO, or their combination. Cell proliferation was assessed using a MTT assay. Alkaline phosphatase (ALP) activity, intracellular Ca2+, and Pi levels were measured using ELISA. Vascular endothelial growth factor (VEGF) and osteocalcin expression levels were analyzed by western blotting. Results: Cell proliferation increased with FORM, with or without BO, after 6 days (p < 0.001). FORM and BO had a synergistic effect on ALP activity (p < 0.001). Intracellular Ca2+ and Pi levels were highest in the BO-FORM group, suggesting superior mineralization (p < 0.05). VEGF and osteocalcin expression was significantly upregulated with FORM, alone and with BO (p < 0.05), indicating improved angiogenesis and bone maturation over 9 days. Conclusions: FORM enhances osteoblast proliferation, differentiation, and mineralization potential, particularly in BO spongiosa granulates. These data support the in vitro potential of formononetin-phytoestrogen in promoting osteoblast differentiation and mineralization potential with BO. These findings suggest that FORM, combined with BO, could improve bone augmentation in clinical applications such as maxillofacial surgery. FORM shows valuable potential for clinical applications, such as maxillofacial surgery, by promoting faster and more effective healing.

Objective: To investigate the effect of repeated povidone-iodine (PVI) application on the ocular surface parameters of patients who received intravitreal injections. Materials and methods: In this prospective study, 52 eyes of 52 patients with age-related macular degeneration who underwent unilateral intravitreal injection at least three times in the last 1 year (intravitreal injection [IVI] group), 52 fellow eyes with no previous intravitreal injection (NIVI group), and 51 eyes of 51 healthy subjects (control) were included. Tear break-up time (TBUT), the Schirmer test, the Oxford staining score, the Ocular Surface Disease Index questionnaire, conjunctival impression cytology, and tear inflammatory cytokine levels (interleukin [IL]-1 beta and IL-6) were analyzed in all participants. Results: The IVI group had lower TBUT and higher Oxford staining score than the NIVI and control groups (P<0.05). No significant difference was found between the groups in the Schirmer test (P=0.161). Conjunctival impression cytology analysis revealed that the IVI group had a significantly lower goblet cell count and significantly higher Nelson staging result than the NIVI and control groups (P<0.05). As a result of tear cytokine analysis, although IVI and NIVI groups had higher IL-1 beta and IL-6 levels than the control group (P<0.05), there was no difference between NIVI and IVI groups (P=0.05). Conclusions: Repeated PVI application caused cytotoxic injury to the ocular surface, resulting in goblet cell loss and squamous metaplasia of epithelial cells. As a result, the stability of the tear film layer was found to be impaired and ocular surfacerelated symptoms developed in patients.

In recent years, phthalates and their metabolites have been associated with metabolic diseases such as diabetes mellitus. To investigate the effects of phthalate metabolites exposure on insulin production and release, 1.1B4 pancreatic beta cells were treated with different concentrations (0.001-1000 mu M) of monoethylhexyl phthalate (MEHP) and monobutyl phthalate (MBP). For such purpose, the 1.1B4 cells were evaluated for their viability, apoptosis rate, lysosomal membrane permeabilization (LMP), mitochondrial membrane potential (Delta psi m), oxidative stress, ER stress status, in addition to their secretory functions. MEHP, not MBP, exhibited a notable reduction in metabolic viability, particularly at higher concentrations (500 and 1000 mu M) following 24-hour exposure. Similarly, both MEHP and MBP induced decreased metabolic viability at high concentrations after 48-and 72-hour exposure. Notably, neither MEHP nor MBP demonstrated a significant impact on apoptosis rates after 24-hour exposure, and MBP induced mild necrosis at 1000 mu M concentration. Cell proliferation rates, indicated by PCNA expression, decreased with 10 and 1000 mu M MEHP and 0.1 and 10 mu M MBP exposures. LMP analysis revealed an increase in 1000 mu M MBP group. Exposure to 0.001 mu M of both MEHP and MBP significantly reduced cellular glutathione (GSH) levels. No significant change in intracellular reactive oxygen species (ROS) levels and Delta psi m was observed, but MBP-exposed cells exhibited elevated levels of lipid peroxidation. Functional assessments of pancreatic beta cells unveiled reduced insulin secretion at low glucose concentrations following exposure to both MEHP and MBP, with concurrent alterations in the expression levels of key proteins associated with beta cell function, including GLUT1, GCK, PDX1, and MafA. Moreover, MEHP and MBP exposures were associated with alterations in ER stress-related pathways, including JNK, GADD153, and NF-kappa B expression, as well as PPAR alpha and PPAR gamma levels. In conclusion, this study provides comprehensive insights into the diverse impacts of MEHP and MBP on 1.1B4 pancreatic beta cells, emphasizing their potential role in modulating cell survival, metabolic function, and stress response pathways.

This study investigates the potential repurposing of gentamicin for treating drug-resistant melanoma by targeting metabolic alterations. Rising global cancer incidence and mortality, coupled with the challenge of drug resistance, necessitate novel therapeutic strategies. Initially, we addressed the influence of antibiotics on mitochondrial function, a crucial player in oxidative phosphorylation (OXPHOS). To assess this impact, we first cultured two different cancer cells, A375 and PC3, in antibiotic-free medium and showed that mitochondrial membrane potential of cells was increased in the absence of antibiotics compared to cells cultured in antibiotic containing medium. Next, we developed vemurafenib resistance in A375 cells, which were continuously cultured in antibiotic-free medium. The resistant cells exhibited a marked increase in oxygen consumption rate, indicating a shift towards OXPHOS. Finally, we treated these vemurafenib-resistant cells and noncancerous human fibroblast cells (CCD-1072Sk) with varying concentrations of gentamicin (1-1000 µM). Remarkably, gentamicin showed selective cytotoxicity towards the resistant cells while sparing non-resistant counterparts and noncancerous cells. Our findings highlight gentamicin's potential as a therapeutic agent in targeting the metabolic vulnerabilities of drug-resistant melanoma, presenting a viable new pathway in cancer treatment.

Background and PurposeColorectal cancer (CRC) is the second most lethal disease, with high mortality due to its heterogeneity and chemo-resistance. Here, we have focused on the epidermal growth factor receptor (EGFR) as an effective therapeutic target in CRC and studied the effects of polyphenols known to modulate several key signalling mechanisms including EGFR signalling, associated with anti-proliferative and anti-metastatic properties.Experimental ApproachUsing ligand- and structure-based cheminformatics, we developed three potent, selective alkylaminophenols, 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), 2-[(1,2,3,4-tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl]phenol (THMPP) and N-[2-hydroxy-5-nitrophenyl(4 & PRIME;-methylphenyl)methyl]indoline (HNPMI). These alkylaminophenols were assessed for EGFR interaction, EGFR-pathway modulation, cytotoxic and apoptosis induction, caspase activation and transcriptional and translational regulation. The lead compound HNPMI was evaluated in mice bearing xenografts of CRC cells.Key ResultsOf the three alkylaminophenols tested, HNPMI exhibited the lowest IC50 in CRC cells and potential cytotoxic effects on other tumour cells. Modulation of EGFR pathway down-regulated protein levels of osteopontin, survivin and cathepsin S, leading to apoptosis. Cell cycle analysis revealed that HNPMI induced G0/G1 phase arrest in CRC cells. HNPMI altered the mRNA for and protein levels of several apoptosis-related proteins including caspase 3, BCL-2 and p53. HNPMI down-regulated the proteins crucial to oncogenesis in CRC cells. Assays in mice bearing CRC xenografts showed that HNPMI reduced the relative tumour volume.Conclusions and ImplicationsHNPMI is a promising EGFR inhibitor for clinical translation. HNPMI regulated apoptosis and oncogenesis by modulating BCL-2/BAX and p53 in CRC cell lines, showing potential as a therapeutic agent in the treatment of CRC.

Background Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa, at infection sites.Objectives As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action.Methods In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C. albicans and P. aeruginosa in in vitro and in vivo systems.Results It was observed that QSMs alone, especially farnesol, showed at least a 1-log reduction against preformed single- and dual-species biofilms of C. albicans and P. aeruginosa. Combination of QSMs with colistin or fluconazole was found to be effective against both single- and dual-species biofilms in vitro. Increased survival was observed in C. elegans when treated with colistin or fluconazole in combination with QSMs, compared with no treatment. Additionally, the QSMs and colistin and farnesol combinations effectively inhibited biofilm formation by C. albicans and P. aeruginosa on bronchial epithelial cells, and reduced IL-1 beta expression in lung bronchial epithelial cells.Conclusions There is a need for effective treatments for bacterial-fungal biofilm infections and, to our knowledge, there have been no studies of QSMs and antimicrobial combinations against dual-species biofilms involving C. albicans and P. aeruginosa. Hence these findings will make a significant contribution to the literature.

Abstract Cucurbitacins have high economic value as they are a major source of food and have pharmacological properties. Cucurbitacin I (CuI) is a plant‐derived natural tetracyclic triterpenoid compound that shows an anticancer effect via inhibiting the JAK2‐STAT3 signaling pathway. The actin cytoskeleton is the most abundant protein in cells and regulates critical events through reorganization in cells. In this study, it is aimed at determining the direct effect of CuI on actin dynamics. The fluorescence profile of G‐actin in the presence of CuI (1–200 nM) shifted to a higher temperature, suggesting that G‐actin binds CuI and that G‐actin–CuI is more thermally stable than the ligand‐free form. CuI dose‐dependently inhibited the polymerization of F‐actin in vitro and disrupted actin filaments in endothelial cells. Docking and MD simulations suggested that CuI binds to the binding site formed by residues I136, I175, D154, and A138 that are at the interface of monomers in F‐actin. The migration ability of cells treated with CuI for 24 h was significantly lower than the control group (p < .001). This study reveals the molecular mechanisms of CuI in the regulation of actin dynamics by binding G‐actin. More importantly, this study indicates a novel role of CuI as an actin‐targeting drug by binding directly to G‐actin and may contribute to the mode of action of CuI on anticancer activities.

Self-healing materials recover mechanical damages to expand the lifetime of the material provided. In this study, self-healing hydrogels have been successfully prepared using a novel and simple technique. Vanillin is a natural monomer, used as a bio-based cross-linker for UV-induced bonding and Schiff-base bonding. Methacrylate-functionalized vanillin (M-VAN) is covalently integrated with the polymer matrix. While M-VAN supports polymer matrix with its vinyl group, its aldehyde functionality helps the formation of dynamic covalent imine bonds via Schiff-base formation. The hydrogel showed excellent self-healing ability overnight under physiological conditions without external addition. In addition, the hydrogel surface was modified by collagen and its cell viability was investigated. The prepared scaffolds showed good cell viability of 124% and 163% compared to the control sample. The developed self-healing material reveals that it has possible uses for future biomedical applications and tissue engineering studies due to the self-healing mechanism taking place under ambient conditions.

In this study, new Schiff bases derived from anthranilic acid hydrazide (3a-j) and quinazolin-4(3H)-one (4a-j) were synthesized with high yields (99-90%) and characterized by FTIR, NMR ( 1 H and 13 C), and HRMS spectroscopic techniques. The effects of the synthesized compounds on the human lung adeno-carcinoma cells (A549, CCL-185, ATCC) and the human bronchial epithelial cells (BEAS-2B, ECACC) were examined. IC50 values of the compounds were found in the range of 12.40 - 424.9 mu M against A549 and 15.81 - 752.30 mu M against BEAS-2B cell lines. Compounds 3i, 3j, 4b , and 4f are the most active com-pounds in the series, with low IC50 values against A549, high against BEAS-2B, and high selectivity. For the most active compounds in the series, molecular docking study was performed to understand ligand-protein interactions between the compounds and Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR1). The docking scores were calculated in the range of-5.870 --6.711 kcal/mol for EGFR and-4.142 --8.501 kcal/mol for VEGFR1. (c) 2023 Elsevier B.V. All rights reserved.

Objective: Inflammation is a complex reaction present in numerous disorders. Indomethacin, a compound possessing an indoline core, is a Nonsteroidal Anti-Inflammatory Drug (NSAID) that is commonly prescribed for inflammation and pain. The actin network, plays a major role in cellular activities and it's regulated by by Rho GTPases has important implications for cellular dynamics and orientation. In this research, we explore the effects of indomethacin on the inflammatory response as mediated via RhoA and pyrin inflammatory complexes using an inflammatory disease model with relation actin cytoskeleton. Materials and Methods: This study used Western blotting to examine the impact of indomethacin on the assembly processes related to the pyrin inflammasome complex and the RhoA signaling pathway in Lipopolysaccharide-stimulated THP-1 cells. Actin-indomethacin interaction was analyzed by Differential Scanning Fluorimetry (DSF). Results: We found that while the expression levels of pyrin decreased, phosphorylated-RhoA increased but overall RhoA levels did not change. The equilibrium dissociation constant (K-D) for the G-actin-indomethacin complex was calculated to be 9.591 +/- 1.608 ng/mL (R-2 = 0.8582) using triangle T-m measurements of indomethacin by DSF. Conclusion: Moreover, the effects of indomethacin on inflammation pathways may provide insight into the molecular mechanisms of pyrin inflammasome formation in various autoimmune diseases.

The active ingredients of Aloe vera have attracted attention for their potential use in nanotechnology-based medical applications and biomaterial production. It has many therapeutic applications in modern world. This study used Aloe vera extract in different concentrations to synthesize Aloe vera-incorporated hybrid nanoflowers (AV-Nfs). The most uniform morphology in the nanoflowers obtained was at a concentration of 2 mL. The AV-Nfs were well characterized by scanning electron microscopy, X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction (XRD). The highest peroxidase-mimicking activity of the components was 1.488 EU/mg at 60°C and pH 6. The DPPH assay determined the antioxidant activity of the components and the MTT assay tested on CCD-1072Sk fibroblast cell line determined the effect of AV-Nfs on cell proliferation. Separate treatment of AV-Nfs with Cu3(PO4)2·3H2O significantly increased cell proliferation according to free Aloe vera and CuSO4. In vitro wound healing results showed that AV-Nfs could significantly close wounds compared to free Aloe vera. In this study, AV-Nfs showed antimicrobial activity against Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli and Klebsiella pneumoniae at minimum inhibitory concentration of 625 μg/mL, suggesting that AV-Nfs may be used in wound healing applications with enhanced biological properties. AV-Nfs showed no activity against the yeast Candida albicans.

In this study, new quinazoline–chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the hybrid compounds were tested against A549 human lung adenocarcinoma and BEAS‐2B healthy bronchial epithelial cell lines in vitro. In addition, the ability of the active compounds to inhibit cell migration was tested. Molecular docking studies were performed to evaluate the ligand–protein interactions, and molecular dynamics simulations were performed to determine the interactions and stability of ligand–protein complexes. In silico absorption, distribution, metabolism, and excretion (ADME) studies were conducted to estimate the drug‐likeness of the compounds. Compounds 4 (IC50 = 51.2 µM) and 5 (IC50 = 44.2 µM) were found to be the most active agents against A549 cells. They are found to be more selective against A549 cells than the reference drug doxorubicin. They also have the ability to significantly inhibit cell migration. They have the best docking scores against epidermal growth factor receptor (EGFR) (−11.300 and −11.226 kcal/mol) and vascular endothelial growth factor receptor 2 (VEGFR2) (−10.987 and −11.247 kcal/mol), respectively. In MD simulations, compounds 4 and 5 have strong hydrogen bond interactions above 80% of simulation times and showed a low ligand root mean square deviation (RMSD) around 2 Å. According to the ADME analysis, compounds 4 and 5 exhibit excellent drug‐likeness and pharmacokinetic characteristics.

In recent years, phthalates and their metabolites have been associated with metabolic diseases such as diabetes mellitus. To investigate the effects of phthalate exposure, 1.1B4 pancreatic beta cells were treated with monoethylhexyl phthalate (MEHP) and monobutyl phthalate (MBP) (0-1000 µM) and cell viability, apoptosis rate, lysosomal membrane permeabilization (LMP), mitochondrial membrane potential (ΔΨm), oxidative stress and ER stress status, and pancreatic beta cell functions were evaluated. MEHP, not MBP, exhibited a notable reduction in metabolic viability, particularly at higher concentrations (500 and 1000 µM) following 24-hour exposure. Similarly, both MEHP and MBP induced decreased metabolic viability at high concentrations after 48- and 72-hour exposure. Notably, neither MEHP nor MBP demonstrated a significant impact on apoptosis rates after 24-hour exposure, and MBP induced mild necrosis at 1000 µM concentration. Cell proliferation rates, indicated by PCNA expression, decreased with 10 and 1000 µM MEHP and 0.1 and 10 µM MBP exposures. LMP analysis revealed an increase in 1000 µM MBP group. Exposure to 0.001 µM of both MEHP and MBP significantly reduced cellular glutathione (GSH) levels. No significant change in intracellular reactive oxygen species (ROS) levels and ΔΨm was observed, but MBP-exposed cells exhibited elevated levels of lipid peroxidation. Functional assessments of pancreatic beta cells unveiled reduced insulin secretion at low glucose concentrations following exposure to both MEHP and MBP, with concurrent alterations in the expression levels of key proteins associated with beta cell function, including GLUT1, GCK, PDX1, and MafA. Moreover, MEHP and MBP exposures were associated with alterations in ER stress-related pathways, including JNK, GADD153, and NF-κB expression, as well as PPARα and PPARγ levels. In conclusion, this study provides comprehensive insights into the diverse impacts of MEHP and MBP on 1.1B4 pancreatic beta cells, emphasizing their potential role in modulating cell survival, metabolic function, and stress response pathways.

In this study, 13 new hybrid compounds (7a-m) were synthesised starting from ursolic acid, and their cytotoxic activities were investigated on the BEAS-2B and A549 cell lines. In addition, the synthesised compounds were tested against Staphylococcus aureus, Escherichia coli, and Candida albicans to determine their anti-microbial properties. The hybrid compounds that exhibited the lowest cytotoxicity against the BEAS-2B were 7k, 7b, and 7g. The cytotoxicity of the compounds against A549 was evaluated, the IC50 value of 7k, 7b, and 7g are found as 0.15 µM, 0.31 µM, and 0.26 µM, respectively. The results showed that the selectivity of 7k was 7 times higher than doxorubicin against the A549 cells. According to the antimicrobial activity studies 7c is found as the most effective compound against S. aureus. Almost all compounds showed a similar inhibition potential against E. coli and C. albicans.

Lungs of cystic fibrosis patients are often colonized or infected with organisms, such as Pseudomonas aeruginosa and other emerging pathogenic bacteria such as Achromobacter xylosoxidans. Further, it is well established that infections of the cystic fibrosis lung airways are caused by polymicrobial infections, although its composition and diversity may change throughout the patient's life. In the present study, we investigated the effects of N-acetylcysteine (NAC) and amikacin, aztreonam, ciprofloxacin, and tobramycin alone and in combination against single- and dual-species biofilms of P. aeruginosa and A. xylosoxidans, in vitro and in the Caenorhabditis elegans infection model. Results showed that tobramycin and ciprofloxacin were the most effective antibiotics, while aztreonam was the least effective antibiotic against both single- and dual-species biofilms of P. aeruginosa and A. xylosoxidans. However, NAC showed little effect on both single- and dual-species, even with a combination of antibiotics. Increased survival was observed in C. elegans when treated with NAC in combination with tobramycin or ciprofloxacin, compared to no treatment or NAC alone. Tobramycin and ciprofloxacin were found effective in biofilms, but more research is needed to better understand the effects of NAC and antibiotics against single- and dual-species biofilms.

Objectives: The consumption of alcohol by adults may lead to severe neurodegeneration and significant behavioral problems. An increase in the harmful effects of alcohol becomes aggravated after the development of alcohol dependence. Furthermore, the serious damage from chronic alcohol intake on the hippocampus has gained attention due to its role on learning and memory. Therefore, the study aimed to examine the retention of spatial reference memory during different points in time regarding alcohol withdrawal in Wistar rats. Materials and Methods: The study has therefore administered alcohol to rats at gradually increasing doses from 4.5 to 12 g/kg/day in a binge-like manner using the intragastric intubation technique for six days followed by 24, 48, or 96 hours of alcohol withdrawal. To evaluate the effects of alcohol withdrawal, the alcohol-exposed rats have been tested regarding their spatial reference memory. Results: An adverse effect from alcohol withdrawal on memory retention was observed in the 24-hour alcohol withdrawal group. This effect decreased at 48 hours of withdrawal, but reappeared at 96 hours. Conclusion: The study’s results suggest that alcohol withdrawal itself, even after a relatively short period of alcohol intake, may also adversely affect memory. Therefore, withdrawal therapy from alcohol should be performed in a controlled manner to protect the brain from extended alcohol withdrawal-induced spatial memory impairments.

Trace elements (TEs) playing critical roles in chemical events that occur at the cellular level in the body are necessary for biological processes in human health. The role of TEs and selenoproteins and their relationship with breast cancer (BC) have not been studied thoroughly and therefore remain relatively unknown. Our study aimed to investigate possible changes in the serum selenoproteins (Glutathione Peroxidase 1 (GPX1), Glutathione Peroxidase 6 (GPX6), Selenoprotein F (Sel-F), Selenoprotein H (Sel-H), Selenoprotein S (Sel-S), Selenoprotein V (Sel-V), Selenoprotein M (Sel-M)), and TEs (Se, Zn, Mn, Cu, and Fe) levels, and TEs ratios (Fe/Se, Fe/Zn, Fe/Mn, Cu/Se, Cu/Zn, and Cu/Mn) in patients with BC before and after treatment (surgery, radiotherapy, and chemotherapy), and to evaluate the results in the patient groups with healthy controls. A total of 35 patients with BC and 25 healthy subjects were included in the study. Blood samples were collected from the patient group on the day prior to treatment, and on the day treatment was completed. Serum GPX1, GPX6, Sel-F, Sel-H, and Sel-S levels were decreased in both before and after treatment groups compared to the control. The treatment of BC resulted in increasing the concentration of Sel-V compared to before treatment levels. The treatment of BC resulted in lowering serum Se, Zn, and Fe concentrations compared to before treatment levels. Also, serum Se, Zn, and Fe levels were decreased in both before and after treatment groups compared to the control. The ratios of Cu/Se, Cu/Zn, and Cu/Mn were increased after treatment compared to the values before treatment. Cu/Se and Cu/Zn ratios were increased, but Fe/Mn ratios were decreased after treatment compared to healthy control. This study indicates that changes in serum levels of TEs such as Zn, Mn, Cu, and Se, as well as their ratios and selenoproteins, may be related to the treatments of BC. Further studies are required to clarify the exact specific mechanisms involved in the status of TEs and selenoproteins in therapeutic strategies of BC.

The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be investigated. This study aimed to compare the effects of three different antihypertensive drugs (telmisartan, perindopril, and nebivolol) on neuroprotection and acetylcholine (ACh) levels against lipopolysaccharide (LPS)-induced injury in a differentiated SH-SY5Y cell line. Cells were treated with retinoic acid for differentiation to a neuronal phenotype. LPS 20 (μg/mL) was applied to the cells for one hour. Then, the cells were treated with 1, 5, and 10 µg/mL concentrations of telmisartan, perindopril, and nebivolol separately for 24 hours, except for the control and LPS alone groups. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ACh levels were analyzed using an enzyme immunosorbent assay in the culture medium. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) expressions were evaluated using western blot analysis. Telmisartan demonstrated the highest cell viability against LPS-induced injury, whereas the protective effect of perindopril was moderate. Nebivolol showed no neuroprotective effect. The protective effect of 10-µg/mL telmisartan was superior to 10 µg/mL perindopril (p=0.006), 5 µg/mL perindopril (p=0.001), 1 µg/mL perindopril (p=0.001), and 1, 5, and 10 µg/mL nebivolol (p<0.001). Among all the study drugs, only telmisartan provided a statistically significant increase in ACh levels after LPS-induced injury. Additionally, the administration of telmisartan provided a concentration-dependent reduction in TNF-α, IL-1β, and NFκB expression against LPS-induced neuroinflammation. These findings suggest that telmisartan has a superior neuroprotective effect against LPS-induced injury in neuron-like cells compared with both perindopril and nebivolol.