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Amaç: Alzheimer hastalığı progresifi, yaygın nörodejeneratif bir hastalık olup demansın en sık görülen türüdür. Bu hastalığın mekanizması kesin olarak bilinmemekle birlikte en önemli etmenlerden biri amiloid beta (Aβ) hücreler arası plakların oluşumudur. Kinik asit (QA) antioksidan özellikleri sayesinde nöroprotektif etki sağlayan bir polifenoldür. Çalışmamızın amacı QA'nın Aβ peptidi kaynaklı oksidatif nörotoksisiteye karşı in vitro koruyucu etkisini araştırmaktır. Yöntemler: QA'nın nöroprotektif etkisini belirlemek için 3-4,5-dimetil-tiyazolil-2,5-difeniltetrazolyum bromür (MTT), antioksidan-oksidan etkilerini belirlemek için Total antioksidan kapasite (TAC)- Total oksidan seviye (TOS) analizleri yapıldı. Bulgular: Aβ, MTT analizinde SH-SY5Y'nin hücre canlılığını belirgin şekilde azalttı. Buna karşılık, QA hücre canlılığını önemli ölçüde artırdı ve QA'nın hücre çoğalmasını indüklediğini gösterdi. Aβ'ye maruz kalma, kontrolle karşılaştırıldığında TOS seviyelerini belirgin şekilde artırdı. Ayrıca, Aβ, SH-SY5Y hücrelerinde TAC aktivitesini azalttı. QA, Aβ'nin indüklediği TOS oluşumunu belirgin şekilde dengeledi. Aynı zamanda, QA, Aβ'ye maruz kalan SH-SY5Y hücrelerinde TAC aktivitesini artırdı. Sonuç: Bulgularımız QA’in Aβ kaynaklı nörotoksisiteyi ve oksidatif stresi önleyerek nöroprotektif etkisini ortaya çıkardı. Anahtar Kelimeler: Alzheimer hastalığı, Antioksidan, Nöroblastom, Kinik asit

Amaç: Prostat kanseri (PC), dünya çapında erkeklerde kanserden ölümlerin en yaygın nedenlerinden biridir ve PC'yi tedavi etmek için yeni ilaçlar halen geliştirilmektedir. Şırınga asidi (SA), çeşitli tümörlerde antiinflamatuar ve metabolik düzenleyici etkiler ve antitümör aktiviteleri sergileyen bir polifenolik bileşiktir. Bu çalışma, SA'nın DU-145 hücreleri üzerindeki antiproliferatif ve antitümör aktivitelerini araştırmayı amaçladı. Yöntemler: SA'nın antiproliferatif etkisini belirlemek için MTT, antioksidan-oksidan etkilerini belirlemek için SOD-MDA analizleri kullanıldı. Bulgular: SA, in vitro olarak DU-145 hücre proliferasyonunu önemli ölçüde baskıladı. Ayrıca SOD düzeylerini düşürürken, MDA düzeylerinde ise ciddi bir artışa neden olmuştur. Sonuç: Bulgularımız SA'nın iyileştirici etkisini hedef alarak PC'nin antitümör potansiyelini ortaya çıkardı.Anahtar Kelimeler: DU-145, MDA, Prostat kanseri, SOD, Şırınga asidi

Aim: The aim of our study is to the evaluation of melatonin (MLT) and Momordica charantia (MC) combination on PC-3 and HT-29 cancer lines and to address the question of where or not MLT increases MC antitumor effect in the PC-3 and HT-29 cancer lines. Material and Method: The PC-3 and HT-29 cell lines were grown in a manufacturer-specified culture medium. Cisplatin, MLT, increasing concentrations of MC, 40 μg/ml MLT + increasing concentrations MC were applied to PC-3 and HT-29 cell lines for 72 hours. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell viability, Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Cellular Migration (Wound Healing test), and Lactate Dehydrogenase (LDH) tests were done 72 hours after drug administration. Results: The combination of MLT 40 μg/ml + MC 100 µg/ml reduced cell viability in both PC-3 and HT-29 cells. Besides, TAC and TOS levels showed a correlation with LDH and MTT assays and were found to be statistically significant (P

Therapeutic approaches based on isolated compounds derived from natural products are more common in preventing diseases involving inflammation and oxidative stress at present. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound with many positive effects in cell models and living systems. SAC has biological activity in various fields, enclosing healing in learning and memory disorders, neurotrophic effects, and antioxidant activity. In this study, we purposed to identify the neuroprotective activity of SAC toward 6-OHDA-induced cell demise in the SH-SY5Ycell line. For this purpose, 6-OHDA-induced cytotoxicity, and biochemical, and gene expression changes were evaluated in SH-SY5Y cells. SH-SY5Y cells grown in cell culture were treated with SAC 24 h before and after 6-OHDA application. Then, cell viability, antioxidant parameters, and gene expressions were measured. Finally, immunofluorescence staining analysis was performed. Our results showed that SAC increased cell viability by 144 % at 80 µg/mL with pre-incubation (2 h). It was observed that antioxidant levels were significantly increased and oxidative stress marker levels were decreased in cells exposed to 6-OHDA after pre-treatment with SAC (p

Nanoparticles are attracting attention for their potential therapeutic applications, particularly in cancer therapy, underscoring their importance in medicine. Cadmium sulfide nanoparticles, known for their robust catalytic and optical properties, are classified as chalcogenides and show promise for cancer diagnosis and treatment. Neuroblastoma, a common solid tumor in childhood, poses a significant health threat with different outcomes depending on its biological subtype. This study evaluated the antiproliferative effects of cadmium sulfide nanoparticles on the SY-SH5Y cell line. Walnut shell extract and Na2S were used to facilitate the synthesis of cadmium sulfide nanoparticles by green synthesis. Characterization of the synthesized cadmium sulfide nanoparticles was performed by Fourier transform infrared spectroscopy, scanning electron microscopy, and x-ray diffraction analyses. The SH-SY5Y cell line was cultured in a standard cell culture medium and then exposed to different cadmium sulfide nanoparticles (10–25–50–75–100 µg/mL) for 24 hours. Cell viability, oxidant, and antioxidant levels were then assessed using a 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür, total antioxidant, and total oxidant assays. The data showed that applying 100 μg/mL cadmium sulfide nanoparticles resulted in a significant decrease in cancer cell viability of up to 40.96 % (p

Abstract Parkinson’s disease (PD) is a chronic neurodegenerative case. As the disease progresses, the response time to doses of levodopa (L-Dopa) becomes shorter and the effects of the drug are severely limited by some undesirable side effects such as the ‘on–off’ phenomenon. In several diseases, including Parkinson’s, nanoparticles can deliver antioxidant compounds that reduce oxidative stress. This study evaluates and compares the neuroprotective effects of L-Dopa-modified zinc nanoparticles (ZnNPs) in the 6-hydroxydopamine (6-OHDA)-induced PD rat model. For this purpose, the synthesis of NPs was carried out. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectrophotometer were used for characterization. The rats were randomized into 9 experimental groups: control, lesion group (6-OHDA), 6-OHDA + 5 mg/kg L-Dopa, 6-OHDA + 10 mg/kg L-Dopa, 6-OHDA + 20 mg/kg L-Dopa, 6-OHDA + 20 mg/kg ZnNPs, 6-OHDA + 40 mg/kg ZnNPs, 6-OHDA + 30 mg/kg ZnNPs + L-Dopa, and 6-OHDA + 60 mg/kg ZnNPs + L-Dopa. Behavioral tests were performed on all groups 14 days after treatment. Phosphatase and tensin homolog, Excitatory amino acid transporter 1/2, and Glutamine synthetase gene analyses were performed on brain samples taken immediately after the tests. In addition, histological and immunohistochemical methods were used to determine the general structure and properties of the tissues. We obtained important findings that L-Dopa-modified ZnNPs increased the activity of glutamate transporters. Our experiment showed that glutamate increases neuronal cell vitality and improves behavioral performance. Therefore, L-Dopa-modified ZnNPs can be used to prevent neurotoxicity. According to what we found, results show that L-Dopa-modified ZnNPs will lend to the effective avoidance and therapy of PD.

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.

(1) Background: Colon cancer is one of the most common cancer types, and treatment options, unfortunately, do not continually improve the survival rate of patients. With the unprecedented development of nanotechnologies, nanomedicine has become a significant direction in cancer research. Indeed, chemotherapeutics with nanoparticles (NPs) in cancer treatment is an outstanding new treatment principle. (2) Methods: Fe3O4 NPs were synthesized and characterized. Caco-2 colon cancer cells were treated during two different periods (24 and 72 h) with Fe3O4 NPs (6 μg/mL), various concentrations of 5-FU (4–16 μg/mL), and Fe3O4 NPs in combination with 5-FU (4–16 μg/mL) (Fe3O4 NPs + 5-FU). (3) Results: The MTT assay showed that treating the cells with Fe3O4 NPs + 5-FU at 16 µg/mL for 24 or 72 h decreased cell viability and increased their LDH release (p < 0.05 and p < 0.01, respectively). Furthermore, at the same treatment concentrations, total antioxidant capacity (TAC) was decreased (p < 0.05 and p < 0.01, respectively), and total oxidant status (TOS) increased (p < 0.05 and p < 0.01, respectively). Moreover, after treatment with Fe3O4-NPs + 5-FU, the IL-10 gene was downregulated and PTEN gene expression was upregulated (p < 0.05 and p < 0.01, respectively) compared with those of the control. (4) Conclusions: Fe3O4 NPs exert a synergistic cytotoxic effect with 5-FU on Caco-2 cells at concentrations below the active drug threshold levels.

Due to their structural characteristics at the nanoscale level, single-walled carbon nanotubes (SWNTs), hold great promise for applications in biomedicine such as drug delivery systems. Herein, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of various Fmoc-amino acid bearing polyethylene glycol (PEG) chains (Mw = 2,000, 5,000, and 12,000). In the first step, full-atom molecular dynamics simulations (MD) were performed to identify the most suitable Fmoc-amino acid for an effective surface coating of SWNT. Fmoc-glycine, Fmoc-tryptophan, and Fmoc-cysteine were selected to attach to the PEG polymer. Here, Fmoc-cysteine and -tryptophan had better average interaction energies with SWNT with a high number of aromatic groups, while Fmoc-glycine provided a non-aromatic control. In the experimental studies, non-covalent modification of SWNTs was achieved by Fmoc-amino acid-bearing PEG chains. The remarkably high amount of Fmoc-glycine-PEG, Fmoc-tryptophan-PEG, and Fmoc-cysteine-PEG complexes adsorbed onto the SWNT surface, as was assessed via thermogravimetric and UV-vis spectroscopy analyses. Furthermore, Fmoc-cysteine-PEG5000 and Fmoc-cysteine-PEG12000 complexes displayed longer suspension time in deionized water, up to 1 and 5 week, respectively, underlying the ability of these surfactants to effectively disperse SWNTs in an aqueous environment. In vitro cell viability assays on human dermal fibroblast cells also showed the low cytotoxicity of these two samples, even at high concentrations. In conclusion, synthesized nanocarriers have a great potential for drug delivery systems, with high loading capacity, and excellent complex stability in water critical for biocompatibility.

High-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cognitive decline is well defined in glioblastomas, the neurotoxic factors underlying this pathology are not well understood in GBM patients. In this study, we aimed to investigate whether GBM-derived exosomes play a role in neuronal toxicity. For this purpose, exosomes obtained from T98G and U373 GBM cells were applied to primary neuron culture at different concentrations. Subsequently, MTT, LDH, GSH, TAS, and TOS tests were performed. Both GBM-derived exosomes induced a dose-dependent and statistically significant increase of LDH release in cerebellar neurons. MTT assay revealed as both T98G and U373 GBM-derived exosomes induced dose-dependent neurotoxic effects in cerebellar neurons. To the best of our knowledge, this study is the first study demonstrating the toxic potential of GBM-derived exosomes to primary neurons, which may explain the peritumoral edema and cognitive decline in GBM patients.