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Cancer, defined by the continuous, uncontrollable proliferation of cells in the human body, is a disease with a rapidly increasing incidence and mortality rate. Scientists are looking for novel ways to cure and prevent this sneaky disease because of the toxicity of contemporary chemotherapy and the cancer cells' resilience to anticancer drugs. Determining the effect of herbal medicines, which do not have as harmful side effects as synthetic drugs, on cancer cell lines is an essential preliminary study in the production of effective drugs against cancer. In this study, the phenolic acid profile, antioxidant capacity, and cytotoxicity of the medicinal plant Mespilus germanica (MG) leaf extract were determined, and its effects on the expression of some apoptotic, necrotic, and autophagic pathway genes of MCF7 (Human breast cancer line) and A549 (Human lung cancer line) and healthy HDF (Human Dermal Fibroblasts) cells were investigated for the first time. The LCMS device detected many important phenolic compounds previously reported to act against cancer cells in Mespilus germanica leaf extract. DPPH and total phenolic content showed high antioxidant capacity. The cytotoxicity of MG was determined by the MTT method. The levels of mRNA transcription for Atg5, Atg3, Ripk1, Bcl2, Bax, Apaf1, Caspase-8, Caspase-7, Caspase-3, and Caspase-9, as well as the expression patterns of the DNA damage markers P53 and Parp-1 genes, were assessed. MG leaf extract did not cause significant toxicity against healthy HDF cells. However, it had a cytotoxic effect on A549 and MCF7 cancer cell lines, increasing the transcription levels of essential genes involved in cell death mechanisms. This research is the first to analyze the phenolic components and antioxidant capabilities of leaf extracts from Mespilus germanica. Additionally, it investigates the impact of these extracts on crucial genes involved in cell death pathways of A549 lung cancer, MCF7 breast cancer, and non-cancerous HDF (Human Dermal Fibroblasts) cells.

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This study aims to investigate the effects of lycopene on apoptotic, autophagic, and necrotic pathways, oxidative status, and DNA damage in diabetic nephropathy at the molecular level. The sample of the study includes seven groups: lycopene (L), high glucose (G), high glucose + lycopene (GL), and control (C) groups tested at 12 and 24 h. The expression levels of genes in oxidative, apoptotic, autophagic, and necrotic cell death pathways are determined by reverse transcription-quantitative polymerase chain reaction analysis. The comet assay method is used for the analysis of DNA damage. It is observed that adding lycopene to high glucose for protective purposes reduces the expression of genes related to apoptosis, autophagy, and necrosis, as well as the DNA damage index, compared to cells given high glucose alone. Lycopene can be a safe and effective alternative agent.

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BACKGROUND: Out of all measure systemic exposure to fluorides can cause defect of skeletal and dental fluorosis. Endoplasmic reticulum (ER) stress is caused by fluorine-induced oxidative stress and importance of vitamin D in its prevention is not known enough in bone cells. This study was carried out to investigate fluorine-induced oxidative stress, ER stress, and death pathways and the effect of vitamin D on them. METHODS: MC3T3-E1 mouse osteoblast cell line was used as the material of the study. The NaF and vitamin D concentrations were determined by the MTT assay. NaF treatments and vitamin D supplementation (pre-add, co-add, and post-add) was administered in the cell line at 24th and 48th hours. The expression of the genes in oxidative stress, ER stress, and death pathways was determined using RT-qPCR and Western blotting techniques. RESULTS: Vitamin D significantly reduced mRNA expression levels of SOD2, CYGB, ATF6, PERK, IRE1, ATG5 and BECN1 whereas caused an increase in levels GPX1, SOD1, NOS2 and Caspase-3 in MC3T3-E1 mouse osteoblast cell line of NaF-induced. In addition, GPX1, SOD1, ATF6, PERK, IRE1, BECN1, Caspase-3 and RIPK1 protein levels were examined by Western blot analysis, and it was determined that vitamin D decreased IRE1 and PERK protein levels, but increased GPX1, SOD1, ATF6 and Caspase-3 protein levels. CONCLUSION: The findings of the study suggest that vitamin D has protective potential against NaF-induced cytotoxicity reasonably through the attenuation of oxidative stress, ER stress, ATG5, IRE1 and by increasesing caspase-3 in vitro conditions.

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This study was planned to evaluate the effect of vitamin D administration on cytotoxicity due to fluoride exposure in vitro. NaF (IC50) and vitamin D (proliferative) were applied to human osteoblast (hFOB 1.19) cells. The major genes of apoptotic, autophagic, and necrotic pathways were determined by RT-PCR. 2-∆∆Ct formulation was used for expression analysis. In the NaF group, caspase 3, Bax, Bad, Bak, Bclx, Atg3, Atg5, Atg6, pG2, LC3-I, LC3-II, RIP1, and RIP3 genes were increased (2.6-15 times). It was observed that the expressions of these genes approached the control when vitamin D was given together with NaF. The Bcl2 gene increased significantly (sixfold) with the effect of NaF, and was down-regulated to some extent with additional vitamin D administration, but still more than in the control. As a result, it was determined that apoptotic, necrotic, and autophagic pathways were activated as the molecular basis of the damage in the bone tissue, which was most affected by fluorine, and these genes were down-regulated and approached the control group with the addition of vitamin D. It was concluded that this is an important data to explain the molecular basis of the protective and therapeutic effect of vitamin D against fluorine toxicity.

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BACKGROUND: Insulin resistance plays an important role in predicting type 2 diabetes that may develops. This study was planned in order to investigate the beneficial effects of quinoa (Chenopodium quinoa) use in glucocorticoid induced-insulin resistance. METHODS AND RESULTS: Forty-two rats were used as the material (experimental) groups: the control group (C), the quinoa-administered group (Q), the insulin resistance-created group (IR), the IR + metformin group (IM), the IR + quinoa for treatment group (IQ) and the quinoa + IR for prophylaxis group (QI). Blood glucose, insulin levels and HOMA-IR were found to be highest (p < 0.05) in the IR group (p < 0.05). Glucose levels decreased significantly with the administration of quinoa and approached the levels of the control, but the insulin levels and the HOMA-IR did not significantly change. It was also observed that other biochemical parameters (ALT, AST, ALP, total cholesterol, total protein, urea and creatinine) changed significantly in the IR group and approached the levels of the control group with the administration of quinoa. Apoptotic (BCL2 5, BAX 9, CAS 3), autophagic (SQSTM1 7, ATG5) and inflammation (IL-1ß, TNF-α) genes were upregulated by 5-11-fold in the IR group. In the groups in which quinoa was administered for treatment and protection, all these genes were found to be upregulated to a lower extent than the IR group. Antioxidant genes (GPX1, SOD1) increased by nine to tenfold in the quinoa groups. CONCLUSION: As a result, after administration of quinoa, it was determined that the glucose level increased due to experimental insulin resistance and the liver and kidney damage indicators decreased. It was determined that quinoa (Chenopodium quinoa) had significant beneficial effects on biochemical parameters and apoptotic, autophagic, antioxidant and inflammatory markers in experimental glucocorticoid-induced insulin resistance.

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The effects of the element fluorine on the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway has a significant role in regulation of intracellular molecular mechanisms. NRK-52E rat kidney epithelial cell line was selected as the material of the study. NaF was used as the fluorine source in the study. The NaF dose was determined with the MTT assay. The NaF concentrations were determined as the proliferation concentration of 10 µM and IC25 (2250 µM) and IC50 (4250 µM) for 24 h. In the study, the erb-b2 receptor tyrosine kinase 2 (ERBB2), phosphoinositide-3-kinase (PI3K), Protein kinase B (PKB,Akt), Mammalian target of rapamycin (mTOR), and the Tumor protein 53 (TP53) genes were considered as the target genes. NaF concentration was administered on the cells. Total mRNA was isolated. mRNAs were turned into cDNA. The expression levels of the target genes were determined by RT-qPCR method. According to the results obtained in the study, the low NaF concentration increased the expression levels of the ERBB2, PI3K, and Akt genes, while the higher concentrations did not significantly affect these levels. The expression of mTOR decreased at all given concentrations. The expression of the TP53 gene did not change at the low concentration, while it increased at the high concentrations. Based on the results, it may be stated that fluorine may inhibit the kinase enzymes in the PI3K/Akt pathway. In summary, in the pathogenesis of the cell damage caused by fluorine in the NRK-52E cell line, the PI3K/Akt/mTOR pathway is an important signal pathway.

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This study was planned to determine the molecular basis and causes of damage to the kidney and the liver, which are the most affected tissues in sheep exposed to chronic fluoride. For this purpose, liver and kidney tissues were obtained from sheep with signs of fluorosis in the age range of 4-6 years. The control group consisted of clinically healthy sheep without fluorosis. The apoptotic and oxidative genes expression of target genes was determined using the real qRT-PCR method. According to the control gene (Gapdh) that was detected that in the liver, the apoptotic genes caspase-8, caspase-9, and Bim increased and caspase-3, Bcl-2, and Bak decreased, while in the kidney, caspase-3 and Bax and caspase-8, Bcl-2, Bcl2l-1, Bim, and Bak decreased. According to the 2-ΔCt values of the oxidative stress genes, it was determined that Cygb, Gstp1, and Ncf1 genes increased significantly in the fluorosis group and Gpx1, sod1, and sod2 genes decreased significantly. In the kidney tissue, Cygb and Gpx1 increased in the fluorosis group, while sod1, sod2, Gstp1, Ncf1 and Ccs, and Nos2 were found to decrease significantly. As a result, it was shown that apoptosis and oxidative mechanisms are activated in the liver and the kidney tissues of sheep with fluorosis and these parameters have an important role in understanding the molecular basis of tissue damage in fluorosis.

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Exposure of fluorine at toxic concentrations causes serious damage by accumulating in especially bones, kidneys, and other soft tissues. Fluorine at cytotoxic concentrations may cause DNA damage. This study aims to determine the level of DNA damage due to sodium fluoride (NaF) at different hours (3rd, 12th, and 24th hours) and in IC50 concentrations designated for each hour and reveal the protective effect of lycopene on possible damage. The best enhancer concentrations (1 µM) of microtitration (MTT) viability test and proliferation of lycopene and IC50 values of NaF at the 3rd, 12th, and 24th hour were 9600, 5500, and 3200 µM, respectively. DNA damage significantly increased in all NaF-treated groups in comparison with the control group (p < 0.05). DNA damage due to NaF+LYC application significantly decreased in comparison with the control group (p < 0.05). Lycopene application significantly increased the expression levels of the Ku70 and Ku80 genes which have a part in DNA repair (p < 0.05). The statistical data showed that application of lycopene which is an important antioxidant molecule may be beneficial for decreasing NaF-induced DNA damage. In conclusion, applying lycopene for cytotoxicity due to fluorine in NRK-52E cell line had different effects based on the dosage and time; thus, it can be a potential option for preventing fluorosis-induced toxicity and developing new treatment approaches.

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Prolonged and excessive fluoride exposure can lead to fluorosis. The kidney is one of the organs that are injured mostly due to fluoride-induced damage. Fluoride can induce DNA damage at cytotoxic concentrations. This study aims to determine the extent of NaF-induced DNA damage and to investigate the effect of vitamin E and selenium combination (ES) in preventing and repairing this damage. For this purpose, we administered different combinations of NaF and ES to NRK-52E cells and determined the effective concentrations of ES and the NaF IC50 values associated with different incubation times (3, 12, and 24 h) by using the MTT assay. The determined quantities of NaF IC50 in association with time and the NaF IC50 + ES combination were administered to the cells. The extent of DNA damage was determined with the comet assay and the expression levels of the Ku70/80 and PARP-1 genes were determined with the RT-qPCR method. DNA damage significantly increased in all experimental groups compared to the control group (p < 0.05). It was found out that the NaF and ES combination statistically reduced the DNA damage compared to the damage observed in the NaF-treated groups (p < 0.05). Treatment of the ES combination significantly increased the expressions of Ku70 and Ku80 genes involved in DNA repair (p < 0.05). We concluded that vitamin E and selenium can potentially be effective in the repair of fluoride-induced DNA damage based on the results of this in vitro study. Our results may shed light on the prevention of DNA damage associated with fluorosis.

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The study was planned to investigate the effects of thymoquinone (TQ), which is a compound in N. sativa, on caspase dependent apoptosis and oxidative DNA damage in high glucose treated PC12 cells. PC12 cells were treated with high glucose (G1-150 mM, G2-250 mM, G3-350 mM), TQ (20 µM), and their combinations. Oxidative DNA damage (8-OHdG (8-Oxo-2'-deoxyguanosine)), and apoptosis (caspase 3, caspase 8, caspase 9 enzymes and M30 protein) parameters were analyzed with ELISA. The 8-OHdG levels decreased in all combination groups compared to the control (p≤0.001). There was no statistically significant difference between caspase 3 and 9. Caspase 8 in TQ, G3, TQG1, TQG2 groups were higher than the control (p≤0.002). Low M30 levels were observed in TQG1 group (p≤0.002). In conclusion, it was observed that in PC12 cell line treated with the high glucose concentrations, TQ administration had a statistically significant effect on oxidative DNA damage and some apoptotic parameters (caspase 8 and M30 protein).

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This study was planned to determine the effects of lycopene treatment on serum protein fractions in experimental diabetic rats. In order to induce diabetes in rats in the diabetes (D) and diabetes + lycopene (DL) groups, rats were given 45 mg/kg single-dose streptozotocin intraperitoneally. Lycopene (10 mg/kg/day dissolved in sunflower oil) was administered to the rats in the lycopene-only (L) and DL groups. Blood glucose levels and HbA1c% in DL group and diabetes group increased (p < 0.05) compared to control and L group. Total protein, albumin, α1, α2, and ß globulin fractions of diabetic and DL groups were lower than control and L groups (p < 0.05). D group had lowest gamma (γ) globulin levels among other groups (p < 0.05). The γ globulin levels was slightly increased than diabetic groups (D and DL), but it was still lower than control and L groups (p < 0.05). The highest value of A/G ratio was observed in diabetic group. Similarly, the % level of A/G ratio of D group was higher than other groups. It was noted that the A/G ratio decreased and reached to control group levels after lycopene treatment.

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