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Chrysin, a naturally occurring flavonoid in plant and bee products, demonstrates notable biological activities, including anti-cancer effects. These properties are partially attributed to its capability to activate immune cells. This study focused on exploring the immunomodulatory potential of chrysin on NK-92 and Jurkat-T cells targeting breast cancer cells (BCC). Chrysin leads to activation of NK-92 and T cells facilitated by the addition of human recombinant IL-2 and PHA-M. The anti-cancer efficacy of chrysin on these immune cells was evaluated in a co-culture setup with EGF-stimulated MCF-7 and MDA-MB-231 cells. Findings revealed that chrysin notably increased the cytotoxicity of NK-92 and T cells towards MCF-7 and MDA-MB-231 cells, with the most significant impact observed on MCF-7 cells (20%). The activation of NK-92 cells, marked by increased IFN-γ production and CD56 expression, correlated with enhanced secretion of cytokines. Additionally, the activation of these cells against BCC was linked with elevated levels of granzyme-B, TNF-α, and nitric oxide (NO). Similarly, the cytotoxic activation of Jurkat-T cells against BCC was characterized by increased production of granzyme-B, IL-2, and IFN-γ. Consequently, these results support the hypothesis that chrysin significantly contributes to the activation and functional enhancement of NK-92 and T-cells against two distinct BCC lines.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses ongoing global health challenges due to its propensity for mutations, which can undermine vaccine efficacy. With no definitive treatment available, urgent research into affordable and biocompatible therapeutic agents is extremely urgent. Angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine subtype 2 (TMPRSS2), and Furin enzymes, which allow the virus to enter cells, are particularly important as potential drug targets among scientists. Olive leaf extract (OLE) has garnered attention for its potential against Coronavirus Disease-9 (COVID-19), yet its mechanism remains understudied. In this study, we aimed to investigate the effects of OLE on ACE-2, TMPRSS2, and Furin protein expressions by cell culture study. Total phenol, flavonoid content, and antioxidant capacity were measured by photometric methods, and oleuropein levels were measured by liquid LC-HR-MS. Cell viability was analyzed by ATP levels using a luminometric method. ACE-2, TMPRSS2, and Furin expressions were analyzed by the Western Blotting method. ACE-2, TMPRSS2, and Furin protein expression levels were significantly lower in a dose dependent manner and the highest inhibition was seen at 100 µg/ml OLE. The results showed that OLE may be a promising treatment candidate for COVID-19 disease. However, further studies need to be conducted in cells co-infected with the virus.

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BACKGROUND: Restorative materials are in prolonged contact with living tissues such as oral mucosa, dentin, pulp, periodontal, and periapical tissues. Therefore, the potentially harmful effects of these materials and their components on oral tissues should be evaluated before clinical use. This study aimed to compare the cell viability of different adhesive systems (ASs) on human dental pulp stem cells (hDPSCs). METHODS: Three ASs that combining methacryloyloxydecyl dihydrogen phosphate (MDP) monomer with new hydrophilic amide monomers [Clearfil Universal Bond Quick(CUBQ), Kuraray Noritake], self-reinforcing 3D monomer [Bond Force II(BFII), Tokuyama)], and dual-cure property [Futurabond DC(FBDC), VOCO] were used. Three (n = 3) samples were prepared for each group. Dental pulp stem cells were isolated from ten patients' extracted third molar teeth. Samples were incubated in Dulbecco's modified Eagle's medium (DMEM) for 24 h (h), 72 h, and 7 days (d) to obtain extracts. For the control group, cells were cultured without DBA samples. Cell viability of ASs extracts was measured using a cell proliferation detection kit (WST-1, Roche). Statistical analysis was performed using two-way ANOVA and post-hoc (Duncan) tests (p < 0.05). RESULTS: At 24 and 72 h statistically significant differences were determined between control and BFII, control and FBDC groups (p < 0.05), while no differences between control and CUBQ groups (p > 0.05). On the 7th d, statistically significant differences were found between the control and experimental groups (p < 0.05), while no differences between experimental groups (p > 0.05). A statistically significant difference was detected for the BFII group over the three-time interval (p < 0.05). The lowest cell viability was observed for the FBDC group at 24 h, and the difference was statistically significant when compared with 72 h and 7th d (p < 0.05). CONCLUSION: All ASs showed different cell viability values at various exposure times. It should be taken into consideration that pH values, as well as the contents of ASs, have a significant effect on the cell viability.

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In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.

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Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors provide promising results for treating hormone receptor-positive breast cancer. However, the efficacy of CDK4/6 inhibitors remains uncertain in triple negative breast cancer (TNBC) patients with particularly carrying RB-deficient tumors. Poly-(ADP-ribose) polymerase (PARP) inhibitors offer a therapeutic strategy for the treatment of BRCA-mutated TNBC patients. However, the acquired drug resistance, changes in the cell cycle regulation, and DNA damage repair have demonstrated the necessity for developing new combination strategies. This preclinical study assessed a combinatory treatment of the CDK4/6 inhibitor abemaciclib with PARP inhibitors talazoparib (TAL) in HCC1937 BRCA-mutated RB-deficient TNBC cells and TAL-resistant HCC1937-R cells through WST-1 analysis, annexin V, cell cycle, acridine orange/propidium iodide staining, RT-PCR, and apoptosis array. Our findings revealed that abemaciclib and TAL combination synergistically suppressed the growth of TNBC cells and overcame TAL resistance through G0/G1 arrest and the activity of both intrinsic and extrinsic apoptotic pathways. These preliminary results suggest that the combination of abemaciclib and TAL could expand the use of these inhibitors in BRCA mutated and RB deficient TNBC patients and potentially overcomes PARP inhibitors resistance.

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OBJECTIVE: Natural compounds have gained considerable attention in recent years due to disadvantages and properties of current chemotherapy drugs in cancer therapy. In addition, the impact of these compounds is specific for each type and/or subtypes of cancer due to different treatment response. Rutaecarpine, an alkaloid obtained from Evodia Rutaecarpa Chinese herb, has anticancer activity by inhibiting topoisomerase and/or cyclo-oxygenase-2 levels. However, the effectiveness of rutaecarpine has not been well known in breast cancer in terms of subtype. Therefore, we investigated the potential therapeutic effects of rutaecarpine on two different subtypes of breast cancer cells. MATERIALS AND METHODS: The cytotoxic and apoptotic effects of rutaecarpine on MCF-7 and MDA-MB-231 cells were analyzed by WST-1, Annexin V, cell cycle, and acridine orange staining. RESULTS: WST-1 results indicated that rutaecarpine significantly inhibited the growth of both cancer cells for 48 h (P < 0.05). In addition, rutaecarpine treatment caused apoptotic cell death through chromatin condensation and nuclear blebbing and G0/G1 arrest in both breast cancer cells. However, the efficacy of rutaecarpine was more profound in MCF-7 cells than MDA-MB-231 cells. CONCLUSIONS: Consequently, rutaecarpine has a potential therapeutic effect on breast cancer. However, the effectiveness of rutaecarpine is dependent on the subtype of breast cancer.

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The cyclin-dependent kinases 4 and 6 have led to a significant improvement in the treatment of hormone-receptor-positive breast cancer. However, the therapeutic potential of abemaciclib in triple-negative breast cancer (TNBC) has not been definitively elucidated. Therefore, the objective of this study was to investigate abemaciclib mediated antiproliferative effects on MDA-MB-231 and MDA-MB-468 TNBC and MCF-10A cell line through annexin V, cell cycle, caspase-3, reverse transcription-polymerase chain reaction analysis, acridine orange, and DAPI staining, for the first time. In addition, the autophagy-related cell death was assessed by autophagy-LC3 assay and acidic vesicular organelles staining. Our findings demonstrated that abemaciclib treatment resulted in significant apoptotic cell death in TNBC cells via G0/G1 arrest, chromatin condensation, the upregulation of caspase-3 and Bax levels, and the downregulation of Bcl-2. However, the formation of a large number of cytoplasmic vacuoles was not associated with autophagy. Therefore, abemaciclib treatment could be an effective treatment for TNBC. However, further studies are needed to elucidate the molecular mechanism of abemaciclib-induced apoptotic as well as atypical cell death derived from lysosomes in TNBC.

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Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a vast number of infections and deaths that deeply affect the world. When the virus encounters the host cell, it binds to angiotensin-converting enzyme 2, then the S protein of the virus is broken down by the transmembrane protease serine 2 with the help of furin, allowing the virus to enter the cell. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. Therefore, the aim of this study is to investigate the relationship between circulating furin levels, disease severity, and inflammation in patients with SARS-CoV-2. A total of 52 SARS-CoV-2 patients and 36 healthy control participants were included in this study. SARS- CoV-2 patients were scored by the disease activity score. Serum furin, presepsin, and interleukin-6 (IL-6) levels were assessed using an enzyme-linked immunosorbent assay. The mean furin, presepsin, and IL-6 levels were significantly higher in the peripheral blood of SARS-CoV-2 compared to the controls (p < 0.001). There were close positive relationship between serum furin and IL-6, furin and presepsin, and furin and disease severity (r = 0.793, p < 0001; r = 0.521, p < 0.001; and r = 0,533, p < 0.001, respectively) in patients with SARS-CoV-2. These results suggest that furin may contribute to the exacerbation of SARS-CoV-2 infection and increased inflammation, and could be used as a predictor of disease severity in COVID-19 patients.

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Valproic acid (VPA) is a selective histone deacetylation (HDAC) inhibitor and exerts anti-cancer properties in different types of cancer. The epithelial-to-mesenchymal transition (EMT) mediating by different signaling cascade can be a potential target in aggressive human cancers. Therefore, we aimed to clarified the unravel relationship between AKT/GSK3ß/ß-catenin signalling pathway and VPA-induced EMT in triple negative breast cancer (TNBC). The cytotoxicity of VPA in MDA-MB-231 TNBC and MCF-10A control cells was evaluated. Alterations in the expression levels of Snail, E-cadherin, AKT, GSK3ß, ß-catenin were analyzed by RT-PCR. Additionally, Annexin V, cell cycle and wound healing assays were performed. Our results showed that VPA remarkably inhibited the growth of TNBC cell and triggered apoptotic cell death through G0/G1 arrest. Furthermore, VPA increased cell migration and activated the EMT process through significantly increasing Snail expression and in turn downregulation of E-cadherin and GKS3ß levels. However, the level of AKT and ß-catenin was reduced after treatment of VPA. Our data showed that VPA induced EMT process and cell migration in TNBC cells. However, AKT/GSK3ß/ß-catenin signaling pathway did not mediate EMT activation.

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