Chrysin Enhances Anti-cancer Activity of Jurkat T Cell and NK-92 Cells Against Human Breast Cancer Cell Lines.

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.

Olive Leaf Extract Downregulates the Protein Expression of Key SARS-CoV-2 Entry Enzyme ACE-2, TMPRSS2, and Furin.

Severe acute respiratory syndrome coronavirus 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 (ACEII), 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 COVID-19, yet its mechanism remains understudied. In this study, we aimed to investigate the effects of OLE on ACEII, 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.  ACEII, TMPRSS2, and Furin expressions were analyzed by the Western Blotting method. ACEII, TMPRSS2, and Furin protein expression levels were significantly lower in dose dependent manner and the highest inhibition was seen at 100 ug/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.

Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study.

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.

Cognition and BDNF levels in prediabetes and diabetes: A mediation analysis of a cross-sectional study.

Aim: Clinical and epidemiological studies suggest links between dementias and Type 2 diabetes (T2DM). The underlying mechanisms of diabetes-related cognitive impairment are largely unknown. This study aims to investigate the role of BDNF in cognitive impairment in prediabetes and T2DM. Methods: The study included 68 patients with prediabetes (preDM), 96 patients with T2DM, and 65 healthy controls. The cognitive function of the patients was evaluated with the Montreal Cognitive Assessment (MoCA) test and serum BDNF levels were measured by Elisa. The MoCA scores and BDNF levels were compared between diabetes groups after adjusting for age, gender, and education using ANCOVA. The role of BDNF in the diabetes-related cognitive impairment was investigated through mediation analysis. Results: Patients with T2DM had significantly lower cognitive performance, particularly in memory. Diabetes was found to be a predictor of both cognitive impairment and BDNF levels. A significant increase in serum BDNF levels was observed in patients with T2DM. However, the mediator role of BDNF in the pathology of cognitive impairment in diabetes was not determined. Conclusion: Cognitive impairment is prevalent in patients with T2DM and should be included in routine screening for complications. The results of the mediation analysis suggest that although BDNF is a biomarker affected by T2DM and cognition, it does not play a mediator role between cognitive impairment and diabetes.

Circulating furin, IL-6, and presepsin levels and disease severity in SARS-CoV-2-infected patients.

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.