Background: This study focuses on the assessment of the antitumor potential of a combination of doxorubicin hydrochloride and silybin for the treatment of breast cancer. Method: Spectrophotometric analysis, Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC) were used to assess the physicochemical characteristics of drugs and their combination. The calibration curve of both drugs obeyed Beer-Lambert’s law. Further spectrophotometric analysis validated the quantification method by confirming the linearity of calibration curves. There were no notable changes in the distinct functional groups observed in the FTIR spectra, suggesting the absence of any chemical interactions. A shifted peak in the drug mixture indicated interaction without degradation, while DSC thermograms showed distinctive thermal transitions. Antiproliferative effects were assessed using cytotoxicity tests on MCF-7 breast cancer cell lines. Results: The silybin-to-doxorubicin mixture in a 2:1 ratio produced the strongest total growth inhibition (TGI = 40 µg/mL) in cytotoxicity tests, which showed modest antiproliferative action. Cellular changes produced by drug concentrations and various ratios were evaluated using morphological analysis, which revealed a concentration-dependent cytotoxic effect. Conclusion: A moderate anticancer activity of a combination of silybin and doxorubicin hydrochloride shows a future direction for continued study.
Introduction: Aerosols generated from heated hair products may pose respiratory risks, particularly for hairdressers due to occupational exposure. While some products show a higher potential for these effects, a clear link toward product and application methods remains unestablished. This study aimed to evaluate a cell-based in vitro inhalation approach to better understand the toxicological impacts, screen existing products, and facilitate the “safe-by-design” approach. Materials and Methods: Four test materials (TM1–TM4), including different products, application techniques, and subtle real-life effects observed after prolonged use, were evaluated, including two methods for TM2 (TM2 and TM2A). Aerosols were generated by product application to real hair strands and sampled by exposure of human lung cells (A549) under optimized conditions (P.R.I.T. ® ExpoCube ® ). Dose–response testing assessed cell viability, mitochondrial function, cellular stress, and interleukin-8 release. Results: Results indicated significant differences in aerosol release based on the test material and application method. Cell viability and mitochondrial function generally remained unaffected; however, there were notable differences in cellular stress and IL-8 release. A score was developed to facilitate a general assessment of the test materials, evaluating both aerosol release and biological effects. It showed promising correspondence between in vitro results and real-life observations. Conclusion: This in vitro –based alternative to animal testing has the potential to provide a strategy to investigate the respiratory effects of cosmetic product aerosols. It might offer a framework for product screening and, as experience with additional test compounds accumulates, could help facilitate the development and acceptance of alternative methods in safe-by-design and safety assessment strategies.
Background: Lanternfish ( Benthosema pterotum ), an abundant deep-sea resource with a unique protein profile, holds significant potential as a source of bioactive peptides. This study was designed to investigate and characterize the immunomodulatory properties of protein hydrolysates derived from lanternfish, prepared using Alcalase (BPHA) and Flavourzyme (BPHF), on the RAW 264.7 murine macrophage cell line. Methods: Lanternfish protein was enzymatically hydrolyzed, and the resulting peptides were fractionated to isolate those with a molecular weight below 3 kDa. RAW 264.7 macrophages were treated with B. pterotum hydrolyzed using Alcalase enzymes (BPHA) and B. pterotum hydrolyzed using Flavourzyme enzymes (BPHF) at concentrations ranging from 100 to 500 µg/mL. The cytotoxicity of the hydrolysates was evaluated using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. To assess immunomodulatory activity, the gene expression levels of pro-inflammatory mediators, including Inducible nitric oxide synthase (iNOS), Tumor necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), and Interleukin-6 (IL-6), were quantified by quantitative real-time PCR in both resting macrophages and in cells stimulated with lipopolysaccharide (LPS) to induce an inflammatory state. Results: The MTT assay confirmed that both BPHA and BPHF were noncytotoxic across all tested concentrations. In resting (nonstimulated) macrophages, both hydrolysates significantly upregulated the expression of iNOS, TNF-α, IL-1β, and IL-6 in a dose-dependent manner, demonstrating a clear immunostimulatory effect. In contrast, when macrophages were exposed to an inflammatory challenge with LPS, the hydrolysates exhibited potent anti-inflammatory activity by significantly downregulating the expression of these same pro-inflammatory genes. Conclusions: Protein hydrolysates derived from lanternfish display a notable dual immunomodulatory capability. They function as immunostimulants in a normal physiological state and act as anti-inflammatory agents during an inflammatory response. These findings underscore the potential of lanternfish hydrolysates as a valuable functional ingredient for applications in nutraceuticals and functional foods aimed at balancing and modulating the immune system.
Introduction: Systematic reviews (SR) collect and integrate data corpuses into consistent, computable, and comparable datasets. The adverse outcome pathway (AOP) framework facilitates the linking of data describing molecular initiating events, through one or more key events (KEs), to adverse biological outcomes. To explore the potential application of data from SRs to the AOP framework, a case study was conducted to explore mapping SR to existing AOP KEs. Methods: SR data consisted of in vitro and in vivo androgen receptor (AR) toxicity information from nonmammalian vertebrate species collected as described by the authors, limiting data comparability. Data were standardized and mapped to terms for Level of Biological Organization, Object, Process, and Action using existing KEs in the AOP-Wiki as a source for endpoint terms. Results: In vitro SR data had 131 of 264 records that mapped to AR transactivation, while in vivo data had 226 of 1891 records directly mappable to 31 different KEs (e.g., increased vitellogenin messenger RNA). When no appropriate terms existed in the AOP-Wiki, standardized terms were proposed for future use. For unstructured data, mapping and standardization required additional interpretation. Conclusions: This study highlights the difficulties in aligning heterogeneously extracted SR data with a structured framework. This work highlights the need for language standardization and the adoption of clear data collection guidance prior to, and during, the SR to enhance data comparability and computability. The adoption of such efforts can advance the ability of resulting data to be reused and applied to frameworks such as AOPs. Lessons learned in this case study are applicable to similar efforts examining the use of automation in data extraction and evaluation.
