Search

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with an increasing incidence rate and limited therapeutic options. Biological sex has an impact on many aspects of PDAC development and response to therapy, yet it is highly unappreciated in both basic and translational research, and worryingly in PDAC clinical trials. In this review, we summarize how biological sex influences PDAC incidence and mortality, genetic and epigenetic landscapes, anti-tumor immunity, responses to hormones, cachexia, and the efficacy of therapy. We highlight the importance of sex as a variable and discuss how to implement it into preclinical and clinical research. These considerations should be of use to researchers aiming at improving understanding of PDAC biology and developing precision medicine therapeutic strategies.

Different vanillin-based aldehydes were used to synthesize novel tetrahydropyrimidines (THPMs) via conventional Biginelli reaction. The THPMs were tested against human normal cells (MRC-5) and cancer cell lines (HeLa, K562, and MDA-MB-231). With IC 50 values of 10.65, 10.70, and 12.76 µM, compounds 4g, 4h, and 4i exerted the strongest cytotoxic effects against K562 cells. The best activity was achieved for 4g on MDA-MB-231 cells (IC 50  = 9.20 ± 0.14 µM). The effects of compounds 4g, 4h, and 4i on the cell-cycle phase distribution of K562 cells were analyzed. Principal component analysis was carried out for the chemometrics analysis to comprehend the relationship between the anticancer activity of the THPMs, pharmacokinetic properties, and partition coefficients, as well as the relationship between the chromatographic behavior and retention parameters. The highest retention rates are found for molecules 4g, 4h, and 4i, which have the longest carbon chains, indicating that the length of the alkyl chain positively affects the molecule's anticancer activity but only if the number of carbon atoms is not higher than seven. Additionally, molecular docking analysis was performed to determine the preferred binding modes of the investigated ligands (4g, 4h, and 4i) with a DNA dodecamer and bovine serum albumin., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Nischarin was reported to be a tumor suppressor that plays a critical role in breast cancer initiation and progression, and a positive prognostic marker in breast, ovarian and lung cancers. Our group has found that nischarin had positive prognostic value in female melanoma patients, but negative in males. This opened up a question whether nischarin has tumor type-specific and sex-dependent roles in cancer progression. In this study, we systematically examined in the public databases the prognostic value of nischarin in solid tumors, regulation of its expression and associated signaling pathways. We also tested the effects of a nischarin agonist rilmenidine on cancer cell viability in vitro. Nischarin expression was decreased in tumors compared to the respective healthy tissues, most commonly due to the deletions of the nischarin gene and promoter methylation. Unlike in healthy tissues where it was located in the cytoplasm and at the membrane, in tumor tissues nischarin could also be observed in the nuclei, implying that nuclear translocation may also account for its cancer-specific role. Surprisingly, in several cancer types high nischarin expression was a negative prognostic marker. Gene set enrichment analysis showed that in tumors in which high nischarin expression was a negative prognostic marker, signaling pathways that regulate stemness were enriched. In concordance with the findings that nischarin expression was negatively associated with pathways that control cancer growth and progression, nischarin agonist rilmenidine decreased the viability of cancer cells in vitro. Taken together, our study lays a ground for functional studies of nischarin in a context-dependent manner and, given that nischarin has several clinically approved agonists, provides rationale for their repurposing, at least in tumors in which nischarin is predicted to be a positive prognostic marker., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ostojić et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We investigated the chemical and medicinal properties of methanolic and acetonic extracts of Armillaria ostoyae and the presence of heavy metals in its dry basidiocarps. The chemical content of extracts was analyzed with the HPLC-DAD-MS/MS method. According to our results, the most abundant mineral was potassium; the most abundant organic acid was malic acid; the most abundant carbohydrate was fructose, and the most abundant polyphenol was chlorogenic acid. The antimicrobial potential was evaluated using the microdilution assay, and the results ranged from 0.62 to 20 mg/mL. Antioxidant potential was studied by DPPH [half-maximal inhibitory concentration (IC50) of the methanolic extract was 619.67 μg/mL and of the acetonic extract was 533.65 μg/mL] and reducing power assays (the results ranged from 0.025 to 0.078 μg/mL). Total phenolic content was presented as gallic acid equivalent (methanolic extract, 6.12 mg GAE/g; acetonic extract, 3.99 mg GAE/g). The antidiabetic potential was explored by applying the α-amylase (the results ranged from 39.62 to 44.33%) and α-glucosidase assays (the results were in the range of 0.27-2.51%). The neuroprotective activity was asserted by the acetylcholinesterase inhibition assay (the results were in the range of 3.06-6.09%). The cytotoxic potential was investigated using the microtetrazolium assay, and the IC50 values ranged from 221.96 to > 400 μg/mL. Heavy metal content of the dry basidiocarps was evaluated using the AAS method and iron was the most abundant metal. A. ostoyae is a conditionally edible mushroom, which was not studied thoroughly before, thus this research will provide valuable knowledge about this species.

Honey mushroom, Armillaria mellea, is an edible and medicinal lignicolous basidiomycete. In this study, we investigated the chemical composition and bioactive properties of its methanolic and acetonic extracts. The chemical characterization of extracts was done with the HPLC-DAD-MS/MS method. The results showed that potassium was the most abundant mineral; chlorogenic acid was the most abundant polyphenol; malic acid was the most abundant organic acid; and among carbohydrates, the most abundant were sorbitol, glucose, fructose, and saccharose. Antioxidative activity was assessed by DPPH (IC50 of the methanolic extract was 608.32 μg/mL and of the acetonic extract 595.71 μg/mL) and reducing power assays (the results ranged between 0.034 and 0.102 μg/mL). Total phenolic content was determined as gallic acid equivalent (methanolic extract: 4.74 mg GAE/g; acetonic extract: 5.68 mg GAE/g). The microdilution assay was used to evaluate the antimicrobial activity of the extracts, and the results ranged from 1.25 to 20 mg/mL. The antidiabetic effect of the extracts was tested by the α-amylase (the results ranged from 34.90% to 41.98%) and α-glucosidase assays (the results were in the range of 0.55-2.79%). The neuroprotective activity was explored by the acetylcholinesterase inhibition assay (the results were in the range of 1.94-7.76%). The microtetrazolium assay was used to investigate the cytotoxic activity of the extracts (the IC50 values ranged from 212.06 to > 400 μg/mL). Although some results suggest that some activities of the extracts are relatively moderate, the honey mushroom can still be considered an excellent source of food and bioactive compounds with medicinal value.

The aim of the study was to investigate the biological activity and chemical composition of Satureja kitaibelii Wierzb. ex Heuff. LC-PDA/MS analyses for the aqueous extracts (A1-stem, leaves and flowers, A2-leaves and flowers) and ethyl-acetate extracts (E1-stem, leaves and flowers, E2-leaves and flowers) obtained by ultrasound-assisted extraction enabled the identification of thirty-four compounds. Quantitative analysis revealed that the aqueous extract obtained from leaves and flowers was the richest in total phenolic acids (65.36 mg/g) and flavonoids (21.17 mg/g). The total polyphenol content was the highest in the aqueous extract obtained from leaves and flowers (274 ± 2.4 mg Gallic Acid equivalents/g). The best antioxidant activity was observed for the same extract using the DPPH (SC50 20 ± 10 µg/mL), ABTS (2.834 ± 0.02 mg Ascorbic Acid/g), FRAP (1.922 ± 0.03 mmol Fe 2+ /mg), and total reducing power tests (16.4 ± 1.0 mg Ascorbic Acid/g). Both ethyl acetate extracts were the most active against strains of Bacillus cereus and Micrococcus flavus (MIC 1.70-1.99 mg/mL and 1.99-3.41 mg/mL, respectively). They were more efficient against Aspergillus ochraceus (MFC 0.86 mg/mL) and towards HeLa cell lines. All the obtained results implied the good potential of the investigated extracts to be used as effective preservatives and functional ingredients in food products and dietary supplements., (© 2022. The Author(s).)

In this study, we tested the methanolic and acetonic extracts of the edible species Meripilus giganteus for their medicinal properties. Here, we present the chemical composition, as well as the antimicrobial, antioxidant, antidiabetic, neuroprotective, and cytotoxic activities, of the aforementioned extracts. The chemical composition of the extracts was analyzed with high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry. The studied extracts contained 13 minerals, 23 polyphenols, 11 organic acids, and 22 carbohydrates. Antimicrobial activity was tested by applying the microdilution assay, and the results ranged from 0.002 to 20 mg/mL. Antioxidant activity was studied with the DPPH assay (half-maximal inhibitory concentration = 673.42 and 712.31 μg/mL for the methanolic and acetonic extracts, respectively) and the reducing power assay (range, 0.042-0.099 μg/mL). Total phenolic content was determined as 4.86 mg gallic acid equivalents (GAE)/g for the methanolic extract and 5.06 mg GAE/g for the acetonic extract. The antidiabetic effect of the extracts was explored with the α-amylase and α-glucosidase assays, and the results ranged from 30.66% to 38.67% and from 11.06% to 17.08%, respectively. The neuroprotective properties of M. giganteus extracts were studied using the acetylcholinesterase inhibition assay, with results ranging from 4.54% to 9.31%. Cytotoxic activity was tested by applying the microtetrazolium assay, with results ranging from 196.24 to 322.83 μg/mL. Although some assays proved relatively limited activities of the M. giganteus extracts studied, they can still be considered as natural sources of bioactive compounds without side effects.