The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells.

A growing body of literature underlines the fundamental role of gut microbiota in the occurrence, treatment, and prognosis of cancer. In particular, the activity of gut microbial metabolites (also known as postbiotics) against different cancer types has been recently reported in several studies. However, their in-depth molecular mechanisms of action and potential interactions with standard chemotherapeutic drugs remain to be fully understood. This research investigates the antiproliferative activities of postbiotics- short-chain fatty acid (SCFA) salts, specifically magnesium acetate (MgA), sodium propionate (NaP), and sodium butyrate (NaB), against the AGS gastric adenocarcinoma cells. Furthermore, the potential synergistic interactions between the most active SCFA salt-NaB and the standard drug dexamethasone (Dex) were explored using the combination index model. The molecular mechanisms of the synergy were investigated using reactive oxygen species (ROS), flow cytometry and biochemometric and liquid chromatography-mass spectrometry (LC-MS)-driven proteomics analyses. NaB exhibited the most significant inhibitory effect (p < 0.05) among the tested SCFA salts against the AGS gastric cancer cells. Additionally, Dex and NaB exhibited strong synergy at a 2:8 ratio (40 µg/mL Dex + 2,400 µg/mL NaB) with significantly greater inhibitory activity (p < 0.05) compared to the mono treatments against the AGS gastric cancer cells. MgA and NaP reduced ROS production, while NaB exhibited pro-oxidative properties. Dex displayed antioxidative effects, and the combination of Dex and NaB (2,8) demonstrated a unique pattern, potentially counteracting the pro-oxidative effects of NaB, highlighting an interaction. Dex and NaB individually and in combination (Dex:NaB 40:2400 µg/mL) induced significant changes in cell populations, suggesting a shift toward apoptosis (p < 0.0001). Analysis of dysregulated proteins in the AGS cells treated with the synergistic combination revealed notable downregulation of the oncogene TNS4, suggesting a potential mechanism for the observed antiproliferative effects. These findings propose the potential implementation of NaB as an adjuvant therapy with Dex. Further investigations into additional combination therapies, in-depth studies of the molecular mechanisms, and in vivo research will provide deeper insights into the use of these postbiotics in cancer, particularly in gastric malignancies.

A Comprehensive Review on the Techniques for Extraction of Bioactive Compounds from Medicinal Cannabis.

Cannabis is well-known for its numerous therapeutic activities, as demonstrated in pre-clinical and clinical studies primarily due to its bioactive compounds. The Cannabis industry is rapidly growing; therefore, product development and extraction methods have become crucial aspects of Cannabis research. The evaluation of the current extraction methods implemented in the Cannabis industry and scientific literature to produce consistent, reliable, and potent medicinal Cannabis extracts is prudent. Furthermore, these processes must be subjected to higher levels of scientific stringency, as Cannabis has been increasingly used for various ailments, and the Cannabis industry is receiving acceptance in different countries. We comprehensively analysed the current literature and drew a critical summary of the extraction methods implemented thus far to recover bioactive compounds from medicinal Cannabis. Moreover, this review outlines the major bioactive compounds in Cannabis, discusses critical factors affecting extraction yields, and proposes future considerations for the effective extraction of bioactive compounds from Cannabis. Overall, research on medicinal marijuana is limited, with most reports on the industrial hemp variety of Cannabis or pure isolates. We also propose the development of sustainable Cannabis extraction methods through the implementation of mathematical prediction models in future studies.

Portulaca oleracea seeds' extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats.

BACKGROUND: Acrylamide (ACR) is a widespread industrial and food contaminant that garnered considerable attention for its carcinogenic, neurotoxic, and reproductive toxic effects. The antioxidant effects of Portulaca oleracea seeds extract (POS) and its fertility-enhancing effects were inspiring to evaluate the protective potential and pinpoint the mechanisms and molecular targets of the UPLC-MS fingerprinted POS extract on ACR-induced testicular toxicity in rats. METHODS: Male Wistar rats were divided into 6 equal groups of negative control, ACR model (10 mg/kg b.wt.), POS at doses of (200 and 400 mg/kg b.wt.) and POS-treated ACR groups. All treatments were given by oral dosing every day for 60 days. RESULTS: Administration of POS extract reversed the ACR-induced epididymides weight loss with improved semen quality and count, ameliorated the ACR-decreased testicular lesion scoring, testicular oxidative stress, testicular degeneration, Leydig cell apoptosis and the dysregulated PCNA and Caspase-3 expression in a dose-dependent manner. It upregulated the declined level of serum testosterone and the expression of steroidogenic genes such as CYP11A1 and 17ß3-HSD with an obvious histologic improvement of the testes with re-establishment of the normal spermatogenic series, Sertoli and Leydig cells. CONCLUSIONS: The supplementation with POS extract may provide a potential protective effect for ACR-induced testicular dysfunction which is mediated by its antioxidant, antiapoptotic and steroidogenic modulatory effects.

Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review.

Fatal unintentional poisoning is widespread upon human exposure to toxic agents such as pesticides, heavy metals, environmental pollutants, bacterial and fungal toxins or even some medications and cosmetic products. In this regards, the application of the natural dietary agents as antidotes has engrossed a substantial attention. One of the ancient known traditional medicines and spices with an arsenal of metabolites of several reported health benefits is ginger. This extended literature review serves to demonstrate the protective effects and mechanisms of ginger and its phytochemicals against natural, chemical and radiation-induced toxicities. Collected data obtained from the in-vivo and in-vitro experimental studies in this overview detail the designation of the protective effects to ginger's antioxidant, anti-inflammatory, and anti-apoptotic properties. Ginger's armoury of phytochemicals exerted its protective function via different mechanisms and cell signalling pathways, including Nrf2/ARE, MAPK, NF-ƙB, Wnt/ß-catenin, TGF-ß1/Smad3, and ERK/CREB. The outcomes of this review could encourage further clinical trials of ginger applications in radiotherapy and chemotherapy regime for cancer treatments or its implementation to counteract the chemical toxicity induced by industrial pollutants, alcohol, smoking or administered drugs.