Background: Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs.Methods: CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO₂NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo.Results: It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway.Conclusions: Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.

Background and Aim: The reproductive performance of dairy cows is of a high economic value to maintain efficient and sustainable productivity. Postpartum anestrus is one of the major infertility problems that cause limitation of dairy cow reproductive performance and productivity. The previous studies have reported using a polyherbal formulation for different purposes, including reproductive performance. This study was conducted to examine the efficacy of polyherbal formulation administration on the reproductive performance of cows and to establish the oral administration of polyherbal formulations as a safe, effective, and economic treatment for dairy cows with postpartum anestrus due to nutritional disorders, negative energy balance, high milk production, and/or heat stress. Materials and Methods: A total of 14 dairy cows with postpartum anestrus were randomly divided into two groups, which were subjected to oral administration of distilled water that served as the control (Ctrl; n=5) or polyherbal treatment (polyherbal treated; n=9) for two shots of treatment (each for 3 successive days) with a 10-day interval. Blood sampling and ultrasonography were performed before treatment and after the first and second shots of treatment. Progesterone (P4) assay was also performed. Results: The estrus induction rate was 66.7% after the first shot of treatment in the polyherbal-treated group, which increased significantly to 88.9% after the second shot of treatment, compared with the Ctrl group (20%). The estrus response was confirmed by ultrasonography and P4 hormone assay, wherein the polyherbal treatment significantly increased the P4 concentration in the polyherbal-treated group after the second shot of treatment compared to that before treatment and in the Ctrl group at all time points. On pregnancy diagnosis, the treated dairy cows showed conception rates of 66.7% and 20.0% in the polyherbal-treated and Ctrl groups, respectively. In contrast, the concentration of malondialdehyde, an oxidative stress marker, and the total antioxidant capacity remained unchanged between both groups before and after treatment. Conclusion: The polyherbal formulation containing tubers of C. rotundus, M. pterygosperma, rhizome of Z. officinale, and A. cepa has the potential to induce estrus response and luteal activity in dairy cows and is a possible treatment for ovarian inactivity in dairy farms.

Background and Aim: Contamination of processed meat by chemicals, either by their addition for enhancing the product quality or as a result of contamination during the manufacturing process, is a crucial food safety issue that threatens human health. This research was conducted to estimate the contamination levels by harmful chemical contaminants, including nitrite, lead, cadmium, and phosphate in the Egyptian processed meats. Materials and Methods: In our study, 20 samples of each frozen sausage, pastirma, and luncheon were collected and prepared for the detection of chemical contaminants, including nitrite, lead, cadmium, phosphorus, and phosphate. Results: Pastirma showed the highest nitrite and lead levels (163.65±22.633 and 0.805±0.173 ppm) and the lowest levels in phosphorus and phosphate (2.294±0.19 and 9.084±0.755 g/kg) whereas sausage recorded the highest concentration of cadmium (0.073±0.008 ppm), phosphorus and phosphate (13.268±1.129 and 52.54±4.472 g/kg, respectively). However, the estimation of nitrite, lead, cadmium, and phosphate levels in sausage, pastirma, and luncheon was considered within the acceptable daily intake. Moreover, target hazard quotient and hazard index of all analyzed chemical contaminants in different processed meat were below one, indicating the safety of these meat products without any danger to human health. The probability of developing cancer was measured using carcinogenic risk (CR) where pastirma and luncheon recorded satisfactory levels away from developing cancer because of lead (4.59E-04 and 1.87E-04, respectively) and cadmium (7.60E-04 and 3.80E-04, respectively) contamination. Surprisingly, the cadmium level in sausage samples represented a relevant CR for consumers (1.90E-03). Conclusion: Periodical surveillance of meat chemical contaminants is a vital issue for human health maintenance.

Pancreatic cancer (PC) is difficult to treat because of its radio-resistance and metastases. Radiotherapy modifies the tumor microenvironment (TME) and affects PC progression. Exosomes are produced in response to radiation, but their nature and mechanisms of action are unclear. We investigated how exosomes from irradiated PC cells (IR-Exo) regulated metastasis both in vitro and in vivo. We isolated exosomes from three human PC cell lines: MIAPaCa-2, BxPC3, and Panc-1. The uptake of IR-Exo by irradiated PC cells decreased the migration and invasion capacities of all PC cell lines in vitro. Additionally, IR-Exos prevented liver metastasis induced by MIAPaCa-2 cells in vivo We detected 2,565 miRNAs in exosomes in a microarray. Seventeen of these genes were differentially expressed between the exosomes isolated from non-irradiated cells (0 Gy-Cells) and IR-Exo. miR-3160-5p was the most upregulated miRNA in IR-Exo. Transfection of miR-3160-5p into PC cells decreased cell migration and invasion. Furthermore, expression of Repulsive Guidance Molecule BMP Co-Receptor B (RGMB), a target molecule of miR-3160-5p, was significantly decreased by the addition of miR-3160-5p. Knockdown of RGMB expression significantly prevented cell migration and invasion. Thus, irradiation increases exosomal miR-3160-5p expression and inhibits cell migration and invasion via a decrease in RGMB expression. This points toward new treatment targets or biomarkers.

Gastrointestinal toxicity is frequently observed secondary to accidental or therapeutic radiation exposure. However, the variation in the intestinal metabolites after abdominal radiation exposure remains ambiguous. In the present study, C57BL/6 mice were exposed to 0, 2, and 20 Gy irradiation dose. The Head and chest of each mouse were covered with a lead shield before x-ray irradiation. 24 h post-irradiation treatment, intestinal tissue of each mouse was excised and prepared for metabolites measurement using gas chromatography-mass spectrometry (GC-MS). Our comprehensive analysis of metabolites in the intestinal tissues detected 44 metabolites after irradiation, including amino acids, carbohydrates, organic acids, and sugars. Amino acid levels in the intestinal tissue gradually rose, dependent on the radiation dose, perhaps as an indication of oxidative stress. Our findings raise the possibility that amino acid metabolism may be a potential target for the development of treatments to alleviate or mitigate the harmful effects of oxidative stress-related gastrointestinal toxicity due to radiation exposure.

Background: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC). Methods: We fed the APC^min/+ mice, which are highly susceptible to spontaneous intestinal adenoma formation, diets supplemented with or without PACs for 7 weeks and assessed adverse effects, the number and size of intestinal polyps, and the expression of pro- and anti-proliferative proteins in the intestine. The mouse gut microbiome composition was analyzed, and the concentrations of gut short-chain fatty acids (SCFAs) were quantified. We also compared CRC incidence in Tamba in Japan, where black soybean is consumed frequently, with that in the rest of Japan. Results: The number and size of intestinal polyps notably decreased in the PAC-fed mice. Compared with control mice, the PAC-fed mice showed lower expression of proliferation markers proliferating cell nuclear antigen and β catenin and a higher expression of the anti-inflammatory protein oligomeric mucus gel-forming. PAC supplementation increased the prevalence and concentrations of beneficial gut microbes and SCFAs, respectively. Conclusions: Diet supplemented with black soybean-derived PACs could prevent CRC development in mice through gut microbiome remodeling. Regions consuming black soybeans have low CRC incidence. Notably, the incidence of CRC, breast cancer, and liver cancer was significantly lower in Tamba than in the rest of Hyogo Prefecture or Japan. Future studies should delineate the mechanisms underlying the CRC-protective effects of PACs. Nevertheless, our results demonstrate the potential of including PACs in dietary recommendations for cancer prevention.