Maintenance of intestinal epithelial barrier integrity by a combination of probiotics, herbal extract, and vitamins.

BACKGROUND: Irritable bowel syndrome (IBS) and Inflammatory bowel disease (IBD) are pathological conditions that severely hamper the quality of life of patients. Especially in pediatric and adolescent patients, the use of Complementary and alternative medicine is an appealing approach as an adjuvant for the management of symptoms, limiting the detrimental effect of the conventional therapy. In this work, we tested the effect of Enterokind Junior (EntJ), a mix of two probiotic strains Lactobacillus reuteri DSM 25175 and Lactobacillus acidophilus DSM 24936, Matricaria Chamomilla, and vitamins, in in vitro model of intestinal inflammation. Caco-2 cells were subjected to LPS treatment or THP-1 cells stimulated with LPS treatment, as paradigms of inflammatory conditions. METHODS: The effect of the probiotic formulation was evaluated by measuring Caco-2 monolayer's Transepithelial Electrical resistance (TEER) and paracellular permeability alterations, tight junction proteins expression and localization by confocal microscopy, and release of pro-inflammatory cytokines (TNF-α and IL-8) by ELISA assay. RESULTS: Results demonstrated that upon impairment of intestinal parameters induced by inflammatory stimuli, the combination of probiotic was able to prevent TEER decrease and paracellular permeability alterations and to maintain the tight junction expression and localization. Moreover, the release of proinflammatory cytokines induced by inflammation was reduced by EntJ treatment. CONCLUSIONS: This work, in line with previous observations, supports a protective role of Lactobacillus reuteri DSM 25175, Lactobacillus acidophilus DSM 24936 and the other components in the maintenance of a healthy gut, holding up the use of this combination as an adjuvant for irritable bowel syndrome-related symptoms management.

Contribution of Mitochondrial Activity to Doxorubicin-Resistance in Osteosarcoma Cells.

Osteosarcoma is considered the most common bone tumor affecting children and young adults. The standard of care is chemotherapy; however, the onset of drug resistance still jeopardizes osteosarcoma patients, thus making it necessary to conduct a thorough investigation of the possible mechanisms behind this phenomenon. In the last decades, metabolic rewiring of cancer cells has been proposed as a cause of chemotherapy resistance. Our aim was to compare the mitochondrial phenotype of sensitive osteosarcoma cells (HOS and MG-63) versus their clones when continuously exposed to doxorubicin (resistant cells) and identify alterations exploitable for pharmacological approaches to overcome chemotherapy resistance. Compared with sensitive cells, doxorubicin-resistant clones showed sustained viability with less oxygen-dependent metabolisms, and significantly reduced mitochondrial membrane potential, mitochondrial mass, and ROS production. In addition, we found reduced expression of TFAM gene generally associated with mitochondrial biogenesis. Finally, combined treatment of resistant osteosarcoma cells with doxorubicin and quercetin, a known inducer of mitochondrial biogenesis, re-sensitizes the doxorubicin effect in resistant cells. Despite further investigations being needed, these results pave the way for the use of mitochondrial inducers as a promising strategy to re-sensitize doxorubicin cytotoxicity in patients who do not respond to therapy or reduce doxorubicin side effects.

Clinical Evidence of Interaction between Nutraceutical Supplementation and Platinum-based Chemotherapy.

Platinum agents, which include cisplatin, oxaliplatin and carboplatin, are chemotherapeutic drugs that represent the first-line treatment for different types of solid tumors, such as ovarian, head and neck, testicular, and bladder cancers. Their beneficial effect is limited by the onset of drug resistance and severe toxicities, involving mainly ototoxicity, neurotoxicity and nephrotoxicity. Recent studies highlight the supplementation of herbal products, vitamins and minerals with antioxidant properties to prevent and protect from side effects. In particular, the introduction of nutraceuticals associated with chemotherapy has improved the patients' quality of life. However, if from one side, complementary and alternative medicine ameliorates chemotherapeutics-induced toxicities, from the other side, it is important to take into consideration the possible interference with drug metabolism. This review aims to consider the current literature focusing on clinical trials that report an association between nutraceutical supplementation and platinum- based chemotherapy to prevent toxicities, highlighting both beneficial and side effects.

Evaluation of Concomitant Use of Anticancer Drugs and Herbal Products: From Interactions to Synergic Activity.

CAM is used by about 40% of cancer patients in Western Countries, with peaks of 80% for breast cancer patients. Cancer patients use CAM to boost immune function, to control cancer symptoms and treatment-related side effects, and to improve health-related quality of life (HR-QoL) and survival. Unfortunately, self-prescription of natural remedies in cancer patients can lead to unexpected toxicities and can reduce the effectiveness of cancer therapy. Although CAM usually refers to all the "natural or organic" products/methods that are generally considered less toxic, there are concerns about drug interactions, especially in patients participating in clinical trials with experimental agents. Despite the claims of the promising and potential benefits made by prescribers, many CAMs lack clear scientific evidence of their safety and efficacy. Given the widespread use of CAM-both clearly declared and overt-in this review, we focused on the most important known data on the risk of interactions between biologics and oncology drugs with the goal of opening up CAM in accordance with the meaning of integrative medicine.

Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress.

The relevance and incidence of intestinal bowel diseases (IBD) have been increasing over the last 50 years and the current therapies are characterized by severe side effects, making essential the development of new strategies that combine efficacy and safety in the management of human IBD. Herbal products are highly considered in research aimed at discovering new approaches for IBD therapy and, among others, Cannabis sativa L. has been traditionally used for centuries as an analgesic and anti-inflammatory remedy also in different gastrointestinal disorders. This study aims to investigate the effects of different C. sativa isolated compounds in an in vitro model of intestinal epithelium. The ability of treatments to modulate markers of intestinal dysfunctions was tested on Caco-2 intestinal cell monolayers. Our results, obtained by evaluation of ROS production, TEER and paracellular permeability measurements and tight junctions evaluation show Cannabidiol as the most promising compound against intestinal inflammatory condition. Cannabidiol is able to inhibit ROS production and restore epithelial permeability during inflammatory and oxidative stress conditions, suggesting its possible application as adjuvant in IBD management.