Avocado and soybean unsaponifiables (ASU) constitute vegetable extracts made from fruits and seeds of avocado and soybean oil. Characterized by its potent anti-inflammatory effects, this ASU mixture is recommended to act as an adjuvant treatment for osteoarthritic pain and slow-acting symptomatic treatment of hip and knee osteoarthritis; autoimmune diseases; diffuse scleroderma and scleroderma-like states (e.g., morphea, sclerodactyly, scleroderma in bands). Besides, it was reported that it can improve the mood and quality of life of postmenopausal women in reducing menopause-related symptoms. This article aims to summarize the studies on biological effects of the avocado–soybean unsaponifiable, its chemical composition, pharmacotherapy as well as applications in autoimmune, osteoarticular and menopausal disorders. Finally, we will also discuss on its safety, toxicological and regulatory practices.

Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. Methods: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. Results: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. Conclusions: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.

High-dose of vitamin C (L-ascorbic acid, ascorbate) exhibits anti-tumoral effects, primarily mediated by pro-oxidant mechanisms. This cytotoxic effect is thought to affect the reciprocal crosstalk between redox balance and cell metabolism in different cancer types. Vitamin C also inhibits the growth of papillary thyroid carcinoma (PTC) cells, although the metabolic and redox effects remain to be fully understood. To shed light on these aspects, PTC-derived cell lines harboring the most common genetic alterations characterizing this tumor were used. Cell viability, apoptosis, and the metabolome were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, and UHPLC/MS. Changes were observed in redox homeostasis, with increased reactive oxygen species (ROS) level and perturbation in antioxidants and electron carriers, leading to cell death by both apoptosis and necrosis. The oxidative stress contributed to the metabolic alterations in both glycolysis and TCA cycle. Our results confirm the pro-oxidant effect of vitamin C as relevant in triggering the cytotoxicity in PTC cells and suggest that inhibition of glycolysis and alteration of TCA cycle via NAD⁺ depletion can play an important role in this mechanism of PTC cancer cell death.

Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor.

Introduction Severe psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders. Methods and analysis A cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed. Ethics and dissemination The study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.