Gut microbiota is essential for the development of the intestinal immune system, protecting the host against pathogens and harmful inflammatory processes. Germ‐free animals have smaller Peyer's patches, fewer immune cells and impaired immunoglobulin A (IgA) secretion, fewer intraepithelial lymphocytes, as well as compromised production of antimicrobial peptides. Mucositis (mucosal barrier injury) is a major oncological problem caused by chemotherapeutic agents. Intestinal mucositis translates into a broad spectra of clinical symptoms (diarrhea, vomiting) and can be worsened by neutropenia and antibiotics. Since IECs do not regulate intestinal homeostasis by themselves, but require symbiotic coordination with commensal bacteria and local gut leukocytic cells, the role of intestinal microbiota in the development and severity of mucositis induced by chemotherapeutic products became an issue. The present chapter reviews the interplay between microbiota, immune system, and anticancer therapy. The published researches in this field showed that microbiota has immunomodulatory effect on the anticancer immune response, both in the presence and in the absence of chemotherapy. Animal and human studies evoked that the anticancer response depends on microbiota variability.
Part of the book: Anti-cancer Drugs
In the human organism, the circadian regulation of carbohydrates metabolism is essential for the glucose homeostasis and energy balance. Unbalances in glucose and insulin tissue and blood levels have been linked to a variety of metabolic disorders such as obesity, metabolic syndrome, cardiovascular diseases and type 2 diabetes. Melatonin, the pineal hormone, is the key mediator molecule for the integration between the cyclic environment and the circadian distribution of physiological and behavioral processes and for the optimization of energy balance and body weight regulation, events that are crucial for a healthy organism. This chapter reviews the interplay between melatonin modulatory physiological effects, glucose homeostasis and metabolic balance, from the endocrinology perspective. The tremendous effect of melatonin in the regulation of metabolic processes is observed from the chronobiology perspective, considering melatonin as a major synchronizer of the circadian internal order of the physiological processes involved in energy metabolism.
Part of the book: Carbohydrate
All multicellular organisms live in a strong bond with the microorganisms from around the world, and the humans are not the exceptions. Human microbiota (a complex bacterial community) contains about 1014 microbial cells, 10 times more than the content of the cells from our body and the microbial genome named microbiome, 1000 more that the human genome. It colonises any surface of the human body, above our skin, in the genitourinary tract, gut and airways. From all this, the gut is the most colonised organ, with an amount of almost 70% of the human microbes. Considering the large size of the gut, compared with a tennis terrain, filled with substances that plays a key, nutritive role for the microbes, polyphenols are micronutrients from our diet, with an emerging role in the modulation of the colonic microbial population composition and activity. Therefore, many studies underline that long-term consumption of diets rich in plants polyphenols offers protection against cancer, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. This chapter reviews the biological effects of plant polyphenols in the context of relevance to human health, especially considering the food functionality area, together with the complexity of the human microbiota and the bioavailability highly dependent on their intestinal absorption.
Part of the book: Phenolic Compounds
Liposomes were proposed as drug vector systems in the treatment of many diseases. The following characteristics recommend the liposomes as attractive candidates for drug transportation: solubilisation, duration of action, targeting potential and internalisation. Methotrexate, a folate antagonist, was originally developed as an antineoplastic agent and subsequently used in inflammatory and/or immunosuppressive diseases. Its side effects have led researchers to direct their efforts to reduce toxicity, while maintaining efficacy of methotrexate. Liposomes with methotrexate as such, as well as its disodium salt, were prepared using two methods. The liposomes were characterized in terms of structure, size, degree of poly‐dispersion and encapsulation efficiency. The effect of methotrexate incorporated in liposomes has been investigated in vitro on human lymphoblastic cell line K562. Methotrexate incorporated into liposomes moderately reduces the proliferation of K562 cells, but significantly inhibits RNA synthesis. The cellular activation is probably the main target of the drug and not the neoplastic proliferation of cells. The methotrexate liposomes exhibited significant anti‐inflammatory activity and showed reduced toxicity. Given that the encapsulating of the drug in vector systems may result in the increasing concentration at the site of action, the methotrexate liposomes represent a targeted therapy with an optimized therapeutic efficacy—risk toxicity ratio.
Part of the book: Liposomes