Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as \u3949-Tetrahydrocannabinol (\u3949-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-Type C. sativa plants, but, unlike \u3949-THC, it is completely nonpsychoactive. Fibre-Type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of \u3949-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and \u3949-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of \u3949-THC deprived hemp

NEW TRENDS IN THE BIOACTIVE COMPOUNDS OF MILK: A REVIEW OF THE FUNCTIONAL ACTIVITIES AND PROCESSING EFFECTS

Milk has a complex highly variable nutritional com-position based on the different species and animal breeds, together with the strategy and management of the animal feed. It is the first food consumed by chil-dren, exclusively for the initial months because it contains all the nutrients necessary for body growth and the development of cognitive functions. Consid-ering the Mediterranean diet, cow and goat milk is consumed fresh or used for the production of dairy products, while sheep and buffalo milk is used exclu-sively for cheese production. In developing countries, sheep milk or milk from particular animal species such as the yak is also used for fresh consumption and is a low-cost food source for consumers. Milk is the only raw food with a complete profile of all nutri-ents, from proteins to fats, carbohydrates, water, min-erals, and vitamins. Several bioactive compounds are present in milk or originate during protein digestion and fat fraction. Thus, milk can be defined as a func-tional food because it adapts to the definition "any food or food ingredient that can provide a health ben-efit over the traditional nutrients it contains"

Ziprasidone as Adjunctive Therapy in Severe Bipolar Patients Treated with Clozapine

Aim. To confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Methods. Eight patients with psychotic bipolar disorder were tested with the BPRS, the HAM-D, and the CGI at T0 and retested after 2 weeks (T1). Plasma clozapine and norclozapine levels and BMI were tested at T0 and T1. Results. Ziprasidone was well tolerated by all the patients. BPRS and HAM-D scores were reduced in all patients. BMI was reduced in patients with a BMI at T0 higher than 25. Plasma levels of clozapine and norclozapine showed an irregular course

A Comparative Study on the Efficacy of NLRP3 Inflammasome Signaling Inhibitors in a Pre-clinical Model of Bowel Inflammation

Nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is pivotal in maintaining intestinal homeostasis and sustaining enteric immune responses in the setting of inflammatory bowel diseases. Drugs acting as NLRP3 blockers could represent innovative strategies for treatment of bowel inflammation. This study was performed in rats with dinitrobenzenesulfonic acid (DNBS)-induced colitis, to investigate how the direct blockade of NLRP3 inflammasome with an irreversible inhibitor (INF39) compares with Ac-YVAD-cmk (YVAD, caspase-1 inhibitor) and anakinra (IL-1β receptor antagonist), acting downstream on NLRP3 signaling. Animals with DNBS-colitis received YVAD (3 mg/kg) or anakinra (100 mg/Kg) intraperitoneally, and INF39 (25 mg/kg) or dexamethasone (DEX, 1 mg/kg) orally for 6 days, starting on the same day of colitis induction. Under colitis, there was a body weight decrease, which was attenuated by YVAD, anakinra or INF39, but not DEX. All test drugs counteracted the increase in spleen weight. The colonic shortening and morphological colonic alterations associated with colitis were counteracted by INF39, anakinra and DEX, while YVAD was without effects. Tissue increments of myeloperoxidase, tumor necrosis factor and interleukin-1β were more effectively counteracted by INF39 and DEX, than YVAD and anakinra. These findings indicate that: (1) direct inhibition of NLRP3 inflammasome with INF39 is more effective than caspase-1 inhibition or IL-1β receptor blockade in reducing systemic and bowel inflammatory alterations; (2) direct NLRP3 inhibition can be a suitable strategy for treatment of bowel inflammation

Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells.

Abstract Aims Cardiac ischaemia does not elicit an efficient angiogenic response. Indeed, lack of surgical revascularization upon myocardial infarction results in cardiomyocyte death, scarring, and loss of contractile function. Clinical trials aimed at inducing therapeutic revascularization through the delivery of pro-angiogenic molecules after cardiac ischaemia have invariably failed, suggesting that endothelial cells in the heart cannot mount an efficient angiogenic response. To understand why the heart is a poorly angiogenic environment, here we compare the angiogenic response of the cardiac and skeletal muscle using a lineage tracing approach to genetically label sprouting endothelial cells. Methods and results We observed that overexpression of the vascular endothelial growth factor in the skeletal muscle potently stimulated angiogenesis, resulting in the formation of a massive number of new capillaries and arterioles. In contrast, response to the same dose of the same factor in the heart was blunted and consisted in a modest increase in the number of new arterioles. By using Apelin-CreER mice to genetically label sprouting endothelial cells we observed that different pro-angiogenic stimuli activated Apelin expression in both muscle types to a similar extent, however, only in the skeletal muscle, these cells were able to sprout, form elongated vascular tubes activating Notch signalling, and became incorporated into arteries. In the heart, Apelin-positive cells transiently persisted and failed to give rise to new vessels. When we implanted cancer cells in different organs, the abortive angiogenic response in the heart resulted in a reduced expansion of the tumour mass. Conclusion Our genetic lineage tracing indicates that cardiac endothelial cells activate Apelin expression in response to pro-angiogenic stimuli but, different from those of the skeletal muscle, fail to proliferate and form mature and structured vessels. The poor angiogenic potential of the heart is associated with reduced tumour angiogenesis and growth of cancer cells

A Case Study of African American Parental Involvement in an Urban Middle School

Studying parental involvement offers the opportunity to develop new strategies and resources to increase involvement at the middle schools serving a similar demographic population. In a large economically disadvantaged urban middle school in the southeastern United States, very little parental involvement occurs from the African American population. The purpose of this qualitative single case study was to examine African American parents\u27 perception about their involvement in their middle school students\u27 education. Guided by Epstein, Simon, and Salinas\u27 parental involvement model, which describes 6 levels of parental involvement, the research questions guiding this project study examined African American parents\u27 perceptions about middle school children\u27s educational experiences, the level of parental involvement in middle school education, and parental beliefs about student success. A purposeful participant pool of 10 African American parents of Grade 7 and 8 students was used for data collection. Ten parents completed the preliminary paper questionnaire, 10 parents participated in 1-on-1 semi-structured interviews, and 7 parents participated in a focus group discussion. Thematic analysis of data followed the open coding process and identified categories and themes. The findings suggested the need for a parent education program involving the use of new strategies and resources for increasing African American parent involvement at the middle school level. Social change will occur by empowering African American parents to be involved in their middle school students\u27 education