Identification of the EBF1/ETS2/KLF2-miR-126-Gene Feed-Forward Loop in Breast Carcinogenesis and Stemness.

MicroRNA (miR)-126 is frequently downregulated in malignancies, including breast cancer (BC). Despite its tumor-suppressive role, the mechanisms underlying miR-126 deregulation in BC remain elusive. Through silencing experiments, we identified Early B Cell Factor 1 (EBF1), ETS Proto-Oncogene 2 (ETS2), and Krüppel-Like Factor 2 (KLF2) as pivotal regulators of miR-126 expression.

In Vitro Cell-Based MTT and Crystal Violet Assays for Drug Toxicity Screening.

The development of novel drug candidates is a current challenge in pharmacology where therapeutic benefits must exceed side effects. Toxicology testing is therefore a fundamental step in drug discovery research. Herein, we describe the first line of toxicology testing program, consisting in cell-based high-throughput screening assays, which have the advantage of being easy, rapid, cheap, and reproducible while providing quantitative information.

Vitamin Nutritional Status in Patients with Pancreatic Cancer: A Narrative Review.

Due to the high mortality rate in Western countries, pancreatic cancer is considered one of the , leaving patients and their families with little hope upon diagnosis. Although surgical and drug therapies are critical for cancer patients to improve life expectancy and alleviation of suffering, nutrition plays a key role in improving cancer treatment outcomes. This narrative review, conducted as part of the activities of the Italian Society of Human Nutrition (SINU) working group in oncology, focuses on the prevalence of vitamin malnutrition among pancreatic cancer patients.

In Vivo Identification of H3K9me2/H3K79me3 as an Epigenetic Barrier to Carcinogenesis.

The highly dynamic nature of chromatin's structure, due to the epigenetic alterations of histones and DNA, controls cellular plasticity and allows the rewiring of the epigenetic landscape required for either cell differentiation or cell (re)programming. To dissect the epigenetic switch enabling the programming of a cancer cell, we carried out wide genome analysis of Histone 3 (H3) modifications during osteogenic differentiation of SH-SY5Y neuroblastoma cells. The most significant modifications concerned H3K27me2/3, H3K9me2, H3K79me1/2, and H3K4me1 that specify the process of healthy adult stem cell differentiation.

Exploring the 1,3-benzoxazine chemotype for cannabinoid receptor 2 as a promising anti-cancer therapeutic.

The discovery of selective agonists of cannabinoid receptor 2 (CB) is strongly pursued to successfully tuning endocannabinoid signaling for therapeutic purposes. However, the design of selective CB agonists is still challenging because of the high homology with the cannabinoid receptor 1 (CB) and for the yet unclear molecular basis of the agonist/antagonist switch. Here, the 1,3-benzoxazine scaffold is presented as a versatile chemotype for the design of CB agonists from which 25 derivatives were synthesized.

DNA-Protein-Interaction (DPI)-ELISA Assay for PPAR-γ Receptor Binding.

Dysregulation of peroxisome proliferator-activated receptor (PPAR)-γ has been described in a plethora of pathological conditions, such as diabetes, obesity, inflammatory-related diseases, and cancer. Therefore, identifying novel drugs that are able to restore PPAR-γ activity is a current challenge, which is however slowed down by the lack of a rapid and reproducible activity assay. To date, only a few methods are able to characterize PPAR-γ activity and most of them are expensive, time-consuming, and not always quantitative.

Assay of CB Receptor Binding.

Type-1 cannabinoid receptor (CB), one of the main targets of endocannabinoids, plays a key role in several pathophysiological conditions that affect both the central nervous system and peripheral tissues. Today, its biochemical identification and pharmacological characterization, as well as the screening of thousands of novel ligands that might be useful for developing CB-based therapies, are the subject of intense research. Among available techniques that allow the analysis of CB binding activity, radioligand-based assays represent one of the best, fast, and reliable methods.

Recent Advances on Type-2 Cannabinoid (CB) Receptor Agonists and their Therapeutic Potential.

In the last decade, selective modulators of type-2 cannabinoid receptor (CB) have become a major focus to target endocannabinoid signaling in humans. Indeed, heterogeneously expressed within our body, CB actively regulates several physio-pathological processes, thus representing a promising target for developing specific and safe therapeutic drugs. If CB modulation has been extensively studied since the very beginning for the treatment of pain and inflammation, the more recent involvement of this receptor in other pathological conditions has further strengthened the pursuit of novel CB agonists in the last five years.

Molecular Research on Platelet Activity in Health and Disease 3.0.

Zhao and Devine [...

Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay.

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay.

Comparative Analysis of Phenolic Composition of Six Commercially Available Chamomile ( L.) Extracts: Potential Biological Implications.

Several phytochemical-containing herbal extracts are increasingly marketed as health-promoting products. In particular, chamomile ( L.) is well known for its anti-inflammatory, analgesic, and antitumor properties.

Molecular Research on Platelet Activity in Health and Disease 2.0.

Hsia and collaborators [...

Dietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites.

Metabolic syndrome (MetS) is a complex pathophysiological state with incidence similar to that of a global epidemic and represents a risk factor for the onset of chronic non-communicable degenerative diseases (NCDDs), including cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and some types of cancer. A plethora of literature data suggest the potential role of gut microbiota in interfering with the host metabolism, thus influencing several MetS risk factors. Perturbation of the gut microbiota's composition and activity, a condition known as dysbiosis, is involved in the etiopathogenesis of multiple chronic diseases.

The Impact of Whole Grain Intake on Gastrointestinal Tumors: A Focus on Colorectal, Gastric, and Esophageal Cancers.

Cereals are one of staple foods in human diet, mainly consumed as refined grains. Nonetheless, epidemiological data indicate that whole grain (WG) intake is inversely related to risk of type 2 diabetes, cardiovascular disease, and several cancer types, as well as to all-cause mortality. Particularly responsive to WG positive action is the gastrointestinal tract, daily exposed to bioactive food components.

Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions.

Cardiovascular diseases (CVD) represent one of the biggest causes of death globally, and their prevalence, aetiology, and outcome are related to genetic, metabolic, and environmental factors, among which sex- and age-dependent differences may play a key role. Among CVD risk factors, platelet hyperactivity deserves particular mention, as it is involved in the pathophysiology of main cardiovascular events (including stroke, myocardial infarction, and peripheral vascular injury) and is closely related to sex/age differences. Several determinants (, hormonal status and traditional cardiovascular risk factors), together with platelet-related factors (, plasma membrane composition, receptor signaling, and platelet-derived microparticles) can elucidate sex-related disparity in platelet functionality and CVD onset and outcome, especially in relation to efficacy of current primary and secondary interventional strategies.

Molecular Research on Platelet Activity in Health and Disease.

This editorial summarizes and discusses the themes of eleven articles (five reviews and six original studies) published in the Special Issue "Molecular Research On Platelet Activity in Health and Disease". They give an international picture of the up-to-date understanding of i) platelet signalling under physiological and pathological conditions, ii) novel technologies for monitoring platelet functions and iii) clinical applications of platelet-based-therapy for management of pathological conditions, not directly related to haemostasis and thrombosis.

The "Janus Face" of Platelets in Cancer.

Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression.

Polyunsaturated fatty acids modulate the delivery of platelet microvesicle-derived microRNAs into human breast cancer cell lines.

Breast cancer is one of the most frequent and malignant types of cancer in women, with an increasing morbidity and mortality rate; in particular, treatment of triple negative breast cancer remains a challenge, since the efforts made with targeted therapies were ineffective. Among surrounding cells influencing the biology of cancer cells, platelets are recognizing as novel players. Activated platelets release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination; among factors contained in platelet-derived MVs, microRNAs are highly involved in cancer development.

Nutrition and Breast Cancer: A Literature Review on Prevention, Treatment and Recurrence.

Breast cancer (BC) is the second most common cancer worldwide and the most commonly occurring malignancy in women. There is growing evidence that lifestyle factors, including diet, body weight and physical activity, may be associated with higher BC risk. However, the effect of dietary factors on BC recurrence and mortality is not clearly understood.

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications.

Niacin (also known as "vitamin B₃" or "vitamin PP") includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death. In the central nervous system, vitamin B₃ has long been recognized as a key mediator of neuronal development and survival.

Essential Dietary Bioactive Lipids in Neuroinflammatory Diseases.

Significance: Under physiological conditions, neurons and glia are in a healthy, redox-balanced environment; when injury perturbs this equilibrium, a neuroinflammatory state is established by activated microglia that triggers pro-inflammatory responses and alters the oxidant/antioxidant balance, thus leading to neuronal loss and neurodegeneration. In neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease, amyothrophic lateral sclerosis, and multiple sclerosis), the brain is in a constitutively self-sustaining cycle of inflammation and oxidative stress that prompts and amplifies brain damage. Recent Advances: Recently, an increasing amount of scientific data highlight the ability of specific nutrients to cross the blood-brain barrier, and to modulate inflammatory and oxidative pathways.

Assay of CB1 Receptor Binding.

Type-1 cannabinoid receptor (CB1), one of the main targets of endocannabinoids, plays a key role in several pathophysiological conditions that affect both central nervous system and peripheral tissues. Today, its biochemical identification and pharmacological characterization, as well as the screening of thousands of novel ligands that might be useful for developing CB1-based therapies, are the subject of intense research. Among available techniques that allow the analysis of CB1 binding activity, radioligand-based assays represent one of the best, fast, and reliable methods.

Downstream effects of endocannabinoid on blood cells: implications for health and disease.

Endocannabinoids (eCBs), among which N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are the most biologically active members, are polyunsaturated lipids able to bind cannabinoid, vanilloid and peroxisome proliferator-activated receptors. Depending on the target engaged, these bioactive mediators can regulate different signalling pathways, at both central and peripheral levels. The biological action of eCBs is tightly controlled by a plethora of metabolic enzymes which, together with the molecular targets of these substances, form the so-called "endocannabinoid system".

Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors.

Aims: Pro-inflammatory cytokines, growth and angiogenic factors released by leukocytes are involved in carcinogenesis and cancer progression, but they are also crucial for fighting tumour growth and spreading. We have previously demonstrated that endocannabinoids modulate cell-to-cell crosstalk during inflammation. Here, we investigated the inflammatory and tumourigenic properties of endocannabinoids in a human urinary bladder carcinoma cell line.

2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts.

Platelets modulate vascular system integrity, and their loss is critical in haematological pathologies and after chemotherapy. Therefore, identification of molecules enhancing platelet production would be useful to counteract thrombocytopenia. We have previously shown that 2-arachidonoylglycerol (2-AG) acts as a true agonist of platelets, as well as it commits erythroid precursors toward the megakaryocytic lineage.