A 50 Hz magnetic field influences the viability of breast cancer cells 96 h after exposure.

BACKGROUND: The exposure of breast cancer to extremely low frequency magnetic fields (ELF-MFs) results in various biological responses. Some studies have suggested a possible cancer-enhancing effect, while others showed a possible therapeutic role. This study investigated the effects of in vitro exposure to 50 Hz ELF-MF for up to 24 h on the viability and cellular response of MDA-MB-231 and MCF-7 breast cancer cell lines and MCF-10A breast cell line. METHODS AND RESULTS: The breast cell lines were exposed to 50 Hz ELF-MF at flux densities of 0.1 mT and 1.0 mT and were examined 96 h after the beginning of ELF-MF exposure. The duration of 50 Hz ELF-MF exposure influenced the cell viability and proliferation of both the tumor and nontumorigenic breast cell lines. In particular, short-term exposure (4-8 h, 0.1 mT and 1.0 mT) led to an increase in viability in breast cancer cells, while long and high exposure (24 h, 1.0 mT) led to a decrease in viability and proliferation in all cell lines. Cancer and normal breast cells exhibited different responses to ELF-MF. Mitochondrial membrane potential and reactive oxygen species (ROS) production were altered after ELF-MF exposure, suggesting that the mitochondria are a probable target of ELF-MF in breast cells. CONCLUSIONS: The viability of breast cells in vitro is influenced by ELF-MF exposure at magnetic flux densities compatible with the limits for the general population and for workplace exposures. The effects are apparent after 96 h and are related to the ELF-MF exposure time.

Effects of extremely low-frequency magnetic fields on human MDA-MB-231 breast cancer cells: proteomic characterization.

Extremely low-frequency electromagnetic fields (ELF-MF) can modify the cell viability and regulatory processes of some cell types, including breast cancer cells. Breast cancer is a multifactorial disease where a role for ELF-MF cannot be excluded. ELF-MF may influence the biological properties of breast cells through molecular mechanisms and signaling pathways that are still unclear. This study analyzed the changes in the cell viability, cellular morphology, oxidative stress response and alteration of proteomic profile in breast cancer cells (MDA-MB-231) exposed to ELF-MF (50 Hz, 1 mT for 4 h). Non-tumorigenic human breast cells (MCF-10A) were used as control cells. Exposed MDA-MB-231 breast cancer cells increased their viability and live cell number and showed a higher density and length of filopodia compared with the unexposed cells. In addition, ELF-MF induced an increase of the mitochondrial ROS levels and an alteration of mitochondrial morphology. Proteomic data analysis showed that ELF-MF altered the expression of 328 proteins in MDA-MB-231 cells and of 242 proteins in MCF-10A cells. Gene Ontology term enrichment analysis demonstrated that in both cell lines ELF-MF exposure up-regulated the genes enriched in "focal adhesion" and "mitochondrion". The ELF-MF exposure decreased the adhesive properties of MDA-MB-231 cells and increased the migration and invasion cell abilities. At the same time, proteomic analysis, confirmed by Real Time PCR, revealed that transcription factors associated with cellular reprogramming were upregulated in MDA-MB-231 cells and downregulated in MCF-10A cells after ELF-MF exposure. MDA-MB-231 breast cancer cells exposed to 1 mT 50 Hz ELF-MF showed modifications in proteomic profile together with changes in cell viability, cellular morphology, oxidative stress response, adhesion, migration and invasion cell abilities. The main signaling pathways involved were relative to focal adhesion, mitochondrion and cellular reprogramming.

Effects of caloric restriction on immunosurveillance, microbiota and cancer cell phenotype: Possible implications for cancer treatment.

Fasting, caloric restriction and foods or compounds mimicking the biological effects of caloric restriction, known as caloric restriction mimetics, have been associated with a lower risk of age-related diseases, including cardiovascular diseases, cancer and cognitive decline, and a longer lifespan. Reduced calorie intake has been shown to stimulate cancer immunosurveillance, reducing the migration of immunosuppressive regulatory T cells towards the tumor bulk. Autophagy stimulation via reduction of lysine acetylation, increased sensitivity to chemo- and immunotherapy, along with a reduction of insulin-like growth factor 1 and reactive oxygen species have been described as some of the major effects triggered by caloric restriction. Fasting and caloric restriction have also been shown to beneficially influence gut microbiota composition, modify host metabolism, reduce total cholesterol and triglyceride levels, lower diastolic blood pressure and elevate morning cortisol level, with beneficial modulatory effects on cardiopulmonary fitness, body fat and weight, fatigue and weakness, and general quality of life. Moreover, caloric restriction may reduce the carcinogenic and metastatic potential of cancer stem cells, which are generally considered responsible of tumor formation and relapse. Here, we reviewed in vitro and in vivo studies describing the effects of fasting, caloric restriction and some caloric restriction mimetics on immunosurveillance, gut microbiota, metabolism, and cancer stem cell growth, highlighting the molecular and cellular mechanisms underlying these effects. Additionally, studies on caloric restriction interventions in cancer patients or cancer risk subjects are discussed. Considering the promising effects associated with caloric restriction and caloric restriction mimetics, we think that controlled-randomized large clinical trials are warranted to evaluate the inclusion of these non-pharmacological approaches in clinical practice.

The Molecular Weaponry Produced by the Bacterium Hafnia alvei in Foods.

Hafnia alvei is receiving increasing attention from both a medical and veterinary point of view, but the diversity of molecules it produces has made the interest in this bacterium extend to the field of probiotics, the microbiota, and above all, to its presence and action on consumer foods. The production of Acyl Homoserine Lactones (AHLs), a type of quorum-sensing (QS) signaling molecule, is the most often-studied chemical signaling molecule in Gram-negative bacteria. H. alvei can use this communication mechanism to promote the expression of certain enzymatic activities in fermented foods, where this bacterium is frequently present. H. alvei also produces a series of molecules involved in the modification of the organoleptic properties of different products, especially cheeses, where it shares space with other microorganisms. Although some strains of this species are implicated in infections in humans, many produce antibacterial compounds, such as bacteriocins, that inhibit the growth of true pathogens, so the characterization of these molecules could be very interesting from the point of view of clinical medicine and the food industry. Lastly, in some cases, H. alvei is responsible for the production of biogenic amines or other compounds of special interest in food health. In this article, we will review the most interesting molecules that produce the H. alvei strains and will discuss some of their properties, both from the point of view of their biological activity on other microorganisms and the properties of different food matrices in which this bacterium usually thrives.

Phages and Enzybiotics in Food Biopreservation.

Presently, biopreservation through protective bacterial cultures and their antimicrobial products or using antibacterial compounds derived from plants are proposed as feasible strategies to maintain the long shelf-life of products. Another emerging category of food biopreservatives are bacteriophages or their antibacterial enzymes called "phage lysins" or "enzybiotics", which can be used directly as antibacterial agents due to their ability to act on the membranes of bacteria and destroy them. Bacteriophages are an alternative to antimicrobials in the fight against bacteria, mainly because they have a practically unique host range that gives them great specificity. In addition to their potential ability to specifically control strains of pathogenic bacteria, their use does not generate a negative environmental impact as in the case of antibiotics. Both phages and their enzymes can favor a reduction in antibiotic use, which is desirable given the alarming increase in resistance to antibiotics used not only in human medicine but also in veterinary medicine, agriculture, and in general all processes of manufacturing, preservation, and distribution of food. We present here an overview of the scientific background of phages and enzybiotics in the food industry, as well as food applications of these biopreservatives.

Pharmacological, non-pharmacological and stem cell therapies for the management of autism spectrum disorders: A focus on human studies.

In the last decade, the prevalence of autism spectrum disorders (ASD) has dramatically escalated worldwide. Currently available drugs mainly target some co-occurring symptoms of ASD, but are not effective on the core symptoms, namely impairments in communication and social interaction, and the presence of restricted and repetitive behaviors. On the other hand, transplantation of hematopoietic and mesenchymal stem cells in ASD children has been shown promising to stimulate the recruitment, proliferation, and differentiation of tissue-residing native stem cells, reducing inflammation, and improving some ASD symptoms. Moreover, several comorbidities have also been associated with ASD, such as immune dysregulation, gastrointestinal issues and gut microbiota dysbiosis. Non-pharmacological approaches, such as dietary supplementations with certain vitamins, omega-3 polyunsaturated fatty acids, probiotics, some phytochemicals (e.g., luteolin and sulforaphane), or overall diet interventions (e.g., gluten free and casein free diets) have been considered for the reduction of such comorbidities and the management of ASD. Here, interventional studies describing pharmacological and non-pharmacological treatments in ASD children and adolescents, along with stem cell-based therapies, are reviewed.

The Strategic Alliance between Clinical and Molecular Science in the War against SARS-CoV-2, with the Rapid-Diagnostics Test as an Indispensable Weapon for Front Line Doctors.

Our work concerns the actual problem of spread of SARS- CoV-2 outbreak which requires fast and correct as possible answer. In current scenario, the need of rapid answer put away the imperative of proper methodology. We focus on the serogical immunoassay for diagnosis of Covid-19 as an important weapon not only for diagnostic purpose, but also for epidemiologic one. The right equilibrium between high speed, low cost and accuracy is obtained with easy-to-use decentralized point-of-care test as the colloidal gold-based immunochromatographic strip assay which detects IgM and IgG antibodies directed against SARS-CoV-2. As our aim is to evaluate the efficacy of Covid-19 rapid tests and of serological assays in real-life settings, we designed a research protocol aimed to establish how to use correctly these diagnostics, taking into account the different possible clinical and epidemiological scenarios.

Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial-mesenchymal transition, angiogenesis and telomere length.

Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.

From by-products to new application opportunities: the enhancement of the leaves deriving from the fruit plants for new potential healthy products.

In the last decades, the world population and demand for any kind of product have grown exponentially. The rhythm of production to satisfy the request of the population has become unsustainable and the concept of the linear economy, introduced after the Industrial Revolution, has been replaced by a new economic approach, the circular economy. In this new economic model, the concept of "the end of life" is substituted by the concept of restoration, providing a new life to many industrial wastes. Leaves are a by-product of several agricultural cultivations. In recent years, the scientific interest regarding leaf biochemical composition grew, recording that plant leaves may be considered an alternative source of bioactive substances. Plant leaves' main bioactive compounds are similar to those in fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. Bioactive compounds can positively influence human health; in fact, it is no coincidence that the leaves were used by our ancestors as a natural remedy for various pathological conditions. Therefore, leaves can be exploited to manufacture many products in food (e.g., being incorporated in food formulations as natural antioxidants, or used to create edible coatings or films for food packaging), cosmetic and pharmaceutical industries (e.g., promising ingredients in anti-aging cosmetics such as oils, serums, dermatological creams, bath gels, and other products). This review focuses on the leaves' main bioactive compounds and their beneficial health effects, indicating their applications until today to enhance them as a harvesting by-product and highlight their possible reuse for new potential healthy products.

Cytotoxicity and Antimicrobial Resistance of Aeromonas Strains Isolated from Fresh Produce and Irrigation Water.

The genus Aeromonas has received constant attention in different areas, from aquaculture and veterinary medicine to food safety, where more and more frequent isolates are occurring with increased resistance to antibiotics. The present paper studied the interaction of Aeromonas strains isolated from fresh produce and water with different eukaryotic cell types with the aim of better understanding the cytotoxic capacity of these strains. To study host-cell pathogen interactions in Aeromonas, we used HT-29, Vero, J774A.1, and primary mouse embryonic fibroblasts. These interactions were analyzed by confocal microscopy to determine the cytotoxicity of the strains. We also used Galleria mellonella larvae to test their pathogenicity in this experimental model. Our results demonstrated that two strains showed high cytotoxicity in epithelial cells, fibroblasts, and macrophages. Furthermore, these strains showed high virulence using the G. mellonella model. All strains used in this paper generally showed low levels of resistance to the different families of the antibiotics being tested. These results indicated that some strains of Aeromonas present in vegetables and water pose a potential health hazard, displaying very high in vitro and in vivo virulence. This pathogenic potential, and some recent concerning findings on antimicrobial resistance in Aeromonas, encourage further efforts in examining the precise significance of Aeromonas strains isolated from foods for human consumption.

Changes in the Lifestyle of the Spanish University Population during Confinement for COVID-19.

The aim of this study was to evaluate the influence of the lockdown due to the COVID-19 pandemic, on eating and physical activity behavior, in a university population. A healthy diet such as the Mediterranean Diet (MD) pattern, rich in fruit and vegetables, can prevent degenerative diseases such as obesity, diabetes, cardiovascular diseases, etc. We conducted a cross-sectional study and data were collected by an anonymous online questionnaire. Participants completed a survey consisting of 3 sections: sociodemographic data; dietary behavior and physical activity; the Mediterranean Diet questionnaire (MEDAS-14) and the Emotional Eater Questionnaire (EEQ). A total of 168 participants completed the questionnaire: 66.7% were women, 79.2% were from Spain, 76.8% were students, 76.2% lived in their family home and 66.1% were of normal weight. During lockdown our population shopped for groceries 1 time or less per week (76.8%); maintained the same consumption of fruits (45.2%), vegetables (50.6%), dairy products (61.9%), pulses (64.9%), fish/seafood (57.7%), white meat (77.4%), red and processed meat (71.4%), pastries and snacks (48.2%), rice/pasta/potatoes (70.2%) and nuts (62.5%), spirits (98.8%) and sugary drinks (91.7%). Cooking time increased (73.2%) and the consumption decreased of low alcohol drinks (60.1%), spirits (75%) and sugary drinks (57.1%), and physical activity also diminished (49.4%). University Employees (UE) gained more weight (1.01 ± 0.02) than students (0.99 ± 0.03) (p < 0.05) during the confinement period. A total of 79.8% of the participants obtained a Medium/High Adherence to the MD during lockdown. Emotional and very emotional eaters were higher in the female group (p < 0.01). In the event of further confinement, strategies should be implemented to promote a balanced and healthy diet together with the practice of physical activity, taking special care of the female and UE groups.

Immunoinflammatory effects of dietary bioactive compounds.

Inflammation is a key mechanism of the immune system that can be elicited by several factors, among them several chemical, physical and biological agents. Once stimulated, the inflammatory response activates a series of signaling pathways and a number of immune cells which promote, in a very coordinated manner, the neutralization of the infectious agent. However, if uncontrolled, the inflammatory status may become chronic leading, potentially, to tissue damage and disease onset. Several risk factors are associated with the development of chronic inflammation and, among these factors, diet plays an essential role. In this chapter the effects of some dietary bioactive compounds, including micronutrients, omega-3 fatty acids, nucleotides and polyphenols, on the immunoinflammatory responses in different cellular, animal and human studies have been summarized.

Apoptotic mechanism activated by blue light and cisplatinum in cutaneous squamous cell carcinoma cells.

New approaches are being studied for the treatment of skin cancer. It has been reported that light combined with cisplatinum may be effective against skin cancer. In the present study, the effects of specific light radiations and cisplatinum on A431 cutaneous squamous cell carcinoma (cSCC) and HaCaT non­tumorigenic cell lines were investigated. Both cell lines were exposed to blue and red light sources for 3 days prior to cisplatinum treatment. Viability, apoptosis, cell cycle progression and apoptotic­related protein expression levels were investigated. The present results highlighted that combined treatment with blue light and cisplatinum was more effective in reducing cell viability compared with single treatments. Specifically, an increase in the apoptotic rate was observed when the cells were treated with blue light and cisplatinum, as compared to treatment with blue light or cisplatinum alone. Combined treatment with blue light and cisplatinum also caused cell cycle arrest at the S phase. Treatment with cisplatinum following light exposure induced the expression of apoptotic proteins in the A431 and HaCaT cell lines, which tended to follow different apoptotic mechanisms. On the whole, these data indicate that blue light combined with cisplatinum may be a promising treatment for cSCC.

Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

Modern high-throughput 'omics' science tools (including genomics, transcriptomics, proteomics, metabolomics and microbiomics) are currently being applied to nutritional sciences to unravel the fundamental processes of health effects ascribed to particular nutrients in humans and to contribute to more precise nutritional advice. Diet and food components are key environmental factors that interact with the genome, transcriptome, proteome, metabolome and the microbiota, and this life-long interplay defines health and diseases state of the individual. Rheumatoid arthritis (RA) is a chronic autoimmune disease featured by a systemic immune-inflammatory response, in genetically susceptible individuals exposed to environmental triggers, including diet. In recent years increasing evidences suggested that nutritional factors and gut microbiome have a central role in RA risk and progression. The aim of this review is to summarize the main and most recent applications of 'omics' technologies in human nutrition and in RA research, examining the possible influences of some nutrients and nutritional patterns on RA pathogenesis, following a nutrigenomics approach. The opportunities and challenges of novel 'omics technologies' in the exploration of new avenues in RA and nutritional research to prevent and manage RA will be also discussed.

Potential Health Benefit of Garlic Based on Human Intervention Studies: A Brief Overview.

Garlic is a polyphenolic and organosulfur enriched nutraceutical spice consumed since ancient times. Garlic and its secondary metabolites have shown excellent health-promoting and disease-preventing effects on many human common diseases, such as cancer, cardiovascular and metabolic disorders, blood pressure, and diabetes, through its antioxidant, anti-inflammatory, and lipid-lowering properties, as demonstrated in several in vitro, in vivo, and clinical studies. The present review aims to provide a comprehensive overview on the consumption of garlic, garlic preparation, garlic extract, and garlic extract-derived bioactive constituents on oxidative stress, inflammation, cancer, cardiovascular and metabolic disorders, skin, bone, and other common diseases. Among the 83 human interventional trials considered, the consumption of garlic has been reported to modulate multiple biomarkers of different diseases; in addition, its combination with drugs or other food matrices has been shown to be safe and to prolong their therapeutic effects. The rapid metabolism and poor bioavailability that have limited the therapeutic use of garlic in the last years are also discussed.

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research.

The interaction between nutrition and human infectious diseases has always been recognized. With the emergence of molecular tools and post-genomics, high-resolution sequencing technologies, the gut microbiota has been emerging as a key moderator in the complex interplay between nutrients, human body, and infections. Much of the host-microbial and nutrition research is currently based on animals or simplistic in vitro models. Although traditional in vivo and in vitro models have helped to develop mechanistic hypotheses and assess the causality of the host-microbiota interactions, they often fail to faithfully recapitulate the complexity of the human nutrient-microbiome axis in gastrointestinal homeostasis and infections. Over the last decade, remarkable progress in tissue engineering, stem cell biology, microfluidics, sequencing technologies, and computing power has taken place, which has produced a new generation of human-focused, relevant, and predictive tools. These tools, which include patient-derived organoids, organs-on-a-chip, computational analyses, and models, together with multi-omics readouts, represent novel and exciting equipment to advance the research into microbiota, infectious diseases, and nutrition from a human-biology-based perspective. After considering some limitations of the conventional in vivo and in vitro approaches, in this review, we present the main novel available and emerging tools that are suitable for designing human-oriented research.

Irreversible inhibition of Δ16HER2 is necessary to suppress Δ16HER2-positive breast carcinomas resistant to Lapatinib.

HER2 tyrosine kinase receptor is a validated target in breast cancer therapy. However, increasing evidence points to a major role of Δ16HER2 splice variant commonly coexpressed with HER2 and identified as a clinically important HER2 molecular alteration promoting aggressive metastatic breast cancer. Consistently, mice transgenic for the human Δ16HER2 isoform (Δ16HER2 mice) develop invasive mammary carcinomas with early onset and 100% penetrance. The present study provides preclinical evidence that Δ16HER2 expression confers de novo resistance to standard anti-HER2-therapies such as Lapatinib and acquired resistance to the selective Src inhibitor Saracatinib in breast cancer. Of note, Dacomitinib, an irreversible small molecule pan-HER inhibitor, was able to completely suppress Δ16HER2-driven breast carcinogenesis. Thus, only Dacomitinib may offer benefit in this molecularly defined patient subset by irreversibly inhibiting Δ16HER2 activation.