SMS-Based Active Surveillance of Adverse Events following Immunization in Children: The VigiVax Study.

Underreporting is the main limitation of spontaneous reporting systems. This cohort-event monitoring study aims to examine the potential of short message service (SMS)-based surveillance compared to traditional surveillance systems. Using VigiVax software, parents of vaccinated children aged two years or younger, in the period March 2021-May 2022, received a single SMS inquiry about adverse events following immunization (AEFI). Responses were collected, validated by health operators and integrated with the information on electronic immunization registries. AEFI reports were automatically submitted to the Italian Pharmacovigilance system. Among 254,160 SMS messages sent, corresponding to 451,656 administered doses (AD), 71,643 responses were collected (28.2% response rate), and 21,231 of them (8.3%) reported AEFI. After a seriousness assessment based on clinical criteria, 50 reports (0.24%) were classified as serious. Among these, a causality assessment identified 31 reports at least potentially related to the vaccination (RR: 6.86/100,000 AD). Febrile seizures following MMRV (measles, mumps, rubella, varicella) vaccination accounted for 11 of these 31 cases, with an incidence of 32 per 100,000 AD. No fatal outcomes were reported. Our findings support the highly favorable risk profile of pediatric vaccinations and the possibility to improve spontaneous reporting through the integration of digital technologies.

Modulating voltage-gated sodium channels to enhance differentiation and sensitize glioblastoma cells to chemotherapy.

BACKGROUND: Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle. METHODS: We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Nav) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Nav activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Nav in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo. RESULTS: We demonstrated that Nav is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Nav made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Nav substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Nav positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Nav. CONCLUSIONS: This insight positions Nav as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment.

[On two cases of systemic listeriosis without dominant neurological compromise]. / Sobre dos casos de listeriosis sistémica sin compromiso neurológico dominante.

Listeria monocytogenes is a Gram-positive aerobic bacterium; found ubiquitously in nature; which mainly affects newborns, older adults, immunosuppressed patients and pregnant women. However, Listeria disease can occur in the healthy population. Invasive listeriosis has three dominant clinical forms, bacteremia, neurolisteriosis and maternal-neonatal infection. Localized forms are infrequently described. The disease occurs mainly secondary to the consumption of contaminated food, including unpasteurized milk or cheese, and occurs in the form of isolated cases or outbreaks, usually beginning a few days after consumption of the contaminated food; although it has been described up to 2 months after ingesting them. There is also the possibility of direct transmission from animals and vertical transmission. Systemic listeriosis without dominant neurological symptoms is a rare event. Two cases are presented. The first was spondylodiscitis in a normal host and the second was Listeria bacteremia in a febrile immunocompromised patient.

Listeria monocytogenes es una bacteria aeróbica Gram positiva; encontrada enforma ubicua en la naturaleza; que afecta sobre todo a recién nacidos, adultos mayores, pacientes inmunodeprimidos y mujeres embarazadas. Sin embargo, la enfermedad por Listeria puede ocurrir en la población sana. La listeriosis invasiva posee 3 formas clínicas dominantes, bacteriemia, neurolisteriosis e infección materno-neonatal. Las formas localizadas se describen infrecuentemente. La enfermedad se produce fundamentalmente en forma secundaria al consumo de alimentos contaminados, incluidos leche o queso no pasteurizados, y sepresenta en forma de casos aislados o brotes, soliendo comenzar a los pocos días del consumo de éstos; aunque se ha descripto hasta 2 meses después de ingerirlos. También existela posibilidad de transmisión directa desde animales y transmisión vertical. La listeriosis sistémica sin cuadro neurológico dominante es un evento raro. Se presentan dos casos. El primero, una espondilodiscitis en huésped normal y el segundo una bacteriemia por Listeria en un paciente inmunocomprometido febril.

Medicinal Mushrooms in Metastatic Breast Cancer: What Is Their Therapeutic Potential as Adjuvant in Clinical Settings?

Breast cancer (BC) is the most commonly diagnosed tumor, remaining one of the leading causes of morbidity and mortality in females worldwide, with the highest rates in Western countries. Among metastatic BC (MBC), triple-negative breast cancer (TNBC) is characterized by the lack of expression of specific receptors, and differs from other subgroups of BC for its increased growth and fast spreading, with reduced treatment possibilities and a worse outcome. Actually, MBC patients are extremely prone to metastasis and consequent relapses, which affect distant target organs (e.g., brain, lung, bone and liver). Hence, the comprehension of biological mechanisms underlying the BC metastatization process is a key requirement to conceive/set up innovative medicinal strategies, with the goal to achieve long-lasting therapeutic efficacy, reducing adverse effects, and also ameliorating Quality of Life (QoL). Bioactive metabolites isolated from medicinal mushrooms (MMs) used as a supportive treatment, combined with conventional oncology, have recently gained wide interest. In fact, mounting evidence has revealed their peculiar promising immunomodulatory, anti-inflammatory and anticancer activities, even though these effects have to be further clarified. Among the group of most promising MMs are Lentinula edodes, Grifola frondosa, Ganoderma lucidum, Ophiocordyceps sinensis and Agaricus blazei, which are already employed in conventional cancer protocols in Asia and China. Recently, a growing number of studies have focused on the pharmacology and feasibility of MM-derived bioactive compounds as a novel valuable approach to propose an effective adjuvant therapy for MBC patients' management. In this review, we summarized the current state of knowledge on the abovementioned MM-derived bioactive compounds and their therapeutic potential in clinical settings.

A Lombard Variety of Sweet Pepper Regulating Senescence and Proliferation: The Voghera Pepper.

Aging and its related disorders are important issues nowadays and the first cause of this physio-pathological condition is the overproduction of ROS. Ascorbic acid is an antioxidant mediator and its anti-aging proprieties are well known. Our previous data demonstrated that Voghera sweet pepper (VP), a distinctive type of pepper cultivated in Italy, is particularly rich in ascorbic acid. Based on these data, the anti-aging effect mediated by extracts of the edible part of VP was evaluated on an in vitro model of both young and old Normal Human Diploid Fibroblasts (NHDF). Using phase contrast microscopy, we observed that VP may help cells in the maintenance of physiological morphology during aging. Cytofluorimetric analyses revealed that VP extracts led to an increase in DNA synthesis and percentage of living cells, linked to a consequent increase in mitotic events. This hypothesis is supported by the enhancement of PCNA expression levels observed in old, treated fibroblasts, corroborating the idea that this extract could recover a young phenotype in adult fibroblasts, confirmed by the study of p16 and p53 expression levels and TEM analyses. Based on these results, we may suppose that VP can lead to the partial recovery of "young-like" phenotypes in old fibroblasts.

A Phyto-mycotherapeutic Supplement, Namely Ganostile, as Effective Adjuvant in Brain Cancer Management: An In Vitro Study Using U251 Human Glioblastoma Cell Line.

The current standard oncotherapy for glioblastoma is limited by several adverse side effects, leading to a short-term patient survival rate paralleled by a worsening quality of life (QoL). Recently, Complementary and Integrative Medicine's (CIM) innovative approaches have shown positive impacts in terms of better response to treatment, side effect reduction, and QoL improvement. In particular, promising potential in cancer therapy has been found in compounds coming from phyto- and mycotherapy. The objective of this study was to demonstrate the beneficial effects of a new phyto-mycotherapy supplement, named Ganostile, in the human glioblastoma cell line U251, in combination with chemotherapeutic agents, i.e., Cisplatin and a new platinum-based prodrug. Choosing a supplement dosage that mimicked oral supplementation in humans (about 1 g/day), through in vitro assays, microscopy, and cytometric analysis, it has emerged that the cells, after 48hr continuous exposure to Ganostile in combination with the chemical compounds, showed a higher mortality and a lower proliferation rate than the samples subjected to the different treatments administered individually. In conclusion, our data support the use of Ganostile in integrative oncology protocols as a promising adjuvant able to amplify conventional and new drug effects and also reducing resistance mechanisms often observed in brain tumors.

Predation cues induce predator specific changes in olfactory neurons encoding defensive responses in agile frog tadpoles.

Although behavioural defensive responses have been recorded several times in both laboratory and natural habitats, their neural mechanisms have seldom been investigated. To explore how chemical, water-borne cues are conveyed to the forebrain and instruct behavioural responses in anuran larvae, we conditioned newly hatched agile frog tadpoles using predator olfactory cues, specifically either native odonate larvae or alien crayfish kairomones. We expected chronic treatments to influence the basal neuronal activity of the tadpoles' mitral cells and alter their sensory neuronal connections, thereby impacting information processing. Subsequently, these neurons were acutely perfused, and their responses were compared with the defensive behaviour of tadpoles previously conditioned and exposed to the same cues. Tadpoles conditioned with odonate cues differed in both passive and active cell properties compared to those exposed to water (controls) or crayfish cues. The observed upregulation of membrane conductance and increase in both the number of active synapses and receptor density at the postsynaptic site are believed to have enhanced their responsiveness to external stimuli. Odonate cues also affected the resting membrane potential and firing rate of mitral cells during electrophysiological patch-clamp recordings, suggesting a rearrangement of the repertoire of voltage-dependent conductances expressed in cell membranes. These recorded neural changes may modulate the induction of an action potential and transmission of information. Furthermore, the recording of neural activity indicated that the lack of defensive responses towards non-native predators is due to the non-recognition of their olfactory cues.

Switching patterns of biological drugs in patients with psoriasis and psoriatic arthritis: insight from the VALORE database network.

BACKGROUND: Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA). OBJECTIVE: The aim of this study was to describe switching patterns of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back. RESEARCH DESIGN AND METHODS: A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed. RESULTS: Thirty-thousand seven hundred bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p< 0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At 1 year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95% CI, 0.67-0.83; 0.58, 95% CI, 0.44-0.77, respectively) than those with TNF-α inhibitors. CONCLUSIONS: Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.

Improving Drug Safety in Pediatric and Young Adult Patients with Hemato-Oncological Diseases: A Prospective Study of Active Pharmacovigilance.

The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study was conducted to assess the safety of oncology pharmacological prescriptions in patients aged 0-24 years at Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and IRCCS CRO National Cancer Institute in Aviano (Italy) between January 2021 and October 2023. Prescriptions and ADRs were evaluated by a multidisciplinary team. A total of 1218 prescriptions for 38 patients were analyzed, and 190 ADRs of grade 3-5 were collected. As compared to historical data, we registered a significant increase (p < 0.001) in the number of ADRs. The risk of ADR was 3.4 times higher in the case of off-label prescriptions compared to on-label ones (OR 3.4; [1.47; 7.89]; p-value = 0.004). The risks of error and near-miss were reported for 6.3% and 18.2% of total prescriptions, respectively. Of the total of 133 interactions, 47 (35.3%) resulted in ADRs. This study shows the importance of pro-active pharmacovigilance to efficiently highlight ADRs, and the fundamental role of multidisciplinary teams (oncologist, pharmacist, pharmacologist, pediatrician, nurse) in improving patients' safety during therapy.

Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8-1.9) compared to RCTs (F/M ratio: 0.5-0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4-100 vs. 6-167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

Feasibility and Acceptability of a Text Message Intervention to Promote Adherence to Nutrition and Physical Activity Guidelines in a Predominantly Hispanic Sample of Cancer Survivors and Their Informal Caregivers: Results from a Pilot Intervention Trial.

Hispanic cancer survivors face unique barriers to meeting American Cancer Society (ACS) nutrition and physical activity guidelines, which reduce the risk of cancer recurrence and mortality and improve quality of life. This pilot intervention trial evaluated the feasibility and acceptability of a two-week ACS guideline-based nutrition and physical activity text message intervention in a predominantly Hispanic sample of cancer survivors and their informal caregivers. A mixed methods approach was used to assess feasibility and acceptability of the intervention. Feasibility and acceptability were measured by meeting a-priori cut-offs of >80% for recruitment, retention, and text message response rate. Participants also completed a semi-structured exit interview by telephone that assessed intervention components. Thirteen cancer survivors and six caregivers (n = 19) participated in this pilot study; 78% self-identified as Hispanic. Mean time since treatment completion for survivors was 11.9 years (SD 8.4), and 67% had breast cancer. Cancer survivors had a higher acceptability rate for physical activity (94%) compared to nutrition messages (86%), whereas equal acceptability rates were observed for both types of messages among caregivers (91%). Texting interventions are a feasible, acceptable, and a cost-effective strategy that have the potential to promote lifestyle behavior change among Hispanic cancer survivors and caregivers.

Diaphragm Fatigue in SMNΔ7 Mice and Its Molecular Determinants: An Underestimated Issue.

Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons leading to muscle weakness and respiratory failure. Mitochondrial dysfunctions are found in the skeletal muscle of patients with SMA. For obvious ethical reasons, the diaphragm muscle is poorly studied, notwithstanding the very important role that respiratory involvement plays in SMA mortality. The main goal of this study was to investigate diaphragm functionality and the underlying molecular adaptations in SMNΔ7 mice, a mouse model that exhibits symptoms similar to that of patients with intermediate type II SMA. Functional, biochemical, and molecular analyses on isolated diaphragm were performed. The obtained results suggest the presence of an intrinsic energetic imbalance associated with mitochondrial dysfunction and a significant accumulation of reactive oxygen species (ROS). In turn, ROS accumulation can affect muscle fatigue, cause diaphragm wasting, and, in the long run, respiratory failure in SMNΔ7 mice. Exposure to the antioxidant molecule ergothioneine leads to the functional recovery of the diaphragm, confirming the presence of mitochondrial impairment and redox imbalance. These findings suggest the possibility of carrying out a dietary supplementation in SMNΔ7 mice to preserve their diaphragm function and increase their lifespan.

The independent and moderating role of choice of non-financial reporting format on forecast accuracy and ESG disclosure.

Over the last two decades, the non-financial disclosure requirement has become a major concern for companies, consumers, governments, and policymakers. While compelling evidence has accumulated over time on the positive effect that moving away from disclosing non-financial information within mandatory financial statements, conflicting findings have emerged on the relative merits that choice of non-financial reporting format, in particular between sustainability and integrated reporting, can have on analysts' forecast accuracy. In addition, recent evidence from a non-voluntary setting has suggested that such choice could influence the effect of ESG disclosure and consequently reduce information asymmetry. Aiming to shed some light on these propositions within a voluntary setting, we conducted an empirical study focusing on a representative sample of listed European companies. We retrieved and analysed the last ten years (2012-2021) of publicly available financial information about the top 600 companies listed in the Eurostoxx. Our findings indicate that both a sustainability and an integrated report are significantly associated with improved forecast accuracy, relative to an annual report. We also find that ESG disclosure is significantly moderated by such choice. The environmental pillar score was found to strongly and positively affect forecast error, independently from other controls including the social and governance pillars. For companies opting to disclose non-financial information within an annual report, alternative forms of communication will therefore become critical to ensure that financial analysts, and ultimately investors, are informed about the company's sustainability-related activities and plans. Future research should be directed at examining the magnitude and direction of these effects among small and medium-size listed companies and in other decision-making settings to test the generalisability of these findings.

The Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor Cells.

Increasing reports of neurological and psychiatric outcomes due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the understanding of neurotoxic mechanisms is still lacking, particularly for the under-investigated αPHP, one of the major MDPV derivatives. In particular, its effects on neural stem/progenitor cell cultures (NSPCs) are still unexplored. Therefore, in the current in vitro study, the effects of increasing αPHP concentrations (25-2000 µM), on cell viability/proliferation, morphology/ultrastructure, genotoxicity and cell death pathways, have been evaluated after exposure in murine NSPCs, using a battery of complementary techniques, i.e., MTT and clonogenic assay, flow cytometry, immunocytochemistry, TEM, and patch clamp. We revealed that αPHP was able to induce a dose-dependent significant decrease of the viability, proliferation and clonal capability of the NSPCs, paralleled by the resting membrane potential depolarization and apoptotic/autophagic/necroptotic pathway activation. Moreover, ultrastructural alterations were clearly observed. Overall, our current findings demonstrate that αPHP, damaging NSPCs and the morpho-functional fundamental units of adult neurogenic niches may affect neurogenesis, possibly triggering long-lasting, irreversible CNS damage. The present investigation could pave the way for a broadened understanding of SCs toxicology, needed to establish an appropriate treatment for NPS and the potential consequences for public health.

Role of Na+/Ca2+ Exchanger (NCX) in Glioblastoma Cell Migration (In Vitro).

Glioblastoma (GBM) is the most malignant form of primary brain tumor. It is characterized by the presence of highly invasive cancer cells infiltrating the brain by hijacking neuronal mechanisms and interacting with non-neuronal cell types, such as astrocytes and endothelial cells. To enter the interstitial space of the brain parenchyma, GBM cells significantly shrink their volume and extend the invadopodia and lamellipodia by modulating their membrane conductance repertoire. However, the changes in the compartment-specific ionic dynamics involved in this process are still not fully understood. Here, using noninvasive perforated patch-clamp and live imaging approaches on various GBM cell lines during a wound-healing assay, we demonstrate that the sodium-calcium exchanger (NCX) is highly expressed in the lamellipodia compartment, is functionally active during GBM cell migration, and correlates with the overexpression of large conductance K+ channel (BK) potassium channels. Furthermore, a NCX blockade impairs lamellipodia formation and maintenance, as well as GBM cell migration. In conclusion, the functional expression of the NCX in the lamellipodia of GBM cells at the migrating front is a conditio sine qua non for the invasion strategy of these malignant cells and thus represents a potential target for brain tumor treatment.

Gestational diabetes mellitus: Impact of adherence on patient management and maternal-neonatal complications.

BACKGROUND: Gestational diabetes mellitus is a form of diabetes whose prevalence is constantly increasing, thus leading to a growth in the necessary resources and organization of diabetes and obstetric facilities. The literature suggests that adherence to diet and therapy in patients with GDM might be highly variable and only sometimes optimal, and that this suboptimal compliance might be associated with more complicated treatment management or some adverse perinatal outcomes. This study evaluates this adherence and the benefits of constant blood glucose monitoring regarding maternalneonatal complications. METHODS: We conducted a multicentre prospective observational study, including all patients diagnosed with gestational diabetes mellitus and aged ≥ 18 years, between January 2019 and November 2021. We measured patients' adherence by clinical diary monitoring (medical evaluation) and observation of data obtained from glycaemic control (glucometer analysis). Patients were divided into three groups the adherent patient group, the non-adherent patient group and the partially adherent patient group; then, we compared the groups to assess the impact of non-adherence on patients' health. RESULTS: 122 (46.9 %) were classified in the adherent group (AG), 91 (35.0 %) in the partially adherent group (PG), and 47 (18.1 %) in the non-adherent group (NG) out of a population of 260 patients. The AG and PG groups were associated with a RRR of 74 % (95 % CI:0.13-1.03, p = 0.057) and 32 % (95 % CI:0.25-1.84, p = 0449) in operative delivery, respectively. Finally, this study proved that full or partial adherence is associated with decreased insulin administration during labour in 67 % (OR=0.33 p = 0.038). CONCLUSION: The study showed that patients' adherence to diet and/or therapy proposed by the diabetologist could significantly influence optimal glycaemic control during pregnancy Better compliance may lead to a lower incidence of operative deliveries and insulin utilization during pregnancy and labour.

NMR-Based Characterization of Wood Decay Fungi as Promising Novel Foods: Abortiporus biennis, Fomitopsis iberica and Stereum hirsutum Mycelia as Case Studies.

Wood Decay Fungi (WDF) are fungi specialized in degrading wood. An interesting perspective is their use as a source of Novel Foods or food ingredients. Here, for the first time, the metabolite profiling of hydroalcoholic and organic extracts from A. biennis, F. iberica, S. hirsutum mycelia was investigated by NMR methodology. Amino acids (alanine, arginine, asparagine, aspartate, betaine, GABA, glutamate, glutamine, histidine, isoleucine, leucine, lysine, phenylalanine, threonine, tryptophan, tyrosine, valine), sugars (galactose, glucose, maltose, trehalose, mannitol), organic acids (acetate, citrate, formate, fumarate, lactate, malate, succinate), adenosine, choline, uracil and uridine were identified and quantified in the hydroalcoholic extracts, whereas the 1H spectra of organic extracts showed the presence of saturated, mono-unsaturated and di-unsaturated fatty chains, ergosterol,1,2-diacyl-sn-glycero-3-phosphatidylethanolamine, and 1,2-diacyl-sasglycero-3-phosphatidylcholine. A. biennis extracts showed the highest amino acid concentration. Some compounds were detected only in specific species: betaine and mannitol in S. hirsutum, maltose in A. biennis, galactose in F. iberica, GABA in F. iberica and S. hirsutum, and acetate in A. biennis and S. hirsutum. S. hirsutum showed the highest saturated fatty chain concentration, whereas DUFA reached the highest concentration in A. biennis. A high amount of ergosterol was measured both in A. biennis and F. iberica. The reported results can be useful in the development of WDF-based products with a high nutritional and nutraceutical value.

Study on the activation of cell death mechanisms: in search of new therapeutic targets in glioblastoma multiforme.

Malignant primary brain tumors remain among the most difficult cancers to treat, in particular, Glioblastoma Multiforme (GBM) is the deadliest brain tumor. The standard therapies currently used are not efficient enough in improving patients' survival and quality of life. Cisplatin (CDDP), a platinum-based drug, has shown efficacy against different solid neoplasms, but it is also associated to different forms of off-target toxicity. To overcome the limitation in the use of CDDP in the treatment of GBM patients, fourth generation platinum compounds are been synthesized, one of them is the Pt(IV)Ac-POA, a prodrug with a medium-chain fatty acid as axial ligand, which acts as a histone 3 deacetylase inhibitor. Moreover, recently, the antioxidant effects of medicinal mushrooms have been shown to induce a lowering of the toxicity of chemotherapy drugs, inducing greater therapeutic efficiency, thus the combined therapy of chemotherapy and micotherapy could be helpful in the treatment of GBM reducing the adverse effects of the former thanks to phytotherapy's antioxidant, anti-inflammatory, immunomodulatory and antitumoral activities. Here, through immunoblotting, ultrastructural and immunofluorescence analysis, we evaluated the contribution in the activation of different cell death pathway of Micotherapy U-Care, a medicinal blend supplement, used together with platinum-based compounds on human glioblastoma U251 cells.

Hericium erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond, How Far from the Shoreline?

A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer's disease, depression, Parkinson's disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies.

Voghera Sweet Pepper: A Potential Ally against Oxidative Stress and Aging.

In the present study, the potential functional properties of the extracts from the edible part of Capsicum annuum L. var. Peperone di Voghera (VP) were studied. The phytochemical analysis revealed a high amount of ascorbic acid, paralleled by a low carotenoid content. Normal human diploid fibroblasts (NHDF) were chosen as the in vitro model models to investigate the effects of the VP extract on oxidative stress and aging pathways. The extract of Carmagnola pepper (CP), another important Italian variety, was used as the reference vegetable. The cytotoxicity evaluation was performed firstly, using a 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, while the VP potential antioxidant and antiaging activity was investigated by immunofluorescence staining focusing on specifically selected proteins. The MTT data revealed the highest cell viability at a concentration of up to 1 mg/mL. The immunocytochemical analyses highlighted an increased expression of transcription factors and enzymes involved in redox homeostasis (Nrf2, SOD2, catalase), improved mitochondrial functionality, and the up-regulation of the longevity gene SIRT1. The present results supported the functional role of the VP pepper ecotype, suggesting a feasible use of its derived products as valuable food supplements.