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Background: The sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) depression substantially contributes to diastolic dysfunction in heart failure (HF), suggesting that SERCA2a stimulation may be a mechanism-based HF therapy. Istaroxime is a drug endowed with both a SERCA2a stimulatory activity and a Na+/K+ pump inhibitory activity for acute HF treatment. Its main metabolite PST3093 shows a more favorable therapeutic profile as compared to the parent drug, but it is still unsuitable for chronic usage. Novel PST3093 derivatives have been recently developed for oral (chronic) HF treatment; compound 8 was selected among them and here characterized. Methods: Effects of compound 8 were evaluated in a context of SERCA2a depression, by using streptozotocin-treated rats, a well-known model of diastolic dysfunction. The impact of SERCA2a stimulation by compound 8 was assessed at the cellular level ad in vivo, following i.v. infusion (acute effects) or oral administration (chronic effects). Results: As expected from SERCA2a stimulation, compound 8 induced SR Ca2+ compartmentalization in STZ myocytes. In-vivo echocardiographic analysis during i.v. infusion and after repeated oral administration of compound 8, detected a significant improvement of diastolic function. Moreover, compound 8 did not affect electrical activity of healthy guinea-pig myocytes, in line with the absence of off-target effects. Finally, compound 8 was well tolerated in mice with no evidence of acute toxicity. Conclusions: The pharmacological evaluation of compound 8 indicates that it may be a safe and selective drug for a mechanism-based treatment of chronic HF by restoring SERCA2a activity.

Background: Positivity (POS) indicates the proclivity to see life and experiences in a positive light. There is limited research on its effects on individuals with Schizophrenia Spectrum Disorders (SSD). Very little is known about the relationship between POS and daily activities in people with SSD. Aim: The study aims to compare the POS rated by patients with SSD with those obtained in an Italian normative sample matched by age and sex and to use the Ecological Momentary Assessment (EMA) to investigate the association between POS and daily time use (i.e. productive activities, leisure activities), functioning and mood in individuals with SSD. Method: 620 SSD patients were recruited from mental health services in Italy as part of the DiAPAson project. POS, symptom severity, functioning, and quality of life (QoL) were assessed. POS scores were compared to a normative sample of 5,002 Italian citizens. Additionally, a subset of 102 patients underwent 7-day assessments using mobile EMA. Results: People with SSD did not significantly differ from the Italian normative sample in POS levels (0.035, p =.190). POS showed a significant inverse association with support network (−0.586, p =.036) and symptomatology (BPRS −0.101; 95% p <.001; BNSS B = −0.113, p <.001). A significant direct association was found between POS and QoL (B = 0.310, p <.001) and functioning (B = 0.058, p <.001). In the subsample using EMA, POS ratings showed significant associations with Positive Emotions (B = 0.167, p <.001) and Negative Emotions (B = −0.201, p <.001). Conclusion: People with SSD exhibited comparable levels of POS to the normative sample. Higher POS was linked to better functioning, QoL, fewer severe symptoms, and increased positive emotions. However, it did not relate to increased productivity or engagement in leisure activities. Further research is needed to understand the relationship between POS and time use in individuals with SSD.

Aim: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. Methods: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines. Results: The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2–8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. Conclusion: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.

Coppa Piacentina is an Italian protected designation of origin (PDO) dry-cured product obtained from the muscle of pork neck and ripened for at least six months. Metabolomics- and volatilomics-based strategies, combined with a chemical characterization of free amino acids were applied to identify biomarkers of long-ripened Coppa Piacentina PDO. Long ripening induced a significantly increase of total free amino acids, mainly represented by glutamic acid, involved in the umami taste perception. Untargeted metabolomics, performed using UHPLC-HRMS, allowed to identify 32 putative gamma-glutamyl-peptides, known as main contributors to the kokumi taste. Unsupervised and supervised multivariate statistics observed a clear modification of these peptides over the ripening, with gamma-glutamyl-peptides which significantly increased in long-ripened samples. A volatilomics-based strategy, conducted with GCxGC-MS, was then performed, and 93 different compounds were identified, with aldehyde and ketones deriving from the lipid auto-oxidation which increased according to ripening.

Background: Evaluating emotional experiences in the life of people with Schizophrenia Spectrum Disorder (SSD) is fundamental for developing interventions aimed at promoting well-being in specific times and contexts. However, little is known about emotional variability in this population. In DiAPAson project, we evaluated between- and within-person differences in emotional intensity, variability, and instability between people with SSD and healthy controls, and the association with psychiatric severity and levels of functioning. Methods: 102 individuals diagnosed with SSD (57 residential patients, 46 outpatients) and 112 healthy controls were thoroughly evaluated. Daily emotions were prospectively assessed with Experience Sampling Method eight times a day for a week. Statistical analyses included ANOVA, correlations, and generalized linear models. Results: Participants with SSD, and especially residential patients, had a higher intensity of negative emotions when compared to controls. Moreover, all people with SSD reported a greater between-person-variability of both positive and negative emotions and greater intra-variability of negative emotions than healthy controls. In addition, the emotion variability in people with SSD does not follow a linear or quadratic trend but is more “chaotic” if compared to controls. Conclusions: Adequate assessments of positive and negative emotional experiences and their time course in people with SSD can assist mental health professionals with well-being assessment, implementing targeted interventions through the identification of patterns, triggers, and potential predictors of emotional states.

Background: Positivity (POS) indicates the proclivity to see life and experiences in a positive light. There is limited research on its effects on individuals with Schizophrenia Spectrum Disorders (SSD). Very little is known about the relationship between POS and daily activities in people with SSD. Aim: The study aims to compare the POS rated by patients with SSD with those obtained in an Italian normative sample matched by age and sex and to use the Ecological Momentary Assessment (EMA) to investigate the association between POS and daily time use (i.e. productive activities, leisure activities), functioning and mood in individuals with SSD. Method: 620 SSD patients were recruited from mental health services in Italy as part of the DiAPAson project. POS, symptom severity, functioning, and quality of life (QoL) were assessed. POS scores were compared to a normative sample of 5,002 Italian citizens. Additionally, a subset of 102 patients underwent 7-day assessments using mobile EMA. Results: People with SSD did not significantly differ from the Italian normative sample in POS levels (0.035, p =.190). POS showed a significant inverse association with support network (−0.586, p =.036) and symptomatology (BPRS −0.101; 95% p <.001; BNSS B = −0.113, p <.001). A significant direct association was found between POS and QoL (B = 0.310, p <.001) and functioning (B = 0.058, p <.001). In the subsample using EMA, POS ratings showed significant associations with Positive Emotions (B = 0.167, p <.001) and Negative Emotions (B = −0.201, p <.001). Conclusion: People with SSD exhibited comparable levels of POS to the normative sample. Higher POS was linked to better functioning, QoL, fewer severe symptoms, and increased positive emotions. However, it did not relate to increased productivity or engagement in leisure activities. Further research is needed to understand the relationship between POS and time use in individuals with SSD.

Objective: In the framework of daily time use, physical activity, and interpersonal relationships in patients with schizophrenia project, we aimed to investigate (a) within and between-group differences in daily time use of individuals with schizophrenia spectrum disorders (SSDs) and unaffected controls, stratifying them by age, sex, and employment status; (b) the associations between daily time use, the severity of psychiatric symptoms, and psychosocial functioning amongst those with SSD. Method: From October 2020 to October 2021, 306 outpatients and 312 individuals living in residential facilities (RFs) with SSD were recruited from 37 centers across Italy and compared on a measure of daily time use with 113 people unaffected by mental health problems. Statistical analyses included chi-squared tests, analysis of variance tests, t tests, Pearson’s correlations, and nonparametric corresponding tests. Results: Individuals with SSD spent significantly more time in sedentary activities, leisure, and religious activities than unaffected controls, independent of age, sex, and employment status. Unaffected controls and outpatients spent more time engaged in productive activities than patients in RFs. Among the latter group, time spent in productive activities decreased significantly after 45 years of age, while time spent in self-care activities increased. Spending time engaged in sedentary activities was associated with greater severity of psychiatric symptoms and lower levels of functioning. Conclusions and Implications for Practice: This study provides a deep understanding of how individuals with SSD spend their time and how this is associated with the severity of their mental health problems. These findings highlight the need for proactive rehabilitation programs to promote productive occupation and social inclusion of people with SSD.

Heart failure (HF) therapeutic toolkit would strongly benefit from the availability of ino-lusitropic agents with a favorable pharmacodynamics and safety profile. Istaroxime is a promising agent, which combines Na1/K1 pump inhibition with sarcoplasmic reticulum Ca21 ATPase (SERCA2a) stimulation; however, it has a very short half-life and extensive metabolism to a molecule named PST3093. The present work aims to investigate whether PST3093 still retains the pharmacodynamic and pharmacokinetic properties of its parent compound. We studied PST3093 for its effects on SERCA2a and Na1/K1 ATPase activities, Ca21 dynamics in isolated myocytes, and hemodynamic effects in an in vivo rat model of diabetic [streptozotocin (STZ)-induced] cardiomyopathy. Istaroxime infusion in HF patients led to accumulation of PST3093 in the plasma; clearance was substantially slower for PST3093 than for istaroxime. In cardiac rat preparations, PST3093 did not inhibit the Na1/K1 ATPase activity but retained SERCA2a stimulatory activity. In in vivo echocardiographic assessment, PST3093 improved overall cardiac performance and reversed most STZinduced abnormalities. PST3093 intravenous toxicity was considerably lower than that of istaroxime, and it failed to significantly interact with 50 off-targets. Overall, PST3093 is a "selective"SERCA2a activator, the prototype of a novel pharmacodynamic category with a potential in the ino-lusitropic approach to HF with prevailing diastolic dysfunction. Its pharmacodynamics are peculiar, and its pharmacokinetics are suitable to prolong the cardiac beneficial effect of istaroxime infusion.

Patients with schizophrenia spectrum disorder (SSD) experience disrupted temporality on the immediate timescale. However, insufficient information is available for longer time frames, and the interaction of temporal perspectives with the clinical manifestations of SSD is unknown. We explored the association between unbalanced time perspectives and symptom severity. Thirty-seven Italian mental health services participating in the DiAPAson project recruited 620 patients with DSM-5 SSD (68 % males, mean age = 41.3 ± 9.5 years). Time perspective biases were measured using the Deviation from the Balanced Time Perspective-revisited (DBTP-r) indicator, based on Zimbardo Time Perspective Inventory (ZTPI) scores. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) and Brief Negative Symptoms Scale (BNSS). Preliminary analyses examined the associations between ZTPI/DBTP-r and BPRS/BNSS total scores. In secondary analyses, we first tested the associations between the ZTPI/DBTP-r and BPRS/BNSS subscales and then compared ZTPI differences between patients with and without hallucinations, delusions, and conceptual disorganisation. Statistical significance was set at Holm-Bonferroni corrected p < 0.05. Low-to-moderate positive correlations were found between the DBTP-r and BPRS/BNSS total scores (r = 0.29/0.22). The strongest associations were between DBTP-r/ZTPI_Past-Negative and anxiety/depression (r = 0.34/0.36), followed by DBTP-r/ZTPI_Present-Fatalistic with thought disturbances (r = 0.22/0.20). DBTP-r was associated with BNSS anhedonia and avolition (r = 0.21/0.24). DBTP-r was higher in patients with hallucinations (ES = 0.391) and conceptual disorganisation (ES = 0.397) than in those without these symptoms. Unbalanced time perspective was positively associated with the severity of primary and secondary SSD features. These findings provide a rationale for empirical tests focused on balancing time perspectives in patients with SSD.

Background: The Experience Sampling Method (ESM) is a valid method of remotely recording activities and mood, but the predictors of adherence to ESM in patients with Schizophrenia Spectrum Disorder (SSD) are not known. Studies on adherence are significant as they highlight the strengths and weaknesses of ESM-based study designs and allow the development of recommendations and practical guidelines for implementing future studies or treatment plans. Objective: The aim of this study was to compare the adherence to ESM in patients with SSD and unaffected control individuals, investigate their patterns, and report the predictors of adherence. Methods: In total, 131 patients with SSD (74 in residential facilities and 57 outpatients) and 115 unaffected control individuals were recruited at 10 different centers in Italy as part of the DiAPAson project. Demographic information, symptom severity, disability level, and level of function were recorded for the clinical sample. Participants were evaluated for daily time use and mood through a smartphone-based ESM 8 times a day for 7 consecutive days. Adherence was measured by the response rate to ESM notifications. Results were analyzed using the chi-square test, ANOVA, Kruskal-Wallis test, and Friedman test, and a logistic regression model. Results: The overall adherence rate in this study was 50% for residents, 59% for outpatients, and 78% for unaffected control individuals. Indeed, patients with SSD had a lower rate of adherence to ESM than the unaffected control group (P≤.001), independent of time slot, day of monitoring, or day of the week. No differences in adherence rates between weekdays and weekends were found among the 3 groups. The adherence rate was the lowest in the late evening time slot (8 PM to 12 AM) and days 6-7 of the study for both patients with SSD and unaffected control individuals. The adherence rate among patients with SSD was not predicted by sociodemographic characteristics, cognitive function, or other

This study evaluated the relationship between negative symptoms, daily time use (productive/non-productive activities, PA/NPA), and negative emotions in schizophrenia-spectrum disorders (SSDs): 618 individuals with SSDs (311 residential care patients [RCPs], 307 outpatients) were surveyed about socio-demographic, clinical (BPRS, BNSS) and daily time use (paper-and-pencil Time Use Survey completed twice/week) characteristics. Among them 57 RCPs and 46 outpatients, matched to 112 healthy controls, also underwent ecological monitoring of emotions (8 times/day for a week) through Experience Sampling Method (ESM). RCPs spent significantly less time in PA than outpatients. Patients with more negative symptomatology spent more time in NPA and less in PA compared to patients with milder symptoms. Higher time spent in NPA was associated with negative emotions (p < 0.001 during workdays) even when correcting for BNSS total and antipsychotic polypharmacy (p = 0.002 for workdays, p = 0.006 for Sundays). Future studies are needed to explore in more detail the relationship between negative emotions, negative symptoms, time use, and functioning in individuals with SSDs, providing opportunities for more informed and personalised clinical treatment planning and research into interactions between different motivational, saliency and behavioural aspects in individuals with SSDs.

Background Schizophrenia spectrum disorders (SSD) compromise psychosocial functioning, including daily time use, emotional expression and physical activity (PA). Objective We performed a cohort study aimed at investigating: (1) the differences in PA, daily activities and emotions between patients with SSD and healthy controls (HC); (2) the strength of the association between these variables and clinical features among patients with SSD. Methods Ninety-nine patients with SSD (53 residential patients, 46 outpatients) and 111 matched HC were assessed for several clinical variables, and levels of functioning by means of standardised clinical measures. Self-reported daily activities and emotions were assessed with a smartphone application for ecological momentary assessment (EMA), and PA levels were assessed with a wearable accelerometer for 7 consecutive days. Findings Patients with SSD, especially those living in residential facilities, spent more time being sedentary, and self-reported more sedentary and self-care activities, experiencing higher levels of negative emotions compared with HC. Moreover, higher functioning levels among patients were associated with more time spent in moderate-to-vigorous activity. Conclusions Sedentary behaviour and negative emotions are particularly critical among patients with SSD and are associated with more impaired clinical outcomes. Clinical implications Mobile-EMA and wearable sensors are useful for monitoring the daily life of patients with SSD and the level of PA. This population needs to be targeted with specific rehabilitative programmes aimed at improving their commitment to structured daily activities.

Positive effects have been observed as a result of Aloe arborescens supplementation in the dry-off phase in dairy cows. Metabolomic approaches can provide additional information about animal physiology. Thus, we characterized plasma metabolome around dry-off in 12 cows supplemented (AL) or not (CTR) with 10 g/d of lyophilized A. arborescens with an untargeted metabolomic approach. Overall, 1658 mass features were annotated. Regardless of treatment, multivariate statistics discriminated samples taken before and after dry-off. Overall, 490 metabolites were different between late lactation and early dry period, of which 237 were shared between AL and CTR. The most discriminant compounds (pentosidine and luteolin 7-O-glucoside) were related to the more fibrous diet. Pathway analysis indicated that pyrimidine and glycerophospholipid metabolisms were down-accumulated, suggesting reduced rumen microbial activity and liver load. Samples from AL were discriminated from CTR either the day of dry-off or 7 days after. At dry-off, aloin and emodin were the most discriminant metabolites, indicating that Aloe's bioactive compounds were absorbed. Seven days later, 534 compounds were different between groups, and emodin was among the most impacted. Pathway analysis highlighted that glycerophospholipid, pyrimidine, and folate metabolisms were affected. These results might indicate that Aloe has positive effects on liver function and a modulatory effect on rumen fermentation.

Milk and dairy products can be affected by a series of chemical modifications induced by non-enzymatic browning and discoloration phenomena. In food science, non-enzymatic browning is also known as Maillard reaction and generates several classes of metabolites, potentially affecting the product's final quality. On the other hand, a pink/brown discoloration results in the potential rejection of a dairy product with a consequential economic loss to producers. Therefore, in this mini-review, we provide a comprehensive understanding of non-enzymatic browning and discoloration occurring in dairy products, by focusing on the broad spectrum of browning-associated metabolites. Within this scenario, omics approaches based on metabolomics and proteomics technologies become essential to provide more insights of the occurring chemical modifications. In addition, the potential researches in the future are also discussed. An updated and concise overview of the most recent metabolomics and proteomics-based findings evaluating the non-enzymatic browning and pink discoloration of dairy products was carried out, providing also constructive insights and inspiration for future studies on cheese browning.

Antipsychotic polypharmacy (APP) in patients with schizophrenia spectrum disorders (SSDs) is usually not recommended, though it is very common in clinical practice. Both APP and SSDs have been linked to worse health outcomes and decreased levels of physical activity, which in turn is an important risk factor for cardiovascular diseases and premature mortality. This real-world, observational study aimed to investigate antipsychotic prescribing patterns and physical activity in residential patients and outpatients with SSDs. A total of 620 patients and 114 healthy controls were recruited in 37 centers across Italy. Each participant underwent a comprehensive sociodemographic and clinical evaluation. Physical activity was monitored for seven consecutive days through accelerometer-based biosensors. High rates of APP were found in all patients, with residential patients receiving more APP than outpatients, probably because of greater psychopathological severity. Physical activity was lower in patients compared to controls. However, patients on APP showed trends of reduced sedentariness and higher levels of light physical activity than those in monopharmacy. Rehabilitation efforts in psychiatric residential treatment facilities were likely to result in improved physical activity performances in residential patients. Our findings may have important public health implications, as they indicate the importance of reducing APP and encouraging physical activity.

Sleep and rest-activity-rhythm (RAR) abnormalities are commonly reported in schizophrenia spectrum disorder (SSD) patients. However, an in-depth characterization of sleep/RAR alterations in SSD, including patients in different treatment settings, and the relationship between these alterations and SSD clinical features (e.g., negative symptoms) is lacking. SSD (N = 137 altogether, N = 79 residential and N = 58 outpatients) and healthy control (HC) subjects (N = 113) were recruited for the DiAPAson project. Participants wore an ActiGraph for seven consecutive days to monitor habitual sleep-RAR patterns. Sleep/rest duration, activity (i.e., M10, calculated on the 10 most active hours), rhythm fragmentation within days (i.e., intra-daily variability, IV; beta, steepness of rest-active changes), and rhythm regularity across days (i.e., inter-daily stability, IS) were computed in each study participant. Negative symptoms were assessed in SSD patients with the Brief Negative Symptom Scale (BNSS). Both SSD groups showed lower M10 and longer sleep/rest duration vs. HC, while only residential patients had more fragmented and irregular rhythms than HC. Compared to outpatients, residential patients had lower M10 and higher beta, IV and IS. Furthermore, residential patients had worse BNSS scores relative to outpatients, and higher IS contributed to between-group differences in BNSS score severity. Altogether, residentials and outpatients SSD had both shared and unique abnormalities in Sleep/RAR measures vs. HC and relative to one another, which also contributed to the patients' negative symptom severity. Future work will help establish whether improving some of these measures may ameliorate the quality of life and clinical symptoms of SSD patients.

Time perspective (TP) influences various aspects of human life. We aimed to explore the associations between TP, daily time use, and levels of functioning among 620 patients (313 residential patients and 307 outpatients) with a diagnosis of Schizophrenia Spectrum Disorders (SSD) recruited from 37 different centres in Italy. The Brief Psychiatric Rating Scale and the Specific Levels of Functioning (SLOF) were used to assess psychiatric symptoms severity and levels of functioning. Daily time use was assessed using an ad hoc paper and pencil Time Use Survey. The Zimbardo Time Perspective Inventory (ZTPI) was used to assess TP. Deviation from Balanced Time Perspective (DBTP-r) was used as an indicator of temporal imbalance. Results showed that the amount of time spent on non-productive activities (NPA) was positively predicted by DBTP-r (Exp(0): 1.36; p .003), and negatively predicted by the Past-Positive (Exp(0): 0.80; p .022), Present-Hedonistic (Exp(0): 0.77; p .008), and Future (Exp(0): 0.78; p .012) subscales. DBTP-r significantly negatively predicted SLOF outcomes (p .002), and daily time use, in particular the amount of time spent in NPA and Productive Activities (PA), mediated their association. Results suggested that rehabilitative programs for individuals with SSD should consider fostering a balanced time perspective to reduce inactivity, increase physical activity, and promote healthy daily functioning and autonomy.

Aims. Care needs represent an essential paradigm in planning residential facility (RF) interventions. However, possible disagreements between users and staff are critical issues in service delivery. The Experience Sampling Method (ESM) tracks experiences in the real world and real time. This study aimed to evaluate the care needs of patients with schizophrenia spectrum disorder (SSD) in RFs and its association with daily activities and mood monitored using the ESM.Methods. As part of the DIAPASON project, 313 residents with SSD were recruited from 99 Italian RFs. Sociodemographic and clinical characteristics were recorded. Care needs, the severity of symptomatology and negative symptoms were assessed. Fifty-six residents were also assessed for 7 consecutive days using the mobile ESM. Descriptive, agreement, predictor and moderator analyses were conducted.Results. The staff rated a higher number of total and met needs than service users (p < 0.001). Only a slight agreement between users and staff on unmet needs was found in self-care (k = 0.106) and information (k = 0.100) needs, while a moderate agreement was found in accommodation (k = 0.484), food (k = 0.406), childcare (k = 0.530), physical health (k = 0.470), telephone (k = 0.458) and transport (k = 0.425) needs. Older age (-0.15; p < 0.01), longer SSD diagnosis (-0.16; p < 0.01), higher collaboration (-0.16; p < 0.01) and lower symptomatology (-0.16; p < 0.01) decreased the number of unmet needs, while being a female (0.27; p < 0.05) and a shorter length of stay in an RF (0.54; p < 0.001) increased the number of unmet needs. A higher number of unmet needs was associated with a lower amount of time spent in leisure activities or reporting a positive mood: on the contrary, more unmet needs were associated with a greater amount of time spent in religious or non-productive activities. The associations between unmet needs rated by staff and users and momentary mood as assessed using the ESM were

Thymus comosus Heuff ex. Griseb. (Lamiaceae) is a wild thyme species endemic for Romanian Carpathian areas, frequently collected as substitute for collective herbal product Serpylli herba, cited as antibacterial and diuretic remedy in traditional medicine. The present study aimed to evaluate the in vivo diuretic effect and in vitro antimicrobial properties of three herbal preparations (infusion—TCI, tincture—TCT and an hydroethanolic extract prepared through an optimized ultrasound-assisted method—OpTC) obtained from the aerial parts of T. comosus Heuff ex. Griseb, also evaluating their comprehensive phenolic profile. In vivo diuretic effect was tested using Wistar rats treated orally with each herbal preparation (125 and 250 mg/kg dispersed in 25 ml/kg isotonic saline solution) and quantified based on cumulative urine output (ml), diuretic action and diuretic activity. Additionally, sodium and potassium excretion were monitored using a potentiometric method with selective electrodes. In vitro antibacterial and antifungal activities were assessed using p-iodonitrotetrazolium chloride assay against six bacterial strains and six fungal strains by monitoring minimum inhibitory concentration (MICs), minimum bactericidal concentrations (MBCs) and minimum fungicidal concentrations (MFCs). Finally, phenolic profile of the aforementioned herbal extracts was evaluated using an ultra-high-pressure liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS) method to check the impact of the different preparations on the most abundant and significant compounds. All the extracts exerted a mild diuretic action, TCT and OpTC inducing the most intense diuretic effect. Both herbal preparations produced a statistically significant, dose-dependent and gradual increase of the urine output, the effect being more intense at 24 h (6.63–7.13 ml/24 h). Potentiometric evaluation of urine samples collected from treated rats revealed a clear and mild

This work aimed to investigate the influence of high-power ultrasound (HPU) technology on the stability of bioactive compounds in strawberry juices obtained from fruits with different stages of ripeness (75% vs. 100%) and stored at 4 degrees C for 7 days. HPU parameters were amplitude (25, 50, 75, and 100%), pulses (50 vs. 100%) and treatment time (5 vs. 10 min). Amplitude and pulse had a significant effect (p <= 0.05) on all bioactive compounds except flavonols and hydroxycinnamic acids. The treatment duration of 5 min vs. 10 min had a significant positive impact on the content of anthocyanins, flavonols and condensed tannins, while the opposite was observed for total phenols, whereas no statistically significant effect was observed for hydroxycinnamic acids. The temperature changes during HPU treatment correlated positively with almost all HPU treatment parameters (amplitude, pulse, energy, power, frequency). Optimal parameters of HPU were obtained for temperature changes, where the highest content of a particular group of bioactive compounds was obtained. Results showed that by combining fruits with a certain ripeness and optimal HPU treatment, it would be possible to produce juices with highly preserved bioactive compounds, while HPU technology has prospects for application in functional food products.

Untargeted metabolomics based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry was combined with sensory analysis to provide new insights into the impact of the feeding system from mountain regions (grassland deriving from permanent meadows) on the chemical fingerprint of Parmigiano Reggiano PDO hard cheese. In the framework of a representative investigation, two different ripening times (12 and 24 months) were also considered. Multivariate statistics allowed discriminating cheese samples from different feeding regimens according to their metabolomics signatures. Interestingly, mountain grassland-based cheese samples were characterized by a more favourable fatty acid profile, recording also feed-derived compounds (such as terpenoids and linoleic acid derivatives) potentially associated with both beneficial effects on human health and sensory properties. According to the sensory analysis, the impact of herbs and grass enhanced the colour and retro-olfactive complexity of Parmigiano Reggiano PDO cheese, with spicy, umami and intense vegetal aromatic notes representing distinctive features.

Blackcurrants are sources of phenolic compounds, such as anthocyanins, possessing strong antioxidant, antimicrobial and antifungal activity. Therefore, the addition of different blackcurrant pomace ingredients may affect the overall meat quality. The actual chemical profile and bioactivities of blackcurrant pomace ingredients may strongly depend on its preparation; for instance, in our study the highest values of the in vitro antioxidant capacity were determined for blackcurrant seeds after supercritical CO2 extraction. Starting from these background conditions, in this work, we evaluated the ability of three different concentrations (namely 1, 3, and 5% w/w) of blackcurrant (BC) seeds following EtOH/water extraction (BC-AE), before supercritical fluid CO2 extraction (BC-RS), and after supercritical fluid CO2 extraction (BC-ASC) to affect different quality parameters of pork meatballs. These latter were stored considering three different time-points, namely 1, 3 and 6 days at 4 °C packed under modified atmosphere (i.e., 70% N2 and 30% CO2). Untargeted metabolomics allowed to identify several lipid and protein-related oxidation products involved in redox reactions, such as 13-L-hydroperoxylinoleic acid, (12S,13S)-epoxylinolenic acid, 9,10-epoxyoctadecenoic acid, glutathione, glutathione disulfide, L-carnosine, l-ascorbic acid, and tocotrienols. Besides, multivariate statistics applied on the metabolomics dataset confirmed that the chemical profile of meatballs was an exclusive combination of both BC inclusion levels and type of BC-ingredients considered. Our findings showed that the higher the concentration of BC seed ingredients in meatballs, the lower the cooking loss and the higher the fibre content. Also, all the ingredients significantly affected the colour parameters.

Dairy propionibacteria are Gram positive Actinomycetota, routinely utilized as starters in Swiss type cheese making and highly appreciated for their probiotic properties and health promoting effects. In this work, within the frame of a circular economy approach, 47 Propionibacterium and Acidipropionibacterium spp. were isolated from goat cheese and milk, and ewe rumen liquor, and characterized in view of their possible utilization for the production of novel pro-bioactive food and feed on scotta, a lactose rich substrate and one of the main by-products of the dairy industry. The evaluation of the Minimum Inhibitory Concentration (MIC) of 13 among the most common antibiotics in clinical practice revealed a general susceptibility to ampicillin, gentamycin, streptomycin, vancomycin, chloramphenicol, and clindamycin while confirming a lower susceptibility to aminoglycosides and ciprofloxacin. Twenty-five isolates, that proved capable of lactose utilization as the sole carbon source, were then characterized for functional and biotechnological properties. Four of them, ascribed to Propionibacterium freudenreichii species, and harboring resistance to bile salts (growth at 0.7-1.56 mM of unconjugated bile salts), acid stress (>80% survival after 1 h at pH 2), osmostress (growth at up to 6.5% NaCl) and lyophilization (survival rate > 80%), were selected and inoculated in scotta. On this substrate the four isolates reached cell densities ranging from 8.11 & PLUSMN; 0.14 to 9.45 & PLUSMN; 0.06 Log CFU mL(-1) and proved capable of producing different vitamin B9 vitamers after 72 h incubation at 30 & DEG;C. In addition, the semi-quantitative analysis following the metabolomics profiling revealed a total production of cobalamin derivatives (vitamin B12) in the range 0.49-1.31 mg L-1, thus suggesting a full activity of the corresponding biosynthetic pathways, likely involving a complex interplay between folate cycle and methylation cycle required in vitamin B12 b

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still undefined. Our aim was to use in silico models to develop an automated approach for discriminating the electrophysiological differences between hiPSC-CM. We propose the dynamic clamp (DC) technique with the injection of a specific IK1 current as a tool for deriving nine electrical biomarkers and blindly classifying differentiated CM. An unsupervised learning algorithm was applied to discriminate CM phenotypes and principal component analysis was used to visualise cell clustering. Pharmacological validation was performed by specific ion channel blocker and receptor agonist. The proposed approach improves the translational relevance of the hiPSC-CM model for studying mechanisms underlying inherited or acquired atrial arrhythmias in human CM, and for screening anti-arrhythmic agents.

In this work, untargeted metabolomics was used to shed light on the impact of different pasture-based diets on the chemical profile of Sarda sheep milk. The study considered 11 dairy sheep farms located in Sardinia, and milk samples were collected in 4 different periods, namely January, March, May, and July 2019, when all sheep had 58, 98, 138, and 178 days in milk, respectively. The animal diet composition was based on the intake of grazed herbage in natural pasture, hay, and concentrate. Overall, the combination of two comprehensive databases on food, namely the Milk Composition Database and Phenol-Explorer, allowed the putative identification of 406 metabolites, with a significant (p < 0.01) enrichment of several metabolite classes, namely amino acids and peptides, monosaccharides, fatty acids, phenylacetic acids, benzoic acids, cinnamic acids, and flavonoids. The multivariate statistical approach based on supervised orthogonal projections to latent structures (OPLS-DA) allowed us to predict the chemical profile of sheep milk samples as a function of the high vs no fresh herbage intake, while the prediction model was not significant when considering both hay and concentrate intake. Among the discriminant markers of the herbage intake, we found five phenolic metabolites (such as hippuric and coumaric acids), together with lutein and cresol (belonging to carotenoids and their metabolites). Additionally, a high discriminant power was outlined for lipid derivatives followed by sugars, amino acids, and peptides. Finally, a pathway analysis revealed that the herbage intake affected mainly five biochemical pathways in milk, namely galactose metabolism, phenylalanine metabolism, alpha-linolenic acid metabolism, linoleic acid metabolism, and aromatic amino acids involved in protein synthesis (namely tyrosine, phenylalanine, and tryptophan).

In the last years, animal proteins from meat and meat-derived products have represented one of the main concerns to achieve a sustainable food production. Within this perspective, the partial replacement of meat with nonmeat substances having a high-protein content, offers interesting opportunities to reformulate more sustainable meat products characterized also by potential health-promoting properties. Therefore, starting from these background conditions, this short review critically summarizes recent findings on extenders from different origins, namely pulses, plant-based ingredients, plant by-products, and unconventional sources, as valuable possibility to improve the technological profile and functional quality of meat, together with providing a focus on their ability to affect the sustainability of meat products.

The present study was designed to evaluate the functional potential of common duckweed (Lemna minor L.) as a source of bioactive compounds of nutraceutical interest. The untargeted profiling of the bioactive components of common duckweed was carried out through ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), in parallel with assessing in vitro antioxidant and enzymatic inhibition properties. The optimization of extraction parameters was determined using the response surface methodology (RSM) through a 3-factor central composite design. The process parameters included extraction temperature, % of ethanol, and ultrasound power, while the response variables were the phenolic content (considering each main phenolic class), total glucosinolates, total carotenoids, the antioxidant potential, and enzyme inhibition activities. The results revealed that common duckweed was a rich source of carotenoids and total flavonoids (mainly flavones and flavonols), followed by phenolic acids, low-molecular-weight phenolics, and glucosinolates. Interestingly, the total flavones, total flavonols and total carotenoid equivalents showed the highest and most positive correlation values with the bioactive properties measured. Finally, the combined RSM approach and unsupervised statistics allowed us to point out the pivotal impact of ethanol percentage in the extraction solvent to recover the highest amounts of bioactive compounds efficiently.

Polyphenols are multifaceted bioactive compounds, but little is known about their real impact on human health after consumption. In this work, the phenolic profiling of quebracho, yellow maize, and violet rice extracts was comprehensively investigated, together with the impact of in vitro digestion and colonic fermentation on the bioaccessibility and bioavailability of these phytochemicals. The different matrices showed distinct profiles, potentially influencing in vitro starch digestion under cooking conditions. Furthermore, after the extracts underwent in vitro gastrointestinal digestion and faecal fermentation, phenolics exhibited a differential bioaccessibility trend at every digestion level, with matrix-dependent behaviour. The bioavailability results suggest that polyphenols are metabolised during colonic fermentation, mainly into tyrosols, phenolic acids, and lignans, which are partially absorbed by Caco-2 cells. By combining metabolomics with in vitro cellular methods, this research provides new insights into the fate of these phytochemicals in the gut, yielding comprehensive data on their consumption in food matrices.

In this work, the synergistic/antagonistic impact of glucose and mixed starter cultures, namely Latilactobacillus sakei, Pediococcus pentosaceus, and Staphylococcus xylosus, was evaluated in Italian salami in terms of metab-olomics and sensory profiles. As expected, Salami manufactured with 0.5 % glucose exhibited a substantial pH drop, showing values close to 5 at 12 days of ripening. Metabolomics revealed 1841 metabolites, mainly belonging to amino acids, peptides, glycerolipids, and nucleic acids, showing a greater hierarchical role of glucose addition when compared with inoculated microbial starters. Distinct metabolomic fingerprints could be observed across treatments, mainly concerning glutamyl peptides like gamma-glutamyl-glutamate (related to the kokumi taste), biogenic amines (spermine), and lipid oxidation products (i.e., the oxylipin 13S-hydroperoxylino-lenic acid). Such differences may drive the differences in sensory profiles recorded among treatments. These findings indicate the need to select ad-hoc starter cultures to improve the safety, quality, and sensory traits of salami.

The impact of duckweed extracts (DEs) on the shelf-life of packaged beef burgers was evaluated through classical assays and untargeted metabolomics. Beef burgers were formulated with an antioxidants-free control (CON), 1 g/kg sodium ascorbate (ASC), and increasing levels of a DEs, namely 1 (DE1), 5 (DE5), and 10 (DE10) g/kg, packaged under modified atmosphere and stored at 4 °C for 19 days. The DEs, abundant in phytochemicals, determined no issues with the hygienic status of the product. DEs modulated the redox status, being ineffective in preserving linolenic acid from peroxidation. However, the oxidation marker 2-nonenoic acid was down-accumulated in the DE10 sample following 19 days of storage, recording a lower glutathione:glutathione disulfide ratio. The accumulation of adipate semialdehyde revealed the inefficiency of DEs in coping with protein oxidation, while DEs prevented the accumulation of biogenic amines. Therefore, this work suggests a potential pro-oxidant role of the formulated DEs.

This study examined the phytochemical profiles (mainly phenolics, carotenoids, and organosulfur compounds) and biological effects of hydroalcoholic extracts of Allium flavum (AF), a species of the Allium genus commonly known as small yellow onion. Unsupervised and supervised statistical approaches revealed clear differences between extracts prepared with samples collected from different areas of Romania. Overall, the AFFF (AF flowers collected from Faget) extract was the best source of polyphenols, also showing the highest antioxidant capacity evaluated through both in vitro DPPH, FRAP, and TEAC anti-radical scavenging assays and cell-based OxHLIA and TBARS assays. All the tested extracts exhibited & alpha;-glucosidase inhibition potential, while only the AFFF extract exhibited anti-lipase inhibitory activity. The phenolic subclasses annotated were positively correlated with the assessed antioxidant and enzyme inhibitory activities. Our findings suggested that A. flavum has bioactive properties worth exploring further, being a potential edible flower with health-promoting implications.

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (INaL) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca2+ leak. Electrical and intracellular Ca2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be consider

The consumption of foods characterized by a wide bioactive-compound profile has been associated with improved health status and reduced risk of developing diseases. Owing to the complexity of food production (e.g. crops and farmed animals), processing (e.g. fermentation), and shelf life (e.g. lipid or protein oxidation), a more comprehensive and holistic analysis is necessary to investigate the intricate metabolic pathways and metabolites involved with or displaying a biological activity. Accordingly, untargeted metabolomics analysis can provide crucial knowledge to support the selection of key metabolites and metabolic pathways to produce foods from animals and crops with a functional value. This short review aims to provide an overview of the applications of metabolomic analysis to screen bioactive compounds in both animal- and plant-based foods.

The application of innovative technologies in psychiatry is promising, but the debate about its feasibility is not settled. Our aim was to investigate and compare adherence to and usability of 7-day monitoring with an Experience Sampling Method (ESM) and Actigraphy among a sample of individuals with a diagnosis of Schizophrenia Spectrum Disorders (SSD) and paired healthy controls. Twenty-two patients living in residential facilities (RFs), 20 outpatients and 26 controls were enrolled in this study as part of the DiAPAson project. Participants wore an actigraph and were evaluated for daily time use and mood with a smartphone-based ESM. Then, they completed questionnaires to assess the usability of the devices and were interviewed. Adherence was assessed as the percentage of time spent wearing actigraph and answering ESM notifications. Residential patients, compared to controls, showed significantly higher usability of the actigraph and lower adherence to both the actigraph and ESM. From the qualitative interviews, four high-order themes emerged: effects of monitoring, adherence and usability, emotions and mental states, and advice. Findings are promising for the application of these methodologies in such populations. The role of multidisciplinary staff in RFs is crucial for guaranteeing the realization of such projects.

Saffron production from Crocus sativus flowers produces large amounts of by-products that may represent an excellent source of polyphenols. The aim of this work was to evaluate infusions originating from different brewing processes and from different saffron flower portions, in terms of both functional and sensory traits. For this aim, total polyphenols and total flavonoids, in vitro antioxidant assays and an untargeted phenolic profiling were applied. In general, tepals showed higher polyphenol and flavonoid content than stamen infusions, and their bioactive content depended more on brewing temperature than brewing time. These findings were consistent with both antioxidant capacity and phenolic profiling. Multivariate statistics highlighted polyphenols discriminating ‘boiled’ vs. ‘cold’ infusions, being mainly flavonoids, phenolic acids and the alkylphenol 5-pentadecylresorcinol (showing a strong down-accumulation at the higher brewing temperatures). Positive correlations could be highlighted between anthocyanins, flavones, flavonols and lignans, and the in vitro antioxidant assays. In general, cold brewing was successful in extracting phenolic compounds and provided better sensory properties, thus indicating that this may represent a valuable strategy to develop saffron-based functional beverages with better consumers' acceptability.

Several studies have demonstrated that stigmas of Crocus sativus contain several bioactive compounds with potential health-promoting properties. However, during the processing of stigmas, large amounts of floral bio-residues are normally discarded as by-products. In this study, using untargeted metabolomics, the comprehensive phytochemical composition of C. sativus stigma and tepals was investigated. Moreover, the antibacterial and anti-biofilm properties of the extracts of C. sativus stigmas and tepals were compared. The study was carried out using two methicillin-resistant staphylococcal reference strains (i.e., Staphylococcus aureus ATCC 43300 and Staphylococcus epidermidis ATCC 35984), representing important Gram-positive biofilm-forming human pathogens. The antibacterial properties were correlated with total polyphenol content, total terpenoid content, and in vitro antioxidant properties of tepals and stigmas. The results demonstrated that stigma and tepal extracts, at the sub-Toxic concentrations, were able to interfere with biofilm formation by ATCC 43300 and ATCC 35984. Besides, the higher antibacterial activity of tepals than stigmas was associated with higher levels of phycompounds. Therefore, our results demonstrated that C. sativus stigmas and bio-residues, such as tepals, are potential antioxidant sources and good candidates as antibacterial agents to prevent biofilm formation. Taken together, these findings showed that C. sativus could be used as functional ingredient by the food and pharmaceutical industries.

An optimized ultrasound-assisted extractive method was developed to obtain a polyphenol-enriched extract from the aerial parts of Thymus comosus Heuff. ex Griseb. et Schenk. Optimization process was conducted based on Design of Experiment (DoE) principles, determining the influence of three independent variables (time, ultrasound amplitude, ethanol concentration) on the total phenolic content of the extract (dependent variable). Additionally, the phenolic composition of the extract was characterized through UHPLC-HRMS, revealing beside the most abundant flavonoid-type compounds the presence of salvianolic acids C, D and L in high amounts. Phytochemical profile of the extract was correlated with its antioxidant activity (tested through five complementary assays) and enzyme-inhibitory potential, showing important antiglucosidase and anticholinesterase effects. Overall, it was concluded that the developed method is suitable for obtaining a good recovery of both phenolic and non-phenolic compounds from Thymus comosus aerial parts, and their presence in the optimized extract is responsible for its pharmacological potential.

Spices, widely used to improve the sensory characteristics of food, contain several bioactive compounds as well, including polyphenols, carotenoids, and glucosynolates. Acting through multiple pathways, these bioactive molecules affect a wide variety of cellular processes involved in molecular mechanisms important in the onset and progress of human diseases. Capparis spinosa L. is an aromatic plant characteristic of the Mediterranean diet. Previous studies have reported that different parts (aerial parts, roots, and seeds) of C. spinosa exert various pharmacological activities. Flower buds of C. spinosa contain several bioactive compounds, including polyphenols and glucosinolates. Two different subspecies of C. spinosa L., namely, C. spinosa L. subsp. spinosa, and C. spinosa L. subsp. rupestris, have been reported. Few studies have been carried out in C. spinosa L. subsp. rupestris. The aim of our study was to investigate the phytochemical profile of floral buds of the less investigated species C. spinosa subsp. rupestris. Moreover, we investigated the effect of the extract from buds of C. spinosa subsp. rupestris (CSE) on cell proliferation, intracellular ROS levels, and expression of the antioxidant and anti-apoptotic enzyme paraoxonase-2 (PON2) in normal and cancer cells. T24 cells and Caco-2 cells were selected as models of advanced-stage human bladder cancer and human colorectal adenocarcinoma, respectively. The immortalized human urothelial cell line (UROtsa) and human dermal fibroblast (HuDe) were chosen as normal cell models. Through an untargeted metabolomic approach based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS), our results demonstrate that C. spinosa subsp. rupestris flower buds contain polyphenols and glucosinolates able to exert a higher cytotoxic effect and higher intracellular reactive oxygen species (ROS) production in cancer cells compared to normal cells. Moreover, upregulation of

In this work, milk samples collected in a cohort of intensive dairy farms of the Po Valley (Italy) were screened for their (poly)-phenolic profile to check the occurrence of phenolic metabolites of biological interest. The selected dairy farms were previously classified on the basis of their cow feeding system, considering the utilization of corn silage as the main ingredient of the rations. Overall, ultra-high-pressure liquid chromatography coupled with mass spectrometry using an Orbitrap analyzer, followed by unsupervised and supervised statistics, allowed identifying clear different phenolic distributions in the milk samples. Accordingly, a great variability in the phenolic profiles of the different milk samples was observed, with two main phenolic clusters outlined by the unsupervised hierarchical clustering approach and not fully correlated to the nutritional strategy considered. The variables’ importance in the projection approach allowed selecting the most important metabolites, resulting in samples’ discrimination. Among the most discriminative compounds, we found phenolic metabolites (such as hippuric acid and 4-hydroxyhippuric acid), followed by lignans (such as enterolactone) and isoflavonoids (such as equol and O-desmethylangolensin). Taken together, our findings suggested that both the feeding systems and the ability of dairy cows to process parent phenolic compounds were the main factors providing the final (poly)-phenolic profile of the milk samples. Future targeted and ad hoc studies appear of great interest to evaluate the potential biological effects of these compounds on cow health

The untargeted metabolomic profile of five pigmented whole rice varieties, namely Ermes, Orange, Nerone, Venere, and Violet, was investigated. Samples were cooked to a comparable starch gelatinization level through an electric commercial rice cooker and in vitro digested to evaluate the fate of rice compounds during in vitro starch digestion. The untargeted metabolomics profiling depicted a broad phytochemical profile of rice grains, including phenolic compounds, terpenoids, and phytosterols, among others. Interestingly, the metabolomic profile showed distinctive shaping following cooking and in vitro digestion in a variety-dependent manner. Multivariate statistics revealed that glycosylated flavonoids and hydrolysis-products of tannins (such as 1,2-digalloyl-beta-D-glucopyranose) were the most discriminant compounds of the in vitro gastrointestinal digestion. The combination of cooking and simulated digestion was found to affect, in a matrix-driven manner, the profile of amino acids and lipids derivatives, together with sterols and terpenoids. Cooked Violet rice grains showed the lowest starch hydrolysis index (i.e., 58.2) and the highest resistant starch content (i.e., 4.8 g/100 g) compared to the other samples. Non-pigmented phenolic compounds could be included among discriminant compounds. After combining cooking and enzyme hydrolysis, Violet rice distinctively showed positive average LogFC values for flavonoids and phenolic acids. Overall, water-soluble anthocyanins were the most retained class of polyphenols following the cooking process, with peonidin 3-(6”-acetyl-glucoside) showing the highest discriminant potential (VIP score = 1.64).

Co-inoculation of arbuscular mycorrhizal fungi (AMF) and bacteria can synergically and potentially increase nitrogen use efficiency (NUE) in plants, thus, reducing nitrogen (N) fertilizers use and their environmental impact. However, limited research is available on AMF-bacteria interaction, and the definition of synergisms or antagonistic effects is unexplored. In this study, we adopted a response surface methodology (RSM) to assess the optimal combination of AMF (Rhizoglomus irregulare and Funneliformis mosseae) and Bacillus megaterium (a PGPR—plant growth promoting rhizobacteria) formulations to maximize agronomical and chemical parameters linked to N utilization in maize (Zea mays L.). The fitted mathematical models, and also 3D response surface and contour plots, allowed us to determine the optimal AMF and bacterial doses, which are approximately accorded to 2.1 kg ha–1 of both formulations. These levels provided the maximum values of SPAD, aspartate, and glutamate. On the contrary, agronomic parameters were not affected, except for the nitrogen harvest index (NHI), which was slightly affected (p-value of < 0.10) and indicated a higher N accumulation in grain following inoculation with 4.1 and 0.1 kg ha–1 of AMF and B. megaterium, respectively. Nonetheless, the identification of the saddle points for asparagine and the tendency to differently allocate N when AMF or PGPR were used alone, pointed out the complexity of microorganism interaction and suggests the need for further investigations aimed at unraveling the mechanisms underlying this symbiosis.

In this work, the Longissimus thoracis pig skeletal muscle was used as a model to investigate the impact of two different diets, supplemented with n-3 polyunsaturated fatty acids from extruded linseed (L) and polyphenols from grape skin and oregano extracts (L+P), on the lipidomic profile of meat. A standard diet for growing-finishing pigs (CTRL) was used as a control. Changes in lipids profile were investigated through an untargeted lipidomics and transcriptomics combined investigation. The lipidomics identified 1507 compounds, with 195 compounds fitting with the MS/MS spectra of LipidBlast database. When compared with the CTRL group, the L+P diet significantly increased 15 glycerophospholipids and 8 sphingolipids, while the L diet determined a marked up-accumulation of glycerolipids. According to the correlations outlined between discriminant lipids and genes, the L diet may act preventing adipogenesis and the related inflammation processes, while the L+P diet promoted the expression of genes involved in lipids' biosynthesis and adipogenic extracellular matrix formation and functioning.

Increasing consumers’ demand for foods with a lower environmental impact requires the introduction of effective traceability technologies ensuring the integrity of the information provided. Blockchain technology (BCT) has been the most used for this purpose. However, to effectively implement a BCT system, it is important to map the determinants that influence its consumers’ acceptance. For these reasons, we conducted a mini-narrative review summarizing the factors that impact on BCT acceptance. The results showed that the aspects related to technology/product features are the most studied, while individual and social variables are less explored. Moreover, the relationships between the acceptability of BCT, the type of foods tracked, and the socio-economic characteristics of countries in which this technology is implemented were not deep.

The stimulation of sarcoplasmic reticulum calcium ATPase SERCA2a emerged as a novel therapeutic strategy to efficiently improve overall cardiac function in heart failure (HF) with reduced arrhythmogenic risk. Istaroxime is a clinical-phase IIb compound with a double mechanism of action, Na+/K+ ATPase inhibition and SERCA2a stimulation. Starting from the observation that istaroxime metabolite PST3093 does not inhibit Na+/K+ ATPase while stimulates SERCA2a, we synthesized a series of bioisosteric PST3093 analogues devoid of Na+/K+ ATPase inhibitory activity. Most of them retained SERCA2a stimulatory action with nanomolar potency in cardiac preparations from healthy guinea pigs and streptozotocin (STZ)-treated rats. One compound was further characterized in isolated cardiomyocytes, confirming SERCA2a stimulation and in vivo showing a safety profile and improvement of cardiac performance following acute infusion in STZ rats. We identified a new class of selective SERCA2a activators as first-in-class drug candidates for HF treatment.

Lactic Acid Bacteria (LAB) could provide a valid alternative to S. cerevisiae as a starter culture for bakery products, avoiding yeast-related health problems while contributing to the technological and functional properties of bread. In this work, we evaluate the role of certain LABs (Leuconostoc citreum SB6, Weissella cibaria UC4051, Weissella confusa UC4051, and the commercial starter cultures Weissella cibaria, and Leuconostoc mesenteroides) in producing functional compounds (pro-technological, health-promoting, and postbiotic-like molecules). For this purpose, we analysed the genotypic and phenotypic features of strains, and we investigated dough fermentation from microbiological and metabolomics approaches. Results evidenced a clear discrimination between the metabolic activity of baker’s yeast and LAB. The most discriminant metabolites derived from proteolysis and lipolysis, such as peptides, amino acids, and fatty acyls. Furthermore, we elucidated the different metabolism of these strains by building gene-metabolite interaction networks that pairwise compared the LAB strains of the same genus. While most of the networks showed a characteristic nucleotide metabolism, only the commercial W. cibaria exhibited an interaction network composed of amino acids and their related genes. In conclusion, our findings reveal that LAB strains under investigation, and particularly the commercial W. cibaria, can enhance the functional properties of bread.