Chemical Profile and Bioactivity of Rubus idaeus L. Fruits Grown in Conventional and Aeroponic Systems.

Raspberry (Rubus idaeus L.) is a fruit of great interest due to its aroma, nutritional properties, and the presence of many bioactive compounds. However, differences among cultivation systems can affect its composition and, consequently, its potential bioactivity. Herein, for the first time, raspberries grown in an aeroponic system were investigated for their chemical profile and antioxidant and anti-inflammatory activity, as well as their enzyme (α-glucosidase and pancreatic lipase) inhibitory properties in comparison to wild and conventionally cultivated fruits. High-performance liquid chromatography coupled with diode array detection (HPLC-DAD) analyses revealed the presence of gallic acid, caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, rutin, and catechin in all the samples. The extracts exhibited in vitro anti-inflammatory activity (inhibition of nitric oxide production) regardless of the cultivation method. Of particular interest is the ability of raspberries to inhibit pancreatic lipase. With the exception of the ß-carotene bleaching test, the raspberries grown in conventional and aeroponic systems were more active in terms of antioxidants than wild fruits, as evidenced by the ABTS (IC50 in the range 1.6-3.4 µg/mL), DPPH (IC50 in the range 8.9-28.3 µg/mL), and FRAP tests (24.6-44.9 µM Fe(II)/g). The raspberries from aeroponic cultivation were generally able to exert the same bioactivity as those obtained from both conventionally cultivated and wild fruits, supporting the consideration that in the future, this technology could reshape agriculture by mitigating resource constraints, fostering sustainable practices and increasing yields.

Pregnancy and neonatal outcomes of SARS-CoV-2 infection discovered at the time of delivery: a tertiary center experience in North Italy.

OBJECTIVES: Although the knowledge on SARS-CoV-2 infection in pregnancy has greatly improved, there is still a lack of information on its role in the later stages of gestation. The aim of this study is to investigate whether SARS-CoV-2 discovered at delivery is associated with any obstetric or neonatal complications. METHODS: A retrospective case-control study was conducted at Department of Obstetrics, University Hospital Maggiore della Carità, Novara, Italy, from March 2020 to March 2023. Pregnant women admitted were tested for SARS-CoV-2. 168 women resulted positive at the time of delivery; the women were asymptomatic or paucisymptomatic. 170 negative women were selected as controls, selecting, for each SARS-CoV-2 positive patient, the patient who gave birth right before, if negative. Demographic and anamnestic characteristics, pregnancy, labor, and neonatal outcomes were evaluated. RESULTS: SARS-CoV-2 positive patients were more likely to have gestational diabetes (13.7 vs. 5.3 %) and required less frequently intrapartum analgesia (11.3 vs. 27 %) and labor augmentation (7.3 vs. 16.5 %). Post-partum hemorrhage rate was lower (13.7 vs. 22.9 %) and a shorter length of first and second stage of labor occurred. There were no statistically significant differences between the two groups regarding the mode of delivery and neonatal outcomes. CONCLUSIONS: SARS-CoV-2 positive patients have shorter labor length and a lower incidence of postpartum hemorrhage. Fewer obstetric interventions, as well as less use of intrapartum analgesia and oxytocin, could explain these findings. Moreover, gestational diabetes could increase susceptibility to infection. SARS-CoV-2 infection discovered at the time of delivery in asymptomatic or paucisymptomatic patients does not appear to increase the rate of cesarean delivery or other obstetric complications, and neonatal outcomes have not worsened.

Nutritionally enriched tomatoes (Solanum lycopersicum L.) grown with wood distillate: chemical and biological characterization for quality assessment.

Bio-based products are nowadays useful tools able to affect the productivity and quality of conventionally cultivated crops. Several bio-based products are currently on the market; one of the newest and most promising is the wood distillate (WD) derived from the pyrolysis process of waste biomass after timber. Its foliar application has been widely investigated and shown to promote the antioxidant profile of cultivated crops. WD was used here as additive for the cultivation of tomato (Solanum lycopersicum L.) plants. The application improved quality (chemical) parameters, minerals, polyphenols, and lycopene contents of tomato fruits. The extracts of WD-treated and untreated tomatoes have been chemically and biologically characterized. The 1 H-NMR and ESI-mass spectrometry analyses of the extracts revealed the presence of different fatty acids, amino acids and sugars. In particular, the WD-treated tomatoes showed the presence of pyroglutamic acid and phloridzin derivatives, but also dihydrokaempferol, naringenin glucoside, cinnamic acid, and kaempferol-3-O-glucoside. When tested in cells, the extracts showed a promising anti-inflammatory profile in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the extracts displayed a slight vasorelaxant activity on rat aorta rings (either endothelium-denuded or endothelium-intact) pre-contracted with phenylephrine or potassium chloride. PRACTICAL APPLICATION: Wood distillate has been used for tomato plant growth. Tomatoes showed improved nutritional parameters, and their extracts displayed antioxidant and anti-inflammatory activities.

Lavandula angustifolia mill. (Lamiaceae) ethanol extract and its main constituents as promising agents for the treatment of metabolic disorders: chemical profile, in vitro biological studies, and molecular docking.

Lavandula angustifolia Mill. (lavender) is one of the most used medicinal plants. Herein, we chemically characterised and investigated the antioxidant properties and the capability to inhibit key enzymes for the treatment of type 2 diabetes (TD2) and obesity such as pancreatic lipase, α-glucosidase, and α-amylase of the ethanolic extract of two lavender samples (La1 and La2) from southern Italy. Both extracts significantly inhibited α-glucosidase, while La1 inhibited α-amylase and lipase more effectively than La2. To investigate whether these properties could be due to a direct interaction of the main constituents of the extracts with the targeted enzymes, molecular docking studies have been performed. As a result, the selected compounds were able to interact with the key residues of the binding site of the three proteins, thus supporting biological data. Current findings indicate the new potential of lavender ethanolic extract for the development of novel agents for T2D and obesity.

The ability of supercritical CO2 carrot and pumpkin extracts to counteract inflammation and oxidative stress in RAW 264.7 macrophages stimulated with LPS or MDA-MB-231 cell-conditioned media.

Supercritical fluid extraction with CO2 (SFE) is an alternative technology to conventional solvent extraction (CSE), to obtain food-grade bioactives from plants. Here, SFE and CSE extracts from carrot and pumpkin matrices, impregnated with hempseed or flaxseed oil as co-solvents, were characterized by HPLC and GC-MS, and their ability to counteract the inflammatory and oxidative phenomena underlying the onset of several pathologies was assessed in vitro. All extracts showed dose-dependent anti-inflammatory potential and demonstrated an ability to interfere with the pro-inflammatory effects of breast cancer cell-conditioned media, and to inhibit reactive oxygen species (ROS) accumulation and nitrite production (NP) in lipopolysaccharide-stimulated macrophages. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is involved in these response mechanisms, as highlighted by the increased mRNA levels of its target genes revealed by quantitative real-time PCR analyses. NP and ROS concentrations negatively correlated with α-tocopherol and most carotenoids, but positively with the total tocopherol/total carotenoid ratio, suggesting an idiosyncratic effect of these bioactives on cell responses and emphasizing the need to focus on extract constituents' interactions.

Iridoid- and flavonoid-enriched fractions of Cornus sanguinea and Cornus mas exert antioxidant and anti-inflammatory effects and inhibit key enzymes in the treatment of metabolic disorders.

Background: Berry fruits are recognized as a "superfood" due to their high content of bioactive compounds and health benefits. Scope and approach: Herein, extracts of Cornus sanguinea and Cornus mas fresh and dried fruits obtained by different extraction procedures (ethanolic and hydroalcoholic maceration, ultrasound-assisted extraction, and Soxhlet apparatus) were analysed using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) and compared to identify the main healthy compounds and their impact on the inhibition of key enzymes (pancreatic lipase, α-glucosidase, and α-amylase) associated with metabolic disorders. The antioxidant activity and inhibition of nitric oxide (NO) and NF-κB pathway were also investigated. Key findings and conclusions: Flavonoids, iridoids, and phenolic acids were the main classes of identified compounds. Herein, kaempferol 3-O-galactoside, kaempferol 3-O-glucoside, quercetin, quercetin 3-O-xyloside, and myricetin 3-O-galactoside were detected for the first time in C. sanguinea. Remarkable antioxidant effects and promising α-glucosidase and lipase inhibitory activity were observed with extracts obtained by hydroalcoholic maceration of both Cornus dried fruits. Consequently, these extracts were subjected to fractionation using Amberlite XAD-16 resin. The most promising biological activities, which are attributed to the presence of some flavonoids and iridoids, were detected with the C. sanguinea fractions, in particular SD2(II). The results of this study offer new insights into the potential development of functional foods, nutraceuticals, and food supplements using the Cornus species.

Enhancing the Anticancer and Anti-Inflammatory Properties of Curcumin in Combination with Quercetin, for the Prevention and Treatment of Prostate Cancer.

Prostate cancer is the second most common cancer in men. Although epidemiologic studies show that a higher intake of polyphenols, curcumin (CUR), and quercetin (QRT), in particular, result in lower prostate cancer risk, the chemopreventive mechanisms underlying the effects of CUR and QRT have not been fully understood yet, and most investigations were conducted with individual compounds. Here, we investigated the anticancer and anti-inflammatory effects of CUR in combination with QRT, respectively, in a human prostate cancer cell line, PC-3, and in LPS-stimulated RAW 264.7 cells, and found that their combination significantly inhibited proliferation and arrested the cell cycle, inducing apoptosis, so exhibiting synergic activities stronger than single drug use. Moreover, via their antioxidant effects, the combination of CUR and QRT modulated several inflammation-mediated signaling pathways (ROS, nitric oxide, and pro-inflammatory cytokines) thus helping protect cells from undergoing molecular changes that trigger carcinogenesis. Although additional studies, including in vivo experiments and translational studies, are required, this study raises the possibility of their use as a safe, effective, and affordable therapeutic approach to prostate cancer.

Hyaluronic Acid: A Powerful Biomolecule with Wide-Ranging Applications-A Comprehensive Review.

Hyaluronic acid (HA) is a glycosaminoglycan widely distributed in the human body, especially in body fluids and the extracellular matrix of tissues. It plays a crucial role not only in maintaining tissue hydration but also in cellular processes such as proliferation, differentiation, and the inflammatory response. HA has demonstrated its efficacy as a powerful bioactive molecule not only for skin antiaging but also in atherosclerosis, cancer, and other pathological conditions. Due to its biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, several HA-based biomedical products have been developed. There is an increasing focus on optimizing HA production processes to achieve high-quality, efficient, and cost-effective products. This review discusses HA's structure, properties, and production through microbial fermentation. Furthermore, it highlights the bioactive applications of HA in emerging sectors of biomedicine.

A Picrocrocin-Enriched Fraction from a Saffron Extract Affects Lipid Homeostasis in HepG2 Cells through a Non-Statin-like Mode.

Dyslipidemia is a lipid metabolism disorder associated with the loss of the physiological homeostasis that ensures safe levels of lipids in the organism. This metabolic disorder can trigger pathological conditions such as atherosclerosis and cardiovascular diseases. In this regard, statins currently represent the main pharmacological therapy, but their contraindications and side effects limit their use. This is stimulating the search for new therapeutic strategies. In this work, we investigated in HepG2 cells the hypolipidemic potential of a picrocrocin-enriched fraction, analyzed by high-resolution 1H NMR and obtained from a saffron extract, the stigmas of Crocus sativus L., a precious spice that has already displayed interesting biological properties. Spectrophotometric assays, as well as expression level of the main enzymes involved in lipid metabolism, have highlighted the interesting hypolipidemic effects of this natural compound; they seem to be exerted through a non-statin-like mechanism. Overall, this work provides new insights into the metabolic effects of picrocrocin, thus confirming the biological potential of saffron and paving the way for in vivo studies that could validate this spice or its phytocomplexes as useful adjuvants in balancing blood lipid homeostasis.

New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration.

Breast cancer remains the greatest cause of cancer-related death in women worldwide. Its aggressiveness and progression derive from intricate processes that occur simultaneously both within the tumour itself and in the neighbouring cells that make up its microenvironment. The aim of the present work was firstly to study how elevated cholesterol levels increase tumour aggressiveness. Herein, we demonstrate that cholesterol, by activating ERRα pathway, promotes epithelium-mesenchymal transition (EMT) in breast cancer cells (MCF-7 and MDA-MB-231) as well as the release of pro-inflammatory factors able to orchestrate the tumour microenvironment. A further objective of this work was to study the close symbiosis between tumour cells and the microenvironment. Our results allow us to highlight, for the first time, that breast cancer cells exposed to high cholesterol levels promote (a) greater macrophages infiltration with induction of an M2 phenotype, (b) angiogenesis and endothelial branching, as well as (c) a cancer-associated fibroblasts (CAFs) phenotype. The effects observed could be due to direct activation of the ERRα pathway by high cholesterol levels, since the simultaneous inhibition of this pathway subverts such effects. Overall, these findings enable us to identify the cholesterol-ERRα synergy as an interesting target for breast cancer treatment.

Santolina pinnata Viv. Exerts Promising Antitumor Activity against Breast Cancer Cells and Anti-Inflammatory Effects in LPS-Stimulated RAW 264.7 Cells.

Cancer is one of the largest causes of mortality in the world, and due to its incidence, the discovery of novel anticancer drugs is of great importance. Many successful anticancer drugs used in clinical practices are derived from natural products. The genus Santolina is a group of species distributed in the Mediterranean area and used in traditional medicine for their biological properties. The aim of this work was to investigate, for the first time, the multi-target biological potential of Italian Santolina pinnata in relation to their chemical profile, by which an interesting natural source of valuable phytochemicals endowed with anticancer and anti-inflammatory features could be assessed. n-Hexane (EHSP) and methanol (EMSP) extracts were investigated by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography (UHPLC), respectively. Anti-proliferative activity was analyzed on MCF-7 and MDA-MB-231 breast cancer cells, as well as on non-tumorigenic MCF-10A cells, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptotic death was assessed by comet assay. Cell motility and invasive features were examined in highly invasive MDA-MB-231 by wound-healing scratches, while, in both breast cancer cell lines, by gel-zymography experiments. The anti-inflammatory potential was analyzed by nitric oxide (NO) production and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) staining experiments in bacterial lipopolysaccharides (LPS) which stimulated RAW 264.7 cells. EHSP and EMSP extracts exhibited anticancer activity against breast cancer cells, promoting apoptotic death, as well as decreasing cell migration and invasive behaviours. The highest activity (IC50 of 15.91 µg/mL) was detected against MDA-MB-231 cells, a highly invasive breast cancer cell line. Both extracts were also able to promote anti-inflammatory effects (IC50 values ranging from 27.5 to 61.14 µg/mL), as well as to reduce NO levels by inducing inhibitory effects on NF-κB nuclear translocation in LPS-stimulated RAW 264.7 cells. The different biological behaviours found between the extracts could be related to their different chemical compositions. Herein, the multi-target biological potential of S. pinnata in inducing antitumor and anti-inflammatory effects was comprehensively demonstrated. These findings will provide important stepping-stones for further investigations and may lead to the development of highly effective S. pinnata extract-based treatments for breast cancer and inflammatory processes.

Proteomic Profiling of Extracellular Vesicles Released by Leptin-Treated Breast Cancer Cells: A Potential Role in Cancer Metabolism.

Tumor extracellular vesicles (EVs), as endocytic vesicles able to transport nucleic acids, proteins, and metabolites in recipient cells, have been recognized fundamental mediators of cell-to-cell communication in breast cancer. The biogenesis and release of EVs are highly regulated processes and both the quantity of EVs and their molecular cargo might reflect the metabolic state of the producing cells. We recently demonstrated that the adipokine leptin, whose circulating levels correlate with adipose tissue expansion, is an inducer of EV release from breast cancer cells. Here, we show a specific proteomic signature of EVs released by MCF-7 breast cancer cells grown in the presence of leptin (Lep-EVs), in attempt to find additional molecular effectors linking obesity to breast cancer biology. An analysis of the proteomic profile of Lep-EVs by LC-MS/MS revealed a significant enrichment in biological processes, molecular functions, and cellular components mainly related to mitochondrial machineries and activity, compared to protein content of EVs from untreated breast cancer cells. Metabolic investigations, carried out to assess the autocrine effects of these vesicles on breast cancer cells, revealed that Lep-EVs were able to increase ATP levels in breast cancer cells. This result is associated with increased mitochondrial respiration evaluated by Seahorse analyzer, supporting the concept that Lep-EVs can modulate MCF-7 breast cancer cell oxidative metabolism. Moreover, taking into account the relevance of tumor immune cell crosstalk in the tumor microenvironment (TME), we analyzed the impact of these vesicles on macrophage polarization, the most abundant immune component in the breast TME. We found that tumor-derived Lep-EVs sustain the polarization of M0 macrophages, derived from the human THP-1 monocytic cells, into M2-like tumor-associated macrophages, in terms of metabolic features, phagocytic activity, and increased expression of CD206-positive population. Overall, our results indicate that leptin by inducing the release of EV-enriched in mitochondrial proteins may control the metabolism of MCF-7 breast cancer cells as well as that of macrophages. Characterization of tumor-derived EV protein cargo in an obesity-associated milieu, such as in the presence of elevated leptin levels, might allow identifying unique features and specific metabolic mechanisms useful to develop novel therapeutic approaches for treatment of breast cancer, especially in obese patients.

CD44-targeted nanoparticles with GSH-responsive activity as powerful therapeutic agents against breast cancer.

DOX-loaded nanoparticles able to actively target CD44-receptors and respond to redox stimuli were proposed as non-conventional chemotherapeutic strategy in breast cancer. A covalent conjugate of human serum albumin and hyaluronic acid was prepared and assembled by a GSH-mediated desolvation in disulfide-crosslinked solid nanoparticles with mean diameter of 120 nm ± 3.4. The effective internalization of nanoparticles in cancer cells via CD44-receptors, together with the more efficient intracellular release, resulted in a significant increase of drug efficacy, with IC50 reduced from 0.9959 and 2.516 µg mL-1 to 0.4014 and 0.3094 µg mL-1 for MCF-7 and MDA-MB-231, respectively. Conversely, no enhancement in drug toxicity was recorded in healthy MCF-10A cells. The efficacy of the proposed formulation was further investigated in the different biological steps involved in metastasis process, paving the way for further in vivo experiments.

Ultrasound-Assisted Extraction, Chemical Characterization, and Impact on Cell Viability of Food Wastes Derived from Southern Italy Autochthonous Citrus Fruits.

Citrus fruits are one of the principal fruits used to produce juices. Over the years, these fruits have been recognized as new health-promoting agents. In this work, food wastes derived from autochthonous citrus fruits of Southern Italy, named Limone di Rocca Imperiale, Arancia Rossa Moro, and Arancia Bionda Tardivo from Trebisacce, were analyzed. After fresh-squeezing juice, peel and pomace were employed to obtain six different extracts using an ultrasound-assisted method in a hydroalcoholic solvent. The extracts were analyzed in terms of qualitative composition, antioxidant properties, and antiproliferative activity on MCF-7, MDA-MB-231, and BJ-hTERT cell lines. GC-MS and LC-ESI-MS analyses showed different compounds: of note, limonin-hexoside, neodiosmin, obacunone glucoside, and diacetyl nomilinic acid glucoside have been identified as limonoid structures present in all the samples, in addition to different polyphenols including naringenin-glucoside, hesperetin-O-hexoside-O-rhamnoside-O-glucoside, diferuloyl-glucaric acid ester, chlorogenic acid, and the presence of fatty acids such as palmitic, myristic, and linoleic acids. These extracts were able to exert antioxidant activity as demonstrated by DPPH and ABTS assays and, although at higher doses, to reduce the cell viability of different solid tumor cell lines, as shown in MTT assays.

Smart Lipid-Polysaccharide Nanoparticles for Targeted Delivery of Doxorubicin to Breast Cancer Cells.

In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid-polymer nanoparticles were proposed as a delivery vehicle of doxorubicin hydrochloride in triple negative breast cancer cell lines. A phosphatidylcholine lipid film was hydrated with a solution of oxidized hyaluronic acid and doxorubicin, chosen as model drug, followed by a crosslinking reaction with cystamine hydrochloride. The obtained spherical nanoparticles (mean diameter of 30 nm) were found to be efficiently internalized in cancer cells by a receptor-mediated endocytosis process, and to modulate the drug release depending on the pH and redox potential of the surrounding medium. In vitro cytotoxicity assays demonstrated the safety and efficacy of the nanoparticles in enhancing the cytotoxic effect of the free anticancer drug, with the IC50 values being reduced by two and three times in MDA-MB-468 and MDA-MB-231, respectively. The combination of self-assembled phospholipid molecules with a polysaccharide counterpart acting as receptor ligand, and stimuli-responsive chemical moieties, was carried out on smart multifunctional nanoparticles able to actively target breast cancer cells and improve the in vitro anticancer activity of doxorubicin.

Resistant Starches and Non-Communicable Disease: A Focus on Mediterranean Diet.

Resistant starch (RS) is the starch fraction that eludes digestion in the small intestine. RS is classified into five subtypes (RS1-RS5), some of which occur naturally in plant-derived foods, whereas the others may be produced by several processing conditions. The different RS subtypes are widely found in processed foods, but their physiological effects depend on their structural characteristics. In the present study, foods, nutrition and biochemistry are summarized in order to assess the type and content of RS in foods belonging to the Mediterranean Diet (MeD). Then, the benefits of RS consumption on health are discussed, focusing on their capability to enhance glycemic control. RS enters the large bowel intestine, where it is fermented by the microbiome leading to the synthesis of short-chain fatty acids as major end products, which in turn have systemic health effects besides the in situ one. It is hoped that this review will help to understand the pros of RS consumption as an ingredient of MeD food. Consequently, new future research directions could be explored for developing advanced dietary strategies to prevent non-communicable diseases, including colon cancer.

Anticancer potential of novel α,ß-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway.

Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 µM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 µM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic death in breast cancer cells, and both compounds showed no significant toxicity on healthy cells (e.g., MCF-10A) and red blood cells. An in-depth mechanistic study based on molecular biology, immunoblotting analysis and in silico docking calculations suggested that α,ß-unsaturated γ-lactam derivatives could interfere with the functioning of PI3K and PDK-1, two key enzymes in the PI3K/AKT signaling pathway, whose overactivation is related to the regulation of cell growth and survival in several malignancies.

Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes.

OBJECTIVE: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. STUDY DESIGN: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. RESULTS: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1-3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03-5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3-9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04-1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) CONCLUSION: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks', when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.

New Insights into the Antioxidant and Anti-Inflammatory Effects of Italian Salvia officinalis Leaf and Flower Extracts in Lipopolysaccharide and Tumor-Mediated Inflammation Models.

This work aimed to investigate and compare the in vitro antioxidant and anti-inflammatory effects of Salvia officinalis L. (sage) from Italy, with the aim of raising its current knowledge in this field. Leaves and flowers (S1-S8), harvested in two areas of Southern Italy, were extracted with methanol as a solvent by maceration or ultrasound-assisted extraction. Sage extracts, analysed by high pressure liquid chromatography-diode-array detection-electrospray ionization-quadrupole-mass spectroscopy (HPLC-DAD-ESI-Q-MS), exerted a promising antioxidant activity investigated using ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ß-carotene bleaching tests, and elicited a significant decrease in reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. The anti-inflammatory activity was analysed in the same in vitro model. All the extracts did not affect cell viability although they showed anti-inflammatory activity, as they induced a decrease in nitrite levels that was greater than 50%, when employed at 50 µg/mL. Furthermore, they elicited a decrease in nitrite levels, as well as a decline in pro-inflammatory cytokine expression. The NF-κB transcription factor proved to be involved in the mechanisms that underlie such effects. Interestingly, sage extracts were able to interfere with the inflammatory activity induced by breast cancer cell-conditioned media (nitrite levels were significantly decreased, p < 0.05; p < 0.01), highlighting for the first time the important role of S. officinalis in controlling inflammation processes related to neoplastic progression.

The mitochondrial aspartate/glutamate carrier (AGC or Aralar1) isoforms in D. melanogaster: biochemical characterization, gene structure, and evolutionary analysis.

BACKGROUND: In man two mitochondrial aspartate/glutamate carrier (AGC) isoforms, known as aralar and citrin, are required to accomplish several metabolic pathways. In order to fill the existing gap of knowledge in Drosophila melanogaster, we have studied aralar1 gene, orthologue of human AGC-encoding genes in this organism. METHODS: The blastp algorithm and the "reciprocal best hit" approach have been used to identify the human orthologue of AGCs in Drosophilidae and non-Drosophilidae. Aralar1 proteins have been overexpressed in Escherichia coli and functionally reconstituted into liposomes for transport assays. RESULTS: The transcriptional organization of aralar1 comprises six isoforms, three constitutively expressed (aralar1-RA, RD and RF), and the remaining three distributed during the development or in different tissues (aralar1-RB, RC and RE). Aralar1-PA and Aralar1-PE, representative of all isoforms, have been biochemically characterized. Recombinant Aralar1-PA and Aralar1-PE proteins share similar efficiency to exchange glutamate against aspartate, and same substrate affinities than the human isoforms. Interestingly, although Aralar1-PA and Aralar1-PE diverge only in their EF-hand 8, they greatly differ in their specific activities and substrate specificity. CONCLUSIONS: The tight regulation of aralar1 transcripts expression and the high request of aspartate and glutamate during early embryogenesis suggest a crucial role of Aralar1 in this Drosophila developmental stage. Furthermore, biochemical characterization and calcium sensitivity have identified Aralar1-PA and Aralar1-PE as the human aralar and citrin counterparts, respectively. GENERAL SIGNIFICANCE: The functional characterization of the fruit fly mitochondrial AGC transporter represents a crucial step toward a complete understanding of the metabolic events acting during early embryogenesis.