Chemical Characterization of Polysaccharide Extracts Obtained from Pomace By-Products of Different White Grape Varieties.

Grape pomace is one of the main by-products in the wine industry and contains some high-added-value compounds, such as polysaccharides. Considering the wide application possibilities of polysaccharides in wine and in the food industry, the revalorization of grape pomace to extract polysaccharides presents itself as an opportunity for by-product management. Therefore, the aim of this study was to characterize polysaccharide extracts obtained from pomace by-products of different white grape varieties. The type and content of polysaccharides, proteins and phenols were analyzed. Statistically significant differences were found between the varietal extracts in the types and concentrations of polysaccharides. The extracts obtained from the Verdejo and Puesta en Cruz varieties showed the highest polysaccharide purity and contents, but the type of polysaccharides was different in each case. The Verdejo provided extracts richer in non-pectic polysaccharides, while the Puesta en Cruz provided extracts richer in pectic polysaccharides. The protein and polyphenol contents were low in all extracts, below 2.5% and 3.7%, respectively. These results open up a new possibility for the revalorization of grape pomace by-products to obtain polysaccharide-rich extracts, although it would be interesting to improve both the yield and the purity of the extracts obtained by studying other extraction techniques or processes.

HPLC-MS2 Analysis of Chlorophylls in Green Teas Establishes Differences among Varieties.

Green teas are nonfermented teas, the quality of which is measured by the green color. However, this category encompasses a high number of tea varieties that differ in cultivation and processing. For example, leaf or stem/bubble tea, plants cultivated under a light or shadow regime, powdered or unpowdered tea, etc. These variables determine the different qualities among green teas (Matcha, Sencha, Gyokuro, etc.) and consequently their different values on the market. Our purpose is to determine if these variables can exert an influence on the chlorophyll profile and to establish a characteristic profile for specific green teas. With such an aim, we analyzed the chlorophyll profiles of 6 different green tea varieties via HPLC-hr ESI/APCI-MS2 and identified up to 17 different chlorophyll compounds. For the first time, 132-hydroxy-chlorophylls, 132-hydroxy-pheophytins, and 151-hydroxy-lactone-pheophytins have been identified in green teas. Shadow teas (Matcha and Sencha) and light-regimen green teas can be statistically differentiated by the total chlorophyll content and the a/b ratio. However, only Matcha tea contains a higher proportion of chlorophylls a and b among the green tea varieties analyzed, justifying the higher quality and price of this variety. Other chlorophyll metabolites (pheophytins, pyropheophytins, and oxidized chlorophylls) are indicative of the various processing and storage conditions.

The Effects of Grape Polysaccharides Extracted from Grape By-Products on the Chemical Composition and Sensory Characteristics of White Wines.

There is an increasing interest in the valorization of wine waste by-products. Grape pomace/marc can be an important source of polyphenols but also of polysaccharides (PSs). Therefore, the aim of this work was to extract PSs from grape pomace and musts and incorporate them into wines to improve their quality and valorize these residues. Two white wines were elaborated and treated with four different PS extracts obtained from white grape pomace, white must, a wine purified extract rich in RG-II, and commercial inactivated yeasts. In general, the use of grape PSs extracted from grape pomace or must improve some characteristics of wine, increasing the polysaccharide and volatile concentrations. These PS extracts can be useful to modulate some taste attributes such as an excess of acidity and bitterness and can also prevent the loss of volatile compounds associated with fruity and floral notes over time. This is the first study that shows the effects of grape polysaccharides on the chemical composition and sensory characteristics of white wines. Considering the obtained results, the grape pomace and surplus of musts can be considered valuable sources to obtain polysaccharide-rich products, opening a new opportunity to take advantage of by-products from the wine industry.

Cell proliferation and neurogenesis alterations in Alzheimer's disease and diabetes mellitus mixed murine models.

The classic neuropathological features of Alzheimer's disease (AD) are accompanied by other complications, including alterations in adult cell proliferation and neurogenesis. Moreover recent studies have shown that traditional markers of the neurogenic process, such as doublecortin (DCX), may also be expressed in CD8+ T cells and ionized calcium-binding adaptor molecule 1 (Iba1+ ) microglia, in the close proximity to senile plaques, increasing the complexity of the condition. Altered glucose tolerance, observed in metabolic alteratioins, may accelerate the neurodegenerative process and interfere with normal adult cell proliferation and neurogenesis. To further explore the role of metabolic disease in AD, we analyzed cell proliferation and neurogenesis using 5'-bromo-2'-deoxyuridine and DCX immunohistochemistry in three different mouse models of AD and metabolic alterations: APP/PS1xdb/db mice, APP/PS1 mice on a long-term high-fat diet, and APP/PS1 mice treated with streptozotozin. As reported previously, an overall reduction in cell proliferation and neurogenesis was observed after streptozotocin administration. In contrast, an increase in cell proliferation and neurogenesis was detected in neurogenic niches in 14- and 26-week-old APP/PS1xdb/db mice, accompanied by a slight increase in cortical cell proliferation. While a similar trend was observed in animals on a high-fat diet, differences were not statistically significant. We observed very few DCX+ /CD8+ cells and no DCX+ /Iba1+ cells were observed in the close proximity to senile plaques in any of the groups. Interestingly, metabolic parameters such as body weight and glucose and insulin levels were identified as reliable predictors of cell proliferation and neurogenesis in APP/PS1xdb/db mice. Furthermore, metabolic parameters were also associated with altered Aß levels in the cortex and hippocampus of APP/PS1xdb/db mice. Altogether, our data suggest that metabolic disease may also interfere with central complications in AD.

Evaluation of grape ripeness, carbonic maceration and pectolytic enzymes to improve the chemical and sensory quality of red sparkling wines.

BACKGROUND: Red sparkling wines are and innovative product for the oenology market, and oenologists are looking for technologies to improve their winemaking. The present study aimed to use both carbonic maceration and pectolytic enzymes applied to premature grapes during the winemaking of red sparkling wines. Both could modify the release of polyphenols, as well as improve the foaming, aroma and sensory properties of the wines. RESULTS: Red sparkling wines made with mature grapes showed the highest content of polyphenols, ethyl esters, alcohol acetates, total volatile acids and foam stability time. They were characterised by a high foam collar and foam area, full-body, astringency, persistence, and olfactory intensity, and were the best evaluated with respect to global perception in the sensory analysis. Treatment with pectolytic enzymes was not effective with unripe grapes. These wines showed a high content of total ethyl esters and the highest content of lactones, producing wines with high olfactory intensity and fruity aromas. Red sparkling wines made by carbonic maceration showed the lowest content of total polyphenols, anthocyanins and proanthocyanidins, as well as high contents of C6 alcohols and total ethyl esters, and were characterised by vegetal aroma notes. Both treatments produced red sparkling wines with good foam characteristics. CONCLUSION: Winemaking of red sparkling wines with premature grapes and pectinolytic enzymes or carbonic maceration did not achieve an improvement with respect to their chemical and sensory qualities. The use of mature grapes and traditional winemaking is the best option for elaborating red quality sparkling wines. © 2020 Society of Chemical Industry.

Effects of different oenological techniques on the elaboration of adequate base wines for red sparkling wine production: phenolic composition, sensory properties and foam parameters.

BACKGROUND: In red sparkling winemaking it is essential to obtain base wines with moderate alcohol content, adequate mouthfeel and color intensity. The aim of this work was to study oenological techniques to obtain adequate base wines for production of red sparkling wine by traditional methods: pre-fermentative cold maceration with dry ice and délestage with premature grapes; and sugar reduction in must and partial dealcoholisation of wine with mature grapes. The effect on oenological parameters, e.g. phenolic content, foam and sensory characteristics, was studied in sparkling wines aged on the lees in bottles for 9 months followed by aging for12 months in bottles after disgorging. RESULTS: Pre-fermentative cold maceration was the only treatment that increased the content of anthocyanins in sparkling wines at both stages of aging. Sparkling wines elaborated using délestage showed the highest mean values of the degree of polymerization of proanthocyanidins. Sparkling wines from mature grapes were given higher valuation in the gustatory phase. Sparkling wines elaborated using pre-fermentative cold maceration were given the highest valuation for foam quality. CONCLUSIONS: Pre-fermentative cold maceration is a viable alternative to common techniques for increasing the anthocyanin content in wines from premature grapes. It would therefore be a good option to obtain adequate base wines. © 2019 Society of Chemical Industry.

Lifestyle Factors in Myopic Spanish Children.

BACKGROUND: Childhood myopia represents a global concern with increasing prevalence in recent decades. Lifestyle factors significantly impact myopia. AIM: To evaluate lifestyle factors in myopic children from a metropolitan area in Europe. METHODS: This was a descriptive study including myopic subjects aged 4-18 years. Patient demographic and clinical data were collected, including cycloplegic refraction in spherical equivalent refraction (SER) and axial length (AL). In addition, a questionnaire on lifestyle factors was conducted between September 2022 and April 2023. RESULTS: A total of 321 myopic children were included, aged 10.72 ± 3.05 years, of whom 51.4% were boys, with SER -2.25 ± 1.9 D and AL 24.54 ± 0.98 mm. The mean age of myopia onset was 7.69 ± 3.05 years. A total of 59.8% had family history of myopia. Those children who had <2 h/day of screen time (on weekdays) presented SER -2 ± 1.91 D, compared to those who had >2 h/day, SER: -2.50 ±1.88 D (p = 0.009). Children who spent <2 h/day doing near work after school were less myopic compared to those who spent >2 h/day (SER: -1.75 ± 1.83 vs. SER: -2.75 ± 1.82, respectively, p = 0.03). However, no significant association was observed between SER and AL and time spent outdoors nor between SER and AL and academic performance (p > 0.05). CONCLUSIONS: Screen time and near-work time appear to be lifestyle factors related to myopia.

Study of the authentic composition of the novel green foods: Food colorants and coloring foods.

The clean label approach is behind the development of the new concept, coloring food, in contrast to regulated food colorants, although few data are available regarding its composition. Consequently, twenty-six commercial green foods (including novel foods) have been analyzed to investigate the authentic composition behind the different labels. It has been identified by HPLC-ESI/APCI-hrTOF-MS2 the complete array of chlorophylls in the regulated green food colorants, several of them identified for the first time in foods. The coloring food alternative is based on mixing blue (such as spirulina) and yellow (such as safflower) hues. Our data suggest that in the analyzed samples, spirulina is water or solvent extracted before being added to the food. The obtained results showed for the first time, the authentic data on the chemical composition of the new green foods.

Occurrence and Exposure Assessment of Major Mycotoxins in Foodstuffs from Algeria.

Cereal-based products, nuts and dried fruits are staple foods for the Algerian population. However, these foodstuffs may be sources of harmful mycotoxins, with negative impacts on human health. The purpose of this study was to investigate the occurrences and levels of aflatoxins (B1, B2, G1 and G2), ochratoxin A (OTA), deoxynivalenol (DON) and zearalenone (ZEA) in 198 samples of nuts, dried fruits and cereal products commercialized in Algeria, as well as to calculate the estimated daily intakes (EDIs). Aflatoxins were found in 26.2% of the nut samples (in peanuts and almonds, but not in walnuts), 38.7% of the dried fruit samples (in dried figs, dates and bradj pastries) and 47.9% of the cereal-based products (in rechta noodles and metlou bread, but not in couscous), with mean concentrations ranging from 0.03 to 0.49 µg/kg. OTA occurred in 16.9% of the cereal-based samples, averaging 0.15 µg/kg, but it was not detected in nuts or dried fruits. The incidence of DON in the cereal-based products was 85.9% on average, with a mean concentration from 90 to 123 µg/kg. ZEA mycotoxin was not detected in any samples. Four peanut samples exceeded the EU maximum level for aflatoxin B1 set at 2 µg/kg, while three of them surpassed the maximum level for the sum of aflatoxins (4 µg/kg). Traditional foods such as bradj, rechta and metlou were significant sources of aflatoxins, with MOE (margin of exposure) values ranging from 648 to 9333, indicating a potential risk for the Algerian population.

Antifungal Activity of Menthol, Eugenol and Their Combination against Aspergillus ochraceus and Aspergillus niger In Vitro and in Stored Cereals.

Aspergillus ochraceus and Aspergillus niger are spoilage and mycotoxin-producing fungi that can contaminate agricultural commodities and derived products. In the present study, menthol, eugenol, and their combination (mix 1:1) were tested to determine their contact and fumigation toxicity against the two fungi. Menthol, eugenol, and their mixture significantly reduced mycelial growth and spore germination at concentrations from 300 to 600 µg/mL, and the inhibitory effects showed clear dose dependence. The minimum inhibitory concentration (MIC) values against A. ochraceus were 500 µg/mL (menthol), 400 µg/mL (eugenol), and 300 µg/mL (mix 1:1), while the MIC values for A. niger were 500 µg/mL (menthol), 600 µg/mL (eugenol), and 400 µg/mL (mix 1:1). Additionally, the analyzed compounds exhibited more than 50% protection against A. ochraceus and A. niger by fumigation of stored cereal grains (maize, barley, and rice) in sealed containers. The binary mixture of menthol and eugenol showed synergistic effects against both fungi in both in vitro direct contact and stored grain fumigation trials. The results of the present study provide a scientific basis for the application of a combination of natural antifungals in food preservation.

The Effects of Aflatoxin B1 Intake in Assaf Dairy Ewes on Aflatoxin M1 Excretion, Milk Yield, Haematology and Biochemical Profile.

The aim of this study was to investigate the in vivo transfer of aflatoxin B1 (AFB1) to Assaf ewes' milk (aflatoxin M1, AFM1) and its effect on animal performance and health. Thirty Assaf ewes were allocated to three groups (C, L, H), and received a different individual daily dose of AFB1 (0, 40 and 80 µg) for 13 days. Milk (days 1, 2, 3, 4, 7, 14, 16 and 18) and blood (days 1, 7, 14 and 18) samples were collected. Milk yield, composition (except protein) and somatic cell counts (SCC) were not affected by AFB1 intake (p > 0.05). Haemoglobin concentration increased (p < 0.05) and haematocrit and alanine aminotransferase levels tended to increase (p < 0.10) in group H on day 14. AFM1 excretion was highly variable and detected in L and H animals from days 1 to 16 (3 days increase, 10 days steady-state, 3 days clearance). Carry-over rate (0.23%) was significantly higher in L (0.22-0.34%) than in H (0.16-0.19%) animals (p < 0.05). AFB1 daily doses of 40 to 80 µg do not impair milk yield; however, it may start affecting animals' health. Milk AFM1 depends mainly on the AFB1 intake whereas carryover rate is positively influenced by the level of milk production.

Influence of food composition on chlorophyll bioaccessibility.

Chlorophylls are ingested and effectively absorbed by our organism daily, but the effect of food composition on its bioaccessibility is unknown. Therefore, the present research analyses the chlorophyll bioaccessibility of ten commercial foods (guacamole, virgin olive oil, tortellini, basil hummus, creamed spinach, vegetable pasta, green tea chocolate, avocado and kiwi juices, and pesto sauce), selected based on their different nutritional (fat, fiber, protein, and carbohydrates) and chlorophyll composition and content. The most unexpected result was to correlate chlorophyll degradation during in vitro digestion with the salt content of the digested food. Surprisingly, independently of the foods' nutritional composition or the chlorophyll content, the chlorophyll profile after in vitro digestion was formed by 90% pheophytins and 10% chlorophylls and pheophorbides. Such a pattern can only be modified when the ingested food contains a high proportion of pheophorbides (˃20%) that prevailed up to the mixed micelles.

Inhibition of Aspergillus Parasiticus Growth and Aflatoxins Production by Natural Essential Oils and Phenolic Acids.

Aflatoxins represent a significant risk to food safety, and strategies are being implemented to reduce their entry into the food chain. The aim of this study was to evaluate the in vitro effect of four essential oils (EOs) (lavandins Grosso and Abrial, Origanum virens, and Rosmarinus officinalis) and four natural phenolic acids (PAs) (caffeic, chlorogenic, ferulic, and p-coumaric) on the growth and aflatoxins (B1, B2, G1, and G2) production by Aspergillus parasiticus. Minimal inhibitory concentration (MIC) and minimal fungicide concentration (MFC) were determined by the broth macrodilution method. Additionally, the mycelia weight was determined at concentration levels lower than MIC. The antiaflatoxigenic activity was evaluated in the two concentrations of the EOs right before MIC and at concentrations below the MIC value for the PAs. To this end, in-house validated methodology based on high-performance liquid chromatography with post-column photochemical derivatization and fluorescence detection (HPLC-PHRED-FLD) was used. EOs of O. virens and lavandins (Grosso and Abrial) completely inhibited mold growth. In addition, a significant reduction in mycelial mass (p < 0.05) was observed for all EOs and PAs at different concentrations. In all cases except for lavandin Abrial, EO concentrations just before the MIC value strongly reduced (p < 0.05) aflatoxins synthesis. Aflatoxins production was completely inhibited by all PAs at a concentration of 20 mM; although at low concentrations, mycotoxin production was stimulated in some cases. The present study provides a scientific basis for further study of the inhibiting mechanisms.

Biomarkers of Exposure to Zearalenone in In Vivo and In Vitro Studies.

The measurement of human exposure to mycotoxins is necessary for its association with adverse health effects. This exposure is usually estimated from contamination levels of foodstuffs, which are the primary source of toxin exposure, and data on food consumption patterns. However, variations in contamination level, intestinal absorption, toxin distribution, and excretion lead to individual variations in toxin exposure that can be more readily measured with a biomarker. This review deals with the latest literature information about ZEN biomarkers in humans, animals, and cell line cultures. Their presence in urine, biomarkers that have effects in the kidney, liver, reproductive system and blood and biomarkers of cell response have been reported. It has highlighted the importance of determining α-zearalenol and ß-zearalenol biomarkers to estimate the probable dietary intake (PDI) of a specific population or to characterize the severity of exposure to ZEN in animals or cell lines. α-ZEL and ß-ZEL are cytotoxic by inhibiting cell proliferation, total protein and DNA syntheses, in this sense, an induction of expression proteins Hsp27 and Hsp70 was observed, and an increase in gene expression (TLR4, NF-kBp65, TNF-α, IL-1ß, IL-6, IL-8, MGMT, α-GST, Hsp70, Nrf2, L-Fabp, HO-1, MAPK8), the determination of which indicates an oxidative stress effect. The integrity of the cell or tissue membrane is assessed by lactate dehydrogenase (LDH), which increase at exposure of ZEN (84.2 µM), and the proportions of some fatty acids of the renal tissue membrane were increased at treatments with ZEN. This review allows starting future studies of animal and population exposure in parallel with those of health effects works.

In Vitro Bioaccessibility Protocol for Chlorophylls.

The daily ingestion of chlorophylls has been estimated at 50 g, but the knowledge about their bioaccessibility is limited. Different in vitro models have been utilized to estimate their potential bioavailability, but among other factors, the diversity of structures, chemical properties, and lability of chlorophylls hamper the investigations. By the first time, three extreme food matrices, one rich in fiber (vegetable puree), one rich in fat (virgin olive oil), and one liquid (fruit juice), have been assayed for chlorophyll bioaccessibility, controlling crucial variables. Chlorophyll polarity and food matrix were the determining factors, but surprisingly, chlorophyll bioaccessibility was affected during the application of the in vitro standardized protocol. Therefore, the present research has identified the reactions that can be biased during the estimation of chlorophyll bioaccessibility, defining a specific protocol in the function of chlorophyll structures.

Field Monitoring of Aflatoxins in Feed and Milk of High-Yielding Dairy Cows under Two Feeding Systems.

Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 (AFB1) that can be excreted in milk of cows after consuming contaminated feed. The aim of this study consisted of a field monitoring to assess the contamination levels of AFB1 in 60 feed samples from two feeding systems for high-yielding dairy cows and of AFM1 in the corresponding raw milk samples. The aflatoxins were analyzed by in-house validated methods based on high-performance liquid chromatography (HPLC) with fluorescence detection. AFB1 was detected in 55% of feed samples (mean 0.61 µg/kg, with 2 samples exceeding the European Union (EU) maximum level set at 5 µg/kg), with greater incidence and concentration in compound feed than in unifeed rations (p < 0.05). AFM1 was detected in 38.3% milk samples (mean 12.6 ng/kg, with 5 samples exceeding the EU maximum level set at 50 ng/kg), with a higher occurrence in milk of cows fed compound feed, as well as in spring milk compared to that produced in winter. The overall transfer ratio of aflatoxins from feed to milk was 3.22%, being higher in cows fed with compound feed and in spring milkings. In a selection of positive matched samples (n = 22), the ratio AFM1/AFB1 exceeded the European Food Safety Authority (EFSA) estimated 6% threshold for high-yielding dairy cows.

Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer's Disease and Type 2 Diabetes.

Alzheimer's disease is the most common form of dementia, and epidemiological studies support that type 2 diabetes (T2D) is a major contributor. The relationship between both diseases and the fact that Alzheimer's disease (AD) does not have a successful treatment support the study on antidiabetic drugs limiting or slowing down brain complications in AD. Among these, liraglutide (LRGT), a glucagon-like peptide-1 agonist, is currently being tested in patients with AD in the Evaluating Liraglutide in Alzheimer's Disease (ELAD) clinical trial. However, the effects of LRGT on brain pathology when AD and T2D coexist have not been assessed. We have administered LRGT (500 µg/kg/day) to a mixed murine model of AD and T2D (APP/PS1xdb/db mice) for 20 weeks. We have evaluated metabolic parameters as well as the effects of LRGT on learning and memory. Postmortem analysis included assessment of brain amyloid-ß and tau pathologies, microglia activation, spontaneous bleeding and neuronal loss, as well as insulin and insulin-like growth factor 1 receptors. LRGT treatment reduced glucose levels in diabetic mice (db/db and APP/PS1xdb/db) after 4 weeks of treatment. LRGT also helped to maintain insulin levels after 8 weeks of treatment. While we did not detect any effects on cortical insulin or insulin-like growth factor 1 receptor m-RNA levels, LRGT significantly reduced brain atrophy in the db/db and APP/PS1xdb/db mice. LRGT treatment also rescued neuron density in the APP/PS1xdb/db mice in the proximity (p = 0.008) far from amyloid plaques (p < 0.001). LRGT reduced amyloid plaque burden in the APP/PS1 animals (p < 0.001), as well as Aß aggregates levels (p = 0.046), and tau hyperphosphorylation (p = 0.009) in the APP/PS1xdb/db mice. Spontaneous bleeding was also ameliorated in the APP/PS1xdb/db animals (p = 0.012), and microglia burden was reduced in the proximity of amyloid plaques in the APP/PS1 and APP/PS1xdb/db mice (p < 0.001), while microglia was reduced in areas far from amyloid plaques in the db/db and APP/PS1xdb/db mice (p < 0.001). This overall improvement helped to rescue cognitive impairment in AD-T2D mice in the new object discrimination test (p < 0.001) and Morris water maze (p < 0.001). Altogether, our data support the role of LRGT in reduction of associated brain complications when T2D and AD occur simultaneously, as regularly observed in the clinical arena.

Vorinostat interferes with the signaling transduction pathway of T-cell receptor and synergizes with phosphoinositide-3 kinase inhibitors in cutaneous T-cell lymphoma.

BACKGROUND: Vorinostat (suberoylanilide hydroxamic acid, SAHA), an inhibitor of class I and II histone deacetylases, has been approved for the treatment of cutaneous T-cell lymphoma. In spite of emerging information on the effect of vorinostat in many types of cancer, little is yet known about this drug's mechanism of action, which is essential for its proper use in combination therapy. We investigated alterations in gene expression profile over time in cutaneous T-cell lymphoma cells treated with vorinostat. Subsequently, we evaluated inhibitors of PI3K, PIM and HSP90 as potential combination agents in the treatment of cutaneous T-cell lymphoma. DESIGN AND METHODS: The genes significantly up- or down-regulated by vorinostat over different time periods (2-fold change, false discovery rate corrected P value<0.05) were selected using the short-time series expression miner. Cell viability was assessed in vitro in cutaneous T-cell lymphoma cells through measuring intracellular ATP content. Drug interactions were analyzed by the combination index method with CalcuSyn software. RESULTS: The functional analysis suggests that vorinostat modifies signaling of T-cell receptor, MAPK, and JAK-STAT pathways. The phosphorylation studies of ZAP70 (Tyr319, Tyr493) and its downstream target AKT (Ser473) revealed that vorinostat inhibits phosphorylation of these kinases. With regards to effects on cutaneous T-cell lymphoma cells, combining vorinostat with PI3K inhibitors resulted in synergy while cytotoxic antagonism was observed when vorinostat was combined with HSP90 inhibitor. CONCLUSIONS: These results demonstrate the potential targets of vorinostat, underlining the importance of T-cell receptor signaling inhibition following vorinostat treatment. Additionally, we showed that combination therapies involving histone deacetylase inhibitors and inhibitors of PI3K are potentially efficacious for the treatment of cutaneous T-cell lymphoma.

Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes.

BACKGROUND: Both Alzheimer's disease (AD) and type 2 diabetes (T2D) share common pathological features including inflammation, insulin signaling alterations, or vascular damage. AD has no successful treatment, and the close relationship between both diseases supports the study of antidiabetic drugs to limit or slow down brain pathology in AD. Empagliflozin (EMP) is a sodium-glucose co-transporter 2 inhibitor, the newest class of antidiabetic agents. EMP controls hyperglycemia and reduces cardiovascular comorbidities and deaths associated to T2D. Therefore, we have analyzed the role of EMP at the central level in a complex mouse model of AD-T2D. METHODS: We have treated AD-T2D mice (APP/PS1xdb/db mice) with EMP 10 mg/kg for 22 weeks. Glucose, insulin, and body weight were monthly assessed. We analyzed learning and memory in the Morris water maze and the new object discrimination test. Postmortem brain assessment was conducted to measure brain atrophy, senile plaques, and amyloid-ß levels. Tau phosphorylation, hemorrhage burden, and microglia were also measured in the brain after EMP treatment. RESULTS: EMP treatment helped to maintain insulin levels in diabetic mice. At the central level, EMP limited cortical thinning and reduced neuronal loss in treated mice. Hemorrhage and microglia burdens were also reduced in EMP-treated mice. Senile plaque burden was lower, and these effects were accompanied by an amelioration of cognitive deficits in APP/PS1xdb/db mice. CONCLUSIONS: Altogether, our data support a feasible role for EMP to reduce brain complications associated to AD and T2D, including classical pathological features and vascular disease, and supporting further assessment of EMP at the central level.

Occurrence and Exposure Assessment of Aflatoxins and Deoxynivalenol in Cereal-Based Baby Foods for Infants.

Aflatoxins are carcinogenic to humans and deoxynivalenol causes digestive disorders, and both mycotoxins occur frequently in cereal-based foods. The purpose of this study was to investigate the occurrence and levels of aflatoxins (B1, B2, G1 and G2) and deoxynivalenol (DON) in cereal-based baby foods as well as to calculate the estimated daily intakes (EDI) in different stages of infancy. Sixty samples of infant cereals (wheat-, corn-, rice-, oat-, and mixed grain-based) were collected during a 2-year period and analyzed by validated methods. Aflatoxins were detected in 12 samples (20%), six of which exceeded the EU maximum level for aflatoxin B1 set at 0.10 µg/kg. Deoxynivalenol appeared in 20% of baby food samples, with one sample exceeding the EU maximum level established at 200 µg/kg. There were no significant differences between gluten-free products for babies aged 4⁻6 months and multi-cereal products for infants aged 7⁻12 months, nor between whole-grain-based and refined ingredients. However, baby food products of organic origin showed significantly higher levels of deoxynivalenol than conventional ones (p < 0.05). It is proposed for the health protection of infants and young children, a vulnerable group, to establish the lowest maximum level for the sum of aflatoxins (B1, B2, G1 and G2) in baby food.