A Diet Containing Rutin Ameliorates Brain Intracellular Redox Homeostasis in a Mouse Model of Alzheimer's Disease.

Quercetin has been studied extensively for its anti-Alzheimer's disease (AD) and anti-aging effects. Our previous studies have found that quercetin and in its glycoside form, rutin, can modulate the proteasome function in neuroblastoma cells. We aimed to explore the effects of quercetin and rutin on intracellular redox homeostasis of the brain (reduced glutathione/oxidized glutathione, GSH/GSSG), its correlation with ß-site APP cleaving enzyme 1 (BACE1) activity, and amyloid precursor protein (APP) expression in transgenic TgAPP mice (bearing human Swedish mutation APP transgene, APPswe). On the basis that BACE1 protein and APP processing are regulated by the ubiquitin-proteasome pathway and that supplementation with GSH protects neurons from proteasome inhibition, we investigated whether a diet containing quercetin or rutin (30 mg/kg/day, 4 weeks) diminishes several early signs of AD. Genotyping analyses of animals were carried out by PCR. In order to determine intracellular redox homeostasis, spectrofluorometric methods were adopted to quantify GSH and GSSG levels using o-phthalaldehyde and the GSH/GSSG ratio was ascertained. Levels of TBARS were determined as a marker of lipid peroxidation. Enzyme activities of SOD, CAT, GR, and GPx were determined in the cortex and hippocampus. ΒACE1 activity was measured by a secretase-specific substrate conjugated to two reporter molecules (EDANS and DABCYL). Gene expression of the main antioxidant enzymes: APP, BACE1, a Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), caspase-3, caspase-6, and inflammatory cytokines were determined by RT-PCR. First, overexpression of APPswe in TgAPP mice decreased GSH/GSSG ratio, increased malonaldehyde (MDA) levels, and, overall, decreased the main antioxidant enzyme activities in comparison to wild-type (WT) mice. Treatment of TgAPP mice with quercetin or rutin increased GSH/GSSG, diminished MDA levels, and favored the enzyme antioxidant capacity, particularly with rutin. Secondly, both APP expression and BACE1 activity were diminished with quercetin or rutin in TgAPP mice. Regarding ADAM10, it tended to increase in TgAPP mice with rutin treatment. As for caspase-3 expression, TgAPP displayed an increase which was the opposite with rutin. Finally, the increase in expression of the inflammatory markers IL-1ß and IFN-γ in TgAPP mice was lowered by both quercetin and rutin. Collectively, these findings suggest that, of the two flavonoids, rutin may be included in a day-to-day diet as a form of adjuvant therapy in AD.

Proanthocyanidins: Impact on Gut Microbiota and Intestinal Action Mechanisms in the Prevention and Treatment of Metabolic Syndrome.

The metabolic syndrome (MS) is a cluster of risk factors, such as central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, which increase the probability of causing premature mortality. The consumption of high-fat diets (HFD), normally referred to high-saturated fat diets, is a major driver of the rising incidence of MS. In fact, the altered interplay between HFD, microbiome, and the intestinal barrier is being considered as a possible origin of MS. Consumption of proanthocyanidins (PAs) has a beneficial effect against the metabolic disturbances in MS. However, there are no conclusive results in the literature about the efficacy of PAs in improving MS. This review allows a comprehensive validation of the diverse effects of the PAs on the intestinal dysfunction in HFD-induced MS, differentiating between preventive and therapeutic actions. Special emphasis is placed on the impact of PAs on the gut microbiota, providing a system to facilitate comparison between the studies. PAs can modulate the microbiome toward a healthy profile and strength barrier integrity. Nevertheless, to date, published clinical trials to verify preclinical findings are scarce. Finally, the preventive consumption of PAs in MS-associated dysbiosis and intestinal dysfunction induced by HFD seems more successful than the treatment strategy.

Whole Alga, Algal Extracts, and Compounds as Ingredients of Functional Foods: Composition and Action Mechanism Relationships in the Prevention and Treatment of Type-2 Diabetes Mellitus.

Type-2 diabetes mellitus (T2DM) is a major systemic disease which involves impaired pancreatic function and currently affects half a billion people worldwide. Diet is considered the cornerstone to reduce incidence and prevalence of this disease. Algae contains fiber, polyphenols, ω-3 PUFAs, and bioactive molecules with potential antidiabetic activity. This review delves into the applications of algae and their components in T2DM, as well as to ascertain the mechanism involved (e.g., glucose absorption, lipids metabolism, antioxidant properties, etc.). PubMed, and Google Scholar databases were used. Papers in which whole alga, algal extracts, or their isolated compounds were studied in in vitro conditions, T2DM experimental models, and humans were selected and discussed. This review also focuses on meat matrices or protein concentrate-based products in which different types of alga were included, aimed to modulate carbohydrate digestion and absorption, blood glucose, gastrointestinal neurohormones secretion, glycosylation products, and insulin resistance. As microbiota dysbiosis in T2DM and metabolic alterations in different organs are related, the review also delves on the effects of several bioactive algal compounds on the colon/microbiota-liver-pancreas-brain axis. As the responses to therapeutic diets vary dramatically among individuals due to genetic components, it seems a priority to identify major gene polymorphisms affecting potential positive effects of algal compounds on T2DM treatment.

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0-700 µM). Colostrum co-treated with DEX was executed at 0.1-5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

Polypharmacy and Drug-Drug Interactions in People Living With Human Immunodeficiency Virus in the Region of Madrid, Spain: A Population-Based Study.

BACKGROUND: Drug-drug interactions (DDIs) that involve antiretrovirals (ARVs) tend to cause harm if unrecognized, especially in the context of comorbidity and polypharmacy. METHODS: A linkage was established between the drug dispensing registry of Madrid and the Liverpool human immunodeficiency virus (HIV) DDI database (January 2017-June 2017). Polypharmacy was defined as the use of ≥5 non-HIV medications, and DDIs were classified by a traffic-light ranking for severity. RESULTS: A total of 22 945 people living with HIV (PLWH) and 6 613 506 individuals without HIV had received medications. ARV regimens were predominantly based on integrase inhibitors (51.96%). Polypharmacy was higher in PLWH (32.94%) than individuals without HIV (22.16%; P < .001); this difference was consistently observed across all age strata except for individuals ≥75 years. Polypharmacy was more common in women than men in both PLWH and individuals without HIV. The prevalence of contraindicated combinations involving ARVs was 3.18%. Comedications containing corticosteroids, quetiapine, or antithrombotic agents were associated with the highest risk for red-flag DDI, and the use of raltegravir- or dolutegravir-based antiretroviral therapy was associated with an adjusted odds ratio of 0.72 (95% confidence interval, .60-.88; P = .001) for red-flag DDI. CONCLUSIONS: Polypharmacy was more frequent among PLWH across all age groups except those aged ≥75 years and was more common in women. The detection of contraindicated medications in PLWH suggests a likely disconnect between hospital and community prescriptions. Switching to alternative unboosted integrase regimens should be considered for patients with risk of harm from DDIs.

Antioxidant and Hepatoprotective Effects of Croton hypoleucus Extract in an Induced-Necrosis Model in Rats.

The aim of this study was to evaluate the antioxidant and hepatoprotective activity of Croton hypoleucus (EC). The present work reports the first pharmacological, toxicological, and antioxidant studies of EC extract on liver injury. Liver necrosis was induced by thioacetamide (TAA). Five groups were established: Croton Extract (EC), thioacetamide (TAA), Croton extract with thioacetamide (EC + TAA), vitamin E with thioacetamide (VE + TAA) and the positive control and vehicle (CT). For EC and EC + TAA, Wistar rats (n = 8) were intragastrically pre-administered for 4 days with EC (300 mg/kg.day) and on the last day, EC + TAA received a single dose of TAA (400 mg/kg). At 24 h after damage induction, animals were sacrificed. In vitro activity and gene expression of superoxide dismutase (SOD), catalase (Cat), and Nrf2 nuclear factor were measured. The results show that EC has medium antioxidant properties, with an IC50 of 0.63 mg/mL and a ferric-reducing power of 279.8 µM/mg. Additionally, EC reduced hepatic damage markers at 24 h after TAA intoxication; also, it increased SOD and Cat gene expression against TAA by controlling antioxidant defense levels. Our findings demonstrated the hepatoprotective effect of EC by reducing hepatic damage markers and controlling antioxidant defense levels. Further studies are necessary to identify the mechanism of this protection.

Experience With the Use of Rituximab for the Treatment of Rheumatoid Arthritis in a Tertiary Hospital in Spain: RITAR Study.

BACKGROUND/OBJECTIVE: There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions. METHODS: Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration. RESULTS: A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7-13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration. CONCLUSIONS: Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therapy.

Silicon Alleviates Nonalcoholic Steatohepatitis by Reducing Apoptosis in Aged Wistar Rats Fed a High-Saturated Fat, High-Cholesterol Diet.

Background: Lipoapoptosis has been identified as a key event in the progression of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have been recommended as a possible effective treatment for nonalcoholic steatohepatitis (NASH). Silicon, included in meat as a functional ingredient, improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a high-saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the antiapoptotic effect of this potential functional meat on the liver has never been tested.Objective: This study was designed to evaluate the effect of silicon on NASH development and the potential antiapoptotic properties of silicon in aged rats.Methods: One-year-old male Wistar rats weighing ∼500 g were fed 3 experimental diets containing restructured pork (RP) for 8 wk: 1) a high-saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g cholesterol/kg diet, and 46.8 mg SiO2/kg (control); 2) the HSHCD as a model of NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO2/kg [high-cholesterol diet (Chol-C)]; and 3) the HSHCD with silicon-supplemented RP with amounts of fat and cholesterol identical to those in the Chol-C diet, but with 750 mg SiO2/kg (Chol-Si). Detailed histopathological assessments were performed, and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage markers were evaluated by Western blotting and immunohistochemical staining.Results: Chol-C rats had a higher mean NAS (7.4) than did control rats (1.9; P < 0.001). The score in Chol-Si rats (5.4) was intermediate and different from that in both other groups (P < 0.05). Several liver apoptosis markers-including hepatocyte terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling, cytosolic cytochrome c, apoptosis-inducing factor, caspases 9 and 3, and the mitochondrial Bcl-2-associated X protein (BAX)-to-B-cell lymphoma 2 (BCL2) ratio-were 9-45% lower in Chol-Si than in Chol-C rats (P < 0.05) and did not differ from values in the control group.Conclusions: Supplemental silicon substantially affects NASH development in aged male Wistar rats fed an HSHCD by partially blocking apoptosis. These results suggest that silicon-enriched RP could be used as an effective nutritional strategy in preventing NASH.

Bioaccessibility of hydroxytyrosol and n-3 fatty acids as affected by the delivery system: simple, double and gelled double emulsions.

This study examines the influence of different food-grade n-3 PUFA-enriched simple emulsion (SE), double emulsion (DE) and gelled double emulsion (GDE) delivery systems on the extent of lipolysis, antioxidant capacity and the bioaccessibility of hydroxytyrosol (HTy). GDE emulsion offered better protection for HTy (89%) than the other systems (79% in SE and DE). The reducing capacity of the emulsions containing HTy were not altered during oral digestion. However, "in vitro" gastric and intestinal phases significantly reduced the antioxidant activity of all systems. The structural and physical state of GDE entailed a slowing-down of triacylglyceride hydrolysis (36.4%) in comparison with that of SE and DE (22.7 and 24.8% for SE and DE, respectively).

The Impact of CXCR4 Blockade on the Survival of Rat Brain Cortical Neurons.

BACKGROUND: Chemokine receptor type 4 (CXCR4) plays a role in neuronal survival/cell repair and also contributes to the progression of cancer and neurodegenerative diseases. Chemokine ligand 12 (CXCL12) binds to CXCR4. In this study, we have investigated whether CXCR4 blockade by AMD3100 (a CXCR4 antagonist, member of bicyclam family) may affect neuronal survival in the absence of insult. Thus, we have measured the mitochondrial membrane potential (MMP), Bax and Bcl-2 protein translocation, and cytochrome c release in AMD3100-treated brain cortical neurons at 7 DIV (days in vitro). METHODS: For this aim, AMD3100 (200 nM) was added to cortical neurons for 24 h, and several biomarkers like cell viability, reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release, caspase-3/9 activity, proteins Bax and Bcl-2 translocation, and cytochrome c release were analyzed by immunoblot. RESULTS: CXCR4 blockade by AMD3100 (200 nM, 24 h) induces mitochondrial hyperpolarization and increases caspase-3/9 hyperpolarization without affecting LDH release as compared to untreated controls. AMD3100 also increases cytochrome c release and promotes Bax translocation to the mitochondria, whereas it raises cytosolic Bcl-2 levels in brain cortical neurons. CONCLUSION: CXCR4 blockade induces cellular death via intrinsic apoptosis in rat brain cortical neurons in absence of insult.

Silicon-Enriched Restructured Pork Affects the Lipoprotein Profile, VLDL Oxidation, and LDL Receptor Gene Expression in Aged Rats Fed an Atherogenic Diet.

BACKGROUND: Research has shown that silicon can play an important role in protecting against degenerative diseases. Restructuring pork by partially disassembling meat permits the incorporation of active components with potential functional effects. However, there has been no research to date on the impact that silicon, as a functional ingredient in restructured pork (RP), has on lipoprotein composition, metabolism, and oxidation. OBJECTIVE: This study was designed to evaluate the effect of silicon-enriched RP on lipemia, lipoprotein profile, and oxidation markers of aged rats fed high-fat, high-energy, cholesterol-enriched diets. METHODS: RP samples similar to commercial sausages (16% protein and 22% fat, wt:wt) were prepared by mixing lean pork and lard alone or with silicon (1.3 g Si/kg fresh matter) under controlled conditions and then freeze-dried. Saturated fat-rich diets were designed by mixing 78.3% purified diet with 21.7% freeze-dried RP. Three groups composed of 8 aged male Wistar rats (1 y old) were fed for 8 wk a control RP (C) diet, a cholesterol-enriched RP (Chol-C) diet [C diet enriched with 1.26% cholesterol plus 0.25% cholic acid, or a cholesterol and silicon-enriched RP (Chol-Si) diet (same as the Chol-C diet but containing silicon)]. Plasma lipid concentrations, lipoprotein profile, the degree of VLDL oxidation, and LDL receptor gene (Ldlr) expression were tested. RESULTS: Compared with the C diet, the Chol-C diet did not modify food intake or body weight but significantly increased (P < 0.05) plasma cholesterol (32%) and total lipids (19%), VLDL and intermediate density lipoprotein + LDL cholesterol (both >600%), total lipids and proteins (both >300%), and the degree of VLDL oxidation [conjugated dienes >250%; thiobarbituric acid-reactive substance (TBARS), 900%] and reduced Ldlr expression (64%) and liver arylesterase activity (54%). The Chol-Si diet partially normalized changes induced by the Chol-C diet. Compared with the Chol-C group, Chol-Si rats had lower VLDL compound concentrations (P < 0.001; e.g., 75% less VLDL cholesterol) and VLDL oxidation (65% less conjugated dienes and 85% less TBARS) but greater Ldlr expression (200%). CONCLUSIONS: Silicon added to RP strongly counterbalanced the negative effect of high-cholesterol-ingestion, functioning as an active hypocholesterolemic, hypolipemic, and antioxidative dietary ingredient in aged rats.

Organic silicon protects human neuroblastoma SH-SY5Y cells against hydrogen peroxide effects.

BACKGROUND: Hydrogen peroxide (H2O2) is a toxic agent that induces oxidative stress and cell death. Silicon (Si) is a biological element involved in limiting aluminium (Al) absorption with possible preventive effects in Alzheimer's disease. However, Si has not yet been associated with other neuroprotective mechanisms. METHODS: The present experiments evaluated in the SH-SY5Y human neuroblastoma cell line the possible role of different Si G5 (50-1000 ng/mL) concentrations in preventing cellular death induced by H2O2 (400 µM, 24 hours). RESULTS: Our findings showed that H2O2 promoted cell death in the human SH-SY5Y cell cultures and this could be prevented by Si treatment. The loss in cell viability mediated by H2O2 was due to an apoptotic and necrotic process. Apoptotic death was incurred by regulating caspase-8 activity in the extrinsic pathway. The apoptotic and necrotic cell death induced by H2O2 was almost totally reversed by Si (50-500 ng/mL), indicating that it down-regulates both processes in H2O2 treated cells. CONCLUSIONS: According to our data, Si is able to increase SH-SY5Y cell survival throughout partially blocking cellular damage related to oxidative stress through a mechanism that would affect H2O2/ROS elimination.

Silicon-enriched meat positively improves plasma lipidaemia and lipoproteinaemia, LDLr, and insulin capability and the signalling pathway induced by an atherogenic diet in late-stage type 2 diabetes mellitus rats.

The impact of silicon as a functional ingredient in restructured meat (RM) on lipoprotein composition, metabolism, and oxidation on type 2 diabetes mellitus (T2DM) markers has never been studied. This study aims to evaluate the effect of silicon-enriched-meat consumption on lipidaemia, lipoprotein profile and metabolism, plasma arylesterase, and TBARS and their relationships with glycaemia, insulinaemia, and insulin-signaling markers in late-stage-T2DM rats fed a high-saturated-fat-high-cholesterol (HSFHC) diet. Saturated-fat diets with or without added cholesterol were formulated by mixing a 70% purified diet with 30% freeze-dried RM with or without added silicon. Three groups of seven Wistar rats each were tested. The ED group received the control RM in the framework of a high-saturated-fat diet as early-stage T2DM control. The other two groups received streptozotocin-nicotinamide administration together with the HSFHC diet containing the control RM (LD) or silicon-enriched RM (LD-Si). Scores were created to define the diabetic trend and dyslipidaemia. The ED rats showed hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, and triglyceride-rich-VLDLs, suggesting they were in early-stage T2DM. LD rats presented hyperglycaemia, hypoinsulinaemia, and reduced HOMA-beta and insulin signaling markers typical of late-stage T2DM along with hypercholesterolaemia and high amounts of beta-VLDL, IDL, and LDL particles and low arylesterase activity. All these markers were significantly (p < 0.05) improved in LD-Si rats. The diabetic trend and diabetes dyslipidaemia scores showed a high and significant correlation (r = 0.595, p < 0.01). Silicon-enriched-meat consumption counterbalances the negative effects of HSFHC diets, functioning as an active hypolipemic, antioxidant, and antidiabetic dietary ingredient in a T2DM rat model, delaying the onset of late-stage diabetes.

Silicon as a Functional Meat Ingredient Improves Jejunal and Hepatic Cholesterol Homeostasis in a Late-Stage Type 2 Diabetes Mellitus Rat Model.

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/ß) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.

Analysis of immunohistomorphological changes in the colonic mucosa in a high-saturated fat and high-cholesterol fed streptozotocin/nicotinamide diabetic rat model.

The mucosal surface of gastrointestinal tract is lined with epithelial cells that establish an effective barrier between the lumen and internal environment through intercellular junctions, preventing the passage of potentially harmful substances. The "intestinal barrier function" consist of a defensive system that prevent the passage of antigens, toxins, and microbial products, while maintains the correct development of the epithelial barrier, the immune system and the acquisition of tolerance toward dietary antigens and intestinal microbiota. Intestinal morphology changes subsequent to nutritional variations, stress, aging or diseases, which can also affect the composition of the microbiota, altering the homeostasis of the intestine. A growing body of evidence suggests that alterations in intestinal barrier function favor the development of exaggerated immune responses, leading to metabolic endotoxemia, which seems to be the origin of many chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). Although the mechanisms are still unknown, the interaction between dietary patterns, gut microbiota, intestinal mucosa, and metabolic inflammation seems to be a key factor for the development of T2DM, among other diseases. This chapter details the different techniques that allow evaluating the morphological and molecular alterations that lead of the intestinal barrier dysfunction in a T2DM experimental model. To induce both diabetic metabolic disturbances and gut barrier disruption, Wistar rats were fed a high-saturated fat and high-cholesterol diet and received a single dose of streptozotocin/nicotinamide. This animal model may contribute to clarify the understanding of the role of intestinal barrier dysfunction on the late-stage T2DM etiology.

The preventive and therapeutic consumption of meat enriched with carob fruit extract, rich in phenolic compounds, improves colonic antioxidant status in late-stage T2DM rats.

Oxidative stress is prevalent in Type 2 Diabetes Mellitus (T2DM) and has been associated with high meat consumption. Carob Fruit Extract (CFE) contains phenolic compounds, making it a suitable functional ingredient. Current study aims to evaluate the effect of CFE-enriched meat (CFE-meat) consumption on the antioxidant status of proximal and distal colon, and its relationship with fecal phenolic compounds in late-stage T2DM rats. Three groups of eight rats were studied: 1) D, fed control-meat; 2) ED, fed CFE-meat since the beginning of the study; 3) DE, fed CFE-meat after confirming T2DM. CFE-meat consumption reduces colonic oxidative stress mainly in the proximal section and helps to ameliorate glutathione metabolism and antioxidant score. Difference between ED and DE groups were associated with colon homeostasis and T2DM progression suggesting greater fermentation but lower absorption in the DE group. CFE appears as a promising tool to improve the antioxidant status observed in late-stage T2DM.

Processing of the platelet amyloid precursor protein in the mild cognitive impairment (MCI).

It has been suggested that mild cognitive impairment (MCI) patients deteriorate faster than the healthy elderly population and have an increased risk of developing dementia. Certain blood molecular biomarkers have been identified as prognostic markers in Alzheimer's disease (AD). The present study was aimed to assess the status of the platelet amyloid precursor protein (APP) metabolism in MCI and AD subjects and establish to what extent any variation could have a prognostic value suggestive of predictive AD in MCI patients. Thirty-four subjects diagnosed with MCI and 45 subjects with AD were compared to 28 healthy elderly individuals for assessing for protein levels of APP, ß-APP cleaving enzyme 1 (BACE1), presenilin 1 (PS1) and a disintegrin and metalloproteinase-10 (ADAM-10) by western blot, and for the enzyme activities of BACE1 and γ-secretase by using specific fluorogenic substrates, in samples of platelets. A similar pattern in the healthy elderly and MCI patients was found for BACE1 and PS1 levels. A reduction of APP levels in MCI and AD patients compared with healthy elderly individuals was found. Augmented levels of ADAM-10 in both MCI and AD were displayed in comparison with age-matched control subjects. The ratio ADAM-10/BACE1 was higher for the MCI group versus AD group. Whereas BACE1 and PS1 levels were only increased in AD regarding to controls, BACE1 and γ-secretase activities augmented significantly in both MCI and AD groups. Finally, differences and similarities between MCI and AD patients were observed in several markers of platelet APP processing. Larger sample sets from diverse populations need to be analyzed to define a signature for the presence of MCI or AD pathology and to early detect AD at the MCI stage.

Impact of Silicon Addition on the Development of Gelled Pork Lard Emulsions with Controlled Lipid Digestibility for Application as Fat Replacers.

Pork lard gelled emulsions stabilized with two proteins [soy protein concentrate (SPC) or a pork rind protein extract (PRP)], both with and without added silicon (Si) from diatomaceous earth powder, were gelled by microbial transglutaminase and к-carrageenan. These gelled emulsions (GEs), intended as fat replacers, were evaluated in different aspects, including microstructure and technological properties during chilling storage. In addition, in vitro gastrointestinal digestion (GID) with an analysis of lipolysis and lipid digestibility was also evaluated. All GEs showed adequate technological properties after 28 days of chilling storage, although the SPC-stabilized GEs showed better gravitational and thermal stability (~4% and ~6%, respectively) during chilling storage than the PRP-stabilized ones (~8 and ~12%, respectively). PRP developed larger flocculates restricting pancreatic lipase-mediated lipolysis during intestinal digestion. The addition of Si to both GE structures protected them against disruption during in vitro digestion. Accordingly, Si appears to slow down fat digestion, as reflected by higher triacylglycerides content after GID (15 and 22% vs. 10 and 18% in GEs without Si) and could become a potential candidate for use in the development of healthier meat products.

Stabilized soy protein emulsion enriched with silicon and containing or not methylcellulose as novel technological alternatives to reduce animal fat digestion.

During the last decade, the consumption of animal saturated fat has been associated with an increased risk of chronic disease. Experience shows that changing the dietary habits of the population is a complicated and slow process, so technological strategies offer new possibilities for the development of functional foods. The present work is focused on studying the impact of using a food-grade non-ionic hydrocolloid (methylcellulose; MC) and/or the inclusion of silicon (Si) as a bioactive compound in pork lard emulsions stabilized with soy protein concentrate (SPC), on the structure, rheology, lipid digestibility and Si bioaccesibility during in vitro gastrointestinal digestion (GID). Four emulsions (SPC, SPC/Si, SPC/MC and SPC/MC/Si) were prepared with a final biopolymer (SPC and/or MC) concentration of 4% and 0.24% Si. The results showed a lower degree of lipid digestion in SPC/MC compared with SPC, specifically at the end of the intestinal phase. Moreover, Si partially reduced fat digestion only when incorporated into the SPC-stabilized emulsion, while this effect was lost in SPC/MC/Si. This was probably due to its retention inside the matrix emulsion, which resulted in lower bioaccesibility than in SPC/Si. Additionally, the correlation between the flow behavior index (n) and the lipid absorbable fraction was significant, suggesting that n can be a predictive marker of the extent of lipolysis. Concretely, our results revealed that SPC/Si and SPC/MC can be used as pork fat digestion reducers and thus, they can replace pork lard in the reformulation of animal products with potential health benefits.

Influence of the Oil Structuring System on Lipid Hydrolysis and Bioaccessibility of Healthy Fatty Acids and Curcumin.

Oleogels (OG) and gelled emulsions (GE) were elaborated with a mixture of olive and chia oils (80:20 ratio) without and with the incorporation of the health-related compound curcumin. These were studied to evaluate the influence of the oil structuring system on the lipid hydrolysis and bioaccessibility of three healthy fatty acids (FA) (palmitic, oleic, and α-linolenic acids) and of curcumin, compared to the oil mixture (bulk oil, BO). The oil structuring system influenced the firmness and texture, and the presence of curcumin significantly altered the color parameters. GE showed higher lipid digestibility, with a greater proportion of absorbable fraction (higher content of free FA and monoacylglycerides) than OG, which behaved similarly to BO. The presence of curcumin affected the degree of lipolysis, reducing lipid digestibility in OG and increasing it in GE. As for FA bioaccessibility, although GE presented higher percentages overall, curcumin significantly increased and decreased FA bioaccessibility in OG and GE, respectively. The oil structuring system also influenced the bioaccessibility of curcumin, which was higher in GE. Therefore, when selecting an oil structuring system, their physicochemical properties, the degree of lipid hydrolysis, and the bioaccessibility of both curcumin and the FA studied should all be considered.