We have previously reported the in vitro hypocholesterolemic, anti-inflammatory, and antioxidant effects of Alcalase-generated lupin protein hydrolysate (LPH). Given that lipoprotein deposition, ...oxidative stress, and inflammation are the main components of atherogenesis, we characterized the LPH composition, in silico identified LPH–peptides with activities related to atherosclerosis, and evaluated the in vivo LPH effects on atherosclerosis risk factors in a mouse model of atherosclerosis. After 15 min of Alcalase hydrolysis, peptides smaller than 8 kDa were obtained, and 259 peptides out of 278 peptides found showed biological activities related to atherosclerosis risk factors. Furthermore, LPH administration for 12 weeks reduced the plasma lipids, as well as the cardiovascular and atherogenic risk indexes. LPH also increased the total antioxidant capacity, decreased endothelial permeability, inflammatory response, and atherogenic markers. Therefore, this study describes for the first time that LPH prevents the early stages of atherosclerosis.
Scope
We have previously demonstrated the anti‐inflammatory and antioxidant properties of in vitro administered Lupinus angustifolius protein hydrolysates (LPHs) on human peripheral blood mononuclear ...cells (PBMCs). This study aims to evaluate the safety and efficacy of a beverage containing LPHs (LPHb) on the immune, oxidative and metabolic status of healthy subjects.
Methods and Results
In this open‐label intervention, 33 participants daily ingest a LPHb containing 1 g LPHs for 28 days. Biochemical parameters are assayed in fasting peripheral blood and urine samples before, during (14 days) and after LPHb ingestion. Participants’ health status and the immune and antioxidant responses of PBMCs are also evaluated throughout the trial. The LPHb ingestion is safe and effective in both increasing the anti‐/pro‐inflammatory response of PBMCs and improving the cellular anti‐oxidant capacity. LPHb also reduces the low‐density lipoprotein‐cholesterol (LDL‐C)/high‐density lipoprotein‐cholesterol (HDL‐C) atherogenic index. LPHb effect is particularly beneficial on decreasing not only the LDL‐C/HDL‐C index but also serum total cholesterol levels in the male cohort that shows the highest baseline levels of well‐known cardiovascular risk factors.
Conclusion
This is the first study to show the pleiotropic actions of a lupine bioactive peptides‐based functional food on key steps of atherosclerosis including inflammation, oxidative stress, and cholesterol metabolism.
The intake of a functional beverage based on Alcalase 2.4 L‐generates lupine protein hydrolysates for 28 days which increases the anti‐inflammatory microenvironment, as well as the cellular antioxidant capacity in healthy subjects. In addition, the intake of this beverage reduces the LDL‐C/HDL‐C atherogenic index.
Metabolic-associated fatty liver disease (MAFLD) is the most important cause of liver disease worldwide. It is characterized by the accumulation of fat in the liver and is closely associated with ...abdominal obesity. In addition, oxidative stress and inflammation are significant features involved in MAFLD. Recently, our group demonstrated that lupin protein hydrolysates (LPHs) had lipid lowering, antioxidant, and anti-inflammatory effects. Sixty male mice fed with a Western diet were intragastrically treated with LPHs (or vehicle) for 12 weeks. Liver and adipose tissue lipid accumulation and hepatic inflammatory and oxidant status were evaluated. A significant decrease in steatosis was observed in LPHs-treated mice, which presented a decreased gene expression of CD36 and LDL-R, crucial markers in MAFLD. In addition, LPHs increased the hepatic total antioxidant capacity and reduced the hepatic inflammatory status. Moreover, LPHs-treated mice showed a significant reduction in abdominal adiposity. This is the first study to show that the supplementation with LPHs markedly ameliorates the generation of the steatotic liver caused by the intake of a Western diet and reduces abdominal obesity in ApoE−/− mice. Future clinical trials should shed light on the effects of LPHs on MAFLD.
Melatonin (MLT), a natural compound found in the animal and vegetable kingdom, participates in several physiological processes. MLT exerts antioxidant and anti-inflammatory activities, among others, ...but information about its action on lipid metabolism is still scarce. For this reason, mice deficient in apolipoprotein E (ApoE−/−) fed a Western diet (WD) were intragastrically treated with different concentrations of MLT (2 and 9 mg/kg) for 12 weeks. The lipid parameters were quantified, and, since links between cardiovascular risk and immune function and oxidative stress have been established, we also analyzed the population of leukocytes and the oxidative stress status. Although there was no change in the weight of the mice, a significant reduction in low-density lipoprotein cholesterol (LDL-C) was observed in mice treated with the higher concentration of MLT tested in this study. Additionally, an improvement in cardiovascular risk indexes was observed. A reduction in the hepatic total cholesterol (TC) and LDL-C levels was also observed in the treated mice. Finally, a decrease in leukocytes and lymphocytes in particular, as well as an increase in the antioxidant status, were shown in MLT-treated mice. In conclusion, MLT is a promising candidate that could be considered as a possible functional ingredient capable of preventing cardiovascular risk.
Iron metabolism plays an essential role in cellular functions. Since virologically suppressed chronic HIV-infected subjects under effective antiretroviral treatment (ART) exhibit a persistent immune ...dysfunction that leads to comorbidities, iron homeostasis may be relevant in this context. We aimed to explore iron metabolism in virologically suppressed chronic HIV infected subjects under a successful ART.
In this retrospective study, traditional iron metabolism biomarkers (total iron, ferritin, transferrin, and transferrin saturation index), as well as soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers were determined in virologically suppressed chronic HIV-infected subjects under at least 2 years of ART (HIV) who also had >350 CD4-T-cells/mm
(N=92) from Spain. As controls, we collected non-HIV age-matched healthy donors (Young, N=25) and elderly subjects (>65 years old; Elderly; N=25). Additionally, an external group of non-HIV patients with ferritin<50 ng/mL diagnosed with absolute iron deficiency (Ferropenic group; N=84) was included. Comparisons between groups were performed using Kruskal-Wallis or Mann-Whitney U-tests, while associations between variables were explored by Spearman's rho correlation coefficient.
We selected samples from HIV-infected subjects (aged 4234-47, 95% males), young age-matched (aged 4030-58, 60% males), and elderly controls (aged 8278-88, 100% males). Compared to both healthy (Young and Elderly) groups, HIV exhibited decreased iron, transferrin saturation, and sTfR, and increased ferritin, but similar hepcidin levels. Notably, associations between sTfR and iron (Young,
=-0.587,
=0.002; Elderly,
=-0.496,
=0.012) or transferrin saturation index (Young,
=-0.581,
=0.002; Elderly,
=-0.489,
=0.013) were negative in both controls while positive in HIV (
=0.464,
<0.0001 and
=0.421,
<0.0001, respectively). Moreover, the expected negative correlation between hepcidin and sTfR, observed in controls (Young,
=-0.533,
=0.006; Elderly,
=-0.473,
=0.017), was absent in HIV (
=0.082;
=0.438). Interestingly, the HIV inflammatory profile differed from the Elderly one, who despite their inflammaging-related profile, succeed in maintaining these associations. Furthermore, subjects from the ferropenic group (aged 4232-51, 5% males), showing significantly lower levels of hepcidin and higher sTfR, as expected, reflected similar correlations as those Young and Elderly, in contrast to HIV.
Virologically suppressed chronic HIV-infected patients under successful ART exhibit altered levels of iron metabolism modulators suggesting a complex functional iron deficiency.
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•Fermented orange juice (FOJ) intake increases urine 6-sulfatoxymelatonin (6-SMT).•Urine antioxidant activity is higher after FOJ consumption than after OJ consumption.•Urine ...antioxidant activity after FOJ intake would be mainly due to 6-SMT content.•FOJ could be a good source of bioavailable melatonin.
Fermentation of orange juice (OJ) by Pichia kluyveri enhances the content of melatonin, a molecule with potent antioxidant effect. This study explores the levels of urine 6- sulfatoxymelatonin (6-SMT) in healthy subjects after fermented orange juice (FOJ) intake, and their association with antioxidant activity status. Nine participants ingested 500 mL of FOJ and their urine was collected at baseline and after 2, 5, 10, 15 and 24 h. After a two-week washout period, the intervention was repeated with OJ. 6-SMT levels were quantified by ELISA and antioxidant activity by TAC, FRAP and ORAC assays. A significant increase in both 6-SMT levels and antioxidant activity in urine was observed after FOJ ingestion compared to OJ. A positive correlation between TAC and 6-SMT levels was observed only after FOJ intake. This study shows for the first time that fermentation process increases melatonin bioavailability of OJ associated with an enhancement in antioxidant status.
Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective ...immunity conferred by the vaccine administration within this group of high-risk patients.
To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response.
Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses.
In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.
...we aimed to explore potential differences in specific dysbiosis in the gut-mucosal microbiome, comparing biopsies from two different locations (ileum and caecum), of HIV-infected subjects with ...different clinical phenotypes. SEE PDF Sequencing data of 16S rRNA from the microbiota present in terminal ileum and caecum samples of study subjects were analysed and compared with bacterial taxonomic databases. ...parameters of richness and alpha-diversity of the gut microbiome showed no statistically significant differences between healthy and HIV-groups (elite controller EC, early-treated ET, late-treated high recovery LT-HR and late-treated low recovery LT-LR) regardless the biopsied intestinal area (Figure 2A) or patient sex (Figure S1). ...abundance analyses were performed without separating by gut location. ...this is the first report to analyse the potential association of the clinical phenotype of HIV-subjects, regarding their CD4 status at cART onset and afterwards, with alterations in the microbiome composition.
Summary Objectives Bacterial lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels have been indistinctly used to measure bacterial translocation independently of the immunovirological stage in ...HIV infection; however, when the association of both markers with different HIV-progression end-points has been studied, discrepant results have been reported. The aim of this study was to assess the relationship between LPS and sCD14 in different HIV-infection immune stages and to determine the relationship between these biomarkers with established HIV-disease-progression-related markers, as T-cell immune activation, high-sensitivity C-reactive protein and D-dimer. Methods Seventy-three chronically HIV-1-infected patients with detectable HIV-1 RNA levels were analyzed. LPS levels by use of limulus lysate assay, sCD14, intestinal fatty acid binding protein and inflammation–coagulation-associated biomarkers were assessed. Results In this study, we found that LPS and sCD14 levels were only associated when low CD4+ T-cell levels and high HIV RNA levels were present. In addition, only sCD14 levels, but not LPS, were independently associated with HIV-disease progression-related markers, supporting the clinical importance of sCD14. Conclusions These results indicate that LPS and sCD14 have a different biological significance and should not be indistinctly used without taking the HIV immunovirological stage into account.
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