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.

Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors. pDCs, CD4 and CD8 T-cells were isolated from 450 ml of whole blood from non HIV-1 infected donors, immune responders (IR), immune non responders (INR), viremic (VIR) and elite controller (EC) participants. pDCs were stimulated overnight with AT-2, CpG-A, CpG-C and GS-9620 or no stimuli. After that, pDCs were co-cultured with autologous CD4 or CD8 T-cells and with/without HIV-1 (Gag peptide pool) or SEB (Staphylococcal Enterotoxin B). Cytokine array, gene expression and deep immunophenotyping were assayed. pDCs showed an increase of activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels after TLR stimulation in the different HIV-disease progression phenotypes. This pDC activation was prominent with CpG-C and GS-9620 and induced an increase of HIV-specific T-cell response even in VIR and INR comparable with EC. This HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production by pDC. These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with the induction of a T-cell mediated antiviral response which is essential for HIV-1 eradication strategies. This work was supported by 10.13039/100005564 Gilead fellowship program, the 10.13039/501100004587 Instituto de Salud Carlos III ( 10.13039/501100008530 Fondo Europeo de Desarrollo Regional , 10.13039/501100002924 FEDER , “a way to make Europe”) and the Red Temática de Investigación Cooperativa en SIDA and by the 10.13039/501100003339 Spanish National Research Council ( 10.13039/501100003339 CSIC ).

Acute coronary syndrome (ACS) is nowadays one of the leading causes of morbid-mortality in HIV-infected population, but innate and adaptive immune mechanisms preceding this event are unknown. In this work we comprehensively and longitudinally observed, by multi-parametric flow cytometry and following a case-control design, increased CCR5⁺CD8⁺ T-cells levels and monocytes expressing activation and adhesion markers in HIV-infected patients who are going to suffer ACS. In addition, we found direct associations between activated CD8⁺ T-cells and myeloid cells that were only statistically significant in the group of patients with ACS and in the follow up time point just before the ACS. Our data highlight the important role of CCR5 in the onset of ACS and suggest this receptor as a marker of cardiovascular risk and potential therapeutic target to prevent the development of such non-AIDS-related event in HIV-infected patients. Note: This work was presented at the CROI 2016 conference (Boston, USA in February 2016).

Objective The aim of this study was to present the results obtained in the Newborn Screening Program (NSP) for sickle cell disease (SCD) in western Andalusia and the autonomous city of Ceuta in the first 3 years of implementation, and to describe the discrepancies found in the diagnosis of hemoglobinopathies between the screening method and the confirmatory tests. Study Design A descriptive and retrospective study was carried out, and the findings obtained in the newborns included in the NSP between November 2018 and December 2021 were analyzed. Results A total of 111,205 samples were screened by high-performance liquid chromatography (HPLC). The birth prevalence of SCD, sickle cell trait, hemoglobin C carriers, and the compound heterozygosity Hb C/β-thalassemia was 1/12,356, 1/467, 1/1,278, and 1/55,602 newborns, respectively. Although there was a correlation between the first-line HPLC screening technique (VARIANTnbs HPLC analyzer, Bio-Rad) and the confirmatory tests in most cases, major discrepancies were found in detecting carriers of G-Philadelphia, D, E, and O-Arab hemoglobin variants, with the former having an incidence of 1/10,110 and the others 1/22,241. The carrier status of Hb G-Philadelphia produced an FAD pattern on the screening method that could be mistaken as Hb D, while Hb O-Arab was identified as an FA5 pattern. Hb D was initially recognized as Hb D in two cases. Conclusion An NSP requires at least two different combined methods in order to identify the hemoglobin variant with sufficient certainty. Furthermore, even though software solutions for HPLC suggest a pattern, it must be confirmed with another technique to obtain a correct interpretation of the chromatograms. Key Points ^# Contributed equally to this work. Received: 08 July 2022 Accepted: 24 October 2022 Article published online: 29 December 2022 © 2022. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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.