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Background: The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis., Methods: The HepG2 hepatoma-derived cell line was employed to establish an in vitro steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-β, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied., Aim: To establish an in vitro steatosis model employing HepG2 cells that mimics molecular processes observed in vivo during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC., Results and Conclusion: Peptide seq-1-treated HepG2 cells show a downregulation of COLIA1, ACTA2, and TGF-β genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease., Competing Interests: Conflict of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mas-Oliva is a co-founder of and has equity in Hamol Biosolutions LLC. The other authors declare no potential conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

During the last years, infections have become a global health emergency, where the appearance of bacteria highly resistant to traditional antibiotics have set off an alarm worldwide. Moreover, the increased incidence and mortality resulting from its aggravated states, sepsis, and septic shock, have been observed with growing concern. In this context, knowing the need for a new concept for treatment, peptides such as antimicrobial peptides (AMP) and host defense peptides (HDP), have started to show interesting properties in the development of new antimicrobial agents and host response modulatory therapies. Nevertheless, since it is a well-known fact that a peptide-based drug development is a long process that consumes a significant number of resources, recent approaches that tend to mitigate these obstacles, have included the implementation of novel in silico strategies for the optimization of naturally occurring AMP and HDP. In this review, we analyze these strategies that seek to improve not only peptide design, but also production, by including the incorporation of computational biology techniques such as molecular dynamics., (Copyright © 2021. Published by Elsevier Inc.)

Background: An elevated level of plasma uric acid has been widely recognized as a risk factor for non-alcoholic fatty liver disease (NAFLD), where oxidative stress and inflammation play an important role in the pathophysiology of the disease. Although the complete molecular mechanisms involved remain unknown, while under physiological conditions uric acid presents antioxidant properties, hyperuricemia has been linked to oxidative stress, chronic low-grade inflammation, and insulin resistance, basic signs of NAFLD., Aim of Study: Employing in vivo experimentation, we aim to investigate whether a high-fat diet rich in cholesterol (HFD), modifies the metabolism of purines in close relationship to molecular events associated with the development of NAFLD. In vitro experiments employing HepG2 cells are also carried out to study the phenomenon of oxidative stress., Methods: Adult male rabbits were fed for 8 weeks an HFD to induce NAFLD. At the beginning of the experiment and every 15 d until the completion of the study, plasma levels of lipids, lipoproteins, and uric acid were measured. Liver tissue was isolated, and histology performed followed by the biochemical determination of hypoxanthine, protein expression of xanthine oxidoreductase (XOR) by western blot analysis, and xanthine oxidase (XO) activity using an enzymatic kinetic assay. Furthermore, we employed in vitro experimentation studying HepG2 cells to measure the effect of hypoxanthine and H 2 O 2 upon the production of radical oxygen species (ROS), XO activity, and cell viability., Results and Conclusion: Hepatic tissue from rabbits fed the HFD diet showed signs of NAFLD associated with an increased ROS concentration and an altered purine metabolism characterized by the increase in hypoxanthine, together with an apparent equilibrium displacement of XOR towards the xanthine dehydrogenase (XDH) isoform of the enzyme. This protein shift visualized by a western blot analysis, associated with an increase in plasma uric acid and hepatocyte hypoxanthine could be understood as a compensatory series of events secondary to the establishment of oxidative stress associated with the chronic establishment of fatty liver disease., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Background and Aims: Atherosclerosis as an inflammatory disease involved in the etiology of cardiovascular disease worldwide, in our days demands an array of different therapeutic approaches in order to soon be able to visualize an effective prevention. Based on an immunotherapeutic approach, we designed a non-invasive vaccine (HB-ATV-8), contained in a micellar nanoparticle composed of lipids and a peptide segment derived from the C-terminus of the cholesterol-ester transfer protein (CETP). Now we extend our successful proof of concept from the rabbit to a porcine model and investigated its effect in an attempt to undoubtedly establish the efficacy of vaccination in a model closer to the human., Methods: A preclinical trial was designed to study the efficacy of vaccine HB-ATV-8 in pigs (Large White × Landrace). Male experimental animals were fed with standard diet (control), high fat diet (HFD) or the same HFD but treated with HB-ATV-8 (HFD + Vaccine) applied nasally for up to 7 months. All biochemical and enzymatic analyses were performed in peripheral venous blood and thoracic aorta and liver samples examined using conventional, two-photon excitation and second harmonic generation microscopy to identify atherosclerotic and hepatic lesions. mRNA concentrations for KLF2, ACTA2, SOD1, COL1A1 genes and protein levels for PPARα and ABCA1 were quantified in aorta and liver respectively using qPCR and Western blot analysis., Results: The administration of vaccine HB-ATV-8 induced anti-CETP IgG antibodies and reduced atherosclerotic and hepatic lesions promoted by the high fat diet. In addition, plasma triglyceride levels of vaccine treated pigs fed the HFD were similar to those of control group, in contrast to high concentrations reached with animals exclusively fed with HFD. Moreover, HFD promotes a tendency to decrease hepatic PPARα levels and increase in aorta gene expression of KLF2, ACTA2, SOD1 and COL1A1, while vaccine application promotes recovery close to control values., Conclusions: Vaccine HB-ATV-8 administration constitutes a promissory preventive approach useful in the control of atherogenesis and fatty liver disease. The positive results obtained, the non-invasive characteristics of the vaccine, the simple design employed in its conception and its low production cost, support the novelty of this therapeutic strategy designed to prevent the process of atherogenesis and control the development of fatty liver disease., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis and cancer are chronic diseases considered two of the main causes of death all over the world. Taking into account that both diseases are multifactorial, they share not only several important molecular pathways but also many ethiological and mechanistical processes from the very early stages of development up to the advanced forms in both pathologies. Factors involved in their progression comprise genetic alterations, inflammatory processes, uncontrolled cell proliferation and oxidative stress, as the most important ones. The fact that external effectors such as an infective process or a chemical insult have been proposed to initiate the transformation of cells in the artery wall and the process of atherogenesis, emphasizes many similarities with the progression of the neoplastic process in cancer. Deregulation of cell proliferation and therefore cell cycle progression, changes in the synthesis of important transcription factors as well as adhesion molecules, an alteration in the control of angiogenesis and the molecular similarities that follow chronic inflammation, are just a few of the processes that become part of the phenomena that closely correlates atherosclerosis and cancer. The aim of the present study is therefore, to provide new evidence as well as to discuss new approaches that might promote the identification of closer molecular ties between these two pathologies that would permit the recognition of atherosclerosis as a pathological process with a very close resemblance to the way a neoplastic process develops, that might eventually lead to novel ways of treatment., (Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis together with multiple sclerosis, psoriasis and rheumatoid arthritis can be used as examples of chronic inflammatory diseases associated with multifactorial components that evolve over the years. Nevertheless, an important difference between these diseases relies on the fact that atherosclerosis develops from early ages where inflammation dominates the very beginning of the disease. This review highlights the inflammatory nature of atherosclerosis and the role the immune system plays in the process of atherogenesis. Although treatment of atherosclerosis has been for years based on lipid-lowering therapies reducing a series of risk factors, the degree of success has been only limited because cardiovascular complications related to the evolution of atherosclerotic lesions continue to appear in the population worldwide. In this sense, alternative treatments for atherosclerosis have come into play where both innate and adaptive immunity have been proposed to modulate atherosclerosis-associated inflammatory phenomena. When tested for their atheroprotective properties, several immunogens have been studied through passive and active immunization with good results and, therefore, the strategy through vaccination to control the disease has been made possible. Many experimental pre-clinical studies demonstrating proof of concept that vaccination using DNA and protein with an effective use of adjuvants and the optimal route of administration now provide a tangible new therapeutic approach that sets the stage for several of these vaccines to be tested in large, randomized, long-term clinical studies. A vaccine ready for human use will only be accomplished through the close association between academia, regulatory government organizations and private industry, allowing the reality of a simple and successful therapy to reduce atherosclerosis and its severe clinical complications., (Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.)

We report the results of 23 patients with aplastic anemia (AA) treated with a program of 14 lymphocytapheresis (LC). Treatments were performed with apheresis machines, models Haemonetics 30-S and Baxter CS3000, using the standard program. This procedure was done because AA in many cases appears as a result of the action of a T cell population that inhibits hematopoiesis. Theoretically, removal of this clonal population would produce hematopoietic recovery. Of the total of 23 patients, 9 were excluded for final evaluation of treatment results because 7 died during or shortly after treatment (0.7-3 months); one patient abandoned treatment after three LC and another died 7 months later because of transformation to acute leukemia. The remaining 14 patients were included in the final evaluation of treatment; seven females and seven males, average age 46.1 years (range 22-69); 13 with severe, and one with moderate AA; 11 with recently diagnosed, and 3 with chronic AA; 12 without previous treatment and two treated before with antilymphocyte globulin + oxymetholone (OXM) + cyclosporine A (CsA) with transient partial remission (PR). Besides lymphocytapheresis, 13 patients received OXM; 4 of them GM-CSF and one low dose CsA. Four patients had complete remission lasting > 59.5 months (range 42-78); eight PR (average duration of > 38.6 months), and two minimal remission (> 37 and 29 months). Platelet, reticulocyte and granulocyte counts increased on average at 48.7, 73.3 and 91.4 days, respectively. In conclusion, 14 (60.8%) of 23 patients with AA showed an improvement related to LC treatment, with a survival probability of 63% from the fourth month, the latter with an added beneficial effect of the other therapies used. Larger numbers of patients have to be treated with LC to determine its real usefulness, mechanism of action and the best conditions for its use.