Juan De Sanctis | Palacky University, Olomouc (original) (raw)

Papers by Juan De Sanctis

Current issues in molecular biology, Apr 17, 2024

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Revista Colombiana de Química/Revista colombiana de quimica, Feb 5, 2024

Este trabajo está bajo una Licencia Creative Commons. El contenido es responsabilidad de los auto... more Este trabajo está bajo una Licencia Creative Commons. El contenido es responsabilidad de los autores y no representa a la

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV ... more Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (> 90%); the compounds were able to inhibit HCV replication withou...

Gaceta Médica de Caracas, 2020

Cancer is a complex disease and numerous treatments have been proposed and used. The breakthrough... more Cancer is a complex disease and numerous treatments have been proposed and used. The breakthrough has been the use of biological therapy with checkpoint inhibitors, decreasing tumor burden. The life expectancy of cancer patients has increased. However, the major problem refers to the high incidence of tumors in the elderly population most of which have comorbidities. The number of healthy aged individuals is low, and usually, clinical trials do not take into account, aged individuals. Therefore, the rationale of tumor therapies in the elderly population is very complex. One interesting initiative is to analyze cancer incidence and survival of a large cohort of individuals that have taken specific therapies for a number of years. The review will focus on three drugs: valproic acid, disulfiram (Antabuse), and metformin. In this short review, we will give some insights into the importance of these drugs in cancer therapy in general and in the aged population.

Recent Patents on Inflammation & Allergy Drug Discovery, Jan 15, 2021

International Journal of Molecular Sciences, Apr 10, 2022

Current Pharmaceutical Design, Nov 19, 2021

Scandinavian Journal of Immunology, May 1, 1998

Immunophenotype analysis and proliferative responses were investigated in bronchoalveolar lavage ... more Immunophenotype analysis and proliferative responses were investigated in bronchoalveolar lavage (BAL) cells from 21 patients with stage‐classified tuberculosis: six with localized pulmonary infiltrate (LPI); seven with diffuse pulmonary infiltrate (DPI); and eight with pleural effusions (PE). Bronchoalveolar lavage cells from these patients contained a high number of cells/ml. The macrophage number was significantly lower in the DPI group (P < 0.05) compared to the LPI or PE groups. Conversely, neutrophils were markedly increased in DPI patients compared to LPI (P < 0.01) and PE (P < 0.01) patients. Lymphocyte infiltration (97.7 ± 2.3% CD3+, > 83% αβ+ and CD4+ > CD8+) was observed in the three groups. A significant increase in the number of total lymphocytes (P < 0.01) and CD4+ cells (P < 0.05) was observed in the LPI group compared to the PE group. In the LPI group CD4+ CD45RO+ cell infiltration was higher than CD4+ CD45RA+ cells (P < 0.001), contrasting to similar numbers of these subpopulations in the DPI group. Lymphocytes from three out of three LPI patients (αβ+ CD4+ CD45RO+) responded against tuberculin purified protein derivative contrasting to the unresponsiveness of five patients with either DPI or PE. This impaired response was reverted in two out of five patients by using peripheral blood monocytes instead of alveolar macrophages. It is suggested that, in humans, αβCD4+CD45RO cells are the main lymphocyte type involved in the initial local cell‐mediated immune response against Mycobacterium tuberculosis.

Experimental Neurology, Sep 1, 2021

Alzheimer's disease (AD) is characterised by the accumulation of intracytoplasmic aggregates ... more Alzheimer's disease (AD) is characterised by the accumulation of intracytoplasmic aggregates of tau protein, which are suggested to spread in a prion-like manner between interconnected brain regions. This spreading is mediated by the secretion and uptake of tau from the extracellular space or direct cell-to-cell transmission through cellular protrusions. The prion-like tau then converts the endogenous, normal tau into pathological forms, resulting in neurodegeneration. The endoplasmic reticulum/Golgi-independent tau secretion through unconventional secretory pathways involves delivering misfolded and aggregated tau to the plasma membrane and its release into the extracellular space by non-vesicular and vesicular mechanisms. Although cytoplasmic tau was thought to be released only from degenerating cells, studies now show that cells constitutively secrete tau at low levels under physiological conditions. The mechanisms of secretion of tau under physiological and pathological conditions remain unclear. Therefore, a better understanding of these pathways is essential for developing therapeutic approaches that can target prion-like tau forms to prevent neurodegeneration progression in AD. This review focuses on unconventional secretion pathways involved in the spread of tau pathology in AD and presents these pathways as prospective areas for future AD drug discovery and development.

PubMed, Apr 1, 1990

This study examined the role of human recombinant interferon-gamma (rIFN-gamma) in the expression... more This study examined the role of human recombinant interferon-gamma (rIFN-gamma) in the expression of interleukin-2 receptors (IL-2R) by human T lymphocytes. rIFN-gamma enhanced total numbers of IL-2R in mitogen-activated but not resting T cells. Scatchard plot analysis indicated that rIFN-gamma increased both high- and low-affinity receptors, with a predominant effect on the latter. Phytohaemagglutinin (PHA)-activated T cells treated with IFN-gamma showed higher IL-2 binding and greater IL-2 internalization and degradation than cells treated with PHA alone. There was a corresponding increase of mitogen-driven proliferative responses, indicating an increase of functional receptors in IFN-treated cultures. IFN-gamma may influence T-cell activation and proliferation by enhancing expression of IL-2R and promoting IL-2 uptake by mitogen-activated lymphocytes.

The Cochrane library, Sep 8, 2021

The Cochrane library, Jun 28, 2022

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the clinical benefit and harms of colchicine as primary prevention of cardiovascular outcomes in the general population. Background Description of the condition Cardiovascular diseases (CVDs) include coronary heart disease (CHD), sudden cardiac death/sudden cardiac arrest, cerebrovascular disease, stroke/transient ischemic attack, rheumatic heart disease, congenital heart disease, deep venous thrombosis, pulmonary embolism, and peripheral arterial disease. From 1990 to 2019, the prevalence of cases of total CVDs has been nearly doubled from 271 million (95% uncertainty interval: 257 to 285 million) to 523 million (95% UI: 497 to 550 million), respectively (Roth 2020). In addition, it has been estimated that CVDs caused 18.6 million (95% uncertainty interval: 17.1 to 19.7 million) deaths in 2019 (Roth 2020). Doubtlessly, CVDs yield a high socioeconomic burden in the general population (Flora 2019). The main cause of CVDs is atherosclerosis which is the result of cellular-molecular interactions in the artery wall (Gotlieb 1991); therefore, it is a chronic inflammatory disease with autoimmune foundations (

Paper, 2020

Despite the high incidence of cancer in the elderly, little is known about the protective immune ... more Despite the high incidence of cancer in the elderly, little is known about the protective immune response against cancer and the treatment of other comorbidities. Inflammaging has been defined to explain a protective inflammatory response in the elderly. New subpopulations of stem cell memory T cells seem to be responsible for a quick memory response to antigens and probably against tumours. Biological immune therapy with anti-checkpoint inhibitors could be an essential tool to treat patients; however, adverse or toxic events are often observed in elderly patients. Several medications used in the elderly, metformin and valproic acid, have been shown to have anti-neoplastic effects. These effects suggest that therapeutic approaches in the elderly should be carefully analysed. Clinical trials are required to assess the exact role of immune response and therapy in tumour incidence and survival in the elderly.

Current Pharmaceutical Design

: Even though an association between inflammation and hypertension has been known for many years,... more : Even though an association between inflammation and hypertension has been known for many years, it has not been simple to ascertain the role of several physiological responses involved. The innate immune response plays a critical role in these physiological responses. Innate immune cells can be activated directly by shear stress, activate the inflammasome and produce numerous cytokines and soluble mediators essential in hypertension. NFkB activation is mainly involved in the activation of innate immune cells. Shear stress also stimulates the expression of DAMP and PAMP receptors, enhancing pathogen and danger signals and magnifying inflammation. The adaptative immune response is activated with the increased antigen presentation resulting from the insults mentioned. Chronic inflammation may lead to autoimmunity. Peripheral hypoxia, a consequence of hypertension, activates hypoxia-inducing factors 1-α and 1-β (HIF-1α, HIF-1β), which modulate innate immune cells and promote inflammation. HIF-1α is involved in the upregulation of oxygen and nitrogen radical production proteins. HIF-1β down-regulates antioxidant enzymes. However, the critical evidence of the role of innate immune cells in hypertension came from the results of clinical trials involving therapies blocking inflammatory cytokines and Toll-like receptor expression. Several lines of research have been conducted on this complex disease. Pro-tolerogenic innate immune cells, myeloid suppressor cells, and M2 macrophages may play a crucial role in promoting or resolving inflammation, cardiovascular diseases and hypertension, and should be studied in detail.

Recent Patents on Inflammation & Allergy Drug Discovery, 2015

This issue of the journal is on the topic of vaccines. In recent years a lot of vaccines have bee... more This issue of the journal is on the topic of vaccines. In recent years a lot of vaccines have been developed. In some cases, vaccines were developed to enhance the immune response to known pathogens, in other cases, e.g., influenza vaccines, new developments were achieved: new adjuvants to induce strong immune response from the first inoculation, etc.

Arch. venez. farmacol. …, 2007

Clinical and Experimental Immunology, Aug 1, 1998

B lymphocytes, purified from peripheral leucocytes from young normolipaemic humans, expressed and... more B lymphocytes, purified from peripheral leucocytes from young normolipaemic humans, expressed and internalized low-density lipoprotein receptors (LDLR). The expression was assessed by a monoclonal anti-LDLR. The internalization of LDL was assessed by LDL labelled with 125 I (125 I-LDL) and 1,1 0-dioctadecyl-3,3,3 0 ,3 0 tetramethyl-indocarboxycyanine perchlorate (LDL-DiI). The expression of LDLR, assessed by anti-LDLR, was: 38 Ϯ 8% (n ¼ 5) for fresh purified cells, 60 Ϯ 10% (n ¼ 12) for non-stimulated cells, 79 Ϯ 5% (n ¼ 10) for IL-2 (100 U/ml)-stimulated cells and 95 Ϯ 5% (n ¼ 8) for pokeweed mitogen (PWM) (1:200 dilution)-stimulated cells. The optimal concentrations of agonist were 100 U/ml of IL-2, and 1:200 dilution of PWM. IL-2 and PWM increased the internalization of LDL-DiI by 1•5-fold. The internalization of LDL-DiI was maximal at 60 mg of protein/ml (48 Ϯ 8%). Scatchard analysis revealed a Kd of 3•2 Ϯ 0•22 × 10-8 M and 2180 Ϯ 190 binding sites in non-stimulated cells, a Kd of 7•73 Ϯ 0•36 × 10-9 M and 12 500 Ϯ 430 binding sites for IL-2 (100 U/ml)-stimulated cells, and a Kd of 7•2 Ϯ 0•43 × 10-9 M and 13 250 Ϯ 450 binding sites for PWM (1:200 dilution)-stimulated cells. Lineweaver-Burk analysis of LDL binding (LDL-DiI) revealed that the apparent Kd for non-stimulated cells was 1•3 Ϯ 0•11 × 10-8 M, and 9•2 Ϯ 0•2 × 10-9 M and 7•5 Ϯ 0•25 × 10-9 M for IL-2-and PWM-stimulated cells, respectively. B lymphocytes from tonsils also showed a high expression of LDLR assessed with anti-LDLR (70 Ϯ 6%). The high expression of LDLR and the avid internalization of LDL suggest that LDL may be important for B cell physiological responses. Keywords low-density lipoprotein low-density lipoprotein receptor B lymphocytes IL-2 pokeweed mitogen

International Journal of Molecular Sciences, Feb 8, 2022

Recent Patents on Inflammation & Allergy Drug Discovery, Dec 4, 2019

Background: Various pieces of evidence have shown that people who consume foods rich in polypheno... more Background: Various pieces of evidence have shown that people who consume foods rich in polyphenolic and flavonoids compounds have a lower incidence of inflammatory, autoimmune diseases and cancer. Objective: The study aimed to review the most potent compounds that affect the immune response and diseases associated with it. Methods: Publications in PubMed and EmBase, from 1974-2018, and patents form Free patents online, Scifinder, Espacenet and Mendeley in which flavonoids, their semi-synthetic and synthetic derivatives are involved in immunosuppressive or immunostimulatory responses in vitro and in vivo. Results: In vitro, flavonoids and their derivatives inhibit various transcriptional factors, which modulate differentiation, proliferation, activation of immune cells and enhance regulatory T cell generation. Some flavonoids exert anti-inflammatory effects through: Blockade of NF-κB, and NLRP3 inflammasome, inhibition of pro-inflammatory cytokine production, IL-1β, IL-2, IL-6, TNF-α, IL-17A, down regulation of chemokines, and reduction of reactive oxygen and nitrogen species. Nevertheless, several reports have shown that some flavonoids enhance immune response by enhancing: oxygen and nitrogen radicals, antibody production, cytotoxic activity against tumours by increasing activating receptors and down regulating inhibitory receptors. In consequence, flavonoids may be potentially useful for treatment of infectious diseases and cancer. Conclusion: The most potent flavonoids in inflammation that modify immune responses are apigenin, quercetin and Epigallocatechin-3-Gallate (EGCG) although, other compounds are still under study and cannot be excluded. The most relevant patents concerning the use of flavones and other polyphenols were revised. A promising future of these compounds in different therapies is discussed.