Among its many functions, prolactin (PRL) participates in immune responses and promotes the activ... more Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T reg) cells are still unknown. Our goal was to determine whether PRL plays a role in T reg function. We measured the expression of PRL and its receptor in T reg and effector T (T eff) cells from 15 healthy individuals. We also evaluated the functional activity of T reg cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T reg cells constitutively expressed PRL receptor, whereas T eff cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T reg cells in vitro, reducing suppression from 37. 4 to 13% when PRL was added to co-cultures of T reg and T eff cells (P!0. 05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNg. We report for the first time that PRL receptor expression was constitutive in T reg cells but not in T eff cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T reg cells, apparently through the induced secretion of Th1 cytokines.
Background: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB... more Background: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. Methods: Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. Results: We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-...
In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The fa... more In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.
Neumología y Cirugía de Tórax Efecto de tres modos ventilatorios como único soporte en un modelo ... more Neumología y Cirugía de Tórax Efecto de tres modos ventilatorios como único soporte en un modelo experimental de inflamación sistémica por lipopolisacárido sobre la hemodinamia, fisiología pulmonar e histología Effect of three ventilation modes as the only support in a pig model with LPS-induced systemic inflammation on pulmonary physiology, histology and hemodynamics
Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; howev... more Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; however, there is controversy as to how the causes for progression from the acute to the chronic phase are defined. In this work, the presence of the parasite is correlated with the occurrence of cell infiltration and fibrosis in cardiac tissues, as well as IgG detection and disease progression in a murine model. Fifty CD1 mice were infected intraperitoneally with Trypanosoma cruzi, while 30 control were administered with saline solution. Parasitemia levels were determined, and IgG titers were quantified by ELISA. At different times, randomly selected mice were euthanized, and the heart was recovered. Cardiac tissue slides were stained with HE and Masson trichrome stain. A significant increase in parasitemia levels was observed after 15 days post-infection (dpi), with a maximum of 4.1 × 10 6 parasites on 33 dpi, ending on 43 dpi; amastigote nests were observed on 15-62 dpi. Histological analysis revealed lymphocytic infiltration and fibrotic lesions from 8 dpi until the end of the study, on 100 dpi. The presence of plasma cells in the myocardium observed on 40-60 dpi, accompanied by seropositivity to ELISA on 40-100 dpi, was regarded as the hallmark of the transition phase. Meanwhile, the chronic phase, characterized by the absence of amastigotes, presence of cell infiltration, fibrotic lesions, and seropositivity, started on 62 dpi. A strong correlation between parasitemia and the presence of amastigote nests was found (r 2 = 0.930), while correlation between the presence of fibrosis and of amastigote nests was weak (r 2 = 0.306), and that between fibrosis and lymphocyte infiltration on 100 dpi was strong (r 2 = 0.899). The murine model is suitable to study Chagas disease, since it can reproduce the chronic and acute phases of the human disease. The acute phase was determined to occur on 1-60 dpi, while the chronic phase starts on 62 dpi, and fibrotic damage is a consequence of the continuous inflammatory infiltration; on the other hand, fibrosis was determined to start on the acute phase, being more apparent in the chronic phase, when Chagas disease-related cardiopathy is induced.
There are different pathologies associated with amyloidogenic processes caused by the increase of... more There are different pathologies associated with amyloidogenic processes caused by the increase of reactive oxygen species (ROS) and the overactivation of inflammatory responses. These alterations are present in different regions of the anterior segment of the eye, and they have been associated with the development and progression of ocular pathologies, such as glaucoma, dry eye syndrome, keratitis, and cataracts among other pathologies. Aim. To discuss briefly the anatomical characteristics of the anterior segment of the eye and describe the interaction between oxidative stress (OS) and inflammatory responses, emphasizing the misfolding of several proteins leading to amyloidogenic processes occurring in the anterior segment and their implications in the development of ocular diseases. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms “eye,” “anterior segment”, “inflammation”, “oxidative stress”, and “amyloidosis”. The search encompassed manuscripts published u...
Introduction: Neuroinflammation has been proposed as a common factor and one of the main inducers... more Introduction: Neuroinflammation has been proposed as a common factor and one of the main inducers of neuronal degeneration. Galectins are a group of β-galactoside-binding lectins, that play an important role in the immune response, adhesion, proliferation, differentiation, migration and cell growth. Up to 15 members of the galectin's family have been identified; however, the expression of galectin-1 and galectin-3 has been considered a key factor in neuronal regeneration and modulation of the inflammatory response. Galectin-1 is necessary to stimulate the secretion of neurotrophic factors in astrocytes and promoting neuronal regeneration. In contrast, galectin-3 fosters the proliferation of microglial cells and modulates cellular apoptosis, therefore these proteins are considered a useful alternative for the treatment of degenerative diseases. Areas covered: This review describes the roles of galectin-1 and galectin-3 in the modulation of neuroinflammation and their potential as therapeutic targets in the treatment for neurodegenerative diseases. Expert opinion: Although data in the literature vary, the effects of galectin-1 and galectin-3 on the activation and modulation of astrocytes and microglia has been described. Due to its anti-inflammatory effects, galectin-1 is proposed as a molecule with therapeutic potential, whereas the inhibition of galectin-3 could contribute to reduce the neuroinflammatory response in neurodegenerative diseases.
Originally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borde... more Originally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borders through migration. It is caused by the protozoan Trypanosoma cruzi. Differences in disease severity have been attributed to a natural pleomorphism in T. cruzi. Several post-translational modifications (PTMs) have been studied in T. cruzi, but to date no work has focused on O-GlcNAcylation, a highly conserved monosaccharide-PTM of serine and threonine residues mainly found in nucleus, cytoplasm, and mitochondrion proteins. O-GlcNAcylation is thought to regulate protein function analogously to protein phosphorylation; indeed, crosstalk between both PTMs allows the cell to regulate its functions in response to nutrient levels and stress. Herein, we demonstrate O-GlcNAcylation in T. cruzi epimastigotes by three methods: by using specific antibodies against the modification in lysates and whole parasites, by click chemistry labeling, and by proteomics. In total, 1,271 putative O-GlcNAcylated proteins and six modification sequences were identified by mass spectrometry (data available via ProteomeXchange, ID PXD010285). Most of these proteins have structural and metabolic functions that are essential for parasite survival and evolution. Furthermore, O-GlcNAcylation pattern variations were observed by antibody detection under glucose deprivation and heat stress conditions, supporting their possible role in the adaptive response. Given the numerous biological processes in which O-GlcNAcylated proteins participate, its identification in T. cruzi proteins opens a new research field in the biology of Trypanosomatids, improve our understanding of infection processes and may allow us to identify new therapeutic targets.
In Chagas disease the clinical, acute and chronic manifestations are the result of the interactio... more In Chagas disease the clinical, acute and chronic manifestations are the result of the interaction between the parasite and the host factors. The balance between inflammatory and anti-inflammatory immune responses is essential for the increase or resolution of the manifestations in individuals infected with T. cruzi. To identify if children with chronic Chagas disease and heart injury is related with non-regulated Th1, Th2 and Th17 responses. We included 31 children with T. cruzi confirmed chronic infection from endemic areas of Mexico. Subsequently, they were separated according to their ECHO and ECG results into three groups according to the severity of cardiac involvement. Circulating Th1, Th2 and Th17 cytokine profiles were performed by Luminex assays and the results were analyzed by bivariate and multivariable analysis. Patients were classified in asymptomatic chronic (group 1, N = 12); individuals with IRBBB in ECG and incipient lesions in ECHO (Group 2, N = 8) and Patients with severe chronic symptomatic disease (Group 3, N = 11). The analysis of immune mediators revealed that patients with severe cardiac manifestations had significant higher levels (p < 0.05) of Th17 related cytokines including IL-17 and IL-6 as well as IFN-γ and IL-2. Also patients with severe cardiomyopathy exhibit increased levels of IL-13 (p < 0.05) after multivariate analysis. High levels of Th17 related cytokines including IL-17, IFN-γ, IL-6 and IL-2 and pro-fibrotic factors such as IL-13 could be associated to the severity of cardiac involvement in children with chronic T. cruzi infection. These cytokines could be useful as indicators for the early identification of cardiac damage associated to the T. cruzi infection.
Aging is the principal risk factor for the development of Alzheimer’s disease (AD). The hallmarks... more Aging is the principal risk factor for the development of Alzheimer’s disease (AD). The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42) and abnormal hyperphosphorylation of Tau (p-Tau) protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP), and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the...
O-GlcNAcylation is a highly dynamic post-translational modification whose level depends on nutrie... more O-GlcNAcylation is a highly dynamic post-translational modification whose level depends on nutrient status. Only two enzymes regulate O-GlcNAcylation cycling, the glycosyltransferase OGT (O-GlcNAc transferase) and the glycoside hydrolase OGA (O-GlcNAcase), that add and remove the GlcNAc moiety to and from acceptor proteins, respectively. During the last 30 years, OGT has emerged as a master regulator of cell life with O-GlcNAcylation being found in viruses, bacteria, insects, protists and metazoans. The study of OGT in different biological systems opens new perspectives for understanding this enzyme in many kingdoms of life. In this review, we summarize recent and older findings regarding the distribution of OGT in living organisms.
Chagas disease is a parasitic infection mainly found in Latin America; it is transmitted by a tri... more Chagas disease is a parasitic infection mainly found in Latin America; it is transmitted by a triatomine, also known as assassin bug or kissing bug. In humans, the parasite causes mostly cardiac disorders. Two-thirds of the Mexican territory are regarded as risk areas for vector transmission of Trypanosoma cruzi, the causal agent. The parasite can be found as a blood-borne trypomastigote or as an intracellular amastigote. The progression and severity of lesions could be due to frequent reinfections or to infection by highly virulent strains. A total of 3,327 individuals younger than 18 years old, living in risk areas for this disease in the rural setting of the States of Queretaro, San Luis Potosi, and Veracruz, underwent a seroepidemiological study. Among them, 37 subjects were seropositive for T. cruzi, and were studied to look for signs of cardiac pathology, which has only been reported in adults. A clinical record was prepared for all included individuals, and electrocardiography (ECG) and echocardiography (ECHO) studies were performed; 25 cases showed lesions compatible with the onset of Chagas cardiomyopathy. The other 12 patients showed either normal ECG and ECHO data or showed abnormal parameters that were not regarded as significant. Lesions found in the onset of Chagas cardiomyopathy in children are herein reported, along with 14 cases of cardiac pathology compatible with Chagas disease. Our results indicate that patients younger than 18 years can show a cardiac pathology similar to that observed in adults.
Graefe's Archive for Clinical and Experimental Ophthalmology, 2016
Purpose Corneal neovascularisation (CNV), with consequent loss of transparency, is due to an imba... more Purpose Corneal neovascularisation (CNV), with consequent loss of transparency, is due to an imbalance of proangiogenic factors. Cell-surface nucleolin (NCL) has been associated with neo-angiogenesis. There are studies identifying NCL translocation from nucleus to the cell surface, which is essential for endothelial cell proliferation. To find the possible role of NCL in the generation of corneal neovessels, the aim of this study is to characterise the NCL presence and cell-localisation in noninjured corneas, as well as to describe the changes in NCL cell and tissue localisation in CNV, and to analyse the effect of bevacizumab on NCL cellular and tissular distribution. Methods Suture-induced CNV was performed in mice. The corneal tissues were obtained and the histological and coimmunofluorescence assays were performed using different proteins, such as CD31, cadherin and isolectin B 4. To determine the possible role of VEGF in NCL presence and localisation in our CNV model, bevacizumab was concomitantly used. Results Nucleolin was principally observed in the nucleus of the basal epithelial cells of normal corneas. Interestingly, angiogenesis-induced changes were observed in the localisation of NCL, not only in tissue but also at the cellular level where NCL was extranuclear in epithelial cells, stromal cells and neovessels. In contrast, these changes were reverted when bevacizumab was used. Besides, NCL was able to stain only aberrant corneal neovessels in comparison with retinal vessels. Conclusions NCL mobilisation outside the nucleus during angiogenesis could have a possible role as a proangiogenic molecule in the corneal tissue.
Prolactin has different functions, including cytokine secretion and inhibition of the suppressor ... more Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (T reg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and T reg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by T reg cells from patients with SLE. CD4 þ CD25 hi CD127 À/low cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of T reg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on T reg and effector T (T eff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in T reg cells than in T eff cells, similar to healthy individuals, whereas there is no difference in the expression between T reg and T eff cells from active patients. In T reg :T eff cell cocultures, addition of prolactin decreases the suppressor effect exerted by T reg cells and increases IFNg secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by T reg cells over T eff cells, thereby favoring an inflammatory microenvironment.
Evidence exists about the relationship between the immune and the endocrine systems through commu... more Evidence exists about the relationship between the immune and the endocrine systems through communication of multiple factors such as cytokines, neuropeptides, neurotransmitters and hormones. Among the hormones, prolactin (PRL) has been shown to participate in the innate and adaptive immune response. In addition to being produced by the pituitary gland, PRL is also produced and secreted by cells of the immune system. The aim of this review is to update information about the involvement of PRL secreted by immune system cells in the immune response.
Medicina Oral Patología Oral y Cirugia Bucal, 2013
Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia... more Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia, and invasive carcinomas developed in the hamster's buccal pouch chemical carcinogenesis model. Study design: Fifty Syrian golden hamsters were equally divided in five groups (A-E); two controls and three experimental group exposed to alcohol, DMBA, or both for 14 weeks. Number of tumors per cheek, volume, histological condition, erbB expression were determined and results were analyzed by the Mann-Whitney U and Dunn's test. Results: Control groups and those exposed to alcohol (A, B and C respectively) only presented clinical and histological normal mucosa; while those exposed to DMBA or DMBA plus alcohol (D and E groups) developed dysplasia and invasive carcinomas. erbB2, erbB3, and erbB4 increased their expression in alcohol-exposed mucosa, dysplasia, and invasive carcinomas. We observed a similar expression level for erbB2 in dysplasia and carcinomas; while, erbB3 and erbB4 were similar only in carcinomas. Conclusion: The DMBA and alcohol can be considered as carcinogen and promoter for oral carcinogenesis. The erbB expression is different according to their histological condition, suggesting differential participation of the erbB family in oral carcinogenesis induced by alcohol and DMBA.
RESUMEN Los glicoconjugados intervienen en diversos procesos biológicos. Cambios en los procesos ... more RESUMEN Los glicoconjugados intervienen en diversos procesos biológicos. Cambios en los procesos de glicosilación, generan trastornos en las funciones biológicas que realizan. Las alteraciones en la glicosilación pueden ser congénitamente determinadas, adquiridas o no enzimáticas. En este trabajo, se revisan los mecanismos de glicosilación que se encuentran alterados en diversas enfermedades humanas.
The cardiovascular system is a complex and well-organized system in which glycosylation plays a v... more The cardiovascular system is a complex and well-organized system in which glycosylation plays a vital role. The heart and vascular wall cells are constituted by an array of specific receptors; most of them are N- glycosylated and mucin-type O-glycosylated. There are also intracellular signaling pathways regulated by different post-translational modifications, including O-GlcNAcylation, which promote adequate responses to extracellular stimuli and signaling transduction. Herein, we provide an overview of N-glycosylation and O-glycosylation, including O-GlcNAcylation, and their role at different levels such as reception of signal, signal transduction, and exogenous molecules or agonists, which stimulate the heart and vascular wall cells with effects in different conditions, like the physiological status, ischemia/reperfusion, exercise, or during low-grade inflammation in diabetes and aging. Furthermore, mutations of glycosyltransferases and receptors are associated with development of...
Among its many functions, prolactin (PRL) participates in immune responses and promotes the activ... more Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T reg) cells are still unknown. Our goal was to determine whether PRL plays a role in T reg function. We measured the expression of PRL and its receptor in T reg and effector T (T eff) cells from 15 healthy individuals. We also evaluated the functional activity of T reg cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T reg cells constitutively expressed PRL receptor, whereas T eff cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T reg cells in vitro, reducing suppression from 37. 4 to 13% when PRL was added to co-cultures of T reg and T eff cells (P!0. 05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNg. We report for the first time that PRL receptor expression was constitutive in T reg cells but not in T eff cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T reg cells, apparently through the induced secretion of Th1 cytokines.
Background: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB... more Background: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. Methods: Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. Results: We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-...
In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The fa... more In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.
Neumología y Cirugía de Tórax Efecto de tres modos ventilatorios como único soporte en un modelo ... more Neumología y Cirugía de Tórax Efecto de tres modos ventilatorios como único soporte en un modelo experimental de inflamación sistémica por lipopolisacárido sobre la hemodinamia, fisiología pulmonar e histología Effect of three ventilation modes as the only support in a pig model with LPS-induced systemic inflammation on pulmonary physiology, histology and hemodynamics
Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; howev... more Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; however, there is controversy as to how the causes for progression from the acute to the chronic phase are defined. In this work, the presence of the parasite is correlated with the occurrence of cell infiltration and fibrosis in cardiac tissues, as well as IgG detection and disease progression in a murine model. Fifty CD1 mice were infected intraperitoneally with Trypanosoma cruzi, while 30 control were administered with saline solution. Parasitemia levels were determined, and IgG titers were quantified by ELISA. At different times, randomly selected mice were euthanized, and the heart was recovered. Cardiac tissue slides were stained with HE and Masson trichrome stain. A significant increase in parasitemia levels was observed after 15 days post-infection (dpi), with a maximum of 4.1 × 10 6 parasites on 33 dpi, ending on 43 dpi; amastigote nests were observed on 15-62 dpi. Histological analysis revealed lymphocytic infiltration and fibrotic lesions from 8 dpi until the end of the study, on 100 dpi. The presence of plasma cells in the myocardium observed on 40-60 dpi, accompanied by seropositivity to ELISA on 40-100 dpi, was regarded as the hallmark of the transition phase. Meanwhile, the chronic phase, characterized by the absence of amastigotes, presence of cell infiltration, fibrotic lesions, and seropositivity, started on 62 dpi. A strong correlation between parasitemia and the presence of amastigote nests was found (r 2 = 0.930), while correlation between the presence of fibrosis and of amastigote nests was weak (r 2 = 0.306), and that between fibrosis and lymphocyte infiltration on 100 dpi was strong (r 2 = 0.899). The murine model is suitable to study Chagas disease, since it can reproduce the chronic and acute phases of the human disease. The acute phase was determined to occur on 1-60 dpi, while the chronic phase starts on 62 dpi, and fibrotic damage is a consequence of the continuous inflammatory infiltration; on the other hand, fibrosis was determined to start on the acute phase, being more apparent in the chronic phase, when Chagas disease-related cardiopathy is induced.
There are different pathologies associated with amyloidogenic processes caused by the increase of... more There are different pathologies associated with amyloidogenic processes caused by the increase of reactive oxygen species (ROS) and the overactivation of inflammatory responses. These alterations are present in different regions of the anterior segment of the eye, and they have been associated with the development and progression of ocular pathologies, such as glaucoma, dry eye syndrome, keratitis, and cataracts among other pathologies. Aim. To discuss briefly the anatomical characteristics of the anterior segment of the eye and describe the interaction between oxidative stress (OS) and inflammatory responses, emphasizing the misfolding of several proteins leading to amyloidogenic processes occurring in the anterior segment and their implications in the development of ocular diseases. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms “eye,” “anterior segment”, “inflammation”, “oxidative stress”, and “amyloidosis”. The search encompassed manuscripts published u...
Introduction: Neuroinflammation has been proposed as a common factor and one of the main inducers... more Introduction: Neuroinflammation has been proposed as a common factor and one of the main inducers of neuronal degeneration. Galectins are a group of β-galactoside-binding lectins, that play an important role in the immune response, adhesion, proliferation, differentiation, migration and cell growth. Up to 15 members of the galectin's family have been identified; however, the expression of galectin-1 and galectin-3 has been considered a key factor in neuronal regeneration and modulation of the inflammatory response. Galectin-1 is necessary to stimulate the secretion of neurotrophic factors in astrocytes and promoting neuronal regeneration. In contrast, galectin-3 fosters the proliferation of microglial cells and modulates cellular apoptosis, therefore these proteins are considered a useful alternative for the treatment of degenerative diseases. Areas covered: This review describes the roles of galectin-1 and galectin-3 in the modulation of neuroinflammation and their potential as therapeutic targets in the treatment for neurodegenerative diseases. Expert opinion: Although data in the literature vary, the effects of galectin-1 and galectin-3 on the activation and modulation of astrocytes and microglia has been described. Due to its anti-inflammatory effects, galectin-1 is proposed as a molecule with therapeutic potential, whereas the inhibition of galectin-3 could contribute to reduce the neuroinflammatory response in neurodegenerative diseases.
Originally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borde... more Originally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borders through migration. It is caused by the protozoan Trypanosoma cruzi. Differences in disease severity have been attributed to a natural pleomorphism in T. cruzi. Several post-translational modifications (PTMs) have been studied in T. cruzi, but to date no work has focused on O-GlcNAcylation, a highly conserved monosaccharide-PTM of serine and threonine residues mainly found in nucleus, cytoplasm, and mitochondrion proteins. O-GlcNAcylation is thought to regulate protein function analogously to protein phosphorylation; indeed, crosstalk between both PTMs allows the cell to regulate its functions in response to nutrient levels and stress. Herein, we demonstrate O-GlcNAcylation in T. cruzi epimastigotes by three methods: by using specific antibodies against the modification in lysates and whole parasites, by click chemistry labeling, and by proteomics. In total, 1,271 putative O-GlcNAcylated proteins and six modification sequences were identified by mass spectrometry (data available via ProteomeXchange, ID PXD010285). Most of these proteins have structural and metabolic functions that are essential for parasite survival and evolution. Furthermore, O-GlcNAcylation pattern variations were observed by antibody detection under glucose deprivation and heat stress conditions, supporting their possible role in the adaptive response. Given the numerous biological processes in which O-GlcNAcylated proteins participate, its identification in T. cruzi proteins opens a new research field in the biology of Trypanosomatids, improve our understanding of infection processes and may allow us to identify new therapeutic targets.
In Chagas disease the clinical, acute and chronic manifestations are the result of the interactio... more In Chagas disease the clinical, acute and chronic manifestations are the result of the interaction between the parasite and the host factors. The balance between inflammatory and anti-inflammatory immune responses is essential for the increase or resolution of the manifestations in individuals infected with T. cruzi. To identify if children with chronic Chagas disease and heart injury is related with non-regulated Th1, Th2 and Th17 responses. We included 31 children with T. cruzi confirmed chronic infection from endemic areas of Mexico. Subsequently, they were separated according to their ECHO and ECG results into three groups according to the severity of cardiac involvement. Circulating Th1, Th2 and Th17 cytokine profiles were performed by Luminex assays and the results were analyzed by bivariate and multivariable analysis. Patients were classified in asymptomatic chronic (group 1, N = 12); individuals with IRBBB in ECG and incipient lesions in ECHO (Group 2, N = 8) and Patients with severe chronic symptomatic disease (Group 3, N = 11). The analysis of immune mediators revealed that patients with severe cardiac manifestations had significant higher levels (p < 0.05) of Th17 related cytokines including IL-17 and IL-6 as well as IFN-γ and IL-2. Also patients with severe cardiomyopathy exhibit increased levels of IL-13 (p < 0.05) after multivariate analysis. High levels of Th17 related cytokines including IL-17, IFN-γ, IL-6 and IL-2 and pro-fibrotic factors such as IL-13 could be associated to the severity of cardiac involvement in children with chronic T. cruzi infection. These cytokines could be useful as indicators for the early identification of cardiac damage associated to the T. cruzi infection.
Aging is the principal risk factor for the development of Alzheimer’s disease (AD). The hallmarks... more Aging is the principal risk factor for the development of Alzheimer’s disease (AD). The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42) and abnormal hyperphosphorylation of Tau (p-Tau) protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP), and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the...
O-GlcNAcylation is a highly dynamic post-translational modification whose level depends on nutrie... more O-GlcNAcylation is a highly dynamic post-translational modification whose level depends on nutrient status. Only two enzymes regulate O-GlcNAcylation cycling, the glycosyltransferase OGT (O-GlcNAc transferase) and the glycoside hydrolase OGA (O-GlcNAcase), that add and remove the GlcNAc moiety to and from acceptor proteins, respectively. During the last 30 years, OGT has emerged as a master regulator of cell life with O-GlcNAcylation being found in viruses, bacteria, insects, protists and metazoans. The study of OGT in different biological systems opens new perspectives for understanding this enzyme in many kingdoms of life. In this review, we summarize recent and older findings regarding the distribution of OGT in living organisms.
Chagas disease is a parasitic infection mainly found in Latin America; it is transmitted by a tri... more Chagas disease is a parasitic infection mainly found in Latin America; it is transmitted by a triatomine, also known as assassin bug or kissing bug. In humans, the parasite causes mostly cardiac disorders. Two-thirds of the Mexican territory are regarded as risk areas for vector transmission of Trypanosoma cruzi, the causal agent. The parasite can be found as a blood-borne trypomastigote or as an intracellular amastigote. The progression and severity of lesions could be due to frequent reinfections or to infection by highly virulent strains. A total of 3,327 individuals younger than 18 years old, living in risk areas for this disease in the rural setting of the States of Queretaro, San Luis Potosi, and Veracruz, underwent a seroepidemiological study. Among them, 37 subjects were seropositive for T. cruzi, and were studied to look for signs of cardiac pathology, which has only been reported in adults. A clinical record was prepared for all included individuals, and electrocardiography (ECG) and echocardiography (ECHO) studies were performed; 25 cases showed lesions compatible with the onset of Chagas cardiomyopathy. The other 12 patients showed either normal ECG and ECHO data or showed abnormal parameters that were not regarded as significant. Lesions found in the onset of Chagas cardiomyopathy in children are herein reported, along with 14 cases of cardiac pathology compatible with Chagas disease. Our results indicate that patients younger than 18 years can show a cardiac pathology similar to that observed in adults.
Graefe's Archive for Clinical and Experimental Ophthalmology, 2016
Purpose Corneal neovascularisation (CNV), with consequent loss of transparency, is due to an imba... more Purpose Corneal neovascularisation (CNV), with consequent loss of transparency, is due to an imbalance of proangiogenic factors. Cell-surface nucleolin (NCL) has been associated with neo-angiogenesis. There are studies identifying NCL translocation from nucleus to the cell surface, which is essential for endothelial cell proliferation. To find the possible role of NCL in the generation of corneal neovessels, the aim of this study is to characterise the NCL presence and cell-localisation in noninjured corneas, as well as to describe the changes in NCL cell and tissue localisation in CNV, and to analyse the effect of bevacizumab on NCL cellular and tissular distribution. Methods Suture-induced CNV was performed in mice. The corneal tissues were obtained and the histological and coimmunofluorescence assays were performed using different proteins, such as CD31, cadherin and isolectin B 4. To determine the possible role of VEGF in NCL presence and localisation in our CNV model, bevacizumab was concomitantly used. Results Nucleolin was principally observed in the nucleus of the basal epithelial cells of normal corneas. Interestingly, angiogenesis-induced changes were observed in the localisation of NCL, not only in tissue but also at the cellular level where NCL was extranuclear in epithelial cells, stromal cells and neovessels. In contrast, these changes were reverted when bevacizumab was used. Besides, NCL was able to stain only aberrant corneal neovessels in comparison with retinal vessels. Conclusions NCL mobilisation outside the nucleus during angiogenesis could have a possible role as a proangiogenic molecule in the corneal tissue.
Prolactin has different functions, including cytokine secretion and inhibition of the suppressor ... more Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (T reg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and T reg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by T reg cells from patients with SLE. CD4 þ CD25 hi CD127 À/low cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of T reg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on T reg and effector T (T eff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in T reg cells than in T eff cells, similar to healthy individuals, whereas there is no difference in the expression between T reg and T eff cells from active patients. In T reg :T eff cell cocultures, addition of prolactin decreases the suppressor effect exerted by T reg cells and increases IFNg secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by T reg cells over T eff cells, thereby favoring an inflammatory microenvironment.
Evidence exists about the relationship between the immune and the endocrine systems through commu... more Evidence exists about the relationship between the immune and the endocrine systems through communication of multiple factors such as cytokines, neuropeptides, neurotransmitters and hormones. Among the hormones, prolactin (PRL) has been shown to participate in the innate and adaptive immune response. In addition to being produced by the pituitary gland, PRL is also produced and secreted by cells of the immune system. The aim of this review is to update information about the involvement of PRL secreted by immune system cells in the immune response.
Medicina Oral Patología Oral y Cirugia Bucal, 2013
Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia... more Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia, and invasive carcinomas developed in the hamster's buccal pouch chemical carcinogenesis model. Study design: Fifty Syrian golden hamsters were equally divided in five groups (A-E); two controls and three experimental group exposed to alcohol, DMBA, or both for 14 weeks. Number of tumors per cheek, volume, histological condition, erbB expression were determined and results were analyzed by the Mann-Whitney U and Dunn's test. Results: Control groups and those exposed to alcohol (A, B and C respectively) only presented clinical and histological normal mucosa; while those exposed to DMBA or DMBA plus alcohol (D and E groups) developed dysplasia and invasive carcinomas. erbB2, erbB3, and erbB4 increased their expression in alcohol-exposed mucosa, dysplasia, and invasive carcinomas. We observed a similar expression level for erbB2 in dysplasia and carcinomas; while, erbB3 and erbB4 were similar only in carcinomas. Conclusion: The DMBA and alcohol can be considered as carcinogen and promoter for oral carcinogenesis. The erbB expression is different according to their histological condition, suggesting differential participation of the erbB family in oral carcinogenesis induced by alcohol and DMBA.
RESUMEN Los glicoconjugados intervienen en diversos procesos biológicos. Cambios en los procesos ... more RESUMEN Los glicoconjugados intervienen en diversos procesos biológicos. Cambios en los procesos de glicosilación, generan trastornos en las funciones biológicas que realizan. Las alteraciones en la glicosilación pueden ser congénitamente determinadas, adquiridas o no enzimáticas. En este trabajo, se revisan los mecanismos de glicosilación que se encuentran alterados en diversas enfermedades humanas.
The cardiovascular system is a complex and well-organized system in which glycosylation plays a v... more The cardiovascular system is a complex and well-organized system in which glycosylation plays a vital role. The heart and vascular wall cells are constituted by an array of specific receptors; most of them are N- glycosylated and mucin-type O-glycosylated. There are also intracellular signaling pathways regulated by different post-translational modifications, including O-GlcNAcylation, which promote adequate responses to extracellular stimuli and signaling transduction. Herein, we provide an overview of N-glycosylation and O-glycosylation, including O-GlcNAcylation, and their role at different levels such as reception of signal, signal transduction, and exogenous molecules or agonists, which stimulate the heart and vascular wall cells with effects in different conditions, like the physiological status, ischemia/reperfusion, exercise, or during low-grade inflammation in diabetes and aging. Furthermore, mutations of glycosyltransferases and receptors are associated with development of...
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Papers by Edgar Zenteno