Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

Elimination diet in food allergy: friend or foe?

Abstract Objectives To review and discuss the role of an elimination diet in food-allergic children, emphasizing nutritional aspects for a better practical approach. Sources Non-systematic review of the literature. Findings Under an elimination diet, food-allergic patients may suffer from growth impairment or obesity and compromised quality of life. Disease phenotype, age, type, number of foods excluded, comorbidities, eating difficulties, economic status, and food availability must be considered for an appropriate diet prescription. Diet quality encompasses diversity and degree of food processing, which may alter immune regulation. Conclusions A friendly food elimination diet prescription depends on a multidisciplinary approach beyond macro and micronutrients.

Immunothrombosis and its underlying biological mechanisms

Abstract The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process named immunothrombosis, which is at the basis of several infectious and inflammation-related thrombotic disorders, including coronavirus disease 2019 (COVID-19). In advanced stages, alterations in both coagulation and immune cell function due to extreme inflammation lead to an increase in blood coagulability, with high rates of thrombosis and mortality. Therefore, understanding underlying mechanisms in immunothrombosis has become decisive for the development of more efficient therapies to treat and prevent thrombosis in COVID-19 and in other thrombotic disorders. In this review, we outline the existing knowledge on the molecular and cellular processes involved in immunothrombosis, focusing on the role of neutrophil extracellular traps (NETs), platelets and the coagulation pathway. We also describe how the deregulation of hemostasis is associated with pathological conditions and can significantly aggravate a patient's condition, using COVID-19 as a clinical model.

Fiebre en pacientes inmunodeprimidos

Introducción: La fiebre es un marcador de enfermedades infecciosas e inflamatorias que se da por una respuesta inmune innata y por diferentes mediaciones entre marcadores moleculares. En el paciente inmunodeprimido, uno o varios mecanismos inmunológicos pueden estar alterados, debido a que la respuesta inmune puede estar deprimida y la fiebre puede denotar un estado patológico grave subyacente. Se realizó una búsqueda exploratoria en las bases de datos PubMed/Medline, Scopus y Scielo entre septiembre y octubre de 2022. Se incluyeron los términos fiebre, pacientes inmunodeprimidos, tratamiento y sistema inmune. Se seleccionaron 41 artículos científicos con diferentes diseños epidemiológicos. Objetivo: Describir aspectos relacionados con la fisiopatología de la fiebre, el tratamiento de la presencia de fiebre en pacientes con virus de inmunodeficiencia humana y síndrome de inmunodeficiencia adquirida, así como también en pacientes receptores de trasplantes de órgano sólido y de trasplantes hematopoyéticos, pacientes neutropénicos y pacientes tratados con corticosteroides y terapia biológica. Desarrollo: El tratamiento del paciente inmunodeprimido con fiebre incluye aspectos fundamentales como una adecuada anamnesis y examen físico, además de pruebas diagnósticas orientadas para establecer la causa de la fiebre. En estos pacientes, las infecciones juegan un papel protagónico y su intervención temprana es fundamental para impactar en la morbimortalidad. Conclusiones: El paciente inmunodeprimido con presencia de fiebre presenta un panorama desafiante para su manejo médico integral. Entre otros aspectos es relevante considerar el tipo y tiempo de inmunosupresión, así como los factores de riesgo, con el fin de orientar los diagnósticos y tratamientos.

Introduction: Fever is a marker of infectious and inflammatory diseases that is caused by an innate immune response and by different mediations between molecular markers. In the immunocompromised patient, one or more immunological mechanisms may be altered because the immune response may be compromised, and fever may denote a serious underlying disease state. An exploratory search was conducted in the PubMed/Medline, Scopus, and Scielo databases between September and October 2022. The terms fever immunocompromised patients, treatment, and immune system. A total of 41 scientific articles with different epidemiological designs were selected. Objective: To describe aspects related to the pathophysiology of fever, management of the presence of fever in patients with Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome, as well as in patients who have received solid organ transplants and hematopoietic transplants, neutropenic patients and patients treated with corticosteroids and biological therapy. Developing: The approach to the immunocompromised patient with fever includes fundamental aspects such as an adequate history and physical examination, as well as diagnostic tests aimed at establishing the cause of the fever. In these patients, infections play a leading role and early intervention is essential to impact morbidity and mortality. Conclusions: The immunocompromised patient with the presence of fever presents a challenging panorama for his/her comprehensive medical approach. Among other aspects, it is relevant to consider the type and duration of immunosuppression, as well as the risk factors, to guide diagnoses and treatments.

Fish oil supplementation in obese rats ameliorates metabolic syndrome response

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

Effects of immune exhaustion and senescence of innate immunity in autoimmune disorders

Innate immune system activation is crucial in the inflammatory response, but uncontrolled activation can lead to autoimmune diseases. Cellular exhaustion and senescence are two processes that contribute to innate immune tolerance breakdown. Exhausted immune cells are unable to respond adequately to specific antigens or stimuli, while senescent cells have impaired DNA replication and metabolic changes. These processes can impair immune system function and disrupt homeostasis, leading to the emergence of autoimmunity. However, the influence of innate immune exhaustion and senescence on autoimmune disorders is not well understood. This review aims to describe the current findings on the role of innate immune exhaustion and senescence in autoimmunity, focusing on the cellular and molecular changes involved in each process. Specifically, the article explores the markers and pathways associated with immune exhaustion, such as PD-1 and TIM-3, and senescence, including Β-galactosidase (β-GAL), lamin B1, and p16ink4a, and their impact on autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and immune-mediated myopathies. Understanding the mechanisms underlying innate immune exhaustion and senescence in autoimmunity may provide insights for the development of novel therapeutic strategies.

Relationship Between the Peripheral Blood Lymphocytes and the Progress of Amyotrophic Lateral Sclerosis in Central China / 华中科技大学学报(医学版)

Objective To explore the relationship between peripheral blood lymphocytes and disease progression in patients with amyotrophic lateral sclerosis(ALS)in central China.Methods A total of 133 ALS patients diagnosed at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology were evaluated for disease progression,and the includ-ed patients were divided into fast progression group and slow progression group.Peripheral blood lymphocyte subsets were de-termined and compared between the two groups.Logistic regression was used to analyze the association between the statistically different lymphocyte subgroups and the rate of disease progression.Results The proportion of CD3+CD19-T lymphocytes in the slow progression group was lower than that of the fast progression group(P＜0.05).However,the NK cell count,NK cell proportion,and the proportion of CD28+helper T cells(CD28+Th cells)were higher than those of the fast progression group(all P＜0.05).In the logistic regression analysis,an increase in NK cell count(OR=0.992,P＜0.05)and an increase in the propor-tion of CD28+Th cells(OR=0.895,P＜0.05)were protective factors for the progression of ALS.Conclusion The characteris-tics of peripheral lymphocytes differed between patients with slow and fast progression.Abnormalities in the innate immune sys-tem may be involved in the progression of ALS.

Regulatory effects of micro-arc oxidation on anti-bacterial and anti-inflammatory properties of metal implants / 中国组织工程研究

BACKGROUND:Micro-arc oxidation can effectively add bioactive elements to the metal surface and improve the anti-bacterial and anti-inflammatory properties of biomedical metal materials,so this technology has become one of the hotspots of biomedical materials. OBJECTIVE:To summarize the anti-bacterial and anti-inflammatory properties of surface coatings prepared by the combination of micro-arc oxidation and other surface modification technologies. METHODS:Articles from January 1996 to December 2022 were searched on CNKI,WanFang and PubMed databases using Chinese and English search terms"micro-arc oxidation,antibacterial properties,anti-inflammatory properties,metal implants".After preliminary screening according to inclusion and exclusion criteria,89 articles were retained and summarized. RESULTS AND CONCLUSION:The ceramic layer prepared by micro-arc oxidation can improve the anti-bacterial and anti-inflammatory properties of titanium,magnesium and other alloys.Combination with other surface modification technologies can effectively solve the effect of pores on the surface properties of the alloy,and further improve the biological properties of the oxide film.It has a wide application prospect in orthopedics and dentistry.At present,most studies are limited to metal coatings,and most of them focus on metal elements with good antibacterial properties such as silver and copper,while only a few studies mention non-metallic coatings such as graphene oxide,hydroxyapatite and chitosan.In the future,extensive studies can be conducted on inorganic coatings and polymer coatings,and more combinations of different bioactive elements can also be adopted to improve antibacterial properties.Currently,studies on the inflammation of implant coatings prepared by micro-arc oxidation are mostly limited to the immune system and focused on macrophages,while studies on neutrophils and platelets are scarce.In the future,a variety of advanced technologies should be combined to explore the specific effects of micro-arc oxidation coating on other immune cells and inflammatory cells.

Application and development of bone tissue engineering scaffolds with bone immune regulatory properties in repairing bone defects / 中国组织工程研究

BACKGROUND:Careful regulation of bone immune response during repair of bone scaffold is important for bone regeneration. OBJECTIVE:To review the influence of bone immune response on bone repair and the design of bone tissue engineering scaffold with regulating bone immune function and its application in bone repair. METHODS:Relevant articles published from 1973 to 2023 were retrieved from Science Direct,PubMed,Web of Science,and CNKI databases.English search terms were"osteoimmunology,macrophages,bone repair materials,bone scaffold,bone defects,bone regeneration".Chinese search terms were"bone immunity,macrophages,bone repair material,bone stent,bone defect,bone regeneration".Totally 80 articles of the latest research progress in this field were summarized and analyzed. RESULTS AND CONCLUSION:(1)A detailed review was conducted on the important time points in the origin and development process of bone immunity,and it was explained that macrophages,as important members of the bone immune regulatory system,can be divided into two phenotypes:M1(pro-inflammatory)and M2(anti-inflammatory),and play a key role in different stages of bone regeneration.During the inflammatory phase,M1 type macrophages can activate osteoclasts,initiate tissue repair processes,and participate in the reconstruction of bone microvascular networks.On the other hand,during the bone tissue regeneration process in the later stages of inflammation,sustained high expression of M1 type macrophages can hinder the formation of new bones.During the repair phase,M2 macrophages can secrete osteogenic cytokines,stimulate osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells,and promote bone formation.On the other hand,long-term activation of M2 macrophages can increase the secretion of fibrogenic molecules,leading to excessive formation of scar tissue and delaying the healing process.Therefore,regulating macrophages to undergo phenotype transformation at appropriate stages and constructing an immune microenvironment beneficial for osteogenesis has great significance for bone regeneration.(2)In the process of designing bone scaffolds with bone immune regulation characteristics,the physical and chemical properties such as scaffold roughness,pore structure,stiffness,hydrophilicity,surface charge,and surface functional groups can be changed to affect non-specific protein and cell adhesion,thereby affecting the interaction between bone scaffolds and the immune system.By designing surface functional coatings of bioactive substances such as hydroxyapatite,bioactive glass,metal ions,extracellular matrix,drugs,cytokines,and exosomes,the immune microenvironment can be actively regulated by releasing bioactive substances after implantation into the body,affecting macrophage polarization and crosstalk between macrophages and bone cells,and promoting more M2 polarization of macrophages,so as to build a bone immune microenvironment that is conducive to bone regeneration.(3)Based on the research and development of bone tissue engineering scaffolds,in addition to focusing on the direct regulatory factors of stem cell osteogenic differentiation,this article also proposes that attention should be paid to the management of the immune microenvironment of stem cell differentiation.By regulating the appropriate bone immune microenvironment,more stem cell osteogenic differentiation can be induced;the osteogenic efficiency of the scaffold can be enhanced,and the concept of"bone immune regulatory characteristics"can be condensed;deeply elucidated the multi-directional regulatory role of the bone immune microenvironment and introduced the existing strategies for changing the physicochemical properties and surface functional coating of scaffolds to endow them with bone immune regulatory potential,providing new ideas for guiding the development of a new generation of bone tissue engineering scaffolds with bone immune regulatory characteristics.However,the bone immune microenvironment is a dynamic equilibrium state,and most of the existing regulatory strategies do not consider the dynamic matching of regulation.Therefore,the research and development of intelligent bone immune regulatory scaffolds with efficient and targeted regulation of the immune microenvironment will be a key focus of attention for scholars in future.

Relationship between oral diseases and depression / 口腔疾病防治

@#Oral health is an integral component of overall well-being, with the oral cavity serving as a channel for external communication and expression of emotions such as stress and pessimism. Oral diseases can intensify feelings of depression, whereas depression can worsen oral health conditions. As a crucial part of the human microbiome, an imbalance in oral microbiota can release oral pathogenic microbes, which, through pathways including the circulation, nervous, and immune systems, can reach the brain and significantly affect the central nervous system. This can lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, further intensifying the development of depression. Similarly, an imbalance in oral microbiota in individuals with depression can intensify the occurrence of oral diseases. The relationship between depression and oral diseases is not isolated but rather a complex interplay in which they mutually influence and act as causative factors. To elucidate the causal relationship between oral diseases and depression and devise strategies for the prevention and treatment of both conditions, we explore the interaction mechanisms between oral diseases and depression from the perspective of oral microbiota. The occurrence of dental caries, periapical periodontitis, and periodontal diseases is closely associated with the excessive proliferation of specific bacteria in the oral cavity, such as Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum. These bacteria can directly invade the brain through the compromised blood-brain barrier, activating pro-inflammatory cytokines and worsening depressive symptoms. Inflammatory conditions and ulcers in the oral mucosa are caused by various factors, including infection and immune abnormalities. Because of compromised immune function in individuals with depression, these inflammatory responses are often more severe and difficult to control. Malocclusion, trigeminal neuralgia, and temporomandibular joint disorders increase the risk of depression because of psychological stress and changes in the immune system. We also outline the diagnostic and therapeutic considerations for oral diseases in patients with depression, emphasizing the importance of early intervention for disease management. Future research will explore the therapeutic potential of oral microbiota in individuals with depression, with the aim to improve symptoms and treatment outcomes by adjusting oral microbiota, thus providing novel avenues for the prevention and treatment of depression.

The Significant Roles of Gut-lung Microbiota in Shaping and Regulating Immunity / 中山大学学报(医学科学版)

The interaction between microbes and the human immune system has long been a focus in biomedical research. Next-generation sequencing has revealed that in addition to gut microbiota， the respiratory tract also harbors microbial communities， forming an interconnected network with the gut microbiota through immune cells and active factors. This review aims to explore how the gut and lung microbiota regulate immune responses， including their roles in local and systemic immune modulation. It also delineates the immunological connections along the gut-lung axis. Further elucidating the influence of microbes on the immune system holds important clinical significance for understanding diseases and exploring novel diagnostic and therapeutic strategies.

The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review

Objectives: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. Methods: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. Results: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). Conclusion: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged. Systematic review registration: PROSPERO CRD42021279246.

Glutamato monosódico y suprasistema neuroendocrinoinmune murino

Introducción: El glutamato monosódico se emplea en humanos desde el pasado siglo como potenciador del sabor. Su inoculación parenteral en murinos durante el período neonatal causa lesiones en varios núcleos hipotalámicos. Objetivo: Describir los efectos del glutamato monosódico sobre el sistema neuroendocrinoinmune en murinos. Metodos: Se realizó una revisión de artículos de libre acceso en las bases de datos PubMed y SciELO entre enero de 2013 y julio de 2020. También se examinó el texto básico de la asignatura Sangre y Sistema Inmune de la carrera de medicina. Desarrollo: Con independencia de su efecto adictivo, varios estudios defienden la inocuidad del glutamato monosódico. Sin embargo, este compuesto puede atravesar la barrera hematoencefálica de neonatos de murinos, y ocasionar trastornos metabólicos, reproductivos y del sistema inmune. Conclusiones: El glutamato monosódico en roedores causa alteraciones en los órganos que integran el suprasistema neuroendocrinoinmune y, por tanto, afecta sus funciones homeostáticas. Los mecanismos patogénicos no se conocen con exactitud.

Introduction: Monosodium glutamate has been used in humans since the last century as a flavor enhancer. Its parenteral inoculation in murine during the neonatal period causes lesions in several hypothalamic nuclei. Objective: To describe the effects of monosodium glutamate on the neuroendocrine immune system in murine samples. Methods: A review of open access articles in the PubMed and SciELO databases was conducted between January 2013 and July 2020. The basic text of the Blood and Immune System course of the medical school was also reviewed. Development: Regardless of its addictive effect, several studies defend the safety of monosodium glutamate. However, this compound can cross the blood-brain barrier of murine neonates, causing metabolic, reproductive and immune system disorders. Conclusions: Monosodium glutamate in rodents causes alterations in the organs that make up the neuroendocrine-immune suprasystem and, therefore, affects their homeostatic functions. The pathogenic mechanisms are not known exactly.

Anatomía Comparada del Bazo de la Rata Blanca (Rattus norvegicus albinus), Una Revisión de la Literatura / Comparative Anatomy of the Spleen of the White Rat, (Rattus norvegicus albinus) a Literature Review

El bazo es el órgano linfático intraperitoneal más grande del organismo, presentando dos funciones principales: defensiva, mediante respuesta inmunitaria y filtración sanguínea. El objetivo de la presente revisión, fue obtener información actualizada sobre la anatomía del bazo de la rata albina (Rattus norvegicus albinus) y comparativa con la anatomía del bazo humano, perro, gato y cerdo, al representar las principales especies de importancia en la medicina, medicina veterinaria y en las ciencias biomédicas. Se realizó una búsqueda de material bibliográfico actualizado en diferentes sitios web científicos. Es así como, se revisaron 71 fuentes bibliográficas, en su gran mayoría artículos científicos (31), libros de anatomía humana y veterinaria (17), artículos especializados (17) y tesis (6). En general existe consenso, sobre la descripción anatómica del bazo, el cual se sitúa en la región hipocondriaca izquierda del abdomen, entre el fondo del estómago y el diafragma, irrigado por la arteria y vena esplénica. Se evidenció que existen similitudes en aspectos macroscópicos, al comparar el bazo de la rata blanca, con el bazo de otras especies (funcionalidad, peso relativo, ubicación topográfica). En aspectos microscópicos, el bazo en humanos y otros mamíferos se compone de estroma, además de parénquima, constituido a su vez por pulpa blanca y roja. En particular, existen diferencias entre el bazo de rata, humano, gato, perro y cerdo, en formas, tamaños y aspectos microscópicos, relacionados con la microcirculación e inmunidad. Mientras que existen semejanzas en procesos patológicos y respuestas a tratamientos farmacológicos y clínicos. Por lo anteriormente expuesto, se concluye que la rata albina constituye un buen modelo biológico, específicamente en aspectos anatómicos microscópicos del bazo de tipo inmunológico. Mientras que el bazo de cerdo es mejor comparativamente, en estudios anatómicos macroscópicos de tipo quirúrgicos, resultando ambos extrapolables, especialmente a la medicina humana.

SUMMARY: The spleen is the largest intraperitoneal lymphatic organ of the body, presenting two main functions: defensive, through immune response and blood filtration. The objective of the present review was to obtain updated information on the anatomy of the spleen of the albino rat (Rattus norvegicus albinus) and to compare it with the anatomy of the human, dog, cat and pig spleen, representing the main species of importance in medicine, veterinary medicine and biomedical sciences. A search for updated bibliographic material was carried out in different scientific websites. Thus, 71 bibliographic sources were reviewed, mostly scientific articles (31), human and veterinary anatomy books (17), specialized articles (17) and theses (6). In general, there is consensus on the anatomical description of the spleen, which is located in the left hypochondriac region of the abdomen between the fundus of the stomach and the diaphragm, irrigated by the splenic artery and vein. It was evidenced that there are similarities in macroscopic aspects when comparing the spleen of the white rat with the spleen of other species (functionality, relative weight, topographic location). In microscopic aspects, the spleen in humans and other mammals is composed of stroma, in addition to parenchyma, constituted in turn by white and red pulp. In particular, there are differences between rat, human, cat, dog and pig spleens in shapes, sizes and microscopic aspects related to microcirculation and immunity. While there are similarities in pathological processes and responses to pharmacological and clinical treatments. For the above mentioned, it is concluded that the albino rat constitutes a good biological model, specifically in microscopic anatomical aspects of the spleen of immunological type. While the pig spleen is comparatively better in macroscopic anatomical studies of surgical type, both are extrapolable especially to human medicine.

La función de las proteínas de choque térmico en las infecciones virales / The Role of Heat Shock Proteins in Viral Infections

Resumen Las proteínas de choque térmico se describieron como una respuesta intracelular al estrés calórico; sin embargo, al paso del tiempo, se observó que estas proteínas tienen múltiples funciones y que participan de manera relevante tanto en los procesos fisiológicos como patológicos. Las actividades que realizan las proteínas de choque térmico se relacionan con su localización, que puede ser intra o extracelular, al momento fisiológico y a las diferentes asociaciones estructurales, que pueden ser desde péptidos derivados de estas, hasta dímeros o multímeros. Con base en estas características funcionales, se les ha denominado proteínas multiempleo o "moonlighting proteins". En este artículo se describen algunas de las actividades de estas proteínas con relación al sistema inmunológico y las infecciones virales, en particular con los procesos inflamatorios.

Abstract Heat shock proteins (HSP) were first described as a cell response to heat stress. However, over time, it has become clear they have multiple functions inside and outside cells, and that they actively participate in different physiological and pathological processes. They perform functions related to their cellular location or physiological moment, which is why they have been called multi-use proteins or "moonlighting proteins". Furthermore, HSP activity is associated with different structural conformations, from peptides derived from them or as dimers or multimers, to mention a few. This article describes these functions and their relationship with the immune system, and their relationship with viral infection, particularly with inflammatory processes.

Obesidad: un factor de riesgo en pacientes con COVID-19

Informes recientes dan cuenta de una fuerte asociación entre la obesidad y la severidad de la infección de COVID-19, lo cual se fundamenta en la presencia de un estado proinflamatorio crónico en el paciente obeso, vinculado a trastornos metabólicos y del sistema inmune. Este trabajo tiene como objetivo revisar los más recientes estudios sobre la asociación positiva que se establece entre la obesidad, como factor de riesgo, y la severidad y mortalidad de los pacientes con COVID-19; también renovar los mecanismos involucrados, para lo cual se seleccionaron artículos publicados -principalmente en los últimos cinco años- en las bases de datos PubMed, SciELO, ClinicalKey y LILACS, y en el motor de búsqueda Google Académico. Estos estudios incluyeron, entre otros parámetros, el Índice de Masa Corporal y su asociación a la severidad y mortalidad por COVID-19. Como resultado, la evidencia clínica sugiere que el sobrepeso y la obesidad presentan una alta prevalencia en los casos severos de pacientes adultos con COVID-19. Se concluye que la obesidad, en estos pacientes, requiere de un manejo particular, pues debe ser considerada un factor de riesgo independiente de otras comorbilidades. Esto se debe a su contribución a una mayor susceptibilidad y severidad, asociándose positivamente con alteraciones del sistema inmune y con reacciones hiperinflamatorias por liberación excesiva de citoquinas, comprometiendo el funcionamiento de órganos y sistemas y potenciando las complicaciones de la infección de SARS-CoV-2 y la mortalidad.

Recent reports indicate a strong association between obesity and the severity of COVID-19 infection, which is based on the presence of a chronic pro-inflammatory state in obese patients, linked to metabolic and immune system disorders. This paper aims to reviewing the most recent studies on the positive association established between obesity, as a risk factor, and severity and mortality of patients with COVID-19; it also aims to renew the involved mechanisms, for which articles published-mainly in the last five years-in the PubMed, SciELO, Clinical Key and LILACS databases, and in the Google Scholar search engine were selected. These studies included, among other parameters, the body mass index and its association to severity and mortality due to COVID-19. As a result, the clinical evidence suggests that overweight and obesity have a high prevalence in severe cases of adult patients with COVID-19. It is concluded that obesity, in these patients, requires a particular management, as it should be considered a risk factor independent of other comorbidities. This is due to its contribution to a greater susceptibility and severity, positively associated to alterations of the immune system and to hyper-inflammatory reactions by excessive release of cytokines, compromising the functioning of organs and systems and enhancing the complications of SARS-CoV-2 infection and mortality.

Alcohol: Immunomodulatory Effects and Cancer

ABSTRACT Alcohol consumption has been linked to numerous pathologic conditions, including infectious diseases and several types of cancer. Alcohol exerts its modulatory effects on the immune system (IS) in a dose- and time-dependent manner. Numerous studies indicate that these alterations affect responses such as peripheral inflammation or decreased antibody production and promote chronic inflammation, leading to cell death. The molecular mechanisms underlying these effects involve generating an oxidative tissue environment, producing cell damage-associated molecular patterns (DAMPs), and activating pattern recognition receptors. In particular, toll-like receptors and their signaling system emerge as central elements whose activity is altered by alcohol intake. There is also some epidemiological evidence demonstrating the causal role of alcohol in the development of various types of cancer, such as head-and-neck cancer, esophageal cancer, colorectal cancer, liver cancer, and breast cancer. Most recent evidence suggests that factors related to alcohol consumption and cancer include increased levels of acetaldehyde, production of reactive oxygen species, alteration in DNA methylation, and modifications in retinoid metabolism. In addition, changes associated with alcohol use on the IS and intestinal microbiota may favor the growth of some types of tumors.

La nutrición como herramienta terapéutica en adultos mayores post COVID-19

La COVID-19 constituye siendo un problema de salud para la mayoría de los países, a pesar de los avances logrados en control de la enfermedad las dudas se centran en las posibles secuelas y complicaciones de la enfermedad; los adultos mayores fueron y continúan siendo un grupo vulnerable a esta enfermedad. Desde el punto de vista terapéutico los requerimientos nutricionales pueden representar un factor de estimulación y estabilización del funcionamiento del sistema inmune. El objetivo de esta investigación fue describir la importancia del manejo nutricional en adultos mayores posterior a la infección por COVID-19. Para esto se realizó una investigación básica, no experimental y descriptiva consistente en una revisión bibliográfica no sistemática donde se utilizaron un total de 21 documentos relacionados con el tema de investigación publicados en los últimos 5 años en bases de datos regionales como Scielo, Lilas, Redalyc y Latindex y de alto impacto como Ice Web of Sciencie, Scopus, PubMed y Medline. Los principales resultados incluyen la identificación de elementos relacionados con la importancia del manejo nutricional en adultos mayores durante y posterior a la infección por COVID-19 y la influencia de la nutrición en el funcionamiento del sistema inmune. Se concluye que el manejo nutricional es importante para garantizar una adecuada evolución de la enfermedad, y mejor aún la recuperación después de pasado la etapa aguda de la enfermedad. El adecuado funcionamiento del sistema inmune se encuentra influenciado por la acción de distintos componentes nutricionales como son proteínas, carbohidratos, vitaminas y minerales.

COVID-19 is still a health problem for most countries, despite the progress made in controlling the disease, doubts center on the possible sequelae and complications of the disease; older adults were and continue to be a vulnerable group to this disease. From the therapeutic point of view, nutritional requirements can represent a factor of stimulation and stabilization of the functioning of the immune system. The objective of this research was to describe the importance of nutritional management in older adults after COVID-19 infection. For this, a basic, non-experimental and descriptive investigation was carried out consisting of a non-systematic bibliographic review where a total of 21 documents related to the research topic published in the last 5 years in regional databases such as Scielo, Lilas, Redalyc were used. and Latindex and high impact such as Ice Web of Science, Scopus, PubMed and Medline. The main results include the identification of elements related to the importance of nutritional management in older adults during and after COVID-19 infection and the influence of nutrition on the functioning of the immune system. It is concluded that nutritional management is important to guarantee an adequate evolution of the disease, and even better the recovery after the acute stage of the disease has passed. The proper functioning of the immune system is influenced by the action of different nutritional components such as proteins, carbohydrates, vitamins and minerals.

Papel de la plasticidad celular en la regeneración intestinalinducida por lesiones / Role of cell plasticity in injury-induced intestinal regeneration

El sistema intestinal posee una capacidad regenerativa intrínseca y fisiológica que tiene lugar a partir de las células madreLgr5+ ubicadas en el fondo de las criptas intestinales, las cuales se diferencian hacia las células progenitoras secretoras y absortivas con sus respectivas células especializadas mediante la activación de señalizaciones intracelulares como Wnt, Hippo y Notch. Condiciones adversas como lesiones e infecciones tisulares inducen esta actividad regenerativa promovida por variados mecanismos que influyen en el microambiente celular. El sistema inmunológico detecta alteraciones en el tejido intestinal y, a través de la activación de células inmunocompetentes y la secreción de citoquinas proinflamatorias, favorece la desdiferenciación de células especializadas hacia células madre para desencadenar la respuesta regenerativa. En cuanto al sistema nervioso entérico, su influencia está sujeta a modificaciones en la microbiota y los hábitos alimenticios, y se encuentra determinada en gran parte, por las células gliales entéricas y la expresión de distintos marcadores de plasticidad, que permiten limitar la lesión y reparar el tejido. Por su parte, la epigenéticamodifica la expresión genética y consecuentemente, la capacidadregenerativa intestinal, variando de acuerdo a cada paciente porla influencia de factores externos como la dieta o el estadopsicobiológico. De esta forma, la respuesta regenerativa intestinalinducida por lesiones, integra múltiples mecanismos y poseeimportantes repercusiones clínicas en cuanto a EII, disbiosise incluso tumorogénesis; conocer los mecanismos que regulanesta actividad puede sentar las bases para la creación de terapias innovadoras en el mismo ámbito(AU)

The intestinal system has an intrinsic and physiological regenerative capacity that takes place from the Lgr5+ stem cells located at the bottom of the intestinal crypts, which differentiate into secretory and absorptive progenitor cells with their specialized cells by activating intracellular signalslike Wnt, Hippo and Notch. Adverse conditions such asinjuries and tissue infections induce this regenerative activity promoted by various mechanisms that influence the cellular microenvironment. The immune system senses disturbances in the intestinal tissue and, through the activation of immunocompetent cells and the secretion of proinflammatorycytokines, favors the dedifferentiation of specialized cells intostem cells to trigger the regenerative response. Regarding theenteric nervous system, its influence is subject to modificationsin the microbiota and dietary habits, and is largely determinedby enteric glial cells and the expression of different plasticitymarkers, which enable to limit injuries and repair tissue. On the other hand, epigenetics modifies genetic expressionand, consequently, intestinal regenerative capacity, varying according to each patient due to the influence of external factors such as diet or psychobiological status. There fore, the intestinal regenerative response induced by lesions integrates multiple mechanisms and has important clinical repercussions in terms of IBD, dysbiosis, and even tumorigenesis; knowing themechanisms that regulate this activity can lay the foundations for the creation of innovative therapies in the same field (AU)

Myasthenia gravis in the complex scenario of LRBA-related immune dysregulation / Miastenia gravis no cenário clínico complexo das imunodesregulações relacionadas ao gene LRBA

Autoimmune diseases have been progressively recognized as a potential complication of primary immunodeficiency, especially for some genetic subtypes of common variable immunodeficiency. Although often associated with other autoimmune disorders, autoimmune myasthenia gravis is occasionally identified as a neuromuscular complication of primary immunodeficiency. We report the case of a Brazilian woman with common variable immunodeficiency-8 due to an LRBA variant, in which myasthenia gravis was identified in association with anti-acetylcholine receptor antibody. Marked clinical improvement occurred after intravenous immunoglobulin therapy.

Doenças autoimunes foram progressivamente reconhecidas como complicações potenciais das imunodeficiências primárias, especialmente para alguns subtipos genéticos das imunodeficiências comuns variáveis. Embora se associe comumente a outras doenças autoimunes, a Miastenia gravis autoimune adquirida foi raramente associada como complicação neuromuscular de imunodeficiências primárias. É descrito neste artigo o caso de paciente brasileira do sexo feminino com diagnóstico de Imunodeficiência Comum Variável tipo 8 por variante no gene LRBA, na qual foi identificada Miastenia gravis em associação a anticorpos antirreceptor de acetilcolina. Ela evoluiu com marcante melhora clínica após a introdução de terapêutica com imunoglobulina endovenosa.