Effects of effective microorganisms on the physiological status, intestinal microbiome, and serum metabolites of Eriocheir sinensis / Efectos de microorganismos eficaces sobre el estado fisiológico, el microbioma intestinal y los metabolitos séricos de Eriocheir sinensis

The compound known as effective microorganisms (EMs) is widely used in aquaculture to improve water quality, but how they affect the health of Chinese mitten crab (Eriocheir sinensis) is unclear, especially in terms of intestinal microbiota and serum metabolites. In this study, we fed juvenile crabs with an EM-containing diet to explore the effects of EM on the physiological status, intestinal microbiome, and metabolites of E. sinensis. The activities of alanine aminotransferase and alkaline phosphatase were significantly enhanced by EM, indicating that EM supplementation effectively enhanced the antioxidant capacity of E. sinensis. Proteobacteria, Tenericutes, Firmicutes, Bacteroidetes, and Actinobacteria were the main intestinal microbes in both the control and EM groups. Linear discriminant effect size analysis showed that Fusobacteriaceae, Desulfovibrio, and Morganella were biomarkers in the control group, and Exiguobacterium and Rhodobacteraceae were biomarkers in the EM group. Metabolomics analysis revealed that EM supplementation increased cellular energy sources and decreased protein consumption, and oxidative stress. Together, these results indicate that EM can optimize the intestinal microbiome and serum metabolites, thereby benefiting the health of E. sinensis.(AU)

Toll-like receptors and Streptococcus mutans: An updated review article

It has been reported that toll-like receptors (TLRs) are the main innate immune receptors that recognize gram-positive pathogen-associated molecular patterns (PAMPs). The molecules can induce expression of the innate immune-related molecules that are essential against the bacteria. Streptococcus mutans (S. mutans) is a potential caries-associated pathogen, and innate immunity plays a key role in inhibiting its development and the progression of inflammatory responses. Recently, the roles played by TLRs against S. mutans and the induction of inflammatory responses were evaluated by several investigations. This review article discusses updated information regarding the roles played by TLRs and their potential therapeutic effects against S. mutans (AU)

The stimulator of interferon genes (STING) agonists for treating acute myeloid leukemia (AML): current knowledge and future outlook

Acute myeloid leukemia (AML) is an aggressive hematologic cancer in adults. Some patients exhibit restricted T cell infiltration and do not respond to routine treatments. This may be prevented by enhancing adaptive immunity by stimulating innate immune cells inside the tumor microenvironment (TME). To activate the adaptive immunological reaction against tumors, type I interferons (IFNs) can promote the presentation of tumor-specific cytotoxic T lymphocyte (CTL) cell recruitment. During the activation of innate immunity, cyclic di-nucleotides (CDNs) bind to and stimulate the stimulator of interferon genes (STING), a protein localized inside the endoplasmic reticulum (ER) membrane, resulting in the expression of type I IFNs. The efficacy of STING agonists as effective stimulators of the anti-tumor response in AML is being investigated in numerous clinical studies. Therefore, the purpose of this investigation was to thoroughly review existing knowledge in this field and provide perspective into the clinical potential of STING agonists in AML (AU)

The role of toll-like receptors (TLRs) and their therapeutic applications in endometrial cancer

Endometrial cancer (EC) is developed nations' most prevalent form of gynecologic cancer. Patients are frequently diagnosed with EC when the tumor is still limited to the uterus. Patients without tumor metastasis have a 5-year survival rate ranging from 80 to 90%; however, almost 16.8% of EC patients develop a metastatic form of the tumor. In the early stages of tumorigenesis, the immune system is able to identify aberrant cells as non-self, therefore providing the optimal pro-inflammatory microenvironment for the elimination of cancer cells. Although, chronic inflammation can be a crucial aspect of tumor development. Toll-like receptors (TLRs), as the main pattern recognition receptors (PRRs) in innate immunity, may stimulate an inflammatory response and provide cell survival in the tumor microenvironment (TME). TLRs are vital immunomodulators that may significantly impact the development of gynecologic malignancies. Therefore, TLR inhibitors are being researched for their possible benefits in treating gynecologic cancers. The aim of this study is to review the current knowledge in this field and provide some insight into the therapeutic potential of TLR inhibitors in EC (AU)

Cardiac arrhythmia and immune response in COVID-19 patients

The coronavirus disease 2019 (COVID-19) pandemic has presented substantial challenges for providing health care due to the numerous complications on the respiratory and cardiovascular systems of people. Cardiac arrhythmia is one of the cardiac complications, and it was observed in COVID-19 patients. Moreover, arrhythmia and cardiac arrest are common in COVID-19 patients in the intensive care unit. The occurrence of cardiac arrhythmia in COVID-19 patients is associated with hypoxia, cytokine storm, myocardial ischemia and inflammatory disease such as congestive heart failure. It is necessary to know the occurrence and mechanisms of tachyarrhythmia and bradyarrhythmia in patients with COVID-19 infection for their proper management. This review provides an overview of the association between COVID-19 and arrhythmias by detailing possible pathophysiological mechanisms (AU)

Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model

Background: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa character-ized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchy-mal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti-inflammatory potential in treating AR. Objective: The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model.Material and Methods: The AR murine model was induced by repeated sensitization and chal-lenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated.Results: Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symp-toms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (STAT6) at messenger RNA and protein levels in the nasal mucosa (AU)

Pulmonary manifestations in a cohort of patients with inborn errors of immunity: an 8-year follow-up study

Background Inborn errors of immunity (IEIs) are a group of congenital diseases caused by genetic defects in the development and function of the immune system. The involvement of the respiratory tract is one of the most common presentations in IEIs.Methods Overall, 117 patients with diagnosed IEIs were followed-up within 8 years at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD). Demographic, clinical, and laboratory data were collected in a questionnaire. Pulmonary function test (PFT), chest X-ray (CXR), and high-resolution computed tomography (HRCT) scans were obtained where applicable.Results Our study population consisted of 48 (41%) patients with predominantly antibody deficiencies (PADs), 39 (32%) patients with congenital defects of phagocytes, 14 (11.9%) patients with combined immunodeficiency (CID), and 16 (14%) patients with Mendelian susceptibility to mycobacterial diseases (MSMD). . Recurrent pneumonia was the most common manifestation, while productive cough appeared to be the most common symptom in almost all diseases. PFT showed an obstructive pattern in patients with PAD, a restrictive pattern in patients with CID, and a mixed pattern in patients with CGD. HRCT findings were consistent with bronchiectasis in most PAD patients, whereas consolidation and mediastinal lesions were more common in the other groups (AU)

Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated? / Rol de la activación del inflammasome en lupus eritematoso sistémico: están las células del sistema inmune innato activados?

Background: Systemic lupus erythematosus (SLE) is characterized by a wide spectrum of clinical and immunological abnormalities. New data have emerged about the role of inflammasomes in autoimmune diseases. We aimed to investigate whether basal inflammasome activation occurs in SLE patients, and whether a relationship between inflammasome-related-cytokines and disease activity exists. Methods: Fourteen (14) consecutive SLE patients and 13 healthy individuals, matched by sex, age and ethnicity, were included. Demographics, laboratory and clinical data were recorded. Peripheral blood mononuclear cells (PBMCs) from patients and controls were obtained and monocytes were isolated by negative selection. Purified monocytes were stimulated with LPS in the presence or absence of Caspase-1 inhibitor. CD14 and Caspase-1 expression were analyzed by flow cytometry. Cytokine levels were determined in plasma and culture supernatants by ELISA. Student's t test and Mann–Whitney tests were used for statistical analysis. Results: The percentage of CD14+/Caspase-1+ was significantly higher in monocytes from SLE patients compared to normal controls (p<0.01). These findings paralleled with higher plasma levels of IL-1β (p<0.05) and IL-18 (p<0.01) in those patients. Purified monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation where Caspase-1, IL-1β and IL-18 were highly expressed. Plasma levels of IL-18 were also significantly higher in SLE patients with active disease (p<0.05). In addition, the production of IL-18 was reduced by 3 fold when Caspase-1 inhibitor was added to the cultures. Conclusions: Monocytes from SLE patients exhibited increased inflammasome activation, characterized by high expression of Caspase-1, IL-1β and IL-18. Caspase-1 specific inhibitor decreased inflammasome activation (in vitro) by suppressing the production of IL-18.(AU)

Introducción: El lupus eritematoso sistémico (LES) se caracteriza por presentar diversas anormalidades clínicas e inmunológicas. El ensamblaje de los componentes del inflamasoma da lugar a la activación de caspasa-1, generando la liberación de citoquinas pro-inflamatorias IL-1β e IL-18. Objetivos: Evaluar si existe una activación basal del inflamasoma en pacientes con LES y determinar la asociación de las citoquinas IL-1β e IL-18 con la actividad de la enfermedad. Materiales y métodos: Se incluyeron 14 (n=14) pacientes consecutivos con LES y 13 (n=13) controles, pareados por edad, sexo y raza. Se recogieron datos clínicos, demográficos y de laboratorio. Los monocitos fueron aislados a partir de células mononucleares de sangre periférica obtenidas de pacientes y controles. Los monocitos purificados fueron estimulados con LPS, en presencia y ausencia de inhibidor de caspasa-1. La expresión de CD14 y caspasa-1 fueron determinados por citometría de flujo. Niveles de citoquinas fueron determinadas en plasma y en sobrenadantes de cultivos mediante técnica de ELISA. Test de Student y Mann-Whitney fueron usados para el análisis estadístico. Resultados: El porcentaje de CD14+/caspasa-1+ fue significativamente superior en monocitos de pacientes con LES vs. controles (p<0,01). En forma paralela, se encontraron niveles plasmáticos significativamente superiores de IL-1β (p<0,05) y de IL-18 (p<0,01) en pacientes con LES. Monocitos purificados de pacientes lúpicos presentaron una robusta respuesta inflamatoria luego de ser estimulados con LPS, donde caspasa-1, IL-1β e IL-18 fueron altamente expresados. Niveles plasmáticos de IL-18 fueron significativamente mayores en pacientes con LES y enfermedad activa (p<0,05). Por otro lado, la producción de IL-18 se redujo casi 3 veces cuando se agregó inhibidor de caspasa-1 en cultivos.(AU)

Group 2 innate lymphoid cells (ILC2s): The spotlight in asthma pathogenesis and lung tissue injury

Asthma is a heterogeneous disease with ranging etiology and severity. Asthma is a disease of chronic inflammation of the airways, with clinical symptoms of wheezing, breathlessness, cough, and chest tightness manifested as chronic fixed or variable airflow obstruction and airway hyperresponsiveness that predispose the airway epithelium to repeated injury, repair, and regeneration. In recent years, innate lymphoid cells (ILC1, ILC2, and ILC3) have been discovered. The predominant ILC type found in the lung tissue is group 2 innate lymphoid cells (ILC2s). Upon damage to the airway epithelium mediating the release of epithelial cytokines (TSLP, IL-33, and IL-25) ensued the activation of ILC2 in an antigen-independent manner. Activated ILC2 produces a significant amount of type 2 cytokines (IL-4, IL-5, IL-9, and IL-13), altogether contributing to type 2 inflammation in the airways. ILC2s are mediators of type 2 immunity for many type 2 inflammatory diseases such as asthma, since ILC2s were reported to play an important role in asthma pathogenesis. Here we discuss the role of ILC2 in the development of asthma and ILC2 effector cytokines (IL-4, IL-5, and IL-13) contributing to airway epithelial structural changes (AU)

COVID-19 natural herd immunity and risk of neuropsychiatric disorders / Inmunidad natural de grupo y riesgo de trastornos neuropsiquiátricos de la COVID-19

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Revisión narrativa sobre la respuesta inmunitaria frente a coronavirus: descripción general, aplicabilidad para SARS-COV-2 e implicaciones terapéuticas / Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications

El nuevo coronavirus (SARS-CoV-2) productor de síndrome respiratorio agudo severo surge en Wuhan, China, en diciembre de 2019. Genera la denominada enfermedad por coronavirus 2019 (COVID-19) y ha llevado a la declaración de emergencia de salud pública global a la Organización Mundial de la Salud. Este nuevo virus SARS-CoV-2 podría compartir características y respuesta inmune a las descritas para otros coronavirus. Dada su actividad sobre la vía del interferón y el modo en el que disregula la inmunidad innata, el uso de tratamientos dirigidos a modular o contener esta pueden ser de interés. Se realiza una revisión narrativa de la evidencia actual acerca de la inmunidad sobre coronavirus y su aplicabilidad para SARS-CoV-2. Se describe también la fisiopatogenia y la actividad leucocitaria subyacente, con intención de clarificar la posible utilidad de biomarcadores inflamatorios y el desarrollo de tratamientos personalizados

The new coronavirus (SARS-CoV-2) that causes a severe acute respiratory syndrome emerges in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV-2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and its applicability to SARS-CoV-2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments

Entendiendo los mecanismos que conducen al escape inmunológico y la patogenia del nuevo coronavirus SARS-CoV-2 / No disponible

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La participación de la inmunidad en la patogenia de la hipertensión arterial / The participation of immunity in the pathogenesis of arterial hypertension

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Deficiencia de vitamina D en pacientes ambulatorios con enfermedad inflamatoria intestinal: prevalencia y asociación con la actividad clínica-biológica / Vitamin D deficiency in outpatients with inflammatory bowel disease: prevalence and association with clinical-biological activity

Introducción: los datos sobre la prevalencia del déficit de vitamina D en pacientes con enfermedad inflamatoria intestinal (EII) en España son escasos. Dicha deficiencia podría asociarse a un peor curso evolutivo. Objetivo: determinar la prevalencia de deficiencia de 25-hidroxivitamina D (25OHD) en una cohorte de pacientes ambulatorios con enfermedad inflamatoria intestinal y evaluar su asociación con la actividad clínica-biológica, la calidad de vida y síntomas psicológicos. Material y métodos: estudio observacional unicéntrico de tipo transversal. Las variables de estudio se obtuvieron mediante entrevista clínica, revisión del historial médico y cuestionarios validados (escala de ansiedad y depresión hospitalaria y cuestionario corto de calidad de vida de la EII). La determinación de 25OHD fue hecha en el mismo laboratorio por inmunoanálisis de electroquimioluminiscencia. Resultados: se analizaron 224 pacientes. La prevalencia de deficiencia de vitamina D en enfermedad de Crohn (EC) y colitis ulcerosa (CU) fue de un 33,3% y un 20,3% respectivamente. En EC, la deficiencia de vitamina D se asoció con una mayor actividad clínica (p < 0,001) y una mayor concentración de calprotectina fecal (p = 0,01). En CU, hubo asociación con la actividad clínica (p < 0,001), el uso de esteroides en el último semestre (p = 0,001) y los ingresos hospitalarios en el año previo (p = 0,003). En un subanálisis de 149 pacientes no se observó asociación de vitamina D con la calidad de vida ni con las subpuntuaciones de la escala de ansiedad y depresión hospitalaria. Conclusiones: la deficiencia de vitamina D es frecuente en pacientes con enfermedad inflamatoria intestinal. Se observó una asociación entre su concentración y los índices clínicos de actividad, así como con los niveles de calprotectina fecal en enfermedad de Crohn

Introduction: there are few data on the prevalence of vitamin D deficiency in patients with inflammatory bowel disease (IBD) in Spain. A deficiency could be associated with a worse course of the disease. Aim: to determine the prevalence of 25-hydroxyvitamin D (25OHD) deficiency in a cohort of outpatients with IBD and assess its association with clinical and biological activity, quality of life and psychological symptoms. Methods: a cross-sectional, single-center observational study was performed. The study variables were obtained via clinical interviews, medical chart review and validated questionnaires (Hospital Anxiety and Depression Scale and Short Quality of Life in Inflammatory Bowel Disease Questionnaire). 25OHD was measured in the same laboratory by an electro-chemiluminescence immunoassay. Results: the study included 224 patients. The prevalence of vitamin D deficiency in Crohn's disease and ulcerative colitis was 33.3% and 20.3%, respectively. In Crohn's disease, vitamin D deficiency was associated with a higher clinical activity (p < 0.001) and a higher concentration of fecal calprotectin (p = 0.01). In ulcerative colitis, it was associated with clinical activity (p < 0.001), the use of steroids during the last six months (p = 0.001) and hospital admission during the previous year (p = 0.003). A sub-analysis of 149 patients failed to detect an association between vitamin D and quality of life or the scores of the Hospital Anxiety and Depression Scale. Conclusions: vitamin D deficiency is common in patients with inflammatory bowel disease. An association was found between vitamin D concentration and clinical activity indexes, as well as fecal calprotectin levels in Crohn's disease

Aspergilosis invasora en el paciente con enfermedad oncohematológica / Invasive aspergillosis in the patient with oncohematologic disease

La aspergilosis invasora es la infección fúngica invasora más frecuente en pacientes con neoplasias hematológicas agudas o tratados con trasplante de progenitores hematopoyéticos debido a la marcada alteración de los mecanismos fisiológicos de inmunidad antifúngica que tiene lugar en estas situaciones. Por este motivo, la profilaxis antifúngica tiene un papel relevante en estos pacientes. La introducción de nuevos agentes antifúngicos ha motivado la actualización de las recomendaciones de profilaxis y tratamiento en distintas guías. Los objetivos de este capítulo son una breve revisión de los mecanismos de la inmunidad frente a los hongos, de la definición de riesgo de desarrollo de infección fúngica invasora y una actualización de las recomendaciones de profilaxis y el tratamiento de la aspergilosis invasora en el conjunto de pacientes con enfermedades hematológicas

Invasive aspergillosis is the most common invasive fungal infection in patients with acute hematological malignancies or treated with hematopoietic stem cell transplantation due to the marked alteration of the physiological mechanisms of antifungal immunity that takes place in these situations. For this reason, antifungal prophylaxis has a relevant role in these patients. The introduction of new antifungal agents has motivated the updating of recommendations for prophylaxis and treatment in different guidelines. The objectives of this chapter are a brief review of the mechanisms of immunity against fungi, the definition of risk for developing an invasive fungal infection and an update of the prophylaxis recommendations and treatment of invasive aspergillosis in the group of patients with hematological diseases

The roles of toll like receptor 3, 7 and 8 in allergic rhinitis pathogenesis

Allergic rhinitis, as an allergic and nasal hypersensitivity disease, is associated with the inflammation of nasal mucosa. It appears that innate immune receptors are the important risk factors in the pathogenesis of the inflammatory disease. Toll-like receptors (TLRs) are the most important receptors of innate immunity; their crucial roles in the recognition of allergens and subsequently pathogenesis of allergic diseases have been evaluated recently. TLR3, 7 and 8 are the intracellular members of the innate immune receptors and recognize intracellular single and double strand RNAs. This review article collected the investigations regarding the roles of TLR3, 7 and 8 in the allergic rhinitis pathogenesis

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Nuevos horizontes para el tratamiento del glaucoma. I: neuroinflamación e inflamasomas / New horizons for the treatment of glaucoma. I: Neuroinflammation and inflammasomes

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