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1.
Medicine (Baltimore) ; 100(35): e27059, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34477138

RESUMEN

ABSTRACT: Prolidase enzyme activity is important for collagen resynthesis. In late stages of osteoarthritis (OA) its activity is decreased.To evaluate prolidase expression in knees of patients undergoing total arthroplasty for OA, and compare with young people undergoing knee arthroscopy due to traumatic injuries.In this cross-sectional study we included 20 patients with OA grade IV who underwent total knee arthroplasty and 20 controls of young patients who underwent arthroscopy for another reason besides OA. All participants were evaluated by knee ultrasound before the procedure. During the procedure, synovial tissue biopsies were taken and analyzed by immunofluorescence to search inflammation. Measures of central tendency, dispersion measures and position measures were used for the case of quantitative variables. Student t test or Mann-Whitney U test, and the logistic regression of Cox, was used.Prolidase expression in the synovial biopsy was significantly lower in the OA group than in the controls (0.017 ±â€Š0.009 vs 0.062 ±â€Š0.094, P < .05). Power Doppler (PD) signal was present in the synovitis of all knee recesses of the OA group in grayscale and in 17 (85%) of knees. The mean of the micro-vessel count in patients with OA was significantly higher vs controls (11 + 5.3 vs 4 + 2.1, P = .001). The neovascularization correlated significantly with the presence of PD signal in patients with OA (1.16, 95% CI, 1.02-1.34, P = .02).The prolidase expression in the synovial membrane evaluated by immunofluorescence, in patients with late stages of knee OA, is low, which may be interpreted as an evidence of decreased collagen resynthesis.


Asunto(s)
Dipeptidasas/análisis , Osteoartritis de la Rodilla/patología , Anciano , Estudios Transversales , Dipeptidasas/fisiología , Femenino , Humanos , Inflamación/patología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Ultrasonografía/métodos
3.
Signal Transduct Target Ther ; 6(1): 328, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34471088

RESUMEN

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , Microambiente Celular/inmunología , Pulmón/inmunología , Receptores CXCR3/inmunología , SARS-CoV-2/inmunología , Enzima Convertidora de Angiotensina 2/inmunología , Animales , Linfocitos T CD8-positivos/patología , COVID-19/patología , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/patología , Interferón-alfa/inmunología , Interleucina-6/inmunología , Pulmón/patología , Pulmón/virología , Macaca mulatta , Masculino
4.
Nat Commun ; 12(1): 5205, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34471128

RESUMEN

Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia. We identify immaturity of Leydig cells, chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. We find that deregulated expression of parentally imprinted genes in myoid and immature Leydig cells, with relevant changes in the ratio of Lamin A/C transcripts and an active DNA damage response in Leydig and peritubular myoid cells are also indicative of senescence of the testicular niche. This study offers molecular insights into the pathogenesis of idiopathic germ cell aplasia.


Asunto(s)
Envejecimiento/fisiología , Daño del ADN , Inflamación , Testículo/metabolismo , Envejecimiento/genética , Comunicación Celular , Quimiocinas , Perfilación de la Expresión Génica , Células Germinativas , Humanos , Inflamación/patología , Células Intersticiales del Testículo , Masculino , Fenotipo , Alineación de Secuencia , Espermatogénesis/genética , Espermatogénesis/fisiología , Espermatogonias/metabolismo , Transcriptoma
5.
Pan Afr Med J ; 38: 396, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34381540

RESUMEN

Introduction: chronic rhinosinusitis (CRS) is characterised by inflammation of the mucosal lining of the nose and paranasal sinuses for at least 12 weeks duration. Other than the diagnostic criteria that is based on clinical features; nasoendoscopy and/or computerized tomographic scan have been included in the diagnosis. This study seeks to outline the clinical evaluation and nasoendoscopic assessment of CRS patients. Methods: a hospital-based analytical study carried out on 154 participants. Clinical assessment and nasoendoscopy were performed and scored according to the discharge, inflammation and polyps/oedema (DIP) scale. Statistical analysis was carried out and results were presented in charts and tables. Results: of the 154 participants, 71 (46.1%) were males and 83 (53.9%) females with a male to female ratio of 1: 1.7. Nasal discharge and blockage were the commonest symptoms. Nasoendoscopy had higher yield in the examination of intranasal polyps (NPs) over anterior rhinoscopy. The prevalence of NPs was 26.6%. The result of DIP nasoendoscopic findings revealed more participants with moderate scores. There was a significant statistical difference between the presence of NPs on nasoendoscopy and DIP score. Conclusion: nasoendoscopy is an important aspect in the diagnosis and evaluation of patients with CRS. It provides a better visualization of NPs; therefore, it should be made routine in the clinical assessment and treatment of patients with CRS. The nasal endoscopic scoring of CRS should be considered as a common practice in clinical setting as well.


Asunto(s)
Endoscopía/métodos , Pólipos Nasales/diagnóstico , Rinitis/diagnóstico , Sinusitis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/patología , Masculino , Persona de Mediana Edad , Pólipos Nasales/patología , Nigeria , Rinitis/patología , Sinusitis/patología , Adulto Joven
6.
Pan Afr Med J ; 38: 408, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34381552

RESUMEN

Hydroxyapatite crystal deposition disease (HADD) of the hand and wrist is rare but can cause acute inflammatory syndromes that mimic infectious arthritis. These symptoms, which rapidly resolve with systemic anti-inflammatory drugs, are a source of diagnostic errors and inappropriate treatment. It is of crucial importance to make the diagnosis in order to avoid iatrogenic surgical management. The aim of this study was to determine the clinical and radiographic signs and the key features on which diagnosis depends. Treatment effectiveness and the course of the disease were also examined. Between 1992 and 2008, 12 patients consulted for an isolated acute local inflammatory syndrome of the hand or wrist, which was accompanied by a unique radiographic picture of calcific density. All patients were reassessed clinically and radiographically with a minimum follow-up of 2 years. All patients had presented with acute local inflammatory syndromes. Nine patients had edema and 8 had swelling and erythema. No patient had fever. The course was favorable in 11 patients and one patient required surgery. No patient had a recurrence at the mean final follow-up of 90 ± 64 months. The symptoms associated with hydroxyapatite crystal deposits suggest septic arthritis with acute joint inflammation. The radiological appearance is characteristic and corrects the diagnosis. Oral anti-inflammatory treatment gives more rapid spontaneous improvement, with complete and long-lasting resolution.


Asunto(s)
Calcinosis/diagnóstico por imagen , Durapatita/metabolismo , Mano/diagnóstico por imagen , Muñeca/diagnóstico por imagen , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Artritis Infecciosa/diagnóstico , Calcinosis/patología , Calcinosis/terapia , Edema/etiología , Femenino , Estudios de Seguimiento , Mano/patología , Humanos , Inflamación/diagnóstico por imagen , Inflamación/patología , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Muñeca/patología
7.
FASEB J ; 35(9): e21798, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34339064

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID-19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR-ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium-binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID-19, pathological similarities of the affected lungs between COVID-19 and S100A8-induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll-like receptor 4/Myeloid differentiation protein-2 (TLR4/MD-2) and mediates hyper-inflammation even after elimination of endotoxin-producing extrinsic pathogens, analogous findings between COVID-19-associated ARDS and pre-metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID-19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID-19-associated ARDS.


Asunto(s)
COVID-19/complicaciones , Calgranulina A/fisiología , Síndrome de Liberación de Citoquinas/etiología , Inflamación/etiología , Pandemias , Síndrome de Dificultad Respiratoria/etiología , SARS-CoV-2/genética , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/fisiología , Animales , Antivirales/farmacología , COVID-19/genética , COVID-19/patología , Calgranulina A/sangre , Calgranulina A/genética , Quimiocina CXCL11/sangre , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/patología , Disacáridos/farmacología , Disacáridos/uso terapéutico , Modelos Animales de Enfermedad , Descubrimiento de Drogas , Células Epiteliales/metabolismo , Células Epiteliales/virología , Humanos , Inflamación/genética , Inflamación/patología , Pulmón/metabolismo , Pulmón/patología , Pulmón/virología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Antígeno 96 de los Linfocitos/fisiología , Macaca mulatta , Ratones , Ratones Transgénicos , Modelos Biológicos , Mutación , Síndrome de Dificultad Respiratoria/genética , Síndrome de Dificultad Respiratoria/metabolismo , Especificidad de la Especie , Fosfatos de Azúcar/farmacología , Fosfatos de Azúcar/uso terapéutico , Receptor Toll-Like 4/fisiología , Regulación hacia Arriba , Internalización del Virus
8.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34445084

RESUMEN

Atherosclerosis is the major cause of the development of cardiovascular disease, which, in turn, is one of the leading causes of mortality worldwide. From the point of view of pathogenesis, atherosclerosis is an extremely complex disease. A huge variety of processes, such as violation of mitophagy, oxidative stress, damage to the endothelium, and others, are involved in atherogenesis; however, the main components of atherogenesis are considered to be inflammation and alterations of lipid metabolism. In this review, we want to focus on inflammation, and more specifically on the cellular elements of adaptive immunity, T and B cells. It is known that various T cells are widely represented directly in atherosclerotic plaques, while B cells can be found, for example, in the adventitia layer. Of course, such widespread and well-studied cells have attracted attention as potential therapeutic targets for the treatment of atherosclerosis. Various approaches have been developed and tested for their efficacy.


Asunto(s)
Aterosclerosis/inmunología , Linfocitos B/inmunología , Inmunidad , Linfocitos T/inmunología , Inmunidad Adaptativa , Animales , Aterosclerosis/patología , Linfocitos B/patología , Humanos , Inmunidad Celular , Inflamación/inmunología , Inflamación/patología , Linfocitos T/patología
9.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34445096

RESUMEN

(1) Background: Inflammation is a major pathomechanism in the development and progression of age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) may contribute to retinal inflammation via activation of its Toll-like receptors (TLR). TLR are pattern recognition receptors that detect the pathogen- or danger-associated molecular pattern. The involvement of TLR activation in AMD is so far not understood. (2) Methods: We performed a systematic literature research, consulting the National Library of Medicine (PubMed). (3) Results: We identified 106 studies, of which 54 were included in this review. Based on these studies, the current status of TLR in AMD, the effects of TLR in RPE activation and of the interaction of TLR activated RPE with monocytic cells are given, and the potential of TLR activation in RPE as part of the AMD development is discussed. (4) Conclusion: The activation of TLR2, -3, and -4 induces a profound pro-inflammatory response in the RPE that may contribute to (long-term) inflammation by induction of pro-inflammatory cytokines, reducing RPE function and causing RPE cell degeneration, thereby potentially constantly providing new TLR ligands, which could perpetuate and, in the long run, exacerbate the inflammatory response, which may contribute to AMD development. Furthermore, the combined activation of RPE and microglia may exacerbate neurotoxic effects.


Asunto(s)
Degeneración Macular/patología , Epitelio Pigmentado de la Retina/patología , Receptores Toll-Like/análisis , Animales , Humanos , Inflamación/patología , Microglía/patología
10.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-34445599

RESUMEN

Not long ago, self-reactive immune activity was considered as pathological trait. A paradigm shift has now led to the recognition of autoimmune processes as part of natural maintenance of molecular homeostasis. The immune system is assigned further roles beneath the defense against pathogenic organisms. Regarding the humoral immune system, the investigation of natural autoantibodies that are frequently found in healthy individuals has led to further hypotheses involving natural autoimmunity in other processes as the clearing of cellular debris or decrease in inflammatory processes. However, their role and origin have not been entirely clarified, but accumulating evidence links their formation to immune reactions against the gut microbiome. Antibodies targeting highly conserved proteins of the commensal microflora are suggested to show self-reactive properties, following the paradigm of the molecular mimicry. Here, we discuss recent findings, which demonstrate potential links of the commensal microflora to the immunological homeostasis and highlight the possible implications for various diseases. Furthermore, specific components of the immune system, especially antibodies, have become a focus of attention for the medical management of various diseases and provide attractive treatment options in the future. Nevertheless, the development and optimization of such macromolecules still represents a very time-consuming task, shifting the need to more medical agents with simple structural properties and low manufacturing costs. Synthesizing only the biologically active sites of antibodies has become of great interest for the pharmaceutical industry and offers a wide range of therapeutic application areas as it will be discussed in the present review article.


Asunto(s)
Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Desarrollo de Medicamentos , Microbioma Gastrointestinal , Homeostasis , Sistema Inmunológico/inmunología , Inflamación/inmunología , Animales , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/patología , Autoinmunidad , Humanos , Sistema Inmunológico/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/patología
11.
Nat Commun ; 12(1): 5074, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34417463

RESUMEN

ß cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human ß cells with inflammation but its expression is reduced in surviving ß cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate ß cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO ß cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between ß cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in ß cells may reduce activating pathologic immune cells and killing of ß cells.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Diabetes Mellitus Tipo 1/patología , Inflamación/patología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Proteínas Proto-Oncogénicas/metabolismo , Animales , Secuencia de Bases , Citotoxicidad Inmunológica , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Progresión de la Enfermedad , Femenino , Humanos , Inmunidad , Inflamación/genética , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Linfocitos T/inmunología , Transcripción Genética
12.
Sci Adv ; 7(32)2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34348897

RESUMEN

We investigated the influence of Bacillus Calmette-Guérin (BCG) vaccination on the unstimulated plasma levels of a wide panel of cytokines, chemokines, acute-phase proteins (APPs), matrix metalloproteinases (MMPs), and growth factors in a group of healthy elderly individuals (age, 60 to 80 years) at baseline (before vaccination) and 1 month after vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrated that BCG vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines and type 1 interferons. BCG vaccination also resulted in decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors. Plasma levels of the aforementioned parameters were significantly lower in vaccinated individuals when compared to unvaccinated control individuals. Thus, our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses.


Asunto(s)
Vacuna BCG/administración & dosificación , COVID-19/inmunología , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Inflamación/prevención & control , Vacunación/métodos , Anciano , Anciano de 80 o más Años , Vacuna BCG/inmunología , COVID-19/epidemiología , COVID-19/virología , Estudios de Casos y Controles , Femenino , Humanos , India/epidemiología , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología
13.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-34445223

RESUMEN

Increasing evidence suggests that systemic inflammation triggers a neuroinflammatory response that involves sustained microglia activation. This response has deleterious consequences on memory and learning capability in experimental animal models and in patients. However, the mechanisms connecting systemic inflammation and microglia activation remain poorly understood. Here, we identify the autotaxin (ATX)/lysophosphatidic acid (LPA)/LPA-receptor axis as a potential pharmacological target to modulate the LPS-mediated neuroinflammatory response in vitro (the murine BV-2 microglia cell line) and in vivo (C57BL/6J mice receiving a single i.p. LPS injection). In LPS-stimulated (20 ng/mL) BV-2 cells, we observed increased phosphorylation of transcription factors (STAT1, p65, and c-Jun) that are known to induce a proinflammatory microglia phenotype. LPS upregulated ATX, TLR4, and COX2 expression, amplified NO production, increased neurotoxicity of microglia conditioned medium, and augmented cyto-/chemokine concentrations in the cellular supernatants. PF8380 (a type I ATX inhibitor, used at 10 and 1 µM) and AS2717638 (an LPA5 antagonist, used at 1 and 0.1 µM) attenuated these proinflammatory responses, at non-toxic concentrations, in BV-2 cells. In vivo, we demonstrate accumulation of PF8380 in the mouse brain and an accompanying decrease in LPA concentrations. In vivo, co-injection of LPS (5 mg/kg body weight) and PF8380 (30 mg/kg body weight), or LPS/AS2717638 (10 mg/kg body weight), significantly attenuated LPS-induced iNOS, TNFα, IL-1ß, IL-6, and CXCL2 mRNA expression in the mouse brain. On the protein level, PF8380 and AS2717638 significantly reduced TLR4, Iba1, GFAP and COX2 expression, as compared to LPS-only injected animals. In terms of the communication between systemic inflammation and neuroinflammation, both inhibitors significantly attenuated LPS-mediated systemic TNFα and IL-6 synthesis, while IL-1ß was only reduced by PF8380. Inhibition of ATX and LPA5 may thus provide an opportunity to protect the brain from the toxic effects that are provoked by systemic endotoxemia.


Asunto(s)
Benzoxazoles/farmacología , Encéfalo/metabolismo , Endotoxemia , Isoquinolinas/farmacología , Lipopolisacáridos/toxicidad , Microglía/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Piperazinas/farmacología , Piperidinas/farmacología , Receptores del Ácido Lisofosfatídico , Animales , Encéfalo/patología , Línea Celular , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Endotoxemia/metabolismo , Endotoxemia/patología , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Ratones , Microglía/patología , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Receptores del Ácido Lisofosfatídico/metabolismo
14.
Biomed Res Int ; 2021: 3376496, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34337004

RESUMEN

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.


Asunto(s)
Polaridad Celular , Medios de Cultivo Condicionados/farmacología , Lactobacillus rhamnosus/química , Macrófagos/patología , Microglía/patología , Recuperación de la Función , Traumatismos de la Médula Espinal/fisiopatología , Animales , Polaridad Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Inflamación/patología , Macrófagos/efectos de los fármacos , Microglía/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Recuperación de la Función/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
15.
Biomolecules ; 11(7)2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34356613

RESUMEN

Renal fibrosis is a hallmark of chronic kidney disease (CKD) and a common manifestation of end-stage renal disease that is associated with multiple types of renal insults and functional loss of the kidney. Unresolved renal inflammation triggers fibrotic processes by promoting the activation and expansion of extracellular matrix-producing fibroblasts and myofibroblasts. Growing evidence now indicates that diverse T cells and macrophage subpopulations play central roles in the inflammatory microenvironment and fibrotic process. The present review aims to elucidate the role of CD8+ T cells in renal fibrosis, and identify its possible mechanisms in the inflammatory microenvironment.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Riñón/inmunología , Miofibroblastos/inmunología , Insuficiencia Renal Crónica/inmunología , Animales , Linfocitos T CD8-positivos/patología , Fibrosis , Humanos , Inflamación/inmunología , Inflamación/patología , Riñón/patología , Miofibroblastos/patología , Insuficiencia Renal Crónica/patología
16.
Biomolecules ; 11(7)2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-34356618

RESUMEN

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood-brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.


Asunto(s)
Adenosina Trifosfato/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Endotelio Vascular/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Transducción de Señal , Trombosis/metabolismo , Animales , Enfermedades de los Pequeños Vasos Cerebrales/patología , Endotelio Vascular/patología , Humanos , Inflamación/metabolismo , Inflamación/patología , Accidente Cerebrovascular Isquémico/patología , Trombosis/patología
17.
Nat Rev Rheumatol ; 17(9): 550-564, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34345021

RESUMEN

Interactions between lymphocytes and stromal cells have an important role in immune cell development and responses. During inflammation, stromal cells contribute to inflammation, from induction to chronicity or resolution, through direct cell interactions and through the secretion of pro-inflammatory and anti-inflammatory mediators. Stromal cells are imprinted with tissue-specific phenotypes and contribute to site-specific lymphocyte recruitment. During chronic inflammation, the modified pro-inflammatory microenvironment leads to changes in the stromal cells, which acquire a pathogenic phenotype. At the site of inflammation, infiltrating B cells and T cells interact with stromal cells. These interactions induce a plasma cell-like phenotype in B cells and T cells, associated with secretion of immunoglobulins and inflammatory cytokines, respectively. B cells and T cells also influence the stromal cells, inducing cell proliferation, molecular changes and cytokine production. This positive feedback loop contributes to disease chronicity. This Review describes the importance of these cell interactions in chronic inflammation, with a focus on human disease, using three selected autoimmune and inflammatory diseases: rheumatoid arthritis, psoriatic arthritis (and psoriasis) and systemic lupus erythematosus. Understanding the importance and disease specificity of these interactions could provide new therapeutic options.


Asunto(s)
Enfermedades Autoinmunes/patología , Inflamación/patología , Linfocitos/patología , Enfermedades Reumáticas/patología , Células del Estroma/patología , Animales , Enfermedades Autoinmunes/inmunología , Humanos , Inflamación/inmunología , Enfermedades Reumáticas/inmunología
18.
Oxid Med Cell Longev ; 2021: 8671713, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34457119

RESUMEN

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.


Asunto(s)
COVID-19/complicaciones , Síndrome de Liberación de Citoquinas/patología , Endotelio Vascular/patología , Inflamación/patología , Estrés Oxidativo , SARS-CoV-2/aislamiento & purificación , Enfermedades Vasculares/patología , COVID-19/virología , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/terapia , Endotelio Vascular/virología , Humanos , Inflamación/etiología , Inflamación/terapia , Enfermedades Vasculares/etiología , Enfermedades Vasculares/terapia
19.
Biosci Rep ; 41(8)2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34350941

RESUMEN

An influenza-like virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 disease and spread worldwide within a short time. COVID-19 has now become a significant concern for public health. Obesity is highly prevalent worldwide and is considered a risk factor for impairing the adaptive immune system. Although diabetes, hypertension, cardiovascular disease (CVD), and renal failure are considered the risk factors for COVID-19, obesity is not yet well-considered. The present study approaches establishing a systemic association between the prevalence of obesity and its impact on immunity concerning the severe outcomes of COVID-19 utilizing existing knowledge. Overall study outcomes documented the worldwide prevalence of obesity, its effects on immunity, and a possible underlying mechanism covering obesity-related risk pathways for the severe outcomes of COVID-19. Overall understanding from the present study is that being an immune system impairing factor, the role of obesity in the severe outcomes of COVID-19 is worthy.


Asunto(s)
Inmunidad Adaptativa/inmunología , COVID-19/patología , Obesidad/inmunología , Obesidad/patología , Humanos , Inflamación/patología , Obesidad/epidemiología , Factores de Riesgo , SARS-CoV-2/inmunología
20.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34360708

RESUMEN

BACKGROUND: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain's neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. METHODS: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. RESULTS: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. CONCLUSIONS: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.


Asunto(s)
Envejecimiento/efectos de los fármacos , Apoptosis/efectos de los fármacos , Atrazina/efectos adversos , Encéfalo/metabolismo , Administración por Inhalación , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Atrazina/farmacología , Encéfalo/patología , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Masculino , Ratones
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