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OBJECTIVE: Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren's syndrome (pSS). METHODS: In both pSS and non-pSS sicca syndrome patients, we examined Trm frequency, cytokine production in salivary glands (SG) and peripheral blood (PB). We also analysed Trm-related gene expression in SG biopsies through bulk and single-cell RNA sequencing (scRNAseq). Additionally, we investigated Trm properties in an immunisation-induced animal model of pSS (experimental SS, ESS) mouse model and assessed the effects of Trm inhibition via intraglandular anti-CD103 monoclonal antibody administration. RESULTS: Transcriptomic pSS SG showed an upregulation of genes associated with tissue recruitment and long-term survival of Trm cells, confirmed by a higher frequency of CD8+CD103+CD69+ cells in pSS SG, compared with non-specific sialadenitis (nSS). In SG, CD8+ CD103+ Trm contributed to the secretion of granzyme-B and interferon-γ, CD8+ Trm cells were localised within inflammatory infiltrates, where PD1+CD8+ T cells were also increased compared with nSS and MALT lymphoma. scRNAseq of PB and pSS SG T cells confirmed expression of CD69, ITGAE, GZMB, GZMK and HLA-DRB1 among CD3+CD8+ SG T cells. In the SG of ESS, CD8+CD69+CD103+ Trm producing Granzyme B progressively expanded. However, intraglandular blockade of CD103 in ESS reduced Trm, reduced glandular damage and improved salivary flow. CONCLUSIONS: CD103+CD8+Trm cells are expanded in the SG of pSS and ESS, participate in tissue inflammation and can be therapeutically targeted.
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Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.
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Carcinogénesis , Cromo , Hexoquinasa , Neoplasias Pulmonares , MicroARNs , Regulación hacia Arriba , MicroARNs/genética , Humanos , Cromo/toxicidad , Hexoquinasa/genética , Hexoquinasa/metabolismo , Carcinogénesis/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Pronóstico , Animales , Proliferación Celular/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Exposición Profesional/efectos adversos , Ratones , IsoenzimasRESUMEN
Senescent T cells are proliferative disabled lymphocytes that lack antigen-specific responses. The development of T-cell senescence in autoimmune diseases contributes to immunological disorders and disease progression. Senescent T cells lack costimulatory markers with the reduction of T cell receptor repertoire and the uptake of natural killer cell receptors. Senescent T cells exert cytotoxic effects through the expression of perforin, granzymes, tumor necrosis factor, and other molecules without the antigen-presenting process. DNA damage accumulation, telomere damage, and limited DNA repair capacity are important features of senescent T cells. Impaired mitochondrial function and accumulation of reactive oxygen species contribute to T cell senescence. Alleviation of T-cell senescence could provide potential targets for the treatment of autoimmune diseases.
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Enfermedades Autoinmunes , Senescencia Celular , Humanos , Agotamiento de Células T , Linfocitos T , Receptores de Células Asesinas NaturalesRESUMEN
As a ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR) is activated by structurally diverse ligands derived from the environment, diet, microorganisms, and metabolic activity. Recent studies have demonstrated that AhR plays a key role in modulating both innate and adaptive immune responses. Moreover, AhR regulates innate immune and lymphoid cell differentiation and function, which is involved in autoimmune pathogenesis. In this review, we discuss recent advances in understanding the mechanism of activation of AhR and its mediated functional regulation in various innate immune and lymphoid cell populations, as well as the immune-regulatory effect of AhR in the development of autoimmune diseases. In addition, we highlight the identification of AhR agonists and antagonists that may serve as potential therapeutic targets for the treatment of autoimmune disorders.
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Enfermedades Autoinmunes , Receptores de Hidrocarburo de Aril , Humanos , Receptores de Hidrocarburo de Aril/metabolismo , Regulación de la Expresión Génica , Linfocitos/metabolismo , LigandosRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which genetic and environmental factors contribute to disease progression. Both innate and adaptive immune cells, including T cells, B cells, activated macrophages and microglia, have been identified to be involved in the pathogenesis of MS, leading to the CNS inflammation, neurodegeneration and demyelination. In recent years, there has been considerable progress in understanding the contribution of tissue-resident immune cells in the pathogenesis of MS. METHODS: We performed a keyword-based search in PubMed database. We combined "multiple sclerosis" with keywords, such as tissue-resident memory T cells, microglia to search for relevant literatures in PubMed. RESULTS AND CONCLUSION: In this review, we comprehensively describe the characteristics of tissue-resident memory T cells and microglia, summarize their role in the pathogenesis of MS, and discuss their interaction with other immune cells in the CNS.
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Esclerosis Múltiple , Humanos , Esclerosis/patología , Sistema Nervioso Central , Microglía , Macrófagos , Enfermedad CrónicaRESUMEN
Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.
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Artritis Reumatoide , Fibroínas , Humanos , Hidrogeles , Fibroínas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/patología , Artritis Reumatoide/metabolismoRESUMEN
OBJECTIVE: Many animal experiments and epidemiological studies have shown that the gut microbiota (GM) plays an important role in the development of obesity, but the specific biological mechanism involved in the pathogenesis of disease remain unknown. We aimed to examine the relationships and functional mechanisms of GM on obesity in peri- and post-menopausal women. METHODS: We recruited 499 Chinese peri- and post-menopausal women and performed comprehensive analyses of the gut microbiome, targeted metabolomics for short-chain fatty acids in serum, and host whole-genome sequencing by various association analysis methods. RESULTS: Through constrained linear regression analysis, we found that an elevated abundance of Bacteroides fragilis (B. fragilis) was associated with obesity. We also found that serum levels of acetic acid were negatively associated with obesity, and that B. fragilis was negatively associated with serum acetic acid levels by partial Spearman correlation analysis. Mendelian randomization analysis indicated that B. fragilis increases the risk of obesity and may causally down-regulate acetic acid levels. CONCLUSIONS: We found the gut with B. fragilis may accelerate obesity, in part, by suppressing acetic acid levels. Therefore, B. fragilis and acetic acid may represent important therapeutic targets for obesity intervention in peri- and post-menopausal women.
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Bacteroides fragilis , Microbioma Gastrointestinal , Ácido Acético , Bacteroides fragilis/fisiología , Femenino , Humanos , Obesidad , PosmenopausiaRESUMEN
BACKGROUND: Recent studies have revealed a role of the ligand for glucocorticoid-induced TNFR family-related protein (GITRL) in mediating functional dysregulations of myeloid-derived suppressor cells (MDSCs) in the pathogenesis of primary Sjögren syndrome (pSS), but the underlying molecular mechanism is largely unclear. In this study, we aimed to elucidate GITRL-mediated signaling pathways in MDSCs during the development of experimental SS (ESS). METHODS: MDSCs were stimulated with recombinant GITRL, the activation of PTEN, AKT and STAT3 in MDSCs was analyzed by Western blot. MDSCs with different treatment were adoptively transferred to ESS mice. ELISA was used to detect the level of autoantibodies. Proportions of Th1 and Th17 cells were examined by flow cytometry. Histological evaluation of glandular destruction was analyzed by hematoxylin and eosin (HE) staining. The interaction of GITR, TRAF3 and PP2A was detected by CoIP. RESULTS: Upon the engagement of GITR on MDSCs, PTEN was activated and led to the inhibition of downstream AKT/STAT3 signaling pathway, therefore, resulting in the impaired immunosuppressive function of MDSCs. In ESS mice, blocking the activity of PTEN could efficiently restore the immunomodulatory effect of MDSCs and alleviate the progression of ESS. Furthermore, TRAF3 was found to bind to GITR, and then recruited PP2A to dephosphorylate PTEN, thus enhancing the activity of PTEN. CONCLUSION: This study elucidated the molecular mechanism underlying the effect of GITRL in regulating the function of MDSCs, which may provide a new therapeutic target for the treatment of pSS.
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Células Supresoras de Origen Mieloide , Síndrome de Sjögren , Factores de Necrosis Tumoral , Animales , Ratones , Inmunosupresores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factor 3 Asociado a Receptor de TNF/metabolismo , Factores de Necrosis Tumoral/metabolismoRESUMEN
Although the expansion of myeloid-derived suppressor cells (MDSCs) has been reported in autoimmune disorders, it is largely unclear how MDSCs contribute to the development of primary Sjögren syndrome (pSS). In this study, we found significantly increased MDSCs with gradually diminished suppressive capacity during disease development in mice with experimental Sjögren syndrome (ESS). The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased along ESS progression, whereas the increased GITRL was found to attenuate the immunosuppressive function of MDSCs. Moreover, blocking GITR signal in MDSCs significantly restored their immunosuppressive function and alleviated ESS progression in mice. In pSS patients, expanded MDSCs were found to express low levels of arginase. Significantly increased serum GITRL levels were closely correlated with patients with higher Sjögren syndrome disease activity index. Furthermore, treatment with recombinant GITRL markedly reduced the immunosuppressive function of human MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive function of MDSCs, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.
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Células Supresoras de Origen Mieloide/inmunología , Síndrome de Sjögren/inmunología , Factores de Necrosis Tumoral/inmunología , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Células Supresoras de Origen Mieloide/metabolismo , Síndrome de Sjögren/metabolismo , Factores de Necrosis Tumoral/metabolismoRESUMEN
Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.
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Medicamentos Herbarios Chinos , Neoplasias , China , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Mercadotecnía , Medicina Tradicional China , Neoplasias/tratamiento farmacológico , Medicamentos sin Prescripción/uso terapéutico , Calidad de VidaRESUMEN
BACKGROUND The guidelines recommend oral carbohydrates up to 2 hr before elective surgery. The objective of this study was to explore the safety and feasibility of preoperative carbohydrate drink in patients undergoing ambulatory surgery. MATERIAL AND METHODS Patients undergoing ambulatory surgery under general anesthesia were enrolled. They were fasted from midnight and randomly assigned to a study group (200 mL of a carbohydrate beverage) or the control group (pure water) and received the assigned drink 2 hr before surgery. Bedside ultrasonography was performed to monitor gastric emptying at T0 (before liquid intake), T1 (5 min after intake), T2 (1 hr after intake), and T3 (2 hr after intake). Subjective feelings of thirst, hunger, anxiety, and fatigue were assessed 1 hr after liquid intake using the visual analogue scale (VAS). RESULTS In both groups, gastric antrum cross-sectional area, gastric content volume, and weight-corrected gastric content volume increased at T1 and returned to baseline at T3. These parameters were significantly higher in the study group at T2 (6.28±1.38 vs. 4.98±0.78, 67.22±29.49 vs. 49.04±15.4, 1.10±0.51 vs. 0.85±0.37, P<0.05). Thirst and hunger VAS scores were reduced in both groups. The study group suffered significantly less hunger (28.44±10.41 vs. 36.03±14.42, P<0.05). Blood electrolytes (sodium, potassium, calcium) and glucose concentration levels were similar in both groups at T2. No gastric regurgitation or pulmonary aspiration was recorded. CONCLUSIONS Administration of 200 mL of oral carbohydrate beverage 2 hr before ambulatory surgery is safe, effective, and can be used for preoperative management of fasting patients.
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Procedimientos Quirúrgicos Ambulatorios , Bebidas , Carbohidratos de la Dieta/administración & dosificación , Adulto , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Electrólitos/sangre , Femenino , Vaciamiento Gástrico , Humanos , Masculino , Persona de Mediana Edad , Cuidados PreoperatoriosRESUMEN
OBJECTIVE: To investigate whether there is a difference in cerebellar development between appropriate -for-gestational-age (AGA) infants and small-for-gestational-age (SGA) infants. METHODS: A total of 165 AGA infants and 105 SGA infants, with a gestational age of 26-40+6 weeks, were enrolled in this study. Within 24-48 hours after birth, ultrasound examination was performed to measure the transverse diameter of the cerebellum, the height of the vermis, the area of the vermis, the perimeter of the vermis, and the area and perimeter of the cerebellum on transverse section. A Pearson correlation analysis was used to investigate the correlation between cerebellar measurements and gestational age. RESULTS: In both AGA and SGA infants, all cerebellar measurements were positively correlated with gestational age (r=0.50-0.81, P<0.05). In AGA and SGA infants, there were no significant differences in the measurements between the 25-27+6 weeks, 28-30+6 weeks, and 31-33+6 weeks of gestational age subgroups (P>0.05), while in the 34-36+6 weeks and 37-40+6 weeks subgroups, the SGA infants had significantly lower measurements than the AGA infants (P<0.05). CONCLUSIONS: The SGA infants with a gestational age of <34 weeks have intrauterine cerebellar development similar to AGA infants, but those with a gestational age of ≥34 weeks have poorer intrauterine cerebellar development than AGA infants.
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Cerebelo , Recién Nacido Pequeño para la Edad Gestacional , Edad Gestacional , Humanos , Lactante , UltrasonografíaRESUMEN
Recent studies have shown that glucocorticoid-induced tumor necrosis factor-receptor-related protein (GITR) and its ligand (GITRL) are critically involved in the pathogenesis of autoimmune arthritis, but the role of GITRL/GITR signaling in modulating CD4(+) follicular helper T (Tfh) cell response during autoimmune arthritis remains largely unclear. We showed that splenic Tfh cells from mice with collagen-induced arthritis expressed higher levels of GITR compared with non-Tfh cells. In vitro, GITRL treatment markedly enhanced the percentage and number of Tfh cells. The administration of GITR fused to fragment crystallizable of IgG protein in mice with collagen-induced arthritis suppressed the Tfh cell response, resulting in ameliorated disease severity, and reduced production of autoantibody and the number of autoantibody-secreting cells in both the spleen and bone marrow. Together, these results indicate that blockade of GITR signaling can ameliorate arthritis progression mainly by modulating the Tfh cell response.
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Artritis Experimental/inmunología , Proteína Relacionada con TNFR Inducida por Glucocorticoide/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Factores de Necrosis Tumoral/metabolismo , Animales , Artritis Experimental/metabolismo , Separación Celular , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Proteína Relacionada con TNFR Inducida por Glucocorticoide/inmunología , Masculino , Ratones , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/fisiología , Factores de Necrosis Tumoral/inmunologíaRESUMEN
Myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-associated immunosuppression, thus affecting effective immunotherapies for cancers. However, the molecular mechanisms involved in regulating the differentiation and function of MDSCs remain largely unclear. In this study, we found that inhibition of microRNA (miR)-9 promoted the differentiation of MDSCs with significantly reduced immunosuppressive function whereas overexpression of miR-9 markedly enhanced the function of MDSCs. Notably, knockdown of miR-9 significantly impaired the activity of MDSCs and inhibited the tumor growth of Lewis lung carcinoma in mice. Moreover, miR-9 regulated MDSCs differentiation by targeting the runt-related transcription factor 1, an essential transcription factor in regulating MDSC differentiation and function. Furthermore, the CREB was found to regulate miR-9 expression in MDSCs. Taken together, our findings have identified a critical role of miR-9 in regulating the differentiation and function of MDSCs.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , MicroARNs/genética , Células Mieloides/citología , Células Mieloides/inmunología , Animales , Carcinoma Pulmonar de Lewis/inmunología , Diferenciación Celular/genética , Línea Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal/biosíntesis , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , MicroARNs/antagonistas & inhibidores , MicroARNs/biosíntesis , Regiones Promotoras Genéticas/genética , beta-Glucanos/farmacologíaRESUMEN
OBJECTIVE: Although Th17 cells have been increasingly recognised as an important effector in various autoimmune diseases, their function in the pathogenesis of Sjögren's syndrome (SS) remains largely uncharacterised. This study aims to determine the role of Th17 cells in the development of experimental SS (ESS). METHODS: The ESS was induced in wildtype and IL-17A knockout (IL-17 KO) C57BL/6 mice immunised with salivary glands (SG) proteins. Phenotypic analysis of immune cells in the draining cervical lymph nodes (CLN) and SG was performed by flow cytometry and immunofluorescence microscopy. To determine the role of Th17 cells in ESS, immunised IL-17 KO mice were adoptively transferred with in vitro-generated Th17 cells and monitored for SS development. The salivary flow rate was measured, whereas inflammatory infiltration and tissue destruction in SG were assessed by histopathology. RESULTS: SG protein-immunised mice developed overt SS symptoms with increased Th17 cells detected in CLN and within lymphocytic foci in inflamed SG. Notably, immunised IL-17 KO mice were completely resistant for SS induction, showing no evidence of disease symptoms and histopathological changes in SG. Adoptive transfer of Th17 cells rapidly induced the onset of ESS in immunised IL-17 KO mice with markedly reduced saliva secretion, elevated autoantibody production and pronounced inflammation and tissue damage in SG. CONCLUSIONS: Our findings have defined a critical role of Th17 cells in the pathogenesis of ESS. Further studies may validate Th17 cell as a potential target for treating SS.
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Ganglios Linfáticos/citología , Proteínas y Péptidos Salivales/inmunología , Síndrome de Sjögren/inmunología , Células Th17/inmunología , Animales , Autoanticuerpos/inmunología , Modelos Animales de Enfermedad , Inmunización , Interleucina-17/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , CuelloRESUMEN
OBJECTIVE: To investigate the growth rate of corpus callosum by cranial ultrasound in very low birth weight preterm infants and to provide a reference for early evaluation and improvement of brain development. METHODS: A total of 120 preterm infants under 33 weeks' gestation were recruited and divided into 26-29(+6) weeks group (n=64) and 30-32(+6) weeks group (n=56) according to the gestational age. The growth rate of corpus callosum was compared between the two groups. The correlation between the corpus callosum length and the cerebellar vermis length and the relationship of the growth rate of corpus callosum with clinical factors and the neuromotor development were analyzed. RESULTS: The growth rate of corpus callosum in preterm infants declined since 2 weeks after birth. Compared with the 30-32(+6) weeks group, the 26-29(+6) weeks group had a significantly lower growth rate of corpus callosum at 3-4 weeks after birth, at 5-6 weeks after birth, and from 7 weeks after birth to 40 weeks of corrected gestational age. There was a positive linear correlation between the corpus callosum length and the cerebellar vermis length. Small-for-gestational age infants had a low growth rate of corpus callosum at 2 weeks after birth. The 12 preterm infants with severe abnormal intellectual development had a lower growth rate of corpus callosum compared with the 108 preterm infants with non-severe abnormal intellectual development at 3-6 weeks after birth. The 5 preterm infants with severe abnormal motor development had a significantly lower growth rate of corpus callosum compared with the 115 preterm infants with non-severe abnormal motor development at 3-6 weeks after birth. CONCLUSIONS: The decline of growth rate of corpus callosum in preterm infants at 2-6 weeks after birth can increase the risk of severe abnormal neuromotor development.
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Desarrollo Infantil , Cuerpo Calloso/crecimiento & desarrollo , Recien Nacido Prematuro/crecimiento & desarrollo , Inteligencia , Actividad Motora , Femenino , Edad Gestacional , Humanos , Recién Nacido , MasculinoRESUMEN
Various polysaccharides purified from plants are considered to be biological response modifiers and have been shown to enhance immune responses. Ficus carica L. is a Chinese traditional plant and has been widely used in Asian countries for its anti-tumor properties. Ficus carica polysaccharides (FCPS), one of the most essential and effective components in Ficus carica L., have been considered to be a beneficial immunomodulator and may be used in immunotherapy. However, the immunologic mechanism of FCPS is still unclear. Dectin-1 is a non-toll-like pattern recognition receptor, predominately expressed on dendritic cells (DCs). Activation of DCs through dectin-1 signaling can lead to the maturation of DC, thus inducing both innate and adaptive immune responses against tumor development and microbial infection. In our study, we found that FCPS could effectively stimulate DCs, partially through the dectin-1/Syk pathway, and promote their maturation, as shown by the up-regulation of CD40, CD80, CD86, and major histocompatibility complex II (MHCII). FCPS also enhanced the production of cytokines by DCs, including IL-12, IFN-γ, IL-6, and IL-23. Moreover, FCPS-treated DCs showed an enhanced capability to stimulate T cells and promote T cell proliferation. Altogether, these results demonstrate that FCPS are able to activate and maturate DCs, thereby up-regulating the immunostimulatory capacity of DCs, which leads to enhanced T cell responses.
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Células Dendríticas/efectos de los fármacos , Ficus/química , Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Línea Celular , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Lectinas Tipo C/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Quinasa Syk , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
Hashimoto's thyroiditis (HT) is an organ-specific immune disease characterized by the presence of lymphocytic infiltration and serum autoantibodies. Previous studies have confirmed the critical role of Th17 cells in the pathopoiesis of HT patients. Additionally, regulatory T cells (Treg) display a dysregulatory function in autoimmune disease. The purpose of this study is to investigate the alteration of Th17 and Treg cells in HT patients and explore contributing factors. We found there was an increased ratio of Th17/Treg in HT patients and a positive correlation with autoantibodies (anti-TgAb). In addition, there was an increased level of GITRL, which has been demonstrated to be correlated with the increassement of Th17 cells in the serum and thyroid glands of HT patients; the upregulated serum level of GITRL has a positive correlation with the percentage of Th17 cells in HT patients. In summary, an increase in GITRL may impair the balance of Th17/Treg, and contribute to the pathopoiesis of Hashimoto's thyroiditis.
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Enfermedad de Hashimoto/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Factores de Necrosis Tumoral/metabolismo , Femenino , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/genética , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Persona de Mediana Edad , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tiroglobulina/inmunología , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Factores de Necrosis Tumoral/genéticaRESUMEN
OBJECTIVE: To compare the differences between full-term and VLBW premature infants at term equivalent for the whole and sub-regional corpus callosum areas in order to provide reference for monitoring the extrauterine development of corpus callosum in VLBW premature infants. METHODS: Brain MR image data of 24 term infants with a gestational age of 39 weeks were collected within 24 hours after birth. Brain MR image of 30 VLBW neonates at 39 weeks' gestational age equivalent were successfully obtained. Routine T1WI, T2WI and DWI were applied. T1-weighted images on the mid-sagittal slice were selected, analyzed and measured. Forty-nine eligible MR images of them were chosen, 21 cases from the full-term infant group and 28 cases from the premature infant group. Corpus callosum and brain MR images were then sketched by two radiographic doctors. All data were analyzed by the Image Processing Function of MATLAB R2010a, and the whole corpus callosum and six sub-regions were obtained. RESULTS: The whole corpus callosum, anterior mid-body, posterior mid-body, isthmus and splenium area in the premature infant group were smaller than those in the full-term infant group (P<0.05), but the differences of Genu and rostral body area between the two groups was not statistically significant (P>0.05). CONCLUSIONS: The areas of the whole corpus callosum, anterior mid-body, posterior mid-body, isthmus and splenium in VLBW preterm infants at term are reduced, suggesting that the posterior end of the corpus callosum is probably most vulnerable to insults following pathogenic factors.
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Cuerpo Calloso/anatomía & histología , Humanos , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Imagen por Resonancia MagnéticaRESUMEN
Sjögren's syndrome is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands and aberrant B-cell hyperactivation are the two salient pathologic features in Sjögren's syndrome. Increasing evidence indicates that salivary gland epithelial cells act as a key regulator in the pathogenesis of Sjögren's syndrome, as revealed by the dysregulated innate immune signaling pathways in salivary gland epithelium and increased expression of various proinflammatory molecules as well as their interaction with immune cells. In addition, salivary gland epithelial cells can regulate adaptive immune responses as nonprofessional antigen-presenting cells and promote the activation and differentiation of infiltrated immune cells. Moreover, the local inflammatory milieu can modulate the survival of salivary gland epithelial cells, leading to enhanced apoptosis and pyroptosis with the release of intracellular autoantigens, which further contributes to SG autoimmune inflammation and tissue destruction in Sjögren's syndrome. Herein, we reviewed recent advances in elucidating the role of salivary gland epithelial cells in the pathogenesis of Sjögren's syndrome, which may provide rationales for potential therapeutic targeting of salivary gland epithelial cells to alleviate salivary gland dysfunction alongside treatments with immunosuppressive reagents in Sjögren's syndrome.