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1.
Medicine (Baltimore) ; 99(18): e20035, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32358383

RESUMEN

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) involves a severe inflammatory response. Systemic glucocorticoids are very important for the treatment of the acute exacerbation period; however, their use causes serious adverse effects. There is still no evidence on whether traditional Chinese medicine (TCM) can be used to reduce the dosage of systemic glucocorticoids in the treatment of patients with AECOPD. METHODS: In this trial, we plan to enroll 204 eligible patients with AECOPD who will be randomly assigned to receive TCM or a placebo. The effect of TCM in the treatment of patients with AECOPD will be measured by the dosage of systemic glucocorticoids (at which COPD assessment test [CAT] scores improve by 50%). Safety will also be assessed. TRIAL REGISTRATION: ChiCTR2000029568.


Asunto(s)
Glucocorticoides/uso terapéutico , Medicina China Tradicional/métodos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Adulto , Anciano , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/administración & dosificación , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Medicina China Tradicional/efectos adversos , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Proyectos de Investigación , Pruebas de Función Respiratoria
2.
Chem Biol Interact ; 323: 109076, 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32240654

RESUMEN

A growing body of evidence indicates that exposure to nonylphenol (NP), a typical persistent organic pollutant (POP), in early life results in the impairment of the central nervous system (CNS), but the underlying mechanism still remains to be elucidated. High levels of pro-inflammatory cytokines in the brain have been implicated in the CNS damages. The animal model of exposure to NP in early life was established by maternal gavage during the pregnancy and lactation in the present study. We found that exposure to NP in early life increased the levels of pro-inflammatory cytokines in the rat prefrontal cortex. Interestingly, the levels of pro-inflammatory cytokines in the intestine as well as in the serum were also increased by NP exposure. Furthermore, the increased permeability of intestinal barrier and blood-brain barrier (BBB), two critical barriers in the gut to brain communication, was observed in the rats exposed to NP in early lives. The decreased expression of zonula occludens-1 (ZO-1) and claudin-1 (CLDN-1), tight junction proteins (TJs) that responsible for maintaining the permeability of intestinal barrier and BBB, was found, which may underlie these increases in permeability. Taken together, these results suggested that the disturbed gut-brain communication may contribute to the increased levels of pro-inflammatory cytokines in the prefrontal cortex caused by NP exposure in early life.


Asunto(s)
Citocinas/metabolismo , Tracto Gastrointestinal/patología , Mediadores de Inflamación/metabolismo , Fenoles/toxicidad , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Animales , Animales Recién Nacidos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/patología , Líquido Cefalorraquídeo/metabolismo , Claudina-1/metabolismo , Citocinas/sangre , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Mediadores de Inflamación/sangre , Intestinos/efectos de los fármacos , Intestinos/patología , Exposición Materna , Permeabilidad , Corteza Prefrontal/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Ratas Sprague-Dawley , Proteína de la Zonula Occludens-1/metabolismo
3.
Medicine (Baltimore) ; 99(14): e19429, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32243363

RESUMEN

It is known that the presence of orthodontic brackets predisposes for a change in the biofilm, facilitating the development of gingivits. The sites are difficult to access with a toothbrush and periodontal curette, worsening inflammation, in addition, a gingival hyperplasia is associated with poor hygiene. The objective of this study is to evaluate the impact of photodinamyc therapy (PDT) as an adjuvant treatment, considering clinical immunoregulatory and microbiological parameters. This randomized, controlled, double-blind clinical study will include 34 patients, both genders, having used fixed appliance for more than 12 months, with gingivitis. Participants will be divided into two groups: G1 (n = 17)- Scaling and Root Planing + PDT placebo and G2 (n = 17)- Scaling and Root Planing + PDT. In G2 the following dosimetric parameters will be used: methylene blue 0.005%, λ= 660 nanometers (nm), 9 Joules (J) per site, irradiance= 3.5Watts (W)/ centimeters (cm), radiant exposure= 318J/cm. All participants will receive oral hygiene guidance prior the curetes scaling. The clinical periodontal data to be analyzed are plaque index, gingival index and probing depth. Crevicular fluid, from 4 pre-determined sites and saliva, will be collected and analysed for IL-6, IL-1ß, IL-8, TNF-α and IL-10 cytokines using ELISA (Enzyme immunoabsorption assay) method. Total Bacteria count will also be performed, by qPCR and Universal16SrRNA gene. All analysis will be realized using in the baseline (T0), 7 (T1) and 21 (T2) days after treatment. Oral health-related quality of life will be assessed using the OHIP-14 questionnaire at times T0 and T2. If sample distribution is normal, the Student T-test will be applied if it is not normal, the Mann-Whitney test will be used. The data will be presented in terms of ±â€ŠPD and The significance level will be set at p < 0.05. Our results may improve quality of life and add data to establish a therapeutic alternative for gingivitis during the orthodontic treatment. Registration: clinicaltrials.gov NCT04037709. https://clinicaltrials.gov/ct2/show/NCT04037709 - Registered in July 2019.


Asunto(s)
Gingivitis/terapia , Mediadores de Inflamación/metabolismo , Azul de Metileno/uso terapéutico , Aparatos Ortodóncicos Fijos , Fotoquimioterapia/métodos , Adolescente , Adulto , Niño , Terapia Combinada , Raspado Dental/métodos , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Gingivitis/tratamiento farmacológico , Gingivitis/microbiología , Humanos , Masculino , Índice Periodontal , Calidad de Vida , Adulto Joven
4.
Medicine (Baltimore) ; 99(14): e19571, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32243375

RESUMEN

BACKGROUND: A traditional Chinese medicine classic herbal formula named Xiaoqinglong decoction (XQLD) is widely used in China for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The efficacy and safety of XQLD for AECOPD was evaluated in this systematic review. METHODS: Five databases, including the Cochrane Library, PubMed, China National Knowledge Infrastructure, Wanfang database, and Chinese Science and Technology Periodical Database were searched up to October 5, 2018 for randomized control trials in treating AECOPD with XQLD. RESULT: Thirty-eight trials were identified. Compared with conventional therapy (CT), XQLD plus CT significantly improve the total clinical efficacy rate (Risk Ratio [RR] = 1.22, 95% confidence interval [CI] = 1.18-1.26, P < .00001). Forced expiratory volume in the first second (FEV1) (mean difference [MD] = 0.37, 95% CI = 0.27-0.46; P < .00001), FEV1%pre (MD = 4.52, 95% CI = 2.42-6.62; P < .00001), FEV1/forced vital capacity (MD = 5.11, 95% CI = 4.21-6.00; P < .00001), PaO2 (MD = 7.17, 95% CI = 4.80-9.54; P < .00001); lowered cough symptom score (MD = -0.65; 95% CI = -0.70 to -0.59; P < .00001), sputum symptom score (MD = -0.41; 95% CI = -0.45 to -0.37; P < .00001), wheezing symptom score (MD = -0.49; 95% CI = -0.60 to -0.38; P < .00001); reduce cough relief time (MD = -1.28; 95% CI = -1.53 to -1.02; P < .00001), sputum relief time (MD = -1.19; 95% CI = -1.42 to -0.96; P < .00001), wheezing relief time (MD = -1.65; 95% CI = -2.63 to -0.68; P = .0009), lassitude relief time (MD = -2.16; 95% CI = -3.44 to -0.89; P = .0009), and PaCO2 (MD = -7.63, 95% CI = -9.62 to -5.63; P < .00001). Benefit for interleukin (IL)-4 (MD = -9.20, 95% CI = -13.59 to -4.81; P < .00001), IL-6 (MD = -5.07, 95% CI = -8.14 to -2.01; P = .001), IL-8 (MD = -5.59, 95% CI = -6.09 to -5.08; P < .00001), tumor necrosis factor (TNF)-α (MD = -5.93, 95% CI = -6.97 to -4.89; P < .00001), Interferon (INF)-γ (MD = 18.03, 95% CI = 13.22-22.84; P < .00001), and C-reactive protein (MD = -3.93, 95% CI = -5.97 to -1.89; P = .0002). For adverse events, there were no difference between XILD plus CT and CT. CONCLUSION: XQLD plus CT was more effective than CT alone for treating chronic obstructive pulmonary disease. Further higher quality trials are needed. The safety of XQLD remained uncertain.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Tos/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Mediadores de Inflamación/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función Respiratoria , Esputo/citología
5.
Gene ; 747: 144661, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32275999

RESUMEN

Recently, increasing evidence has reported that circRNAs are non-coding RNAs and they bind with the corresponding miRNAs to modulate the target genes. However, the detailed role of circRNAs in the pathogenesis of DN still remains poorly known. Currently, we aimed to study how circ_0000285 functions in DN development. We found that circ_0000285 was significantly increased in DN mice models and mouse podocytes incubated with HG. Then, circ_0000285 was overexpressed in mouse podocytes and we observed that overexpression of circ_0000285 promoted podocytes injury. Moreover, miR-654-3p was precited as a target of circ_0000285. It was shown that circ_0000285 was strongly pulled down by circ_0000285 specific probe and circ_0000285 specific probe was used to successfully enrich miR-654-3p. In addition, we reported that miR-654-3p was obviously down-regulated in DN. Inhibitors of miR-654-3p greatly reversed the effects of circ_0000285 siRNA on podocytes injury. Moreover, the inflammation release was restrained by loss of circ_0000285, while induced by miR-654-3p inhibitors. IL-6, L-1ß and TNF-α level was remarkably depressed by the knockdown of circ_0000285 and miR-654-3p inhibitors induced that. Furthermore, MAPK6 was confirmed as a direct downstream target of miR-654-3p. As shown, MAPK6 was markedly suppressed by circ_0000285 siRNA, which was rescued by the decrease of miR-654-3p. These findings revealed that circ_0000285 promoted podocyte injury via sponging miR-654-3p and activating MAPK6 in DN.


Asunto(s)
Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , MicroARNs/metabolismo , Proteína Quinasa 6 Activada por Mitógenos/metabolismo , Podocitos/patología , ARN Circular/metabolismo , Animales , Secuencia de Bases , Citocinas/metabolismo , Progresión de la Enfermedad , Regulación de la Expresión Génica , Mediadores de Inflamación/metabolismo , Masculino , Ratones , MicroARNs/genética , Proteína Quinasa 6 Activada por Mitógenos/genética , Podocitos/metabolismo , ARN Circular/genética
6.
Life Sci ; 251: 117645, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32268154

RESUMEN

Acute pancreatitis (AP) is a noninfectious inflammatory disease with high morbidity and mortality, which is characterized by severe inflammation and tissue necrosis. Cordycepin (CRD), derived from Cordyceps militaris, possesses anti-inflammatory effects and immunomodulation properties. Here, we investigated the protective effects of CRD on pancreatic injury and clarified potential mechanisms in AP model. There were established caerulein-induced AP and CRD pretreatment models in vivo and in vitro, as showed by serum enzymes, histopathological alterations and pro-inflammatory cytokines. Pretreatment with CRD notably downregulated the serum amylase and lipase levels and apparently reduced pancreatic histopathological alterations in AP mice. Meanwhile, the MPO staining confirmed that CRD pretreatment modulated the infiltration of neutrophils in AP mice. Furthermore, CRD markedly decreased the levels of pro-inflammatory factors (IL-6, IL-1ß, and TNF-α) though inhibiting the activation of nuclear factor-κB (NF-κB) and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in AP mice. In pancreatic acinar cancer cell 266-6, CRD pretreatment decreased cholecystokinin(CCK)-induced inflammatory response was consistent with those in vivo. Mechanistically, CRD was also revealed to activate activated protein kinase (AMPK) and attenuated inflammation both in vivo and in vitro. On the whole, this study indicated that CRD protects mice from pancreatic inflammatory process and damage by suppressed NF-κB and NLRP3 inflammasome activation via AMPK, which probably contributed to the potential therapy for AP.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Desoxiadenosinas/farmacología , Inflamasomas/metabolismo , Inflamación/prevención & control , Pancreatitis/prevención & control , Enfermedad Aguda , Animales , Biomarcadores/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sustancias Protectoras/farmacología
8.
Gene ; 744: 144591, 2020 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-32220601

RESUMEN

Polycystic ovary syndrome (PCOS) is a kind of endocrine disease among women across the global. Recently, many researches have reported circular RNAs can act as significant molecular biomarkers for diseases, especially in tumors. Several Circular RNAs are reported to be aberrantly expressed in PCOS patients. Here, we investigated the biological effects of hsa_circ_0118530 on human granulosa cells, KGN. We observed that hsa_circ_0118530 was greatly elevated in PCOS patients and granulosa cells (including KGN and COV434 cells) compared to normal IOSE80 cells. hsa_circ_0118530 siRNA was transfected into KGN cells. We found that KGN cell viability was repressed, cell apoptosis was induced while cell migration was greatly inhibited. TGF-ß1 was utilized to induce EMT process. As shown, loss of hsa_circ_0118530 significantly enhanced E-cadherin mRNA and protein levels while depressed N-cadherin expression. Furthermore, we indicated that decrease of hsa_circ_0118530 was able to inhibit ROS accumulation, MDA levels while induced SOD activity. Next, it was demonstrated that releases of inflammatory cytokine were suppressed by hsa_circ_0118530 down-regulation. Additionally, miR-136 was predicted and confirmed as the target of hsa_circ_0118530. For another, the functions of hsa_circ_0118530 on KGN cell progression, oxidative stress and inflammation releases were obviously reversed by miR-136 suppression. In conclusion, knockdown of hsa_circ_0118530 repressed PCOS progression via sponging miR-136.


Asunto(s)
Células de la Granulosa/metabolismo , MicroARNs/metabolismo , Síndrome del Ovario Poliquístico/genética , ARN Circular/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Células de la Granulosa/citología , Humanos , Mediadores de Inflamación/metabolismo , Estrés Oxidativo/genética , Síndrome del Ovario Poliquístico/metabolismo , ARN Circular/biosíntesis
9.
Mol Pharmacol ; 97(5): 324-335, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32173651

RESUMEN

Skin serves not only as a protective barrier to microbial entry into the body but also as an immune organ. The outer layer, the epidermis, is composed predominantly of keratinocytes, which can be stimulated to produce proinflammatory mediators. Although some inflammation is useful to defend against infection, excessive or persistent inflammation can lead to the development of inflammatory skin diseases, such as psoriasis, a common skin disorder affecting approximately 2% of the US population. We have previously found that phosphatidylglycerol (PG) derived from soy can inhibit inflammation in a contact irritant ear edema mouse model. Here, we investigated the ability of soy PG to inhibit inflammatory mediator expression in response to activators of the pattern recognition receptors, toll-like receptor-2 (TLR2) and -4 (TLR4). We found that in epidermal keratinocytes, soy PG inhibited TLR2 and TLR4 activation and inflammatory mediator expression in response to a synthetic triacylated lipopeptide and lipopolysaccharide, respectively, as well as an endogenous danger-associated molecular pattern. However, at higher concentrations, soy PG alone enhanced the expression of some proinflammatory cytokines, suggesting a narrow therapeutic window for this lipid. Dioleoylphosphatidylglycerol (DOPG), but not dioleoylphosphatidylcholine, exerted a similar inhibitory effect, completely blocking keratinocyte inflammatory mediator expression induced by TLR2 and TLR4 activators as well as NFκB activation in a macrophage cell line (RAW264.7); however, DOPG was not itself proinflammatory even at high concentrations. Furthermore, DOPG had no effect on NFκB activation in response to a TLR7/8 agonist. Our results suggest that DOPG could be used to inhibit excessive skin inflammation. SIGNIFICANCE STATEMENT: Although inflammation is beneficial for clearing an infection, in some cases, the infection can be excessive and/or become chronic, thereby resulting in considerable tissue damage and pathological conditions. We show here that the phospholipid phosphatidylglycerol can inhibit the activation of toll-like receptors 2 and 4 of the innate immune system as well as the downstream inflammatory mediator expression in response to microbial component-mimicking agents in epidermal keratinocytes that form the physical barrier of the skin.


Asunto(s)
Mediadores de Inflamación/metabolismo , Queratinocitos/metabolismo , Patrón Molecular Asociado a Patógenos/farmacología , Fosfatidilgliceroles/farmacología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Calgranulina B/farmacología , Humanos , Imidazoles/farmacología , Lipopéptidos/farmacología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Células RAW 264.7 , Receptores de Reconocimiento de Patrones/metabolismo , Proteínas Recombinantes/farmacología , Soja/química
10.
Medicine (Baltimore) ; 99(13): e19612, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32221085

RESUMEN

Pulmonary arterial hypertension (PAH) is a disease associated with high mortality, but notable sex differences have been observed between males and females. For this reason, further research on the mechanisms underlying sex differences in PAH is required to better understand and treat the disease. This study mainly focused on gene expression levels to investigate potential differences in the pathogenesis and progression of PAH between the male and female sexes.Sex-specific differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus datasets GSE117261 and GSE38267. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted, and a protein-protein interaction (PPI) network was established based on the identified DEGs to predict potential mechanisms involved in the observed sex differences in the pathogenesis of PAH.We identified 26 female- and 53 male-specific DEGs from lung tissue and 498 female-specific DEGs in blood samples. No male-specific DEGs were identified from blood samples. GO and KEGG pathway analyses revealed that female-specific DEGs in lung tissue were enriched in inflammatory response and cytokine-cytokine receptor interaction, whereas male-specific DEGs were mainly enriched in cellular chemotaxis and the nuclear factor of kappa light polypeptide gene enhancer in B-cell (NF-kappa B) signaling pathway. Lipocalin 2 (LCN2) was the only gene that was differentially expressed in both the lung tissue and the blood of female patients.In conclusion, inflammation and immunity may play key roles in the pathogenesis of female PAH, and LCN2 may act as a serum biomarker of female PAH, whereas the pathogenesis in males is more complicated.


Asunto(s)
Hipertensión Arterial Pulmonar/fisiopatología , Caracteres Sexuales , Biomarcadores , Bases de Datos Genéticas , Femenino , Expresión Génica , Ontología de Genes , Genes Supresores de Tumor , Humanos , Mediadores de Inflamación/metabolismo , Lipocalina 2/biosíntesis , Masculino , FN-kappa B/metabolismo , Proteínas Nucleares , Mapas de Interacción de Proteínas , Transducción de Señal , Regulación hacia Arriba
11.
Medicine (Baltimore) ; 99(8): e19207, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080108

RESUMEN

Cigarette smoking is associated with thicker carotid intima-media thickness (IMT), probably partly through inflammatory pathways. However, to what extent does inflammation mediate the smoking-carotid atherosclerosis association is unclear. We investigated the mediating effect of inflammation on the association between cigarette smoking and carotid IMT, and quantified the respective contributions of inflammatory markers to this association.A total of 1752 participants from Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort (GBCS-CVD) were included. Using causal mediation analysis under the counterfactual framework, we decomposed total effects of cigarette smoking on IMT into indirect effects (through inflammatory response) and direct effects (not through inflammatory response).After adjusting for traditional risk factors, the indirect effects of per 10/L increment in leukocyte and granulocyte, per mg/L increment in high-sensitivity C-reactive protein (hs-CRP), and per mg/dL increment in fibrinogen on carotid IMT was 0.0028 mm (95% confidence interval [CI], 0.0011-0.0047), 0.0019 mm (95% CI, 0.0006-0.0034), 0.0017 mm (95% CI, 0.0006-0.003), and 0.001 mm (95% CI, 0.0001-0.0021), respectively. No evidence for a mediating role of lymphocyte was found. The proportion of the smoking-IMT association mediated by leukocyte, granulocyte, hs-CRP, and fibrinogen was 12.57% (95% CI, 8.50%-22.11%), 8.50% (95% CI, 5.76%-15.09%), 7.64% (95% CI, 5.20%-13.79%), and 4.48% (95% CI, 3.04%-8.03%), respectively. Restricting data analysis to men showed similar results.The effects of cigarette smoking on IMT were partly mediated by leukocyte, hs-CRP, and fibrinogen. The mediating role of leukocyte was likely mainly driven by higher granulocyte.


Asunto(s)
Grosor Intima-Media Carotídeo , Fumar Cigarrillos/fisiopatología , Mediadores de Inflamación/metabolismo , Inflamación/fisiopatología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores Socioeconómicos
12.
Medicine (Baltimore) ; 99(8): e19214, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080113

RESUMEN

Langerhans cells (LCs) and plasmacytoid dendritic cells (pDCs) play an important role in the cutaneous immune response to viral infection. Verruca vulgaris (VV) is a chronic benign disease caused by human papillomavirus (HPV) infection.To investigate the possible roles of LCs, pDCs and toll-like receptor (TLR)7/9 signaling pathways in the pathogenesis of VV, we detected the expression of CD1a, CD2AP, CD123, TLR7/9, IFN regulatory factor 7 (IRF7), and interleukin-1 receptor-associated kinase 1 (IRAK1) in VV lesions.The expression of CD1a, CD2AP, CD123, TLR7/9, IRF7, and IRAK1 in 20 VV lesions was tested by immunohistochemistry. The density and number of stained cells were compared between VV lesions and the perilesional normal skin.The density and number of CD1a-, CD2AP-, CD123-, TLR9-, and IRAK1-positive cells in the papillary layer of VV lesions were significantly higher than those in the perilesional normal skin (P < .05). There were no significant differences in the density and positive rate of CD1a+ cells in the epidermis and of TLR7 and IRF7 cells in the dermis between VV lesions and the perilesional normal skin at the edge (P > .05).In VV, the number of LCs increases only in the dermis, indicating that LC's antigen-presenting function might not be inhibited. The increased number of pDCs in VV lesions suggests that HPV infection may recruit the pDCs to the virus-infected epithelium. We speculate that the TLR7/9 downstream signaling pathway is not fully activated in VV, leading to difficulty of HPV removal and the relapse of HPV-infected lesions.


Asunto(s)
Células Dendríticas/metabolismo , Células de Langerhans/metabolismo , Receptor Toll-Like 7/metabolismo , Receptores Toll-Like/metabolismo , Verrugas/fisiopatología , Adolescente , Adulto , Células Dendríticas/inmunología , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Células de Langerhans/inmunología , Masculino , Transducción de Señal , Receptor Toll-Like 9/metabolismo , Verrugas/inmunología , Adulto Joven
13.
Adv Exp Med Biol ; 1240: 1-23, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32060884

RESUMEN

Interleukin 1 (IL-1) has long been known for its pleiotropic effects on inflammation that plays a complex, and sometimes contrasting, role in different stages of cancer development. As a major proinflammatory cytokine, IL-1ß is mainly expressed by innate immune cells. IL-1α, however, is expressed by various cell types under physiological and pathological conditions. IL-1R1 is the main receptor for both ligands and is expressed by various cell types, including innate and adaptive immune cell types, epithelial cells, endothelial cells, adipocytes, chondrocytes, fibroblasts, etc. IL-1 and IL-1R1 receptor interaction leads to a set of common signaling pathways, mainly the NF-kB and MAP kinase pathways, as a result of complex positive and negative regulations. The variety of cell types with IL-1R1 expression dictates the role of IL-1 signaling at different stages of cancer, which under certain circumstances leads to contrasting roles in tumor development. Recent availability of IL-1R1 conditional knockout mouse model has made it possible to dissect the role of IL-1/IL-1R1 signaling transduction in different cell types within the tumor microenvironment. This chapter will focus on the role of IL-1/IL-1R1 in different cell types within the tumor microenvironment and discuss the potential of targeting this pathway in cancer therapy.


Asunto(s)
Interleucina-1/inmunología , Interleucina-1/metabolismo , Transducción de Señal , Microambiente Tumoral , Animales , Humanos , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-1/antagonistas & inhibidores , Ratones Noqueados , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología
14.
Animal ; 14(S1): s144-s154, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32024563

RESUMEN

Inflammatory cascades are a critical component of the immune response to infection or tissue damage, involving an array of signals, including water-soluble metabolites, lipid mediators and several classes of proteins. Early investigation of these signaling pathways focused largely on immune cells and acute disease models. However, more recent findings have highlighted critical roles of both immune cells and inflammatory mediators on tissue remodeling and metabolic homeostasis in healthy animals. In dairy cattle, inflammatory signals in various tissues and in circulation change rapidly and dramatically, starting just prior to and at the onset of lactation. Furthermore, several observations in healthy cows point to homeostatic control of inflammatory tone, which we define as a regulatory process to balance immune tolerance with activation to keep downstream effects under control. Recent evidence suggests that peripartum inflammatory changes influence whole-body nutrient flux of dairy cows over the course of days and months. Inflammatory mediators can suppress appetite, even at levels that do not induce acute responses (e.g. fever), thereby decreasing nutrient availability. On the other hand, inhibition of inflammatory signaling with non-steroidal anti-inflammatory drug (NSAID) treatment suppresses hepatic gluconeogenesis, leading to hypoglycemia in some cases. Over the long term, though, peripartum NSAID treatment substantially increases peak and whole-lactation milk synthesis by multiparous cows. Inflammatory regulation of nutrient flux may provide a homeorhetic mechanism to aid cows in adapting to rapid changes in metabolic demand at the onset of lactation, but excessive systemic inflammation has negative effects on metabolic homeostasis through inhibition of appetite and promotion of immune cell activity. Thus, in this review, we provide perspectives on the overlapping regulation of immune responses and metabolism by inflammatory mediators, which may provide a mechanistic underpinning for links between infectious and metabolic diseases in transition dairy cows. Moreover, we point to novel approaches to the management of this challenging phase of the production cycle.


Asunto(s)
Bovinos/fisiología , Conducta Alimentaria , Homeostasis , Mediadores de Inflamación/metabolismo , Inflamación/veterinaria , Transducción de Señal , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Bovinos/inmunología , Citocinas/metabolismo , Femenino , Gluconeogénesis/efectos de los fármacos , Lactancia , Hígado/efectos de los fármacos , Hígado/metabolismo , Leche/metabolismo , Periodo Periparto
15.
PLoS One ; 15(2): e0228919, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32040536

RESUMEN

Cigarette smoking and tuberculosis are a significant cause of death worldwide. Several epidemiological studies have demonstrated cigarette smoking is a risk factor for tuberculosis. Electronic cigarettes have recently appeared as a healthier alternative to conventional smoking, although their impact in tuberculosis is not well understood. The aim of this study was to explore the effect of electronic cigarettes in phagocytosis of Mycobacterium tuberculosis and cytokines production. In vitro infection was carried out by exposing THP-1 macrophages to four electronic vapor extracts and the intracellular burden of M. tuberculosis was determined. The percentage of infection was evaluated by confocal microscopy and the cytokine production by Luminex. A reduction of intracellular M. tuberculosis burden in THP-1 macrophages was found after its exposure to electronic vapor extract; the same trend was observed by confocal microscopy when Mycobacterium bovis BCG-GFP strain was used. Electronic cigarettes stimulate a pro-inflammatory cytokine response. We conclude that electronic cigarettes impair the phagocytic function and the cytokine response to M. tuberculosis.


Asunto(s)
Citocinas/biosíntesis , Sistemas Electrónicos de Liberación de Nicotina , Mycobacterium tuberculosis/patogenicidad , Fagocitosis , Fumar/efectos adversos , Supervivencia Celular , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/patología , Mycobacterium tuberculosis/crecimiento & desarrollo , Mycobacterium tuberculosis/inmunología , Humo/efectos adversos , Células THP-1
16.
PLoS One ; 15(2): e0227524, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32101556

RESUMEN

Experimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon α1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFNα-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFNα-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNFα were suppressed when IFNα-C was simultaneously present. TNF-α mediated induction of NF-κB and signaling by IL-17A were attenuated by IFNα-C. Differentiated ARPE-19 cells were treated with TNFα in the presence or absence IFNα-C and analyzed by immmunhistochemistry. IFNα-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNFα was prevented by IFNα-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFNα-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFNα-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigen-specific T cell proliferation that was inhibited in the presence of IFNα-C. IFNα-C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis.


Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Interferón Tipo I/química , Péptidos/uso terapéutico , Retina/patología , Uveítis/tratamiento farmacológico , Administración Oral , Animales , Enfermedades Autoinmunes/patología , Enfermedades Autoinmunes/fisiopatología , Línea Celular , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Impedancia Eléctrica , Electrorretinografía , Proteínas del Ojo/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-17/metabolismo , Ratones , FN-kappa B/metabolismo , Retina/efectos de los fármacos , Retina/fisiopatología , Proteínas de Unión al Retinol/metabolismo , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/patología , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Uveítis/patología , Uveítis/fisiopatología
17.
Mol Immunol ; 120: 61-66, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32078859

RESUMEN

Myocardial infarction (MI) or heart attack is a deadly event with high prevalence. In the present study, we investigated the effects of the polypeptide copolymer glatiramer acetate (GA) in H9c2 rat cardiomyocytes exposed to oxygen-glucose deprivation/reperfusion injury. Immediately following MI, an acute inflammatory response is triggered that causes activation of various proinflammatory cytokines, infiltration of immune cells, and neovascularization. This response is largely mediated by some genes such as TNF-α, IL-6, ICAM-1, and VEGF. Additionally, the rapid influx of oxidants, such as reactive oxygen species (ROS), leads to a harmful state of oxidative stress. Here, we found that GA could reduce OGD/R-induced inflammation and oxidative stress by inhibiting the expression of TNF-α, IL-6, ICAM-1, and VEGF, and suppressing the production of ROS via reduced NADPH oxidase 1 (NOX1) expression. To elucidate the pathways involved in these promising results, we took a close look at the impact of the endothelial growth response-1 (Egr-1), a transcriptional factor recognized as a mediator of MI-related inflammation and cellular injury. Using siRNA for Egr-1, we found that GA could reduce the expression of ICAM-1 and VEGF by inhibiting Egr-1 expression. Together, our findings indicate a novel therapeutic potential of GA in the treatment of MI.


Asunto(s)
Cardiotónicos/farmacología , Proteína 1 de la Respuesta de Crecimiento Precoz/antagonistas & inhibidores , Acetato de Glatiramer/farmacología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Animales , Línea Celular , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Glucosa/metabolismo , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Oxígeno/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo
18.
Mol Immunol ; 120: 83-92, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32106023

RESUMEN

Pulmonary fibrosis is a progressive chronic inflammatory lung disease whose pathogenesis is complicated. Platelets and neutrophils play important roles in the progression of pulmonary inflammation. We have reported that cangrelor, a non-sepesific GPR17 antagonist, alleviates pulmonary fibrosis partly by inhibiting macrophage inflammation in mice. Cangrelor is also a well-known anti-platelet agent. To test whether cangrelor mitigated pulmonary fibrosis partly through the inhibition of platelets, bleomycin (BLM) was used to induce pulmonary fibrosis in C57BL/6 J mice. We found that cangrelor (10 mg/kg) not only significantly decreased BLM-induced release of inflammatory cytokines (PF4, CD40 L and MPO), but also decreased the increment of platelets, neutrophils and platelet-neutrophil aggregates in the fibrotic lung and in the peripheral blood of BLM-treated mice. In addition, cangrelor decreased the number of CD40 and MPO double positive neutrophils and the expression level of CD40 in BLM-treated mouse lungs. Based on these results we conclude that cangrelor alleviates BLM-induced lung inflammation and pulmonary fibrosis in mice, partly through inhibition of platelet activation, therefore reducing the infiltration of neutrophils due to the adhesion of platelets and neutrophils mediated by CD40 - CD40 L interaction. Cangrelor could be a potential therapeutic medicine for pulmonary fibrosis.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Activación Plaquetaria/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Adenosina Monofosfato/uso terapéutico , Animales , Bleomicina/toxicidad , Antígenos CD40/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Infiltración Neutrófila/inmunología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Activación Plaquetaria/inmunología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/inmunología
19.
Ann Hematol ; 99(4): 703-714, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32103323

RESUMEN

Monoclonal gammopathy of renal significance (MGRS) is characterized by the nephrotoxic monoclonal immunoglobulin secreted by an otherwise asymptomatic or indolent B cell or plasma cell clone, without hematologic criteria for treatment. These MGRS-associated diseases can involve one or more renal compartments, including glomeruli, tubules, and vessels. Hydrophobic residue replacement, N-glycosylated, increase in isoelectric point in monoclonal immunoglobulin (MIg) causes it to transform from soluble form to tissue deposition, and consequently resulting in glomerular damage. In addition to MIg deposition, complement deposition is also found in C3 glomerulopathy with monoclonal glomerulopathy, which is caused by an abnormality of the alternative pathway and may involve multiple factors including complement component 3 nephritic factor, anti-complement factor auto-antibodies, or MIg which directly cleaves C3. Furthermore, inflammatory factors, growth factors, and virus infection may also participate in the development of the diseases. In this review, for the first time, we discussed current highlights in the mechanism of MGRS-related lesions.


Asunto(s)
Anticuerpos Monoclonales/metabolismo , Enfermedades Renales/etiología , Paraproteinemias/etiología , Paraproteínas/metabolismo , Autoanticuerpos/inmunología , Autoanticuerpos/metabolismo , Complemento C3/metabolismo , Factor Nefrítico del Complemento 3/metabolismo , Convertasas de Complemento C3-C5/antagonistas & inhibidores , Convertasas de Complemento C3-C5/metabolismo , Vía Alternativa del Complemento , Crioglobulinemia/etiología , Crioglobulinemia/metabolismo , Glicosilación , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/etiología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/metabolismo , Mediadores de Inflamación/metabolismo , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Proteínas de Neoplasias/metabolismo , Paraproteinemias/complicaciones , Paraproteinemias/genética , Paraproteinemias/metabolismo , Procesamiento Proteico-Postraduccional , Factor de Crecimiento Transformador beta/metabolismo
20.
Anesthesiology ; 132(2): 357-372, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31939851

RESUMEN

BACKGROUND: Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development. METHODS: The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed. RESULTS: Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1ß, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1ß, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment. CONCLUSIONS: Inhibition of inflammatory mediator-triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.


Asunto(s)
Neoplasias Óseas/metabolismo , Dolor en Cáncer/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Mediadores de Inflamación/metabolismo , Nocicepción/fisiología , Animales , Neoplasias Óseas/complicaciones , Dolor en Cáncer/etiología , Células Cultivadas , Femenino , Masculino , Ratones , Ratones Endogámicos C3H , Embarazo
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