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BACKGROUND: Angiostrongylus cantonensis is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in certain geographical areas. Current diagnostic methods include detection of the parasite in cerebrospinal fluid (CSF) and eosinophilic immune examination after lumbar puncture, which may be risky and produce false-positive results. 18F- Fluorodeoxyglucose (FDG), a Positron emission tomography (PET) tracer, has been used to assess different pathological or inflammatory changes in the brains of patients. In this study, we hypothesized that A. cantonensis infection-induced inflammatory and immunomodulatory factors of eosinophils result in localized pathological changes in the brains of non-permissive hosts, which could be analyzed using in vivo 18F-FDG PET imaging. METHODOLOGY/FINDINGS: Non-permissive host ICR mice and permissive host SD rats were infected with A. cantonensis, and the effects of the resulting inflammation on 18F-FDG uptake were characterized using PET imaging. We also quantitatively measured the distributed uptake values of different brain regions to build an evaluated imaging model of localized neuropathological damage caused by eosinophilic inflammation. Our results showed that the uptake of 18F-FDG increased in the cerebellum, brainstem, and limbic system of mice at three weeks post-infection, whereas the uptake in the rat brain was not significant. Immunohistochemical staining and western blotting revealed that Iba-1, a microglia-specific marker, significantly increased in the hippocampus and its surrounding area in mice after three weeks of infection, and then became pronounced after four weeks of infection; while YM-1, an eosinophilic chemotactic factor, in the hippocampus and midbrain, increased significantly from two weeks post-infection, sharply escalated after three weeks of infection, and peaked after four weeks of infection. Cytometric bead array (CBA) analysis revealed that the expression of TNF in the serum of mice increased concomitantly with the prolongation of infection duration. Furthermore, IFN-γ and IL-4 in rat serum were significantly higher than in mouse serum at two weeks post-infection, indicating significantly different immune responses in the brains of rats and mice. We suggest that 18F-FDG uptake in the host brain may be attributed to the accumulation of large numbers of immune cells, especially the metabolic burst of activated eosinophils, which are attracted to and induced by activated microglia in the brain. CONCLUSIONS: An in vivo 18F-FDG/PET imaging model can be used to evaluate live neuroinflammatory pathological changes in the brains of A. cantonensis-infected mice and rats.
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Angiostrongylus cantonensis , Encéfalo , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Ratas Sprague-Dawley , Infecciones por Strongylida , Animales , Angiostrongylus cantonensis/inmunología , Infecciones por Strongylida/inmunología , Infecciones por Strongylida/parasitología , Infecciones por Strongylida/diagnóstico por imagen , Infecciones por Strongylida/patología , Encéfalo/parasitología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/inmunología , Ratones , Ratas , Eosinófilos/inmunología , Inflamación/inmunología , Masculino , Modelos Animales de Enfermedad , Lectinas/metabolismo , Femenino , beta-N-AcetilhexosaminidasasRESUMEN
BACKGROUND: The immunoglobulin E (IgE) response to Angiostrongylus cantonensis infection increases in the host. This study analyzed the IgG and IgE responses detected in different body fluids of A. cantonensis-infected mice. METHODS: BALB/c (high susceptibility), CBA (medium), and C57BL/6 and C57BL/10 (resistance) strain mice were used in this study. The levels of IgM, IgG, and IgE in the serum and cerebrospinal fluid (CSF) from infected mice were compared. A. cantonensis-reactive antigens from BALB/c and C57BL/6 mice CSF were also analyzed. RESULTS: Antibodies against fifth-stage larvae (L5) antigens increased in mice CSF, particularly IgE, relate to worm rejection and the susceptibility of different mouse strains. The increased IgE level in BALB/c mice CSF is lower than that from others, suggesting IgE response in brain is more important than that in serum. Anti-L5 and anti-excretory/secretory (ES) antigen IgE and IgG responses in CSF were analyzed. In addition, the antibody-dependent eosinophil-mediated cytotoxicity induced by anti-excretory/secretory (ES) antigen antibodies may be the reason of severe brain inflammation in infected BALB/c mice. IgE and IgG antibodies against a 105 kDa protein of L5 antigen was detected at week 3 post-infection in C57BL/6 mice and week 5 post-infection in BALB/c mice. We suggest that 105 kDa protein is related with the antibody response of A. cantonensis-infected mice. CONCLUSION: We found that IgE antibodies in mice CSF against L5 antigens related to worm rejection in mice brains. This study may help to identify specific angiostrongyliasis markers that can be applied for clinical diagnosis and treatment in future.
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Angiostrongylus cantonensis , Infecciones por Strongylida , Ratones , Animales , Formación de Anticuerpos , Ratones Endogámicos CBA , Ratones Endogámicos C57BL , Inmunoglobulina E , Encéfalo/patología , Inmunoglobulina G , Ratones Endogámicos BALB CRESUMEN
Schistosomiasis is a major global health problem. Schistosomes secrete antigens into the host tissue that bind to chemokines or inhibit immune cell receptors, regulating the immune responses to allow schistosome development. However, the detailed mechanism of chronic schistosome infection-induced liver fibrosis, including the relationship between secreted soluble egg antigen (SEA) and hepatic stellate cell (HSC) activation, is still unknown. We used mass spectrometry to identify the SEA protein sequences from different infection weeks. In the 10th and 12th infection weeks, we focused on the SEA components and screened out the special protein components, particularly fibrosis- and inflammation-related protein sequences. Our results have identified heat shock proteins, phosphorylation-associated enzymes, or kinases, such as Sm16, GSTA3, GPCRs, EF1-α, MMP7, and other proteins linked to schistosome-induced liver fibrosis. After sorting, we found many special proteins related to fibrosis and inflammation, but studies proving their association with schistosomiasis infection are limited. Follow-up studies on MICOS, MATE1, 14-3-3 epsilon, and CDCP1 are needed. We treated the LX-2 cells with the SEA from the 8th, 10th, and 12th infection weeks to test HSC activation. In a trans-well cell model in which PBMCs and HSCs were co-cultured, the SEA could significantly induce TGF-ß secretion, especially from the 12th week of infection. Our data also showed that TGF-ß secreted by PBMC after the SEA treatment activates LX-2 and upregulates hepatic fibrotic markers α-SMA and collagen 1. Based on these results, the CUB domain-containing protein 1 (CDCP1) screened at the 12th infection week could be investigated further. This study clarifies the trend of immune mechanism variation in the different stages of schistosome infection. However, how egg-induced immune response transformation causes liver tissue fibrosis needs to be studied further.
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Obesity is associated with multiple comorbidities, such as metabolic abnormalities and cognitive dysfunction. Moreover, accumulating evidence indicates that neurodegenerative disorders are associated with chronic neuroinflammation. GLP-1 receptor agonists (RAs) have been extensively studied as a treatment for type 2 diabetes. Emerging evidence has demonstrated a protective effect of GLP-1 RAs on neurodegenerative disease, which is independent of its glucose-lowering effects. In this study, we aimed to examine the effects of a long-acting GLP-1 RA, exenatide, on high-fat diet (HFD)-induced neuroinflammation and related brain function impairment. First, mice treated with exenatide exhibited significantly reduced HFD-increased body weight and blood glucose. In an open field test, exenatide treatment ameliorated the reduction in local motor activity and anxiety in HFD-fed mice. Moreover, HFD induced astrogliosis, microgliosis, and upregulation of IL-1ß, IL-6 and TNF-α in hippocampus and cortex. Exenatide treatment reduced HFD-induced astrogliosis and IL-1ß and TNF-α expressions. Moreover, exenatide increased phosphor-ERK and M2-type microglia marker arginase-1 expression in the hippocampus and cortex. In addition, we found that scavenger receptor-A4 protein expression was induced by HFD and was subsequently inhibited by exenatide. SR-A4 knockout reversed the locomotor activity impairment but not the anxiety behavior caused by HFD consumption. SR-A4 knockout also reduced HFD-induced neuroinflammation, as shown by the reduced expression of GFAP and IBA-1 compared with that in wild-type control mice. These results demonstrate that exenatide decreases HFD-increased neuroinflammation and promotes anti-inflammatory M2 differentiation. The inhibition of SR-A4 by exenatide exerts anti-inflammatory activity.
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Diabetes Mellitus Tipo 2 , Enfermedades Neurodegenerativas , Ratones , Animales , Exenatida/farmacología , Exenatida/uso terapéutico , Microglía , Receptor del Péptido 1 Similar al Glucagón/agonistas , Enfermedades Neuroinflamatorias , Regulación hacia Abajo , Diabetes Mellitus Tipo 2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Gliosis , Obesidad/metabolismo , Dieta Alta en Grasa/efectos adversos , Péptido 1 Similar al Glucagón/metabolismo , Locomoción , Ansiedad/tratamiento farmacológico , Ratones Endogámicos C57BLRESUMEN
JAK/STAT plays a key role in regulating uropathogenic Escherichia coli (UPEC) infection in urothelial cells, probably via antimicrobial peptide (AMP) production, in diabetic patients with urinary tract infections. Whether multiple pathways regulate AMPs, especially lipid-carrying protein-2 (LCN2), to achieve a vital effect is unknown. We investigated the effects of an LCN2 pretreatment on the regulation of the JAK/STAT pathway in a high-glucose environment using a bladder cell model with GFP-UPEC and phycoerythrin-labeled TLR-4, STAT1, and STAT3. Pretreatment with 5 or 25 µg/mL LCN2 for 24 h dose-dependently suppressed UPEC infections in bladder cells. TLR-4, STAT1, and STAT3 expression were dose-dependently downregulated after LCN2 pretreatment. The LCN2-mediated alleviation of UPEC infection in a high-glucose environment downregulated TLR-4 and the JAK/STAT transduction pathway and decreased the UPEC-induced secretion of exogenous inflammatory interleukin (IL)-6 and IL-8. Our study provides evidence that LCN2 can alleviate UPEC infection in bladder epithelial cells by decreasing JAK/STAT pathway activation in a high-glucose environment. LCN2 dose-dependently inhibits UPEC infection via TLR-4 expression and JAK/STAT pathway modulation. These findings may provide a rationale for targeting LCN2/TLR-4/JAK/STAT regulation in bacterial cystitis treatment. Further studies should explore specific mechanisms by which the LCN2, TLR-4, and JAK/STAT pathways participate in UPEC-induced inflammation to facilitate the development of effective therapies for cystitis.
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Cistitis , Infecciones por Escherichia coli , Infecciones Urinarias , Escherichia coli Uropatógena , Humanos , Vejiga Urinaria/metabolismo , Péptidos Antimicrobianos , Quinasas Janus/metabolismo , Receptor Toll-Like 4/metabolismo , Transducción de Señal , Factores de Transcripción STAT/metabolismo , Infecciones Urinarias/microbiología , Cistitis/tratamiento farmacológico , Cistitis/metabolismo , Infecciones por Escherichia coli/microbiología , Células Epiteliales/metabolismo , Glucosa/metabolismo , Lipocalina 2/metabolismoRESUMEN
BACKGROUND: Aedes aegypti and Aedes albopictus are two important vectors of several important arboviruses, including the dengue, chikungunya, and Zika viruses. Insecticide application is an important approach to reduce vector abundance during Aedes spp.-borne outbreaks in the absence of effective vaccines and treatments. However, insecticide overuse can result in the development of resistance, and careful monitoring of resistance markers is required. METHODS: This meta-analysis and systematic review explored the spatial and temporal patterns of insecticide resistance in Asia from 2000 to 2021. PubMed, Scopus, EbscoHost, and Embase were used to enhance the search capability. The random-effects model was applied for the 94 studies that met our inclusion criteria for qualitative synthesis and meta-analysis. RESULTS: Four major insecticides were studied (malathion, dichlorodiphenyltrichloroethane, permethrin, and deltamethrin). Dichlorodiphenyltrichloroethane resistance rates were high in both Ae. aegypti and Ae. albopictus (68% and 64%, respectively). Conversely, malathion resistance was less prevalent in Ae. aegypti (3%), and deltamethrin resistance was less common in Ae. albopictus (2%). Ae. aegypti displayed consistently high resistance rates (35%) throughout the study period, whereas the rate of insecticide resistance in Ae. albopictus increased from 5% to 12%. The rates of the major kdr mutations F1534C, V1016G, and S989P were 29%, 26%, and 22%, respectively. CONCLUSIONS: Insecticide resistance in both Ae. aegypti and Ae. albopictus is widespread in Asia, although the rates vary by country. Continuous monitoring of the resistance markers and modification of the control strategies will be important for preventing unexpected outbreaks. This systematic review and meta-analysis provided up-to-date information on insecticide resistance in dengue-endemic countries in Asia.
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BACKGROUND: Schistosomiasis is one of the most devastating tropical diseases in the world. Currently, praziquantel (PZQ) represents the best pharmacological option for the treatment of schistosomiasis as it effectively kills the worm. However, the inability to reverse established liver damages often makes treatment futile. In the current study, we investigate whether combining the use of wogonin, a compound that was found to be liver-protective, with PZQ can attribute to the greatest beneficial effect in Schistosoma mansoni-infected mice. METHODS: To determine the protective effect of PZQ-wogonin treatment on S. manosni-infected mice, histopathological analysis was done to evaluate the granuloma size and fibrotic areas in the liver. Western blotting was performed to analyze several injuries-related markers including fibrotic markers, inflammasomes, and apoptotic markers. Scanning electron microscopy was done to evaluate the effect of wogonin on the worms, and the worm and egg burden was calculated. RESULTS: Our results showed that PZQ-wogonin treatment significantly improved liver histopathology of S. mansoni-infected mice. Further analysis showed that PZQ-wogonin combinations are more effective in reducing fibrosis, inflammation, and apoptosis in the liver than that of individual drug use. Furthermore, our results revealed that wogonin is anthelmintic; and it works better with PZQ in reducing hepatic egg burden, further lessen the disease progression. CONCLUSION: In general, this combinatorial strategy may represent a new and effective approach to schistosomiasis treatment.
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Antihelmínticos , Esquistosomiasis mansoni , Esquistosomiasis , Animales , Flavanonas , Hígado , Ratones , Praziquantel , Schistosoma mansoniRESUMEN
Antimicrobial peptides (AMPs), which are natural antibiotics, protect against pathogens invading the urinary tract. RNase 7 with antimicrobial properties has rapid and powerful suppressive effects against Gram-positive and Gram-negative bacterial infections. However, its detailed antibacterial mechanisms have not been fully determined. Here, we investigate whether RNase 7 had an impact on bladder cells under uropathogenic Escherichia coli (UPEC) infection in a high-glucose environment using in vitro GFP-UPEC-infected bladder cell and PE-labeled TLR4, STAT1, and STAT3 models. We provide evidence of the suppressive effects of RNase 7 on UPEC infection and UPEC-induced inflammatory responses by regulating the JAK/STAT signaling pathway using JAK inhibitor and STAT inhibitor blocking experiments. Pretreatment with different concentrations of RNase 7 for 24 h concentration-dependently suppressed UPEC invasion in bladder cells (5 µg/mL reducing 45%; 25 µg/mL reducing 60%). The expressions of TLR4, STAT1, and STAT3 were also downregulated in a concentration-dependent manner after RNase 7 pretreatment (5 µg/mL reducing 35%, 54% and 35%; 25 µg/mL reducing 60%, 75% and 64%, respectively). RNase 7-induced decrease in UPEC infection in a high-glucose environment not only downregulated the expression of TLR4 protein and the JAK/STAT signaling pathway but also decreased UPEC-induced secretion of exogenous inflammatory IL-6 and IL-8 cytokines, although IL-8 levels increased in the 25 µg/mL RNase 7-treated group. Thus, inhibition of STAT affected pSTAT1, pSTAT3, and TLR4 expression, as well as proinflammatory IL-6 and IFN-γ expression. Notably, blocking JAK resulted in the rebound expression of related proteins, especially pSTAT1, TLR4, and IL-6. The present study showed the suppressive effects of RNase 7 on UPEC infection and induced inflammation in bladder epithelial cells in a high-glucose environment. RNase 7 may be an anti-inflammatory and anti-infective mediator in bladder cells by downregulating the JAK/STAT signaling pathway and may be beneficial in treating cystitis in DM patients. These results will help clarify the correlation between AMP production and UTI, identify the relationship between urinary tract infection and diabetes in UTI patients, and develop novel diagnostics or possible treatments targeting RNase 7.
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Infecciones por Escherichia coli , Ribonucleasas , Infecciones Urinarias , Escherichia coli Uropatógena , Células Epiteliales/metabolismo , Infecciones por Escherichia coli/metabolismo , Femenino , Glucosa/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Ribonucleasas/metabolismo , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Vejiga Urinaria/patología , Infecciones Urinarias/microbiologíaRESUMEN
Cryptosporidium spp. is a group of protozoans that cause diarrheal disease in both humans and animals. In Taiwan, very little information is available about the epidemiology of Cryptosporidium spp. in domesticated animals, especially in Eastern Taiwan where agriculture is one of the main industries. Therefore, this study aimed to investigate the occurrence of Cryptosporidium spp. in livestock in Hualien Country of Eastern Taiwan and identify their genotypes. Excrements from dogs (n = 81), cattle (n = 156), and pigs (n = 142) were randomly collected from different pastures or farm in Hualien Country. Microscopic examination and nested PCR were performed on all samples and both showed identical results, with 4.94% (4/81) of dogs, 24.36% (38/156) of cattle, and 16.20% (23/142) of pigs being infected with Cryptosporidium species. Positive samples were then sequenced and analyzed. DNA sequencing revealed that all four positive samples isolated from dogs were Cryptosporidium canis (C. canis); 38 positive samples from cattle were identified as C. bovis (8/38), C. canis (1/38), C. ryanae (4/38), and C. scrofarum (25/38); and 22 positive samples isolated from pigs were identified as C. scrofarum while one was identified as C. suis. In addition, the infective rates of animals from indoor farms (57.14% of all positive samples) are much higher than the rates from pastures. This study provided evidence of the occurrence of Cryptosporidium spp. in Hualien country, and farming conditions largely affect their infection rates. Therefore, precautions should be made to control Cryptosporidium spp. transmission.
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Enfermedades de los Bovinos , Criptosporidiosis , Cryptosporidium , Enfermedades de los Porcinos , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Criptosporidiosis/epidemiología , Cryptosporidium/genética , Perros , Heces , Genotipo , Ganado , Prevalencia , Porcinos , Enfermedades de los Porcinos/epidemiología , Taiwán/epidemiologíaRESUMEN
Schistosomiasis is a tropical parasitic disease, in which the major clinical manifestation includes hepatosplenomegaly, portal hypertension, and organs fibrosis. Clinically, treatment of schistosomiasis involves the use of praziquantel (PZQ) and supportive care, which does not improve the patient's outcome as liver injuries persist. Here we show the beneficial effects of using PZQ in combination with Schisandrin B (Sch B). Concomitant treatment with PZQ and Sch B resulted in a significant improvement of hepatosplenomegaly and fibrosis, compared with single-agent treatment. We also demonstrated that PZQ-Sch B treatment ameliorates injuries in the lungs and intestine better than the sole use of PZQ or Sch B. In addition, PZQ-Sch B treatment improves the survival of S. mansoni-infected mice, and the treatment combination yields better therapeutic outcomes, as indicated by a partial improvement in neurological function. These results were accompanied by a reduction in neurological injuries. Collectively, we suggest that PZQ-Sch B concomitant therapy may be useful to alleviate schistosomiasis-associated liver injuries and prevent systemic complications.
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Antihelmínticos , Compuestos Policíclicos , Esquistosomiasis mansoni , Animales , Antihelmínticos/farmacología , Ciclooctanos , Lignanos , Ratones , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/uso terapéutico , Praziquantel , Schistosoma mansoni , Esquistosomiasis mansoni/complicaciones , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitologíaRESUMEN
The significance of this work is that ambient PM2.5 is a direct transmission mode for influenza virus infection to the human alveolar epithelium. The concentration of PM2.5 was 11.7 ± 5.5 µg/m3 in Taipei during 24 December 2019-13 January 2020. Approximately 79% of inhaled PM2.5 is able to reach the upper-to-lower airway, and 47% of PM2.5 is able to reach the alveolar epithelium for influenza virus infection. Influenza A and B viruses were detected in PM2.5 on 9 days, and the influenza A/H5 virus was detected on 15 days during the study period. FL and Pyr were negatively correlated with the influenza A virus. D(ah)P and Acp were positively correlated with the influenza B and A/H5 viruses, respectively. Cd, V, and Zn were positively correlated with the influenza A, B, and A/H5 viruses, respectively. Next, influenza A, B, and A/H5 viral plasmids interacted with carbon black, H2O2, DEPs, and UD. We observed that H2O2 significantly decreased levels of complementary DNA of the three influenza viruses. DEPs and UD significantly decreased influenza A and A/H5 viral levels. In conclusion, chemicals in PM2.5 may play vital roles in terms of viable influenza virus in the atmosphere.
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Contaminantes Atmosféricos , Orthomyxoviridae , Contaminantes Atmosféricos/análisis , Humanos , Peróxido de Hidrógeno , Material Particulado/análisisRESUMEN
Many challenges, such as virus infection, extreme weather and long cultivation periods, during the development of fish larvae have been observed, especially in aquaculture. Gene delivery is a useful method to express functional genes to defend against these challengers. However, the methods for fish larvae are insufficient. In our earlier report, low-molecular-weight chitosan (LMWCS) showed a strong positive charge and may be useful for polyplex formulation. Herein, we present a simple self-assembly of LMWCS polyplexes (LMWCSrNPs) for gene delivery into zebrafish larvae. Different weight ratios of LMWCS/gamma-polyglutamic acid (γ-PGA)/plasmid DNA were analyzed by gel mobility assay. Delivery efficiency determined by green fluorescent protein (GFP) expression in zebrafish liver (ZFL) cells showed that delivery efficiency at a weight ratio of 20:8:1 was higher than others. Zeta potential and transmission electron microscopy (TEM) analysis showed that the round shape of the particle size varied. In our earlier reports, IRF9S2C could induce interferon-stimulated gene (ISG) expression to induce innate immunity in zebrafish and pufferfish. Further delivery of pcDNA3-IRF9S2C-HA plasmid DNA into ZFL cells and zebrafish larvae by LMWCSrNP successfully induced ISG expression. Collectively, LMWCSrNP could be a novel gene delivery system for zebrafish larvae and might be used to improve applications in aquaculture.
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Quitosano/química , Portadores de Fármacos/química , Técnicas de Transferencia de Gen , Ácidos Nucleicos/administración & dosificación , Ácido Poliglutámico/análogos & derivados , Animales , Supervivencia Celular , Células Cultivadas , Fenómenos Químicos , Portadores de Fármacos/síntesis química , Expresión Génica , Genes Reporteros , Larva , Peso Molecular , Ácido Poliglutámico/síntesis química , Ácido Poliglutámico/química , Análisis Espectral , Pez CebraRESUMEN
BACKGROUND: Macrophages play crucial roles in immune responses during the course of schistosomal infections. METHODS: We currently investigated influence of immunocompetent changes in macrophages via microarray-based analysis, mRNA expression analysis, detection of serum cytokines, and subsequent evaluation of the immune phenotypes following the differentiation of infection-induced lymphocytes in a unique T1/T2 double-transgenic mouse model. RESULTS: The gradual upregulation of genes encoding YM1, YM2, and interleukin (IL)-4/IL-13 receptors in infected mice indicated the role of type 2 alternatively activated macrophages (M2, AAMφs) in immune responses after Schistosoma japonicum egg production. FACS analysis showed that surface markers MHC class II (IA/IE) and CD8α+ of the macrophages also exhibited a dramatic change at the various time points before and after egg-production. The transgenic mouse experiments further demonstrated that the shifting of macrophage phenotypes influenced the percentage of helper T (Th)-2 cells, which was observed to be higher than that of Th1 cells, which increased only at 3 and 5 weeks post-infection. The differentiation of effector B cells showed a similar but more significant trend toward type-2 immunity. CONCLUSION: These results suggest that the infection of mice with S. japonicum resulted in a final Th2- and Be2-skewed immune response. This may be due to phenotypic changes in the macrophages. The influence of alternatively activated macrophages was also activated by S. japonicum egg production. This study elucidated the existence of variations in immune mechanisms at the schistosome infection stages.
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Macrófagos , Esquistosomiasis Japónica , Animales , Inmunidad , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Fenotipo , Esquistosomiasis Japónica/inmunología , Células TH1 , Células Th2RESUMEN
BACKGROUND/PURPOSE: Schistosomiasis is an important tropical disease caused by Schistosoma. Although the pathogenesis of liver fibrosis has been intensively studied, the choice of effective treatment is still inadequate. In this study, we aimed to investigate the potential of using Casticin to treat Schistosoma mansoni-induced liver fibrosis. METHODS: BALB/c mice were divided into three groups - control, infection, and treatment group. The infection and treatment group were percutaneously infected with 100-120 cercariae. Mice from the treatment group were treated with 20 mg/kg/day Casticin for 14 consecutive days to investigate the potential protective effects of Casticin. Mice were sacrificed and were used for histological, RNA, protein, and parasite burden analysis. RESULTS: Our results showed that hepatic fibrosis was significantly attenuated, as indicated by histology and reduction of fibrotic markers such as collagen AI, transforming growth factor ß (TGF-ß), and α-smooth muscle actin (α-SMA). Furthermore, Casticin treatment significantly reduced worm burden. Anthelmintic effect of Casticin was also observed by scanning electron microscopy. CONCLUSION: Collectively, our study suggested that Casticin may be a beneficial candidate in treating S. mansoni infection.
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Antihelmínticos , Antiinfecciosos , Esquistosomiasis mansoni , Animales , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Antiinfecciosos/farmacología , Flavonoides , Humanos , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Ratones , Ratones Endogámicos BALB C , Praziquantel/farmacología , Praziquantel/uso terapéutico , Schistosoma mansoni , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Esquistosomiasis mansoni/patologíaRESUMEN
After many years of the excessive use of praziquantel against Schistosoma mansoni (S. mansoni), it has already led to the development of drug resistance. While schistosomiasis is still affecting millions of people every year, vaccination may be one realistic alternative way to control the disease. Currently, S. mansoni 14-kDa fatty acid-binding protein (Sm14) has shown promising results as a vaccine antigen. Yet, the use of an adjuvant may be necessary to further increase the effectiveness of the vaccine. Herein, we investigated the potential of using heat-killed Cutibacterium acnes (C. acnes) as an adjuvant for recombinant Sm14 (rSm14). Immunization of mice with C. acnes-adjuvanted rSm14 showed increased humoral immune responses, compared with mice immunized with rSm14 alone. Additionally, C. acnes-adjuvanted rSm14 vaccination provided higher protection to mice against S. mansoni infection and liver injuries. These results suggest that C. acnes increases the immunogenicity of rSm14, which leads to better protection against S. mansoni infection. Therefore, heat-killed C. acnes may be a promising adjuvant to use with rSm14.
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Proteínas de Transporte de Ácidos Grasos/inmunología , Proteínas del Helminto/inmunología , Inmunogenicidad Vacunal , Propionibacteriaceae/química , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/prevención & control , Vacunas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Diabetic individuals have a higher incidence of urinary tract infection (UTI) than non-diabetic individuals, and also require longer treatment. We evaluated the effects of insulin pretreatment on the regulation of JAK/STAT transduction pathways in UPEC-infected bladder cells in a high-glucose environment. A bladder cell model with GFP-UPEC and fluorescent-labeled TLR4, STAT1, STAT3, and insulin receptor antibodies, was used to evaluate the relationship between insulin receptor signaling, TLR-4-mediated, and JAK/STAT-dependent pathways. Pretreatment with 20 and 40 µg/mL insulin for 24 h significantly and dose-dependently reduced UPEC infection in SV-HUC-1 cells. Additionally, the expression levels of STAT1 and STAT3 were downregulated in a dose-dependent manner. However, insulin receptor (IR) expression was not affected by insulin pretreatment. Our results showed that insulin-mediated reduction of UPEC infection in a high-glucose environment was not only due to the downregulation of JAK1/2 and phosphorylated STAT-1/3, but also because of the decreased expression of TLR-4 proteins and pro-inflammatory IL-6. Here, we demonstrated that insulin reduced not only UPEC infection in bladder epithelial cells, but also inhibited the JAK/STAT transduction pathway during infection in a high-glucose environment. This study provides evidence to support the use of insulin in the treatment of UPEC infection in patients with type 2 diabetes (T2D).
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Sm28GST is one of the candidate antigens for Schistosoma mansoni vaccine. Already Sm28GST vaccine formulations have shown to be protective against S. mansoni infection. Currently, efforts have been put into finding an adjuvant to enhance the immunity induced by Sm28GST. In the present work, we investigated whether heat-killed Propionibacterium acnes can be served as a potential adjuvant for recombinant Sm28GST (rSm28GST) antigen. As the results showed, P. acnes successfully modulated the Th1 humoral immune response induced by rSm28GST. Stronger Th1 cytokines responses were also observed in mice immunized with P. acnes-adjuvanted rSm28GST. Immunization of mice with P. acnes-adjuvanted rSm28GST was able to reduce worm burden and hepatic egg burden by 54.20 and 73.61%. Reduced granuloma size and count, as well as improved liver histology, were seen in P. acnes-adjuvanted rSm28GST immunized mice. These data suggest that P. acnes may evoke a stronger rSm28GST-induced immune response, higher resistance to S. mansoni infection, and more profound protection against S. mansoni-induced liver damages.
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Antígenos Helmínticos/inmunología , Glutatión Transferasa/inmunología , Propionibacterium acnes , Esquistosomiasis mansoni , Vacunas/inmunología , Adyuvantes Inmunológicos , Animales , Anticuerpos Antihelmínticos , Calor , Ratones , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/prevención & control , Células TH1/inmunologíaRESUMEN
BACKGROUND: The regulation of the balance between inflammatory and anti-inflammatory events during the treatment of pulmonary infection is very important. Soluble Schistosoma egg antigens (SEA) can effectively inhibit the expression of cytokines during hepatic acute inflammation. However, the mechanisms by which these proteins suppress the inflammatory responses in lung cells remain unclear. The purpose of this study was to investigate the ability of SEA to inhibit pulmonary inflammation. METHODS: The effects of SEA were investigated in LPS-treated lung IMR-90 cells. The involvement of the JAK/STAT-1 signaling pathway in these effects was evaluated by employing CBA assays, quantitative polymerase chain reaction, and western blotting experiments. RESULTS: Pretreatment of IMR-90 cells with appropriate concentrations of SEA protected cells against the cytotoxic effects of LPS-induced inflammation in a time-dependent manner. SEA pretreatment significantly attenuated the LPS-induced activation of the JAK/STAT1 signaling pathway, including the upregulation of JAK1/2 and STAT1, as well as the production of inflammatory cytokines. The level of phosphorylated STAT1 gradually declined in response to increasing concentrations of SEA. Based on these findings, we hypothesize that SEA-induced anti-inflammatory effects initiate with the downregulation of the IFN-γ-JAK-STAT1 signaling pathway, resulting in the attenuation of LPS-induced inflammation in IMR-90 cells. CONCLUSION: Our study is the first to demonstrate the anti-inflammatory activity of SEA in an in vitro model of pulmonary inflammation, involving the modulation of JAK/STAT1 signaling. We propose SEA as potential therapeutic or preventive agents for the selective suppression of STAT1 and the control of inflammatory response in lung IMR-90 cells.
Asunto(s)
Antígenos Helmínticos/farmacología , Fibroblastos/efectos de los fármacos , Inflamación/prevención & control , Janus Quinasa 1/metabolismo , Lipopolisacáridos/farmacología , Óvulo/química , Factor de Transcripción STAT1/metabolismo , Schistosoma/inmunología , Transducción de Señal , Animales , Línea Celular , Humanos , Janus Quinasa 1/inmunología , Lipopolisacáridos/metabolismo , Factor de Transcripción STAT1/inmunología , Schistosoma/químicaRESUMEN
BACKGROUND: Patients with diabetes mellitus (DM) have higher incidence and more severe urinary tract infections (UTIs) for longer duration than those of the patients without DM. It causes more complicated etiologies during uropathogenic Escherichia coli (UPEC) infection. However, studies regarding the molecular mechanism are scarce. METHODS: The present study (1) aimed to verify if sugar influences the process of UPEC-induced cystitis and invasion into the uroepithelial cells and (2) illustrated the mechanism of effects for sugar enhanced the UPEC infection into uroepithelial cells is related to TLR-4-mediated and JAK/STAT1-dependent pathway. RESULTS: The results of the present study indicated that sugar can enhance UPEC infection in uroepithelial cells by up-regulating the transduced circuit between TLR-4-mediated UPEC interaction and JAK/STAT-1 signal pathways. The results of the inhibitor-co-incubating experiments demonstrated that the mechanism involved in the synergistic amplification of TLR-4-mediated UPEC interaction and JAK/STAT1 signaling pathways is responsible for the increased UPEC infection in uroepithelial cells. CONCLUSION: The results also proved that STAT-1 plays a critical role in the regulation of UPEC invasion and infection in the uroepithelial cells, especially those pretreated with glucose. The present study suggests a possible therapeutic approach to preferentially suppress UPEC infection during UTIs in the patients with diabetes.
Asunto(s)
Factor de Transcripción STAT1/metabolismo , Transducción de Señal , Azúcares/metabolismo , Receptor Toll-Like 4/metabolismo , Escherichia coli Uropatógena , Urotelio/metabolismo , Línea Celular , Células Epiteliales/metabolismo , Infecciones por Escherichia coli/patología , Regulación de la Expresión Génica , Humanos , Receptor Toll-Like 4/genética , Infecciones Urinarias/metabolismo , Infecciones Urinarias/patología , Urotelio/microbiología , Urotelio/patologíaRESUMEN
Angiostrongylus cantonensis is one of the most widespread parasites causing central nervous system (CNS) diseases in mammals. Since the mitochondrion is an essential cell organelle responsible for both physiological and pathological processes, its dysfunction might lead to inflammation and multiple disorders. In this study we aimed to investigate the changes in mitochondrial dynamics that occur in the mouse brain upon infection with A. cantonensis, using molecular biology techniques such as polymerase chain reaction (PCR), western blot analysis, transmission electron microscopy (TEM), and different staining methods. Here, we show that mouse brain infected with A. cantonensis exhibits altered mitochondrial dynamics, including fission, fusion, and biogenesis. Additionally, we demonstrate that caspases and B-cell lymphoma 2 (BCL-2) were significantly upregulated in A. cantonensis-infected brain. These results are indicative of the occurrence of apoptosis during A. cantonensis infection, which was further confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. These findings suggest the change in mitochondrial dynamics in A. cantonensis-infected brain, providing another point of view on the pathogenesis of meningoencephalitis caused by A. cantonensis infection.