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1.
Immunobiology ; 224(3): 347-352, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30987761

RESUMO

A high level of serum IgE is a hallmark of helminthic disease. Secretory IgE can bind FcεRI or FcεRII/CD23. The combination of IgE and FcεRI, a high-affinity interaction, has long received attention and is believed to facilitate helminth control, while the properties of CD23-bound IgE have long been unexplored. Here, we established a Clonorchis sinensis (C. sinensis) infection model with different mouse strains and investigated membrane-bound IgE on B cells during infection. We show that after infection, the increase in CD23 expression on B cells was obvious, even in relatively resistant C57BL/6 mice, as well as in susceptible BALB/c and FVB mice. Although the serum IgE amount was lower in C57BL/6 mice than in BALB/c and FVB mice, the level of IgE binding to peripheral B cells was also elevated. Additionally, the IgE on B cells was soon undetectable in vitro due to dissociable binding. The results of the present study demonstrate the dramatic increase in CD23-bound IgE on B cells after C. sinensis infection. The significance of CD23-bound IgE in Ag transport and presentation has gained consideration in allergy development for its potential ability to promote the Th2 response. Therefore, even though the association of IgE and CD23 is not as substantial as that of IgE and FcεRI, membrane-bound IgE on B cells may be worth further study regarding clonorchiasis and other parasitic infections.

2.
BMC Immunol ; 19(1): 29, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355335

RESUMO

BACKGROUND: Excretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-ESPs) are well-known to regulate T cell responses. However, their direct influence on the differentiation of B cell subsets remains largely elusive. This study investigated the effects of EgPSC-ESPs on the differentiation of IL-10-producing B cells (B10), and explored the possible role of Toll-like receptor 2 (TLR-2) signaling in this process. RESULTS: In comparison to phosphate buffered saline (PBS), B cells exposed to the excretory-secretory products (ESPs) generated higher percentages of B10 cells, with higher expression of IL-10 mRNA, and larger amount of IL-10 production, which were in a dose dependent way. The mRNA and protein expression of TLR-2 in the ESPs-stimulated B cells were significantly higher than those in PBS, which was consistent to the results in B cells isolated from EgPSC infected mice. Moreover, TLR-2-/- B cells in response to ESPs stimulation expressed lower levels of IL-10 mRNA and produced undetectable IL-10 in comparison to those in normal B cells. In addition, Phosphatase and tensin homolog deleted on chromosome ten/AKT/Phosphatidylinositol-3 kinase (PTEN/AKT/PI3K) pathway was activated in ESPs-treated B cells, which was also dependent on TLR-2 signaling. Pam3CSK4, the agonist of TLR-2, could mock the effects of ESPs on the expression of PTEN, AKT and PI3K. CONCLUSION: Overall, this study revealed that TLR-2 signaling was required for B10 induction mediated by EgPSC-ESPs, which might be an immunomodulatory target against the parasite infection.

3.
Cell Death Dis ; 9(10): 1033, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305621

RESUMO

Ischemic postconditioning provides robust neuroprotection, therefore, determining the molecular events may provide promising targets for stroke treatment. Here, we showed that the expression of functional mitochondrial voltage-dependent anion channel proteins (VDAC1, VDAC2, and VDAC3) reduced in rat vulnerable hippocampal CA1 subfield after global ischemia. Ischemic postconditioning restored VDACs to physiological levels. Stabilized VDACs contributed to the benefits of postconditioning. VDAC1 was required for maintaining neuronal Ca2+ buffering capacity. We found that microRNA-7 (miR-7) was responsible for postischemic decline of VDAC1 and VDAC3. Notably, miR-7 was more highly expressed in the peripheral blood of patients with acute ischemic stroke compared to healthy controls. Inhibition of miR-7 attenuated neuronal loss and ATP decline after global ischemia, but also diminished the infarct volume with improved neurological functions after focal ischemia. Thus, ischemic postconditioning protects against mitochondrial damage by stabilizing VDACs. MiR-7 may be a potential therapeutic target for ischemic stroke.

4.
Inflammation ; 41(1): 213-220, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29047038

RESUMO

The roles of TLR4 in mediation of innate immune response and in regulation of adaptive immune responses triggered by Clonorchis sinensis remain unknown. In the present study, splenocytes derived from C3H/HeN (TLR4 wild ) and C3H/Hej mice (TLR4 mut ) that were infected with 45 metacercariae of C. sinensis were harvested, then stimulated by C. sinensis excretory/secretory products (ESP) or medium (control) for 48 h, respectively. Meanwhile, bone marrow-derived dendritic cells (BMDCs) from normal C3H/HeN and C3H/Hej mice were prepared and stimulated with medium, ESP, LPS, or ESP+LPS for 24 h, respectively. The supernatants were collected, and the concentrations of type 1 and type 2 relative cytokines were determined by ELISA. The maturation of BMDCs indicated by surface markers of CD80, CD86, and MHC II was evaluated by flow cytometry. The results showed that the levels of IFN-γ, IL-6, TNF-α, and IL-10 in the splenocytes from C. sinensis-infected TLR4 mut mice were significantly lower than those from TLR4 wild mice when they were further exposed to ESP. For BMDCs, the productions of the cytokines IL-12p70 and IL-10, but not IL-4, in the BMDCs from TLR4 mutation mice were predominantly decreased compared with those from TLR4 wild mice when the BMDCs were co-stimulated by ESP combined with LPS. Flow cytometry analysis showed that ESP could significantly decrease the high levels of CD80, CD86, and MHC II which were elevated by LPS. In conclusion, these data suggest that TLR4 may play a regulatory role in type 1 immune responses during C. sinensis infection.


Assuntos
Clonorquíase/metabolismo , Clonorchis sinensis/metabolismo , Citocinas/metabolismo , Células Dendríticas/metabolismo , Baço/metabolismo , Células Th1/metabolismo , Equilíbrio Th1-Th2 , Células Th2/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Células Cultivadas , Clonorquíase/imunologia , Clonorquíase/parasitologia , Clonorchis sinensis/imunologia , Citocinas/imunologia , Células Dendríticas/imunologia , Células Dendríticas/parasitologia , Interações Hospedeiro-Patógeno , Camundongos Endogâmicos C3H , Camundongos Mutantes , Mutação , Coelhos , Baço/imunologia , Baço/parasitologia , Células Th1/imunologia , Células Th1/parasitologia , Células Th2/imunologia , Células Th2/parasitologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
5.
Am J Transl Res ; 9(9): 4206-4216, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28979694

RESUMO

This study sought to investigate the anti-inflammatory effect of Polyene Phosphatidylcholine (PPC), a clinical drug that is used to treat hepatopathy, on lipopolysaccharide (LPS)-stimulated macrophages and on bovine collagen II-induced arthritis (CIA) rats. In stimulated primary and Raw264.7 macrophages by LPS, PPC significantly down-regulated the relative expression of mRNA such as IL-6, TNF-α, TLR-2, TLR-4, MyD88, and NF-κB while up-regulated IL-10 and TGF-ß expression. Moreover, the concentration of IL-6, TNF-α, IL-10, and TGF-ß in the cultured supernatants showed the similar tendency with their mRNA alterations. In addition, PPC could significantly inhibit the LPS-induced expression of MyD88 and NF-κB p65 in both mRNA and protein levels. These results suggest that PPC could down-regulate the LPS-stimulated inflammation in macrophages through TLR-2/TLR-4/MyD88/NF-κB pathway in vitro. Furthermore, to explore its effects in vivo, PPC was administrated to CIA rats. In comparison to CIA group, PPC-treated rats showed decreased arthritis score and osteopenia. Besides, PPC exhibited its ability to alleviate the degree of synovial hyperplasia, inflammatory cell infiltration, and destruction of cartilage and bone, thus remarkably improving the condition of CIA rats. In short, this study demonstrated that PPC had the potential to be an anti-inflammatory drug to treat inflammatory disorders such as rheumatoid arthritis.

6.
Parasit Vectors ; 10(1): 348, 2017 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-28732522

RESUMO

BACKGROUND: Excretory-secretory products (ESPs) released by helminths are well-known to regulate T cell responses in the host. However, their direct influence in the differentiation of naïve T cells, and especially B cells, remains largely unknown. This study investigated the effects of Echinococcus granulosus protoscoleces ESPs (EgPSC-ESPs) on the differentiation of IL-10-producing B cells (B10), IL-17A-producing B cells (B17) and Th17 cells. METHODS: BALB/c mice injected with EgPSC were used to evaluate the in vivo profiles of B10, B17 and Th17 cells. In vitro purified CD19+ B and naïve CD4+ T cells were cultured in the presence of native, heat-inactivated or periodate-treated EgPSC-ESPs, and the differentiation of these cell subsets were compared. RESULTS: In contrast to the control group, infected mice showed higher frequencies of B10, B17 and Th17 cells, and higher levels of IL-10 and IL-17A in the sera. Interestingly, B17 cells were first identified to express CD19+CD1dhigh. In vitro, B cells cultured with native ESPs exhibited a higher percentage of B10 cells but lower percentage of B17 and Th17 cells compared to the PBS group. Moreover, the relative expression of IL-10 and IL-17A mRNA were consistent with the altered frequencies. However, ESPs subjected to heat-inactivation or periodate treatment exhibited an inverse effect on the induction of these cell subsets. CONCLUSIONS: Our findings indicate that ESPs released by EgPSC can directly regulate the differentiation of B10, B17 and Th17 cells, which appear to be heat-labile and carbohydrate-dependent.


Assuntos
Antígenos de Helmintos/imunologia , Subpopulações de Linfócitos B/imunologia , Equinococose/imunologia , Echinococcus granulosus/metabolismo , Células Th17/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular , Células Cultivadas , Equinococose/parasitologia , Echinococcus granulosus/imunologia , Feminino , Interações Hospedeiro-Parasita , Inflamação , Interleucina-10/biossíntese , Interleucina-10/genética , Interleucina-17/biossíntese , Interleucina-17/genética , Camundongos , Camundongos Endogâmicos BALB C , Células Th17/fisiologia
7.
Sci Rep ; 7(1): 3909, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28634394

RESUMO

Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice. The results showed that the levels of collagen depositions, α-SMA and hydroxyproline (Hyp) contents in TLR4 mut mice infected by C. sinensis were significantly lower than in those of TLR4 wild ones. Furthermore, we found that the activation of TGF-ß signaling was impaired in the TLR4 mut mice, compared with wild mice when they were challenged to the same dose of C. sinensis metacercariae. Moreover, the mice with TLR4 mutation showed a decreased activation of hepatic stellate cells indicated by the expression of α-SMA, when compared with TLR4 wild mice. These data demonstrate that TLR4 contributes to PABF caused by C. sinensis and TLR4 signaling may be a potential medical target for treatment of PABF.

8.
Asian Pac J Trop Med ; 10(5): 524-527, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28647192

RESUMO

OBJECTIVE: To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus (E. granulosus). METHODS: We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1 (DNASTAR Inc., Madison, WI), and the phylogenetic analysis was performed by using MEGA5.1 (CEMI, Tempe, AZ, USA). In addition, linear and conformational epitopes were analysed, including secondary structure, NXT/S glycosylation, fibronectin type III (FnIII) domain and glycosylphosphatidylinositol anchor signal (GPI-anchor). The secondary structure was predicted by PSIPRED method. RESULTS: Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence, X90928. However, EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates, respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine, X90928, and they belonged to Subgroup 1. However, in comparison to X90928, several amino acid mutations occurred in most isolates besides oncosphere, which potentially altered the immunodominant linear epitopes, glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. CONCLUSIONS: This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates, and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

9.
Biomed Rep ; 6(2): 181-187, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28357070

RESUMO

The aim of the present study was to predict and analyze the secondary structure, and B and T cell epitopes of Echinococcus granulosus antigen 5 (Ag5) using online software in order to investigate its immunogenicity and preliminarily evaluate its potential as an effective antigen peptide vaccine for cystic echinococcosis. The PortParam program was used to analyze molecular weight, the theoretical isoelectric point, instability index and other physicochemical properties. The secondary structure of the Ag5 protein was predicted using Self-Optimized Prediction method With Alignment and the tertiary structure of the Ag5 protein was predicted using 3DLigandSite together with Center for Biological Sequence Analysis Prediction Servers. Furthermore, the Immune Epitope Database software was used to predict B cell epitopes, and T cell epitopes were predicted with the BioInformatics and Molecular Analysis Section and SYFPEITHI programs. The results demonstrated that α-helixes, ß-turns, random coils and extended strands account for 23.35, 10.95, 41.32, and 24.38% of the secondary structure of the Ag5 protein, respectively. Ten potential B cell epitopes of Ag5 were identified as the amino acids sequences 27-39, 70-80, 117-130, 146-168, 250-262, 284-293, 339-349, 359-371, 403-412 and 454-462, and seven potential T cell epitopes were identified as the amino acid sequences 52-60, 57-65, 182-190, 231-239, 273-281, 318-326 and 467-475. Thus, ten B cell epitopes and seven T cell epitopes were identified on Ag5, suggesting the strong immunogenicity of this protein, which could be applied to design antigen peptide vaccines for echinococcosis.

10.
Sci Rep ; 7: 44017, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28266596

RESUMO

LIM and SH3 domain protein (LASP-1) is responsible for the development of several types of human cancers via the interaction with other proteins; however, the precise biological functions of proteins interacting with LASP-1 are not fully clarified. Although the role of LASP-1 in hepatocarcinogenesis has been reported, the implication of LASP-1 interactors in HBV-related hepatocellular carcinoma (HCC) is not clearly evaluated. We obtained information regarding LASP-1 interactors from public databases and published studies. Via bioinformatics analysis, we found that LASP-1 interactors were related to distinct molecular functions and associated with various biological processes. Through an integrated network analysis of the interaction and pathways of LASP-1 interactors, cross-talk between different proteins and associated pathways was found. In addition, LASP-1 and several its interactors are significantly altered in HBV-related HCC through microarray analysis and could form a complex co-expression network. In the disease, LASP-1 and its interactors were further predicted to be regulated by a complex interaction network composed of different transcription factors. Besides, numerous LASP-1 interactors were associated with various clinical factors and related to the survival and recurrence of HBV-related HCC. Taken together, these results could help enrich our understanding of LASP-1 interactors and their relationships with HBV-related HCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Hepatite B/complicações , Proteínas com Domínio LIM/metabolismo , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/virologia , Biologia Computacional , Feminino , Humanos , Neoplasias Hepáticas/virologia , Masculino , Mapas de Interação de Proteínas
11.
PLoS One ; 12(2): e0171005, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28151995

RESUMO

Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells) and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice) induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson's trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (P<0.01). Importantly, increased Th2 subset and Treg subset all positively correlated with hydroxyproline contents (P<0.01). This result for the first time implied that the increased hepatic Th2 and Treg cell subsets were likely to play potential roles in the formation of biliary fibrosis in C. sinensis-infected mice.


Assuntos
Doenças dos Ductos Biliares/parasitologia , Clonorquíase/patologia , Clonorchis sinensis/patogenicidade , Linfócitos T Reguladores/patologia , Células Th2/patologia , Animais , Doenças dos Ductos Biliares/patologia , Clonorquíase/imunologia , Feminino , Fibrose , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/parasitologia , Cirrose Hepática/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Linfócitos T Reguladores/parasitologia , Células Th2/parasitologia
12.
Behav Brain Res ; 322(Pt A): 70-82, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-28077315

RESUMO

Diabetes mellitus often results in a number of complications involving impaired brain function, including cognitive deficits and depression. However, the potential mechanisms for diabetes-related cognitive deficits and depression are not fully understood. Neurons in the hippocampal, cortical and amygdala functional regions are more susceptible to damage during hyperglycemia. Neuroprotection in the brain can rescue cognitive deficits and depression induced by hyperglycemia. This study investigated the potential mechanisms underlying diabetes-related congnitive deficits and depression, determined whether the inflammatory factor inducible nitric oxide synthase (iNOS) and the nitric oxide (NO)/soluble guanylyl cyclases (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, play key roles in cognitive deficits and depression associated. In the present study, diabetic animal models were induced by streptozotocin (STZ, 150mg/kg) in mice, and aminoguanidine (AG), a selective inhibitor of iNOS, was given by intraperitoneal injection for 10 weeks. Blood glucose, activities of NOS and the levels of NO in serum and brain regions were measured. The spatial memory was detected using the Morris water maze test, depressive behavior was evaluated by the tail suspension test (TST), forced swimming test (FST), closed field test (CFT) and open field test (OFT). We also detected neuronal survival and cleaved caspase-3 positive ratios in three brain regions and the levels of iNOS, sGC, cGMP and PKG in hippocampus and frontal cortex. Data indicated that diabetic mice exerted impairments in spatial memory, decreased locomotor activity and increased immobile time in diabetic mice. In addition, diabetic mice had significantly decreased surviving neuronal density and showed signs of obvious neuronal injury in the hippocampus, frontal cortex and amygdala. iNOS overexpression and its associated signaling pathway NO/sGC/cGMP/PKG in the hippocampus and frontal cortex were implicated during hyperglycemia. However, AG improved the behavior disorders, reduced the activity of iNOS, protected nerve cells and inhibited the level of iNOS, sGC, PKG and cleaved caspase-3 in the hippocampus and cortex. These results suggested that iNOS/NO/sGC/cGMP/PKG signal pathway is a key feature of cognitive deficits and depression associated with diabetes. AG ameliorated cognitive deficits and depression in diabetic mice by exerting anti-inflammatory and neuroprotective effects by suppressing iNOS-associated signaling pathways.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Psicotrópicos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/patologia , Transtornos Cognitivos/complicações , Transtornos Cognitivos/enzimologia , Transtornos Cognitivos/psicologia , Transtorno Depressivo/complicações , Transtorno Depressivo/enzimologia , Transtorno Depressivo/psicologia , Complicações do Diabetes/enzimologia , Complicações do Diabetes/psicologia , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/psicologia , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Hipoglicemiantes/farmacologia , Masculino , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Brain Res ; 1657: 262-268, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28017669

RESUMO

The critical factor considered in a depression induced by diabetes is the inflammation eliciting hippocampal, amygdala and thalamic neuronal injury. Therefore, inhibiting inflammatory reactions in the brain and reducing neuronal injury can alleviate depression in rodents suffering from diabetes mellitus. The oral administration of astaxanthin has been employed in emotional disorders and diabetic complications due to its anti-depressant, anti-inflammatory and anti-apoptotic functions. However, it has not been reported whether astaxanthin can improve diabetes-related depression-like behavior, and its potential mechanisms have not been elucidated. The objective of the present study is to elucidate the effect of astaxanthin on depression in diabetic mice and to understand the underlying molecular mechanisms. In this study, experimental diabetic mice were given a single intraperitoneal injection of streptozotocin (STZ, 150mg/kg, dissolved in citrate buffer) after fasting for 12h. The diabetic model was assessed 72h after STZ injection, and mice with a fasting blood glucose level more than or equal to 16.7mmol/L were used in this study, and oral astaxanthin (25mg/kg) was provided uninterrupted for ten weeks. Depression-like behavior was evaluated by the tail suspension test (TST) and forced swimming test (FST). The glial fibrillary acidic protein (GFAP) and cleaved caspase-3-positive cells were measured by immunohistochemistry, and the western blotting was used to test the protein levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and cyclooxygenase (COX-2). The results showed that astaxanthin had an anti-depressant effect on diabetic mice. Furthermore, we observed that astaxanthin significantly reduced the number of GFAP-positive cells in the hippocampus and hypothalamus, and also the expression of cleaved caspase-3 in the hippocampus, amygdala and hypothalamus was decreased as well. Moreover, astaxanthin could down-regulate the expression of IL-6, IL-1ß and COX-2 in the hippocampus. These findings suggest that the mechanism of astaxanthin in preventing depression in diabetic mice involves the inhibition of inflammation/inflammation inhibition, thereby protecting neurons in hippocampus, amygdala and hypothalamus against hyperglycemic damage.


Assuntos
Anti-Inflamatórios/farmacologia , Depressão/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/imunologia , Tonsila do Cerebelo/patologia , Animais , Antidepressivos/farmacologia , Caspase 3/metabolismo , Ciclo-Oxigenase 2/metabolismo , Depressão/imunologia , Depressão/patologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/psicologia , Avaliação Pré-Clínica de Medicamentos , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/imunologia , Hipocampo/patologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/imunologia , Hipotálamo/patologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/psicologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos ICR , Distribuição Aleatória , Xantofilas/farmacologia
14.
Acta Trop ; 167: 26-30, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27986546

RESUMO

Ticks are able to transmit various pathogens-viruses, bacteria, and parasites-to their host during feeding. Several molecular epidemiological surveys have been performed to evaluate the risk of tick-borne pathogens in China, but little is known about pathogens circulating in ticks from eastern China. Therefore, this study aimed to investigate the presence of bacteria and parasites in ticks collected from Xuzhou, a 11258km2 region in eastern China. In the present study, ticks were collected from domestic goats and grasses in urban districts of Xuzhou region from June 2015 to July 2016. After tick species identification, the presence of tick-borne bacterial and parasitic pathogens, including Anaplasma phagocytophilum, Borrelia burgdorferi, Rickettsia sp., Bartonella sp., Babesia sp., and Theileria sp., was established via conventional or nested polymerase chain reaction assays (PCR) and sequence analysis. Finally, a total of 500 questing adult ticks, identified as Haemaphysalis longicornis, were investigated. Among them, 28/500 tick samples (5.6%) were infected with A. phagocytophilum, and 23/500 (4.6%) with Theileria luwenshuni, whereas co-infection with these pathogens was detected in only 1/51 (2%) of all infected ticks. In conclusion, H. longicornis is the dominant tick species in the Xuzhou region and plays an important role in zoonotic pathogen transmission. Both local residents and animals are at a significant risk of exposure to anaplasmosis and theileriosis, due to the high rates of A. phagocytophilum and T. luwenshuni tick infection.


Assuntos
Anaplasma phagocytophilum/genética , Ixodidae/microbiologia , Ixodidae/parasitologia , Theileria/genética , Anaplasmose/parasitologia , Anaplasmose/transmissão , Animais , Babesia/genética , Bartonella/genética , Borrelia burgdorferi/genética , China/epidemiologia , Cabras/microbiologia , Cabras/parasitologia , Epidemiologia Molecular , Poaceae/microbiologia , Poaceae/parasitologia , Reação em Cadeia da Polimerase , Rickettsia/genética , Inquéritos e Questionários , Theileriose/parasitologia , Theileriose/transmissão , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/parasitologia , Doenças Transmitidas por Carrapatos/transmissão
15.
PLoS One ; 11(7): e0158286, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27454179

RESUMO

Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.


Assuntos
Biomarcadores , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Biologia Computacional/métodos , Vírus da Hepatite B , Hepatite B/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Adulto , Carcinoma Hepatocelular/mortalidade , Mapeamento Cromossômico , Análise por Conglomerados , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
16.
Infect Genet Evol ; 43: 321-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27267304

RESUMO

Clonorchis sinensis (C. sinensis) infection can lead to biliary fibrosis. MicroRNAs (miRNAs) play important roles in regulation of genes expression in the liver diseases. However, the differential expression of miRNAs that probably regulates the portal fibrogenesis caused by C. sinensis has not yet been investigated. Hepatic miRNAs expression profiles from C. sinensis-infected mice at different time-points were analyzed by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR). 349 miRNAs were differentially expressed in the liver of the C. sinensis-infected mice at 2, 8 or 16weeks post infection (p.i.), compared with those at 0week p.i., and there were 143 down-regulated and 206 up-regulated miRNAs among them. These all dysregulated miRNAs were potentially involved in the pathological processes of clonorchiasis by regulation of cancer-related signaling pathway, TGF-ß signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, PI3K /AKT signaling pathway, etc. 169 of these dysregulated miRNAs were predicted to be involved in the TGF/Smads signaling pathway which plays an important role in the biliary fibrosis caused by C. sinensis. Additionally, miRNA-32, miRNA-34a, miRNA-125b and miRNA-497 were negatively correlated with Smad7 expression, indicating these miRNAs may specifically down-regulate Smad7 expression and participate in regulation of biliary fibrosis caused by C. sinensis. The results of the present study for the first time demonstrated that miRNAs were differentially expressed in the liver of mice infected by C. sinensis, and these miRNAs may play important roles in regulation of peribiliary fibrosis caused by C. sinensis, which may provide possible therapeutic targets for clonorchiasis.


Assuntos
Clonorquíase/genética , Clonorchis sinensis/patogenicidade , Fígado/metabolismo , MicroRNAs/genética , Proteína Smad7/genética , Animais , Clonorquíase/parasitologia , Clonorchis sinensis/crescimento & desenvolvimento , Feminino , Fibrose , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína Smad7/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
17.
Parasitol Res ; 115(6): 2299-305, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26944417

RESUMO

During clonorchiasis, immune responses of hosts are responsible for the removal of the worms and also are involved in the progress of the pathological damage caused by Clonorchis sinensis. Interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, has emerged as a potent inducer to bile duct proliferation and fibrosis; however, little is known of this signaling in the pathogen-caused periductal inflammation and fibrosis. In the present study, using immunohistochemistry, real-time PCR, enzyme-linked immunosorbent assay (ELISA), and flow cytometry, we studied the expression of IL-33/ST2 during C. sinensis infection, as well as their potential roles in C. sinensis-induced host immune responses. The results showed that a higher level of IL-33 was detected in the sera of patients of clonorchiasis (n = 45), compared with in those of healthy donors (n = 16). Similarly, in FVB mice experimentally infected with C. sinensis, a higher level of IL-33 was detected at latent stage both in the serum and in the liver, as well as the up-regulated expression of ST2 receptor on the inflammatory cells, especially on CD4(+) T cells in the liver of infected mice. Our results, for the first time, indicated that the increased IL-33/ST2 may be involved in the regulation of immunopathology induced by C. sinensis.


Assuntos
Clonorquíase/imunologia , Clonorchis sinensis/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/sangue , Interleucina-33/metabolismo , Animais , Ductos Biliares/patologia , Linfócitos T CD4-Positivos/imunologia , Clonorquíase/sangue , Clonorquíase/parasitologia , Clonorchis sinensis/patogenicidade , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Fibrose/patologia , Citometria de Fluxo , Humanos , Fígado/patologia , Camundongos , Reação em Cadeia da Polimerase em Tempo Real
18.
Parasit Vectors ; 9: 137, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26965989

RESUMO

Toxoplasma gondii is an obligate intracellular protozoan that poses a great threat to human health and economic well-being worldwide. The effects of environmental factors such as changing climate and human activities on the ecology of this protozoan are being discovered. Accumulated evidence shows that changes of these environmental factors can exert influence on the occurrence, transmission and distribution of T. gondii. This article reviews studies from different geographical regions with varying climates, social cultures and animal welfare standards. It aims to illustrate how these environmental factors work, highlighting their importance in influencing the ecology of T. gondii, as well as providing clues which may contribute to preventing transmission of this important zoonotic pathogen.


Assuntos
Ecossistema , Meio Ambiente , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose Animal/parasitologia , Toxoplasmose/parasitologia , Animais , Humanos
19.
PLoS One ; 10(11): e0143217, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26599407

RESUMO

Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor ß1 (TGF-ß1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis.


Assuntos
Clonorquíase/imunologia , Clonorquíase/parasitologia , Clonorchis sinensis/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Clonorquíase/sangue , Clonorquíase/patologia , Colágeno/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Cinética , Fígado/imunologia , Fígado/parasitologia , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Óvulo/metabolismo , Baço/imunologia , Baço/parasitologia
20.
J Infect Dev Ctries ; 9(10): 1147-55, 2015 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-26517491

RESUMO

INTRODUCTION: Clonorchis sinensis is one of the most important foodborne pathogens in humans, and can cause biliary diseases such as gallstones, cholecystitis, cholangitis, and cholangiocarcinoma. Toll-like receptors (TLRs) as sensors are crucial to initiating both innate and adaptive immune defenses against pathogens. However, little is known about the hepatic expression of TLRs of hosts induced by C. sinensis infection. METHODOLOGY: In the present study, the expression and distribution of TLR2 and TLR4 were investigated in a mouse model of clonorchiasis on days 28, 56, 84, and 112 post-infection (PI) using real-time quantitative reverse transcription polymerase chain reaction (PCR) and immunohistochemically staining, respectively. The levels of cytokines that are mediated by TLR2 and TLR4 were also evaluated using a cytometric bead array. RESULTS: Results showed that the transcripts of TLR2 and TLR4 were upregulated on day 28 PI in C. sinensis-infected mice compared with non-infected ones (p < 0.01). In addition, their proteins were strongly immunohistochemically positive in the cytoplasm and membrane of endothelial cells, fibroblasts, and biliary epithelium cells of C. sinensis-infected mice. The levels of interleukin (IL)-4, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were increased with activation of TLR2 and TLR4. CONCLUSIONS: The expression of TLR2 and TLR4 is upregulated against C. sinensis infection, which suggests that TLR2 and TLR4 might be involved in immune responses during C. sinensis infection.


Assuntos
Clonorquíase/imunologia , Clonorquíase/patologia , Clonorchis sinensis/imunologia , Perfilação da Expressão Gênica , Fígado/patologia , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Camundongos Endogâmicos C3H , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
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