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1.
Brain Stimul ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31606448

RESUMO

BACKGROUND: Transcranial direct current stimulation (tDCS) has been explored in epilepsy with limited samples, varied parameters, and inconclusive results. We aimed to study the efficacy of tDCS for patients with refractory focal epilepsy. METHOD: We conducted a randomized, double-blind, sham-controlled, and three-arm (Group 1 (sham), Group 2 (20-min), and Group 3 (2 × 20-min)) tDCS parallel multicenter study. The primary outcome measurement was seizure frequencies (SFs). The study consisted of 28-days baseline, 14-days treatment, and 56-days follow-up. The cathode was placed over the epileptogenic focus, and the current intensity was 2 mA. The generalized estimating equations model, one-way analysis of variance, chi-square and Kruskal-Wallis test were used for analysis. RESULTS: Of the 82 enrolled patients, 70 patients were included for final analysis (Group 1, n = 21; Group 2, n = 24; and Group 3, n = 25). There was a significant reduction in SFs for both active tDCS groups compared with the sham group. Patients in Group 2 showed a significantly 50.73-21.91% greater reduction in SFs that lasted for 4 weeks (p = 0.008-0.060). Patients in Group 3 showed a significantly 63.19-49.79% greater reduction in SFs compared with the sham group that lasted for 5 weeks (p = 0.011-0.045). Patients in Group 3 had a 64.98-66.32% greater reduction in SFs at W9-W10, when compared with Group 2 (p = 0.021-0.022). CONCLUSION: Fourteen consecutive days tDCS significantly decreased SFs in patients with refractory focal epilepsy, with 2 × 20-min daily stimulation protocol being superior to 20-min daily stimulation protocol.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31587094

RESUMO

In this study, ambient PM2.5 samples were collected from October 2014 to August 2015 in urban area of Luoyang (LY) and Pingdingshan (PDS), two medium-size industrial cities in central China. Sixteen priority polycyclic aromatic hydrocarbons (PAHs) were analyzed to investigate the seasonal variation, potential pollution sources, and health risk of PAHs bound to PM2.5 (PM2.5-bound PAHs). The diagnostic ratios analysis and positive matrix fraction (PMF) model were used to identify potential sources of PM2.5-bound PAHs. The annual average concentrations of PM2.5 and PM2.5-bound PAHs were 128 µg m-3 and 73 ng m-3 for LY, and 119 µg m-3 and 182 ng m-3 for PDS, respectively, both displaying seasonal trends with higher concentrations in winter and autumn than in spring and summer. BaP equivalent concentrations were 14.4 and 16.5 ng m-3 in LY and PDS, respectively. The predominant PAHs were 4-6 ring PAHs, with contribution of more than 80% at both sampling sites. PMF analysis revealed that coal combustion was the most important source of PM2.5-bound PAHs in LY and PDS, accounting for 37% and 39%, respectively, followed by traffic emissions (34% and 33% in LY and PDS, respectively). The average inhalation cancer risk (ICR) for a lifetime of 70 years were 12.5 × 10-4 and 14.3 × 10-4 in LY and PDS, respectively, which were much higher than US EPA guideline limit of 10-6. The traffic source and coal combustion source contributed the highest ICR values in LY and PDS, respectively.

3.
J Surg Oncol ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31602661

RESUMO

BACKGROUND AND OBJECTIVES: To investigate non-lung cancer specific mortality between stage IA non-small cell lung cancer (NSCLC) tumors less than and equal to 2 cm treated with lobectomy and sublobectomy. METHODS: Surveillance, epidemiology, and end results database was queried for patients who underwent lobectomy and sublobectomy. Propensity score matching (PSM) was used to achieve balance in clinicopathological characteristics. We used Fine-and-Gray hazard functions to analyze cause-specific mortality and risk factors. Standardized mortality ratios were calculated to describe cause specific mortality relative to the general population. RESULTS: After PSM, 3,844 patients underwent lobectomy and 1,922 patients underwent sublobectomy. Three leading causes of non-lung cancer mortality were cardiovascular disease (CVD), chronic obstructive pulmonary diseases (COPD), and other cancers. The 5-year cumulative non-lung cancer mortality of lobectomy and sublobectomy groups were 11.4% and 14.0%, respectively (P = .090). Multivariate analyses revealed that age, sex, histology, tumor size, and marital status (P < .01) were independent predictors of non-lung cancer specific mortality. In both groups, risks of CVD specific mortality were comparable to that in the general population, whereas the risk of COPD specific mortality was higher relative to the general population. CONCLUSIONS: As a significant competing event, non-lung cancer specific mortality is comparable between stage IA NSCLC tumors less than equal to 2 cm treated with lobectomy and sublobectomy.

5.
Fish Shellfish Immunol ; 95: 151-162, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31605765

RESUMO

G protein-coupled receptors (GPCRs) are important transmembrane receptors that participate in diverse physiological processes including metabolism, cell growth and immune processes by transmitting extracellular signals to intracellular effectors. In this study, a gene belonging to the GPCR family was cloned from Eriocheir sinensis and named EsGPCR89. The full-length gene includes an open reading frame (ORF) of 465 amino acid residues, and bioinformatic analysis confirmed the high conservation between species. EsGPCR89 was detected in various tissues of E. sinensis, and was up-regulated in brain following Staphylococcus aureus infection. Expression levels of cerebral antimicrobial peptides (AMPs) were also up-regulated following bacterial challenge, reflecting their function in cerebral immunity. Additionally, EsGPCR89 silencing in hemocytes by RNA interference, down-regulated AMPs in brain after S. aureus infection. Moreover, through Immunisation assay and Polyacrylamide gel electrophoresis (SDS-PAGE) experiments, we could infer that bacterially infected hemocytes released effectors under the regulation of EsGPCR89, thereby activating transcription of cerebral AMPs. These results demonstrate that EsGPCR89 plays important roles in cerebral antimicrobial function via hemocytes.

6.
Fish Shellfish Immunol ; 95: 259-267, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655268

RESUMO

The Rab family is the most significant subfamily of small GTP-binding proteins. These proteins have widespread intracellular localization and play an important role in many biological processes. Rab7 plays a crucial role in the innate immune system of crustaceans. In the present study, we cloned and characterized Rab7 from Chinese mitten crab (Eriocheir sinensis), designated EsRab7. The full-length of the EsRab7 cDNA sequence is 1,257 bp and contains a 618-bp open reading frame encoding a 205-amino acid polypeptide. Bioinformatics analysis showed that the Rab7 protein was highly conserved during evolution. Quantitative real-time PCR showed the highest tissue expression in muscle, followed by hepatopancreas. EsRab7 was significantly upregulated in hemocytes after stimulation by Gram-positive Staphylococcus aureus or Gram-negative Vibrio parahaemolyticus. Further studies showed that EsRab7 knockdown during bacterial stimulation resulted in decreased bacterial phagocytosis. In addition, EsRab7 regulated the expression of antimicrobial peptides via the Toll signaling pathway. Collectively, these results demonstrate that EsRab7 plays critical roles in antimicrobial function in the Chinese mitten crab.

7.
Drug Des Devel Ther ; 13: 3281-3290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571830

RESUMO

Background: Ovarian cancer is the third leading cause of death among gynecological cancers in women in China. Chemotherapy is an important method for comprehensive treatment of ovarian cancer, but the curative effect is poor. Purpose: In this study, gemcitabine (GEM) -loaded RGD modified liposomes (LPs) were developed by the emulsification-solvent evaporation method and evaluated for their antitumor activity in vitro and in vivo. Methods: The physicochemical properties of LPs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of RGD-GEM-PEG LPs in ovarian cancer. Results: RGD-PEG3500-DSPE GEM LPs had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 106.7 nm and 0.13 respectively. The ER% and DL% of the formulation were 79.6±3.1% and 6.1±1.4% respectively. Compared with the free drug, RGD modified GEM LPs had sustained-release properties in vitro. In vivo, compared with the DiD-RGD-PEG3500-DSPE GEM LPs group, free DiD-GEM and DiD-GEM LPs had no obvious fluorescence intensity in tumor of mice at all times, indicating that ordinary liposomes and drugs had no tumor targeting function. RGD-PEG3500-DSPE GEM LPs showed a superior antiproliferative effect on SKOV3 cells and had a better antitumor effect in vivo than non-modified LPs. Conclusion: These results indicated that RGD-PEG3500-DSPE GEM LPs were a promising candidate for antitumor drug delivery.

8.
Transpl Immunol ; : 101250, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655110

RESUMO

Organ transplantation is an effective way to treat many end-stage diseases. In order to overcome post-transplant rejection, immunosuppressive agents have been widely used, but the long-term survival of transplanted organs still has not been achieved in the clinic. For decades, tolerance is the "holy grail" that transplant immunologists have longed for. The well-known approaches to induce immune tolerance are through adoptively transferred regulatory T cells and achieving chimeric states. In addition, there are a variety of promising potential strategies, including costimulatory blockade, regulating differentiation of immune cell subgroups, adoptive infusion of immunoregulatory cells, using apoptotic cells to induce tolerance, stem cell regenerative medicine to reconstitute tissue and organs, helminthic therapy, using exosomes carrying phagocytic antigen and phagocytic vesicles to induce tolerance, and blocking CD3 and targeted clearance of memory T cells. In this paper, we review the current developments and the potential of these strategies to achieve transplantation tolerance.

9.
J Biol Chem ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537644

RESUMO

Alternatively spliced hypervariable immunoglobulin domain-encoding molecules, called Dscam, have been widely detected as components of the arthropod immune system. Although its ability to specifically bind pathogens and enable phagocytosis of bacteria has been elucidated, the signal transduction mechanisms or effectors that activate post-Dscam binding pathogens remain poorly characterized. Here we reveal the alternative splicing exons of Dscam's cytoplasmic tail and its isoforms in the hemocytes of crab (Eriocheir sinensis), showing that the expression of Dscam was acutely induced after an immune challenge, which suggested its functioning for innate immunity. Significantly decreased expression levels of antimicrobial molecular peptides (AMPs) were detected in Dscam-silenced crab hemocytes in vitro, which coincided with their vulnerability to infection by Staphylococcus. aureus and higher bacterial concentrations occurring in Dscam-silenced crabs in vivo. Further experimental investigation demonstrated that Dscam regulated AMPs' expression via the SH3 binding domain in the first constant exon translated protein of the cytoplasmic tail bound with the SH3 domain of the Dock, an SH3/SH2 adaptor protein required for axon guidance. Dock promoted ERK phosphorylation via indirect binding, then regulated dorsal phosphorylation and translocation from the cytoplasm to the nucleus, subsequently promoting AMPs's expression for the effective removal of bacteria. To our best knowledge, this comprehensive study is the first to highlight the critical role of the alternatively-spliced Dscam cytoplasmic tail in antimicrobial control activity. It also suggests possible crosstalk occurring between Dscam and other pattern recognition receptors.

10.
Phytomedicine ; 64: 153073, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31542661

RESUMO

BACKGROUND: Ginkgo biloba (Gb) extracts have been used as a traditional Chinese medicine. Gb contains flavonoids, which are considered to be its active ingredients and have been used in the treatment of a variety of diseases. However, few scientific research studies on the side effects of flavonoid in Gb have been reported. PURPOSE: The present study aimed to investigate the effect of bilobetin on the kidney of Sprague-Dawley (SD) rats. STUDY DESIGN AND RESULT: In this study, rats were injected with 50 mg/kg of bilobetin, a biflavone isolated from Gb, for 7 days and aristolochic acid was used as positive controls. The results showed that the body weight and urine output of the rats were dramatically decreased, and urinary protein increased after the intraperitoneal injection of bilobetin compared with the control group. Bilobetin treatment showed vacuolar degeneration in the renal tubular epithelium, glomerular atrophy by histostaining, and podocyte fusion by electron microscopy. This study further showed that bilobetin promoted the trafficking of aquaporin 2 (AQP-2) onto the plasma membrane to achieve the function of urine concentration by in vivo study in rats and in vitro study in IMCD-3 cells. The redistribution of AQP-2 is due to increased expression of cGMP in IMCD-3 cells, which in turn promoted the phosphorylation of AQP-2 at site Ser-256. The proteinuria caused by bilobetin may be attributed to podocyte cell cycle arrest at G2/M transition, which is may associated with AKT and MAPK signaling. CONCLUSIONS: The current study showed that bilobetin has some side effects on kidneys at a dose of 50 mg/kg in SD rats and provides insight into the potential detrimental effects of monomeric ingredients in Gb.

11.
Sci Total Environ ; 697: 134047, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31491641

RESUMO

In this study, simultaneous nitrification and denitrification (SND) process was successfully established in a hybrid sequencing batch biofilm reactor (HSBBR). High removal efficiency of NH4+-N (98.0±2.4% to 99.8±0.4%) and COD (86.6±4.0% to 91.6±1.8%) was observed in the salinity range of 0.0 to 2.4%. SND via nitrite, replacing SND via nitrate, became the main nitrogen removal pathway at 1.6% and 2.4% salinity. Suspended sludge and biofilm shared similar microbial composition. Dominant genera were substituted by salt-adaptable microbes as salinity increasing. Abundance of autotrophic ammonia-oxidizing bacteria (Nitrosomonas) increased with elevated salinity, while autotrophic nitrite-oxidizing bacteria (Nitrospira) exhibited extreme sensitivity to salinity. The presence of Gemmata demonstrated that heterotrophic nitrification co-existed with autotrophic nitrification in the SND process. Aerobic denitrifiers (Denitratisoma and Thauera) were also identified. Thiothrix, Sedimenticola, Sulfuritalea, Arcobacter (sulfide-based autotrophic denitrifier) and Hydrogenophaga (hydrogen-based autotrophic denitrifier) were detected in both S-sludge and biofilm. The occurrence of ANAMMOX bacteria Pirellula and Planctomyces indicated that ANAMMOX process was another pathway for nitrogen removal. Nitrogen removal in the HSBBR was accomplished via diverse pathways, including traditional autotrophic nitrification/heterotrophic denitrification, heterotrophic nitrification, aerobic and autotrophic denitrification, and ANAMMOX.

12.
Dev Comp Immunol ; 103: 103496, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513820

RESUMO

Scavenger receptors (SRs) are pattern recognition receptors (PRRs) vital for innate immunity. As well as their importance in immune recognition, microbe phagocytosis, and the clearance of modified endogenous molecules, they also activate downstream immune responses as co-receptors. In the current study, we identified a class B scavenger receptor in Eriocheir sinensis (EsSR-B2). The full-length gene is 2,517 bp and encodes a 517 amino acid polypeptide. EsSR-B2 is expressed widely in all tested tissues and is induced by microbial stimulation. Recombinant EsSR-B2 binds to bacteria and pathogen-associated molecular patterns in vitro. Upon knockdown of EsSR-B2 and bacterial challenge with Staphylococcus aureus or Vibrio parahaemolyticus, phagocytosis rates in hemocytes are decreased. Moreover, the expression of several antimicrobial peptides (AMPs) in response to distinct microorganism stimulation is decreased following EsSR-B2 silencing. Thus, EsSR-B2 is a PRR that protects E. sinensis against invading pathogens by promoting phagocytosis and enhancing AMP expression.

13.
Med Sci Monit ; 25: 6965-6971, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31525175

RESUMO

BACKGROUND Autologous saphenous vein is the most common choice for coronary artery bypass grafting. This study was conducted to identify and characterize differentially expressed genes (DEGs) induced by overexpressing DEPTOR in human saphenous vein endothelial cells (hsVECs) that might play roles in restenosis. MATERIAL AND METHODS hsVECs isolated from the saphenous veins were transfected with DEPTOR overexpression vector and analyzed for mTOR expression. RNA was prepared from the cells and sequenced using high-throughput sequencing technology (RNA-Seq). The DEGs were analyzed based on enrichment scores in GO terms and KEGG pathways. RESULTS The cells had typical hsVEC morphology and characteristics based on the HE staining and immunohistochemical and immunofluorescence assays. The expression of mTOR increased, and 102 genes were upregulated, and 409 genes were downregulated after DEPTOR overexpression. KEGG analysis showed that the DEGs were mainly enriched in 20 signal pathways, such as Focal adhesion and ECM-receptor interaction pathways. The DEGs were enriched in GO terms such as integrin binding and glycosaminoglycan binding. For cellular components, GO analysis revealed that the DEGs were enriched in main axon, plasma membrane part, cell junction, and proteinaceous extracellular matrix. DEGs included many cytokines, such as bone morphogenetic protein-7, interleukin-8, interleukin-1ß, and inhibin, which have important effects on vascular growth and inflammation. CONCLUSIONS The overexpression of DEPTOR in hsVECs results in DEGs that are involved in cell proliferation and differentiation, intercellular junction, and extracellular matrix receptor. These findings may provide valuable molecular information for improving venous permeability through manipulation of DEPTOR and related mTOR pathways.

15.
J Cardiovasc Electrophysiol ; 30(11): 2377-2386, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31512322

RESUMO

AIMS: Ventricular arrhythmias (VAs) originating from the para-Hisian region represent a challenging location. The long-term success rate of catheter ablation above the septal leaflet of the tricuspid valve is not ideal. This study aimed to investigate the safety and efficacy of catheter ablation for para-Hisian VAs via a direct approach under the septal valve with reversed C-curve technique. METHODS AND RESULTS: Twenty-five consecutive patients with para-Hisian VAs were included. Systematic mapping was performed in the right ventricle septum, including both the regions above and under the septal valve. Radiofrequency (RF) ablation was preferentially performed under the valve with reversed C-curve technique in all patients. If the ablation failed under the valve, it was then performed above the valve and even in aortic sinus cusps. The earliest ventricular activation preceding surface QRS (V-QRS) under the valve was significantly larger than that above the valve (34.8 ± 5.3 vs 27.8 ± 5.7 ms, P < .01). RF ablation under the valve with reversed C-curve technique achieved acute success in 22 of 25 (88%) patients. Junctional rhythm developed during ablation in 3 of 25 (12%) patients and no atrioventricular block occurred. In the remaining three patients, RF application above the valve failed to eliminate the VAs and one of them achieved successful ablation in the right coronary cusp. During a mean follow-up of 17.8 ± 9.4 months, no patients presented with VAs recurrence and no postprocedure complications occurred. CONCLUSIONS: Catheter ablation under the valve with reversed C-curve technique shows to be effective and safe for para-Hisian VAs.

16.
Ann Thorac Surg ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31445050

RESUMO

BACKGROUND: Lung is the most common site of extrahepatic metastasis of hepatocellular carcinoma (HCC). The aim of this study was to identify prognostic factors for pulmonary metastasectomy of HCC. METHODS: 103 patients who underwent pulmonary metastasectomy for HCC between January 2005 and December 2016 were retrospectively evaluated. Patient demographic data and characteristics of the primary tumors and pulmonary metastasis were investigated to identify factors significantly correlated with prognosis. RESULTS: Of 103 patients, 75 (72.8%) had one site pulmonary metastasis, 22 (21.4%) had two, and six (5.8%) had three or more. Liver recurrence at the time of pulmonary metastasectomy was noted in 34 patients. The estimated 5-year overall survival (OS) rate was 38.5% after pulmonary metastasectomy. Univariate prognostic analysis showed that liver recurrence at the time of pulmonary metastasectomy, extent of resection, laterality of pulmonary metastasis, tumor location, number of metastatic sites, and metastatic tumor size were significantly associated with favorable OS after pulmonary metastasectomy. Multivariate analysis revealed that liver recurrence at the time of pulmonary metastasectomy and the number of metastatic sites were independent prognostic factors. Subgroup analysis with a combination of these two independent prognostic factors revealed 5-year OS rates for patients with zero, one, and two risk factors of 58.5%, 23.8%, and 0.0%, respectively. CONCLUSIONS: Pulmonary metastasectomy is safe and effective treatment for well-selected patients with pulmonary metastasis of HCC. Liver recurrence at the time of pulmonary metastasectomy and the number of metastatic sites were identified as independent prognostic factors. The number of risk factors significantly influenced patient survival.

17.
Syst Biol Reprod Med ; : 1-7, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434522

RESUMO

It is crucial to identify the subfertile men with varicocele who will benefit the most from varicocelectomy, and the factors which help in predicting the response to varicocelectomy. We aimed to evaluate the impact of varicocelectomy on total motile sperm count (TMSC) and spontaneous pregnancy (SP) rates. A comprehensive literature search was performed using Medline/PubMed and Google Scholar up to December 26, 2018, with no restriction on language and year of publication. Published articles reporting different degrees of TMSC before and after varicocelectomy in infertile men with varicocele (palpable and/or clinical) were extracted. In addition, SP rates as a function of TMSC after varicocelectomy were reviewed. Potential biases were analyzed to rule out skewing factors. Mean TMSC was graded as: <2 million - profound, 2-5 million - severe, 5-10 million - moderate, and >10 million - mild. Data were analyzed using Stata11. Among the total 96 articles identified through electronic and manual searches of references, nine articles fulfilling the inclusion criteria were included. All degrees of TMSC resulted in a significant postoperative improvement, with only small differences, among the profound [10.20 million (95% confidence interval [CI]: 9.11-11.30, p < 0.0001)], severe [15.77 million (95% CI: 10.65-20.89, p < 0.0001)], and moderate groups [19.18 million (95% CI: 10.40-27.96, p < 0.0001)]. However, the mild group demonstrated a highly significant improvement [49.68 million (95% CI: 38.74-60.62, p < 0.0001)]. After varicocelectomy, the SP rate was highest in the TMSC >20 million group (55.4%), followed by TMSC 5-20 million group (45.4%), and TMSC <5 million group (26.3%). In comparison, the TMSC <1.5 million group demonstrated the lowest SP rate (16.0%). Moderate evidence suggests that varicocelectomy results in a significantly improved TMSC. The improvement in TMSC and SP rates is higher in patients who present a mild or moderate decreased TMSC. Abbreviations: TMSC: total motile sperm count; SP: spontaneous pregnancy; ART: assisted reproductive technology; IVF: in-vitro fertilization; IUI: intrauterine insemination; WMD: weighted mean difference; CI: confidence interval.

19.
CNS Neurosci Ther ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31429206

RESUMO

The International League Against Epilepsy (ILAE) defined drug-resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well-tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%-40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.

20.
J Biol Chem ; 294(40): 14704-14716, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31395655

RESUMO

The Hippo-signaling pathway plays a critical role in both normal animal physiology and pathogenesis. Because pharmacological interventions targeting this pathway have diverse clinical implications, a better understanding of its regulation in various conditions and organisms is crucial. Here, we identified deleted in azoospermia-associated protein 2 (DAZAP2) in the Chinese mitten crab (Eriocheir sinensis), designated EsDAZAP2, as a Hippo-regulatory protein highly similar to proteins in various species of insects, fish, and mammals. We found that a bacterial infection significantly induces EsDAZAP2 expression, and an EsDAZAP2 knockdown both suppresses antimicrobial peptide (AMP) expression in vitro and results in increased viable bacterial counts and mortality in vivo, suggesting that EsDAZAP2 plays a critical role in innate immunity. Using yeast two-hybrid screening and co-immunoprecipitation assays, we found that EsDAZAP2 regulates the Toll pathway rather than the immune deficiency and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Our findings also demonstrate that EsDAZAP2 binds to the Hippo protein, Salvador (Sav). Moreover, by examining the regulation of Dorsal, a transcription factor that regulates AMP expression in E. sinensis, we provide experimental evidence indicating that EsDAZAP2 promotes Hippo pathway activation in innate immunity, with EsDAZAP2 and Hippo binding to different Sav domains. To the best of our knowledge, this is the first report of a DAZAP2-regulated Hippo-signaling pathway operating in animal innate immunity.

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