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1.
Sci Total Environ ; 698: 134289, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514034

RESUMO

Microeukaryotes are the key ecosystem drivers mediating marine productivity, the food web and biogeochemical cycles. The northwestern Pacific Ocean (NWPO), as one of the world's largest oligotrophic regions, remains largely unexplored regarding diversity and biogeography of microeukaryotes. Here, we investigated the community composition and geographical distribution of microeukaryotes collected from the euphotic zone of three different regions in the NWPO using high-throughput sequencing of the 18S rRNA gene and quantified the contributions of environmental factors on the distributions of microeukaryotes. The relative abundance of different group taxa, except for Ciliophora, presented distinct patterns in each region, and Metazoa and Dinoflagellata dominated the community, contributing approximately half of reads abundance. Spatial and environmental factors explained 66.01% of community variation in the NWPO. Temperature was the most important environmental factor significantly correlated with community structure. Bacterial biomass was also significantly correlated with microeukaryotic distribution, especially for Dinoflagellata and Diatomea. Network analysis showed strong correlations between microeukaryotic groups and free-living bacteria and different bacterial taxa were correlated with specific microeukaryotic groups, indicating that their interactions enabled microeukaryotic groups to adapt to diverse environments. This study provides a first glance at the diversity and geographical distribution of microeukaryotes in the NWPO and sheds light on the biotic and abiotic factors in shaping the microeukaryotic community in the ocean.

2.
Methods Mol Biol ; 2079: 211-218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31728973

RESUMO

Exosomes are considered as sources of disease biomarkers since they are stable carriers of genetic material and proteins. We recently demonstrated that chimeric RNA in exosomes derived from patient fluids can be detected and further used for disease diagnosis. Here we describe a systematic method to obtain exosomes from body fluids for detecting expression of specific chimeric RNA based on a RT-qPCR strategy.

3.
Cells ; 8(11)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671754

RESUMO

In female mammals, the abnormal apoptosis of ovarian granulosa cells (GCs) impairs follicular development and causes reproductive dysfunction. Many studies have indicated that the FGFR1 gene of the PI3K signaling pathway and the p65 subunit of the transcription factor NF-κB may regulate the proliferation and apoptosis of GCs involved in follicular development. However, little is known about whether p65 regulates the transcription of FGFR1, as well as the biological effects of p65 and FGFR1 on the survival of GCs and follicular development. In porcine follicles and GCs, we found that p65 and FGFR1 were exclusively expressed in the GCs of follicles, and the mRNA and protein levels of p65 and FGFR1 significantly increased from small to large follicles. Both p65 and FGFR1 were found to activate the PI3K signaling pathway, and the expressions of proliferation markers (PCNA and MKI67) and the anti-apoptotic gene BCL2 were significantly increased by p65 and FGFR1. Furthermore, both p65 and FGFR1 were observed to promote cell proliferation and inhibit the cell apoptosis of GCs, and p65 was confirmed to bind at the -348/-338 region of FGFR1 to positively regulate its transcription. Moreover, p65 was further found to enhance the pro-proliferation and anti-apoptotic effects of FGFR1. Taken together, p65 may target the -348/-338 region of FGFR1, promote the transcription of FGFR1, and enhance the pro-proliferation effect and anti-apoptotic effect of FGFR1 to facilitate the growth of follicles. This study will provide useful information for further investigations on the p65-mediated-FGFR1 signaling pathway during folliculogenesis in mammals.

4.
J Cell Mol Med ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675172

RESUMO

Previous studies have implicated the attractive and promising role of miR-590-3p to restore the cardiac function following myocardial infarction (MI). However, the molecular mechanisms for how miR-590-3p involves in cardiac fibrosis remain largely unexplored. Using human cardiac fibroblasts (HCFs) as the cellular model, luciferase report assay, mutation, EdU assay and transwell migration assay were applied to investigate the biological effects of miR-590-3p on the proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts. We found that miR-590-3p significantly suppressed cell proliferation and migration of HCFs. The mRNA and protein expression levels of α-SMA, Col1A1 and Col3A were significantly decreased by miR-590-3p. Moreover, miR-590-3p directly targeted at the 3'UTR of ZEB1 to repress the translation of ZEB1. Interfering with the expression of ZEB1 significantly decreased the cell proliferation, migration activity, mRNA and protein expressions of α-SMA, Col1A1 and Col3A. Furthermore, the expressions of miR-590-3p and ZEB1 were identified in infarct area of MI model in pigs. Collectively, miR-590-3p suppresses the cell proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. These works will provide useful biological information for future studies on potential roles of miR-590-3p as the therapeutic target to recover cardiac function following MI.

5.
J Electrocardiol ; 58: 46-50, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31715375

RESUMO

OBJECTIVE: To investigate the characteristics of early recurrence (ER) of atrial tachyarrhythmia (ATA) defined as atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) during a 90-day blanking period after pulmonary vein isolation by cryoablation (PVI-C) in patients with symptomatic drug refractory AF. Specifically, to determine if ER of ATA during the blanking period can predict late recurrence (LR) during a 12-month follow-up period. METHOD: A total of 51 patients with symptomatic AF (who received PVI-C) were monitored by trans-telephonic wireless electrocardiogram (TWECG) event recording during the landmark 90-day blanking period following an index ablation. Recurrent ATA was defined as any AF, AT, or AFL lasting longer than 30 s (as recorded by 12­lead ECG, 24-hour Holter monitor, or TWECG). For data analysis, patients were grouped into ER and non-ER cohorts during the 90-day blanking period and then cohorted into LR or non-LR groups during the 12-month follow-up. RESULTS: During the 90-day blanking period, 23 patients had an ER event of ATA while 28 patients had a non-ER experience. Also, during the 12-month follow-up period, 15 patients had a LR event while 36 patients were free from ATA (and placed in the non-LR cohort). Overall, the average success rate of cryoablation for AF was 70.6% at the 12-month follow-up period. Compared to the non-LR group, patients with LR showed a higher average percentage of diabetes mellitic (33.3% vs. 5.56%; P = 0.008) and had a larger mean left atrium diameter (41.2 ±â€¯4.3 mm vs. 36.5 ±â€¯4.2 mm; P = 0.0006). During evaluation of the 90-day blanking period, the LR group had more frequent attacks of ATA than compared to the non-LR group (27.7% vs. 2.4%; P < 0.001). Only two patients (7.1%) without ER in the blanking period (non-ER cohort) had relapsed into a LR of ATA during the one-year period. After multi-logistic regression analysis, ER could individually predict the risk of LR (RR = 58.8; P = 0.001). CONCLUSION: In our study, ER of ATA was a common phenomenon during the 90-day blanking period after PVI-C for AF, and it mostly occurred in the first month following the index ablation across all patients. ER is not equal to the LR of ATA; however, patients with an ER event had a higher risk of a LR during the 12-month follow-up period.

6.
Antiviral Res ; 173: 104651, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751591

RESUMO

Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. Here, A9, a receptor tyrosine kinase inhibitor (RTKI) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (TGEV) infection in cell-based assays. Moreover, A9 exhibited potent antiviral activity against the replication of various CoVs, including murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). We further performed a comparative phosphoproteomic analysis to investigate the mechanism of action of A9 against TGEV infection in vitro. We specifically identified p38 and JNK1, which are the downstream molecules of receptor tyrosine kinases (RTKs) required for efficient TGEV replication, as A9 targets through plaque assays, qRT-PCR and Western blotting assays. p38 and JNK1 inhibitors and RNA interference further showed that the inhibitory activity of A9 against TGEV infection was mainly mediated by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. All these findings indicated that the RTKI A9 directly inhibits TGEV replication and that its inhibitory activity against TGEV replication mainly occurs by targeting p38, which provides vital clues to the design of novel drugs against CoVs.

7.
Acta Biochim Pol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770484

RESUMO

BACKGROUND: Epithelial ovarian cancer is the most malignant gynecologic neoplasm accounting for 90% of the ovarian cancer patients. OBJECTIVE: Researchers proved that epigenetic alterations could disrupt gene expression as often as genetic alterations. Secreted frizzed related protein (SFRP1), a Wnt antagonist, exerts a significant effect on ovarian cancer. The aim of this research was to investigate the effects and the mechanism of action of SFRP1 on epithelial ovarian cancer. METHODS: Clinical specimens (including fallopian tubes epithelium from 60 epithelial ovarian cancer patients' and 20 healthy subjects who were undergoing surgical treatments), transgenic mice (overexpressing SFRP1 gene), and 4 epithelial ovarian cancer cell lines (including OVCAR4, SKOV3, COV644, TOV21G) were used in this study. Overexpression of SFRP1 in cells was carried out on OVCAR4 cells by transfection using Lipofectamine 2000. Gene transcription was analyzed by qRT-PCR. The methylation of SFRP1 gene was quantified by methylation-specific PCR. The level of protein expression was measured by Western blot or immunohistochemistry analysis. Cell proliferation was analyzed by CCK8 methods. The ability of cell migration and invasion were measured by wound healing assay and transwell assay. RESULTS: Abnormal expression level and hypermethylation status of SFRP1 were found in clinical epithelial ovarian cancer samples and cell lines. We observed that SFRP1 knockdown could promote proliferation, migration and invasion abilities of epithelial ovarian cancer cells. Additionally, we discovered a potential inhibitory effect of SFRP1 on Wnt/ß-catenin signaling pathway in epithelial ovarian cancer cells. Furthermore, the anti-tumor effect of SFRP1 was tested in SFRP1 transgenic mice. CONCLUSION: SFRP1 inhibited epithelial ovarian cancer through inhibiting Wnt/ß-catenin pathway, suggesting that SFRP1 could be considered as a potential therapeutic target in epithelial ovarian cancer.

8.
Food Chem ; : 125878, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31771910

RESUMO

ß-Carotene is a natural nutrient that serves as a natural food colorant. However, the weak physical stability restricts its development in food industrial production. Here, the influences of a variety of external environmental conditions on the stability of ß-carotene enriched zein-carboxymethyl chitosan (CMCS)-tea polyphenols (TP) ternary composite nanoparticles were investigated. Compared with zein unitary and zein-CMCS binary complexes, it was interesting to note that ternary complexes had the best stability against color fading and there was little impact on its nanoparticle size during storage with change in temperature. Besides excellent antioxidant properties, ternary complexes were extremely effective in inhibiting ß-carotene color degradation when exposed to ultraviolet light. Based on our results, the novel zein-CMCS-TP nanoparticles are expected to be an effective delivery system to encapsulate hydrophobic bioactive compounds, which is a promising approach to improve their storage stability against external environmental stresses.

9.
Macromol Rapid Commun ; : e1900547, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778285

RESUMO

The functionalization and application of nano-objects generated using a polymerization induced self-assembly (PISA) procedure is becoming a focus in recent years. In this contribution, using ethanol as solvent, poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA) as macro-initiator/stabilizer, and 2-(perfluorohexyl)ethyl methacrylate (PFHEMA) and glycidyl methacrylate (GMA) as comonomers, the initiators for continuous activator regeneration atom transfer radical polymerization (ICAR ATRP)-based PISA is realized. The lower GMA content system tends to form spheres with large diameters and heavy contrast, while the lower PFHEMA content system tends to form the spheres or short worms with small diameters. However, the system with further increased GMA content results in the failed ICAR ATRP PISA procedure with the formation of precipitates by the cross-linking reaction between pendant epoxy groups. Furthermore, using the efficient reaction between the epoxy group on GMA and thiol group on mercapto-succinic acid agent, the carboxyl groups can be introduced into the inner cavity of the nano-objects and used for incorporation with the Fe2+ and Fe3+ ions, and the organic-inorganic nanoparticles Fe3 O4 @POEOMA are finally prepared in the presence of a reductant.

10.
Opt Lett ; 44(23): 5864-5867, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774799

RESUMO

Spectroscopic single-molecule localization microscopy (sSMLM) simultaneously captures the spatial locations and emission spectra of single molecular emissions and enables simultaneous multicolor super-resolution imaging. Existing sSMLM relies on extracting spectral signatures, such as weighted spectral centroids, to distinguish different molecular labels. However, the rich information carried by the complete spectral profiles is not fully utilized; thus, the misclassification rate between molecular labels can be high at low spectral analysis photon budget. We developed a machine learning (ML)-based method to analyze the full spectral profiles of each molecular emission and reduce the misclassification rate. We experimentally validated our method by imaging immunofluorescently labeled COS-7 cells using two far-red dyes typically used in sSMLM (AF647 and CF660) to resolve mitochondria and microtubules, respectively. We showed that the ML method achieved 10-fold reduction in misclassification and two-fold improvement in spectral data utilization comparing with the existing spectral centroid method.

11.
Orthop Surg ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755205

RESUMO

OBJECTIVES: To describe the epidemiological characteristics of patients with spinal metastases between 2007 and 2019. METHODS: Patients with spinal metastases were identified from several clinical centers in China between January 2007 and July 2019. Demographics, primary tumor types, spinal involvement, and Clinical indicators of each patient were reviewed. RESULTS: A total of 1196 patients were included in this study, 717 males (59.95%) and 479 females (40.05%), with a male to female ratio of 1.50:1. Most patients (63.71%) were in the ages range of 50 to 69 years. The mean age was 58.6 ± 11.6 (range 13-89) years and the median age was 59.0 years. The average age of females was younger than that of males, and the difference was statistically significant. The proportion of male patients over 60 years old was higher than that of females, and the difference was statistically significant. The most common primary tumor was lung cancer (n = 437, 36.54%), followed by unknown origin (n = 194, 16.22%), kidney cancer (n = 78, 6.52%), breast cancer (n = 76, 6.35%), and liver/biliary cancer (n = 75, 6.27%). The most common primary tumor was lung cancer in both males and females, followed by unknown origin in males and breast cancer in females. There were 730 patients (61.04%) in the subgroup of the number<3; the highest level was lumbar vertebrae, with 250 patients (34.25%). The remaining 466 patients (38.96%) were included in the subgroup of the number ≥ 3; the highest level was tumor metastasis of multiple-level of spine, with 334 patients (71.67%). Among the 1196 patients, spinal cord injury occurred in 54.01% of patients, 76.34% of patients developed moderate and above pain, 55.69% of patients had metastatic spinal cord compression, and only 26.67% of patients had a clear history of primary tumors. CONCLUSION: This study provided a relatively detailed description of epidemiological characteristics in spinal metastases in China, which could assist orthopaedic surgeons to understand the clinical characteristics of spinal metastases, and is of great significance in guiding clinical diagnoses and scientific research.

12.
Int J Biol Macromol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739072

RESUMO

The Chitosanase (Genbank No. AAA19865.1, SsCsn46) from Streptomyces sp. N174 was mutated via the deletion of 198A, 199A, 200H and 201D. Mutant chitosanase (m-SsCsn46) and wild chitosanase (SsCsn46) were secretory expressed at high level and purity in Pichia pastoris GS115. The activity of m-SsCsn46 was 30,000 U/mg and reduced by almost 40% of the maximum activity of wild type SsCsn46 (50,000 U/mg). Both enzymes had a high maximum activity at pH 6.0 and 50 °C, and maintained 40% of maximum activity at temperature 40-60 °C at pH 6.0 and or pH 5-7 at 50 °C after 2-hour treatment. The hydrolysis of chitosan by SsCsn46 yielded predominantly chitooligosaccharides with degree of polymerization (DP) 3-5 while m-SsCsn46 preferred to produce chitopentasaccharide from chitosan. Chitopentasaccharide improved gut microbiota significantly (by reducing the proportion of harmful pathogen population and increasing the proportion of the probiotic population) in mice when compared with the chitooligosaccharides with DPs 3-5. Thus, the mutant chitosanase from Streptomyces sp. N174 prefers to produce functional chitopentasaccharide from chitosan and m-SsCsn46 provides a potential tool for producing high-purity functional chitooligosaccharides.

13.
Biomater Sci ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724659

RESUMO

Bladder cancer is a common urinary tract tumor in clinic, and its morbidity and mortality are always high. Surgical treatment is operator dependent, residual tumor cells often lead to tumor recurrence, and chemotherapy after surgery causes high side effects. So, it is urgent to develop new methods for the theranostics of bladder cancer. Among them, functional nanomaterials have shown good application in tumor theranostics, but they are rarely used in bladder cancer. In our work, we demonstrate the fabrication of folate-modified vincristine-loaded polydopamine-coated Fe3O4 superparticles (Fe3O4@PDA-VCR-FA SPs), and applied them in the theranostics of bladder cancer. The PDA shell not only improves the colloidal stability and biocompatibility, but also enhances the photothermal effect and prolongs the blood circulation half-life. The half-life of Fe3O4@PDA-VCR-FA SPs in blood is calculated as 2.83 h, and the tumor retention rate is 5.96 %ID g-1, these data are significantly higher than those before folic acid modification. The superparamagnetism of Fe3O4 and loading of vincristine endow Fe3O4@PDA-VCR-FA SPs with magnetic resonance imaging and chemotherapy capabilities. Further by employing NIR laser-triggered photothermal therapy, bladder tumors were ablated completely, and no recurrence was observed. Blood and histological tests of the major organs confirm that Fe3O4@PDA-VCR-FA SPs show good biosafety.

14.
IUBMB Life ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31743955

RESUMO

The expression of long noncoding RNAs (lncRNAs) is closely associated with cancer development and progression, making these lncRNAs potentially novel therapeutic targets. In this study, we aimed to explore the potential function of lncRNA-uc061hsf.1 in esophageal squamous cell carcinoma (ESCC). The expression of lncRNA-uc061hsf.1 in ESCC tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, and metastasis were detected via CCK-8, flow cytometry, and Transwell assays. The interaction between p53 and lncRNA uc061hsf.1 was analyzed using luciferase reporter gene and qRT-PCR. Through this approach, we identified the novel lncRNA uc061hsf.1, which was expressed in low level in ESCC and was correlated with lymph node metastasis and poor differentiation in ESCC patients. Knockdown or overexpression of lncRNA uc061hsf.1 in ESCC cells promoted or inhibited cell proliferation and metastasis, respectively. Mechanistically, lncRNA uc061hsf.1 was induced by p53, and luciferase reporter gene confirmed that lncRNA uc061hsf.1 was a direct transcriptional target of p53. We further found that uc061hsf.1 was able to regulate expression of the transcription factor FoxA1, thereby potentially influencing tumor cell migration. In conclusion, these results suggest that p53-regulated lncRNA uc061hsf.1 is a cancer suppressor gene which is associated with tumor progression in ESCC.

15.
Int J Oncol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31746420

RESUMO

Hepatitis B virus (HBV)­related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non­coding RNAs (lncRNAs), which are non­coding RNAs >200 nt in length that were previously considered to be transcriptional noise, have been found to be dysregulated in HBV­related HCC with the help of high­throughput omics techniques. Subsequent investigations revealed that aberrant expression of lncRNAs may affect the risk of HBV­related HCC through diverse mechanisms, including epigenetic silencing of transcriptional activation, alternative splicing, molecular sponging, modulating protein stability, and by serving as precursors of miRNAs. Although the sensitivity and specificity of lncRNAs must be further validated, a number of circulating lncRNAs have been identified as useful biomarkers for HBV­related HCC. In addition to these findings, recent studies also unveiled that certain genetic polymorphisms in lncRNAs may affect the occurrence and prognosis of HBV­related HCC. The aim of the present review was to provide an overview of the mechanisms underlying the involvement of lncRNAs in HBV­related HCC. Subsequently, lncRNAs found to be dysregulated in HBV­related HCC were focused on and current findings on circulating lncRNAs and their genetic polymorphisms were discussed.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31746538

RESUMO

Antiperovskite Co 3 InC 0.7 N 0.3 nanomaterials with highly enhanced ORR performance was successfully achieved by tuning nitrogen contents through a MOF-derived strategy. The obtained nanomaterial has surpassed all currently reported noble-metal-free antiperovskites and even most of those perovskites on onset potential (0.957 V at J = 0.1 mA cm -2 ) and half-wave potential (0.854 V). The OER and Zinc-air battery performance demonstrate its multifunctional oxygen catalytic activities. DFT calculation was performed and for the first time, a 4e- dissociative ORR pathway on (200) facets of antiperovskite was revealed. Detailed comparative studies on its free energy proved that nitrogen substitution could strengthen the OH desorption as well as hydrogenation that accounts for the enhanced ORR performance. This work expands our scope for material design via tailoring the nitrogen contents for optimal reaction free energy and hence performance. It is expected to arouse general interest in exploring more electrocatalytic activities in antiperovskites system.

17.
Org Lett ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710496

RESUMO

A novel supramolecular polypseudorotaxane was successfully constructed with pseudo[3]rotaxanes between pyridine-2,6-dicarboxylic acid imidazolium (G1) and cucurbit[8]uril (CB[8]) and the subsequent coordination with lanthanide ions. Significantly, compared with the pyridine-2,6-dicarboxylic acid imidazolium complex G1@Tb3+, CB[8]-mediated polypseudorotaxane CB[8]@G12@Tb3+ not only displayed enhanced lanthanide luminescence behavior with a 29.1-fold time enhancement (from 45.76 µs to 1.33 ms) of the excited-state lifetime (τ) and a 8.7-fold increase (from 0.89% to 7.81%) in the quantum yield (Φ) but also exhibited a specific fluorescence response to antibiotics in an aqueous solution and a solid film.

18.
J Dairy Sci ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677844

RESUMO

Previous research reported that fermented yak milk had a diverse microbial composition. For this study, raw yak milk, qula, and fermented yak milk samples were collected from the Aba Tibetan autonomous region of China. The genus and species microbial composition of these samples were analyzed by high-throughput sequencing of 16S rRNA and groEL gene amplicons, and the volatile profile of the samples was quantified by gas chromatography-mass spectrometry. The results indicated variation in abundance of microbiota at the genus level among the fermented yak milk samples, with Lactobacillus as the most abundant genus in the majority of samples, ranging from 41.6 to 98.26%. The volatile profile of the samples varied among those collected from different villages. Correlations between bacterial composition and volatile compounds of the samples were also observed. Lactobacillus displayed a significant correlation with volatile compounds such as benzaldehyde, 2,3-pentanedione, ethanol, and ethyl acetate, whereas the samples with relatively high abundance of Streptococcus and Lactococcus displayed relatively low contents of volatile compounds.

19.
BMC Pediatr ; 19(1): 410, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684895

RESUMO

BACKGROUND: Primary immunodeficiency disease (PID) is a disorder caused by an inherited flaw in the immune system that increases the susceptibility to infections. METHODS: In this study, 112 children with PID were diagnosed and classified based on the 2017 criteria presented by the International Union of Immunological Societies (IUIC) in a single tertiary care center from January 2013 to November 2018. We retrospectively studied the clinical features of those PID children and followed-up them as well. RESULTS: It was revealed that male/female ratio was 6:1. The most frequent diagnosed PID was severe combined immunodeficiency (SCID) (28.6%) and hyper-IgM (HIGM) syndrome (24.1%), followed by predominantly antibody deficiencies (17.8%). Combined immunodeficiencies with associated or syndromic features (12.5%) and congenital defects of phagocyte number, function, or both (10.7%) were less common in our center compared with SCID and HIGM syndrome. Besides, we found that 20 children (17.8%) had a positive family history of PID, and almost all cases (97.3%) had a history of recurrent infection. Recurrent respiratory tract infection was among the most common symptoms, followed by the bacterial infection of the skin and mucous membranes and diarrhea. Additionally, adverse event following immunization (AEFI) was found in 20.5% of the patients, and immune disorder was commonly observed in PID patients. In the present study, 47 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 2-year overall survival (OS) rate for these patients was 78.7% (37/47). It is noteworthy that OS widely differed among PID patients with different phenotypes who underwent allo-HSCT. The 2-year OS rate for SCID, HIGM syndrome, and the remaining of PID patients who underwent allo-HSCT was 14.3, 83.3, and 100%, respectively. CONCLUSIONS: PID typically emerges at early age. Recurrent infection and serious infection were the most common clinical manifestations. Allo-HSCT is a relatively effective therapeutic strategy for PID patients.

20.
Drug Des Devel Ther ; 13: 3199-3206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686782

RESUMO

Background: p66Shc, a Src homologue and collagen homologue (Shc) adaptor protein, mediates oxidative stress signaling. The p66Shc-null mice have increased lifespan and enhanced resistance to oxidative stress. Studies have also indicated its potential role in inner ear aging, which can lead to deafness. Objective: The aim of this study was to determine the effects of p66Shc down-regulation on the marginal cells (MCs) of the inner ear stria vascularis. Methods: Primary MCs were isolated from neonatal rats and treated with glucose oxidase to induce oxidative stress. The cells were transduced with adenovirus expressing siRNA, and the knockdown was verified by Western blotting. The reactive oxygen species (ROS) levels and apoptosis were analyzed using the DCFH-DA probe and Annexin-V/7-AAD staining respectively. The ultrastructure of the differentially-treated cells was examined by transmission electron microscopy (TEM).Results: The in vitro oxidative stress model was established successfully in rat MCs. Knockdown of p66Shc alleviated the high ROS levels and apoptosis in the glucose oxidase-treated cells. In addition, glucose oxidase significantly increased the number of peroxisomes in the MCs, which was decreased by p66Shc inhibition. Conclusion: Oxidative stress increases p66Shc levels in the marginal cells of the inner ear, which aggravates ROS production and cellular injury. Blocking p66Shc expression can effectively reduce oxidative stress and protect the MCs.

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