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1.
EBioMedicine ; 52: 102650, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058941

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that down-regulates hepatic low-density lipoprotein receptor (LDLR) by binding and shuttling LDLR to lysosomes for degradation. The development of therapy that inhibits PCSK9 has attracted considerable attention for the management of cardiovascular disease risk. However, only monoclonal antibodies of PCSK9 have reached the clinic use. Oral administration of small-molecule transcriptional inhibitors has the potential to become a therapeutic option. METHODS: Here, we developed a cell-based small molecule screening platform to identify transcriptional inhibitors of PCSK9. Through high-throughput screening and a series of evaluation, we found several active compounds. After detailed investigation on the pharmacological effect and molecular mechanistic characterization, 7030B-C5 was identified as a potential small-molecule PCSK9 inhibitor. FINDINGS: Our data showed that 7030B-C5 down-regulated PCSK9 expression and increased the total cellular LDLR protein and its mediated LDL-C uptake by HepG2 cells. In both C57BL/6 J and ApoE KO mice, oral administration of 7030B-C5 reduced hepatic and plasma PCSK9 level and increased hepatic LDLR expression. Most importantly, 7030B-C5 inhibited lesions in en face aortas and aortic root in ApoE KO mice with a slight amelioration of lipid profiles. We further provide evidences suggesting that transcriptional regulation of PCSK9 by 7030B-C5 mostly depend on the transcriptional factor HNF1α and FoxO3. Furthermore, FoxO1 was found to play an important role in 7030B-C5 mediated integration of hepatic glucose and lipid metabolism. INTERPRETATION: 7030B-C5 with potential suppressive effect of PCSK9 expression may serve as a promising lead compound for drug development of cholesterol/glucose homeostasis and cardiovascular disease therapy. FUND: This work was supported by grants from the National Natural Science Foundation of China (81473214, 81402929, and 81621064), the Drug Innovation Major Project of China (2018ZX09711001-003-006, 2018ZX09711001-007 and 2018ZX09735001-002), CAMS Innovation Fund for Medical Sciences (2016-I2M-2-002, 2016-I2M-1-011 and 2017-I2M-1-008), Beijing Natural Science Foundation (7162129).

2.
Environ Int ; 136: 105497, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31999971

RESUMO

Minerals and microorganisms are integral parts of natural environments, and they inevitably interact. Antibiotic-resistance genes (ARGs) significantly threaten modern healthcare. However, the effects of natural minerals on ARG propagation in aquatic systems are not fully understood. The present work studied the effects of natural sphalerite (NS) nanoparticles on the horizontal transfer of ARGs from Escherichia coli DH5α (CTX) (donor) to E. coli C600 (Sm) (recipient), and from E. coli DH5α (MCR) (donor) to E. coli C600 (Sm), and their underlying mechanisms. NS particles (0.5-50 mg L-1) induced an NS-concentration-dependent increase in conjugative transfer frequency. The underlying mechanisms associated with the facilitated ARG transfer included the production of intracellular reactive oxygen species, the SOS response, changes in bacterial cell morphology, and alteration of mRNA levels of bacterial cell membrane protein-related genes and genes associated with conjugative ARG transfer. The information herein offers new mechanistic understanding of risks of bacterial resistance resulting from NS.

3.
Pediatr Pulmonol ; 55(3): 713-718, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31909893

RESUMO

INTRODUCTION: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in children. Meteorological factors are known to influence seasonal RSV epidemics, but the relationship between meteorological factors and RSV infection in children is not well understood. We aimed to explore the relationship between meteorological factors and RSV infections among hospitalized children, using different statistical models. METHODS: We conducted a retrospective review concerning children with RSV infections admitted to a tertiary pediatric hospital in Wenzhou, China, between January 2008 and December 2017. The relationship between meteorological factors (average daily temperatures, average daily relative humidity, rainfall, rainfall days, and wind speed) and the incidence of RSV in hospitalized children was analyzed using three time-series models, namely an autoregressive integrated moving average (ARIMA) model, a generalized additive model (GAM), and a least absolute shrinkage and selection operator (LASSO)-based model. RESULTS: In total, 15 858 (17.6%) children tested positive for RSV infection. The ARIMA model revealed a marked seasonal pattern in the RSV detection rate, which peaked in winter and spring. The model was a good predictor of RSV incidence (R2 : 83.5%). The GAM revealed that a lower temperature and higher wind speed preceded increases in RSV detection. The LASSO-based model revealed that temperature and relative humidity were negatively correlated with RSV detection. CONCLUSIONS: Seasonality of RSV infection in hospitalized children correlated strongly with temperature. The LASSO-based model can be used to predict annual RSV epidemics using weather forecast data.

4.
Biochem Biophys Res Commun ; 521(3): 799-805, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706575

RESUMO

Lpg0189 is a type II secretion system-dependent extracellular protein with unknown function from Legionella pneumophila. Herein, we determined the crystal structure of Lpg0189 at 1.98 Šresolution by using single-wavelength anomalous diffraction (SAD). Lpg0189 folds into a novel chair-shaped architecture, with two sheets roughly perpendicular to each other. Bioinformatics analysis suggests Lpg0189 and its homologues are unique to Legionellales and evolved divergently. The interlinking structural and bioinformatics studies provide a better understanding of this hypothetical protein.

5.
Pharmacol Res ; 151: 104512, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726100

RESUMO

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an onco-embryonic antigen presented on chronic lymphocytic leukemia (CLL), but not on normal adult tissues, which promotes CLL-cell survival. Here, ROR1 was identified as a new client of Heat Shock Protein 90 (HSP90) via a mass spectrometry-based screen for ROR1-associated partners followed by co-immunoprecipitation (co-IP) analysis. A binding motif (ELHHPNIV) on ROR1 for HSP90 was revealed, which forms a αC-ß4 loop and is necessary for HSP90-facilitated ROR1 stabilization. We also found that targeting HSP90 leads to ROR1 degradation in a ubiquitin-proteasome dependent pathway, by which pro-survival ROR1 signaling was attenuated in CLL. Based on our previous finding that a humanized monoclonal antibody against ROR1 increases the activity of Ibrutinib against CLL, which is currently undergoing evaluation in clinical trials for the treatment of B-cell lymphoid malignancies, we then provided evidence that treatment with HSP90 inhibitor (17-DMAG) enhances anti-CLL activity of Ibrutinib in vitro and in vivo, by down-modulating ROR1. iTRAQ-based quantitative proteomic analysis of other HSP90 oncogenic clients in addition to ROR1, followed by GO/KEGG enrichment analysis, showed that Bruton's Tyrosine Kinase (BTK), B-lymphoid Tyrosine Kinase (BLK), Lymphocyte-specific Protein Tyrosine Kinase (LCK), or LCK/YES-Related Novel Protein Tyrosine Kinase (LYN), as HSP90 clients, were significantly involved in 11 biological processes and 6 signaling pathways. However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1. Collectively, our data suggested that depletion of ROR1 induced by targeting HSP90 might facilitate the enhancement of Ibrutinib activity against CLL.

6.
Mol Plant Microbe Interact ; 33(1): 55-65, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31184525

RESUMO

Symbiotic viruses exist in many insects; however, their functions in host insects are not well understood. In this study, we explored the role of acyrthosiphon pisum virus (APV) in the interaction of its host aphid Acyrthosiphon pisum with plants. APV is primarily located in aphid salivary glands and gut and propagated in the insect. APV is horizontally transmitted to host plants during aphid feeding, but the virus does not replicate in the host plant. When the pea host race of aphids colonized two low-fitness plants, Medicago truncatula and Vicia villosa, the virus titers in both the aphids and plants significantly increased. Furthermore, APV infection strongly promoted the survival rate of the pea host race on V. villosa. Transcriptomic analysis showed that only 0.85% of aphid genes responded to APV infection when aphids fed on V. villosa, with a fold change in transcript levels of no more than fourfold. The improved survival due to APV infection was apparently related to the inhibitory effect of the virus on levels of phytohormone jasmonic acid (JA) and JA-isoleucine. Our data suggest a benefit of the symbiotic virus to its aphid host and demonstrate a novel case of symbiotic virus-mediated three-species interaction.

7.
Stem Cells Int ; 2019: 1847098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827524

RESUMO

Establishment of a functional vascular network, which is required in tissue repair and regeneration, needs large-scale production of specific arterial or venous endothelial cells (ECs) from stem cells. Previous in vitro studies by us and others revealed that shear stress induces EC differentiation of bone marrow-derived mesenchymal stem cells and embryonic stem cells. In this study, we focused on the impact of different magnitudes of shear stress on the differentiation of mouse-induced pluripotent stem cells (iPSCs) towards arterial or venous ECs. When iPSCs were exposed to shear stress (5, 10, and 15 dyne/cm2) with 50 ng/mL vascular endothelial growth factor and 10 ng/mL fibroblast growth factor, the expression levels of the general EC markers and the arterial markers increased, and the stress amplitude of 10 dyne/cm2 could be regarded as a proper promoter, whereas the venous and lymphatic markers had little or no expression. Further, shear stress caused cells to align parallel to the direction of the flow, induced cells forming functional tubes, and increased the secretion of nitric oxide. In addition, Notch1 was significantly upregulated, and the Notch ligand Delta-like 4 was activated in response to shear stress, while inhibition of Notch signaling by DAPT remarkably abolished the shear stress-induced arterial epithelium differentiation. Taken together, our results indicate that exposure to appropriate shear stress facilitated the differentiation of mouse iPSCs towards arterial ECs via Notch signaling pathways, which have potential applications for both disease modeling and regenerative medicine.

8.
ACS Appl Bio Mater ; 2(3): 1270-1277, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-31750420

RESUMO

Intracellular survival of pathogenic bacteria leads to high chances of bacterial persistence and relapse in the bacteria-infected host. However, many antibiotics fail to clear the intracellular bacteria due to their low internalization by cells. In order to increase delivery of antibiotics in cells and eliminate intracellular bacteria, we developed antibiotic-derived lipid nanoparticles. First, we synthesized antibiotic-derived lipid conjugates using two widely used antibiotics including penicillin G (PenG) and levofloxacin (Levo). Then, we formulated them into antibiotic-derived lipid nanoparticles and evaluated their antibacterial effects. We found that penicillin G derived phospholipid nanoparticles (PenG-PL NPs) were able to enhance cellular uptake of penicillin G as compared with free penicillin G and eliminate up to 99.9998% of ~108.5 intracellular methicillin sensitive Staphylococcus aureus (S. aureus) in infected A549 cells, a lung epithelial cell line. The PenG-PL NPs showed the potential for inhibiting intracellular S. aureus and are promising to be further studied for in vivo antibacterial applications.

9.
BMJ Open ; 9(11): e031184, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740468

RESUMO

OBJECTIVE: This study investigates the distribution, burden and trends of injuries in Sichuan, China. DESIGN: A surveillance study using injury data collected by the National Injury Surveillance System. SETTING AND PARTICIPANTS: 312 511 injury cases reported in the National Injury Surveillance System in Sichuan, China, from 2006 to 2015. PRIMARY OUTCOME MEASURES: Years of potential life lost (YPLL) were calculated to determine the disease burden from injuries. Trend analysis was performed to assess the trends in specific injuries over time. RESULTS: A total of 312 511 injury cases were reported in the last 10 years in Sichuan with 192 904 (men: 58.58%) and 119 607 (men: 67.11%) cases from the urban and rural surveillance hospitals, respectively. The annual number of injury cases increased from 21 257 in 2006 to 44 112 in 2015 with an average annual increase of 8.45%. The top three common causes of injury were fall (29.3%), animal-related injury (19.1%) and road-related injury (14.6%) in the urban area and fall (38.4%), road-related injury (17.2%) and blunt injuries (16.0%) in the rural area. YPLLs from injuries accounted for 13% of the total YPLLs in the urban area. CONCLUSIONS: The number of injury cases varied according to rural/urban areas and gender and increased sharply in Sichuan over the last decade. It is necessary to develop targeted prevention and control measures to reduce the disease burden of injuries.

10.
Toxins (Basel) ; 11(11)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739564

RESUMO

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 µg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/ß, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway.

11.
Int J Epidemiol ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31650183

RESUMO

BACKGROUND: Harmful substances in solid fuel and tobacco smoke are believed to enter the bloodstream via inhalation and to be metabolized in the liver, leading to chronic liver damage. However, little is known about the independent and joint effects of solid fuel use and smoking on risks of chronic liver disease (CLD) mortality. METHODS: During 2004-08, ∼0.5 million adults aged 30-79 years were recruited from 10 areas across China. During a 10-year median follow-up, 2461 CLD deaths were recorded. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the individual associations of self-reported long-term cooking fuel and tobacco use with major CLD death. RESULTS: Overall, 49% reported solid fuel use and 26% smoked regularly. Long-term solid fuel use for cooking and current smoking were associated with higher risks of CLD deaths, with adjusted HRs of 1.26 (95% CI, 1.02-1.56) and 1.28 (1.13-1.44), respectively. Compared with never-smoking clean fuel users, the HRs were 1.41 (1.10-1.82) in never-smoking solid fuel users, 1.55 (1.17-2.06) in regular-smoking clean fuel users and 1.71 (1.32-2.20) in regular-smoking solid fuels users. Individuals who had switched from solid to clean fuels (1.07, 0.90-1.29; for median 14 years) and ex-regular smokers who stopped for non-medical reasons (1.16, 0.95-1.43; for median 10 years) had no evidence of excess risk of CLD deaths compared with clean fuel users and never-regular smokers, respectively. CONCLUSIONS: Among Chinese adults, long-term solid fuel use for cooking and smoking were each independently associated with higher risks of CLD deaths. Individuals who had stopped using solid fuels or smoking had lower risks.

12.
Lab Invest ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537899

RESUMO

Chemotherapy-induced premature ovarian failure (POF) in women is currently clinically irreversible. Bone marrow mesenchymal stem cells (BMSCs) are a promising cellular therapeutic strategy for POF. However, the underlying mechanism governing the efficacy of BMSCs in treating POF has not been determined. In this study, we show that BMSC and BMSC-derived exosome transplantation can significantly recover the estrus cycle, increase the number of basal and sinus follicles in POF rats, increase estradiol (E2) and anti-Mullerian hormone (AMH) levels, and reduce follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in the serum. Furthermore, we demonstrate that BMSC-derived exosomes prevent ovarian follicular atresia in cyclophosphamide (CTX)-treated rats via the delivery of miR-144-5p, which can be transferred to cocultured CTX-damaged granulosa cells (GCs) to decrease GC apoptosis. A functional assay revealed that overexpression of miR-144-5p in BMSCs showed efficacy against CTX-induced POF, and the improvement in the repair was related to the inhibition of GC apoptosis by targeting PTEN. The opposite effect was exhibited when miR-144-5p was inhibited. Taken together, our experimental results provide new information regarding the potential of using exosomal miR-144-5p to treat ovarian failure.

13.
Cancer Biol Med ; 16(2): 220-233, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31516744

RESUMO

Objective: Heat shock factor 1 (HSF1), a transcriptional regulator of heat shock proteins (HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far. Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies. Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth. Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression. Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance. Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer.

14.
Cell Cycle ; 18(20): 2800-2813, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478454

RESUMO

Myotubularin related protein 7 (MTMR7), a key member of the MTMR family, depicts phosphatase activity and is involved in myogenesis and tumor growth. We have previously identified MTMR7 in the proteomic profile of mouse spermatogonial stem cell (SSC) maturation and differentiation, implying that MTMR7 is associated with neonatal testicular development. In this study, to further explore the distribution and function of MTMR7 in mouse testis, we studied the effect of Mtmr7 knockdown on neonatal testicular development by testicular and SSC culture methods. Our results revealed that MTMR7 is exclusively located in early germ cells. Deficiency of MTMR7 by morpholino in neonatal testis caused excessive SSC proliferation, which was attributable to the aberrant PI3K/AKT signaling activation. Altogether, our study demonstrates that MTMR7 maintains SSC homeostasis by inhibiting PI3K/AKT signaling activation.

15.
Sleep Breath ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473914

RESUMO

PURPOSE: Obstructive sleep apnea syndrome (OSAS) was suggested to exert an effect on renal function. However, the specific mechanism was still unknown. We try to find the association among OSAS, adiponectin, and cystatin C and the effect of adiponectin on renal function in OSAS patients. METHODS: Seventeen healthy men and seventy-three men which only had OSAS were included in the end. Apnea-hypopnea index (AHI), oxygen desaturation index (ODI), the percentage of total sleep time spent with SpO2 < 90% (T90%), lowest O2 saturation (LaSO2), Epworth Sleepiness Scale (ESS) score, serum adiponectin, and high-sensitive C-reactive protein (hsCRP) were detected in all subjects, and renal function was evaluated with creatinine, cystatin C, and estimated glomerular filtration rate (eGFR). RESULTS: Demographic data, creatinine, and eGFR did not differ among the studied groups. Decreased serum adiponectin levels were associated with severe OSAS. OSAS patients had a higher hsCRP and cystatin C than those without OSAS. Serum adiponectin levels had a negative association with cystatin C. After adjusted for confounders, adiponectin, hsCRP, and ODI had a significant prediction on the cystatin C (ß = - 0.218, p = 0.011; ß = 0.226, p = 0.037; and ß = 0.231, p = 0.029). CONCLUSIONS: Decreased serum adiponectin was associated with increased cystatin C in male OSAS patients. These results suggest that serum adiponectin might be a regulatory factor for renal function in OSAS.

16.
Environ Sci Technol ; 53(16): 9926-9936, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31319665

RESUMO

Reactive chlorine species (RCS) such as HOCl and chlorine radical species is a strong oxidant and has been widely used for water disinfection. This study investigated a photoelectrochemical (PEC) method of RCS production from ubiquitous chloride ions using a WO3 film electrode and visible light. The degradation of organic substrates coupled with H2 evolution using a WO3 electrode was compared among electrochemical (EC), photocatalytic (PC), and PEC conditions (potential bias: +0.5 V vs Ag/AgCl; λ > 420 nm). The degradation of 4-chlorophenol, bisphenol A, acetaminophen, carbamazepine, humic acid, and fulvic acid and the inactivation of E. coli were remarkably enhanced by in situ RCS generated in PEC conditions, whereas the activities of the PC and EC processes were negligible. The activities of the WO3 film were limited by rapid charge recombination in the PC condition, and the potential bias of +0.5 V did not induce any significant reactions in the EC condition. The PEC activities of WO3 were limited in the absence of Cl- but significantly enhanced in the presence of Cl-, which confirmed the essential role of RCS in this PEC system. The PEC mineralization of organic compounds was also markedly enhanced in the presence of Cl- where dark chemical chlorination by NaOCl addition induced a negligible mineralization. The H2 generation was observed only at the PEC condition and was negligible at PC and EC conditions. On the other hand, the oxidation of chloride on a WO3 photoanode produced chlorate (ClO3-) as a toxic byproduct under UV irradiation, but the visible light-irradiated PEC system generated no chlorate.


Assuntos
Escherichia coli , Luz , Eletrodos , Oxirredução , Estresse Oxidativo
17.
Micromachines (Basel) ; 10(6)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185602

RESUMO

Intracellular gene delivery is normally required to study gene functions. A versatile platform able to perform both chemical transfection and viral transduction to achieve efficient gene modification in most cell types is needed. Here we demonstrated that high throughput chemical transfection, virus packaging, and transduction can be conducted efficiently on our previously developed superhydrophobic microwell array chip (SMAR-chip). A total of 169 chemical transfections were successfully performed on the chip in physically separated microwells through a few simple steps, contributing to the convenience of DNA delivery and media change on the SMAR-chip. Efficiencies comparable to the traditional transfection in multi-well plates (~65%) were achieved while the manual operations were largely reduced. Two transfection procedures, the dry method amenable for the long term storage of the transfection material and the wet method for higher efficiencies were developed. Multiple transfections in a scheduled manner were performed to further increase the transfection efficiencies or deliver multiple genes at different time points. In addition, high throughput virus packaging integrated with target cell transduction were also proved which resulted in a transgene expression efficiency of >70% in NIH 3T3 cells. In summary, the SMAR-chip based high throughput gene delivery is efficient and versatile, which can be used for large scale genetic modifications in a variety of cell types.

18.
J Med Microbiol ; 68(8): 1211-1218, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31225788

RESUMO

INTRODUCTION: Lower respiratory tract infections (LRTIs), particularly those acquired in hospitals, are an important cause of childhood morbidity and mortality. Understanding the aetiology and epidemiology of LRTIs is necessary for clinical management, reduction of antibiotic usage, vaccine development and prevention of nosocomial infection. AIM: In this study, we aimed to detect 13 viruses and atypical bacteria in nasopharyngeal secretion specimens from hospitalized children with LRTIs. METHODOLOGY: From January 2014 to December 2016, nasopharyngeal secretion specimens were prospectively collected from 3232 children aged between 1 and 72 months. Nucleic acid was extracted and analysed using the SureX13 respiratory pathogen multiplex kit as per the manufacturer's instructions. RESULTS: A total of 2874 (88.9 %) children tested positive for viral and/or atypical bacterial infections, and 965 (29.9 %) were co-infected with multiple pathogens. The most frequently detected respiratory tract pathogens (RTPs) were rhinovirus, respiratory syncytial virus, parainfluenza virus and adenoviruses. The rates of RTP and co-infection positivity in the toddler group were significantly higher than those in the infant and preschool groups. CONCLUSION: The SureX13 respiratory pathogen multiplex kit has the ability to effectively detect a range of RTPs in hospitalized paediatric patients with LRTIs.


Assuntos
Bactérias/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/normas , Kit de Reagentes para Diagnóstico/normas , Infecções Respiratórias/diagnóstico , Vírus/isolamento & purificação , Fatores Etários , Bactérias/classificação , Bactérias/genética , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , China/epidemiologia , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Humanos , Lactente , Masculino , Nasofaringe/microbiologia , Nasofaringe/virologia , Prevalência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Análise de Sequência de DNA , Vírus/classificação , Vírus/genética
19.
J Med Virol ; 91(9): 1625-1632, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066075

RESUMO

BACKGROUND: Human parainfluenza virus (HPIV), usually combined with other pathogens, causes lower respiratory tract infection (LRTI) in children. However, clinical characteristics of HPIV coinfection with other pathogens were unclear. This study aimed to investigate the viral and atypical bacterial etiology of LRTI in children and compare the clinical characteristics of HPIV single infection with those of coinfection. METHODS: This study included 1335 patients, aged between 1 to 71 months, diagnosed with LRTI in Yuying Children's Hospital, Zhejiang, China, from December 2013 to June 2015. Nasopharyngeal secretions were collected, and respiratory pathogens were detected using Multiplex polymerase chain reaction. The clinical data of patients were collected and analyzed. RESULTS: At least 1 pathogen was detected in 1181/1335 (88.5%) patients. The pathogens identified most frequently were respiratory syncytial virus, human rhinovirus, HPIV, adenovirus, and human metapneumovirus. The coinfection rate was 24.8%. HPIV coinfection with other viruses was more associated with running nose, shortness of breath, and oxygen support compared with HPIV single infection. Moreover, HPIV coinfection with atypical bacteria was more related to running nose, moist rales, and longer hospital duration compared with HPIV single infection, and also to longer hospital duration compared with coinfection with other viruses. CONCLUSIONS: This study demonstrated that viral infections were highly associated with LRTI and the rate of coinfection was high. HPIV single infection was milder than coinfection with other viruses. Moreover, HPIV coinfection with atypical bacteria was more serious than HPIV single infection and coinfection with other viruses.

20.
Biosci Rep ; 39(5)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30992389

RESUMO

The aim of the present study was to assess the association between neutrophil-lymphocyte ratio (NLR) and arterial stiffness and provide a predictive index for diagnosing atherosclerosis in patients with acute coronary syndrome (ACS). We enrolled patients with ACST who were confirmed by coronary angiography. Data were collected by questionnaire and blood indexes. Brachial-ankle pulse wave velocity (baPWV) was measured using BP-203RPE III network arteriosclerosis detection equipment. Correlation analysis of traditional cardiovascular risk factors and baPWV was performed, and multivariate line regression analysis was conducted to explore the relevant factors for baPWV. A total of 210 patients were included in the final analyses according to the inclusion criteria. Patients with a high baPWV had a lower lymphocyte count than those with a low baPWV (1.2 ± 0.4 vs. 1.4 ± 0.4, P = 0.004). The NLRs of the low and high bvPWV groups were 3.1 ± 1.5 and 4.0 ± 2.1, respectively; no significant difference was observed. The results suggest that there is a positive relationship between baPWV and NLR (r = 0.403, P = 0.005) and neutrophils (r = 0.319, P = 0.016). Multivariate line regression suggested that NLR was positively associated with baPWV (B = 0.372, P = 0.000). The present results indicate that NLR is independently associated with arterial stiffness in patients with ACS. NLR, an inexpensive, easily measurable, widely available biomarker, could be an additional tool for assessing cardiovascular risk in clinical practice.

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