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1.
Clin J Pain ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31977369

RESUMO

OBJECTIVES: The objectives of this study were to investigate the correlations between the minimum effective volume (MEV) of lidocaine 1.5% for an ultrasound-guided popliteal sciatic nerve block (PSNB) and individual factors including the cross-sectional nerve area, sex, age, body mass index (BMI) and the depth of the sciatic nerve and to evaluate the safety of combined femoral and sciatic nerve blocks by monitoring the plasma concentration of local anesthetics (LAs). METHODS: Forty patients received combined single-shot femoral and continuous sciatic nerve blocks. The femoral nerve block was performed with an in-plane technique and 15▒mL of lidocaine 1.5%. A continuous peripheral nerve block annular tube was positioned between the tibial and peroneal nerves inside the paraneural sheath. Thirty minutes after the femoral nerve block, a loading dose of 5▒mL of lidocaine 1.5% was given to block the sciatic nerve after obtaining the maximum compound muscle action potential (CMAP) amplitude using nerve conduction studies (NCSs). Additional lidocaine 1.5% was pumped at a rate of 30▒mL/h through the indwelling annular tube if after 8 minutes, the CMAP amplitude was still present. The CMAP amplitude monitored by the NCSs and pinprick tests were recorded every 2 minutes after the administration of lidocaine 1.5%. When the CMAP amplitude decreased to nearly 0▒mV, this MEV was recorded. The influences of the cross-sectional area of the sciatic nerve, sex, age, BMI and the depth of the sciatic nerve on the MEV were analyzed using stepwise multiple linear regression. Blood samples were collected from ten patients to evaluate the safety of combined femoral and sciatic nerve blocks by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Blood was drawn at 0 minutes before femoral nerve injection, 0 minutes before sciatic nerve injection, 8 minutes after sciatic nerve injection and 0, 10, 20, 30, 45, 60, 75, 90, and 120 minutes after the pumping of lidocaine 1.5% stopped. RESULTS: A significant correlation was found between the MEV of lidocaine 1.5% and the cross-sectional area of the sciatic nerve (r=0.459), with a regression equation of the MEV (mL)=5.969 + 0.095× (the cross-sectional area of the sciatic nerve). The coefficient of determination was 0.211 (P<0.05). The MEV of lidocaine 1.5% for complete sciatic nerve blocks ranged from 7 to 15▒mL. The maximum concentrations of lidocaine, monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were 1672.9 (227.6), 265.7 (32.7) and 42.2 (22.4) ng/mL, respectively. CONCLUSIONS: There is a positive correlation between the cross-sectional area of the sciatic nerve and the MEV. The regression equation can help to predict the MEV of lidocaine 1.5% for PSNBs. The maximum concentrations of lidocaine and its metabolites did not approach toxic threshold limits in this study.

2.
J Interv Cardiol ; 2019: 2750173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772520

RESUMO

Background: Contrast-induced nephropathy (CIN) becomes more and more frequent after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). There have been no reported meta-analyses to determine the role of these risk factors in predicting CIN in patients with STEMI undergoing PCI. So we made this meta-analysis to summarize the incidence of CIN in patients with STEMI undergoing PCI and to study associations between CIN and several risk factors that are mentioned in most prevention guidelines. Hypothesis: The overall incidence of CIN in patients with STEMI undergoing PCI is not low. Many risk factors could influence the occurrence of CIN, such as hypertension, diabetes mellitus (DM), and lower estimated glomerular filtration rate. Methods: Databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Chinese BioMedical (CBM), were searched for articles published before May 21, 2019, to identify all relevant studies on CIN. The pooled data were analyzed using either fixed-effects or random-effects models depending on heterogeneity (assessed via the I 2 index). Results: Twelve articles encompassing a total of 6342 patients were included. The overall pooled CIN incidence was 13.3% (95% CI: 10.4-17.1). The forest plots showed positive associations between CIN and the presence of hypertension, diabetes mellitus, history of prior myocardial infarction, age, damaged left anterior descending artery, Killip class ≥2, decreased left ventricular ejection fraction, lower estimated glomerular filtration rate, and left ventricular ejection fraction <40%; the odds ratios for these factors were 1.85 (95% CI: 1.57-2.18; p < 0.00001), 1.83 (95% CI: 1.47-2.29; p < 0.00001), 2.14 (95% CI: 1.46-3.14; p < 0.0001), 7.79 (95% CI: 5.24-10.34; p < 0.00001), 1.92 (95% CI: 1.15-3.22; p=0.01), 3.12 (95% CI: 2.21-4.40; p < 0.00001), -6.15 (95% CI: -9.52 to -2.79; p=0.0003), -15.06 (95% CI: -24.75 to -5.36; p=0.002), and 5.53 (95% CI: 1.10-27.95; p=0.04), respectively. Conclusion: The overall incidence of CIN in patients with STEMI undergoing PCI was not low and was closely associated with hypertension, diabetes mellitus, history of prior myocardial infarction, age, damaged left anterior descending artery, Killip class ≥2, decreased left ventricular ejection fraction, lower estimated glomerular filtration rate, and left ventricular ejection fraction <40%.

3.
Immunol Res ; 67(4-5): 398-407, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31773490

RESUMO

Limited protective effects of commercially available vaccines necessitate the development of novel pneumococcal vaccines. We recently reported a pneumococcal systemic vaccine containing two proteins, Pneumococcal surface protein A (PspA of family 1 and 2) and a bacterium-like particle-based pneumococcal mucosal vaccine containing PspA2 and PspA4 fragments, both eliciting broad protective immune responses. We had previously reported that subcutaneous (s.c.+s.c.+s.c.) immunization with the systemic vaccine induced more pronounced humoral serum IgG responses, while intranasal (i.n.+i.n.+i.n.) immunization with the mucosal vaccine elicited a more pronounced mucosal secretory IgA (sIgA) response. We hypothesized that a combinatorial administration of the two vaccines might elicit more pronounced and broader protective immune responses. Therefore, this study aimed to determine the efficacy of combinatorial prime-boost immunization using both systemic and mucosal vaccines for a pneumococcal infection. Combinatorial prime-boost immunization (s.c.+i.n. and i.n.+s.c.) induced not only IgG, but also mucosal sIgA production at high levels. Systemic priming and mucosal boosting immunization (s.c.+i.n.) provided markedly better protection than homologous prime-boost immunization (s.c.+s.c.+s.c. and i.n.+i.n.+i.n.). Moreover, it induced more robust Th1 and Th17 cell-mediated immune responses than mucosal priming and systemic boosting immunization (i.n.+s.c.). These results indicate that combinatorial prime-boost immunization potentially induces a robust systemic and mucosal immune response, making it an optimal alternative for maximum protection against lethal pneumococcal infections.

4.
ACS Omega ; 4(18): 17773-17781, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31681883

RESUMO

By using the first-principles calculations in combination with the Boltzmann transport theory, we systematically study the thermoelectric properties of AlX (X = S, Se, Te) monolayers as indirect gap semiconductors. The unique electronic density of states, which consists of a rather sharp peak at the valence band maxima and an almost constant band at the conduction band minima, makes AlX (X = S, Se, Te) monolayers excellent thermoelectric materials. The optimized power factors at room temperature are 22.59, 62.59, and 6.79 mW m-1 K-2 under reasonable electronic concentration for AlS, AlSe, and AlTe monolayers, respectively. The figure of merit (zT) increases with temperature and the optimized zT values of 0.52, 0.59, and 0.26 at room temperature are achieved under moderate electronic concentration for AlS, AlSe, and AlTe monolayers, respectively, indicating that two-dimensional layered AlX (X = S, Se, Te) semiconductors, especially AlSe, can be potential candidate matrices for high-performance thermoelectric nanocomposites.

5.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693229

RESUMO

Colorectal cancer (CRC) is a type of malignant cancer that has become particularly prevalent worldwide. It is of crucial importance to CRC treatment that the underlying molecular mechanism of CRC progression is determined. The NRAS gene is an important small G protein that is involved in various biological processes, including cancers. NRAS is an oncogene in many neoplasms but its function and regulation in CRC have seldom been investigated. In this study, it was uncovered that the NRAS protein was significantly upregulated in CRC tissues. According to a bioinformatics prediction, we identified that miR-144 may target NRAS to suppress its expression. In vitro experiments indicated that miR-144 decreased NRAS expression in different CRC cell lines (SW480, LoVo, and Caco2). By inhibiting NRAS, miR-144 repress SW480 cell proliferation and migration. Moreover, miR-144 decelerated the growth of SW480 xenograft tumors in vivo by targeting NRAS. In summary, our results identified a novel miR-144-NRAS axis in CRC that could promote the research and treatment of CRC.

6.
Biochemistry ; 58(46): 4610-4620, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31638374

RESUMO

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, requires iron for survival. In Mtb, MhuD is the cytosolic protein that degrades imported heme. MhuD is distinct, in both sequence and structure, from canonical heme oxygenases (HOs) but homologous with IsdG-type proteins. Canonical HO is found mainly in eukaryotes, while IsdG-type proteins are predominantly found in prokaryotes, including pathogens. While there are several published structures of MhuD and other IsdG-type proteins in complex with the heme substrate, no structures of IsdG-type proteins in complex with a product have been reported, unlike the case for HOs. We recently showed that the Mtb variant MhuD-R26S produces biliverdin IXα (αBV) rather than the wild-type mycobilin isomers. Given that mycobilin and other IsdG-type protein products like staphylobilin are difficult to isolate in quantities sufficient for structure determination, here we use the MhuD-R26S variant and its product αBV as a proxy to study the IsdG-type protein-product complex. First, we show that αBV has a nanomolar affinity for MhuD and the R26S variant. Second, we determined the MhuD-R26S-αBV complex structure to 2.5 Å, which reveals two notable features: (1) two αBV molecules bound per active site and (2) a novel α-helix (α3) that was not observed in previous MhuD-heme structures. Finally, through molecular dynamics simulations, we show that α3 is stable with the proximal αBV alone. MhuD's high affinity for the product and the observed structural and electrostatic changes that accompany substrate turnover suggest that there may be an unidentified class of proteins that are responsible for the extraction of products from MhuD and other IsdG-type proteins.

7.
ACS Infect Dis ; 5(9): 1493-1504, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31283163

RESUMO

One of the major threats to human life nowadays is widespread antibiotic resistance. Antibiotics are used to treat bacterial infections by targeting their essential pathways, such as the biosynthesis of bacterial cell walls. Bacterial transglycosylase, particularly glycosyltransferase family 51 (GT51), is one critical player in the cell wall biosynthesis and has long been known as a promising yet challenging target for antibiotic development. Here, we review the structural studies of this protein and summarize recent progress in developing its specific inhibitors, including synthetic substrate analogs and novel compounds identified from high-throughput screens. A detailed analysis of the protein-ligand interface has also provided us with valuable insights into the future antibiotic development against the bacterial transglycosylase.

8.
J Ethnopharmacol ; 241: 111801, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878546

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats. MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis. RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production. CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.

9.
Med Microbiol Immunol ; 208(2): 215-226, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707297

RESUMO

Streptococcuspneumoniae, or pneumococcus, is a major respiratory-tract pathogen that causes high levels of mortality and morbidity in infants and elderly individuals. Despite the development of various capsular polysaccharide vaccines to prevent pneumococcal disease, it remains epidemic. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein existing in all strains of S. pneumoniae, and it can elicit immunizing protection against pneumococcal infection. In our previous studies, a fusion protein (PsaA-PspA23), consisting of PspA and pneumococcal surface antigen A (PsaA), displayed greater immunogenicity and provided better protection in mice against S. pneumoniae strains than either PsaA or PspA. In this study, the fusion protein PsaA-PspA23, together with PspA4, was formulated with four adjuvants Al(OH)3, MF59, AS03, and AS02, and subsequently subjected to dose optimization and immunological evaluation for determination of the antibody titers, bacterial burden, survival rates, and levels of cytokines in mice. All vaccines with high adjuvant doses displayed higher antigen-specific immunoglobulin G (IgG) titers. Bacterial burdens were notably decreased to different extents in the lungs and blood of mice immunized with the antigen and various adjuvants. Among these adjuvants, AS02 provided outstanding protection against challenge with pathogenic bacteria from different families and clades; it also induced high titers of IgG1 and IgG2a. Moreover, only AS02 elicited high levels of cytokines, such as TNF-α, IFN-γ, IL-2, and IL-4. These results suggest that PsaA-PspA23 and PspA4 formulated with AS02 may potentially be used as a subunit vaccine against deadly pneumococcal infection.


Assuntos
Adesinas Bacterianas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Adesinas Bacterianas/genética , Animais , Anticorpos Antibacterianos/sangue , Carga Bacteriana , Proteínas de Bactérias/genética , Citocinas/análise , Modelos Animais de Doenças , Feminino , Lipoproteínas/genética , Camundongos Endogâmicos BALB C , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Análise de Sobrevida , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
10.
PLoS One ; 14(2): e0210749, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730999

RESUMO

Globally, human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in newborns, young children, and the elderly for which there is no vaccine. The RSV fusion (F) glycoprotein is a major target for vaccine development. Here, we describe a novel monoclonal antibody (designated as R4.C6) that recognizes both pre-fusion and post-fusion RSV F, and binds with nanomole affinity to a unique neutralizing site comprised of antigenic sites II and IV on the globular head. A 3.9 Å-resolution structure of RSV F-R4.C6 Fab complex was obtained by single particle cryo-electron microscopy and 3D reconstruction. The structure unraveled detailed interactions of R4.C6 with antigenic site II on one protomer and site IV on a neighboring protomer of post-fusion RSV F protein. These findings significantly further our understanding of the antigenic complexity of the F protein and provide new insights into RSV vaccine design.


Assuntos
Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Sítios de Ligação de Anticorpos , Fragmentos Fab das Imunoglobulinas/química , Vírus Sinciciais Respiratórios/química , Proteínas Virais de Fusão/química , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linhagem Celular , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Spodoptera , Proteínas Virais de Fusão/imunologia
11.
Phytother Res ; 33(4): 1074-1083, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30768733

RESUMO

Osteoporosis is characterized by low bone mineral density and microarchitectural deterioration of bone tissue. N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (MBOC) is one of the macamides isolated from Maca (Lepidium meyenii Walp.), a cruciferous plant from the Andes of Peru. In this study, C3H/10T1/2 mesenchymal stem cells were treated with MBOC in osteogenic induction medium. An ovariectomized (OVX) mouse model was used to investigate the effect of 1-month MBOC treatment on the prevention of postmenopausal osteoporosis. Remarkably, trabecular thickness, trabecular number, and bone volume/tissue volume of the distal femoral metaphysis were significantly increased in OVX + MBOC mice compared with OVX mice, as revealed by microcomputed tomography analysis. Trabecular separation was decreased in OVX + MBOC mice compared with OVX mice. Consistently, MBOC increased the levels of osteocalcin and runt-related transcription factor 2 in OVX mice, as well as the expression of runt-related transcription factor 2, osterix, and alkaline phosphatase in C3H/10T1/2 cells. Mechanistically, MBOC activates the canonical Wnt/ß-catenin signaling pathway via inhibiting phosphorylation of GSK-3ß at Tyr216 and maintaining ß-catenin expression. Collectively, the current study demonstrates the robustness of MBOC in the induction of mesenchymal stem cells osteogenic differentiation and consequent bone formation, suggesting that MBOC may be a potentially effective drug to treat postmenopausal osteoporosis.


Assuntos
Lepidium/química , Osteoporose/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Diferenciação Celular , Proliferação de Células , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Osteoporose/patologia
12.
Mol Med Rep ; 19(4): 2758-2766, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720143

RESUMO

This study was conducted to establish a stable hypobaric hypoxia brain injury model. SD rats were randomly separated into control and model groups, and placed outside or inside of a hypobaric chamber, respectively. Subsequent to 24 h anoxic exposure, plasma superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) and lactate dehydrogenase (LDH) were measured using commercial biochemical kits. Hematoxylin­eosin (H&E), Nissl's and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to observe the morphology of neurons in the hippocampus. The protein expression levels of apoptotic protease activating factor­1 (Apaf­1), hypoxia inducible factor­1α (HIF­1α), caspase­3, cleaved caspase­3, Bcl­2­associated X protein (Bax) and cytochrome c (cyto­c) were detected using western blot and immunohistochemistry analyses. Hypoxic substantially induced morphological lesions in the hippocampus concomitant with the physical behavioral performance deficit. Furthermore, hypoxia markedly exacerbated the levels of MDA, LDH and GSSG, and restrained GSH (P<0.01) and SOD (P<0.05) levels compared with the control group. In addition, hypoxia significantly induced the protein expression of Apaf­1, HIF­1α, caspase­3, cleaved caspase­3, Bax and Cyto­c (P<0.01) compared with the control group. Finally, a lower number and volume of Nissl bodies were verified in the hypoxic group. TUNEL results demonstrated a greater number of apoptotic cells in the hypoxic group. The present study demonstrates a model of rat hypoxic brain injuries induced by a hypobaric chamber at 9,000 m for 24 h. Furthermore, the redox enzyme, HIF­1α and mitochondrial apoptosis­associated protein, along with H&E and Nissl's staining, may be applied to evaluate the degree of injury.


Assuntos
Altitude , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Hipóxia/complicações , Animais , Comportamento Animal , Biomarcadores , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Expressão Gênica , Hipóxia/genética , Hipóxia/metabolismo , Imuno-Histoquímica , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Estresse Oxidativo , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
13.
Clin Gastroenterol Hepatol ; 17(7): 1303-1310.e18, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29654915

RESUMO

BACKGROUND & AIMS: The Chinese herbal medicine, MaZiRenWan (MZRW), has been used for more than 2000 years to treat constipation, but it has not been tested in a randomized controlled trial. We performed a trial to evaluate the efficacy and safety of MZRW, compared with the stimulant laxative senna or placebo, for patients with functional constipation (FC). METHODS: We performed a double-blind, double-dummy, trial of 291 patients with FC based on Rome III criteria, seen at 8 clinics in Hong Kong from June 2013 through August 2015. Patients were observed for 2 weeks and then assigned randomly (1:1:1) to groups given MZRW (7.5 g, twice daily), senna (15 mg daily), or placebo for 8 weeks. Patients were then followed for 8 weeks and evaluated at baseline and weeks 4, 8 (end of treatment), and 16 (end of follow up). Participants recorded information on stool form and frequency, feeling of complete evacuation, and research medication taken. Data on individual bowel symptoms, global symptom improvement, and adverse events were collected. A complete response was defined as an increase ≥1 complete spontaneous bowel movement (CSBM)/week from baseline (the primary outcome). Secondary outcomes included response during the follow-up period, colonic transit, individual and global symptom assessments, quality of life measured with 36-item short form Chinese version, and adverse events. RESULTS: Although there was no statistically significant difference in proportions of patients with a complete response to MZRW (68%) vs. senna (57.7%) (P = .14) at week 8, there was a statistically significant difference vs. placebo (33.0%) (P < .005). At the 16-week timepoint (after the 8-week follow-up period), 47.4% of patients had a complete response to MZRW, 20.6% had a complete response to senna, and 17.5% had a complete response to placebo (P < .005 for MZRW vs. placebo). The group that received MZRW group also had significant increases in colonic transit and reduced severity of constipation, straining, incomplete evacuation, and global constipation symptoms compared with the groups that received placebo or senna in (P < .05 for all comparisons). CONCLUSIONS: In a randomized controlled trial of 291 patients with FC, we found MZRW to be well-tolerated and effective in increasing CSBM/week. MZRW did not appear to be more effective than senna and might be considered as an alternative to this drug. ClincialTrials.gov no: NCT01695850.

14.
Chemphyschem ; 20(3): 489-498, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30548521

RESUMO

Organometal halide perovskites have been outstanding from enormous amount of functional materials thanks to their highly cost-effective processability and prominent light harvesting capacity. Unfortunately, poor long-term stability seriously hinders their further development. The recent experimental observations suggest that Cesium is a promising candidate to enhance the stability of MAPbI3 . To explore the inherent mechanism, a first-principles investigation based on density functional theory, including hybrid functional, has been performed to analyze the electronic and optical properties of perovskite series MA0.75 Cs0.25 PbI3-y Bry . The results indicate that perovskite compound MA0.75 Cs0.25 PbI2 Br is significantly superior to the other doped series in terms of optical absorption within the visible-light range. In the meanwhile, both Bader charge analysis and charge density distribution show that the compound of MA0.75 Cs0.25 PbI2 Br is the most stable among all the doped perovskite series. Moreover, it is clearly manifested that the impact of cesium is mainly embodied in the enhancement of the stability rather than in the improvement of optical absorption. Our study sheds a new light on screening new-type light harvesting materials, and provides theoretical insight into the rationale design of highly efficient and stable photovoltaic devices based on these functional materials.

15.
J Cell Biochem ; 2018 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-30417502

RESUMO

Gastric cancer (GC) is a worldwide health problem. Uncovering the underlining molecular mechanisms of GC is of vital significance. Here, we identified a novel oncogene WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in GC. WWP1 could promote GC cell proliferation and migration in vitro and expedite GC growth in vivo. We also found out two microRNAs (miRNAs): miR-129-5p and -3p could both target WWP1. Interestingly, miR-129-5p bound to the CDS region of WWP1 mRNA. The miR-129 pairs (miR-129-5p and -3p) play pivotal roles in GC to suppress its proliferation and migration in vitro and slow down GC growth in vivo by repressing WWP1. In summary, we identified two tumor suppressive miRNAs which share the same precursor that could regulate the same oncogene WWP1 in GC. Our finding would add new route for GC research and treatment.

16.
Immunol Res ; 66(4): 528-536, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30128745

RESUMO

Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Despite the multitude of capsular polysaccharide vaccines used to guard against pneumococcal disease, fatal pneumococcal disease remains epidemic due to the narrow range of protection afforded by the capsular polysaccharide vaccines and rate of change in serotypes. The most promising solution is to develop an improved protein-based vaccine with broad protection. In this study, we tested a bivalent vaccine containing antigens mixed with the fusion protein PsaA-pneumococcal surface protein A (PspA)23 and single protein PspA4, including conserved PsaA and PspA from clades 2, 3, and 4 with coverage for families 1 and 2. The vaccine induced a significant increase of anti-PspA IgG, which demonstrated cross-reactivity with the 22 different S. pneumoniae strains from serotypes contained in PPV23 by Western blot. The wide ranging protection was determined by challenging mice with S. pneumoniae from PspA clades 1 to 5. Bacterial loads in the blood and lung and survival rate after challenge were measured. After immunization, the number of bacteria in mice was significantly reduced. The clearance rates with all strains were greater than 90% in the lung, and bacterial loads in the blood were decreased to lower than 10 CFU/ml. The survival rates in immunized animals also were greatly increased (all over 50%) compared with controls. Therefore, this bivalent PspA vaccine may be a good substitute for capsular polysaccharide vaccines.


Assuntos
Adesinas Bacterianas/imunologia , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Pulmão/imunologia , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/fisiologia , Animais , Anticorpos Antibacterianos/sangue , Carga Bacteriana , Reações Cruzadas , Feminino , Humanos , Imunoglobulina G/sangue , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Sorogrupo , Vacinação
17.
Microb Pathog ; 123: 115-119, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29959043

RESUMO

Streptococcus pneumoniae is a major respiratory tract pathogen causing high levels of mortality and morbidity in infants and the elderly. In spite of the multitude of capsular polysaccharide vaccines used to guard against pneumococcal disease, fatal pneumococcal disease remains epidemic. Immunization with pneumococcal surface protein A (PspA), a highly immunogenic surface protein present in all strains of S. pneumoniae, can elicit protection against deadly pneumococcal infection. We have previously evaluated PspA in systemic vaccination. However, the mucosal immune system, as a first line of defense against respiratory infection, plays the most important role against the invasion of S. pneumoniae. In this study, we employed bacterium-like particles (BLPs) as an adjuvant for a PspA mucosal vaccine. The BLPs served as a carrier for PspA proteins bound to their surface. Mice were immunized intranasally with the PspA-BLP pneumococcal vaccine consisting of PspA3 from pneumococcal family 2. Not only did the immunized mice show a high level of serum IgG antibodies but also a high level of SIgA antibodies in the respiratory tract. After immunization with the PspA3-BLP vaccine, the mice were broadly protected against fatal intranasal challenge with homologous and heterogenous pneumococcal strains of different PspA families regardless of serotype, and the colony count was notably decreased in the lungs. Therefore, the PspA3-BLP pneumococcal vaccine has the potential to serve as a novel mucosal vaccine to enhance both systemic and mucosal immune responses to this disease.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/prevenção & controle , Streptococcus pneumoniae/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Carga Bacteriana/imunologia , Proteínas de Bactérias/administração & dosagem , Proteção Cruzada/imunologia , Imunização/métodos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/microbiologia , Sistema Respiratório/imunologia
18.
Protein Expr Purif ; 151: 56-61, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29908315

RESUMO

Streptococcus pneumoniae is a major pathogen that causes life-threatening diseases, such as pneumonia, otitis media, bacteremia, and meningitis, worldwide and especially in young children and the elderly. Pneumococcal surface protein A (PspA) is a widely studied candidate protein vaccine that represents a promising replacement for current polysaccharide and polysaccharide-conjugate vaccines. In this study, we describe a simple method to produce PspA of clade 4 from an Escherichia coli expression system using hydroxylapatite and ion-exchange chromatography. Using this method, we successfully expressed soluble PspA4 in 10 L of autoinducing culture medium, with a wet-cell yield of 19 g/L and a final PspA4 concentration of 22.8 mg/L. Additionally, we improved PspA4 purity from 17% to 70% in a single step through the use of hydroxylapatite, resulting in acquisition of recombinant PspA4 (>95% purity) at a final yield of 43% from the starting cell-lysis solution. We subsequently verified the secondary structure molecular weight of recombinant PspA4 by circular dichroism and mass spectrometry, respectively. These results demonstrated a highly efficient method for mass producing PspA4 protein and that can also be applied for purification of PspA proteins from other clades.


Assuntos
Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/isolamento & purificação , Durapatita/química , Escherichia coli/metabolismo , Cromatografia por Troca Iônica , Escherichia coli/genética , Fermentação , Expressão Gênica , Estrutura Secundária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação
19.
Infect Immun ; 86(6)2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29610257

RESUMO

Streptococcus pneumoniae is a major cause of invasive pneumococcal disease, septicemia, and meningitis that can result in high morbidity rates in children under 5 years old. The current polysaccharide-based vaccines can provide type-specific immunity, but a broad-spectrum vaccine would provide greater coverage. Therefore, developing pneumococcal-protein-based vaccines that can extend to more serum types is highly important. In this study, we vaccinated mice via the subcutaneous (s.c.) route with a systemic vaccine that is a mixture of fusion protein PsaA-PspA23 and a single protein, PspA4, with aluminum hydroxide as an adjuvant. As a comparison, mice were immunized intranasally with a mucosal vaccine that is a mixture of PspA2-PA-BLP (where PA is protein anchor and BLP is bacterium-like particle) and PspA4-PA-BLP, via the intranasal (i.n.) route. The two immunization processes were followed by challenge with Streptococcus pneumoniae bacteria from two different PspA families. Specific IgG titers in the serum and specific IgA titers in the mucosa were determined following immunizations. Bacterial loads and survival rates after challenge were compared. Both the systemic vaccine and the mucosal vaccine induced a significant increase of IgG against PspAs. Only the mucosal vaccine also induced specific IgA in the mucosa. The two vaccines provided protection, but each vaccine showed an advantage. The systemic vaccine induced higher levels of serum antibodies, whereas the mucosal vaccine limited the bacterial load in the lung and blood. Therefore, coimmunizations with the two types of vaccines may be implemented in the future.


Assuntos
Proteínas de Bactérias/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/metabolismo , Animais , Anticorpos Antibacterianos/sangue , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Vacinas Pneumocócicas/administração & dosagem , Proteínas Recombinantes
20.
Mol Cancer ; 17(1): 11, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351796

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a severe health problem worldwide. Clarifying the mechanisms for the deregulation of oncogenes and tumour suppressors in CRC is vital for its diagnosis, treatment, prognosis and prevention. Hu antigen R (HuR), which is highly upregulated in CRC, functions as a pivotal oncogene to promote CRC progression. However, the underlying cause of its dysregulation is poorly understood. METHODS: In CRC tissue sample pairs, HuR protein levels were measured by Western blot and immunohistochemical (IHC) staining, respectively. HuR mRNA levels were also monitored by qRT-PCR. Combining meta-analysis and microRNA (miRNA) target prediction software, we predicted miRNAs that targeted HuR. Pull-down assay, Western blot and luciferase assay were utilized to demonstrate the direct binding of miR-22 on HuR's 3'-UTR. The biological effects of HuR and miR-22 were investigated both in vitro by CCK-8, EdU and Transwell assays and in vivo by a xenograft mice model. JASPAR and SABiosciences were used to predict transcriptional factors that could affect miR-22. Luciferase assay was used to explore the validity of putative Jun binding sites for miR-22 regulation. ChIP assay was performed to test the Jun's occupancy on the C17orf91 promoter. RESULTS: We observed a significant upregulation of HuR in CRC tissue pairs and confirmed the oncogenic function of HuR both in vitro and in vivo. We found that an important tumour-suppressive miRNA, miR-22, was significantly downregulated in CRC tissues and inversely correlated with HuR in both CRC tissues and CRC cell lines. We demonstrated that miR-22 directly bound to the 3'-UTR of HuR and led to inhibition of HuR protein, which repressed CRC proliferation and migration in vitro and decelerated CRC xenografted tumour growth in vivo. Furthermore, we found that the onco-transcription factor Jun could inhibit the transcription of miR-22. CONCLUSIONS: Our findings highlight the critical roles of the Jun/miR-22/HuR regulatory axis in CRC progression and may provide attractive potential targets for CRC prevention and treatment.


Assuntos
Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Proteína Semelhante a ELAV 1/genética , Regulação Neoplásica da Expressão Gênica , Genes jun , MicroRNAs/genética , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Bases de Dados Genéticas , Modelos Animais de Doenças , Genes Reporter , Xenoenxertos , Humanos , Camundongos , Modelos Biológicos , Oncogenes , Interferência de RNA , Transcrição Genética
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