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1.
J Hazard Mater ; 383: 121157, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31518807

RESUMO

High doses of molybdenum (Mo) and cadmium (Cd) cause adverse reactions on animals, but the joint toxic effects of Mo and Cd on duck renal tubular epithelial cells are not fully illustrated. To investigate the combined effects of Mo and Cd on oxidative stress and mitochondrial apoptosis in primary duck renal tubular epithelial cells, the cells were either treated with (NH4)6Mo7O24·4H2O (480, 960 µM Mo), 3CdSO4·8H2O (2.5, 5.0 µM Cd) or combination of Mo and Cd for 12 h, and then the joint cytotoxicity was evaluated. The results demonstrated that Mo or/and Cd exposure could induce release of intracellular lactate dehydrogenase, reactive oxygen species generation, acidification, increase levels of malondialdehyde and [Ca2+]i, decrease levels of glutathione, glutathione peroxidase, catalase, superoxide dismutase, total antioxidant capacity, Na+/K+-ATPase, Ca2+-ATPase, and mitochondrial membrane potential; upregulate mRNA levels of Caspase-3, Bak-1, Bax, and cytochrome C, inhibit Bcl-2 mRNA level, and induce cell apoptosis in a dose-dependent manner. Furthermore, the changes of these indicators in co-treated groups were more remarkable. The results indicated that exposure to Mo or/and Cd could induce oxidative stress and apoptosis via the mitochondrial pathway in duck renal tubular epithelial cells and the two metals may have a synergistic effect.

2.
Bioresour Technol ; 295: 122248, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31627065

RESUMO

Dissolved oxygen (DO) supply plays essential roles in microbial organic acid production. Candida glabrata, as a dominant strain for producing pyruvic acid, principally converts glucose to pyruvic acid through glycolysis. However, this process relies excessively on high extracellular DO content. In this study, in combination with specific motif analysis of gene promoters, hypoxia-inducible factor 1 (HIF1) was engineered to improve the transcription level of some enzymes related to pyruvic acid synthesis under low DO level and directly led to increased pyruvic acid production and glycolysis efficiency. Moreover, the intracellular stability of HIF1 was further optimized from different aspects to maximize pyruvic acid accumulation. Finally, the pyruvic acid titer in a 5-L batch bioreactor with 10% DO level reached 53.1 g/L. As pyruvic acid is involved in the biosynthesis of various products, these findings suggest that HIF1-enabled regulation method has significant potential for increasing the synthesis of other chemicals in microorganisms.


Assuntos
Candida glabrata , Ácido Pirúvico , Reatores Biológicos , Glucose , Fator 1 Induzível por Hipóxia
3.
Fitoterapia ; 139: 104393, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31669721

RESUMO

The extract of Dioscorea zingiberensis C.H. Wright rhizomes is found to be effective in the therapy of cardiovascular disease. Steroidal saponins make substantial contribution. Previous study has proposed that methylprotodioscin (MP) may promote cholesterol efflux by increasing ABCA1 expression. But the other main saponins ingredients are not referred to. The aim of the present work was to reveal the effect and mechanism of protodioscin (PD), MP and pseudoprotodioscin (PPD) on the synthesis-related gene expression of cholesterol and triglycerides. MTT assay apoptosis assay with annexin AV-APC and 7-AAD double staining were performed. MicroRNA assay and qRT-PCR were used to analyze the gene expression which regulates synthesis of cholesterol and triglycerides. Western blot was to demonstrate the levels of target proteins. Cholesterol efflux assay was executed to study the stimulative effect of saponins on cholesterol efflux. In Hep G2 cells, PPD increased ABCA1 protein and mRNA levels, and promoted the effluxion of ApoA-1-mediated cholesterol. The underlying mechanisms involved that PPD inhibited SREBP1c and SREBP2 transcription by decreasing microRNA 33a/b levels. This procedure reciprocally led to the increase of ABCA1 levels. In THP-1 macrophages, PPD showed the similar effect, which reduced HMGCR, FAS and ACC mRNA levels and promoted low density lipoprotein receptor by decreasing the PCSK9 levels. These studies demonstrated that PPD is a potential agent for cholesterol efflux, SREBPs and microRNA 33a/b inhibition, which related to the gene expression for the synthesis of cholesterol and triglycerides.

4.
Nanoscale ; 11(46): 22261-22269, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31746907

RESUMO

Low-cost and highly effective transition metal oxides are being widely researched as one of the most promising electrocatalysts for the oxygen evolution reaction (OER). However, traditional transition metal oxides suffer from sluggish reaction kinetics due to their intrinsically poor electronic conductivity. Herein, we demonstrate a facile polydopamine-assisted carburization strategy for the confined synthesis of novel NiOx/Ni ultrathin heterostructured nanosheets. Benefiting from the large exposed surface area and fast charge transfer, the obtained ultrathin NiOx/Ni heterostructured nanosheets exhibit an overpotential of 358 mV at a current density of 10 mA cm-2 and a small Tafel slope of 51 mV dec-1, outperforming other reported representative nickel oxide based materials and commercial Ir/C catalysts. In addition, a sustainable and efficient overall water-splitting electrolyzer integrated ultrathin NiOx/Ni nanosheets with commercial Pt/C can be effectively and stably driven by solar cells.

5.
Clin Chim Acta ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31770510

RESUMO

The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31774640

RESUMO

Li-metal anode attracts great focus owing to its ultrahigh specific capacity and the lowest redox potential. However, uncontrolled growth of Li dendrite leads to severe safety hazards with limited cycle life. Herein, Al2O3 loading mesoporous carbon (Al2O3@MOF-C) derived from Al-based metal-organic frameworks (Al-MOFs) was investigated as the stable host matrix for Li metal, in which, Al2O3 was served as nano-seeds for the Li deposition and decrease the Li nucleation overpotential. Except that, the high specific surface area and wide pore distribution can also buffer the volume changes of Li and fasten electron transfer, hence a dendrite-free morphology was observed even after 50 cycles at 2 mA cm-2. High Li coulombic efficiency of 97.9% after 100 cycles at 1 mA cm-2, 1 mAh cm-2 and 97.6% after 50 cycles with increased capacity to 6 mAh cm-2 were observed for Al2O3@MOF-C electrodes. Good performances were also obtained for full cells: Li-S, and LiFePO4 batteries. The performances of Al2O3@MOF-C were compared with Li foil and Cu@Li in full cell configurations. The electrochemical tests of full cells based on Al2O3@MOF-C indicated that this Al-based functional host matrix can enhance the Li-utilization and lead to significant improvement of the cycling performance of Li anodes.

7.
J Chromatogr A ; : 460651, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31753482

RESUMO

Most of the reported covalent organic frameworks (COFs) are hydrophobic, limiting their adsorption application in sample pretreatment field. In this work, sulphonate functionalized magnetic covalent organic frameworks (COFs) composites were first synthesized by loading gold nanoparticles on Fe3O4@COF(TpBD) surface and then functionalized by sodium 3-mercaptopropanesulphonate immobilization via Au-S bonding formation (denoted as Fe3O4@COF(TpBD)@Au-MPS nanocomposites), which were further utilized as adsorbents for magnetic solid-phase extraction (MSPE) of fluoroquinolones. Compared with Fe3O4@COF(TpBD), the composites exhibited higher affinity to fluoroquinolones. Under optimized conditions, the developed MSPE method coupled with HPLC-MS/MS showed good linearity (R2 ≥0.9989) and yielded low limits of detection (0.1-1.0 µg kg-1) for fluoroquinolones. Moreover, the proposed method was successfully applied to extract fluoroquinolones from spiked meats (pork, chicken and bovine). The satisfactory recoveries were in the range of 82-110.2% with the relative standard deviations (RSDs) lower than 7.7%. These results indicated that the Fe3O4@COF(TpBD)@Au-MPS is a promising magnetic adsorbent for trace fluoroquinolones determination in meat samples. This work not only provided a facile strategy for COF functionalization, but also developed an efficient method for detecting fluoroquinolones in foodstuffs.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31753654

RESUMO

Silver nanowires (i.e., AgNWs) can act as effective surface-enhanced Raman spectroscopy (i.e., SERS) substrates to detect small molecules. However, a lot of prepared AgNWs were often wrapped by polyvinylpyrrolidone (i.e., PVP) thin film to form an insulating layer to produce ill-defined AgNWs-PVP-AgNWs interface, limiting the plasmonic coupling among the stacked AgNWs. Herein, we reported a facile method in removal of PVP ligands from AgNWs for high performance and reusable SERS substrate. Sodium borohydride (NaBH4) was used to completely remove the PVP ligands from the surface of AgNWs and produce a clean AgNWs-AgNWs interface that effectively enhances the localized surface plasmon resonance (i.e., LSPR) was produced, greatly improving the SERS activity of the AgNWs thin film. The SERS detection of rhodamine 6G (i.e., R6G) used with PVP AgNWs and without PVP AgNWs is 1.0 × 10-9 and 1.0 × 10-15 M, and the average enhancement factor (EF) is about 0.86 × 104 and 9.35 × 104, respectively. Moreover, the recyclable behavior of the AgNWs with several analyte molecules is much more interesting than that of the PVP@AgNWs. The SERS detection of AgNWs for R6G, the 3-mercaptopropionic acid (i.e., 3-MPA) and melamine with good recyclability in nanomolar and millimolar concentration can be easily detected.

9.
Brain Res Bull ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743748

RESUMO

Curtailment of sleep in modern society leads to a spectrum of neuropsychiatric disorders. However, the molecular mechanisms underlying the effects of sleep deprivation (SD) remain elusive and currently there is no effective therapy to alleviate these effects. Here, we aimed to examine SD-induced cellular and molecular alterations in mouse prefrontal cortex (PFC) and whether subchronic citalopram (CTM) treatment can negate these alterations. Three-month-old C57BL/6 J mice were divided into control (Ctrl), SD, CTM alone and CTM + SD groups. CTM and CTM + SD group mice were treated with CTM for five consecutive days at a dose of 10 mg/kg per day before the experimental procedure. SD and CTM + SD group mice were sleep-deprived for 24 h using an automated treadmill method. We found that 24 h SD causes a marked reduction in the levels of phosphorylated calcium/calmodulin kinase II (pCaMKII), phosphorylated cyclic AMP-responsive element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in mouse PFC. Patch clamp recording of pyramidal neurons from acute PFC slices revealed that SD decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), suggesting a SD-induced postsynaptic alteration. Interestingly, subchronic CTM treatment prevents such SD-induced reductions in pCaMKII, pCREB and BDNF levels, and in mEPSC amplitude. These data suggest that CTM offers neuroprotection against SD-induced molecular and electrophysiological alterations.

10.
Int J Hyperthermia ; 36(1): 1129-1136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31744350

RESUMO

Background: Tertiary hyperparathyroidism (THPT) is very common in hemodialysis patients with secondary hyperparathyroidism. However, a medical treatment is not indicated for THPT.Purpose: To investigate the feasibility, safety and efficacy of microwave ablation (MWA) in treating THPT.Materials and methods: Twenty-three patients with THPT were enrolled and treated with MWA. Clinical characteristics, serum levels of intact parathyroid hormone (iPTH), calcium, phosphorus and alkaline phosphatase (ALP), as well as treatment outcomes, were evaluated pre- and post-MWA. All patients were followed for >36 months for all assessable clinical data.Results: All patients successfully completed MWA. The mean follow-up was 47.0 ± 8.4 months. Immediately 1-day post-MWA, iPTH, calcium, phosphorus and ALP levels significantly decreased (all p < 0.001). During the long-term follow-up, iPTH levels increased gradually until 24 months and then remained at stable levels. After MWA, serum calcium reached stable levels at 24 months, while phosphorus and ALP reached stable levels at 6 months, and the levels were in the normal range or slightly higher than the upper normal limit. No obvious blood flow signals or significant recurrence was observed in the surgical nodules during follow-up. In the last follow-up, all nodules were persistent, but their maximum diameter and average volume were significantly lower after MWA (both p < 0.001), with an average reduction of 75.9 ± 11.3%. All patients had no major complications during MWA and follow-up.Conclusions: MWA is feasible, safe, effective and minimally invasive in treating THPT. Thus, MWA can be a nonsurgical alternative for treating THPT patients who are ineligible for surgery.

11.
Int J Mol Med ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31746346

RESUMO

The steroidal saponin RCE­4 (1ß, 3ß, 5ß, 25S)­spirostan­1, 3­diol 1­[α­L­rhamnopyranosyl­(1→2)­ß­D­xylopyranoside], isolated from Reineckia carnea, exerts significant anti­cervical cancer activity by inducing apoptosis. The potential effect of RCE­4 on proliferation inhibition and autophagy induction has rarely been studied. Therefore, the focus of the present study was to investigate the effects of RCE­4 on proliferation, and to elucidate the detailed mechanisms involved in autophagy induction in cervical cancer cells. CaSki cells were treated with RCE­4 or/and autophagy inhibitors, and the effect of RCE­4 on cellular proliferation was assessed by MTT assay. The pro­autophagic properties of RCE­4 were subsequently confirmed using monomeric red fluorescent protein­green fluorescent protein­microtubule­associated proteins 1A/1B light chain 3B (LC3) adenoviruses and CYTO­ID autophagy assays, and by assessing the accumulation of lipid­modified LC3 (LC3II). The mechanisms of RCE­4­induced autophagy were investigated by western blot analysis. The results demonstrated that inhibiting autophagy significantly promoted RCE­4­induced cell death, indicating that autophagy served a protective role following RCE­4 treatment. In addition, RCE­4­induced autophagy was reflected by increased expression levels of the serine/threonine­protein kinase ULK1, phosphorylated (p)­ULK1, p­Beclin­1 and LC3II, the formation of autophagosomes and autolysosomes, and sequestosome 1 (p62) degradation. Subsequent analysis indicated that RCE­4 activated the AMP­activated protein kinase (AMPK) pathway by upregulating AMPK and p­AMPK, and also inhibited the PI3K and extracellular signal­regulated kinase (ERK) signaling pathways by downregulating p­PI3K, p­Akt, p­mTOR, Ras, c­Raf, p­c­Raf, dual specificity mitogen­activated protein kinase kinase (MEK)1/2, p­MEK1/2 and p­Erk1/2. Additionally, with increased treatment times RCE­4 may impair lysosomal cathepsin activity and inhibit autophagy flux by suppressing the expression of AMPK, p­AMPK, ULK1, p­ULK1 and p­Beclin­1, and upregulating that of p62. These results indicated that the dual RCE­4­induced inhibition of the PI3K and ERK pathways may result in a more significant anti­tumor effect and prevent chemoresistance, compared with the inhibition of either single pathway; furthermore, dual blockade of PI3K and ERK, and the AMPK pathway may be involved in the regulation of autophagy caused by RCE­4. Taken together, RCE­4 induced autophagy to protect cancer cells against apoptosis, but AMPK­mediated autophagy was inhibited in the later stages of RCE­4 treatment. In addition, autophagy inhibition improved the therapeutic effect of RCE­4. These data highlight RCE­4 as a potential candidate for cervical cancer treatment.

12.
Mol Genet Genomic Med ; : e1028, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31713353

RESUMO

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital malformation in the world. Both environment and genetics are involved with the etiology of the disease. Genome-wide association studies have identified two single nucleotide polymorphisms (SNPs) at chromosome 20q12 to be associated with NSCL/P. The current study aimed to explore the association of the two SNPs at 20q12 with NSCL/P and different subtypes in a Southern Chinese Han cohort. METHODS: A total of 430 NSCL/P patients and 451 controls were recruited in the current study. Two SNPs including rs17820943 and rs6072081 at 20q12 were genotyped in the study cohort using Taqman SNP genotyping analysis. Chi-Square test was used to compare allele and genotype frequencies of NSCL/P patients and control group. RESULTS: Case-control analysis showed that the allele and genotype of rs17820943 and rs6072081 were significantly associated with NSCL/P (p < .01). Comparison between subtypes of NSCL/P and controls showed that frequencies of the G allele and GG genotype of rs6072081 (p = 4.52 × 10-4 and p = .001 respectively), and those of the T allele and TT genotype of rs17820943 (p = 6.7 × 10-5 and p = 1.71 × 10-4 respectively) were decreased in cleft lip and palate (CLP). No significant association of the two SNPs with cleft lip only (CLO) and cleft palate only (CPO) was found (p > .05). CONCLUSION: These results showed that rs17820943 and rs6072081 at 20q12 were associated with NSCL/P, especially with the CLP subtype in a Southern Chinese Han cohort.

13.
Neurol Sci ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713753

RESUMO

OBJECTIVE: This study investigated the effects of transcranial direct current stimulation (tDCS) combined with conventional swallowing training on the swallowing function in brainstem stroke patients with cricopharyngeal muscle dysfunction (CPD). METHODS: Twenty-eight brainstem stroke patients with CPD were assigned randomly to an anodal tDCS group or a sham tDCS group. The patients received anodal tDCS or sham tDCS over the bilateral oesophageal cortical area combined with simultaneous catheter balloon dilatation and conventional swallowing therapy for 20 days. Swallowing function was assessed using the functional oral intake scale (FOIS) and the functional dysphagia scale (FDS) and by measuring the pharyngoesophageal Segment Opening (PESO) before and immediately after the intervention. RESULTS: Both groups showed a significant improvement in the FDS, FOIS and PESO scores immediately after the intervention (all p < .005). However, compared with the sham stimulation group, the anodal tDCS group showed greater improvements in the FDS, FOIS and PESO scores immediately after the intervention (all p < .005). CONCLUSION: The bihemispheric anodal tDCS combined with simultaneous catheter balloon dilatation and conventional swallowing therapy effectively improves the swallowing function in patients with CPD caused by a brainstem stroke. tDCS may be an effective adjuvant therapy in CPD rehabilitation.

14.
Hum Brain Mapp ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713952

RESUMO

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

15.
Eur J Surg Oncol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31677940

RESUMO

BACKGROUND: Both radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) are minimally invasive approach for hepatocellular carcinoma (HCC) at early stage. This study aimed to compare the efficacy of RFA and LH for treating HCC with a large cohort. METHODS: From March 2014 to July 2016, 477 patients who underwent RFA (n = 314) or LH (n = 163) for HCC tumors meeting the criteria were included. Overall survival (OS) and recurrence-free survival (RFS) were compared. Propensity score matching (PSM) was performed to balance for the factors that may affect the choice of treatment. RESULTS: Collectively, the 1-, 2- and 3-year OS rates were significantly greater after LH than RFA, as well the corresponding RFS rates, before and after PSM by 2:1. However, the RFA group had fewer major complications (P=0.004), shorter postoperative stays (P=0.023) and lower hospital charges (P<0.001) than the LH group. In the subgroup analysis, RFA demonstrated comparable RFS in treating less than 3 cm tumor (P=0.22) located in noncentral bisection (SII, SIII, SVI, SVII) and tumor between 3 cm and 5 cm (P=0.07) located in central bisections (SIV, SV, SVIII). The female, HBV infection, and RFA are factors of worse OS, and the latter two factors also indicated higher RFS. CONCLUSIONS: Though, LH possessed superior intrahepatic control rate than RFA in most condition of tumor smaller than 5 cm, the RFA could be an optimal approach achieved comparable outcomes in patients with centrally located HCC, with fewer major complications, shorter postoperative stays and lower hospital charges.

16.
Cell Death Dis ; 10(11): 833, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685801

RESUMO

RBBP6 has been implicated in tumorigenesis but its role in tumor metastasis and progression has not been evaluated. Interestingly, here we show that RBBP6 is upregulated in colorectal cancer (CRC) where its expression level is positively correlated with distant metastasis. In this study, we identified RBBP6, a RING Finger-domain E3 ubiquitin ligase, served as an independent prognostic factor and predicted poor outcome for CRC patients. RBBP6 promoted cell proliferation, migration, and invasion in CRC cells and promoted tumor growth, lung metastasis, and liver metastasis in mouse models. Mechanistically, we revealed that RBBP6 bound and ubiquitylated IκBα, an inhibitor of the NF-κB-signaling pathway. RBBP6-mediated ubiquitination and degradation of IκBα significantly enhanced p65 nuclear translocation, which triggered the activation of NF-κB pathway and then induced the epithelial-mesenchymal transition (EMT) process and cell metastasis. Furthermore, by DNA methylation results and ChIP analysis, we demonstrated that the promoter of RBBP6 was hypomethylated, and was activated by multi-oncogenic transcription factors. In conclusion, our findings suggest that RBBP6 may be a potential prognostic biomarker and therapeutic target for CRC invasion and metastasis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31699591

RESUMO

In this work, a primary method was constructed for detecting hydrazine in plant, thus accomplished the closed-loop monitoring of hydrazine circulation within manufacture, environment, plants, animals and human. From a series of sensors, QYL-1 was selected to present the hydrazine sensing properties. As a preliminary tool, QYL-1 suggested the ultra-wide linear range (0-20.0 equivalent) and high selectivity, which were extremely essential for linking the monitoring in various scale and field. For the first time, concentration-dependent tracking of hydrazine was successfully performed in Arabidopsis Thaliana root tips. Afterwards applications in water samples and living MCF-7 cells then fulfilled the demonstration of closing the loop by linking both the upstream and downstream nodes. More than raising a practical method, this work offered initial information for the closed-loop monitoring of hydrazine circulation, which might be significant for the ideal systematic managing in future.

18.
J Ultrasound Med ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31702068

RESUMO

OBJECTIVES: To prepare optimized prostate-specific membrane antigen (PSMA) single-chain variable fragment (scFv)-loaded nanobubbles (NBs) as a novel targeted ultrasound (US) contrast agent for diagnosis and treatment of prostate cancer (PCa). METHODS: Prostate-specific membrane antigen scFv-loaded NBs were prepared by membrane hydration and biotin-streptavidin conjugation. Flow cytometry was used to observe the binding rate of the targeted NBs to PSMA-expressing cells. Contrast-enhanced US was used to monitor targeted and nontargeted NBs administered to nude mice with 22RV1, LNCaP, and PC-3 xenograft tumors. The specific binding ability of the targeted NBs was further examined by fluorescence imaging of tumor cryosections. RESULTS: Uniformly sized targeted NBs were successfully prepared (mean ± SD, 485.3 ± 28.4 nm). The NBs showed good stability and bound specifically to LNCaP and 22RV1 cells with high PSMA expression in vitro but did not bind to PC-3 cells without PSMA expression. The targeted NBs presented good US enhancement, and the results of the in vivo xenograft tumor nude mouse model showed that the peak contrast intensity in LNCaP and 22RV1 cells was significantly higher for the targeted NBs than the nontargeted NBs (P < .05), whereas there was no significant difference in PC-3 cells. Immunofluorescence results obtained from tumor sections confirmed that the targeted NBs were capable of targeting PSMA-expressing tumor cells. CONCLUSIONS: These novel PSMA scFv-loaded NBs have proven to be an excellent US contrast agent for imaging PSMA-expressing PCa and have the potential to not only enable efficient and safe molecular imaging but also to serve as a delivery system for targeted PCa therapies.

19.
J Immunol Methods ; : 112685, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678214

RESUMO

Promiscuous peptides that can be presented by multiple human leukocyte antigens (HLAs) have great potential for the development of vaccines with wide population coverage. However, the current available methods for the prediction of peptides that bind to major histocompatibility complex (MHC) are mainly aimed at the rapid or mass screening of potential T cell epitopes from pathogen antigens or proteomics. The current approaches do not allow deciphering the contribution of the residue at each peptide position to the promiscuous binding ability of the peptide or obtaining guidelines for the design of promiscuous peptides. In this study, we re-evaluated and characterized four matrix-based prediction models that have been extensively used for the prediction of HLA-binding peptides and found that the prediction models generated based on the average relative binding (ARB) matrix shared a consistent and conservative threshold for all well-studied HLA class I alleles. Evaluations performed using datasets of HLA supertype-specific peptides with various cross-binding abilities and peptide mutant analogues indicated that the ARB-based binding matrices could be used to decipher and design promiscuous peptides that bind to multiple HLA molecules. A web-based tool called PromPDD was developed using ARB matrix-based models, and this tool enables the prediction, deciphering and design of promiscuous peptides that bind to multiple HLA molecules within or across HLA supertypes in a simpler and more direct manner. Furthermore, we expanded the application of PromPDD to HLA class I alleles with limited experimentally verified data by generating pan-specific matrices using a derived modular method, and 2641 HLA molecules encoded by HLA-A and HLA-B genes are available in PromPDD. PromPDD, which is freely available at http://www.immunoinformatics.net/PromPDD/, is the first tool for the deciphering and design of promiscuous peptides that bind to HLA class I molecules.

20.
J Cell Biochem ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724756

RESUMO

Associated with reduced hydrogen sulfide (H2 S) production in Hcy metabolic disorders, Plasma Hcy accumulation can bring about vascular dysfunction. Nevertheless, recently proposed therapies for vascular damage by estrogen could contribute to promoting endogenous hydrogen sulfide production. This study explores whether estrogen can come into play in protection in hyperhomocysteinemia and hypertensive patients at a population level, and then analyses the specific mechanism of estrogen protection in homocysteine (Hcy)-treated human umbilical vein endothelial cells (HUVECs) at the foundational level. A case-control study, conducted on 1277 female hypertension and non-hypertensive patients from Hunan Provincial People's Hospital, showed that the Hcy concentration of hypertensive patients emerged higher than that of healthy controls (P < .001), and that of estrogen was the reverse (P < .001). Estrogen had a negative correlation with systolic blood pressure and plasma Hcy concentration. HUVECs were treated with estrogen and Hcy in the basic experimental part, and 17ß-estradiol (E2ß) stimulated proliferation and inhibited damage in Hcy-treated umbilical vein endothelial cells. Treatment with Hcy dampens the expression of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) then cuts down H2 S production in cultured HUVECs, however, E2ß reverses this process. To sum up, we have demonstrated a significant correlation between estrogen, Hcy concentration and systolic blood pressure reduction, which is bound up with Hcy metabolism and endogenous hydrogen sulfide production. The role of E2ß was further strengthened by CBS and the CSE inhibitor through overthrowing the change in hydrogen sulfide of Hcy-treated HUVECs.

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