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1.
J Exp Clin Cancer Res ; 38(1): 387, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488195

RESUMO

In the original publication of this article [1], the Fig. 7 is wrong, but does not affect discussions and conclusions drawn in the article.

2.
Org Biomol Chem ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475277

RESUMO

A B(C6F5)3-catalyzed divergent cyanosilylation of chromones has been successfully realized. A variety of 4-oxochromane-2-carbonitriles were furnished as kinetic products in high yields via 1,4-cyanosilylations. An unexpected C-O bond cyanosilylation was achieved when the temperature was raised to 80 °C, affording 4-oxo-4-(2-hydroxylphenyl)but-2-enenitriles as thermodynamic products in 72-94% yields, which was confirmed by DFT results.

3.
Mol Oncol ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385424

RESUMO

Most human cancers develop from stem and progenitor cell populations through the sequential accumulation of various genetic and epigenetic alterations. Cancer stem cells have been identified from medulloblastoma (MB), but a comprehensive understanding of MB stemness, including the interactions between the tumor immune microenvironment and MB stemness, is lacking. Here, we employed a trained stemness index model based on an existent one-class logistic regression (OCLR) machine-learning method to score MB samples; we then obtained two stemness indices, a gene expression-based stemness index (mRNAsi) and a DNA methylation-based stemness index (mDNAsi), to perform an integrated analysis of MB stemness in a cohort of primary cancer samples (n = 763). We observed an inverse trend between mRNAsi and mDNAsi for MB subgroup and metastatic status. By applying the univariable Cox regression analysis, we found that mRNAsi significantly correlated with overall survival (OS) for all MB patients, whereas mDNAsi had no significant association with OS for all MB patients. In addition, by combining the Lasso-penalized Cox regression machine-learning approach with univariate and multivariate Cox regression analyses, we identified a stemness-related gene expression signature that accurately predicted survival in patients with Sonic hedgehog (SHH) MB. Furthermore, positive correlations between mRNAsi and prognostic copy number aberrations in SHH MB, including MYCN amplifications and GLI2 amplifications, were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.

4.
J Exp Clin Cancer Res ; 38(1): 336, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375140

RESUMO

In the original publication of this article [1], the authors reported the order of the authors was incorrect and needs to be revised. The original article has been updated to rectify this error.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31410834

RESUMO

Fixed-bed studies were performed to evaluate the removal efficiency of copper (Cu(II)) from aqueous solution using chitosan-coated bentonite (CCB), chitosan-coated sand (CCS), and chitosan-coated kaolinite (CCK). The thermal and morphological properties of CCB, CCK, and CCS were characterized using thermogravimetric analysis, Fourier transform infrared spectroscopy, and the Brunauer-Emmett-Teller method. Dynamic experiments were carried out to investigate the effect of solution pH (3.0 to 5.0) and initial Cu(II) concentration (200 to 1000 mg/L) on the time to reach breakthrough (tb), total volume of treated effluent (Veff), and adsorption capacity at breakthrough (qb). Results show that increasing the initial Cu(II) concentration inhibits the column performance where lower Veff, tb, and qb were obtained. Decreasing the pH from 5.0 to 3.0 led to improved removal efficiency with higher values of Veff, tb, and qb. Under pH 3.0 and 200 mg/L, the maximum removal efficiency of 68.60%, 56.10%, and 58.90% for Cu(II) was attained using CCB, CCS, and CCK, respectively. The Thomas model was determined to adequately predict the breakthrough curves based on high values of coefficient of determination (R2 ≥ 0.8503). Regeneration studies were carried out using 0.1 M HCl and 0.1 M NaOH solution in the saturated column of CCB, CCK, and CCS.

6.
Eur J Med Chem ; 182: 111611, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31445230

RESUMO

Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyze the hydrolysis of phosphorylated substrates under acidic to neutral conditions. Elevated serum concentrations of PAP are observed in patients suffering from osteoporosis, identifying this enzyme as a potential target for the development of novel therapeutic agents to treat this disease. α-Alkoxy-substituted naphthylmethylphosphonic acid derivatives have been identified previously as molecules that bind with high affinity to PAPs, and docking studies suggest that longer alkyl chains may increase the binding affinities of such compounds. Here, we synthesized several derivatives and tested their inhibitory effect against pig and red kidney bean PAPs. The most potent inhibitor within this series is the octadecyl derivative, which has a Ki value of ∼200 nM. Crystal structures of the dodecyl and octadecyl derivatives bound to red kidney bean PAP show that the length of the alkyl chain influences the ability of the phosphonate group to interact directly with the bimetallic center. These structures represent the first examples of potent inhibitors bound to a PAP that have drug-like properties. This study provides a starting point for the development of much needed new treatments for osteoporosis.

8.
J Environ Manage ; 249: 109418, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442910

RESUMO

The remnant of heavy oil, often expressed as total petroleum hydrocarbons (TPHs), in soil and/or sludge is commonly encountered by and often ruins the habitat of some indigenous insects. Recent studies indicate that some of the insects could stand the impact and some not just survived but might serve as an oil degrader. The potential of using indigenous insects in treating oil pollution is of interests in this study. In Asia, the potential oil-exposed rhinoceros beetle, Oryctes rhinoceros, was studied herein due to two major interests: one is its tolerance to heavy oil, and the other its ability to remove the oil. Two sets of the experiments spiked with different amounts of heavy oil were conducted in series, and the results of the larval mortality rate, growth rate, feces production, substrate conversion ratio and percent of oil removal were monitored as performance indicators during these treatments. The obtained results showed that the ingestion of heavy oil at a 5000 mg/kg level significantly deteriorated the survival rate (37% left) of the tested larvae, yet oil-experienced larvae could survive in up to 10,000 mg/kg of heavy oil (100% survived). As for the heavy oil removal via larval ingestion, at a 10,000 mg/kg level of oil in the substrate, the percent of weekly removal of heavy oil by larva ingestion was consistent throughout the second run at 56.4 ±â€¯5.6%. These results demonstrated the potential use of beetle larvae as a bioreactor in pollutant removal.

9.
Neurosci Lett ; 709: 134377, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31352043

RESUMO

The song control system in the brain of songbirds is important for the production and acquisition of song and exhibits some of the largest neural sex differences observed in vertebrates. The robust nucleus of the arcopallium (RA) is a premotor nucleus, playing a key role in controlling singing. RA projection neurons (PNs) receives denser synapse inputs including excitatory in males than in females. However, the inhibitory synaptic transmission in the RA has not been reported. In the present study, using whole-cell voltage-clamp recording, spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) of the males and females were recorded. The average frequency and amplitude of sIPSCs/mIPSCs in males were higher than females. These results demonstrate the sexually dimorphic of the inhibitory synaptic transmission in the RA PNs and the RA PNs in males receive more inhibitory synaptic transmission. These findings contribute to further illuminate the neural mechanisms under the sexually dimorphism song production of adult zebra finches.

10.
Molecules ; 24(13)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277493

RESUMO

In the present research, treatment of contaminated groundwater via adsorption of As(V) with an initial concentration of 50.99 µg/L using chitosan-coated bentonite (CCB) was investigated. The effect of adsorbent mass (0.001 to 2.0 g), temperature (298 to 328 K), and contact time (1 to 180 min) on the removal efficiency was examined. Adsorption data was evaluated using isotherm models such as Langmuir, Freundlich, and Dubinin-Radushkevich. Isotherm study showed that the Langmuir (R2 > 0.9899; χ2 ≤ 0.91; RMSE ≤ 4.87) model best correlates with the experimental data. Kinetics studies revealed that pseudo-second order equation adequately describes the experimental data (R2 ≥ 0.9951; χ2 ≤ 0.8.33; RMSE ≤ 4.31) where equilibrium was attained after 60 min. Thermodynamics study shows that the As(V) adsorption is non-spontaneous (ΔG0 ≥ 0) and endothermic (ΔH0 = 8.31 J/mol) that would result in an increase in randomness (ΔS0 = 29.10 kJ/mol•K) within the CCB-solution interface. FT-IR analysis reveals that hydroxyl and amino groups are involved in the adsorption of As(V) from groundwater. Results of the present research serve as a tool to determine whether CCB is an environmentally safe and cost effective material that could be utilized in a permeable reactive barrier system for the remediation of As(V) from contaminated groundwater.

11.
Proc Natl Acad Sci U S A ; 116(26): 12986-12995, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31182587

RESUMO

The aberrant hedgehog (Hh) pathway plays important roles in multiple cancer types, therefore serving as a promising drug target. Current clinically available hedgehog-targeted drugs act mostly by antagonizing the upstream component smoothened; however, both primary and acquired resistance to FDA-approved smoothened inhibitor (SMOi) drugs have been described. We have recently demonstrated that the BET inhibitor effectively suppresses SMOi-resistant Hh-driven cancers through antagonizing transcription of GLI1 and GLI2, the core transcriptional factors of Hh pathway, suggesting epigenetic or transcriptional targeted therapy represents an anti-Hh therapeutic strategy that can overcome SMOi resistance. Here we performed an unbiased screening of epigenetic or transcriptional targeted small molecules to test their inhibitory effects on GLI1 and GLI2 transcription or cell viability of Hh-driven tumor lines. THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), is identified as the top hit in our screening. We then confirmed that antagonizing CDK7 by either small-molecule inhibitors or the CRISPR-Cas9 approach causes substantial suppression of GLI1 and GLI2 transcription, resulting in effective inhibition of Hh-driven cancers in vitro and in vivo. More importantly, antagonizing CDK7 retains inhibitory activity against Hh-driven cancers with almost all so-far described primary or acquired SMOi resistance. Furthermore, we reveal a synergy between CDK7 inhibition and BET inhibition on antagonizing aberrant Hh pathway and Hh-driven cancers that are either responsive or resistant to SMOi. Our results illustrate transcriptional inhibition through targeting CDK7 as a promising therapeutic strategy for treating Hh-driven cancers, especially those with primary or acquired resistance to SMOi drugs.

12.
Anal Bioanal Chem ; 411(17): 3871-3880, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31209551

RESUMO

Polymerase chain reaction (PCR) is a powerful technique for the detection and quantification of nucleic acids and has enormous applications to research in molecular biology. Certain inherited diseases, caused by single nucleotide mutations, however, are difficult to identify by PCR, using DNA primers and probes, in a situation where a false diagnosis may lead to incorrect or delayed treatment. With the aim of enhancing the specificity of PCR, we used novel chemically synthesized oligonucleotides containing site-specific methyl phosphotriester (MPTE) inter-nucleoside linkage(s) as primers and probes. The methyl phosphotriester linkages carry no charge, so the reduction in the electrostatic repulsion of an MPTE-DNA/DNA duplex shows stronger hybridization affinity compared to a DNA/DNA duplex. However, the electrosteric effects introduced by the methyl group may result in instability of the double-stranded DNA (dsDNA) formed. With the use of specific MPTE modification sites and optimization of the number of MPTE modifications, greater delta melting temperature (ΔTm) may be obtained, in concert with adjustment of PCR operating conditions, especially with respect to the annealing temperature, to achieve more discriminatory results between the target template and the perfectly matched primer and the mismatched primer. In single nucleotide polymorphism (SNP) genotyping, the results demonstrated that MPTE-modified probes can improve specificity. In summary, MPTE-modified oligonucleotides are a promising DNA analog applied to PCR primers and probes to enhance the specificity and to provide more precise detection results for various applications, such as for genetic diagnosis. In summary, two common DNA polymerases we tested could successfully recognize the MPTE-modified primers and probes. Under the optimal operating conditions, MPTE modification has the ability to improve the discrimination of single nucleotide polymorphism by increasing the ΔTm of the perfect match and mismatch sequences and to provide more precise detection results for various applications, such as genetic diagnosis.


Assuntos
Primers do DNA/química , Fosfatos/química , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sondas de DNA , DNA Polimerase Dirigida por DNA/metabolismo , Genótipo , Metilação , Técnicas de Diagnóstico Molecular
13.
Clin Exp Ophthalmol ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215760

RESUMO

IMPORTANCE: Detection of early onset neovascular age-related macular degeneration (AMD) is critical to protecting vision. BACKGROUND: To describe the development and validation of a deep-learning algorithm (DLA) for the detection of neovascular age-related macular degeneration. DESIGN: Development and validation of a DLA using retrospective datasets. PARTICIPANTS: We developed and trained the DLA using 56 113 retinal images and an additional 86 162 images from an independent dataset to externally validate the DLA. All images were non-stereoscopic and retrospectively collected. METHODS: The internal validation dataset was derived from real-world clinical settings in China. Gold standard grading was assigned when consensus was reached by three individual ophthalmologists. The DLA classified 31 247 images as gradable and 24 866 as ungradable (poor quality or poor field definition). These ungradable images were used to create a classification model for image quality. Efficiency and diagnostic accuracy were tested using 86 162 images derived from the Melbourne Collaborative Cohort Study. Neovascular AMD and/or ungradable outcome in one or both eyes was considered referable. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: In the internal validation dataset, the AUC, sensitivity and specificity of the DLA for neovascular AMD was 0.995, 96.7%, 96.4%, respectively. Testing against the independent external dataset achieved an AUC, sensitivity and specificity of 0.967, 100% and 93.4%, respectively. More than 60% of false positive cases displayed other macular pathologies. Amongst the false negative cases (internal validation dataset only), over half (57.2%) proved to be undetected detachment of the neurosensory retina or RPE layer. CONCLUSIONS AND RELEVANCE: This DLA shows robust performance for the detection of neovascular AMD amongst retinal images from a multi-ethnic sample and under different imaging protocols. Further research is warranted to investigate where this technology could be best utilized within screening and research settings.

14.
JACC Cardiovasc Interv ; 12(12): 1164-1171, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31221307

RESUMO

OBJECTIVES: The authors sought to better understand the stent geometry of the Lotus valve after transcatheter aortic valve replacement (TAVR) and its potential implications for valve size selection. BACKGROUND: The authors hypothesized that the greatest interference between the frame and aortic valvar complex occurs across the aortic valve leaflets. METHODS: The authors retrospectively analyzed the multidetector computed tomography (MDCT) scans of 32 consecutive patients undergoing Lotus valve (Boston Scientific, Natick, Massachusetts) implantation. The prosthesis cross section was analyzed at 3-mm increments along its length. The plane where the frame had the smallest area was defined as the waist. The corresponding plane of the waist on pre-procedural MDCT was identified by surrounding structures such as calcium deposits, commissural fusion, and commissural gaps, and was referred to as the supra-annulus. The spline of the supra-annulus was circumscribed with reference to the post-implant stent geometry at the waist. RESULTS: The waist was 5.8 ± 1.7 mm higher than the native annulus on post-procedural MDCT. The waist had a nearly 2-fold larger compression rate than the stent at the native annulus level (36.3 ± 10.4% vs. 18.9 ± 9.6%; p < 0.01), irrespective of valve morphologies. The supra-annulus was 5.9 ± 1.6 mm higher than the annulus on pre-procedural MDCT. Patients had an approximately 17% decrease in area from the annulus to the supra-annulus (18.3 ± 4.4% for bicuspid morphology and 16.0 ± 3.5% for tricuspid morphology). CONCLUSIONS: Major interference between the implanted prosthesis and anatomy occurred at a level above the annulus. The decrease in area from the annulus to supra-annulus may explain the feasibility of implanting a smaller valve than that suggested by traditional annular measurements.

15.
Breast Cancer Res Treat ; 177(2): 419-426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203487

RESUMO

PURPOSE: The present study aimed to determine suitable optimal classifiers and investigate the general applicability of computer-aided diagnosis (CAD) to compare magnetic resonance (MR)-CAD with MR imaging (MRI) in distinguishing benign from malignant solid breast masses. METHODS: We analyzed a total of 251 patients (mean age: 44.8 ± 12.3 years; range: 21-81 years) with 274 breast masses (154 benign masses, 120 malignant masses) using a Gaussian mixture model and a random forest machine model for segmentation and classification. RESULTS: The diagnostic performance of MRI alone and MRI plus CAD were compared with respect to sensitivity, specificity, and area under the curve (AUC), using receiver operating characteristic curve analysis. The discriminating power to detect malignancy using MR-CAD with an AUC of 0.955 (sensitivity was 95.8% and the specificity was 92.9%) was significantly higher than that of MRI alone with an AUC of 0.785 (sensitivity was 71.7% and the specificity was 85.7%). CONCLUSION: CAD is feasible to differentiate breast lesions, and it can complement MRI, thereby making it easier to diagnose breast lesions and obviating the need for unnecessary biopsies.

16.
Zhongguo Zhen Jiu ; 39(6): 632-6, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31190501

RESUMO

OBJECTIVE: To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotine-exposure-induced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats. METHODS: A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotine-ST 36 group (N + ST 36 group) and a nicotine-GB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotine-exposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture. RESULTS: Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all P<0.01), additionally, alveoli were fused and ruptured, alveolar wall thickened, the numbers of alveoli reduced, the interspace of alveoli enlarged and the diameter increased (P<0.01). Compared with the N group, in the N+ST 36 group, PEF and Cdyn were increased, PIF, RI and RE reduced (P<0.05, P<0.01), the alveolar fusion and rupture relieved, the numbers of alveoli increased, alveolar wall thinner, the interpsace of alveoli became normal and the diameter was reduced significantly (P<0.01). In the N+GB 34 group, the changes of lung function and morphological indicators were not significant (P>0.05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotine-exposure-induced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).


Assuntos
Eletroacupuntura , Pulmão , Nicotina , Pontos de Acupuntura , Animais , Animais Recém-Nascidos , Feminino , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Nicotina/toxicidade , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
17.
J Exp Clin Cancer Res ; 38(1): 263, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208444

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common tumors in the worldwide, it develops resistance to radiotherapy during treatment, understanding the regulatory mechanisms of radioresistance generation is the urgent need for HCC therapy. METHODS: qRT-PCR, western blot and immunohistochemistry were used to examine MCM3 expression. MTT assay, colony formation assay, terminal deoxynucleotidyl transferase nick end labeling assay and In vivo xenograft assay were used to determine the effect of MCM3 on radioresistance. Gene set enrichment analysis, luciferase reporter assay, western blot and qRT-PCR were used to examine the effect of MCM3 on NF-κB pathway. RESULTS: We found DNA replication initiation protein Minichromosome Maintenance 3 (MCM3) was upregulated in HCC tissues and cells, patients with high MCM3 expression had poor outcome, it was an independent prognostic factor for HCC. Cells with high MCM3 expression or MCM3 overexpression increased the radioresistance determined by MTT assay, colony formation assay, TUNEL assay and orthotopic transplantation mouse model, while cells with low MCM3 expression or MCM3 knockdown reduced the radioresistance. Mechanism analysis showed MCM3 activated NF-κB pathway, characterized by increasing the nuclear translocation of p65, the expression of the downstream genes NF-κB pathway and the phosphorylation of IKK-ß and IκBα. Inhibition of NF-κB in MCM3 overexpressing cells using small molecular inhibitor reduced the radioresistance, suggesting MCM3 increased radioresistance through activating NF-κB pathway. Moreover, we found MCM3 expression positively correlated with NF-κB pathway in clinic. CONCLUSIONS: Our findings revealed that MCM3 promoted radioresistance through activating NF-κB pathway, strengthening the role of MCM subunits in the tumor progression and providing a new target for HCC therapy.

18.
J Pain ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31085334

RESUMO

Our preliminary experiment indicated the activation of with-nolysine kinases 1 (WNK1) in bone cancer pain (BCP) rats. This study aimed to investigate the underlying mechanisms via which WNK1 contributed to BCP. A rat model of BCP was induced by Walker-256 tumor cell implantation. WNK1 expression and distribution in the lumbar spinal cord dorsal horn and dorsal root ganglion were examined. SPS1-related proline/alanine-rich kinase (SPAK), oxidative stress-responsive kinase 1 (OSR1), sodium-potassium-chloride cotransporter 1 (NKCC1), and potassium-chloride cotransporter 2 (KCC2) expression were assessed. Pain behaviors including mechanical allodynia and movement-evoked pain were measured. BCP rats exhibited significant mechanical allodynia, with increased WNK1 expression in the dorsal horn and dorsal root ganglion neurons, elevated SPAK/OSR1 and NKCC1 expression in the dorsal root ganglion, and decreased KCC2 expression in the dorsal horn. WNK1 knock-down by small interfering alleviated mechanical allodynia and movement-evoked pain, inhibited WNK1-SPAK/OSR1-NKCC1 activities, and restored KCC2 expression. In addition, closantel (a WNK1-SPAK/OSR1 inhibitor) improved pain behaviors, downregulated SPAK/OSR1 and NKCC1 expression, and upregulated KCC2 expression in BCP rats. Activation of WNK1-SPAK/OSR1 signaling contributed to BCP in rats by modulating NKCC1 and KCC2 expression. Therefore, suppression of WNK1-SPAK/OSR1 may serve as a potential target for BCP therapy. PERSPECTIVE: Our findings demonstrated that the WNK1-SPAK/OSR1 signaling contributed to BCP in rats via regulating NKCC1 and KCC2. Suppressing this pathway reduced pain behaviors. Based on these findings, the WNK1-SPAK/OSR1 signaling may be a potential target for BCP therapy.

19.
Sci Total Environ ; 678: 466-475, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31077925

RESUMO

As methyltheobromine (MTB) has been increasingly detected in wastewater, it would be necessary to develop more intensive and effective approaches to remove MTB. As Co species immobilized on carbonaceous materials appears as a promising catalyst, doping carbon with nitrogen has been also validated to significantly enhance catalytic activities for Oxone activation. Therefore, it is desired to develop a composite of immobilizing Co species on N-doped carbonaceous supports for activating Oxone to degrade MTB. Unfortunately, very few studies have demonstrated such composites for activating Oxone to degrade MTB as this type of composites are conventionally prepared via complex procedures. Alternatively, this study aims to develop such a composite conveniently by using a cobaltic coordination polymer (CP) as a precursor. Specifically Co2+ and 4,4-bipyridine (BIPY) are selected for formulating a special one-dimensional CP, which is then carbonized to convert Co to Co nanoparticles (NPs) and transform BIPY to carbon nitride (CN) matrices. Because of 1-D coordinated structure of CoBIPY, the resulting magnetic Co NPs are well-distributed and protected within CN to form a magnetic Co-embedded carbon nitride composite (MCoCN). In comparison to pristine CN and Co3O4, MCoCN exhibits much higher catalytic activities to activate Oxone for degrading MTB completely within 7 min. MCoCN also shows a much lower activation energy of 24.6 kJ/mol than other reported catalysts for activating Oxone to degrade MTB. The findings of this study validate that the 1-D coordination polymer of CoBIPY is a useful precursor to prepare MCoCN for effectively activating Oxone to degrade MTB.

20.
Lipids ; 54(5): 265-276, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31087415

RESUMO

To provide molecular evidence on the thermogenic mechanism of primary brown adipocytes, western blot analysis was used to detect brown adipose tissue (BAT)-specific gene expressions. BAT protects the mammals from hypothermia injury with a large amount of mitochondria and high expression of uncoupling Protein 1 (UCP1), which is the vital protein to determine the heat production in BAT. In our previous study, the compound ZW290 (the structure shown in Fig. 1) was obtained by molecular docking with a UCP1 inducer. In the present study, ZW290 not only significantly upregulated the expression of UCP1 protein (p < 0.01) and its related signaling pathway in the primary brown adipocytes, but also remarkably decreased the mitochondrial membrane potential and the concentration of adenosine triphosphate (ATP) (p < 0.01). Kunming (KM) mice were kept under acute cold exposure (-20°C) to evaluate the preventive and protective effects of ZW290 on cold injury, and revealed its regulating mechanism in vitro. The rectal and body temperatures of ZW290-treated mice were significantly higher than those of the control (or model) group both at room temperature and at -20°C (p < 0.001). Hematoxylin-eosin (HE) staining and immunohistochemistry indicated that ZW290 notably decreased the size of lipid droplets in BAT and increased the content of mitochondria and the expression of UCP1 in BAT and white adipose tissue (WAT). Furthermore, the survival rate showed that ZW290 could prolong the overall survival of mice. Therefore, we obtained the conclusion that ZW290 might transform energy into heat by inhibiting ATP synthesis and increasing the expression of UCP1. Additionally, ZW290 may enhance cold tolerance by increasing heat production through increasing the content of mitochondria and the expression of UCP1 in BAT and WAT.

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