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1.
Chemosphere ; 238: 124607, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524603

RESUMO

A fluoride exposure mouse model is established to evaluate the relationship between mitochondrial respiratory chain complexes and renal dysfunction. Morphological changes in kidney tissues were observed. Renal function and cell proliferation in the kidneys were evaluated. The expression of mitochondrial fusion protein including mitofusin-1 (Mfn1) and optic atrophy 1 (OPA1), and mitochondrial respiratory chain complex subunits, including NDUFV2, SDHA, CYC1 and COX Ⅳ, were detected via real-time polymerase chain reaction, immunohistochemistry staining and Western blot, respectively. Results showed that the structures of renal tubule, renal glomerulus and renal papilla were seriously damaged. Renal function was impaired, and cell proliferation was remarkably inhibited by excessive fluoride in kidney. The mRNA and protein expression levels of Mfn1, OPA1, NDUFV2, CYC1 and COX Ⅳ were significantly increased after excessive fluoride exposure. However, the mRNA and protein expression of SDHA significantly decreased. Overall, our findings revealed that excessive fluoride can damage kidney structure, inhibit renal cell proliferation, interfere with the expression of mitochondrial respiratory chain complexes and elevate mitochondrial fusion. Consequently, renal function disorder occurred.

2.
J Colloid Interface Sci ; 558: 323-333, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605934

RESUMO

For the development of metal-air batteries and fuel cells, highly efficient and inexpensive electrocatalysts are one of the main issues for scalable applications of these advanced energy devices. Herein, based on the in situ conversion of FeS to γ-FeOOH with a two-dimensional (2D) layered structure, a special nanohybrid, N, S co-doped porous carbon nanosheets loaded with γ-FeOOH, is fabricated by carbonization of Fe3+-coordinated polydopamine, which uniformly coats the surface of bacterial cellulose. The nanocomposites exhibit high activity towards the cathodic oxygen reduction reaction (ORR), characterized by a more positive half-wave potential (10 mV) than the commercial Pt/C (20 wt%) electrocatalyst in alkaline medium. Additionally, the nanohybrid has excellent stability and a high methanol tolerance towards the ORR. Further experiments and density functional theory (DFT) calculations demonstrate that the doped N, S in the carbon matrix and the (0 1 0) plane of γ-FeOOH are the ORR active sites. A zinc-air battery equipped with this nanohybrid presents better a power density (92 mW cm-2) and specific capacity (740 mA h g-1) than the Pt/C electrocatalyst, demonstrating its promising potential for application in energy conversion devices.

3.
J Colloid Interface Sci ; 559: 313-323, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675662

RESUMO

Antibiotic resistance is a common phenomenon observed during treatment with antibacterials. Use of nanozymes, especially those with synergistic enzyme-like activities, as antibacterials could overcome this problem, but their synthesis is limited by their high cost and/or complex production process. Herein, vanadium oxide nanodots (VOxNDs) were prepared via a one-step bottom-up ethanol-thermal method using vanadium trichloride as the precursor. VOxNDs alone possess bienzyme mimics of peroxidase and oxidase. Accordingly, highly efficient antibacterials against drug-resistant bacteria can be obtained through synergistic catalysis; the oxidase-like activity decomposes O2 to generate superoxide anion radical (O2-) and hydroxyl radicals (OH), and the intrinsic peroxidase-like activity can further induce the production of OH from external H2O2. Consequently, H2O2 concentration could decrease up to four magnitude orders with VOxNDs to achieve an antibacterial efficacy similar to that of H2O2 alone. Wound healing in vivo further confirms the high antibacterial efficiency, good biocompatibility, and application potential of the synergistic antibacterial system due to the "nano" structure of VOxNDs. The method of synthesis of nanodot antibacterials described in this paper is inexpensive, and the results of this study reveal the multi-enzymatic synergism of nanozymes.

4.
Food Chem ; 308: 125569, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31644967

RESUMO

In this study, the solubility of phloretin (PT) was enhanced via steviol glycoside (STE)-based micelle (MC) and solid dispersion (SD). Computer simulation, characterization, interaction with serum albumin (SA) and in vitro release were carried out to investigate the solubilization mechanisms and the difference in their solubilization capacities. For PT-loaded MC (STE-PT MC), PT was encapsulated into the hydrophobic core of a spherical micelle with a droplet diameter of 5 nm. For PT-loaded SD (STE-PT SD), PT was completely dispersed with the amorphous state in STE. Most of those PTs were directly dissolved in water, and few were encapsulated by STE micelles. The amorphous state combined with relatively large micelles contributed to the high solubilization capacity of STE-PT SD. In addition, PT of STE-PT SD exhibited a higher dissolution rate and more effective interaction with SA than that of STE-PT MC. No undesirable chemical interaction between PT and STE occurred.

5.
Food Chem ; 306: 125613, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610331

RESUMO

Reduction of bitter taste in protein hydrolysates is a challenging task. The aim of this study was to apply a simple two-step approach to prepare low bitter hydrolysates and investigate the influence of peptide modifications on taste characteristics. Protein hydrolysates were prepared from porcine muscle and plasma through simultaneous hydrolysis using endo- and exo-peptidases combined with peptide glycation by glucosamine (GlcN). Spectroscopic analysis and quantification of major alpha-dicarbonyl compounds (α-DCs) indicated the relatively low extent of Maillard reaction in GlcN-glycated protein hydrolysates. Thermal degradation of high MW peptides (>10 kDa) might play a major role in Maillard reaction, reflected by the formation of more Maillard reacted peptides (1-5 kDa), especially in plasma samples. Sensory evaluation indicated that glycation by GlcN can alter taste profiles of protein hydrolysates, which may be attributed to the formation of Maillard reacted peptides and peptide modifications revealed by LC-MS/MS analysis.

6.
J Hazard Mater ; 382: 121018, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446354

RESUMO

The broad spectrum detection of veterinary drugs is very important for rapid and large-scale safe screen of animal-derived foods. Metal-organic frameworks (MOFs), as a kind of emerged functional porous materials are quite promising in the chemical sensing and molecular detection. In this work, we report the high-performance broad spectrum detection of 15 commonly-used veterinary drugs through the fluorescence quenching in a newly-designed chemically stable Al-based MOF, Al3(µ3-O)(OH)(H2O)2(PPTTA)3/2 (BUT-22). To the best of our knowledge, this is the first systematic investigation for the application of MOFs in the detection/sensing of veterinary drugs through fluorescence quenching method. The quenching efficiencies of the tested veterinary drugs on BUT-22 are all beyond 82%, and the limits of detection (LOD) are low at parts per billion (ppb) levels. Interestingly, BUT-22 also enables the selective detection of nicarbazin (NIC) through the clearly-observed red shift of its maximum fluorescence emission wavelength. Moreover, the fluorescence quenching mechanism was explored with the help of theoretical calculations. Our work indicates that MOFs are favorable materials for the detection of veterinary drugs, being potentially useful in monitoring drug residues of animal-derived foods.

7.
J Hazard Mater ; 382: 121047, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450204

RESUMO

The temporal influence of reaction atmosphere and chlorine on arsenic release in combustion, gasification and pyrolysis of sawdust was studied using an on-line analysis system. The arsenic release amount in combustion atmosphere was higher than that in CO2 gasification and argon pyrolysis. The derived values of activation energy followed the order: combustion < gasification < pyrolysis. Furthermore, the enhancement effect of chlorine species on arsenic release percentage in air combustion was also higher than that in gasification and pyrolysis conditions. The total proportion of arsenic release in combustion with additive chlorine is bigger than the case in gasification and pyrolysis, especially when 20% chlorine is added. According to equilibrium analysis, arsenic oxides were identified as the main gaseous arsenic species and their formation were decreased in the oxygen-deficient environment, mainly accounting for lesser arsenic release proportion in gasification and pyrolysis than combustion. The release of arsenic was promoted to a different extent with additive chlorine, mainly caused by the AsCl3 (g) formation. By the findings of the experiments and theoretical analyses, the possible reaction pathways and release mechanisms of arsenic species were proposed.

8.
Front Biosci (Landmark Ed) ; 25: 536-548, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585902

RESUMO

Hyperhomocysteinemia induces stress response in endoplasmic reticulum (ERS). Here, we tested whether blockage of homocysteine (Hcy) induced ERS and subsequent apoptosis in vascular smooth muscle cells can be inhibited by  blockage of PERK/eIF2α/ATF4/CHOP signaling. Short-term exposure of vascular smooth muscle cells to Hcy led to the phosphorylation of PERK (pPERK), which in turn, phosphorylated eIF2 alpha (peIF2a) and inhibited the unfolded protein response. Long-term Hcy exposure, however, increased the expression of ATF-4 and CHOP and led to apoptosis. Treatment of cells with salubrinal, a specific inhibitor for eIF2a decreased the expression of ATF-4 and CHOP, and prevented apoptosis. Together, the results show that PERK pathway is involved in Hcy-induced vascular smooth muscle cell apoptosis and that blocking the PERK pathway protects against this injury.

9.
J Enzyme Inhib Med Chem ; 35(1): 118-128, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31694418

RESUMO

A series of novel quinolinone derivatives bearing dithiocarbamate moiety were designed and synthesised as multifunctional AChE inhibitors for the treatment of AD. Most of these compounds exhibited strong and clearly selective inhibition to eeAChE. Among them, compound 4c was identified as the most potent inhibitor to both eeAChE and hAChE (IC50 = 0.22 µM for eeAChE; IC50 = 0.16 µM for hAChE), and it was also the best inhibitor to AChE-induced Aß aggregation (29.02% at 100 µM) and an efficient inhibitor to self-induced Aß aggregation (30.67% at 25 µM). Kinetic and molecular modelling studies indicated that compound 4c was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4c had good ability to cross the BBB, showed no toxicity on SH-SY5Y neuroblastoma cells and was well tolerated in mice at doses up to 2500 mg/kg (po).

10.
J Hazard Mater ; 383: 121156, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31505427

RESUMO

LaMnO3-based catalysts with perovskite structure have gained increasing interest for Hg0 oxidation owing to their excellent catalytic activity, high thermal stability and unique redox behavior. Understanding the Hg0 oxidation behavior on LaMnO3 will broaden the application of LaMnO3-based perovskites in Hg0 removal field. Density functional theory (DFT) calculations were conducted to examine the catalytic mechanism of Hg0 oxidation by HCl on LaMnO3 surface. The results indicate that Mn-terminated LaMnO3(010) surface is more active and stable than La-terminated surface. Hg0 and HgCl2 are chemisorbed on LaMnO3(010) surface. HgCl can be molecularly chemisorbed on LaMnO3(010) and serve as an intermediate in Hg0 oxidation reaction. HCl dissociatively adsorbs on LaMnO3(010) and generates surface active chlorine complexes. Langmuir-Hinshelwood mechanism, where the chemisorbed Hg0 reacts with the dissociatively adsorbed HCl, is responsible for Hg0 oxidation by HCl on LaMnO3(010). Catalytic Hg0 oxidation over the surface contains four-steps: Hg0 → Hg(ads) → HgCl(ads) → HgCl2(ads) → HgCl2, and the second step (Hg(ads) → HgCl(ads)) is the rate-determining step because of its relatively larger energy barrier (0.74 eV).

11.
Toxicol In Vitro ; 62: 104667, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629901

RESUMO

Serum is an important component in cell culture medium. It also possesses potent antioxidant properties. Therefore, the conventional protocols for detecting reactive oxygen species (ROS) in cultured cells with fluorescent probes include washing and suspending cells with serum-free buffers, such as PBS. This transient serum deprivation is essential for the ROS detecting. Unfortunately, it may also cause unexpected results, which push us to choose more optimal experiment conditions. In the present study, we found an acute lytic cell death induced by xanthohumol (XN), which obstructed ROS detecting in human leukemia cell line HL-60 cells. XN induced ROS burst, caused cell swelling, membrane permeability increase, LDH release, and ultimately an acute lytic cell death and cell rupture. These effects could be alleviated by the antioxidant N-Acetyl-L-cysteine (NAC). Apoptosis, pyroptosis or necroptosis were not observed in this process. Results also indicated that 2% serum addition had already completely scavenged ROS induced by 10 µM XN. Taken together, it is strongly suggested to detecting ROS in a serum-free medium when studying where and how ROS generated in cells. The concentration at the ROS maximum point (10 µM XN in this study) can be selected as the optimal concentration.

12.
Biomed Mater ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31715589

RESUMO

Corneal transplantation remains solely, the current major solution in the treatment of severe corneal diseases. However, it faces a restriction due to the limitation of corneal donors. The tissue-engineered cornea is a potential substitution in this area that can help to avert this limitation. The present research envisages the development of a novel tissue-engineered corneal stroma consisting of bacterial cellulose/poly vinyl alcohol (BC/PVA) hydrogel composites for reconstructing the cornea. It was found that the properties of BC/PVA exhibited a better suitability for its use as a corneal stroma material compared to the bacterial cellulose (BC) hydrogel. The human corneal stromal cells (hCSCs) were used to evaluate the cytotoxicity of the materials, wherein BC/PVA displayed excellent biocompatibility with these cells. Furthermore, in the in-vivo studies, the BC/PVA was transplanted intrastromally in rabbits. After 4 weeks, the cornea remained almost transparent, and without obvious inflammation, sensitization or neovascularization as confirmed by the clinical and histological examination. Our results demonstrate that BC/PVA was well-tolerated in the rabbit cornea, and may be a potential substitute for corneal stroma.

13.
Metallomics ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720660

RESUMO

Selenium is closely related to the occurrence of heart disease, and an appropriate amount of selenium can alleviate inflammatory changes caused by various factors. Lipopolysaccharide (LPS), as a specific component of the cell wall of Gram-negative bacteria, is often used to construct various inflammatory models. In order to explore the effect of selenium on LPS-induced myocardial inflammation in chickens, we chose 4-month-old laying hens to be fed with a selenium-rich diet containing 0.5 g kg-1 Se, and injected LPS into the abdominal cavity at the age of 8 months to establish an inflammation model. We observed the myocardial tissue lesions by light microscopy, and detected miR-128-3p, p38MAPK, and NF-κB pathway-associated inflammatory factors and Th1/Th2 related factors by qRT-PCR and Western blot. The results showed that LPS stimulation inhibited miR-128-3p, which increased the expression of p38MAPK and NF-κB, while the expression of TNF-α, IL-1, PTGE, COX-2 and iNOS increased. Additionally, the expression of IL-4 and IL-6 increased and IFN-γ decreased, suggesting an imbalance of Th1/Th2. We also found that LPS treatment not only increased the content of H2O2 and MDA in the myocardium, but also increased the expression of HSP60, HSP70 and HSP90, while the activity of SOD, GPX and CAT and the content of GSH decreased. Interestingly, the addition of selenium can alleviate the changes in the above indicators. Finally, we concluded that selenium inhibits the occurrence of oxidative stress and ultimately alleviates myocardial inflammation induced by LPS through the miR-128-3p-p38MAPK-NF-κB pathway.

14.
Chemosphere ; 242: 125206, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31678849

RESUMO

Phthalates, a class of high production-volume chemicals widely used as plasticizers, have been shown to impair ovarian functions in female animals, but epidemiological evidence is very limited. In this case-control study, the associations between phthalate exposure and premature ovarian failure (POF) in women were assessed. A total of 173 POF cases and 246 control women were recruited in Zhejiang, China. The urinary concentrations of 8 phthalate metabolites and the serum levels of ovary-related hormones were determined. Mono-isobutyl phthalate (MiBP) was the metabolite with the highest median concentration of 27.23 µg/g of creatinine in the whole group. Compared with the lowest quartile, higher urinary concentrations of MiBP were significantly associated with increased odds of POF (OR = 1.38, 95% CI: 0.73-2.61 for the fourth quartile; p for trend = 0.01). The estradiol/FSH ratio, a marker of ovarian function, in control women was significantly negatively associated with the urinary concentrations of most tested phthalate metabolites. Our results suggest that exposure to some phthalates may impair ovarian function and increase the odds of POF in women.

15.
Nano Lett ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31694380

RESUMO

In recent years, small nanoparticles (NPs) with a diameter of less than 10 nm have aroused considerable interest in biomedical applications. However, their intratumor performance, as well as the antitumor efficacy, has not been well understood due to their size-dependent pharmacokinetics, which presents a formidable challenge for delivering a comparable amount of different small NPs to tumor tissues. Utilizing the multistage delivery strategy, we construct G3-, G5-, and G7-iCluster delivery systems by using poly(amidoamine) (PAMAM) dendrimers of different generations (G3-, G5-, and G7-PAMAM) as building blocks. The iCluster nanoparticles showed comparable pharmacokinetics and similar initial tumor deposition due to their similarity in size and surface chemistry. After accumulating at a tumor site, individual small dendrimers were released, and thus, their intratumor performance was comparatively investigated. Our results indicated that a subtle change in generation markedly affects their intratumor activities. G5-iCluster outperformed G3-iCluster and G7-iCluster in the treatment efficacy in an orthotopic pancreatic tumor model. The mechanistic study revealed that G3-PAMAM showed reduced particle retention in tumor tissue due to its small size and weak cell internalization, while G7-PAMAM was much less penetrative because of its relatively large size and strong particle-cell interaction. In contrast, G5-PAMAM exhibited balanced tumor penetration, cell internalization, and tumor retention. Our finding highlights the huge influence of the subtle difference of small NPs in their intratumor performance.

16.
Brain Behav ; : e01455, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714027

RESUMO

BACKGROUND: PCDH19 has become the second most relevant gene in epilepsy after SCN1A. Seizures often provoked by fever. METHODS: We screened 152 children with fever-sensitive epilepsy for gene detection. Their clinical information was followed up. RESULTS: We found eight PCDH19 point mutations (four novel and four reported) and one whole gene deletion in 10 female probands (seven sporadic cases and three family cases) who also had cluster seizures. The common clinical features of 16 patients in 10 families included fever-sensitive and cluster seizures, mainly focal or tonic-clonic seizures, and absence of status epilepticus, normal intelligence, or mild-to-moderate cognitive impairment, the onset age ranges from 5 months to 20 years. Only four patients had multiple or focal transient discharges in interictal EEG. Focal seizures originating in the frontal region were recorded in four patients, two from the parietal region, and one from the occipital region. CONCLUSION: PCDH19 mutation can be inherited or de novo. The clinical spectrum of PCDH19 mutation includes PCDH19 Girls Clustering Epilepsy with or without mental retardation, psychosis, and asymptomatic male. The onset age of PCDH19 Girls Clustering Epilepsy can range from infancy to adulthood. Sisters in the same family may be sensitive to the same antiepileptic drugs. And our report expands the mutation spectrum of PCDH19 Girls Clustering Epilepsy.

17.
Dev Cell ; 51(3): 399-413.e7, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689386

RESUMO

Chronic kidney disease affects 10% of the population with notable differences in ethnic and sex-related susceptibility to kidney injury and disease. Kidney dysfunction leads to significant morbidity and mortality and chronic disease in other organ systems. A mouse-organ-centered understanding underlies rapid progress in human disease modeling and cellular approaches to repair damaged systems. To enhance an understanding of the mammalian kidney, we combined anatomy-guided single-cell RNA sequencing of the adult male and female mouse kidney with in situ expression studies and cell lineage tracing. These studies reveal cell diversity and marked sex differences, distinct organization and cell composition of nephrons dependent on the time of nephron specification, and lineage convergence, in which contiguous functionally related cell types are specified from nephron and collecting system progenitor populations. A searchable database, Kidney Cell Explorer (https://cello.shinyapps.io/kidneycellexplorer/), enables gene-cell relationships to be viewed in the anatomical framework of the kidney.

19.
Cancer Res ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690669

RESUMO

The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized, encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here, we focused on the cross-talk between macrophages, chemotherapy, and heparanase and the combined effect on tumor progression. Macrophages were markedly activated by chemotherapeutics paclitaxel (PCT) and cisplatin, evidenced by increased expression of pro-inflammatory cytokines, supporting recent studies indicating that chemotherapy may promote rather than suppress tumor re-growth and spread. Strikingly, cytokine induction by chemotherapy was not observed in macrophages isolated from heparanase-knockout mice, suggesting macrophage activation by chemotherapy is heparanase-dependent. PCT-treated macrophages enhanced the growth of lewis lung carcinoma tumors which was attenuated by a CXCR2 inhibitor. Mechanistically, PCT and cisplatin activated methylation of histone H3 on lysine 4 (H3K4) in wild-type but not heparanase-knockout macrophages. Furthermore, the H3K4 presenter WDR5 functioned as a molecular determinant that mediated cytokine induction by PCT. This epigenetic, heparanase-dependent host-response mechanism adds a new perspective to the tumor-promoting functions of chemotherapy, and offers new treatment modalities to optimize chemotherapeutics.

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