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1.
J Hazard Mater ; 382: 121008, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470299

RESUMO

In this study, nanoscale zerovalent iron (nZVI) with copper (Cu) bimetallic particles, whichare applied for degradation of Ciprofloxacin (CIP) under weak magnetic field (WMF), were synthesized using green tea extracts (GT-nZVI/Cu). The surface morphology and physicochemical properties of the novel catalytic materials were characterized. It was found that GT-nZVI was more stable and performed better in oxidation resistance than the nZVI synthesized by traditional chemical methods. Besides, the catalytic reactivity of GT-nZVI/Cu was measured with and without WMF, it is obvious from the experimental results the performance of GT-nZVI/Cu system was enhanced significantly with WMF. Moreover, WMF still had a certain effect even after being removed, which is called remanence effect. The mass spectrometry (MS) was utilized to analyze the degradation products of CIP, and the contribution of adsorption and Fenton/Fenton-like oxidation of GT-nZVI/Cu during CIP removal process was further evaluated. It was found that as the removal process progressed, the contribution ratio of Fenton/Fenton-like oxidation rose rapidly and exceeded adsorption after 20 min. Eventually, attempts have been made to regenerate GT-nZVI/Cu, in which physical recovery (ultrasonic) was the main route, and the CIP removal rate decreased as the regeneration times increased. This research provides new insights into the green synthesis and regeneration of nZVI and is expected to realize the practical application of nZVI.

2.
Sci Total Environ ; 698: 134166, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494421

RESUMO

The development of efficient and regenerable adsorbent coupled with advanced oxidation for enhanced thallium (Tl) removal has been a recent focus on wastewater treatment. In this study, a magnetite-based biochar derived from watermelon rinds was synthesized and used as a sustainable adsorbent and catalyst for hypochlorite oxidation and removal of Tl(I) from wastewater. The addition of hypochlorite substantially enhanced the Tl(I) removal under normal pH range (6-9). Maximum Tl adsorption capacity of 1123 mg/g was achieved, which is 12.3% higher than the highest value previously reported. The magnetic biochar can be regenerated using 0.1 mol/L HNO3 solution for elution in only 5 min, with a Tl desorption efficiency of 78.9%. The Tl removal efficiency was constantly higher than 98.5% during five consecutive recycle tests, indicating the effective reuse performance of the adsorbent. Oxidation, surface precipitation, pore retention and surface complexation were the main mechanisms for Tl(I) removal. The re-dissolution of Tl compounds and ion exchange of Tl cations with proton were the main mechanisms for adsorbent regeneration. Given the fast oxidation rate, high adsorption capacity, steady reusability and facile separability, this magnetic biochar-hypochlorite technique is a promising means for Tl(I) removal from wastewater. The catalytic hypochlorite oxidation induced by the magnetic biochar has also great potential to the effective removal of other pollutants.

3.
J Colloid Interface Sci ; 559: 197-205, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627143

RESUMO

Mesoporous silica nanoparticle (MSN) demonstrates great potentials as a loading platform for bactericidal agents, but may be limited by its application form of bulk or powder. Herein, we developed MSN surface-enriched composite membranes with remarkable photodynamic antimicrobial activities via a facile electrospinning method. The mixture of zein and polycaprolactone (PCL) was served as the polymeric matrix, while the methylene blue (MB) loaded MSN was modified by trichloro (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane (THFS) and acted as reactive oxygen species (ROS) generator to exert their antimicrobial performances. Owing to its low surface energy, the fluorinated MSN tended to be enriched on the surface of the nanofiber, hence significantly enhancing the ROS generation. Moreover, benefiting from the surface enrichment of the fluorinated nanoparticles, the composite membrane displayed obvious surface hydrophobicity and exhibited discernible bacterial repellency. Subsequently, upon visible light (660 nm) irradiation, the composite membrane demonstrated remarkable photodynamic antibacterial activities against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) but without essential detrimental impacts on the mammalian cells. We envision that this self-enriched MSN composite membrane may find broad applications in bacterial infection-resistant areas.

4.
Mater Sci Eng C Mater Biol Appl ; 107: 110266, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761238

RESUMO

The purpose of this study was to facilely develop biomimetic amino modified mesoporous silica xerogel (AMSX) and study how AMSX regulated loading and in vitro sustained delivery of carboxyl-containing drug levorotary ofloxacin (LOFL). Characteristics of AMSX, including morphology, porous structure, elements and crystalline state were investigated and pharmaceutical performance of AMSX for the delivery of LOFL was studied. The result showed that AMSX was accumulational spherical nanoparticles with mesoporous structure. Hydrogen bonding force was formed between carboxylic groups of LOFL and amino groups grafted on the surface of AMSX. Furthermore, a three-level three-factorial Box-Behnken experimental design was applied to optimize the amount of major agent for synthesizing AMSX with expected drug loading capacity and also to figure out how AMSX regulated in vitro delivery of LOFL. It is believed that the present work will provide novel insights for designing mesoporous silica as drug carrier and favored the development of sustained release system.

5.
Chemosphere ; 239: 124806, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726521

RESUMO

Nitrobenzene (NB) is recalcitrant to microbial biodegradation due to the electron-deficient character of the nitro group (NO2-). Prior work has found that the reductant could enhance NB biodegradation by providing excess electron donors. However, the existing theory couldn't explain the increase-and-decrease pattern of the NB biodegradation rate with an increase in a reductant concentration. Our results suggest that the reductant affects NB biodegradation by two mechanisms: the available electron donors and the stimulation or inhibition of biomass growth, which are linked by a pseudo-first-order reaction kinetics. In addition, the results showed that directly inoculating the plain soil into the aquatic system and then allowing the synergistic effect of the organic reductant (ascorbic acid) and the substrate (peptone) enhance NB biodegradation. Employing the new method, 200 mg L-1 NB was transformed in 72 h. GC-MS analysis detected two novel intermediate metabolites, indicating that NB was degraded into aniline and further transformed into acetanilide and 9-octadecenamide before its mineralization. This study sheds light on how to exploit the synergistic effects of the availability of excess electron donors and biomass growth by controlling the reductant and a substrate in the right concentration range (e.g., ascorbic acid < 0.8 mgL-1 + peptone).

6.
J Hazard Mater ; 383: 121215, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31546220

RESUMO

Blast furnace dust (BFD), a hazardous metallurgical waste, is generated during the iron-making process and consists plenty of Fe and C. This study is among the first to apply BFD in catalytic-ceramic-filler (CCF) preparation and degradation of ciprofloxacin (CIP). The novel BFD based Fe-Ni CCF obviously enhanced the removal of CIP (from around 42%-72% after 3 h) in comparation with troditional Fe-C ceramic-filler(CF). The Fe-Ni CCF was further applied in a coupled system of electrolysis assisted catalytic micro-electrolysis (E-CME) process for CIP wastewater treatment. Under optimal operating conditions (iron rod as anode, voltage of 10v and HRT of 3 h), nearly 97% of CIP, 90% of total organic carbon (TOC) and 99% of total phosphorus (TP) were removed by E-CME process in near-neutral solution. The degradation mechanism analysis by LC-MS revealed that polyhydroxy sub-stituted, piperazine rings cleavage and so on were the main reaction of CIP in E-CME process. Additionally, the chemical oxygen demand (COD) residue after E-CME process could be effectively eliminated by up-flow anaerobic filter (UAF), owing to the significant improvement of wastewater biodegradability by E-CME pretreatment. This study provides a new way for co-friend recycling of BFD and a highly-efficient, cost-sffective technology for CIP wastewater treatment.

7.
Chem Biol Interact ; 315: 108871, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669218

RESUMO

Clopidogrel, a clinically used antiplatelet agent, can be readily hydrolyzed by human carboxylesterase 1A (CES1A) to release an inactive metabolite clopidogrel carboxylic acid (CCA). In this study, clopidogrel was used as a tool substrate to investigate the interspecies variation of clopidogrel hydrolysis in hepatic microsomes from various mammals including human and six laboratory animals (such as mouse, rat, rabbit, beagle dog, minipig and cynomolgus monkey). The results demonstrated that clopidogrel could be hydrolyzed into CCA by all tested hepatic microsomes from human or other mammals, but the hydrolytic rates greatly varied among species. Inhibition assays demonstrated that BNPP (an inactivator of mammalian CES) strongly inactivated clopidogrel hydrolytic activity in all tested hepatic microsomes, suggested that mammalian CES were major contributor(s) responsible for clopidogrel hydrolysis in hepatic preparations from all above-mentioned species. By contrast, the response of a reversible inhibitor of human CES1A on clopidogrel hydrolysis in these liver preparations varied significantly among different species. Moreover, the enzymatic kinetics and the apparent kinetic parameters of clopidogrel hydrolysis in hepatic microsomes from various animal species were evaluated and compared to each other. These findings provide crucial information for deeply understanding the differences in catalytic behaviors of mammalian CES, which will be very helpful for choosing suitable laboratory animal(s) for whole tests of CES1A substrate-drugs.

8.
J Cell Mol Med ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747719

RESUMO

Based on multiple studies in animal models, mesenchymal stem cell (MSC)-based therapy appears to be an innovative intervention approach with tremendous potential for the management of kidney disease. However, the clinical therapeutic effects of MSCs in either acute kidney injury (AKI) or chronic kidney disease (CKD) are still under debate. Hurdles originate from the harsh microenvironment in vivo that decreases the cell survival rate, paracrine activity and migratory capacity of MSCs after transplantation, which are believed to be the main reasons for their limited effects in clinical applications. Melatonin is traditionally regarded as a circadian rhythm-regulated neurohormone but in recent years has been found to exhibit antioxidant and anti-inflammatory properties. Because inflammation, oxidative stress, thermal injury, and hypoxia are abnormally activated in kidney disease, application of melatonin preconditioning to optimize the MSC response to the hostile in vivo microenvironment before transplantation is of great importance. In this review, we discuss current knowledge concerning the beneficial effects of melatonin preconditioning in MSC-based therapy for kidney disease. By summarizing the available information and discussing the underlying mechanisms, we aim to improve the therapeutic effects of MSC-based therapy for kidney disease and accelerate translation to clinical application.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31748989

RESUMO

Desorption of hydrophobic organic contaminants (HOCs) from sedimentary materials plays a vital role in dictating the fate and transport of HOCs in the environment. Desorption irreversibility is a commonly observed phenomenon in laboratory sorption/desorption studies of HOCs. A desorption-resistant fraction (DRF) typically exists during the desorption process. To correctly evaluate the DRF of HOCs can considerably contribute to the understanding of availability and bioavailability of HOCs. This can substantially benefit contaminant remediation and cleanup operations. Conventional batch method to measure the DRF replies on repetitive washing of the sediments, which is time-consuming and can be impractical. This study presents an experimental protocol to quantify the DRF of the sediment-sorbed organic contaminants in a rapid manner. This protocol utilizes cosolvent to expedite desorption kinetics and adopts an ultrafiltration/centrifugation combined method to achieve a complete separation of sediment and solution phases. This proposed experimental protocol can facilitate the quantification of the DRF of sorbed contaminants to understand and minimize the uncertainties associated with risk-based pollution remediation approach. This protocol has the potential to be widely used in environmental studies to characterize sorption and desorption properties of HOCs with soil and sedimentary materials.

10.
Gene ; : 144242, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743770

RESUMO

OBJECTIVE: To investigate fibroblast growth factor 21 (Fgf21) alterations that may affect hair growth and the underlying molecular mechanisms by constructing Fgf21 global knockout (KO) mice using microinjection-mediated CRISPR/Cas9. RESULTS: Following genomic DNA sequencing, we identified 18 mice carrying Ffg21 mutations among the total 63 offspring mice obtained by injecting 340 embryos, which yielded a mutation rate of 28.6 percent. Of these 18 mice, three had both alleles knocked out and 15 were monoallelic KO mice. Compared with the wild-type (WT) mice, the phenotypic analysis showed that the litter size of Fgf21 KO mice significantly reduced (p<0.05), but physiological indexes of the birth weight, gender rate, body weight(0-8 week) and body weight of adult male and female were no significant difference (p>0.05). Compared to WT mice, physiological anatomy indicated that the morphological characters of vital organs in Fgf21 KO mice were normal.Depilation experiments demonstrated that compared to the WT mice, the hair regrowth speed was reduced in the Fgf21 KO mice. The number of hair shafts in these mice considerably decreased, as indicated by the tissue sample analyses. Real-time quantitative PCR showed that Erk and Akt expression in the KO mice was significantly decreased (P < 0.05), whereas western blotting demonstrated that the expression of Erk and Akt proteins and their phosphorylation levels in KO mice decreased at different rates (P < 0.05). CONCLUSIONS: Fgf21 was shown to affect hair follicle development and growth cycle, which may be associated with Pi3k/Akt and Mapk/Erk signaling pathways.

11.
Acta Diabetol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745647

RESUMO

AIMS: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. METHODS: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). RESULTS: In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs ≥ 5% were below $50,000/QALY gained. CONCLUSIONS: Intervening in those with ≥ 7% diabetes risk based on the GDRS or ≥ 9% on the ARIC 2009 score would be cost-effective. A risk score threshold ≥ 5% together with elevated FPG would also allow targeting interventions cost-effectively.

12.
Mol Med Rep ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746416

RESUMO

In this study, six compounds were isolated and purified from dandelion, and only sample I exhibited notable antifungal effect on Candida albicans (CA). high­performance liquid chromatography­diode­array detector­electrospray ionization­tandem mass spectrometry analysis showed that sample I comprised 4­coumaric acid, ferulic acid, quercetin pentoside, 3,5­di­O­caffeoylquinic acid, 4,5­di­O­caffeoylquinic acid, luteolin, and two unknown compounds, at a relative percent composition of 11.45, 3.96, 10.48, 34.24, 3.91, 11.80, 3.65 and 4.21%, respectively. Further antimicrobial experiments showed that the minimum inhibitory concentration of sample I was 32.0 mg/ml, and sample I mainly acts on bacterial growth in the exponential phase of CA growth. Optical density and infrared analyses conclusively suggested that sample I damages the structure of CA cells, particularly the cell wall and cell membrane, resulting in macromolecule leakage of intracellular nucleic acids and cell metabolism disruption. In conclusion, dandelion sample I was reported to increase CA cell membrane permeability by affecting the glycosidic bond in ß­(1­3)­D glucan and destroying the cell wall, ultimately leading CA to death.

13.
Physiol Plant ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747055

RESUMO

High temperature reduces crop production; however, little is known about the effects of high night temperature (HNT) on the development of male and female reproductive organs, pollination, kernel formation, and grain yield in maize (Zea mays L.). Therefore, a temperature-controlled experiment was carried out using heat-sensitive maize hybrid and including three temperature treatments of 32/22 (day/night; control), 32/26, and 32/30°C during 14 consecutive days encompassing the flowering stage. When exposed to 30°C night temperature, grain yield and kernel number reduced by 23.8 and 25.1%, respectively, compared with the control. The decrease in grain yield was mainly due to the lower kernel number rather than change in kernel weight under HNT exposure around flowering. No significant differences in grain yield and kernel number were found between 22 and 26°C night temperatures. HNT had no significant effects on the onset of flowering time and anthesis-silking interval but significantly reduced time period of pollen shedding duration and pollen viability, and increased leaf night respiration. Different from high daytime temperature, HNT had no lasting effects on daytime leaf photosynthesis, biomass production, and assimilate transportation. From the perspective of source-flow-sink relationship, the unchanged source and flow capacities in daytime are supposed to alleviate the adverse effects on sink strength caused by HNT compared daytime heat stress. These new findings commendably filled the knowledge gaps concerning heat stress in maize. This article is protected by copyright. All rights reserved.

14.
J Trace Elem Med Biol ; : 126419, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31711786

RESUMO

BACKGROUND: Trace elements are an essential requirement for human health and development and changes in trace element status have been associated with pregnancy complications such as gestational diabetes mellitus (GDM), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth. Elemental metabolomics, which involves the simultaneous quantification and characterisation of multiple elements, could provide important insights into these gestational disorders. METHODS: This study used an Agilent 7900 inductively coupled plasma mass spectrometer (ICP-MS) to simultaneously measure 68 elements, in 166 placental cord blood samples collected from women with various pregnancy complications (control, hypertensive, PE, GDM, FGR, pre-term, and post-term birth). RESULTS: There were single element differences across gestational outcomes for elements Mg, P, Cr, Ni, Sr, Mo, I, Au, Pb, and U. Hypertensive and post-term pregnancies were significantly higher in Ni concentrations when compared to controls (control = 2.74 µg/L, hypertensive = 6.72 µg/L, post-term = 7.93 µg/L, p < 0.05), iodine concentration was significantly higher in post-term pregnancies (p < 0.05), and Pb concentrations were the lowest in pre-term pregnancies (pre-term = 2.79 µg/L, control = 4.68 µg/L, PE = 5.32 µg/L, GDM = 8.27 µg/L, p < 0.01). Further analysis was conducted using receiver operating characteristic (ROC) curves for differentiating pregnancy groups. The ratio of Sn/Pb showed the best diagnostic power in discriminating between control and pre-term birth with area under the curve (AUC) 0.86. When comparing control and post-term birth, Mg/Cr (AUC = 0.84), and Cr (AUC = 0.83) had the best diagnostic powers. In pre-term and post-term comparisons Ba was the best single element (81.5%), and P/Cu provided the best ratio (91.7%). CONCLUSIONS: This study has shown that analysis of multiple elements can enable differentiation between fetal cord blood samples from control, hypertensive, PE, GDM, FGR, pre and post-term pregnancies. This data highlights the power of elemental metabolomics and provides a basis for future gestational studies.

15.
J Vet Med Sci ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31694992

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) keeps causing economic damages in the swine sector across the globe. There has been emergence of the European (EU) genotype of porcine reproductive and respiratory syndrome virus (Genotype-I PRRSV) in China in recent years. The presently available vaccines cannot unable to provide safeguard against PRRSV infection completely. This study was aimed to construct recombinant adenovirus expressing the ORF3 and ORF5 genes of the EU-type PRRSV strain. Then, the recombinant adenovirus vaccines for EU-type PRRSV (rAd-E3518, rAd-E35, rAd-E3 and rAd-E5) which we constructed and evaluated were constructed and identified by western blot and PCR. All recombinant adenovirus vaccines were evaluated for humoral and cellular responses and EU-type PRRSV challenge in pigs. The results showed that the group of rAd-E3518 + Quil A developed higher GP3 and GP5 specific antibody responses compared to the group of rAd-E3518. The majority of the neutralizing antibody titers were higher than 1:16 (P<0.05), the fusion of IL-18 has increased significantly PRRSV-stimulated secretion of IFN-γ and IL-4 in porcine serum, the group of rAd-E3518+Quil A produced highest T-lymphocytes (CD3+CD4+ and CD3+CD8+T cells) proliferative in peripheral blood of pigs. The animals were challenged with the EU-type PRRSV strain and the viral load was detected in the several tissues, the viral load of rAd-E3518 and rAd-E3518+Quil A were lower than the wild-type adenovirus group. Our findings provide evidence to confirm that the recombinant adenovirus vaccine can protect pigs from EU-PRRSV infection.

17.
Acta Biomater ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672585

RESUMO

Four-dimensional (4D) bioprinting, in which the concept of time is integrated with three-dimensional (3D) bioprinting as the fourth dimension, has currently emerged as the next-generation solution of tissue engineering as it presents the possibility of constructing complex, functional structures. 4D bioprinting can be used to fabricate dynamic 3D-patterned biological architectures that will change their shapes under various stimuli by employing stimuli-responsive materials. The functional transformation and maturation of printed cell-laden constructs over time are also regarded as 4D bioprinting, providing unprecedented potential for bone tissue engineering. The shape memory properties of printed structures cater to the need for personalized bone defect repair and the functional maturation procedures promote the osteogenic differentiation of stem cells. In this review, we introduce the application of different stimuli-responsive biomaterials in tissue engineering and a series of 4D bioprinting strategies based on functional transformation of printed structures. Furthermore, we discuss the application of 4D bioprinting in bone tissue engineering, as well as the current challenges and future perspectives. STATEMENTS OF SIGNIFICANCE: In this review, we have demonstrated the 4D bioprinting technologies, which integrate the concept of time within the traditional 3D bioprinting technology as the fourth dimension and facilitate the fabrications of complex, functional biological architectures. These 4D bioprinting structures could go through shape or functional transformation over time via using different stimuli-responsive biomaterials and a series of 4D bioprinting strategies. Moreover, by summarizing potential applications of 4D bioprinting in the field of bone tissue engineering, these emerging technologies could fulfill unaddressed medical requirements. The further discussions about future challenges and perspectives will give us more inspirations about widespread applications of this emerging technology for tissue engineering in biomedical field.

18.
Biosci Rep ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710081

RESUMO

Mitochondrial reactive oxygen species (ROS) cause Ca2+ release from the Endoplasmic reticulum (ER) via ryanodine receptors (RyRs) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). Here we tested a novel hypothesis that hypoxia-induced RyR-mediated Ca2+ release may, in turn, promote mitochondrial ROS generation contributing to hypoxic cellular responses in PASMCs. Our data reveal that application of caffeine to elevate intracellular Ca2+ concentration ([Ca2+]i) by activating RyRs results in a significant increase in ROS production in cytosol and mitochondria of PASMCs. Norepinephrine to increase [Ca2+]i due to the opening of inositol 1,4,5-triphosphate receptors (IP3Rs) produces similar effects. Exogenous Ca2+ significantly increases mitochondrial-derived ROS generation as well. Ru360 also inhibits the hypoxic ROS production. The RyR antagonist tetracaine or RyR2 gene knockout (KO) suppresses hypoxia-induced responses as well. Inhibition of mitochondrial Ca2+ uptake with Ru360 eliminates N- and Ca2+-induced responses. RISP KD abolishes the hypoxia-induced ROS production in mitochondria of PASMCs. Rieske iron-sulfur protein (RISP) gene knockdown (KD) blocks caffeine- or NE-induced ROS production. Taken together, these findings have further demonstrated that ER Ca2+ release causes mitochondrial Ca2+ uptake and RISP-mediated ROS production; this novel local ER/mitochondrion communication-elicited, Ca2+-mediated, RISP-dependent ROS production may play a significant role in hypoxic cellular responses in PASMCs.

19.
Int J Mol Sci ; 20(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683916

RESUMO

Although metabolic perturbations are sensitive indicators for low-dose toxic effects, the metabolic mechanisms affected by rac-metalaxyl and metalaxyl-M in mammals from a metabolic profiling perspective remain unclear. In this study, the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M in mice were carefully investigated using integrative nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based metabolomics. Histopathology, NMR-based untargeted urine profile, multivariate pattern recognition, metabolite identification, pathway analysis, UPLC-MS/MS based targeted serum amino acids, and tryptophan pathway analysis were determined after rac-metalaxyl and metalaxyl-M exposure, individually. Histopathology indicated that metalaxyl-M induced greater hepatocellular inflammatory, necrosis, and vacuolation in mice than rac-metalaxyl at the same exposure dosage. The metabolic perturbations induced by rac-metalaxyl and metalaxyl-M were directly separated using partial least-squares discriminant analysis (PLS-DA). Furthermore, metabolite identification and pathway analysis indicated that rac-metalaxyl mainly induced ten urine metabolite changes and four pathway fluctuations. However, metalaxyl-M induced 19 urine metabolite changes and six pathway fluctuations. Serum amino acids and tryptophan pathway metabolite changes induced by rac-metalaxyl and metalaxyl-M were also different even at the same exposure level. Such results may provide specific insight into the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M, and contribute to providing available data for health risk assessments of rac-metalaxyl and metalaxyl-M at a metabolomics level.

20.
Neurotoxicology ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730894

RESUMO

OBJECTIVES: Epidemiology studies indicated that coke-oven workers with long-term exposure to polycyclic aromatic hydrocarbons (PAHs) often have some neurobehavioral abnormalities especially impairment for cognitive function, while the underlying mechanisms are not fully understood. Numerous studies have indicated the antioxidant and anti-apoptosis roles of heat shock protein 70 (Hsp70). The genetic polymorphisms in HSP70 genes are associated with multiple diseases including neurotoxicity. However, it is unclear whether HSP70 polymorphisms are related to the neurotoxicity of PAH. We, therefore, investigate the possible association between HSP70 polymorphisms and neurobehavioral abnormalities. METHODS: 188 coke-oven workers and 137 control workers were recruited in this study. Emotional and cognitive function was assessed using the WHO/NCTB. HSP70 polymorphisms (HSP70-1 G190C, HSP70-2 G1267 A and HSP70-hom T2437C) were checked by PCR-RFLP. RESULTS: The results indicated that HSP70-1 CC genotypes in coke-oven workers were associated with poor neurobehavioral performance such as the attention /response speed and visual perception/memory, while the HSP70-2 AA genotypes were associated with lower short-term auditory memory. CONCLUSIONS: HSP70-1 CC and HSP70-2 AA genotypes in coke-oven workers may increase the risk for neurobehavioral damage, especially attention, learning and memory.

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