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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117458, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31437766

RESUMO

The matter of fluoroquinolone residues in various foods still arouses wide public concern nowadays. In the present work, the strategy of excitation-emission matrix (EEM) fluorescence data coupled with second-order calibration method based on alternating normalization-weighted error (ANWE) algorithm was used to determine ofloxacin, lomefloxacin and ciprofloxacin in milk powder, milk and beef. Owning the unique "second-order advantage", the ANWE-assisted analytical method was proved to successfully and eco-friendly resolve the overlapped fluorescence spectra of multi-component in complex food matrixes without tedious pretreatment steps and sophisticated high-cost instrumentations. The feasibility of the proposed method was validated by experiments. The average spiked recoveries of three fluoroquinolones range from 82.6% to 110.5% with relative standard deviations lower than 7.4%, and the limits of detection range from 0.18 and 2.41 ng mL-1. For further evaluation, analytical figures of merit such as sensitivity and selectivity, as well as the RSDs of intra-day (≦10.6%) and inter-day (≦9.4%) were calculated. The satisfactory analytical results demonstrated that the proposed strategy could be a competitive alternative for simple, rapid and simultaneous determination of multiple fluoroquinolones in animal-derived food samples.

2.
J Theor Biol ; 484: 110018, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31550442

RESUMO

The cell-fate induction based on the saddle-node bifurcation is undoubtedly a very important concept in developmental biology, which provides a possible mechanism to explain the intrinsic irreversibility in the developmental process. In this paper, the effect of a colored noise, which is associated with the inductive stimulus, on the saddle-node landscape of cell-fate induction is investigated, especially, the effect of the change of correlation time of colored noise on cell-fate induction. The main results show clearly that the change of correlation time of colored noise could induce the transitions of the system. This implies that the colored noise associated with inductive stimulus may have a profound effect on the saddle-node bifurcation landscape of cell-fate induction. This will also help us to understand more deeply the role of cell-fate induction in developmental biology.

3.
Ecotoxicol Environ Saf ; 187: 109879, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31677567

RESUMO

Cadmium (Cd) is a major environmental pollutant. Maternal Cd exposure throughout pregnancy caused fetal growth restriction (FGR). However, the pivotal time window of Cd-evoked FGR and its mechanism are unknown. Here, we will establish a murine model to explore the effects of maternal Cd exposure at different stages of gestation on fetal growth and placental progesterone biosynthesis. Pregnant mice were randomly divided into four groups. For Cd groups, mice were given with CdCl2 (150 mg/L) through drinking water at early (GD0-GD6), middle (GD7-GD12) and late (GD13-GD17) gestation, respectively. The controls received reverses osmosis (RO) water. Results showed that maternal cadmium exposure only in late gestation lowered fetal weight and length. Correspondingly, placental Cd level in late gestational Cd exposure is the highest among three different gestational stages. Although gestational Cd exposure had few adverse effects in the weight and diameter of mouse placenta, placental vascular development, as determined by H&E staining and cluster of differentiation-34 (CD-34) immunostaining, was impaired in mice exposed to Cd during late pregnancy. Additionally, late gestational exposure to cadmium markedly reduced progesterone level in maternal serum and placenta. In line, the expression of key progesterone synthetases, including steroidogenic acute regulatory protein (StAR) and 3ß-hydroxyl steroid dehydrogenase (3ß-HSD), was obviously downregulated in placenta from mice was exposed Cd during late pregnancy. These data suggest that maternal Cd exposure during late pregnancy, but not early and middle pregnancy, induces fetal growth restriction partially via inhibiting placental progesterone synthesis.

4.
J Ethnopharmacol ; 247: 112232, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606534

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-Tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the main active component of Polygoni Multiflori Radix, a root of the homonymous plant widely used in traditional Chinese medicine. TSG has protective effects on the liver, reduces cholesterol and possesses anti-oxidant, anti-tumor, and anti-atherosclerotic properties. However, the pharmacological effects and mechanisms of action of Polygonum multiflorum on atherosclerosis (AS) have not been studied yet. PURPOSE: The aim of this research was to study the effects of Polygoni Multiflori Radix Praeparata (PMRP) and its major active chemical constituent TSG on AS in ApoE-deficient (ApoE-/-) mice fed with high fat diets to provide a scientific basis in the use of PMRP and TSG against cardiovascular diseases. METHODS: High fat diet induced AS in ApoE-/- mice were treated with PMRP, TSG (low and high doses), and simvastatin (SIM) for 8 weeks. At the end of the treatment, mouse serum lipid levels, triglycerides (TG), and total cholesterol (TC) were measured by an oxidase method (other indicators were determined by ELISA), while the content in oxidized low density lipoprotein (ox-LDL) and the expression of inflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) in the serum and aortic samples were measured by ELISA. Atherosclerotic plaque morphology was evaluated by oil red O in thoracic aorta. In addition, 16S rDNA-V4 hypervariable region genome sequence of all microbes in the fecal sample from each group was analyzed to evaluate potential structure changes in the gut microbiota after treatment with PMRP and TSG. RESULTS: TSG markedly inhibited AS plaque formation in ApoE-/- mice. Furthermore, PMRP and TSG improved lipid accumulation by reducing TG and ox-LDL levels. TSG inhibited inflammation by the down-regulation of IL-6, TNF-α, VCAM-1 and MCP-1 expression in serum, and PMRP inhibited inflammation by reducing VCAM-1, ICAM-1 and CCRA expression in aortic tissue. In addition, TSG reduced or prevented AS by the regulation of the composition of the overall gut microbiota, such as Firmicutes, Bacteroidetes, Tenericutes, Proteobacteria phyla, Akkermensia genera and Helicobacter pylori. CONCLUSION: PMRP and TSG improved lipid accumulation and inflammation, and regulated the intestinal microbial imbalance in ApoE-/- mice. TSG exerted a preventive effect in the development and progression of AS.

5.
Biosens Bioelectron ; 147: 111790, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669805

RESUMO

In this study, modified hollow titanium dioxide and SnS2 quantum dots (SnS2 QDs) were used to build a novel electrochemiluminescence immunoassay (ECLIA) for ultrasensitive detection of chloramphenicol (CAP). The titanium dioxide hollow spheres (THS) modified with polyethyleneimine (PEI) and gold nanoparticles (Au NPs) was synthesized as a probe material for the novel ECLIA, meanwhile it also could be a coreaction accelerator which could greatly improve the interaction efficiency between SnS2 QDs and S2O82-. Then the modified THS was combined with chloramphenicol antibody to form ECLIA probes, and colloidal gold synthesized as a platform for an ECLIA by ascorbic acid (AA) reduction. A competitive immunoassay strategy was used for the detection of CAP, where CAP in the sample would compete with the coating antigen for the limited antibodies. The proposed ECLIA for CAP detection exhibited high sensitivity with a wide linear range from 0.01 ng mL-1 to 100 ng mL-1 and a low detection limit at 3.1 pg mL-1. Furthermore, it could be seen from electrochemical analysis that the effect of THS on the enhancement of ECL signal is about twice as high as that of ordinary titanium dioxide. Importantly, this work not only successfully applied THS to amplify electrochemical-luminescence signal in the ECLIA, but also successfully prepared a stable and highly selective sensor for ultrasensitive detection of CAP.

6.
J Sci Food Agric ; 100(1): 161-167, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31471904

RESUMO

BACKGROUND: Rapid and accurate diagnosis of nitrogen (N) status in field crops is of great significance for site-specific N fertilizer management. This study aimed to evaluate the potential of hyperspectral imaging coupled with chemometrics for the qualitative and quantitative diagnosis of N status in tea plants under field conditions. RESULTS: Hyperspectral data from mature leaves of tea plants with different N application rates were preprocessed by standard normal variate (SNV). Partial least squares discriminative analysis (PLS-DA) and least squares-support vector machines (LS-SVM) were used for the classification of different N status. Furthermore, partial least squares regression (PLSR) was used for the prediction of N content. The results showed that the LS-SVM model yielded better performance with correct classification rates of 82% and 92% in prediction sets for the diagnosis of different N application rates and N status, respectively. The PLSR model for leaf N content (LNC) showed excellent performance, with correlation coefficients of 0.924, root mean square error of 0.209, and residual predictive deviation of 2.686 in the prediction set. In addition, the important wavebands of the PLSR model were interpreted based on regression coefficients. CONCLUSION: Overall, our results suggest that the hyperspectral imaging technique can be an effective and accurate tool for qualitative and quantitative diagnosis of N status in tea plants. © 2019 Society of Chemical Industry.

7.
Opt Express ; 27(22): 31207-31216, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684355

RESUMO

Optical performance of the lead halide perovskites with zero-dimension (0D) structure has been in a hot debate for optoelectronic applications. Here, Cs4PbBr6 hexagonal micro-particles with a remarkable green emission are first fabricated via a low-temperature solution-process employed ethanol as solvent. Our results underline that the existence of bromine vacancies and the introduction of hydroxyl induce a narrowed band gap with the formation of a defect level, which contributes to the extrinsic photoluminescence (PL) properties synergistically. Thanks to the high exciton binding energy and the unique morphology with a regular geometric structure of the as-obtained micro-particles, two-photon pumped amplified spontaneous emission (ASE) and single mode lasing from an individual Cs4PbBr6 particle are realized. Our results not only provide an insight into the origin of optical emission from Cs4PbBr6, but also demonstrate that the versatile Cs4PbBr6 offers a new opportunity for novel nonlinear photonics applications as an up-conversion laser.

8.
Medicine (Baltimore) ; 98(44): e17722, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689810

RESUMO

BACKGROUND: Ulcerative colitis (UC) and Crohn disease (CD) are the 2 main types of inflammatory bowel diseases (IBDs). Several studies have been conducted to investigate the association of Glutathione S-Transferase M1 (GSTM1) null genotype with UC and CD, but the results are inconsistent. Here, we performed a meta-analysis to clarify this controversy based on relative large sample size. METHODS: A systematic article searching was conducted in the PubMed, EMBASE, SCOPUS, WOS, ProQuest, Chinese National Knowledge Infrastructure (CNKI), and Chinese Wanfang databases up to August 31, 2019. Meta-analysis results were synthesized by using crude odds ratio (OR) with its 95% confidence interval (CI). Heterogeneity, sensitivity analysis, subgroup analysis, and publication bias were assessed by using STATA 11.0 software. RESULTS: A total of 15 relevant studies including 4353 IBDs patients (1848 CD cases, 2505 UC cases) and 5413 controls were included in this meta-analysis. Totally, we found a significant association between GSTM1 null genotype and risk to IBDs in the overall populations (OR = 1.37, 95%CI = 1.13-1.65, P = .001). Stratified by ethnicity, we found a significant association between GSTM1 null genotype and risk to IBDs in the Asian population (OR = 2.54, 95%CI = 2.15-3.00, P = .001), but not in the Caucasian population. Stratified by disease type, we found a significant association between GSTM1 null genotype with CD in the Asian population (OR = 2.37, 95%CI = 1.11-5.06, P = .026), and with UC in the Asian (OR = 2.48, 95%CI = 1.93-3.20, P = .001) population. In addition, funnel plot and Egger linear regression test suggests no publication bias in all genetic models. CONCLUSION: GSTM1 null genotype is associated with susceptibility to IBD, UC, and CD in the Asian population. Further well-designed studies are still needed to confirm these findings.


Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Masculino , Razão de Chances
9.
Bioresour Technol ; 296: 122319, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31689612

RESUMO

A kind of reduced graphene oxide decorated with titanium-based (RGO/TiO2) composites are successfully synthesized and employed in this current study as a novel nonprecious metal catalyst for enhancing bioelectricity generation and cathodic oxygen reduction reaction (ORR) in single chamber microbial fuel cells (MFCs). Compared with commercial Pt/C, RGO/TiO2 shows obviously enhanced oxygen reduction reaction activity due to the appropriately-permeated, large electrochemical active area, enough exposure of electrocatalytic active sites of RGO/TiO2. The air-cathode MFC with RGO/TiO2-1 cathode achieves 1786.7 mW m-3 of power density, 86.7% ±â€¯1.2% of COD removal and 31.6% ±â€¯1.1% of CE, which are higher than commercial Pt/C. Moreover, RGO/TiO2-1 cathode exhibits high-effective electrocatalytic activity, and the power density of RGO/TiO2-1 can keep a stable level and only has a minor decline (5.35%) during 30-cycles operation. These results indicate that RGO/TiO2-1 is a potential cathode catalyst, markedly enhancing cathode ORR, wastewater treatment efficiency, and bioelectricity generation of MFC.

10.
CNS Neurosci Ther ; 25(11): 1277-1281, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31696644

RESUMO

AIMS: We aimed to investigate the effect of different pulse numbers of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the motor cortex on cortical excitability in healthy participants. METHODS: Fifteen healthy participants received 600 and 1200 pulses of 5-Hz rTMS on separate days in a random order. Stimulation (duration, 2 seconds and interval, 1 seconds) was delivered over the left primary motor cortex for the hand, at 90% of resting motor threshold (rMT). The rMT and motor evoked potential (MEP) were measured before stimulation, and at 0 and 30 minutes after rTMS. RESULTS: No significant differences were observed between the two conditions for MEP (P = .919) or rMT (P = .266). Compared with baseline, MEP was increased significantly at 0 (P < .001) and 30 minutes (P < .001) after stimulation. After stimulation, rMT was decreased at 0 minute for the 600 and 1200 pulse conditions (P < .001), but had recovered by 30 minutes (P = .073). CONCLUSION: Subthreshold 5-Hz rTMS increased motor cortex excitability in healthy humans. However, the number of pulses may exhibit a ceiling effect in that beyond a certain point, that is, increasing the number of pulses may exhibit no further increase in cortical excitability.

11.
Microb Biotechnol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691493

RESUMO

Despite their important roles in host nutrition and metabolism, and potential to cause disease, our knowledge of the fungal community in the mammalian gut is quite limited. To date, diversity and composition of fungi in swine gut still remains unknown. Therefore, the first internal transcribed spacer of fungi in faecal samples from three breeds of pigs (10 pigs for each breed) was sequenced based on an Illumina HiSeq 2500 platform, and the relationship between the fungal community and the concentrations of main short-chain fatty acids (SCFAs) was also analysed. Results indicated that Chenghua (local, higher body fat rate), Yorkshire (foreign, higher lean meat and growth rate) and Tibetan (plateau, stronger disease resistance) pigs harboured distinct fungal community. The Basidiomycota and Ascomycota presented as the two predominant phyla, with Loreleia, Russula and Candida as the top three genera in all samples. Network analysis revealed a total of 35 correlations among different fungal genera, with 27 (77.14%) positive and 8 (22.86%) negative pairwise interactions. Canonical correspondence analysis suggested that fungi in the faeces of pigs were more correlated to the concentration of acetate and butyrate rather than propionate. Spearman's correlation further showed that Tomentella was positively correlated to both acetate and butyrate, and Loreleia was positively correlated to propionate (P < 0.05), while Nephroma and Taiwanofungus were negatively correlated to acetate and propionate (P < 0.05). These findings expanded our knowledge on the intestinal fungi in pigs with different genotypes and phenotypes, indicating that fungi may play an indispensable role during the metabolism of host and the maintenance of intestinal health. The cross-feeding between fungi and other microorganisms may be crucial during the digestion of dietary carbohydrates and the associated physiological processes, which is worthy to be further studied.

12.
J Biosci Bioeng ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672431

RESUMO

CotA-laccases are potential enzymes that are widely used in decolorization of dyes and degradation of toxic substances. In this study, a novel CotA-laccase gene from Bacillus pumilus W3 was applied for rational design. After a series of site-directed genetic mutations, the mutant S208G/F227A showed a 5.1-fold higher catalytic efficiency (kcat/Km) than the wild-type CotA-laccase did. The optimal pH of S208G/F227A was 3.5 with ABTS as substrate. The residual activity of mutant S208G/F227A was more than 80% after incubated for 10 h at pH 7-11. Mutant S208G/F227A showed optimal temperature at 80°C with ABTS as substrate. The thermal stability of mutant laccase S208G/F227A was lower than that of wild-type CotA-laccase. This study showed that Gly208 and Ala227 play key roles in catalytic efficiency and it is possible to improve catalytic efficiency of CotA-laccase through site-directed mutagenesis.

13.
ACS Chem Neurosci ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756074

RESUMO

Antiepileptic drugs (AEDs) are the primary agents prescribed for clinical management of limbic epilepsy. However, high incidence of pharmacoresistance and a limited armory of drugs for inhibiting the pathological progression of epilepsy pose major obstacles to managing epilepsy. Here, we investigated the effect of Tetramethylpyrazine (TMP), the main bioactive alkaloid isolated from the oriental medicine Ligusticum chuanxiong Hort., against the epileptogenesis progression of acute hippocampal and corneal (6 Hz) electrical kindling models of TLE. TMP dose-dependently limited the progression of seizures and reduced the after-discharge duration (ADDs) in a hippocampal mouse kindling model. Mice treated with TMP (20, 50 mg/kg, i.p.) remained in stage 1 of epileptic progression for a protracted period, requiring additional stimulation to induce stages 2-5 epileptic phenotypes. TMP (50 mg/kg) also inhibited 6 Hz corneal kindling progression. In contrast, TMP did not reverse the phenotypes induced in a generalized seizures (GS) model, or the maximal electroshock (MES) or pentylenetetrazole (PTZ)-induced models of epilepsy. Furthermore, patch clamp recordings revealed no effect of TMP (10 µM) on CA1 hippocampal neurons' intrinsic properties but suppressed the (i) frequency of spontaneous excitatory post synaptic currents (sEPSCs), (ii) paired pulse ratio (PPR), and (iii) long-term potentiation (LTP) induction in the Schaffer collateral-CA1 pathway. TMP suppressed the activity of calcium, but not sodium, channels. Taken together, these results suggest that TMP has an anti-epileptogenic effect, likely through suppression of excitatory synaptic transmission by its effects on inhibition of calcium channels; these traits distinguish TMP from currently available AEDs. As mice administered TMP did not show any neurologic impairment in the object recognition and open field tests, the data support further development of TMP as a promising treatment for epilepsy.

15.
Neuroscience ; 419: 72-82, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682827

RESUMO

Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG and AG were negatively related to headache frequency and positively related to health condition and disease history. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain on the brain.

16.
CNS Neurosci Ther ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710183

RESUMO

AIMS: To evaluate the clinical significance of coatomer protein complex subunit beta 2 (COPB2) in patients with glioma using a bioinformatics analysis. METHODS: Oncomine, GEO, and The Cancer Genome Atlas databases were used to examine the COPB2 transcript levels in glioma tissues. Gene expression profiles with clinical information from low-grade glioma and glioblastoma (GBM) projects were analyzed for associations between COPB2 expression and clinicopathologic characteristics. Kaplan-Meier survival and Cox regression analyses were used for survival analysis. Gene set enrichment analysis (GSEA) was conducted to screen the pathways involved in COPB2 expression. Gene set variation analysis (GSVA) and correlograms were performed to verify the correlations between COPB2 and inflammatory responses. Canonical correlation analyses examined whether COPB2-high patients have more infiltrating inflammatory and immune cells. RESULTS: COPB2 was highly expressed in gliomas and high COPB2 expression correlated with shorter overall survival time and several poor clinical prognostic variables. GSEA indicated that some immune-related pathways and other signaling pathways in cancer were associated with the COPB2-high phenotype. The GSVA and canonical correlation analysis demonstrated that COPB2 expression was closely linked to inflammatory and immune responses, and higher immune cell infiltration. CONCLUSIONS: COPB2 may be a potential prognostic biomarker and an immunotherapeutic target for glioma.

17.
Am J Chin Med ; 47(7): 1541-1569, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31752524

RESUMO

Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF-ß1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague-Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor-ß1 (TGF-ß1) in LX2 cells and liver tissues were determined. Furthermore, gain-of and loss-of function of miR-21 in miR-21-regulated TGF-ß1/Smad signaling pathway were analyzed in LX2 cells. Liver tissues and serum were collected for pathological analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Corilagin treatment reduced mRNA or protein levels of miR-21, CTGF, α-SMA, TIMP-1, TGF-ß1, COL1A1, p-Smad2, p-Smad3, and p-Smad2/3 both in vitro and in vivo. While corilagin increased mRNA and protein levels of Smad7 and MMP-9. After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF-ß1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of α-SMA and COL1A1 in liver tissues and TGF-ß1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF-ß1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis.

18.
Bone ; : 115117, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31676407

RESUMO

The mechanism and effective treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) are still uncertain. Our previous study revealed that zoledronate (ZOL) preferentially inhibited osteoclasts formation and platelet-derived growth factor-BB (PDGF-BB) secretion, causing suppression of angiogenesis and osteogenesis in vitro. The present study aimed to elucidate whether PDGF-BB had therapeutic effects on rat model of BRONJ by enhancing angiogenesis and angiogenesis. Firstly, rat model of BRONJ was established by ZOL and dexamethasone administration, followed by teeth extraction. The occurrence of BRONJ was confirmed and detected dead bone formation by maxillae examination, micro-CT scan and HE staining (10/10). Compared to control rats (0/10), both angiogenesis and mature bone formation were suppressed in BRONJ-like rats, evidenced by enzyme-linked immunosorbent assay (ELISA) for VEGF (P < 0.01), immunohistochemistry of CD31 (P < 0.05) and OCN (P < 0.01). Moreover, in the early stage of bone healing, the number of preosteoclasts (P < 0.001) and PDGF-BB secretion (P < 0.05) were significantly decreased in bisphosphonates-treated rats, along with the declined numbers of microvessels (P < 0.05) and osteoblasts (P < 0.05). In vitro study, CCK8 assay, alizarin red S staining and western blot assay showed that mandible-derived bone marrow mesenchymal stem cells (BMMSCs) in BRONJ-like rats presented suppressed functions of proliferation, osteogenesis and angiogenesis. Interestingly, recombinant PDGF-BB was able to rescue the impaired functions of BMMSCs derived from BRONJ-like rats at more than 10 ng/ml. Then fibrin sealant with or without recombinant PDGF-BB were tamped into the socket after debridement in BRONJ rats. After 8 weeks, fibrin sealant containing PDGF-BB showed significant therapeutic effects on BRONJ-like rats (bone healing: 8/10 vs 3/10, P < 0.05) with enhancing microvessels and mature bone formation. Our study suggested that the inhibition of angiogenesis and osteogenesis, the potential mechanisms of BRONJ, might partly result from suppression of PDGF-BB secretion in the early stage of bone healing. PDGF-BB local treatment after debridement might avail the healing of BRONJ by increasing angiogenesis and osteogenesis.

19.
ACS Chem Neurosci ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31697467

RESUMO

Naringenin (2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one is a natural flavonoid found in fruits from the citrus family. Because (2S)-naringenin is known to racemize, its bioactivity might be related to one or both enantiomers. Computational studies predicted that (2R)-naringenin may act on voltage-gated ion channels, particularly the N-type calcium channel (CaV2.2) and the NaV1.7 sodium channel-both of which are key for pain signaling. Here we set out to identify the possible mechanism of action of naringenin. Naringenin inhibited depolarization-evoked Ca2+ influx in acetylcholine-, ATP-, and capsaicin-responding rat dorsal root ganglion (DRG) neurons. This was corroborated in electrophysiological recordings from DRG neurons. Pharmacological dissection of each of the voltage-gated Ca2+ channels subtypes could not pinpoint any selectivity of naringenin. Instead, naringenin inhibited NaV1.8-dependent and tetrodotoxin (TTX)-resistant while sparing tetrodotoxin sensitive (TTX-S) voltage-gated Na+ channels as evidenced by the lack of further inhibition by the NaV1.8 blocker A-803467. The effects of the natural flavonoid were validated ex vivo in spinal cord slices where naringenin decreased both the frequency and amplitude of sEPSC recorded in neurons within the substantia gelatinosa. The antinociceptive potential of naringenin was evaluated in male and female mice. Naringenin had no effect on the nociceptive thresholds evoked by heat. Naringenin's reversed allodynia was in mouse models of postsurgical and neuropathic pain. Here, driven by a call by the National Center for Complementary and Integrative Health's strategic plan to advance fundamental research into basic biological mechanisms of the action of natural products, we advance the antinociceptive potential of the flavonoid naringenin.

20.
Sci Rep ; 9(1): 16989, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740703

RESUMO

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

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