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1.
Mol Cell Biochem ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33078341

RESUMO

Silica-induced apoptosis of alveolar macrophages (AMs) is an essential part of silicosis formation. Autophagy tends to present a bidirectional effect on apoptosis. Our previous study found that the blockade of autophagy degradation might aggravate the apoptosis of AMs in human silicosis. We presume that targeting the autophagic pathway is regarded as a promising new strategy for silicosis fibrosis. As a main active component of the Atractylodes rhizome, Atractylenolide III (ATL-III) has been widely applied in clinical anti-inflammation. However, the effect and mechanism of ATL-III on autophagy in AMs of silicosis are unknown. In this study, we found that ATL-III might inhibit autophagy by mTOR-dependent manner, thereby improving the blockage of autophagic degradation in AMs. ATL-III alleviated the apoptosis of AMs in human silicosis. Furthermore, Rapamycin reversed the protective effect of ATL-III in AMs. These results indicate that ATL-III may be a potentially protective ingredient targeting autophagy for workers exposed to silica dust. These findings also suggest that inhibition of autophagy may be an effective way to alleviate the apoptosis of AMs in silicosis.

2.
Toxicology ; 446: 152611, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031904

RESUMO

Cadmium (Cd), a heavy metal produced by various industries, contaminates the environment and seriously damages the skeletal system of humans and animals. Recent studies have reported that Cd can affect the viability of cells, including osteoblasts, both in vivo and in vitro. However, the mechanism of Cd-induced apoptosis remains unclear. In the present study, primary rat osteoblasts were used to investigate the Cd-induced apoptotic mechanism. We found that treatment with 2 and 5 µM Cd for 12 h decreased osteoblast viability and increased apoptosis. Furthermore, Cd increased the generation of reactive oxygen species (ROS), and, thus, DNA damage measured via p-H2AX. The level of the nuclear transcription factor p53 was significantly increased, which upregulated the expression of PUMA, Noxa, Bax, and mitochondrial cytochrome c, downregulated the expression of Bcl-2, and increased the level of cleaved caspase-3. However, pretreatment with the ROS scavenger N-acetyl-l-cysteine (NAC) or the p53 transcription specific inhibitor PFT-α suppressed Cd-induced apoptosis. Our results indicate that Cd can induce apoptosis in osteoblasts by increasing the generation of ROS and activating the mitochondrial p53 signaling pathway, and this mechanism requires the transcriptional activation of p53.

3.
Medicine (Baltimore) ; 99(33): e21556, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872004

RESUMO

Moxa floss is the primary material used in moxibustion, an important traditional Chinese medicine therapy that uses ignited moxa floss to apply heat to the body for disease treatment. Till date, there is no available data regarding quality control of different grades of moxa floss. The objectives of this study were to explore the probative value of the electronic nose (e-nose) in differentiating different quality grades of commercial moxa floss sold in China, and to investigate if data mining techniques could be used to optimize the sensor array while retaining classification accuracy of the samples. The e-nose with 12 metal oxide semiconductor type sensors was used to analyze the odor profiles of 15 commercial moxa floss samples of different quality grades. Feature selection algorithms using principal component analysis (PCA) and BestFirst (BC) coupled with correlation-based feature subset selection (CfsSubsetEval) method were used to obtain the most efficient feature subsets. Results for the BC feature selection method identified 3 optimized sensors (S2, S6, and S11), suggesting that aromatic compounds relate more to the identification of the samples. Radial basis function (RBF), multilayer perceptron (MLP), and random forests (RF) performed well in discriminating the samples, retaining prediction accuracies above 85%, which achieved cost-effectiveness and operational simplicity, while retaining prediction accuracy. The e-nose could be a rapid and nondestructive method for objective preliminary classification of quality grades of moxa floss and may be used for future studies related to moxa products safety and quality.


Assuntos
Medicamentos de Ervas Chinesas/classificação , Nariz Eletrônico , Moxibustão , Fumaça/análise , Algoritmos , China , Mineração de Dados , Humanos , Análise de Componente Principal
4.
Clin Exp Optom ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32944992

RESUMO

BACKGROUND: To evaluate the surgical outcomes of pars plana vitrectomy (PPV) with air tamponade in medium-large macular holes (MHs). METHODS: Data for 26 eyes of 26 consecutive patients with medium-large full-thickness MHs (> 400 µm) who underwent PPV, internal limiting membrane (ILM) peeling, and sterile air tamponade were studied retrospectively. Best-corrected visual acuity and the closure rate were noted. The follow-up period was one to 20 months (median, four months). RESULTS: The age range of the patients was 53-73 years (median, 65 years). The mean minimum diameter of the MHs was 550 ± 99 µm. Prior to surgery, 10 eyes (38 per cent) were stage three, and 16 eyes (62 per cent) were stage four. The pre-operative symptom duration ranged from one month to 24 months (median, four months). Twenty-four MHs (92.3 per cent) were successfully closed after a single operation. Two (7.7 per cent) patients had a persistent MH. The average visual acuity, calculated as the logarithm of the minimal angle of resolution, improved from 1.44 ± 0.45 pre-operatively to 0.54 ± 0.29 at the end of the follow-up period (p < 0.001, paired t-test). CONCLUSION: Vitrectomy with ILM peeling and sterile air tamponade is an effective and safe surgical technique for managing medium-large MHs with a shorter history and does not require intravitreal long-acting gas tamponade while maintaining a long-term, face-down position.

5.
PLoS Negl Trop Dis ; 14(9): e0008652, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32877407

RESUMO

China once suffered greatly from schistosomiasis japonica, a major zoonotic disease. Nearly 70 years of multidisciplinary efforts have achieved great progress in disease control, with infections in both humans and bovines significantly reduced to very low levels. However, reaching for the target of complete interruption of transmission at the country level by 2030 still faces great challenges, with areas of ongoing endemicity and/or re-emergence within previously 'eliminated' regions. The objectives of this study were, by using meta-analytical methods, to estimate the overall prevalence of Schistosoma japonicum infections in abundant commensal rodent species in mainland China after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. In doing so we thereby aimed to further assess the role of wild rodents as potential reservoirs in ongoing schistosome transmission. Published studies on infection prevalence of S. japonicum in wild rodents in mainland China since 1980 were searched across five electronic bibliographic databases and lists of article references. Eligible studies were selected based on inclusion and exclusion criteria. Risks of within and across study biases, and the variations in prevalence estimates attributable to heterogeneities were assessed. The pooled infection prevalence and its 95% confidence intervals (CIs) were calculated with the Freeman-Tukey double arcsine transformation. We identified a total of 37 relevant articles involving 61 field studies which contained eligible data on 8,795 wild rodents across mainland China. The overall pooled infection prevalence was 3.86% (95% CI: 2.16-5.93%). No significant change in the overall pooled prevalence was observed between 1980-2003 (n = 23 studies) and 2004-current (n = 38 studies). However, whilst the estimated prevalence decreased over time in the marshland and lake regions, there was an apparent increase in prevalence within hilly and mountainous regions. Among seven provinces, a significant prevalence reduction was only seen in Jiangsu where most endemic settings are classified as the marshland and lakes. These estimates changed over season, ranging from 0.58% in spring to 22.39% in winter, in association with increases in rodent density. This study systematically analyzed S. japonicum infections in wild rodents from the published literature over the last forty years after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. Although numbers of schistosomiasis cases in humans and bovines have been greatly reduced, no such comparable overall change of infection prevalence in rodents was detected. Furthermore, there appeared to be an increase in S. japonicum prevalence in rodents over time within hilly and mountainous regions. Rodents have been projected to become the dominant wildlife in human-driven environments and the main reservoir of zoonotic diseases in general within tropical zones. Our findings thus suggest that it is now necessary to include monitoring and evaluation of potential schistosome infection within rodents, particularly in hilly and mountainous regions, if we are ever to reach the new 2030 elimination goals and to maximize the impact of future public, and indeed One Health, interventions across, regional, national and international scales.

6.
Sci Total Environ ; 750: 141638, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32858297

RESUMO

Cadmium is a common environmental pollutant that accumulates in the bone and kidneys and causes severe health and social problems. However, the effects of Cd on the occurrence of osteoporosis and its mechanism of action in this process are unclear. To test whether Cd-induced osteoporosis is mediated via P2X7/PI3K/AKT signaling, duck bone marrow mesenchymal stem cells (BMSCs) and bone marrow macrophage cells (BMMs) were treated with Cd for 5 days, and duck embryos were treated with Cd. Micro-CT analysis indicated that Cd-induced osteoporosis occurs in vivo, and histopathology and immunohistochemical analyses also revealed that Cd induced bone damage and the downregulation of osteogenic and bone resorption-related proteins. Cd exposure significantly inhibited the differentiation of BMSCs and BMMs into osteoblasts and osteoclasts in vitro, and promoted osteoblast and osteoclast apoptosis. Cd exposure significantly downregulated the P2X7/PI3K/AKT signaling pathway in vivo and in vitro, and inhibition of this signaling pathway significantly aggravated osteoblast and osteoclast differentiation. Cd exposure also upregulated the OPG/RANKL ratio in vivo and in vitro, further inhibiting osteoclast differentiation. These results demonstrate that Cd causes osteoporosis in duck by inhibiting P2X7/PI3K/AKT signaling and increasing the OPG/RANKL ratio. These results establish a previously unknown mechanism of Cd-induced osteoporosis.

7.
Differentiation ; 114: 58-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771207

RESUMO

Osteoclasts are terminally multinucleated cells that are regulated by nuclear factor-activated T cells c1 (NFATc1), and are responsible for bone resorption while the tartrate resistant acid phosphatase (TRAP) enzymes releases into bone resorption lacunae. Furthermore, tumor suppressor p53 is a negative regulator during osteoclastogenesis. Osteoprotegerin (OPG) inhibits osteoclastogenesis and bone resorption by activating autophagy, however, whether p53 is involved in OPG-mediated inhibition of osteoclastogenesis remains unclear. In the current study, OPG could enhance the expression of p53 and tuberin sclerosis complex 2 (TSC2). Moreover, the expression of p53 is regulated by autophagy during OPG-mediated inhibition of osteoclastogenesis. Inhibition of p53 by treated with pifithrin-α (PFTα) causing augments of osteoclastogenesis and bone resorption, also reversed OPG-mediated inhibition of osteoclastogenesis by reducing the expression of TSC2. In addition, knockdown of TSC2 using siRNA could rescue OPG-mediated inhibition of osteoclastogenesis by reducing autophagy, which is manifested by the decrease of the expression of Beclin1 and the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta 1 (S6K1, also known as p70S6K). Collectively, p53 plays a critical role during OPG-mediated inhibition of osteoclastogenesis via regulating the TSC2-induced autophagy in vitro.

8.
Int J Nanomedicine ; 15: 4959-4967, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764929

RESUMO

Background: Particle-based drug delivery systems (DDSs) have a demonstrated value for drug discovery and development. However, some problems remain to be solved, such as limited stimuli, visual-monitoring. Aim: To develop an intelligent multicolor DDSs with both near-infrared (NIR) controlled release and macroscopic color changes. Materials and Methods: Microparticles comprising GO/pNIPAM/PEGDA composite hydrogel inverse opal scaffolds, with dextran and calcium alginate hydrogel were synthesized using SCCBs as the template. The morphology of microparticle was observed under scanning electron microscopy, and FITC-dextran-derived green fluorescence images were determined using a confocal laser scanning microscope. During the drug release, FITC-dextran-derived green fluorescence images were captured using fluorescent inverted microscope. The relationship between the power of NIR and the drug release rate was obtained using the change in optical density (OD) values. Finally, the amount of drug released could be estimated quantitatively used the structural color or the reflection peak position. Results: A fixed concentration 8% (v/v) of PEGDA and 4mg/mL of GO was chosen as the optimal concentration based on the balance between appropriate volume shrinkage and structure color. The FITC-dextran was uniformly encapsulated in the particles by using 0.2 wt% sodium alginate. The microcarriers shrank because of the photothermal response and the intrinsic fluorescence intensity of FITC-dextran in the microparticles gradually decreased at the same time, indicating drug release. With an increasing duration of NIR irradiation, the microparticles gradually shrank, the reflection peak shifted toward blue and the structural color changed from red to orange, yellow, green, cyan, and blue successively. The drug release quantity can be predicted by the structural color of microparticles. Conclusion: The multicolor microparticles have great potential in drug delivery systems because of its vivid reporting color, excellent photothermal effect, and the good stimuli responsivity.


Assuntos
Portadores de Fármacos/química , Microesferas , Resinas Acrílicas/química , Alginatos/química , Cor , Dextranos/química , Liberação Controlada de Fármacos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Hidrogéis/química , Fenômenos Ópticos , Polietilenoglicóis/química
9.
Mol Med Rep ; 22(3): 2551-2563, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705200

RESUMO

Cadmium (Cd) is a heavy metal that can accumulate and cause damage to a variety of tissues and organs. The kidney is the primary target organ for Cd accumulation and toxic damage. Autophagy, which is a critical intracellular process, serves an important role in maintaining the homeostasis of the intracellular environment. Endoplasmic reticulum stress (ERS) is another key process that functions to promote cell survival or results in cell injury and death. Both autophagy and ERS are associated with oxidative stress; however, the mechanism by which ERS is regulated by autophagy in Cd­induced nephrotoxicity remains unclear. The present study employed a rat NRK­52E cell model, where alterations in cell morphology, density and viability, the accumulation of reactive oxygen species, an increase in malondialdehyde generation and a decrease in antioxidant enzyme activity and apoptosis were induced by Cd treatment. Cd induced the activation of nuclear factor erythroid 2­related factor 2 (NRF2), an obstruction of autophagic flux and ERS, which were attenuated by puerarin administration. Furthermore, puerarin failed to alleviate ERS following knockdown of autophagy­related protein 7 in NRK­52E cells. Overexpression of Ras­related protein Rab­7, which promotes the fusion of autophagosomes and lysosomes, efficiently reduced ERS. Taken together, these results indicate that puerarin administration restored the autophagic flux to alleviate ERS, via blocking the activation of NRF2.

10.
Chemosphere ; 255: 126999, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32679628

RESUMO

Currently there are few reports on the combined immunotoxicity of zearaleone (ZEA) and deoxynivalenol (DON). Since the two coexist naturally, it is necessary to understand the immunotoxicity caused by the two mycotoxins alone and in combination. To examine T lymphocytes activation and immune effect during activation, we used mouse primary spleen T lymphocytes as the experimental material and concanavalin (Con A) as the stimulator. The effects of ZEA, DON, and their combined exposure on T lymphocytes immune related function and the relationship between the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and mycotoxin induced T lymphocytes apoptosis were studied in vitro. Specifically, T lymphocytes were isolated from primary mouse splenic lymphocytes, activated by Con A and then exposed to different concentrations of ZEA, DON, and their combinations. Our results showed that ZEA and DON alone and their combinations (20:1) can decrease the cell viability of T lymphocytes activated by Con A. The inhibitory effect of the combined groups was greater than that of the single mycotoxins, showing a synergistic effect. In addition, single or combined mycotoxins can lead to intracellular and surface ultrastructure damage of T lymphocytes, inhibit the expression of CD25 and CD278 and inhibit the synthesis of effect molecules poreforming protein (PFP), granzyme A (GZMA), and tumor necrosis factor-α (TNF-α). Meanwhile, the single mycotoxin or combined mycotoxins can promote the apoptosis of T lymphocytes which was accompanied by the overactivation of MAPK. After using the inhibitors of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK) in the MAPK pathway, we found that the apoptosis of the cells induced by the ZEA was significantly decreased, and the apoptosis of the cells induced by DON had no significant changes. This suggests that the activation of MAPK induced by ZEA can promote the apoptosis of T lymphocytes, but the activation of MAPK induced by DON is not directly related to T cell apoptosis.


Assuntos
Imunotoxinas/toxicidade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-2 , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Micotoxinas/toxicidade , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa
11.
Toxicology ; 442: 152538, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32693121

RESUMO

Cadmium (Cd) is one of worldwide environmental pollutants that causes bone homeostasis, which depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts (OB). However, the Cd toxicity on OB and its mechanism are unclear. Autophagy is an evolutionarily conserved degradation process in which domestic intracellular components are selectively digested for the recycling of nutrients and energy. This process is indispensable for cell homeostasis maintenance and stress responses. Dysregulation at the level of autophagic activity consequently disturbs the balance between bone formation and bone resorption and mediates the onset and progression of multiple bone diseases, including osteoporosis. TAK1 has been recently emerged as an activator of AMPK and hence an autophagy inducer. AMPK is a key molecule that induces autophagy and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by mTORC1. In this study, we found that Cd treatment caused the formation of autophagosomes, LC3-II lipidation and p62 downregulation, and the increased autophagic flux, indicating that Cd treatment induced autophagy in OBs. Cd treatment induced TAK1 activation mediated AMPK phosphorylation, which promoted autophagy via phosphorylation of ULK1 at S317. Meanwhile, Cd treatment dramatically decreased mTORC1, S6K1, 4E-BP1, S6, ULK1S555 and ULK1S757 phosphorylation, suggesting that mTORC1 activity was inhibited and inactive mTORC1 prevents ULK1 activation by phosphorylating ULK1 at SerS555 and Ser757. Our data strongly suggest that TAK1 mediates AMPK activation, which activates ULK1 by phosphorylating ULK1S317 and suppressing mTORC1-mediated ULK1S555 and ULK1S757 phosphorylation. Our study has revealed a signaling mechanism for TAK1 in Cd-induced autophagy in OBs.

12.
J Control Release ; 326: 265-275, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32687940

RESUMO

Paclitaxel is one of the most widely used anticancer agents, but strong side effects and low bioavailability limit its clinical efficacy. The use of tumor microenvironment-responsive prodrugs is promising to solve these problems, and a smart linkage is crucial to achieve the efficient release of paclitaxel from such prodrugs in tumor. Herein, an acid-responsive acetone-based acyclic ketal linkage is used to construct paclitaxel prodrugs with different length of poly(ethylene glycol) (PEG). The PEGylated acetone-based acyclic-ketal-linked prodrugs of paclitaxel (PKPs) self-assembled into nanoparticles that were stable in normal physiological environment but released paclitaxel rapidly in mildly acidic environment in tumor. The length of PEG had considerable impact on size and critical micelle concentration of PKP nanoparticles, thereby affecting prodrug hydrolysis kinetics, pharmacokinetics, biodistribution, and antitumor activity for PKP nanoparticles. In an A2780 xenograft mouse model, PKP nanoparticles displayed improved pharmacokinetics and superior antitumor efficacy against Taxol. Our results demonstrate that acyclic-ketal-based prodrugs are useful for the development of acid-responsive anticancer nanomedicines.

13.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3155-3160, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726024

RESUMO

To discuss the effect of deterioration on the quality of Armeniacae Semen Amarum by observing the changes of macroscopic characteristics, active components and rancidness degrees of Armeniacae Semen Amarum in deterioration process. The traditional macroscopic identification was used to observe, identify and classify the morphologic and organleptic characteristics of Armeniacae Semen Amarum. The contents of amygdalin and fatty oil(two representatives of active components) were detected by HPLC and general rule 0713 in Chinese Pharmacopoeia, respectively. Acid value and peroxide value of the samples were selected as the representative indices of different rancidness degrees, and the general rule 2303 was adopted as the method for quantitative analysis. Then principal component analysis(PCA), partial least square analysis discrimination analysis(PLS-DA) were further utilized to establish the discriminative models of samples with different rancidness degrees, and also to screen out the largest contribution factors. In sensory evaluation, Armeniacae Semen Amarum samples were divided into three groups: non-rancid, slightly-rancid, and noticeably-rancid. The color of seed coat, cotyledon and surface of noticeably-rancid samples was deepened, and the odor differed much from non-rancid samples. Average content of amygdalin and fatty oil in non-rancid samples was 4.12% and 67.77%, respectively, both meeting the requirements of Chinese Pharmacopoeia; and decreased to some extent in slightly-rancid samples. However, the content of amygdalin sharply dropped to 0.074% in noticeably-rancid samples. The acid value and peroxide value were increased significantly with the intensifying of the rancidness degree, from only 1.363 and 0.016 74 in non-rancid samples to 1.865 and 0.023 70 in slightly-rancid samples, even doubled in noticeably-rancid samples(2.167 and 0.033 82). The discriminative models established by PCA and PLS-DA could complete the task of distinguishing the non-rancid samples from noticeably-rancid ones. The contribution degree of amygdalin content as one of the input attributes of discriminative model was higher than 1. Rancidness affected the quality of Armeniacae Semen Amarum, resulting in appearance changes, decrease in content of active components, and increase in acid value and peroxide value. Obviously, noticeably-rancid samples were non-conforming to Chinese Pharmacopoeia and no longer suitable for medicinal use. Rancidness can significantly reduce the quality of Armeniacae Semen Amarum, and even could possibly produce toxicity, which should attach more attention.


Assuntos
Amigdalina , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Sêmen
14.
Sci Rep ; 10(1): 10658, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32581243

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

15.
Reprod Domest Anim ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32542809

RESUMO

The fertilization capacity of sex-sorted sperms is seriously decreased, which inhibits its wide application. However, little information is still available about the effect of vitamin C (VC) and lycopene (Lyc) on the fertilization capacity of sex-sorted bull sperm. In this study, the washing medium and fertilization medium of sex-sorted sperm from three bull individuals were supplemented with different concentrations of VC (0, 1 × 10-3 , 1 × 10-4 , 1 × 10-5 , 1 × 10-6  M) or Lyc (0, 1 × 10-4 , 1 × 10-5 , 1 × 10-6 , 1 × 10-7 ). After washing twice and incubation for 1.5 hr, the malondialdehyde (MDA) level, phosphatidylserine (PS) translocation, membrane potential (Δψm) and IVF (in vitro fertilization) ability of sex-sorted sperm were investigated. For the sex-sorted sperm of bulls A, B and C, 1 × 10-3  M VC or 1 × 10-4  M Lyc treatment significantly decreased their MDA levels and PS translocation and increased their Δψm levels and cleavage rates after IVF. When blastocysts were concerned, 1 × 10-4  M Lyc significantly improved the blastocyst rates and their IFN-tau expression of bulls A and C. In conclusion, supplementation of 1 × 10-3  M VC or 1 × 10-4  M Lyc in washing and fertilization medium contributed greatly to improving the fertilization capacity of sex-sorted bull sperm during IVF procedure.

16.
Toxicol In Vitro ; 67: 104923, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32599263

RESUMO

Calcium is essential to various physiological and pathophysiological cellular processes. Calcium-sensing receptor (CasR), a seven-transmembrane-spanning protein that responds to changes in extracellular Ca2+, partly modulates calcium homeostasis, thereby influencing bone metabolism. In this study, we aimed to elucidate the role of CasR in Cd-induced calcium homeostasis disruption and OB apoptosis, and the underlying mechanisms. Cd treatment dramatically increased the protein expression of CasR and elevated the intracellular calcium concentration. Meanwhile, OBs apoptosis rate and caspase-dependent apoptosis protein levels, including cleaved caspase 3, cleaved caspase 9 and the ratio of Bax/Bcl-2 were increased. However, downregulation of CasR by CasR siRNA effectively suppressed the effects of Cd on theses phenomena. At the same time, we illustrated that CasR siRNA pretreatment blocked Cd-inhibited the phosphorylation of PKC and decreased Cd-induced the phosphorylation of PI3K/AKT. Our results suggested that CasR-mediated PKC and PI3K/AKT signaling pathways involve in calcium oscillation and apoptosis in OB caused by Cd maybe responsible for the bone homeostasis.

17.
PLoS One ; 15(6): e0235415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598354

RESUMO

To better understand the mechanism of inherent salt resistance in Jerusalem artichoke (Helianthus tuberosus L.), physiological and metabolic responses of tubers at the initiation stage of sprouting under different salt stress levels were evaluated in the present study. As a result, 28 metabolites were identified using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Jerusalem artichoke tubers showed minor changes in metabolic response under moderate salt stress when they had not yet sprouted, where metabolism was downregulated at the start of sprouting and then upregulated significantly after plants became autotrophic. However, mild and severe salt stress levels caused different metabolic response patterns. In addition, the accumulation of fructose and sucrose was enhanced by moderate salt stress, while glucose was highly consumed. Aspartate and asparagine showed accelerated accumulation in sprouting Jerusalem artichoke tubers that became autotrophic, suggesting the enhancement of photosynthesis by moderate salt stress.


Assuntos
Frutose/metabolismo , Glucose/metabolismo , Helianthus/metabolismo , Tubérculos/metabolismo , Estresse Salino , Sacarose/metabolismo , Helianthus/crescimento & desenvolvimento , Fotossíntese , Tubérculos/crescimento & desenvolvimento
18.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2389-2394, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495597

RESUMO

This study was aimed to develop a simple, rapid and reliable method for identifying Armeniacae Semen Amarum from different processed products and various rancidness degrees. The objective odor information of Armeniacae Semen Amarum was obtained by electronic nose. 105 batches of Armeniacae Semen Amarum samples were studied, including three processed products of Armeniacae Semen Amarum, fried Armeniacae Semen Amarum and peeled Armeniacae Semen Amarum, as well as the samples with various rancidness degrees: without rancidness, slight rancidness, and rancidness. The discriminant models of different processed products and rancidness degrees of Armeniacae Semen Amarum were established by Support Vector Machine(SVM), respectively, and the models were verified based on back estimation of blind samples. The results showed that there were differences in the characteristic response radar patterns of the sensor array of different processed products and the samples with different rancidness degrees. The initial identification rate was 95.90% and 92.45%, whilst validation recognition rate was 95.38% and 91.08% in SVM identification models. In conclusion, differentiation in odor of different processed and rancidness degree Armeniacae Semen Amarum was performed by the electronic nose technology, and different processed and rancidness degrees Armeniacae Semen Amarum were successfully discriminated by combining with SVM. This research provides ideas and methods for objective identification of odor of traditional Chinese medicine, conducive to the inheritance and development of traditional experience in odor identification.


Assuntos
Medicamentos de Ervas Chinesas , Nariz Eletrônico , Medicina Tradicional Chinesa , Sêmen , Máquina de Vetores de Suporte
19.
Toxicology ; 441: 152520, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32522522

RESUMO

Environmental cadmium (Cd) pollution can ultimately lead to chronic toxicity via food consumption. Previous studies have demonstrated that long-term low-dose Cd exposure decreases bone mineral density and bone mineralization. Cd may increase receptor activator of nuclear factor-κ B ligand (RANKL) expression by osteoclasts, and inhibit the expression of osteoprotegerin. However, the molecular mechanism underlying Cd toxicity toward osteoclasts is unclear. In this study, bone marrow monocytes were isolated from C57BL/6 mice and treated with macrophage colony-stimulating factor and RANKL to induce the formation of osteoclasts. The results show that low-dose Cd exposure induced osteoclast differentiation. Cd also increased the intracellular calcium concentration of osteoclasts by triggering release of calcium ions from the endoplasmic reticulum into the cytoplasm. Furthermore, the elevation of intracellular calcium levels was shown to activate the calmodulin (CaM)/calmodulin-dependent protein kinase (CaMK) pathway. NFATc1 is a downstream protein of CaM/CaMK signaling, as well as a key player in osteoclast differentiation. Overall, we conclude that Cd activates the CaM/CaMK/NFATc1 pathway and regulates osteoclast differentiation by increasing intracellular calcium concentration. Our data provide new insights into the mechanisms underlying osteoclast differentiation following Cd exposure. This study provides a theoretical basis for future investigations into the therapeutic application of CaMK inhibitors in osteoporosis induced by Cd exposure.


Assuntos
Cádmio/toxicidade , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Calmodulina/metabolismo , Diferenciação Celular/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Cádmio/farmacologia , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Osteoclastos/fisiologia , Reação em Cadeia da Polimerase em Tempo Real
20.
Reprod Fertil Dev ; 32(7): 676-689, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32317092

RESUMO

To explore the mechanisms leading to the poor quality of IVF blastocysts, the single-cell whole-genome methylation sequencing technique was used in this study to analyse the methylation patterns of bovine blastocysts derived from invivo, fresh (IVF) or vitrified (V_IVF) oocytes. Genome methylation levels of blastocysts in the IVF and V_IVF groups were significantly lower than those of the invivo group (P<0.05). In all, 1149 differentially methylated regions (DMRs) were identified between the IVF and invivo groups, 1578 DMRs were identified between the V_IVF and invivo groups and 151 DMRs were identified between the V_IVF and IVF groups. For imprinted genes, methylation levels of insulin-like growth factor 2 receptor (IGF2R) and protein phosphatase 1 regulatory subunit 9A (PPP1R9A) were lower in the IVF and V_IVF groups than in the invivo group, and the methylation level of paternally expressed 3 (PEG3) was lower in the V_IVF group than in the IVF and invivo groups. Genes with DMRs between the IVF and invivo and the V_IVF and IVF groups were primarily enriched in oocyte maturation pathways, whereas DMRs between the V_IVF and invivo groups were enriched in fertilisation and vitrification-vulnerable pathways. The results of this study indicate that differences in the methylation of critical DMRs may contribute to the differences in quality between invitro- and invivo-derived embryos.

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