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1.
Artigo em Inglês | MEDLINE | ID: mdl-33854310

RESUMO

Background: Circular RNAs (circRNAs) have been identified to play roles in the respiratory diseases. Here, this study aimed to elucidate the function of circRNA oxysterol binding protein like 2 (circOSBPL2) in the development of smoke-related chronic obstructive pulmonary diseases (COPD). Methods: The expression of circ-OSBPL2, microRNA (miR)-193a-5p, and bromodomain-containing protein 4 (BRD4) was detected using qRT-PCR and Western blot assays. Cigarette smoke extract (CSE)-induced human bronchial epithelial cells (HBECs) was applied to mimic smoke-related COPD in vitro. Flow cytometric analysis of cell apoptosis and ELISA analysis of interleukins (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) levels were performed. The malondialdehyde (MDA) and superoxide dismutase (SOD) production levels were analyzed according to the kit instructions. The binding interaction between miR-193a-5p and circ-OSBPL2 or BRD4 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assays. Results: Circ-OSBPL2 was highly expressed in lung tissues of smokers without or with COPD, particularly in smokers with COPD. Also, the expression of circ-OSBPL2 was dose and time-dependently elevated in CSE-induced HBECs. Circ-OSBPL2 down-regulation in HBECs attenuated CSE-evoked cell proliferation arrest, and cell apoptosis, inflammation and oxidative stress promotion. Mechanistically, circ-OSBPL2 served as a sponge for miR-193a-5p, and miR-193a-5p inhibition reversed the effects of circ-OSBPL2 knockdown on CSE-mediated HBECs. Besides that, miR-193a-5p directly targeted BRD4, and miR-193a-5p re-expression in HBECs abolished CSE-induced HBEC injury, which was reverted by BRD4 up-regulation. Additionally, we also found circ-OSBPL2 could indirectly regulate BRD4 via miR-193a-5p. Conclusion: Circ-OSBPL2 contributed to the apoptosis, inflammation, and oxidative stress of HBECs in smoke-related COPD by miR-193a-5p/BRD4 axis, suggesting a novel insight on the pathogenesis of COPD and a potential therapeutic strategy for future clinic intervention in COPD.

2.
Sci Total Environ ; 783: 146954, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33866171

RESUMO

Wastewater treatment plants (WWTPs) have become an important source of microplastics (MPs) contamination and most MPs remain in the sludge inducing potential impacts on sludge disposal. However, little is known about the influence of MPs on the characteristics of sludge, which is essential for sludge disposal. In this study, the dewaterability of activated sludge in response to chronic exposure (60 days) to MPs of different sizes (213.7 nm ~ 4.2 mm) and polymers (polystyrene, polyethylene, and polyvinyl chloride) were investigated. Overall, different particle sizes caused more evident effects on sludge dewatering than different polymer types did. Millimeter MPs (~4 mm) dramatically reduced the dewaterability of sludge by 29.6% ~ 47.7%. These effects were mainly caused by the physical crushing of MPs on sludge flocs, except polyvinyl chloride (PVC)-MPs, possibly containing additives, induced toxicity on sludge. Moreover, 100 mg/L nano-size MPs (213 nm) also reduced the dewatering performance of sludge. The potential mechanism is that nano-size MPs inhibited sludge activity and decreased the abundance of key microorganisms, which subsequently altered the composition and spatial distribution of extracellular polymeric substances (EPS), and finally impeded sludge dewatering. Our results highlight the impacts of different sizes of MPs on the characteristics of sludge, affecting the final disposal of sludge.

3.
Viruses ; 13(3)2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802878

RESUMO

The dicistrovirus intergenic region internal ribosome entry site (IGR IRES) uses an unprecedented, streamlined mechanism whereby the IRES adopts a triple-pseudoknot (PK) structure to directly bind to the conserved core of the ribosome and drive translation from a non-AUG codon. The origin of this IRES mechanism is not known. Previously, a partial fragment of a divergent dicistrovirus RNA genome, named ancient Northwest territories cripavirus (aNCV), was extracted from 700-year-old caribou feces trapped in a subarctic ice patch. The aNCV IGR sequence adopts a secondary structure similar to contemporary IGR IRES structures, however, there are subtle differences including 105 nucleotides upstream of the IRES of unknown function. Using filter binding assays, we showed that the aNCV IRES could bind to purified ribosomes, and toeprinting analysis pinpointed the start site at a GCU alanine codon adjacent to PKI. Using a bicistronic reporter RNA, the aNCV IGR can direct translation in vitro in a PKI-dependent manner. Lastly, a chimeric infectious clone swapping in the aNCV IRES supported translation and virus infection. The characterization and resurrection of a functional IGR IRES from a divergent 700-year-old virus provides a historical framework for the importance of this viral translational mechanism.

4.
J Nanobiotechnology ; 19(1): 85, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766052

RESUMO

BACKGROUND: Graphene oxide (GO), a novel carbon-based nanomaterial, has promising applications in biomedicine. However, it induces potential cytotoxic effects on the gastrointestinal (GI) tract cells, and these effects have been largely uncharacterized. The present study aimed to explore the toxic effects of GO on the intestinal tract especially under pre-existing inflammatory conditions, such as inflammatory bowel disease (IBD), and elucidate underlying mechanisms. RESULTS: Our findings indicated that oral gavage of GO worsened acute colitis induced by 2.5% dextran sodium sulfate (DSS) in mice. In vitro, GO exacerbated DSS-induced inflammation and apoptosis in the FHC cell line, an ideal model of intestinal epithelial cells (IECs). Further, the potential mechanism underlying GO aggravated mice colitis and cell inflammation was explored. Our results revealed that GO treatment triggered apoptosis in FHC cells through the activation of reactive oxygen species (ROS)/AMP-activated protein kinase (AMPK)/p53 pathway, as evidenced by the upregulation of cytochrome c (Cytc), Bax, and cleaved caspase-3 (c-cas3) and the downregulation of Bcl-2. Interestingly, pretreatment with an antioxidant, N-acetyl-L-cysteine, and a specific inhibitor of AMPK activation, Compound C (Com.C), effectively inhibited GO-induced apoptosis in FHC cells. CONCLUSIONS: Our data demonstrate that GO-induced IECs apoptosis via ROS/AMPK/p53 pathway activation accounts for the exacerbation of colitis in vivo and aggravation of inflammation in vitro. These findings provide a new insight into the pathogenesis of IBD induced by environmental factors. Furthermore, our findings enhance our understanding of GO as a potential environmental toxin, which helps delineate the risk of exposure to patients with disturbed intestinal epithelial barrier/inflammatory disorders such as IBD.

5.
J Ethnopharmacol ; : 114057, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33771643

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga dahurica (Turcz.) Maxim (C. dahurica) has a long history of treating breast cancer. From the Qing Dynasty to the Tang Dynasty and even earlier, C. dahurica has been documented in the treatment of breast carbuncle (Breast cancer is classified as breast carbuncle in Chinese medicine). In traditional prescriptions such as "Sheng Ge Decoction", "Sheng Ma Powder" and "Breast Carbuncle Pill", as the main medicine, C. dahurica plays an important role. At present, the systematic studies on the in vitro and in vivo effects of Cimicifuga against breast cancer are rare, especially the C. dahurica. AIM OF THE STUDY: In this article, we evaluated the in vitro activity and in vivo effects of CREE (extract of the root of C. dahurica) against breast cancer, and discussed the possible mechanism of CREE in promoting breast cancer cell apoptosis. MATERIALS AND METHODS: The main component in the CREE was analyzed by HPLC. The effects of CREE on the proliferation, migration and invasion of human breast cancer cells were evaluated through SRB, colony assay, LDH release, wound healing and transwell assay. The pro-apoptotic effect of CREE was investigated in Hochest33342 and Annexin V-FITC/PI assay. To verify the results of CREE in vivo effects, we applied nude mice subcutaneous xenograft experiments. The possible mechanism of CREE treating breast cancer was investigated through mitochondrial membrane potential and western blot experiments. RESULTS: CREE contains cycloartane triterpene saponins. CREE can significantly inhibit the proliferation, migration and invasion of human breast cancer MCF-7 and MDA-MB-231 cells in vitro and it can effectively inhibit the growth of MDA-MB-231 cell subcutaneous tumors in vivo. Besides, we also found that CREE up-regulated the expression levels of Bax, caspase-9/3 and cytochrome C, and down-regulated the expression of Bcl-2. Therefore, regulation of the mitochondrial pathway may be one of the mechanisms by which CREE promotes breast cancer cell apoptosis. CONCLUSIONS: CREE exhibits sufficient anti-breast cancer activity in vivo and in vitro, this study provides persuasive evidence for the further research and development of C. dahurica. unlisted.

6.
Sci Total Environ ; 770: 145301, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33515877

RESUMO

Bisphenol A (BPA) is widely used to manufacture packaging materials for various daily necessities and causes harmful effects in organs, especially liver injury, by generating oxidative stress. Oridonin, an active diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, has been reported to possess a wide range of pharmacological activities including anti-inflammatory, antioxidative and antiapoptotic effects. However, the role of oridonin in BPA--induced liver injury and its potential protective mechanism have not been well characterized. In this research, we explored the metabolic alterations in the liver tissue of rats after exposure to BPA with or without pretreatment with oridonin for 14 days by metabolomics analysis based on UPLC-MS/MS. Rats were randomly divided into groups as follows: Control, Vehicle, Oridonin (10 mg/kg), Bisphenol A (500 mg/kg), bisphenol A + Oridonin (500 + 10 mg/kg), Bisphenol A + Diammonium glycyrrhizinate (500 + 40 mg/kg). The biochemical results showed that oridonin significantly reduced the levels of AST and ALT (P < 0.05), ameliorated the abnormal histopathological changes and reduced hepatic apoptosis compared with the BPA group. Furthermore, metabolomics results revealed that purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism were reprogrammed, based on 28 identified significant differential metabolites among the Vehicle, BPA and BPA + oridonin groups. In-depth studies demonstrated that pretreatment with oridonin may play a protective role by restoring BPA-induced changes in oxidative stress and the activity of oxidase (XOD) (P < 0.05). Additionally, oridonin could inhibit the activity of XOD by binding to it, therefore decreasing the reactive oxygen species (ROS) level, upregulating the content of hypoxanthine and xanthine, and reducing the level of uric acid in the liver (P < 0.05). This research presents the potential protective mechanisms of oridonin on BPA-induced liver injury at the metabolic level, which might be used to identify new protective agents that prevent BPA-induced liver injury.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Animais , Compostos Benzidrílicos/metabolismo , Compostos Benzidrílicos/toxicidade , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Cromatografia Líquida , Diterpenos de Caurano , Fígado/metabolismo , Estresse Oxidativo , Oxirredutases/metabolismo , Fenóis , Ratos , Espectrometria de Massas em Tandem
7.
Biomed Pharmacother ; 135: 111215, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33418303

RESUMO

Neuropathic pain is still a critical public health problem worldwide. Thereby, the search for novel and more effective strategies against neuropathic pain is urgently considered. It is known that neuroinflammation plays a crucial role in the pathogenesis of neuropathic pain. SedumLineare Thunb. (SLT), a kind of Chinese herb originated from the whole grass of Crassulaceae plant, was reported to possess anti-inflammatory activity. However, whether SLT has anti-nociceptive effect on neuropathic pain and its possible underlying mechanisms remains poorly elucidated. In this study, a rat model of neuropathic pain induced by spared nerve injury (SNI)was applied. SLT (p.o.) was administered to SNI rats once every day lasting for 14 days. Pain-related behaviors were assessed by using paw withdrawal threshold (PWT) and CatWalk gait parameters. Expression levels of inflammatory mediators and pain-related signaling molecules in the spinal cord were detected using western blotting assay. The results revealed that SLT (30, 100, and 300 mg/kg, p.o.) treatment for SNI rats ameliorated mechanical hypersensitivity in a dose-dependent manner. Application of SLT at the most effective dose of 100 mg/kg to SNI rats not only significantly blocked microglial activation, but also markedly reduced the protein levels of spinal HMGB1, TLR4, MyD88, TRAF6, IL-1ß, IL-6, and TNF-α, along with an enhancement in gait parameters. Furthermore, SLT treatment dramatically inhibited the phosphorylation levels of both IKK and NF-κB p65 but obviously improved both IκB and IL-10 protein expression in the spinal cord of SNI rats. Altogether, these data suggested that SLT could suppress spinal TLR4/NF-κB signaling pathway in SNI rats, which might at least partly contribute to its anti-nociceptive action, indicating that SLT may serveas a potential therapeutic agent for neuropathic pain.

8.
Chem Commun (Camb) ; 57(8): 1042-1045, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33409516

RESUMO

An unprecedented Mo-organic molecular cage built on interesting {MoVI2O5} secondary building blocks and BTC ligands, which has been successfully synthesized and systematically characterized, presents the first example of an isopolyoxomolybdates(vi)-organic molecular cage. An investigation into the related Cs+-exchange experiment was performed in detail.

9.
PLoS One ; 16(1): e0245608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33465122

RESUMO

Accumulating evidence has suggested a correlation of tumor infiltrating B cells (TiBcs) and a good prognosis of cancer diseases. In some cases, TiBcs appear to have experienced antigen stimulation since they have undergone class-switching and somatic hypermutation and formed tertiary lymphoid structures around tumors together with T cells. Assuming TiBcs include those that recognize some tumor antigens, we sought to investigate their possible usefulness for cell-mediated immunotherapies. To expand usually small number of TiBcs in vitro, we modified our B cell culture system: we transduced B cells with ERT2-Bach2 so that they grow unlimitedly provided with tamoxifen, IL-21 and our original feeder cells. Such cells differentiate into plasma cells and produce antibodies upon withdrawal of tamoxifen, and further by addition of a Bach2-inhibitor in vitro. As a preliminary experiment, thus expanded splenic B cells expressing a transgenic antigen receptor/antibody against hen egg lysozyme were intravenously injected into mice pre-implanted with B16 melanoma cells expressing membrane-bound HEL in the skin, which resulted in suppression of the growth of B16 tumors and prolonged survival of the recipient mice. To test the usefulness of TiBcs for the immunotherapy, we next used APCmin/+ mice as a model that spontaneously develop intestinal tumors. We cultured TiBcs separated from the tumors of APCmin/+ mice as above and confirmed that the antibodies they produce recognize the APCmin/+ tumor. Repeated injection of such TiBcs into adult APCmin/+ mice resulted in suppression of intestinal tumor growth and elongation of the survival of the recipient mice. Serum antibody from the TiBc-recipient mice selectively bound to an antigen expressed in the tumor of APCmin/+ mice. These data suggest a possibility of the novel individualized cancer immunotherapy, in which TiBcs from surgically excised tumor tissues are expanded and infused into the donor patients.

10.
J Toxicol Sci ; 46(1): 43-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408300

RESUMO

Graphene oxide (GO) is one of the most promising nanomaterials used in biomedicine. However, studies about its adverse effects on the intestine in state of inflammation remain limited. This study aimed to explore the underlying effects of GO on intestinal epithelial cells (IECs) in vitro and colitis in vivo. We found that GO could exert toxic effects on NCM460 cells in a dose- and time-dependent manner and promote inflammation. Furthermore, GO caused lysosomal dysfunction and then blockaded autophagy flux. Moreover, pharmacological autophagy inhibitor 3-Methyladenine could reverse GO-induced LC3B and p62 expression levels, reduce expression levels of IL-6, IL-8, TLR4, and CXCL2, and increase the level of IL-10. In vivo, C57BL/6 mice were treated with 2.5% dextran sulfate sodium (DSS) in drinking water for five consecutive days to induce colitis. Then, GO at 60 mg/kg dose was administered through the oral route every two days from day 2 to day 8. These results showed that GO aggravated DSS-induced colitis, characterized by shortening of the colon and severe pathological changes, and induced autophagy. In conclusion, GO caused the abnormal autophagy in IECs and exacerbated DSS-induced colitis in mice. Our research indicated that GO may contribute to the development of intestinal inflammation by inducing IECs autophagy dysfunction.

11.
Sci Total Environ ; 750: 141685, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32862004

RESUMO

Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine ß synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats.


Assuntos
Cistationina gama-Liase , Metformina , Animais , Compostos Benzidrílicos/toxicidade , Cromatografia Líquida , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Humanos , Fígado/metabolismo , Masculino , Metformina/toxicidade , Fenóis , Ratos , Espectrometria de Massas em Tandem , Regulação para Cima
12.
Food Chem ; 339: 127885, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866704

RESUMO

The current study develops an effective, convenient, low-cost, and environmentally friendly method for determining trans-resveratrol (TRA) in peanut oils, the unique proportion of peanut oil, by employing natural cotton fibers without any pretreatment as extraction sorbent and an in-syringe extraction device. The primary factors affecting the extraction recovery are optimized in detail. The condition of 200.0 mg of cotton fibers, six push-pull times, 2.0 mL of n-hexane as washing solvent and 2.0 mL of ethanol as desorption solvent is selected as the best. The linear range is demonstrated to be 10-1000 ng/g with a satisfactory correlation coefficient (R2 = 0.9995), while the limit of detection is calculated as 2.47 ng/g. In addition, the recoveries of TRA are obtained in the range of 93.8-104.4% with RSDs less than 5.5%. Finally, the developed method is successfully applied to determine TRA concentrations in commercial peanut oils and other edible oils.


Assuntos
Arachis/química , Cromatografia Líquida de Alta Pressão/métodos , Fibra de Algodão , Óleo de Amendoim/química , Resveratrol/análise , Adsorção , Arachis/metabolismo , Hexanos/química , Isomerismo , Limite de Detecção , Reprodutibilidade dos Testes , Resveratrol/isolamento & purificação , Extração em Fase Sólida/instrumentação , Extração em Fase Sólida/métodos , Espectrofotometria Ultravioleta
13.
J Mol Cell Biol ; 13(2): 116-127, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33340314

RESUMO

Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality; thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.

14.
Sci Total Environ ; 762: 144586, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33373748

RESUMO

Carbonaceous aerosols and gaseous pollutants emitted from wildfires play a crucial role in both the global climate system and regional air quality. Here, using multisource satellite and ground-based observations combined with reanalysis data, we investigate the three-dimensional evolution of biomass-burning emissions from a forest wildfire event in Liangshan, Southwest China, which occurred from 29 March to 1 April 2020. The meteorological field analysis showed that the negative anomaly of relative humidity and precipitation, as well as the positive anomaly of near-surface wind speed, created favourable conditions for the occurrence and spread of this wildfire event. During the fire, satellite observations suggested a maximum fire radiation power of over 100 MW. In addition, there were significant short-term effects of fire activity on regional air quality, with downwind surface PM2.5 concentrations at the Xichang site reaching a maximum of approximately 470 µg·m -3 on March 31. Driven by a southwesterly airflow, large amounts of smoke aerosols were transported rapidly to downstream areas, significantly deteriorating air quality, with the maximum value of the aerosol optical depth (AOD) exceeding 2. Moreover, the quantitative evaluation based on Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) reanalysis showed that the instantaneous maximum values of the column mass concentration of black carbon (BC) and organic carbon (OC) reached 9.8 g·m-2 and 1.8 g·m-2 during the fire respectively. Further analysis suggested that the interaction between the lower and upper atmosphere constrained the smoke aerosols to altitudes below approximately 5 km, which was also supported by the vertical distribution of elevated smoke aerosols observed by the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP).

15.
Entropy (Basel) ; 22(6)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-33286457

RESUMO

The equipment condition monitoring based on computer hearing is a new pattern recognition approach, and the system formed by it has the advantages of noncontact and strong early warning abilities. Extracting effective features from the sound data of the running power equipment help to improve the equipment monitoring accuracy. However, the sound of running equipment often has the characteristics of serious noise, non-linearity and instationary, which makes it difficult to extract features. To solve this problem, a feature extraction method based on the improved complementary ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) and multiscale improved permutation entropy (MIPE) is proposed. Firstly, the ICEEMDAN is utilized to obtain a group of intrinsic mode functions (IMFs) from the sound of running power equipment. The noise IMFs are then identified and eliminated through mutual information (MI) and mean mutual information (meanMI) of IMFs. Next, the normalized mutual information (norMI) and MIPE are calculated respectively, and norMI is utilized to weigh the corresponding MIPE result. Finally, based on the separability criterion, the weighted MIPE results are feature-dimensionally reduced to obtain the multiscale entropy feature of the sound. The experimental results show that the classification accuracies of the method under the conditions of no noise and 5 dB reach 96.7% and 89.9%, respectively. In practice, the proposed method has higher reliability and stability for the sound feature extraction of the running power equipment.

16.
Med Oncol ; 37(12): 113, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196891

RESUMO

The incidence of gastric cancer cachexia is high and the clinical management is poor, so the study aimed to clarify the mechanism of muscle wasting to better screen patients with gastric cancer cachexia. Gastric cancer patients undergoing radical gastrectomy were divided into cachexia with sarcopenia (CS, n = 13) and normal (N, n = 10) two groups. The possible mechanism of skeletal muscle reduction was explored through Tandem Mass Tag (TMT) technique, Perls staining, Western blot analysis and measurement of oxidative stress indicators. The preoperative weight, weight loss, body mass index, calorie intake and skeletal muscle index values of the CS group were significantly lower than those of the N group (P < 0.05). We identified 114 differentially expressed proteins (DEP) in the muscles of two groups using TMT analysis. Bioinformatics analysis of DEP revealed that ferritin, iron and oxidative stress may be related to skeletal muscle consumption. Following Perls staining and measurement iron concentration in skeletal muscles, we found that the iron in the muscles of the CS group was significantly increased, and at the same time, western blot analysis showed that the expression of ferritin in the CS group was significantly increased and regulated by hepcidin-ferroportin axis. Finally, the CS group showed increased oxidative stress and weakened antioxidant stress systems in the muscles compared with the N group when oxidative stress indicators were analyzed. In conclusion, iron overload may be related to muscle loss in patients with gastric cancer cachexia. Gastric cancer patients with elevated ferritin are more likely to have muscle wasting.

18.
Clin Epigenetics ; 12(1): 162, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126908

RESUMO

BACKGROUND AND AIMS: Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. METHODS: Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. RESULTS: Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I-II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. CONCLUSION: Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. CHINESE CLINICAL TRIAL REGISTRY: Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

19.
Phytother Res ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32869425

RESUMO

Oridonin (Ori) is a natural tetracyclic diterpenoid active compound with excellent antitumor activity, but the mechanism of Ori on esophageal cancer cell, TE1, remains unclear. In this study, we examined the levels of intracellular iron, malondialdehyde, and reactive oxygen species after Ori treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1 cell proliferation is associated with ferroptosis. To understand the molecular mechanism of Ori, we performed UPLC-MS/MS metabolomics profiling on TE1 cells, which show that gamma-glutamyl amino acids (gamma-glutamylleucine, gamma-glutamylvaline), 5-oxoproline, glutamate, GSH, and GSSG are changed significantly after Ori treatment. Meanwhile, the activity of gamma-glutamyl transpeptidase 1 (GGT1) decreased. This revealed that Ori inhibited the gamma-glutamyl cycle in TE1 cells. Furthermore, we found that Ori can covalently bind to cysteine to form the conjugate oridonin-cysteine (Ori-Cys), resulting in the inhibition of glutathione synthesis, which is consistent with the decrease in the enzymatic activity of glutamate cysteine ligase catalytic subunit (GCLC). Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. In conclusion, our experiments indicated that Ori can inhibit the gamma-glutamyl cycle, thereby inducing ferroptosis to exert anti-cancer activity.

20.
Biomed Chromatogr ; : e4976, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852057

RESUMO

Multidrug resistance remains a huge challenge in the chemotherapy of cancer and numerous studies have reported that P-glycoprotein is the most common mechanism of multidrug resistance. Verapamil has been shown to be able to reverse development of multidrug resistance mediated by P-glycoprotein. However, the mechanism of action for verapamil in reversing multidrug resistance at the metabolic level has been rarely reported. In this research, we report the reversal effect of verapamil on multidrug resistance and its mechanisms of action using metabolomics. The results show that the P-glycoprotein-mediated chemotherapy drug resistance was significantly reversed by verapamil in resistant SW620/Ad300 cells. In-depth studies demonstrated that verapamil at reversal concentration had no effect on the P-glycoprotein expression level, but increased intramolecular accumulation of paclitaxel in SW620/Ad300 cells. Metabolomics revealed that the multidrug resistance of SW620/Ad300 cells was related to changes in glycerophospholipid metabolism, sphingolipid metabolism and citric acid cycle, and verapamil could antagonize the multidrug resistance by reversing the above-mentioned glycerophospholipid metabolism and sphingolipid metabolism. This research shows the multidrug resistance reversal mechanism of verapamil at the metabolic level, which helps in understanding the exact multidrug resistance mechanism of verapamil and might be potentially useful to find new multidrug resistance reversal agents. The combination of verapamil (VRP) and paclitaxel (PTX) yielded synergistic effects. VRP had no effect on the expression of P-gp, but increased intramolecular accumulation of PTX. VRP antagonized the MDR by regulating glycerophospholipid metabolism and sphingolipid metabolism.

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