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1.
Talanta ; 221: 121635, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076155

RESUMO

In this paper, a UPLC-ESI-MS was established to analyze macamide and macaene fractions from Lepidium meyenii (Maca). The antioxidant activity of Maca crude extract (MCE), total macamides (TMM) and total macaenes (TME) was evaluated by DPPH radical scavenging, ABTS radical scavenging and reducing power. The ability of MCE, TMM and TME against multiple cancer cell lines (leukemia HL-60, lung cancer A549, liver cancer SMMC-7721, breast cancer MCF-7, and colon cancer SW480) was used to evaluate their anticancer activity. The results demonstrate that TMM has the best free radical scavenging ability and reducing power compared to MCE, TME, and TMM, TME has the weakest antioxidant capacity compared to them. The difference in antioxidant properties between TMM and TME may be caused by benzylated alkamide in the chemical structure. TMM also has a good inhibitory effect on the five cancer cells. N-benzyl-(9Z, 12Z, 15Z)-octadecatrienamide (NBot) is the most cytotoxicity inhibitory of the macamides tested. The inhibitory effect of N-benzyl-9Z, 12Z-octadecadienamide (NBod) on colon cancer SW480 is near that of control group, while the inhibitory rates of NBot on leukemia HL-60, lung cancer A549, liver cancer SMMC-7721, and breast cancer MCF-7 are near those of the control group. Hence, NBot can be considered to have great potential as a natural drug with high efficiency and low side effects for cancer therapy.

2.
BMC Pregnancy Childbirth ; 20(1): 604, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032548

RESUMO

BACKGROUND: Pregnancy tests can be used for the early diagnosis of fetal problems and can prevent abnormal birth in pregnancies. Yet, testing preferences among Chinese women are poorly investigated. METHODS: We developed a Discrete Choice Experiment with 5 attributes: test procedure, detection rate, miscarriage rate, time to wait for result, and test cost. By studying the choices that the women make in the hypothetical scenarios and comparing the attributes and levels, we can analyze the women's preference of prenatal testing in China. RESULTS: Ninety-two women completed the study. Respondents considered the test procedure as the most important attribute, followed by detection rate, miscarriage rate, wait time for result, and test cost, respectively. The estimated preference weight for the non-invasive procedure was 0.928 (P < 0.0001). All other attributes being equal, the odds of choosing a non-invasive testing procedure over an invasive one was 2.53 (95% confidence interval, 2.42-2.64; P < 0.001). Participants were willing to pay up to RMB$28,810 (approximately US$4610) for a non-invasive test, RMB$6061(US$970) to reduce the miscarriage rate by 1% and up to RMB$3356 (US$537) to increase the detection rate by 1%. Compared to other DCE (Discrete Choice Experiment) studies regarding Down's syndrome screening, women in our study place relatively less emphasis on test safety. CONCLUSIONS: The present study has shown that Chinese women place more emphasis on detection rate than test safety. Chinese women place great preference on noninvasive prenatal testing, which indicate a popular need of incorporating noninvasive prenatal testing into the health insurance coverage in China. This study provided valuable evidence for the decision makers in the Chinese government.

3.
Part Fibre Toxicol ; 17(1): 50, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008402

RESUMO

BACKGROUND: The biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been gradually confirmed, however, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms. RESULTS: We firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE-/- mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group, and the histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE-/- mice. Compared to the control group, the serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression induced by SiNPs. CONCLUSIONS: Our results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE-/- mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage.

4.
Eur Radiol ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052467

RESUMO

OBJECTIVES: To investigate age-related changes on passive muscle stiffness in healthy individuals and measure the shear modulus in different age groups. METHODS: Shear wave elastography (SWE) movies of gastrocnemius medialis (GM) were collected during passive stretching induced by ankle rotation from plantarflexion (PF) to dorsiflexion (DF). A series of SWE images at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, 0°, DF 10°, DF 20°, and DF 30° were collected and shear moduli measured accordingly for analyses. RESULTS: Eighty-six healthy volunteers (27 children, 31 middle-aged adults, and 28 older people) were recruited. No significant difference was observed in the shear modulus between the three groups at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, and 0° (p > 0.05). The difference in the shear modulus among the three groups became significant as DF increased. At ankle angles of DF 10°, DF 20°, and DF 30°, the shear modulus was the greatest in the older group, followed by the middle-aged group and then the children group (p = 0.007, 0.000, and 0.000, respectively). CONCLUSIONS: Passive muscle stiffness increases with age, and the difference between age groups was pronounced only after reaching a certain degree of stretching. KEY POINTS: • The influence of age on passive muscle stiffness becomes pronounced only after reaching a certain degree of stretching. • Age should be considered when evaluating passive muscle stiffness in muscular disorders.

6.
Water Res ; 188: 116482, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33039829

RESUMO

Solar energy is considered one of the most promising energy sources for the degradation of pollutants in the water treatments. An innovative solar photo-thermochemical system involving peroxydisulfate (PDS) as an oxidant and xenon lamp as a solar irradiation light source was applied with hopes to degrade organic matters and alleviate the ultrafiltration (UF) membrane fouling when treating the real surface water. Moreover, heat-activated PDS pretreatment was used as a comparison to explore the respective proportions of solar light and heating effects, finding that solar light effect dominated the activation of PDS to degrade natural organic matters (NOMs) when the reaction temperature was below 50 °C and they both contributed to the production of free radicals at the temperature of >50 °C. The results indicated that solar-activated PDS pretreatment significantly alleviated membrane fouling caused by Songhua River water with the highest transmembrane pressure (TMP) reduction of approximately 69.6% at 70 °C. Organic substances (characterized by DOC, UV254 and the maximum florescent intensity) and micropollutant (atrazine) in the feed water were better degraded in the presence of solar light. Both total fouling index (TFI) and hydraulic irreversible fouling index (HIFI) were moderate correlated with the UV254 and DOC, whereas remarkably correlated with the Fmax of component 2 (C2) and component 3 (C3). In addition, no significant correlation was observed between fouling indexes (TFI and HIFI) and the Fmax of component 1 (C1). The membrane irreversible fouling was attributed to the accumulation of cake layers mainly composed of protein-like substances on the membrane surface. Solar-activated PDS pretreatment would efficiently degrade the protein-like substances and terrestrially derived humic-like matters to control UF membrane fouling. The findings are beneficial to develop new strategies for membrane fouling alleviation based on the solar irradiation and PDS oxidation.

7.
Surg Oncol ; 35: 426-427, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33038848

RESUMO

INTRODUCTION: Digital intelligent technology represented by three-dimensional (3D) visualization technology and surgical navigation system may provide preoperative and intraoperative anatomical information more accurately than CT and MRI [1]. Besides, the fusion of 3D model with surgical visual field through surgical navigation system may also compensate for the defects of visual fields and tactile sense to some extent in laparoscopic liver surgery [2]. VIDEO: A 49-year-old male patient with a tumor mainly located at the left inner area of liver and oppressing the middle hepatic vein (MHV). We formulated preoperative planning by using the Medical Image 3D Visualization System (MI3DVS, software copyright No: 2008SR18798) [3]. It was acknowledged that the right hepatic vein (RHV) was strong enough to drain the right anterior hepatic sector. Ultimately, 3D laparoscopic extended left hepatectomy with resection of the MHV was selected as the optimal operation scheme for the patient due to the RHV would avoid hepatic venous congestion in segment V and VIII after resection of the MHV, and more liver parenchyma than left trisegmentectomy would be retained. The operation was performed under assistance of the Laparoscopic Hepatectomy Navigation System (LHNS, software copyright No. 2018SR840555) [4]. RESULTS: The total operation time was 180 min, estimated blood loss of 200 ml. The final histopathological diagnosis showed an 8*6*6-cm-sized hepatocellular carcinoma. And the patient was discharged on postoperative day 6 without any complications. CONCLUSION: Digital intelligent technology may be helpful to formulate preoperative planning and identify intraoperative important anatomical structures in 3D laparoscopic extended left hepatectomy with resection of the MHV.

8.
BMC Plant Biol ; 20(1): 473, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059598

RESUMO

BACKGROUND: Diacylglycerol kinases (DGKs) are signaling enzymes that play pivotal roles in response to abiotic and biotic stresses by phosphorylating diacylglycerol (DAG) to form phosphatidic acid (PA). However, no comprehensive analysis of the DGK gene family had previously been reported in B. napus and its diploid progenitors (B. rapa and B. oleracea). RESULTS: In present study, we identified 21, 10, and 11 DGK genes from B. napus, B. rapa, and B. oleracea, respectively, which all contained conserved catalytic domain and were further divided into three clusters. Molecular evolutionary analysis showed that speciation and whole-genome triplication (WGT) was critical for the divergence of duplicated DGK genes. RNA-seq transcriptome data revealed that, with the exception of BnaDGK4 and BnaDGK6, BnaDGK genes have divergent expression patterns in most tissues. Furthermore, some DGK genes were upregulated or downregulated in response to hormone treatment and metal ion (arsenic and cadmium) stress. Quantitative real-time PCR analysis revealed that different BnaDGK genes contribute to seed oil content. CONCLUSIONS: Together, our results indicate that DGK genes have diverse roles in plant growth and development, hormone response, and metal ion stress, and in determining seed oil content, and lay a foundation for further elucidating the roles of DGKs in Brassica species.

9.
Front Immunol ; 11: 1933, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072067

RESUMO

Background: Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods: We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results: A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion: Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

10.
Arch Biochem Biophys ; 695: 108611, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33002446

RESUMO

BACKGROUND: Sepsis-induced cardiac dysfunction is one of the leading complications of sepsis, contributing to the high morbidity and mortality of septic patients. Several lines of evidence have demonstrated that autophagy and pyroptosis may be involved in septic cardiac dysfunction. In this study, we examined the impact of zinc finger antisense 1 (ZFAS1) on sepsis-induced myocardial dysfunction via regulating pyroptosis and autophagy. METHOD: Mice with cecal ligation and puncture (CLP)-induced sepsis was constructed in vivo. Myocardial injury was assessed by H&E staining, immunohistochemistry (IHC) for NLRP3, caspase 1, and interleukin (IL)-1ß, as well as ELISA assay for serum levels of creatine kinase (CK), CK-MB, tumor necrosis factor α (TNF-α), and IL-1ß. Primary cardiomyocytes exposed to lipopolysaccharide (LPS) were established to simulate sepsis-induced cardiac dysfunction in vitro. Cell viability was examined by MTT assay and concentration of TNF-α and IL-1ß was measured by ELISA. Flow cytometry, immunofluorescent staining and western blotting were performed to assess pyroptosis and autophagy. The transcriptional regulation of SP1 on ZFAS1 was determined using ChIP assay. Luciferase reporter assay was performed to verify the ZFAS1/miR-590-3p interaction. Besides, activation of AMPK/mTOR signaling was detected using western blotting. RESULTS: Highly expressed ZFAS1 was observed in sepsis-induced cardiac dysfunction in the in vivo and in vitro model. Knockdown of ZFAS1 robustly abolished LPS-induced pyroptosis and attenuated the inhibition of autophagy. SP1 was identified to be an essential transcription factor to positively regulate ZFAS1 expression. Moreover, miR-590-3p functioned as a downstream effector to reverse ZFAS1-mediated sepsis-induced cardiac dysfunction. AMPK/mTOR signaling was involved in miR-590-3p-regulated autophagy and pyroptosis of cardiomyocytes. Furthermore, the regulatory network of ZFAS1/miR-590-3p on AMPK/mTOR signaling was verified in vivo. CONCLUSION: ZFAS1, activated by SP1, aggravates the progression of sepsis-induced cardiac dysfunction via targeting miR-590-3p/AMPK/mTOR signaling-mediated autophagy and pyroptosis of cardiomyocytes.

11.
Environ Res ; 192: 110300, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038368

RESUMO

Airborne particulate matter (PM) is a complex mixture containing various kinds of harmful components. Exposure to air PM is associated with childhood respiratory disease, but epidemiological data are limited concerning the circulating respiratory injury protein on the etiology of childhood respiratory disease. Specifically, the role of PM toxic components or its biological effective dose (adduct) in respiratory injury remains unclear. To demonstrate the dose-response relationship and the main mechanism on circulating club cell secretory protein (CC16) from PM compositions among children, we enrolled 273 boarding schoolchildren in China, including 110 and 163 children of whom were in the low- and high-PM exposed areas, respectively. In this study, we measured the internal exposure levels, including serum polycyclic aromatic hydrocarbons (PAH) adduct, urinary metals, and AhR expression, and detected the serum CC16 level as a lung injury marker. Environmental tobacco exposure in children was assessed by urinary cotinine. We found that significantly higher levels of serum CC16, benzo[a]pyridin-7,8-dihydroglycol-9,10-epoxide (BPDE)-albumin adduct, urinary molybdenum, selenium, arsenic, cadmium and barium, and lower level of AhR expression in high-PM exposed group. There was a good association between serum BPDE-albumin adduct and CC16 (ß = 0.222, P = 0.006). There was no association on urinary metals and serum CC16. BPDE-albumin adduct was directly associated with serum CC16 alternation [direct effect = 0.2044, 95% confidence interval (CI) = (0.0426, 0.36)]. PM could cause serum CC16 increased in children. PAH and its adduct might play a key role in lung injury during PM exposure.

12.
J Ethnopharmacol ; : 113462, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058924

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Tongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease. Previous studies have confirmed that TMYX can improve vascular endothelial function in patients with coronary heart disease by upregulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels remains unclear. AIM OF THE STUDY: This study aimed to reveal whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels. The underlying cAMP/PKA and NO-cGMP signaling pathway-dependent mechanism is also explored. MATERIALS AND METHODS: The left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish the NR model. TMYX (4.0 g/kg) was orally administered throughout the experiment. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were used to evaluate the NR and ischemic areas. Pathological changes in the myocardium were assessed by hematoxylin-eosin staining. An automated biochemical analyzer and kit were used to detect the activities of myocardial enzymes and myocardial oxidants, including CK, CK-MB, LDH, reactive oxygen species, superoxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins related to the cAMP/PKA and NO/cGMP signaling pathways were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was used to detect coronary artery diastolic function in vitro. RESULTS: TMYX elevated the EF, FS, LVOT peak, LVPWd and LVPWs values, decreased the LVIDd, LVIDs, LV-mass, IVSd, and LV Vols values, demonstrating cardio-protective effects, and reduced the NR and ischemic areas. Pathological staining showed that TMYX could significantly reduce inflammatory cell number and interstitial edema. The activities of CK, LDH, and MDA were reduced, NO activity was increased, and oxidative stress was suppressed after treatment with TMYX. TMYX not only enhanced the expression of Gs-α, AC, PKA, and eNOS but also increased the expression of sGC and PKG. Furthermore, TMYX treatment significantly decreased ROCK expression. We further showed that TMYX (25-200 mg/mL) relaxed isolated coronary microvessels. CONCLUSIONS: TMYX attenuates myocardial NR after ischemia and reperfusion by activating the cAMP/PKA and NO/cGMP signaling pathways, further upregulating NO activity and relaxing coronary microvessels.

13.
Int Immunopharmacol ; 89(Pt B): 107086, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068868

RESUMO

AIMS: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. MAIN METHODS: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway. RESULTS: Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1ß, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1ß, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation. CONCLUSION: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33082818

RESUMO

Background: Acupuncture at Zusanli (ST36), Quchi (LI11), and Tianshu (ST25) is commonly used in septic patients by traditional Chinese physicians. The protective effect of acupuncture at ST36 on the intestinal barrier is associated with Cholinergic Anti-Inflammatory Pathway (CAIP). However, its detailed mechanism and whether acupuncture at LI11 and ST25 have similar effects to ST36 remain unclear. Aim: To explore the effects of electroacupuncture (EA) at ST36, LI11, and ST25 on septic rats and investigate the role of the spleen in the treatment of EA at ST36. Methods: A septic rat model caused by cecal ligation and puncture (CLP) and a postsplenectomy (SPX) CLP rat model were established. Rats were divided into nine groups depending on different treatments. Serum levels of TNF-α, IL-10, D-lactic acidosis (D-LA), double amine oxidase (DAO), and T-lymphocyte subgroup level in intestinal lymph nodes were compared. Results: EA could not improve the 2-day survival of CLP rats. For CLP rats, EA at ST36 and LI11 significantly decreased the levels of TNF-α, IL-10, DAO, and D-LA in serum and normalized intestinal T-cell immunity. For SPX CLP rats, EA at ST36 failed to reduce serum concentrations of TNF-α, IL-10, and D-LA but increased the values of CD3+CD4+/CD3+CD8+ cells and Treg/Th17 cells. Conclusions: EA at ST36 and LI11, respectively, could alleviate inflammation reaction, protect the intestinal barrier, and maintain intestinal T-cell function in septic rats. Spleen participated in the protective effect of EA at ST36 in sepsis.

15.
Genet Med ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33077892

RESUMO

PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration. METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses. RESULTS: Here we have identified four patients with cone-rod dystrophy or maculopathy from three families carrying pathogenic variants in TLCD3B. Consistent with the phenotype observed in patients, the Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina. CONCLUSION: Our results provide a link between loss-of-function variants in a ceramide synthase gene and human retinal dystrophy. Establishment of the Tlcd3b knockout murine model, an in vivo photoreceptor cell degeneration model due to loss of a ceramide synthase, will provide a unique opportunity in probing the role of ceramide in survival and function of photoreceptor cells.

16.
Chem Commun (Camb) ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079099

RESUMO

Precise control over specific functions in the time domain is ubiquitous in biological systems. Here, we demonstrate time-gated fluorescence signalling under dissipative conditions exploiting an ATP-fueled self-assembly process. A temporal ATP-concentration gradient allows the system to pass through three states, among which only the intermediate state generates a fluorescent signal from a hydrophobic dye entrapped in the assemblies. The system can be reactivated by adding a new batch of ATP. The results indicate a strategy to rationally programme the temporal emergence of functions in complex chemical systems.

17.
Circulation ; 142(14): 1374-1388, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33017217

RESUMO

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues. METHODS: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies. RESULTS: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene(ERG) exerts an important role in maintaining normal aortic wall function. CONCLUSIONS: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.

18.
Acta Pharmacol Sin ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934346

RESUMO

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg-1 ·day-1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 µM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

19.
Oncol Rep ; 44(5): 2130-2142, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32901893

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer in China, and the prognosis of patients remains poor mainly due to the occurrence of lymph node and distant metastasis. The long non­coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to have tumor­suppressive properties and to play an important role in epithelial­to­mesenchymal transition (EMT) in some solid tumors. However, whether MEG3 is involved in EMT in ESCC remains unclear. In the present study, the MEG3 expression level and its association with tumorigenesis were determined in 43 tumor tissues of patients with ESCC and in ESCC cells using reverse transcription­quantitative PCR analysis. Gene microarray analysis was performed to detect differentially expressed genes (DEGs). Based on the functional annotation results, the effects of ectopic expression of MEG3 on cell growth, migration, invasion and EMT were assessed. MEG3 expression level was found to be markedly lower in tumor tissues and cells. Statistical analysis revealed that MEG3 expression was significantly negatively associated with lymph node metastasis and TNM stage in ESCC. Fluorescence in situ hybridization assay demonstrated that MEG3 was expressed mainly in the nucleus. Ectopic expression of MEG3 inhibited cell proliferation, migration, invasion and cell cycle progression in EC109 cells. Gene microarray results demonstrated that 177 genes were differentially expressed ≥2.0 fold in MEG3­overexpressing cells, including 23 upregulated and 154 downregulated genes. Functional annotation revealed that the DEGs were mainly involved in amino acid biosynthetic process, mitogen­activated protein kinase signaling, and serine and glycine metabolism. Further experiments indicated that the ectopic expression of MEG3 significantly suppressed cell proliferation, migration, invasion and EMT by downregulating phosphoserine aminotransferase 1 (PSAT1). In pathological tissues, PSAT1 and MEG3 were significantly negatively correlated, and high expression of PSAT1 predicted poor survival. Taken together, these results suggest that MEG3 may be a useful prognostic biomarker and may suppress EMT by inhibiting the PSAT1­dependent glycogen synthase kinase­3ß/Snail signaling pathway in ESCC.

20.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867345

RESUMO

Dalbergia benthami Prain (D.benthami) is an important legume species of the Dalbergia family, due to the use of its trunk and root heart in traditional Chinese medicine (TCM). In the present study, we reported the isolation, characterization and pharmacological activities of robustic acid (RA) from the ethyl acetate extract of D. benthami Prain. The SwissADME prediction showed that the RA satisfied the Lipinski's rule of five (molecule weight (MW): 380.39 g/mol, lipid-water partition coefficient (log P): 3.72, hydrogen bond donors (Hdon): 1, hydrogen bond acceptors (Hacc): 6, rotatable bonds (Rbon): 3. Other chemical and pharmacological properties of this RA were also evaluated, including topological polar surface area (TPSA) = 78.13 Šand solubility (Log S) = -4.8. The probability values of the antineoplastic, anti-free radical activities and topoisomerase I (TopoⅠ) inhibitory activity were found to be 0.784, 0.644 and 0.379, respectively. The molecular docking experiment using the Surflex-Dock showed that the Total Score and C Score of RNA binding with the human DNA-Topo I complex were 7.80 and 4. The MTS assay experiment showed that the inhibitory rates of RA on HL-60, MT4, Hela, HepG2, SK-OV-3 and MCF-7 cells were 37.37%, 97.41%, 81.22%, 34.4%, 32.68% and 51.4%, respectively. In addition, RA exhibited an inhibitory effect on the angiogenesis of zebrafish embryo, a good TopoⅠ inhibitory activity at a 10 mM concentration and in a dose-dependent manner, excellent radical scavenging in the DPPH and ABTS assays, and the free radical scavenging rate was close to the positive control (BHT) at different concentrations (0.5-2.0 mg/mL). Furthermore, 18 potential targets were found for this RA by PharmMapper, including ANXA3, SRC, FGFR2, GSK3B, CSNK2B, YARS, LCK, EPHA2, MAPK14, RORA, CRABP2, PPP1CC, METAP2, MME, TTR, MET and KDR. The GO and KEGG pathway analysis revealed that the "protein tyrosine kinase activity", "rap1 signaling pathway" and "PI3K-Akt signaling pathway" were significantly enriched by the RA target genes. Our results will provide new insights into the pharmaceutical use of this species. More importantly, our data will expand our understanding of the molecular mechanisms of RA functions.

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