Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.814
Filtrar
1.
Ecotoxicol Environ Saf ; 208: 111609, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396129

RESUMO

With the wide application of neodymium oxide nanoparticles (NPs-Nd2O3) in various fields, their health hazards have aroused public concern in recent years. However, data regarding the cytotoxicity of NPs-Nd2O3 is limited. In this study, we investigated the function and mechanism of long-chain non-coding RNAs (lncRNAs) in NPs-Nd2O3-induced airway inflammation. Treatment with NPs-Nd2O3 induced an inflammatory response in human bronchial epithelial cells (16HBE) by upregulating the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8). The levels of LDH and intracellular ROS in the cells treated by various doses of NPs-Nd2O3 also increased significantly. After treatment with 10 µg/ml NPs-Nd2O3, RNA microarray and real-time quantitative polymerase chain reaction (qRT-PCR) showed a significant upregulation of lncRNA loc105377478. Functional experiments suggested lncRNA loc105377478 enhanced the expression of IL-6, IL-8 and ROS in NPs-Nd2O3-treated 16HBE cells, and it was further demonstrated that lncRNA loc105377478 promoted the activation of NF-κB by negatively regulating ADIPOR1 expression. Moreover, the expression of IL-6 and IL-8 in NPs-Nd2O3-treated 16HBE cells was regulated by lncRNA loc105377478, which was mediated by the NF-κB signaling pathway. In conclusion, lncRNA loc105377478 promotes NF-κB activation by negatively regulating ADIPOR1 expression, thereby upregulating the expression of IL-6 and IL-8 in 16HBE cells treated with NPs-Nd2O3.

2.
Biomed Chromatogr ; : e5072, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33453065

RESUMO

Jin-hong tablets (JHT), a well-known Traditional Chinese Patent Medicine (TCPM), has been effectively used for the treatment of chronic superficial gastritis (CSG) in clinic. The metabolic profile of TCPMs is the key part of discovering their bioactive components. In this study, a five-step strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and metabolynxTM software combined with mass defect filter (MDF) technique was developed to delineate the metabolic profile of JHT in vivo. As a result, a total of 163 JHT-related xenobiotics (38 prototypes and 125 metabolites) were identified or tentatively characterized in rat biological samples, and the phase I and II metabolism process mainly included demethylation, hydroxylation, sulfation and glucuronidation. In addition, after oral administration of JHT, a large amount of alkaloids-related ingredients were detected in rat plasma samples, indicating that alkaloids may play an important role in the treatment of CSG with JHT. This study is beneficial for understanding of JHT's in vivo metabolic profiles and characteristics, which helps to reveal its in vivo effective components and provides a solid basis for further studies on its functional mechanism.

3.
Biofouling ; : 1-17, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33401982

RESUMO

In the present review, 182 antifouling (AF) natural products from marine microorganisms, algae and marine invertebrates reported from August 2014 to May 2020 are presented. Amongst these compounds, over half were isolated from marine-derived microorganisms, including 70 compounds from fungi and 31 compounds from bacteria. The structure-relationship of some of these compounds is also briefly discussed. Based on the work reported, a general workflow was drafted to refine the procedures for the commercialization of any novel AF compounds. Finally, butenolide, which is considered a potential environmentally friendly antifoulant, is used as a case study to show the procedures involved in AF compound work from the aspect of discovery, structure optimization, toxicity, stability, AF mechanism and coating incorporation, which highlight the current challenges and future perspectives in AF compound research.

4.
Mol Cell Biochem ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33420899

RESUMO

JS-K as an exogenous NO donor could release NO after activation by glutathione S-transferases (GSTs). The present study explores the effects of JS-K on MAPK pathway in HepG2 and Bel-7402 cells. JS-K significantly prompted apoptosis and SB203580 (a p38 inhibitor) and SP600125 (a JNK inhibitor) prior to JS-K could partly reverse apoptosis and activation of cleaved-caspase-3 and cleaved PARP. However, U0126 (a MEK inhibitor) strengthened the cell apoptosis and the expressions of cleaved-caspase-3 and cleaved PARP. JS-K caused phosphorylation of p38 MAPK and JNK but attenuated phosphorylation of ERK, which were reversed by Carboxy-PTIO (a NO scavenger). Meanwhile, the phosphorylation of HSP27, c-JUN and ATF-2 were activated in JS-K-treated cells. SB203580 and SP600125 could attenuate phosphorylation of p38 MAPK and JNK, respectively. The phosphorylation in downstream substrates of p38 MAPK and JNK was also abolished by SB203580 and SP600125 in JS-K-treated cells. Additionally, JS-K decreased phosphorylation of c-Raf, which subsequently caused a decrease of MEK1/2 phosphorylation. Several downstream targets of ERK1/2 including p90RSK and transcription factors (e.g., Elk-1, c-Myc and c-Fos) were inhibited. U0126 potentiated JS-K-induced inhibitory effect of Raf/MEK/ERK pathway. The same results were also observed in the downstream substrates of ERK1/2 including p90RSK, Elk-1, c-Myc and c-Fos. Moreover, Carboxy-PTIO abolished the inhibitory effect of Raf/MEK/ERK pathway triggered by JS-K. Finally, JS-K significantly suppressed the growth of rat primary hepatic carcinoma via MAPK pathway in vivo. Taken together, JS-K can induce hepatocellular carcinoma cells apoptosis through its activation of JNK and p38 MAPK and inactivation of Raf/MEK/ERK signaling pathways.

5.
Brain Res ; 1751: 147200, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33166509

RESUMO

A considerable portion of patients with well-controlled seizures and visually normal brain structures experience seizure recurrence after anti-seizure medication is withdrawn. Microstructural abnormalities of the cortex may play an essential role in epilepsy relapse. Patients with idiopathic/cryptogenic epilepsy were registered. At the follow-up endpoint, 18 patients with relapse (PR+ group), 20 patients without relapse (PR- group), and 30 healthy controls were included. High-resolution T1-weighted images were obtained at the time of drug withdrawal. Microstructural features including cortical thickness, surface area, cortical volume and mean curvature in 68 cortical areas were calculated. A general linear model was applied to investigate intergroup differences, and then post hoc analysis was performed. Additionally, factor analysis was conducted to extract components from imaging measures showing a difference between PR- and PR+ groups, and independent associations between components and epilepsy relapse were assessed using a logistic regression model. Cortical thickness of the left paracentral lobule, left temporal pole and right superior frontal gyrus; surface area of the bilateral lingual gyrus and bilateral pericalcarine cortex; and cortical volume of the bilateral pericalcarine cortex had significant intergroup differences (false discovery rate correction, P < 0.05). All measures, except for cortical thickness of the left temporal pole, showed differences between PR- and PR+ groups. Two dominant components were extracted from these measures, and both were independently associated with epilepsy relapse. In conclusion, epilepsy patients with relapse presented distinct microstructural features of cortex at the time of drug withdrawal, which may serve as a potential biomarker for predicting seizure recurrence.

6.
J Dairy Sci ; 104(1): 391-396, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33189295

RESUMO

Mammalian lignans are phytoestrogens with important bioactivities, and their concentrations in livestock milk may influence the health of consumers. This research aimed to establish a method to quantify multiple mammalian lignans in the biofluids of dairy sheep using ultra-HPLC-triple quadropole mass spectrometry with multiple-reaction monitoring. Secoisolariciresinol, 2-[(4-hydroxy-3-methoxyphenyl)methyl]-3-[(3-hydroxyphenyl)methyl]-1,4-butanediol, enterodiol (ED), enterolactone (EL), ED-sulfate (ED-S), and EL-sulfate (EL-S) were purified from the urine of flaxseed cake-fed dairy sheep. The structures of these lignans were identified by a combination of mass and nuclear magnetic resonance spectra. These purified lignans were used as standards to optimize their quantification conditions in urine, milk, and plasma of dairy sheep. On this basis, the lignan metabolites in biofluids were quantified. To improve analysis sensitivity, plasma and milk were pretreated with acetonitrile containing 1% formic acid and passed through a HybridSPE-PL 55261-U column (Supelco, Bellefonte, PA). The limit of quantification of the lignans ranged from 1.43 to 18.3 ng/mL in plasma, and from 1.01 to 18.7 ng/mL in milk. The linearity of the calibration curves ranged from their limit of quantification to at least 217 ng/mL in plasma, and 217 ng/mL in milk. Regression coefficient of the calibration curves were above 0.99 for secoisolariciresinol, 2-[(4-hydroxy-3-methoxyphenyl)methyl]-3-[(3-hydroxyphenyl)methyl]-1,4-butanediol, ED, EL, ED-S, and EL-S, indicating satisfactory relationships between the peak areas and concentrations in the quantification range. The relative concentrations of ED-glucuronide and EL-glucuronide (EL-G) in different biofluids were compared based on their chromatogram peak areas. The sheep plasma contained all forms of mammalian lignans (i.e., ED, EL, ED-S, EL-S, ED-glucuronide, and EL-G.); the urine contained ED, EL, ED-S, and EL-S; and the milk contained ED, EL, ED-S, EL-S, and EL-G. Milk-to-plasma concentration ratios of the mammalian lignans indicated that the free forms were more permeable than the sulfated conjugates. Mammalian lignans found in sheep plasma and milk may provide health benefits to the sheep and sheep-product consumers. The analytical method established in this work could be used to quantify mammalian lignans in livestock products.

7.
J Antibiot (Tokyo) ; 74(2): 152-155, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32843724

RESUMO

One new chromanone derivative, alterchromanone A (1), and four known curvularin-type macrolides (2-5) were isolated from the crude extract of the mangrove-derived endophytic fungus Alternaria longipes. Their structures were elucidated by MS and NMR spectroscopic analyses and by a comparison with data from the literature. The absolute configuration of 1 was assigned by combination of experimental and calculated electronic circular dichroism (ECD) spectra. Compound 1 exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 value of 56.3 µg ml-1. According to the structural features of these compounds, the plausible biosynthetic pathways of 1-5 were also proposed.

8.
Dev Comp Immunol ; 116: 103913, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33137394

RESUMO

Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase, a highly conserved enzyme widely expressed in eukaryotic cells, which accounts for a majority of the serine/threonine phosphatase activity in cells implicated in regulation of immune signaling pathways and antiviral response. However, most of studies about PP2A have been conducted in mammals but few in crustaceans. In this study, two subunits of PP2A (named as CqPP2Ab and CqPP2Ac) were characterized to be involved in white spot syndrome virus (WSSV) infection in the haematopoietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus. The open reading frame (ORF) of CqPP2Ab was 1341 bp encoding 446 amino acids with seven WD40 domains, and the ORF of CqPP2Ac was 930 bp encoding 309 amino acids with a PP2Ac domain. Tissue distribution analysis showed that the mRNA transcript of CqPP2Ab and CqPP2Ac were both widely expressed in all the tested tissues with the highest expression in hemocyte, followed by high expression in Hpt. The gene expressions of CqPP2Ab and CqPP2Ac were both significantly down-regulated at 6 h post WSSV infection (6 hpi) in Hpt cells. Importantly, the expression of viral immediate early gene IE1 and late viral gene envelope protein VP28 were both significantly increased post WSSV infection after gene silencing of CqPP2Ab or CqPP2Ac in Hpt cells, suggesting that CqPP2Ab and CqPP2Ac could inhibit WSSV infection in Hpt cells, probably by increasing the antimicrobial substances expression in consideration to the significantly reduced expression of anti-lipopolysaccharide factor, crustin, and lysozyme after gene silencing of CqPP2Ab or CqPP2Ac, respectively. These findings provide a new light on the mechanism of WSSV infection and the antiviral response in crustaceans.

9.
Behav Brain Res ; 399: 113038, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33276033

RESUMO

Antidepressants currently used in clinical practice have limitations such as low efficacy, slow onset and various adverse reactions. It has become necessary to develop novel antidepressants beyond monoaminergic drugs. L-701,324 is a potent NMDA receptor antagonist, and the purpose of this study was to investigate the possible antidepressant effects of L-701,324 in mice. Here, various methods including the forced swim test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model of depression, western blotting and immunofluorescence, were used together. A single injection of L-701,324 exhibited antidepressant-like potential in the FST and TST without affecting the locomotor activity of mice. Repeated injection of L-701,324 not only prevented CUMS-induced depressive-like behaviors in mice, but also ameliorated the downregulating effects of CUMS on the hippocampal BDNF signaling cascade and neurogenesis. Furthermore, K252a, a potent inhibitor of the BDNF system, fully blocked the antidepressant-like activity of L-701,324 in mice. K252a administration also abolished the activating actions of L-701,324 on the hippocampal BDNF signaling cascade and neurogenesis in CUMS-treated mice. Collectively, these data indicated that L-701,324 possesses antidepressant-like activity in mice, which was mediated, at least in part, by promoting the hippocampal BDNF system.

10.
Life Sci ; 265: 118762, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189825

RESUMO

AIMS: This study is to investigate the role of adenovirus type 36 (Ad36) in inducing differentiation of human adipose-derived stem cells (hADSCs) into brown adipocytes. MAIN METHODS: The hADSCs were induced to differentiate into adipocytes by a cocktail method and Ad36, respectively. They were collected on the 2nd, 4th, 6th, and 8th day, respectively. LncRNA ROR was silenced by siRNA. RT-qPCR and Western-blot were used to detect the mRNA and protein levels. Transmission electron microscopy was used to observe the mitochondria. KEY FINDINGS: The mRNA and protein expression levels of LncRNA ROR, Cidea, Dio2, Fgf21, Ucp1, Prdm16, Cox5b, Atp5o, Atp6, and Nd2 in the Ad36 induction group were significantly higher than those in the cocktail induction group. The expression levels of Leptin mRNA and protein in the Ad36 induction group were significantly lower than those in the cocktail induction group. After siRNA knockdown of LncRNA ROR, mRNA and protein expression levels of Cidea, Dio2, Fgf21, Ucp1, Prdm16, Cox5b, Atp5o, Atp6 and Nd2 were significantly lower than the control group during the induction of hADSC differentiation into adipocytes by Ad36. Additionally, mitochondria in the Ad36 induction group was increased compared to that in the cocktail induction group. SIGNIFICANCE: Ad36 may promote the differentiation of hADSCs into brown adipocytes by up-regulating LncRNA ROR.


Assuntos
Adenoviridae/metabolismo , Infecções por Adenovirus Humanos/metabolismo , Adipócitos Marrons/virologia , Células-Tronco Mesenquimais/metabolismo , RNA Longo não Codificante/metabolismo , Adipócitos Marrons/metabolismo , Adipócitos Marrons/fisiologia , Adipócitos Marrons/ultraestrutura , Western Blotting , Diferenciação Celular , Regulação da Expressão Gênica , Inativação Gênica , Humanos , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
12.
Dev Comp Immunol ; 116: 103947, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33253753

RESUMO

White spot syndrome virus (WSSV) is currently the most severely viral pathogen for farmed crustaceans such as shrimp and crayfish, which has been causing huge economic losses for crustaceans farming worldwide every year. Unfortunately, study on the molecular mechanisms of WSSV has been restricted by the lack of crustacean cell lines for WSSV propagation as well as the incompletely annotated genomes for host species, resulting in limited elucidation for WSSV pathogenesis at present. In addition to the findings of anti-WSSV response in shrimp, some of novel cellular events involved in WSSV infection have been recently revealed in crayfish, including endocytosis and intracellular transport of WSSV, innate immune pathways in response to WSSV infection, and regulation of viral gene expression by host genes. Despite these advances, many fundamental gaps in WSSV pathogenesis are still remaining, for example, how WSSV genome enters into nucleus and how the progeny virions are fully assembled in the host cell nucleus. In this review, recent findings in WSSV infection mechanism and the antiviral immunity against WSSV in crayfish are summarized and discussed, which may provide us a better understanding of the WSSV pathogenesis as well as new ideas for the target design of antiviral drugs against WSSV in crustaceans farming.

13.
N Biotechnol ; 61: 116-123, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33301924

RESUMO

An amplification-based single-molecule fluorescence in situ hybridization (asmFISH) assay is introduced that exploits improved probe design for highly specific imaging of individual transcripts in fixed cells and tissues. In this method, a pair of DNA ligation probes are ligated on RNA templates upon specific hybridization, followed by probe circularization based on enzymatic DNA ligation and rolling circle amplification for signal boosting. The method is more efficient and specific than the padlock probe assay for detection of the same RNA molecules and discrimination of single nucleotide polymorphisms. Moreover, asmFISH is a versatile method which can be applied not only to cultured cells, but also to fresh frozen and formalin-fixed, paraffin-embedded tissue sections.

14.
J Colloid Interface Sci ; 582(Pt B): 447-458, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896674

RESUMO

In this paper, we designed and prepared a novel metal organic framework (MOF)/holey graphene (HG) composites as electrode materials for electrochemistry and capacitive deionization (CDI). The MOF nanoparticles were attached to the surface of the HG sheets to form layered porous structure, which promoted the transport of ions and electrons in the electrode/electrolyte interfaces. Additionally, the synergistic effect of these composite electrodes, which combined pseudocapacitance performance of MOF and the high conductivity of graphene, contributed to enhancing the performance of electrochemistry and CDI. The MOF/HG-2 exhibited high capacitances of 526 F g-1 at current rates of 0.1 A g-1, low charge transfer resistance of 0.53 Ω, and excellent cycling stability (retention of about 90.3% after 5000 cycles at 2 A g-1). As electrode materials for CDI, the MOF/HG-2 displayed a remarkable electrosorption capacity of 39.6 mg g-1 with initial salt concentration of 800 mg L-1, and there was no obvious attenuation after 20 CDI regeneration cycles. These results confirmed that MOF/HG was a promising electrode material for the actual application of CDI.

15.
J Med Chem ; 64(1): 644-661, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33356246

RESUMO

The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A PI3Kα-selective inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a PI3Kα-selective inhibitor by applying structure-based drug design (SBDD) and computational analysis. A novel series of compounds, exemplified by 2,2-difluoroethyl (3S)-3-{[2'-amino-5-fluoro-2-(morpholin-4-yl)-4,5'-bipyrimidin-6-yl]amino}-3-(hydroxymethyl)pyrrolidine-1-carboxylate (1) (PF-06843195), with high PI3Kα potency and unique PI3K isoform and mTOR selectivity were discovered. We describe here the details of the design and synthesis program that lead to the discovery of 1.

16.
Int Arch Allergy Immunol ; 182(1): 76-82, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32961539

RESUMO

The purpose of this systematic review and meta-analysis was to explore the literature and collate data comparing the mortality of coronavirus disease 2019 (COVID-19) patients with and without asthma. The databases PubMed, Scopus, Embase, Google Scholar, and medRxiv.org were searched for studies comparing the clinical outcomes of asthmatic patients with those of nonasthmatic patients diagnosed with COVID-19. Mortality data were summarized using the Mantel-Haenszel OR with 95% CI in a random-effects model. Five retrospective studies met the inclusion criteria. A meta-analysis of data from 744 asthmatic patients and 8,151 nonasthmatic patients indicated that the presence of asthma had no significant effect on mortality (OR = 0.96; 95% CI 0.70-1.30; I2 = 0%; p = 0.79). Results were stable in a sensitivity analysis. A descriptive analysis of other clinical outcomes indicated no difference in the duration of hospitalization and the risk of intensive care unit (ICU) transfer between asthmatic and nonasthmatic patients. To conclude, preliminary data indicates that asthma as a comorbidity may not increase the mortality of COVID-19. Data on the influence of asthma on the risk of hospitalization, the duration of hospitalization, the requirement of ICU admission, and disease severity is still too limited to draw any strong conclusions. Further studies with a larger sample size are required to establish strong evidence.


Assuntos
Asma/mortalidade , /mortalidade , Comorbidade , Humanos
17.
Environ Int ; 146: 106252, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33242729

RESUMO

OBJECTIVE: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository. METHODS: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion. RESULTS: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites. CONCLUSIONS: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity.

18.
Mater Sci Eng C Mater Biol Appl ; 119: 111399, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321576

RESUMO

Bio-functional fillers including bio-ceramic, degradable metallic and composite particles are commonly introduced into bone tissue engineering (BTE) scaffolds to endow the materials with specific biological functions for enhanced bone defect therapy. In this work, MgO nanoparticles (NPs) were employed as a potential platform for precise loading and sustained release of Ag+. The results showed that MgO NPs possessed strong adsorption capacity (almost 100%) towards Ag+ in AgNO3 solutions with different concentrations (0.1, 1 and 10 mM). After the adsorption of Ag+ in AgNO3 solutions, cube-shaped MgO NPs transformed to lamella-structured nano-composites (NCs) composed of Mg(OH)2 and Ag2O, which were referred as MgO-xAg (x = 0.1, 1 or 10) NCs depending on the employed concentration of AgNO3 solution. After being suspended in distilled water, as-prepared positively charged NCs underwent a fast degradation process during the initial 4 days. From day 4 and 14, steady release behaviors of Mg2+ and/or Ag+ from the NCs were noticed. With the lowest loading amount of Ag+, MgO-0.1Ag NCs did not exhibit significant modulatory effect on SaOS-2 cell response. On the contrary, MgO-10Ag NCs loaded with the highest amount of Ag+ showed significant cyto-toxicity towards SaOS-2 cells. With appropriate amount of Ag+ loading, MgO-1Ag NCs showed significantly stimulatory effects on SaOS-2 cell proliferation and differentiation. This is evidenced by the enhanced cell viability, alkaline phosphatase (ALP) activity and collagen (COL) production as well as the gene expressions of ALP, COL and osteoprotegerin (OPG) in MgO-1Ag group. Moreover, MgO-1Ag exhibited strong bactericidal capacity against both Escherichia coli and Staphylococcus aureus. Together, the results indicate that MgO could be employed as a potential platform for precise loading and sustained release of Ag+. MgO-1Ag NCs are promising to be used as bio-functional fillers in BTE scaffolds for simultaneously promoted osteogenesis and bacterial killing.

19.
Eur J Med Chem ; 209: 112922, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069436

RESUMO

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93 µM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

20.
Front Endocrinol (Lausanne) ; 11: 595448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343511

RESUMO

Objectives: To retrospectively analyze the correlation between anti-Müllerian hormone (AMH) and the number of oocytes obtained by controlled ovarian hyperstimulation (COH) in women of different ages and explore the factors affecting in vitro fertilization and embryo transfer (IVF-ET) in clinical pregnancy of infertile women to provide evidence for infertile women to choose assisted reproduction strategies. Methods: Infertile women who received IVF-ET or intracytoplasmic sperm injection and embryo transfer (ICSI-ET) treatment in the reproductive center of XX hospital between October 2018 and September 2019 were included. Patient data on medical records, age, body mass index (BMI), years of infertility, basic follicle-stimulating hormone (FSH), basic luteinizing hormone (LH), basic estradiol (E2), anti-Müllerian hormone level (AMH), antral follicle count (AFC), gonadotropins (Gn) medication days, Gn dosage, endometrial thickness on transplantation day, the number of retrieved oocytes, the number of mature oocytes obtained, the number of embryos transferred, clinical pregnancy status, etc., were collected. Results: A total of 314 patients were enrolled in this study, with an average age of 31.0 ± 4.5 years. The infertility period ranged from 0-21 years. The AMH level showed a downward trend with increasing age. Overall, the AMH level of women of all ages was positively correlated with the number of retrieved oocytes (r = 0.335, p < 0.001). The AMH level of women between 22 and 28 years old was positively correlated with the number of retrieved oocytes (r = 0.164, p < 0.061) but it was not statistically significant. Similarly, the AMH level of women aged 29-35 and 36-43 was positively correlated with the number of retrieved oocytes (r = 0.356, p < 0.001; r = 0.461, p < 0.001). The average age of the pregnant group (30.6 ± 4.4 years) was lower than that of the non-pregnant group (32.2 ± 4.6 years) (p < 0.001). The number of oocytes obtained (9.8 ± 4.5) and the number of embryos transferred (1.9 ± 0.4) in the pregnant group was significantly higher than that in the non-pregnant group (9.2 ± 4.5; 1.7 ± 0.5); the difference was statistically significant. The multivariate logistic regression model showed that age (OR = 0.574 95% CI: 0.350-0.940), AMH (OR = 1.430 95% CI: 1.130-1.820) and the number of oocytes obtained (OR = 1.360 95% CI: 1.030-1.790) were factors affecting clinical pregnancy. Conclusion: We found that the level of AMH in infertile women decreased with age and the number of oocytes obtained in infertile women was positively correlated with AMH. Moreover, the number of oocytes and embryo transferred in the pregnant group was significantly higher than those in the non-pregnant group. Furthermore, age, AMH and the number of oocytes affected the clinical pregnancy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA