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1.
Artigo em Inglês | MEDLINE | ID: mdl-32008167

RESUMO

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

2.
J Cell Physiol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003017

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Prognosis is often unfavorable. In this study, the effects of microRNA-802 (miR-802) on HCC progression were assessed in vivo and in vitro. miR-802 was found to be significantly upregulated in HCC tumor tissue compared to paired adjacent nontumor tissue. In vitro, transfection with a miR-802 mimic accelerated SMMC-7721 cellular proliferation, increased accumulation of the cell-cycle S-phase cell populations, as well as cell migration. In vivo injection of a miR-802 agomir promoted HCC proliferation in nude mice. Targets of miR-802 were predicted by miRWalk, miRanda, RNA22, and Targetscan. By luciferase reporter assay RUNX3 was identified as a direct target of miR-802. As judged by western blot analysis, RUNX3 was upregulated when miR-802 was inhibited. These data demonstrate increased miR-802 expression in patients with HCC and that miR-802 overexpression promotes tumor cell growth, in a RUNX3-dependent manner.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32065366

RESUMO

To investigate co-transport behavior of ammonium and colloids in saturated porous media under different hydrochemical conditions, NH4+ was selected as the target contaminant, and silicon and humic acid (HA) were selected as typical organic and inorganic colloids in groundwater. Column experiments were then conducted to investigate the transport of NH4+ colloids under various hydrochemical conditions. The results showed that because of the different properties of colloidal silicon and HA after combining with NH4+, the co-transport mechanism became significantly different. During transport by the NH4+-colloid system, colloidal silicon occupied the adsorption sites on the medium surface to promote the transport of NH4+, while humic acid (HA) increased the number of adsorption sites of the medium to hinder the transport of NH4+. The co-transport of NH4+ and colloids is closely related to hydrochemical conditions. In the presence of HA, competitive adsorption and morphological changes of HA caused NH4+ to be more likely to be transported at a higher ionic strength (IS = 0.05 m, CaCl2) and alkalinity (pH = 9.3). In the presence of colloidal silicon, blocking action caused the facilitated transport to be dependent on higher ionic strength and acidity (pH = 4.5), causing the recovery of NH4+ to improve by 7.99%, 222.25% (stage 1), and 8.63%, respectively. Moreover, transport increases with the colloidal silicon concentrations of 20 mg/L then declines at 40 mg/L, demonstrating that increased concentrations will lead to blocking and particle aggregation, resulting in delayed release in the leaching stage. Graphical abstract.

5.
J Hazard Mater ; 390: 122176, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32006849

RESUMO

The fundamental mechanism behind oil/water separation materials is their surface wettability that allows either oil or water to pass through. The conventional materials for oil/water separation generally have extreme wettability, namely superhydrophilic for water separation and superhydrophobic for oil separation. Using easily accessible materials that are medium hydrophobic or even relatively hydrophilic for preparing highly efficient oil/water separators have rarely been reported. In this work, a new strategy by triggering phase transition of infused lubricant from liquid to solid state in porous structure is realized in fabricating slippery lubricant infused porous structure for oil/water separations. By infusing polyester fabric with coconut oil, after phase transition, excellent water repellency and oil permeability by an absorbing-permeating mechanism are achieved, despite the low water contact angle on the new material. Although the new phase transformable slippery lubricant infused porous structure, features much milder hydrophobicity than conventional oil/water separators, it can remove diverse types of oil from water with high efficiencies. The phase transformable slippery lubricant infused porous structure is able to maintain their water repellency after immersing in high concentration salt (10 wt% NaCl), acid (25 % HCl), alkaline (25 % NH3·H2O) solutions for 120 h, showing remarkably functional durability in harsh environment. The lubricant phase transition mechanism proposed in this study is universally applicable to porous substrates with various chemical compositions and pore structures, such as porous sponges or even daily life breads, for creating efficient oil/water separators, which can serve as a novel accessible design principle of phase transformable slippery lubricant infused porous structure for eco-friendly oil/water separators.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32061180

RESUMO

Biocompatible and proteolysis-resistant poly-ß-peptides have broad applications and are dominantly synthesized via the harsh and water sensitive ring-opening polymerization of ß-lactams in the glovebox or using a Schlenk line, catalyzed by strong base LiN(SiMe 3 ) 2 . We developed a controllable and water insensitive ring opening polymerization of ß-amino acid N-thiocarboxyanhydrides (ß-NTAs) that can be operated in open vessels to prepare poly-ß-peptides in high yields, with diverse functional groups, variable chain length, narrow dispersity and defined architecture. These merits imply wide applications of ß-NTA polymerization and resulting poly-ß-peptides, which is validated by the find of a HDP mimicking poly-ß-peptide with potent antimicrobial activities. The living ß-NTA polymerization enables the controllable synthesis of random, block copolymers and easy tuning of both terminal groups of polypeptides, which facilitated unravelling the antibacterial mechanism using the fluorophore-labelled poly-ß-peptide.

7.
J Child Sex Abus ; : 1-17, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040387

RESUMO

The purpose of this study was to investigate Chinese parents' attitudes, knowledge, and practices with their preschool-aged children on sexual abuse prevention education, and to explore the associated factors of parental educative practices on child sexual abuse (CSA) prevention. Four hundred and forty parents of young children from 16 classes in 3 preschools in Beijing completed the questionnaire anonymously and voluntarily (response rate = 80%). Less than one third of parents believed that children most often were sexually abused by familiar persons, and less than 30% of parents believed that if a child has been sexually abused, there will usually be no obvious physical evidence. Parents were reluctant to discuss CSA protective skills with their young children. Less than half of the parents had told their children that if sexual abuse happens, parents or other trusted adults should be told. The multivariate linear regression equation showed that both parents' knowledge (B = 0.11, SE B = 0.05, p = 0 .03) and attitudes (B = 0.27, SE B = 0.10, p = .01) were significant factors for parents' communication about CSA prevention with their children. Findings from this study suggest that it is urgent to implement the sexual abuse prevention education with Chinese parents of preschoolers. Applications and limitations of these findings are discussed.

8.
Int J Biol Macromol ; 149: 450-458, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004605

RESUMO

Polysaccharide (HFSGF) was purified from Sargassum fusiforme. Autohydrolysis and gel column chromatography were performed to fractionate HFSGF into three components (HFSGF-S, HFSGF-L and HFSGF-H). Compositional analysis, mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate the structural features of HFSGF. HFSGF-S was a mixture of sulfated galacto-fuco-oligomers, from the branches terminal ends; in HFSGF-L, the branches of HFSGF, was a sulfated galactofucan, containing a backbone of 1,3-linked α-L-fucan sulfated at C2/4 and/or C4 and interspersed with galactose (Gal); and in HFSGF-H, the backbone of HFSGF, was composed of alternating 1,2-linked α-D-mannose (Man) and 1,4-linked ß-D-glucuronic acid (GlcA), branched with sulfated galactofucan or sulfated fucan, 1,3-linked α-L-fucan sulfated at C2/4 and/or C4 and partly interspersed with Gal. Some fucose (Fuc) residues were also partially branched with xylose (Xyl). The anti-lung cancer activities of HFSGF-L and HFSGF-H against human lung cancer A549 cells in vitro and A549 xenograft tumor growth in vivo were determined. HFSGF-H had higher activity in vitro (IC50 ~12 mg/mL for 24 h) and in vivo (tumor inhibition ~51%.) than HFSGF-L, indicating that HFSGF-H might be a leading compound for a potential new therapeutics for the treatment of lung cancer.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32083767

RESUMO

Peptides have important biological functions. However, peptides' susceptibility to proteolysis is a big hurdle to their application. We demonstrated, for the first time, that poly(2-oxazoline) can work as functional mimics of peptides. Using host defense peptide as a model, we showed poly(2-oxazoline) based glycine pseudopeptides can mimic host defense peptide and have potent in vitro and in vivo activities against methicillin-resistant Staphylococcus aureus that cause formidable infections. The poly(2-oxazoline) showed potent activity against persister cells that are highly resistant to antibiotics. S taphylococcus aureus were unable to acquire resistance upon poly(2-oxazoline), owning to the reactive oxygen species related antimicrobial mechanism. Poly(2-oxazoline) treated Staphylococcus aureus were still sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross-resistance in using antimicrobial poly(2-oxazoline). Our study highlighted poly(2-oxazoline) as a new type of functional mimics of peptides and opened up new avenues in designing and exploring peptide mimetics for biological functions and applications.

10.
J Cell Physiol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960961

RESUMO

Numerous studies demonstrate that circular RNAs (circRNAs) are critical regulators of the occurrence and progression of tumors. However, research on the involvement of circRNAs in lung squamous cell carcinoma (LUSC) is limited. In our study, circTIMELESS (also named hsa_circ_0000408 in the Human circRNA Database) was upregulated in both LUSC tissues and LUSC cells, and circTIMELESS expression was positively associated with the TNM stage. Moreover, circTIMELESS silencing markedly suppressed invasion in vitro and disrupted proliferation in vitro as well as in vivo. Additional investigations have shown that circTIMELESS functions as a miR-136-5p "sponge" and regulates miR-136-5p expression. Furthermore, the impact of miR-136-5p upregulation was consistent with the results of circTIMELESS silencing, both of which inhibited the proliferation and invasion of LUSC cells. Additional results showed that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) is targeted by miR-136-5p. The results of recovery experiments showed that ROCK1 overexpression partly rescued the impact of circTIMELESS silencing and miR-136-5p upregulation on proliferation and invasion. Consequently, our findings confirmed that circTIMELESS exists in LUSC and acts as a tumor promoter through the miR-136-5p/ROCK1 axis. Based on these findings, circTIMELESS may be potentially utilized as a therapeutic target for LUSC.

11.
J Gen Virol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935178

RESUMO

Bovine herpesvirus 5 (BoHV-5) is a pathogen of cattle responsible for fatal meningoencephalitis. Like alpha herpesvirus subfamily members, BoHV-5 also encodes microRNA in lytic infections of epithelial cells. BoHV-5-miR-B10 was the most abundant miRNA detected in a high-throughput sequencing study. Here, we evaluated the kinetics of miR-B10 expression after BoHV-5 productive infection by stem-loop real-time quantitative PCR. miR-B10 candidate target sites in the virus were predicted, and BoHV-5 UL39 was confirmed as a target gene by dual-luciferase assay with the design of an miR-B10 tough decoy (TuD). The UL39 gene encoding ribonucleotide reductase (RR) large subunit plays an important role in the early stage of BoHV-5 lytic infection. As BoHV-5-miR-B10 is located in internal and terminal repeat regions, we generated a TuD gene-integrated BoHV-5 strain, which effectively down-regulated miR-B10-3p. Strikingly, the suppression of miR-B10-3p significantly improved BoHV-5 replication. Taking these findings together, our study established an efficient method to deliver and express TuD RNA for viral miRNA suppression, and demonstrated that virus-encoded miRNA suppresses viral-genome biogenesis with a feedback mode, which might serve as a brake for viral replication. Herpesviruses infect humans and a variety of animals. Almost all herpesviruses can encode miRNAs, but the functions of these miRNAs remain to be elucidated. Most herpesvirus-encoded miRNA harbours dual copies, which is difficult to be deleted by current genetic modulation. Here, we developed an efficient method to deliver and express TuD RNA to efficiently suppress viral miRNA with multiple copies. Using this method, we demonstrated for the first time that viral miRNA feedback regulates viral replication by suppressing the expression of RR.

12.
Nanoscale ; 12(4): 2498-2506, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31930248

RESUMO

Efficient interfacial light-electric interconversion in van der Waals heterostructures is critical for their optoelectronic applications. Using time-resolved terahertz spectroscopy and transient absorption spectroscopy, the charge transfer and the dynamical interlayer excitons were investigated in the heterostructures comprising monolayer WSe2 and monolayer graphene with varying stacking order on a sapphire substrate. Herein, a more comprehensive understanding of ultrafast charge transfer and exciton dynamics in two-dimensional heterostructures is shown. Owing to the effective electric field induced by the sapphire substrate, the WSe2/graphene heterostructure exhibits positive terahertz photoconductivity after photoexcitation, while negative terahertz photoconductivity is observed in the graphene/WSe2 heterostructure. The transient absorption spectra indicate that the exciton lifetimes also exhibit a considerable difference, where WSe2/graphene exhibits the longest exciton lifetime, followed by monolayer WSe2, while graphene/WSe2 exhibits the shortest lifetime. These observations provide a new idea for using van der Waals heterostructures in electronic and photonic devices.

13.
J Agric Food Chem ; 68(4): 1118-1125, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31895982

RESUMO

The conventional colloidal gold immunochromatographic assay (AuNP-ICA) cannot meet the requirements for the rapid and sensitive detection of Escherichia coli (E. coli) O157:H7 because of its poor sensitivity. Herein, a novel two-step cascade signal amplification strategy that integrates in situ gold growth and nanozyme-mediated catalytic deposition was proposed to enhance the detection sensitivity of conventional AuNP-ICA dramatically. The enhanced strip displayed ultrahigh sensitivity in E. coli O157:H7 detection and had a detection limit of 1.25 × 101 CFU/mL, which is approximately 400-fold lower than that of traditional AuNP-ICA (5 × 103 CFU/mL). The amplified strip had no background signal in the T-line zone in the absence of E. coli O157:H7 even after one round of cascade signal amplification. The enhanced strip demonstrated excellent selectivity against E. coli O157:H7 with a negligible cross-reaction to nine other common pathogens. Intra-assays and interassays showed that the improved strip has acceptable accuracy and precision for determining E. coli O157:H7. The average recoveries in a real milk sample ranged from 87.33 to 112.15%, and the coefficients of variation were less than 10%. The enhanced strip also showed great potential in detecting a single E. coli O157:H7 cell in a 75 µL solution.


Assuntos
Escherichia coli O157/isolamento & purificação , Imunoensaio/métodos , Leite/microbiologia , Animais , Bovinos , Escherichia coli O157/genética , Limite de Detecção
14.
Int Immunopharmacol ; 80: 106126, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931363

RESUMO

Intervertebral disc degeneration (IDD), a major cause of discogenic low back pain, is a musculoskeletal disorder involving the apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Marein is a major active flavonoid ingredient extracted from the hypoglycemic plant Coreopsis tinctoria with several beneficial biological activities including anti-diabetic effects. Nevertheless, there are no reports concerning the effects of marein on IDD. Our study aimed to evaluate the effects of marein on high glucose (HG)-induced injury and ECM degradation in human NPCs (HNPCs). CCK-8 assay was applied to evaluate cell viability. Flow cytometry analysis, a cell death detection ELISA, and caspase-3 activity assay were used to assess apoptosis. The mRNA expression of ECM-related proteins matrix metalloproteinase (MMP)-3, MMP-13, Collagen II, and aggrecan were determined by qRT-PCR. The changes of the nuclear factor-kappa B (NF-κB) pathway were examined by western blot. Stimulation with HG significantly reduced cell viability and induced apoptosis in HNPCs. Moreover, HG exposure increased MMP-3 and MMP-13 expression and decreased Collagen II and aggrecan expression in HNPCs. Notably, marein effectively alleviated HG-induced viability reduction, apoptosis and ECM degradation in HNPCs. We also found that marein inhibited HG-induced ROS generation and NF-κB activation in HNPCs. Inhibition of NF-κB pathway reinforced HG-induced injury and ECM degradation in HNPCs. In summary, marein protected HNPCs against HG-induced injury and ECM degradation at least partly by inhibiting the ROS/NF-κB pathway.

15.
J Control Release ; 320: 1-18, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931050

RESUMO

The protein corona significantly changes the nanoparticle (NP) identity both physicochemically and biologically, and in situ regulation of specific plasma protein adsorption on NP surfaces has emerged as a promising strategy for disease-targeting therapy. In the past decade, great progress in protein corona regulation has been achieved via surface chemistry-based nanomedicine development. This review first outlines the latest advances in bio-nano interactions, with special attention to factors that influence the protein corona, including NP physicochemical properties, the biological environment and the duration time. Second, NP surface chemistry strategies designed to inhibit and regulate protein corona formation are highlighted, with special emphasis on albumin, transferrin, apolipoprotein (apo) E, vascular endothelial growth factor (VEGF) and retinol binding protein 4 (RBP4). Finally, the current techniques used to characterize the protein corona are briefly discussed.

16.
ACS Infect Dis ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31922723

RESUMO

Multidrug-resistant (MDR) bacteria have emerged quickly and have caused serious nosocomial infections. It is urgent to develop novel antimicrobial agents for treating MDR bacterial infections. In this study, we isolated 45 strains of bacteria from hospital patients and found shockingly that most of these strains were MDR to antimicrobial drugs. This inspired us to explore antimicrobial peptide polymers as synthetic mimics of host defense peptides in combating drug-resistant bacteria and the formidable antimicrobial challenge. We found that peptide polymer 80:20 DM:Bu (where DM is a hydrophilic/cationic subunit and Bu is a hydrophobic subunit) displayed fast bacterial killing, broad spectrum, and potent activity against clinically isolated strains of MDR bacteria. Moreover, peptide polymer 80:20 DM:Bu displayed potent in vivo antibacterial efficacy, comparable to the performance of polymyxin B, in a Pseudomonas aeruginosa (P. aeruginosa) infected rat full-thickness wound model. The peptide polymer can be easily synthesized from ring-opening polymerization with remarkable reproducibility in structural properties and biological activities. The peptide polymer's potent and broad spectrum antimicrobial activities against MDR bacteria in vitro and in vivo, resistance to proteolysis, and high structural diversity altogether imply a great potential of peptide polymer 80:20 DM:Bu in antimicrobial applications as synthetic mimics of host defense peptides.

17.
Trials ; 21(1): 107, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973702

RESUMO

BACKGROUND: Anxiety disorders are the most prevalent class of lifetime disorders in China, and generalized anxiety disorder (GAD) is one of the most common but frequently overlooked anxiety disorders. Conventional pharmacological treatments for GAD have varying degrees of side effects, dependency, and/or withdrawal syndromes. Traditional Chinese medicine (TCM) is considered a valuable therapeutic option for anxiety disorders and a potentially effective technique to reduce the side effects associated with antipsychotic drugs. This trial aimed to evaluate the clinical efficacy and safety of Antianxiety Granule, a granular Chinese medicine compound, for treatment of GAD. METHODS/DESIGN: The current work is a multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial with a 6-week treatment schedule. The study consists of three periods: a 1-7-day screening period, a 6-week primary treatment period, and a 1-week follow-up period. Follow-up assessments will be conducted 1 week after the last visit with a face-to-face interview or by telephone. The clinical efficacy of Antianxiety Granule for the treatment of GAD will be evaluated by examining the change in the Hamilton anxiety scale (HAMA) score, state-trait anxiety inventory (STAI) score, and TCM symptom scale in patients with GAD who receive daily TCM treatment. Moreover, an intention-to-treat (ITT) analysis will also be used in this randomized controlled trial (RCT). DISCUSSION: Our study is a multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the safety and efficacy of Antianxiety Granule for the treatment of GAD. The results of this trial will provide valuable clinical evidence for the treatment of GAD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016039. Registered on 8 May 2018.

18.
DNA Repair (Amst) ; 86: 102755, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812126

RESUMO

Radiation-induced bystander effects have been demonstrated within organisms. Recently, it is found that the organisms can also signal irradiation cues to their co-cultured partners in a waterborne manner. In contrast, there is a limited understanding of radiation-induced airborne signaling between individuals, especially on the aspect of DNA damage responses (DDR). Here, we establish a co-culture experimental system using Caenorhabdis elegans in a top-bottom layout, where communication between "top" and "bottom" worms is airborne. The radiation response of top worms is evaluated using radio-adaptive response (RAR) of embryonic lethality (F1), which reflects an enhancement in repair potential of germ cells to subsequent DNA damage. It is shown that gamma-irradiation of bottom worms alleviates the embryonic lethality of top worms caused by 25 Gy of subsequent gamma-irradiation, i.e. RAR, indicating that a volatile signal might play an essential role in radiation-induced inter-worm communication. The RAR is absent in the top worms impaired in DNA damage checkpoint, nucleotide excision repair, and olfactory sensory neurons, respectively. The induction of RAR is restricted to the mitotic zone of the female germline of hermaphrodites. These results indicate that the top worms sense the volatile signal through cephalic sensory neurons, and the neural stimulation distantly modulates the DDR in germ mitotic cells, leading to the enhancement of DNA damage repair potential. The volatile signal is produced specifically by the L3-stage bottom worms and functionally distinct from the known sex pheromone. Its production and/or release are regulated by water-soluble ascaroside pheromones in a population-dependent manner.

19.
Nat Rev Cancer ; 20(1): 57-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31806884

RESUMO

Altered cellular metabolism is a hallmark of gliomas. Propelled by a set of recent technological advances, new insights into the molecular mechanisms underlying glioma metabolism are rapidly emerging. In this Review, we focus on the dynamic nature of glioma metabolism and how it is shaped by the interaction between tumour genotype and brain microenvironment. Recent advances integrating metabolomics with genomics are discussed, yielding new insight into the mechanisms that drive glioma pathogenesis. Studies that shed light on interactions between the tumour microenvironment and tumour genotype are highlighted, providing important clues as to how gliomas respond to and adapt to their changing tissue and biochemical contexts. Finally, a road map for the discovery of potential new glioma drug targets is suggested, with the goal of translating these new insights about glioma metabolism into clinical benefits for patients.

20.
Exp Cell Res ; 386(2): 111717, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715142

RESUMO

Periodontal ligament stem cell (PDLSC)-based tissue engineering is an important method for regenerating lost bone in periodontitis. Maintaining or enhancing the osteogenic differentiation of PDLSCs, as well as enhancing the resistance of PDLSCs to oxidative stress, is necessary in this process. As a common hypoglycemic drug, metformin has been reported to have multiple effects on cell functions. This study found that low concentrations of metformin did not affect cell proliferation but did inhibit adipogenic differentiation and promote osteogenic differentiation of PDLSCs. This positive effect was associated with activation of Akt signaling by metformin. Moreover, applying metformin as either a pretreatment or co-treatment could reduce the amount of reactive oxygen species, enhance antioxidant capacity, and rescue the cell viability and osteogenic differentiation that were negatively affected by H2O2-induced oxidative stress in PDLSCs. In addition, metformin was found to activate the Nrf2 signaling pathway in PDLSCs, and knockdown of Nrf2 by siRNA impaired the protective effect of metformin. Taken together, these results indicate that metformin not only promotes osteogenic differentiation of PDLSCs, but also protects PDLSCs against oxidative stress-induced damage, suggesting that metformin could be potentially useful in promoting PDLSC-based bone regeneration in the treatment of periodontitis.

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