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1.
Arch Pharm (Weinheim) ; : e2000236, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079446

RESUMO

Ten coumarin-3-formamido derivatives, N-benzyl-coumarin-3-carboxamide (2), N-fluorobenzyl-coumarin-3-carboxamide (3-5), N-methoxybenzyl-coumarin-3-carboxamide (6-8), N-((1-methyl-1H-imidazol-5-yl)methyl)-coumarin-3-carboxamide (9), N-(thiophen-2-ylmethyl)-coumarin-3-carboxamide (10), and N-(furan-2-ylmethyl)-coumarin-3-carboxamide (11), were synthesized and characterized. Compound 5 crystallizes in a monoclinic system P21 /c space group with four chemical formulas in a unit cell; molecules of compound 5 are self-assembled into a two-dimensional supramolecular structure by intermolecular hydrogen bonds and C⋯C π stacking. The potential anticancer effects of these compounds on HeLa (cervical carcinoma), MCF-7 (breast), A549 (lung), HepG2 (liver), and human umbilical vein (HUVEC) cells were examined. Compared with compounds 1-8 and 10-11, compound 9 exhibits potent in vitro cytotoxicity against HeLa cells and lower cytotoxicity against normal cells. Therefore, further in-depth investigations of compound 9 were performed. Absorption titration experiments and fluorescence spectroscopy studies suggested that compound 9 binds to DNA through the intercalation mode.

2.
Soft Matter ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073837

RESUMO

Localized drug delivery offers great therapeutic efficacy at local tissues while avoiding the systemic toxicity of drugs. Yet it demands the development of structurally-stable drug carrier systems with excellent injectability, as well as the capability to facilitate controlled release of multiple drugs. Herein, we describe the design and synthesis of a supramolecular hydrogel (Cis/Peptide@NP/Irino) for the combined delivery of cisplatin (Cis) and irinotecan (Irino). The self-assembled hydrogel consisted of an inner phase of irinotecan-loaded PLGA nanoparticles (NP/Irino) and an outer phase of cisplatin-loaded peptide nanofibers (Cis/Peptide). Through the structural reinforcement of PLGA nanoparticles, the Cis/Peptide@NP/Irino hydrogel exhibited better mechanical properties than Cis/Peptide or Peptide hydrogels. With excellent shear-thinning properties, it facilitated the development of a localized drug delivery system with an improved retention time in vivo. The hydrogel incorporated two anticancer drugs, Cis and Irino, at the Peptide and PLGA domains, respectively, and exhibited a faster release of Cis prior to the continuous release of Irino in vitro. Furthermore, the Cis/Peptide@NP/Irino formulation showed a better inhibition efficacy against the proliferation of cancerous A549 cells, with the synergism of Cis and Irino exceeding that of the simple solution mixtures, which was plausibly due to the enhanced cellular uptake of drugs through endocytosis. We believe that structurally-stable supramolecular hydrogels show great promise in the local delivery of various drug combinations for cancer therapy.

3.
Front Immunol ; 11: 1487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903550

RESUMO

A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-associated molecular patterns. The activation of certain PRRs can lead to the assembly of macromolecular oligomers termed inflammasomes, which are responsible for pro-inflammatory cytokine maturation and secretion and thus activate host inflammatory responses. About 10 years ago, the absent in melanoma 2 (AIM2) was independently discovered by four research groups, and among the "canonical" inflammasomes [including AIM2, NLR family pyrin domain (NLRP)1, NLRP3, NLR family apoptosis inhibitory protein (NAIP)/NLR family, caspase activation and recruitment domain (CARD) containing (NLRC)4, and pyrin], AIM2 so far is the only one that simultaneously acts as a cytosolic DNA sensor due to its DNA-binding ability. Undoubtedly, such a double-faceted role gives AIM2 greater mission and more potential in the mediation of innate immune responses. Therefore, AIM2 has garnered much attention from the broad scientific community during its first 10 years of discovery (2009-2019). How the AIM2 inflammasome is related to oral diseases has aroused debate over the past few years and is under active investigation. AIM2 inflammasome may potentially be a key link between oral diseases and innate immunity. In this review, we highlight the current knowledge of the AIM2 inflammasome and its critical role in the pathogenesis of various oral diseases, which might offer future possibilities for disease prevention and targeted therapy utilizing this continued understanding.

4.
J Matern Fetal Neonatal Med ; : 1-10, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942938

RESUMO

OBJECTIVE: To explore whether omega-3 fatty acid supplementation is associated with lower risk of preterm delivery. METHODS: Searching the RCTs which were compared preterm birth between women with omega-3 fatty acid supplementation and without before December 2019 on Medline, EMBASE and Cochrane's Library, then performing a meta-analysis. RESULTS: 26 trials were identified, included 20124 women. There was almost no association between omega-3 fatty acid supplementation and lower risk of preterm delivery (risk ratio 0.92, 95% confidence interval 0.85 to 1.01, I 2 = 9%), gestational duration (0.30, -0.05 to 0.64, I 2 = 48%). In subgroup analyses, preterm delivery lower rate occurred in groups with mixed DHA and EPA supplementation not only DHA supplementation groups (P for interaction = 0.02); The dose of equivalent greater than 1 g made a higher reduction in preterm birth significantly. CONCLUSIONS: Omega-3 fatty acid supplementation was not associated with reduced risk of preterm delivery compared with placebo or no treatment during pregnancy. Relationship between Omega-3 fatty acid supplementation and other pregnant outcomes need more evidence and clinical studies.

5.
Appl Microbiol Biotechnol ; 104(20): 8719-8733, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32880690

RESUMO

Arabinofuranose substitutions on xylan are known to interfere with enzymatic hydrolysis of this primary hemicellulose. In this work, two novel α-L-arabinofuranosidases (ABFs), TtABF51A from Thielavia terrestris and EpABF62C from Eupenicillium parvum, were characterized and functionally analyzed. From sequences analyses, TtABF51A and EpABF62C belong to glycoside hydrolase (GH) families 51 and 62, respectively. Recombinant TtABF51A showed high activity on 4-nitrophenyl-α-L-arabinofuranoside (83.39 U/mg), low-viscosity wheat arabinoxylan (WAX, 39.66 U/mg), high-viscosity rye arabinoxylan (RAX, 32.24 U/mg), and sugarbeet arabinan (25.69 U/mg), while EpABF62C preferred to degrade arabinoxylan. For EpABF62C, the rate of hydrolysis of RAX (94.10 U/mg) was 2.1 times that of WAX (45.46 U/mg). The optimal pH and reaction temperature for the two enzymes was between 4.0 and 4.5 and 65 °C, respectively. Calcium played an important role in the thermal stability of EpABF62C. TtABF51A and EpABF62C showed the highest thermal stabilities at pH 4.5 or 5.0, respectively. At their optimal pHs, TtABF51A and EpABF62C retained greater than 80% of their initial activities after incubation at 55 °C for 96 h or 144 h, respectively. 1H NMR analysis indicated that the two enzymes selectively removed arabinose linked to C-3 of mono-substituted xylose residues in WAX. Compared with the singular application of the GH10 xylanase EpXYN1 from E. parvum, co-digestions of WAX including TtABF51A and/or EpABF62C released 2.49, 3.38, and 4.81 times xylose or 3.38, 1.65, and 2.57 times of xylobiose, respectively. Meanwhile, the amount of arabinose released from WAX by TtABF51A with EpXYN1 was 2.11 times the amount with TtABF51A alone. KEY POINTS: • Two novel α-l-arabinofuranosidases (ABFs) displayed high thermal stability. • The thermal stability of GH62 family EpABF62C was dependent on calcium. • Buffer pH affects the thermal stability of the two ABFs. • Both ABFs enhance the hydrolysis of WAX by a GH10 xylanase.

6.
Colloids Surf B Biointerfaces ; 196: 111345, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32950841

RESUMO

Soybean protein isolate (SPI) powders were prepared at different ultrafine grinding time, and the functional and flavor properties of microparticulation SPI were evaluated. With extending ultrafine grinding time, a narrow and uniform particle size distribution in SPI powders was produced. The particle sizes of protein powders at grinding time 0, 2, 4, 6 and 8 h significantly reduced from 217 ± 16.5-137.5 ± 10.7 nm, while the absolute values of zeta-potential significantly increased from 25 ± 0.93-32.4 ± 117 mV (P < 0.05). The microstructure of SPI at grinding time 0-8 h changed from smooth to irregular. With prolonging the ultrafine grinding processing time, the solubility, foaming and emulsifying properties of SPI powders were improved, the content ofα-helix, ß-sheet and random coils increased, while ß-turn decreased. Furthermore, the ultrafine grinding time clearly influenced the volatile compounds of SPI powders. The main flavor compounds were aldehydes, alcohols, acids, ketones and alkanes. SPI powders for grinding time 2, 4, 6 and 8 h exhibited the higher total content of volatile compounds compared to that for 0 h. So the ultrafine grinding treatment at appropriate time could affect the functional and flavor properties of SPI.

7.
Int J Med Sci ; 17(14): 2225-2231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922185

RESUMO

Background: Lactate dehydrogenase (LDH) has been proved to be a prognostic factor for the severity and poor outcomes of coronavirus disease 2019 (COVID-19). In most studies, patients with various levels of COVID-19 severity were pooled and analyzed which may prevent accurate evaluation of the relationship between LDH and disease progression and in-hospital death. In this study, we aimed to evaluate the association of LDH with in-hospital mortality in severe and critically ill patients with COVID-19. Methods: This single-center retrospective study enrolled 119 patients. Survival curves were plotted using Kaplan-Meier method and compared by log-rank test. Multivariate Cox regression models were used to determine the independent risk factors for in-hospital mortality. Receiver-operator curves (ROCs) were constructed to evaluate the predictive accuracy of LDH and other prognostic biomarkers. Results: Compared to the survival group, LDH levels in the dead group were significantly higher [559.5 (172, 7575) U/L vs 228 (117, 490) U/L, (P < 0.001)]. In Multivariate Cox regression, it remained an independent risk factor for in-hospital mortality (Hazard ratio 5.985, 95.0%CI: 1.498-23.905; P=0.011). A cutoff value of 353.5 U/L predicted the in-hospital mortality with a sensitivity of 94.4% and a specificity of 89.2% respectively. Conclusion: LDH is a favorable prognostic biomarker with high accuracy for predicting in-hospital mortality in severe and critically ill patients with COVID-19. This may direct physicians worldwide to effectively prioritize resources for patients at high risk of death and to implement more aggressive treatments at an earlier phase to save patients' lives.


Assuntos
Infecções por Coronavirus/mortalidade , Estado Terminal/mortalidade , Mortalidade Hospitalar , L-Lactato Desidrogenase/sangue , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Biomarcadores/sangue , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
9.
J Cell Mol Med ; 24(20): 11837-11848, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896985

RESUMO

Stem cell transplantation is nearly available for clinical application in the treatment of ischaemic heart disease (IHD), where it may be joined traditional methods (intervention and surgery). The angiogenic ability of seed cells is essential for this applicability. The aim of this study was to reveal the presence of CD34+ angiogenic stem cells in human decidua at the first trimester and to use their strong angiogenic capacity in the treatment of IHD. In vitro, human decidual CD34+ (dCD34+ ) cells from the first trimester have strong proliferation and clonality abilities. After ruling out the possibility that they were vascular endothelial cells and mesenchymal stem cells (MSCs), dCD34+ cells were found to be able to form tube structures after differentiation. Their angiogenic capacity was obviously superior to that of bone marrow mesenchymal stem cells (BMSCs). At the same time, these cells had immunogenicity similar to that of BMSCs. Following induction of myocardial infarction (MI) in adult rats, infarct size decreased and cardiac function was significantly enhanced after dCD34+ cell transplantation. The survival rate of cells increased, and more neovasculature was found following dCD34+ cell transplantation. Therefore, this study confirms the existence of CD34+ stem cells with strong angiogenic ability in human decidua from the first trimester, which can provide a new option for cell-based therapies for ischaemic diseases, especially IHD.

10.
J Oncol ; 2020: 8309492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765606

RESUMO

DEXD/H box helicase 60 (DDX60) is a new type of DEAD-box RNA helicase, which is induced to express after virus infection. It might involve in antiviral immunity by promoting RIG-I-like receptor-mediated signal transduction. In addition, previous studies had shown that the expression of DDX60 is related to cancer, but there was still a lack of relevant research in breast cancer. In this study, we used the information of patients with breast cancer in the TCGA database for statistical analysis and found that the breast cancer patients with low expression of DDX60 exhibited radiosensitivity. Comparing the radiotherapy groups with the nonradiotherapy groups, for patients with low expression of DDX60, the adjusted hazard ratio (HR) values for radiotherapy were 0.244 (0.064-0.921) and 0.199 (0.062-0.646) in the training and validation datasets, with the p values 0.040 and 0.007, respectively. However, for patients with high expression of DDX60, the adjusted hazard ratio (HR) values were 3.582 (0.627-20.467) and 2.421 (0.460-12.773), with the p values 0.054 and 0.297, respectively. These results suggested that the expression of DDX60 might strongly associate with individualized radiosensitivity in patients with breast cancer.

11.
Database (Oxford) ; 20202020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32761142

RESUMO

The National Center for Biotechnology Information (NCBI) Taxonomy includes organism names and classifications for every sequence in the nucleotide and protein sequence databases of the International Nucleotide Sequence Database Collaboration. Since the last review of this resource in 2012, it has undergone several improvements. Most notable is the shift from a single SQL database to a series of linked databases tied to a framework of data called NameBank. This means that relations among data elements can be adjusted in more detail, resulting in expanded annotation of synonyms, the ability to flag names with specific nomenclatural properties, enhanced tracking of publications tied to names and improved annotation of scientific authorities and types. Additionally, practices utilized by NCBI Taxonomy curators specific to major taxonomic groups are described, terms peculiar to NCBI Taxonomy are explained, external resources are acknowledged and updates to tools and other resources are documented. Database URL: https://www.ncbi.nlm.nih.gov/taxonomy.

12.
Int J Nanomedicine ; 15: 5061-5072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764936

RESUMO

Purpose: Zirconia is one of the most promising implant materials due to its favorable physical, mechanical and biological properties. However, until now, we know little about the mechanism of osseointegration on zirconia. The purpose of this study is to evaluate the effect of Syndecan (Sdc) on osteoblastic cell (MC3T3-E1) adhesion and proliferation onto zirconia materials. Materials and Methods: The mirror-polished disks 15 mm in diameter and 1.5 mm in thick of commercial pure titanium (CpTi), 3mol% yttria-stabilized tetragonal zirconia polycrystalline (3Y-TZP) and nano-zirconia (NanoZr) are used in this study. MC3T3-E1 cells were seeded onto specimen surfaces and subjected to RNA interference (RNAi) for Syndecan-1, Syndecan-2, Syndecan-3, and Syndecan-4. At 48h post-transfection, the cell morphology, actin cytoskeleton, and focal adhesion were observed using scanning electron microscopy or laser scanning confocal fluorescence microscopy. At 24h and 48h post-transfection, cell counting kit-8 (CCK-8) assay was used to investigate cell proliferation. Results: The cell morphology of MC3T3-E1 cells on CpTi, 3Y-TZP, and NanoZr changed into abnormal shape after gene silencing of Syndecan. Among the Syndecan family, Sdc-2 is responsible for NanoZr-specific morphology regulation, via maintenance of cytoskeletal conformation without affecting cellular attachment. According to CCK-8 assay, Sdc-2 affects the osteoblastic cell proliferation onto NanoZr. Conclusion: Within the limitation of this study, we suggest that Syndecan affects osteoblastic cell adhesion on CpTi, 3Y-TZP, and NanoZr. Sdc-2 might be an important heparin-sensitive cell membrane regulator in osteoblastic cell adhesion, specifically on NanoZr, through the organization of actin cytoskeleton and affects osteoblastic cell proliferation.


Assuntos
Osseointegração/fisiologia , Osteoblastos/citologia , Osteoblastos/fisiologia , Sindecanas/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Animais , Adesão Celular/fisiologia , Membrana Celular/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Camundongos , Microscopia Eletrônica de Varredura , Osseointegração/genética , Propriedades de Superfície , Sindecana-2/genética , Sindecana-2/metabolismo , Sindecanas/genética , Titânio/química , Ítrio/química , Zircônio/química
13.
BMC Plant Biol ; 20(1): 374, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787836

RESUMO

BACKGROUND: Triterpenoids from birch (Betula platyphylla Suk.) exert antitumor and anti-HIV activities. Due to the complexity of plant secondary metabolic pathways, triterpene compounds in plants is not always determined by a single gene; they may be controlled by polygene quantitative traits. Secondary metabolism related to terpenoids involves tissue specificity and localisation of key biosynthetic enzymes. Terpene synthesis is influenced by light, hormones and other signals, as well as upstream transcription factor regulation. RESULTS: Anchor Herein, we identified and characterised two birch MYB transcription factors (TFs) that regulate triterpenoid biosynthesis. BpMYB21 and BpMYB61 are R2R3 TFs that positively and negatively regulate responses to methyl-jasmonate (MeJA) and salicyclic acid (SA), respectively. Expression of BpMYB21 and BpMYB61 was elevated in leaves and stems more than roots during July/August in Harbin, China. BpMYB21 expression was increased by abscisic acid (ABA), MeJA, SA and gibberellins (GAs). BpMYB61 expression in leaves and BpMYB21 expression in stems was reduced by ABA, MeJA and SA, while GAs, ethylene, and injury increased BpMYB61 expression. BpMYB21 was localised in nuclei, while BpMYB61 was detected in cell membranes and nuclei. Promoters for both BpMYB21 (1302 bp) and BpMYB61 (850 bp) were active. BpMYB21 and BpMYB61 were ligated into pYES3, introduced into AnchorINVScl (yeast strain without exogenous genes), INVScl-pYES2-SSAnchorAnchor (transgenic yeast strain harbouring the SS gene from birch), and INVScl-pYES2-SE (transgenic yeast strain harbouring the SE gene from birch), and the squalene content was highest in AnchorINVScl-pYES-MYB21-SS (transgenic yeast strain harbouring SS and MYB21 genes) and INVScl-pYES3-MYB61 (transgenic yeast strain harbouring the MYB61 gene). In BpMYB21 transgenic birch key triterpenoid synthesis genes were up-regulated, and in BpMYB61 transgenic birch AnchorFPS (farnesyl pyrophosphate synthase) and SS (squalene synthase) were up-regulated, but HMGR (3-hydroxy-3-methylglutaryl coenzyme a reductase), BPWAnchor (lupeol synthase), SE (squalene epoxidase) and BPY (b-amyrin synthase) were down-regulated. Both BpMYB21 and BpMYB61 specifically activate SE and BPX (cycloartenol synthase synthesis) promoters. CONCLUSIONS: These findings support further functional characterisation of R2R3-MYB genes, and illuminate the regulatory role of BpMYB21 and BpMYB61 in the synthesis of birch triterpenoids.

14.
Best Pract Res Clin Anaesthesiol ; 34(2): 325-344, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32711838

RESUMO

Life-threatening hypersensitivity reactions are more likely to occur in patients with a history of allergy, atopy, or asthma. Hence, in a patient who presented with a history of multiple drug allergies (MDA), an allergological assessment should be performed prior to surgical procedure. Drug allergies, being one of the causes of catastrophic events occurring in the perioperative period, are of major concern to anesthesiologists. Neuromuscular blocking agents are regularly used during anesthesia and are one of the most common causes of perioperative anaphylaxis. They are estimated to be responsible for 50%-70% of perioperative hypersensitivity reactions. Antibiotics and latex represent the next two groups of drug allergy. Allergic reactions to propofol are rare with an incidence of 1:60,000 exposures. Although intraoperative drug anaphylaxis is rare, it contributes to 4.3% of deaths occurring during general anesthesia. These recommendations discuss pathophysiology of MDA, preoperative evaluation, and anesthesia considerations as well as the prevention and management of allergic reactions in anesthetized patients with a history of MDA.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32687695

RESUMO

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration-time data. The genotypes for ABCB1, UGT1A1, and UGT1A9 single-nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single-nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single-dose and multidose studies, respectively. Sitafloxacin AUC and Cmax increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that Cmax was lower in the ABCB1 (rs1045642) mutation group, whereas t1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the Cmax or t1/2 and thereby merit further clinical evaluation.

16.
Stem Cell Res Ther ; 11(1): 295, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680565

RESUMO

BACKGROUND: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis, and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells play crucial roles in responding to these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a means of cell-cell and cell-matrix communication in biological processes. METHODS: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red, and ALP staining to evaluate the functions of exosomes induced by a mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, real-time PCR, FISH, luciferase reporter assay, and western blotting assay were used to investigate the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway. RESULTS: In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to HPDLSC proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking mechanical strain. The luciferase reporter assay demonstrated that miR-181b-5p may target phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. Real-time PCR and western blotting assay verified that miR-181b-5p enhanced the protein kinase B (PKB, also known as AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and promoted HPDLSC induced by inflammation. CONCLUSIONS: This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation via the miR-181b-5p/PTEN/AKT signaling pathway and promote HPDLSC osteogenic differentiation by BMP2/Runx2, suggesting a potential mechanism for maintaining periodontal homeostasis.

17.
Huan Jing Ke Xue ; 41(7): 2981-2994, 2020 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608870

RESUMO

Based on the data from a continuous emission monitoring systems network in 2015, this study analyzed the compliance rates of exhaust gas in the processes of China's iron and steel industry, and established a high-resolution steel plant emission inventory for China (HSEC, 2015), based on the bottom-up method. The contribution of emissions from the iron and steel industry to regional air quality was quantitatively simulated using a CAMx model. The results showed that in 2015, the total emissions of SO2, NOx, PM10, PM2.5, PCDD/Fs, VOCs, CO, BC, OC, EC, and F were 374800 t, 720500 t, 334800 t, 150300 t, 1.91 kg, 842900 t, 34788500 t, 6400 t, 8300 t, 800 t, and 7700 t, respectively. From a regional perspective, the iron and steel industry in Shanghai and Tianjin has the highest emission intensity per unit area and contributes a high proportion to regional air pollution. From a process perspective, in 2015, the exhaust concentration of flue gas in the main process gradually decreased, with a high compliance rate, and the emission factor significantly decreased to lower than that in the existing research results. From a species perspective, in 2015, NOx emission from the steel industry contributed the most to regional air quality, and there is therefore a great emission reduction potential for NOx.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 241: 118653, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-32623304

RESUMO

The chirality of penicillamine (Peni) results in different clinic applications. Host-guest complex based drug delivery system that differentiates the two enantiomers and provides delayed release is of significance in medication. We hereby used ß-CD to encapsulate d- and l-Peni. IRMPD spectra show different characteristic vibrations to distinguish the two enantiomers. Besides common peaks found at 3000-3100 cm-1 and 3520 cm-1, featured peaks are found around 2900 cm-1 and 3400 cm-1. It is found that the featured vibrations of [ß-CD + l-Peni + H]+ are more red-shifted than those of [ß-CD + d-Peni + H]+. Through DFT calculations on the complex configurations sampled from molecular dynamics simulations, d-Peni is found embedded inside ß-CD with a lower free energy of 11.5 kJ mol-1 in the lowest configuration than that of the lowest [ß-CD + l-Peni + H]+ configuration, in which l-Peni is found lying upon the ß-CD. The featured vibrational peaks are attributed to the specific NH⋯O, OH⋯O intermolecular hydrogen bonds. The red-shifted characteristic peaks of [ß-CD + l-Peni + H]+ in IRMPD spectra owe to the stronger NH⋯O hydrogen bonds.

19.
Biomater Sci ; 8(15): 4206-4215, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32555884

RESUMO

Fabrication of cyclic graft (cg) copolymer-based polymeric prodrugs by conjugation of drug molecules to cg copolymers via a dynamic covalent bond capable of responding to biorelevant signals integrates simultaneously the merits of cg copolymers and polymeric prodrugs for enhanced stability of nanocarriers and precise modulation of drug release kinetics. To completely eliminate the compromised drug conjugation efficiency due to the steric hindrance of hydrophilic grafts, it will be useful to develop cg polymeric prodrugs with heterogeneous grafts composed of hydrophilic polymers and drug species, respectively. For this purpose, we reported in this study the synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic oligo (ethylene glycol) (OEG) and reducibly conjugated camptothecin (CPT), cg-poly(oligo(ethylene glycol) monomethyl ether methacrylate)-b-poly((2-hydroxyethyl methacrylate)-disulfide link-camptothecin) (cg-P(OEGMA)-b-P(HEMA-SS-CPT), cg-prodrugs), via an integrated strategy of a previously reported diblock copolymer-based template and post-polymerization intermolecular click conjugation of a reducible CPT prodrug. The micelles self-assembled from cg-prodrugs on one hand had sufficient salt stability due to the branched cg structure, and on the other hand showed a reduction-triggered cleavage of the disulfide link for a promoted CPT release. Most importantly, we uncovered two interesting phenomena of the cg-based polymeric prodrugs as delivery vehicles: (i) the dimensions of both self-assemblies formed by the cg and bottlegraft (bg) polymers depend substantially on the molecular size of the cg and bg polymers likely due to the steric hindrance of the grafted structures of the cg and bg molecules and relatively low aggregation number of the self-assembled structures, and (ii) cg-prodrug-based micelles exhibited greater in vitro cytotoxicity against cancer cells despite the lower drug loading content (DLC) than the bg-based analogues, which results primarily from the faster reduction-triggered degradation and drug release as well as the greater cellular uptake efficiency of the former micelle prodrugs. Taken together, the developed cg-prodrugs provide great potential for chemotherapy, and the aforementioned interesting results will definitely inspire more upcoming studies on the future design and development of novel cg polymers for biomedical applications.

20.
Pharmacotherapy ; 40(7): 614-622, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32476160

RESUMO

BACKGROUND: It is known that γ-glutamyl hydrolase (GGH) is involved in the disposition of methotrexate (MTX), and GGH activity is regulated by DNA methylation in acute lymphoblastic leukemia (ALL) cells. The present study explores the methylation status of the GGH promoter in peripheral blood and its association with MTX levels and toxicities in Chinese children with ALL. METHODS: Serum MTX concentrations were determined by fluorescence polarization immunoassay. Methylation quantification and genotyping for GGH rs3758149 and rs11545078 was performed by Sequenom MassARRAY in 50 pediatric patients with ALL. RESULTS: Overall, the investigated region of the GGH promoter was in hypomethylated status. The methylation levels of cytosine phosphate guanine (CpG)_7, CpG_12, CpG_17, and CpG_20 were significantly higher in patients with B-cell ALL than other immunotypes (p<0.05). The methylation levels of CpG_13.14, CpG_17, and CpG_19 showed a significant negative correlation with MTX C24 hr (p<0.05). The methylation level of CpG_8.9 correlated significantly with MTX C42 hrs (p<0.05). The methylation level of CpG_19 was significantly lower in patients with MTX toxicities (p<0.05). CONCLUSIONS: The methylation levels of the GGH promoter might affect MTX exposure and toxicities. These findings provided reasonable explanations for the variability of MTX responses in patients with childhood ALL.

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