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1.
J Org Chem ; 86(6): 4405-4412, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33656886

RESUMO

An unexpected side product of a McMurry reaction was found to be a new [2.2]pyrenophane consisting of two pyrene units with different substitution patterns as well as different types and degrees of distortion from planarity. The new pyrenophane exhibits both monomer and intramolecular excimer fluorescence. Natural bond orbital (NBO) analysis revealed that there is an intramolecular charge-transfer interaction from the more distorted pyrene system to the less distorted one. The origin of the new pyrenophane was traced back to an impurity that was present a full five steps prior to the McMurry reaction from which it was isolated. The pathway to the pyrenophane shadowed that of the main synthetic route.

2.
Microb Cell Fact ; 20(1): 67, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691697

RESUMO

BACKGROUND: Most patients with acute myeloid leukemia (AML) remain uncurable and require novel therapeutic methods. Gain-of-function FMS-like tyrosine kinase 3 (FLT3) mutations are present in 30-40% of AML patients and serve as an attractive therapeutic target. In addition, FLT3 is aberrantly expressed on blasts in > 90% of patients with AML, making the FLT3 ligand-based drug conjugate a promising therapeutic strategy for the treatment of patients with AML. Here, E. coli was used as a host to express recombinant human FLT3 ligand (rhFL), which was used as a specific vehicle to deliver cytotoxic drugs to FLT3 + AML cells. METHODS: Recombinant hFL was expressed and purified from induced recombinant BL21 (DE3) E. coli. Purified rhFL and emtansine (DM1) were conjugated by an N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) linker. We evaluated the potency of the conjugation product FL-DM1 against FLT3-expressing AML cells by examining viability, apoptosis and the cell cycle. The activation of proteins related to the activation of FLT3 signaling and apoptosis pathways was detected by immunoblotting. The selectivity of FL-DM1 was assessed in our unique HCD-57 cell line, which was transformed with the FLT3 internal tandem duplication mutant (FLT3-ITD). RESULTS: Soluble rhFL was successfully expressed in the periplasm of recombinant E. coli. The purified rhFL was bioactive in stimulating FLT3 signaling in AML cells, and the drug conjugate FL-DM1 showed activity in cell signaling and internalization. FL-DM1 was effective in inhibiting the survival of FLT3-expressing THP-1 and MV-4-11 AML cells, with half maximal inhibitory concentration (IC50) of 12.9 nM and 1.1 nM. Additionally, FL-DM1 induced caspase-3-dependent apoptosis and arrested the cell cycle at the G2/M phase. Moreover, FL-DM1 selectively targeted HCD-57 cells transformed by FLT3-ITD but not parental HCD-57 cells without FLT3 expression. FL-DM1 can also induce obvious apoptosis in primary FLT3-positive AML cells ex vivo. CONCLUSIONS: Our data demonstrated that soluble rhFL can be produced in a bioactive form in the periplasm of recombinant E. coli. FL can be used as a specific vehicle to deliver DM1 into FLT3-expressing AML cells. FL-DM1 exhibited cytotoxicity in FLT3-expressing AML cell lines and primary AML cells. FL-DM1 may have potential clinical applications in treating patients with FLT3-positive AML.

3.
Front Immunol ; 12: 592841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717071

RESUMO

It was previously published that single-nucleotide polymorphism rs2476601 (PTPN22 [protein tyrosine phosphatase non-receptor type 22]-C1858T) might be related to increased sensibility to Mycobacterium tuberculosis and M. leprae infection. However, the results were inconclusive despite a high degree of similarity between both parameters. Herein, we carried out this meta-analysis to systematically summarize and articulate the correlation between PTPN22-C1858T polymorphism and mycobacterial infection. The susceptibility of PTPN22-C1858T carriers with autoimmune conditions receiving immunosuppressive therapy to M. tuberculosis and M. leprae infection was determined. A systematic retrieval of studies on relevance of PTPN22-C1858T polymorphism to susceptibility of M. tuberculosis or M. leprae infection was performed in Chinese National Knowledge Infrastructure, PubMed and Embase databases. We regarded Odds ratios (ORs) and 95% confidence intervals (CIs) as the determined effect size. Finally, four and two case-control studies on tuberculosis and leprosy, respectively, were included. In all genetic models, without indicated association between PTPN22-C1858T polymorphism and tuberculosis's susceptibility. [C versus T: OR = 0.22 (95% CI: 0.09-0.50, PH = 0.887); CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, PH = 0.889); TT+CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, PH = 0.889)]. A significantly increased risk of leprosy was perceived in patients with the PTPN22-C1858T polymorphism [C versus T: OR = 2.82 (95% CI: 1.02-7.81, PH = 0.108)]. While the PTPN22-C1858T polymorphism is irrelevant to higher susceptibility to the infection of M. tuberculosis in Caucasians and Asians, it is relevant to increased susceptibility to the infection of M. leprae. However, the results of M. leprae are supposed to interpreted with prudence owing to the limited quantity of studies and heterogeneity. Further well-designed studies with sufficient populations are required to verify our conclusions.

4.
Small ; 17(11): e2006596, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33620759

RESUMO

Cell therapeutics hold tremendous regenerative potential and the therapeutic effect depends on the effective delivery of cells. However, current cell delivery carriers with unsuitable cytocompatibility and topological structure demonstrate poor cell viability during injection. Therefore, porous shape-memory cryogel microspheres (CMS) are prepared from methacrylated gelatin (GelMA) by combining an emulsion technique with gradient-cooling cryogelation. Pore sizes of the CMS are adjusted via the gradient-cooling procedure, with the optimized pore size (15.5 ± 6.0 µm) being achieved on the 30-min gradient-cooled variant (CMS-30). Unlike hydrogel microspheres (HMS), CMS promotes human bone marrow stromal cell (hBMSC) and human umbilical vein endothelial cell (HUVEC) adhesion, proliferated with high levels of stemness for 7 d, and protects cells during the injection process using a 26G syringe needle. Moreover, CMS-30 enhances the osteogenic differentiation of hBMSCs in osteoinductive media. CMS can serve as building blocks for delivering multiple cell types. Here, hBMSC-loaded and HUVEC-loaded CMS-30, mixed at a 1:1 ratio, are injected subcutaneously into nude mice for 2 months. Results show the development of vascularized bone-like tissue with high levels of OCN and CD31. These findings indicate that GelMA CMS of a certain pore size can effectively deliver multiple cells to achieve functional tissue regeneration.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33557516

RESUMO

Bimetallic organic frameworks (Bi-MOFs) have been recognized as one of the most ideal precursors to construct metal oxide semiconductor (MOS) composites, owing to their high surface area, various chemical structures, and easy removal of the sacrificial MOF scaffolds through calcination. Herein, we synthesized Zn/Ni Bi-MOF for the first time via a facile ion exchange postsynthetic strategy, formed a three-dimensional framework consisting of infinite one-dimensional chains that is unattainable through the direct solvothermal approach, and then transformed the Zn/Ni Bi-MOF into a unique ZnO/NiO heterostructure through calcination. Notably, the obtained sensor based on a ZnO/NiO heterostructure exhibits an ultrahigh response of 280.2 toward 500 ppm n-propanol at 275 °C (17.2-fold enhancement compared with that of ZnO), remarkable selectivity, and a limit of detection of 200 ppb with a notable response (2.51), which outperforms state-of-the-art n-propanol sensors. The enhanced n-propanol sensing properties may be attributed to the synergistic effects of several points including the heterojunction at the interface between the NiO and ZnO nanoparticles, especially a one-dimensional chain MOF template structure as well as the chemical sensitization effect of NiO. This work provides a promising strategy for the development of a novel Bi-MOF-derived MOS heterostructure or homostructure with well-defined morphology and composition that can be applied to the fields of gas sensing, energy storage, and catalysis.

6.
Arch Oral Biol ; 123: 105034, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33472098

RESUMO

OBJECTIVE: This study aimed to investigate the effect of epigallocatechin gallate (EGCG) on the proliferation, mineralization, inflammation and hypoxia responses of human dental pulp stem cells (hDPSCs) in vitro and its effect on inflammatory pulp tissue in rats in vivo. DESIGN: The optimum concentration of EGCG was selected by creating a dose response curve. Expression of odontogenic/osteogenic-related genes and inflammatory cytokines after stimulation with Lipopolysaccharide (LPS) was detected by real-time PCR. Under hypoxic conditions, cell proliferation and expression of reactive oxygen species (ROS) and superoxide dismutase (SOD) were detected.In vivo, the maxillary first molars of SD rats were pulpotomized and stimulated with 5 mg/mL LPS for 30 min. Normal saline and EGCG were used to flush the pulp chamber. After 2 months, samples were removed for micro-CT scanning and HE staining. RESULTS: CCK-8 assay revealed that 10 µg/mL EGCG had no significant effect on the proliferation of hDPSCs. EGCG inhibited expression of IL-1ß, IL-6, and TNF-α. Furthermore, EGCG rescued cell proliferation ability, increased SOD activity and reduced ROS expression under hypoxia.In vivo, reduced inflammatory cell accumulation was observed in the coronal pulp in the EGCG group, while in the control group, diffuse inflammatory cells were observed in the radicular pulp. CONCLUSION: EGCG had no obvious effects on calcified nodule formation but significantly inhibited the inflammatory response of hDPSCs and inhibited apoptosis of hDPSCs caused by hypoxia injury. In vivo, EGCG exerts inhibitory effects on pulp tissue inflammation.


Assuntos
Catequina/análogos & derivados , Polpa Dentária/citologia , Células-Tronco/efeitos dos fármacos , Animais , Apoptose , Catequina/farmacologia , Hipóxia Celular , Células Cultivadas , Humanos , Inflamação , Ratos , Ratos Sprague-Dawley
7.
Chem Commun (Camb) ; 57(4): 484-487, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33326519

RESUMO

The absorption and emission properties of various diphenyl-dibenzofulvene (DP-DBF) derivatives were investigated, and their crystallization-induced emission enhancement (CIEE) performances were found to show a clear correlation with the twist angle around the C[double bond, length as m-dash]C bond of the DP-DBF structure.

8.
AAPS PharmSciTech ; 21(8): 318, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175290

RESUMO

The study is designed to formulate, optimize, and evaluate astaxanthin (ASTA)-loaded nanostructured lipid carrier (NLC) with an aim to improve its stability, water solubility, skin permeability and retention and reduce drug-related side effects. ASTA was extracted from Haematococcus pluvialis. ASTA-NLC was formulated by the technique of melt emulsification-ultrasonic and optimized taking solid:liquid lipid ratio, total lipid:drug ratio, drug concentration, emulsifier types, and amounts as independent variables with particle sizes (PS) and entrapment efficiency (EE) as dependent variables. The optimized formulation (N21) exhibited spherical surfaced stable nanoparticles of 67.4 ± 2.1 nm size and 94.3 ± 0.5% EE. Formulation N21 was then evaluated for its physiological properties, physicochemical properties, drug content, in vitro release and skin penetration, and retention analysis. The ASTA-NLC was found to be nonirritating, homogenous, and with excellent stability and water solubility. In vitro release studies showed the cumulative release rate of NLC was 83.0 ± 3.4% at 48 h. The skin penetration and retention studies indicated that cumulative permeability was 174.10 ± 4.38 µg/cm2 and the retention was 8.00 ± 1.62 µg/cm2 within 24 h. It can be concluded that NLC serves as a promising carrier for site specific targeting with better stability and skin penetration.

9.
Comput Math Methods Med ; 2020: 8926750, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133228

RESUMO

With the development of computer technology, many machine learning algorithms have been applied to the field of biology, forming the discipline of bioinformatics. Protein function prediction is a classic research topic in this subject area. Though many scholars have made achievements in identifying protein by different algorithms, they often extract a large number of feature types and use very complex classification methods to obtain little improvement in the classification effect, and this process is very time-consuming. In this research, we attempt to utilize as few features as possible to classify vesicular transportation proteins and to simultaneously obtain a comparative satisfactory classification result. We adopt CTDC which is a submethod of the method of composition, transition, and distribution (CTD) to extract only 39 features from each sequence, and LibSVM is used as the classification method. We use the SMOTE method to deal with the problem of dataset imbalance. There are 11619 protein sequences in our dataset. We selected 4428 sequences to train our classification model and selected other 1832 sequences from our dataset to test the classification effect and finally achieved an accuracy of 71.77%. After dimension reduction by MRMD, the accuracy is 72.16%.

10.
Front Bioeng Biotechnol ; 8: 584807, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195148

RESUMO

Thermophilicity is a very important property of proteins, as it sometimes determines denaturation and cell death. Thus, methods for predicting thermophilic proteins and non-thermophilic proteins are of interest and can contribute to the design and engineering of proteins. In this article, we describe the use of feature dimension reduction technology and LIBSVM to identify thermophilic proteins. The highest accuracy obtained by cross-validation was 96.02% with 119 parameters. When using only 16 features, we obtained an accuracy of 93.33%. We discuss the importance of the different characteristics in identification and report a comparison of the performance of support vector machine to that of other methods.

11.
Front Cell Dev Biol ; 8: 591487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195258

RESUMO

Excessive oxidative stress responses can threaten our health, and thus it is essential to produce antioxidant proteins to regulate the body's oxidative responses. The low number of antioxidant proteins makes it difficult to extract their representative features. Our experimental method did not use structural information but instead studied antioxidant proteins from a sequenced perspective while focusing on the impact of data imbalance on sensitivity, thus greatly improving the model's sensitivity for antioxidant protein recognition. We developed a method based on the Composition of k-spaced Amino Acid Pairs (CKSAAP) and the Conjoint Triad (CT) features derived from the amino acid composition and protein-protein interactions. SMOTE and the Max-Relevance-Max-Distance algorithm (MRMD) were utilized to unbalance the training data and select the optimal feature subset, respectively. The test set used 10-fold crossing validation and a random forest algorithm for classification according to the selected feature subset. The sensitivity was 0.792, the specificity was 0.808, and the average accuracy was 0.8.

12.
J Phys Chem Lett ; 11(22): 9543-9551, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33115232

RESUMO

Ultrasensitive surface-enhanced Raman spectroscopy (SERS) still faces difficulties in quantitative analysis because of its susceptibility to local optical field variations at plasmonic hotspots in metallo-dielectric nanostructures. Current SERS calibration approaches using Raman tags have inherent limitations due to spatial occupation competition with analyte molecules, spectral interference with analyte Raman peaks, and photodegradation. Herein, we report that plasmon-enhanced electronic Raman scattering (ERS) signals from metal can serve as an internal standard for spatial and temporal calibration of molecular Raman scattering (MRS) signals from analyte molecules at the same hotspots, enabling rigorous quantitative SERS analysis. We observe a linear dependence between ERS and MRS signal intensities upon spatial and temporal variations of excitation optical fields, manifesting the |E|4 enhancements for both ERS and MRS processes at the same hotspots in agreement with our theoretical prediction. Furthermore, we find that the ERS calibration's performance limit can result from orientation variations of analyte molecules at hotspots.

13.
Stem Cells Int ; 2020: 5154707, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014068

RESUMO

Dentin formation was dependent on osteo-/odontogenic differentiation of dental pulp stem cells (DPSCs). It was observed in previous studies that antibiotic treatment in a clinical and animal model resulted in impaired mineralization of dental tissues. We previously reported that microbiota maintained the function of bone marrow mesenchymal stem cells, while whether microbiota dysbiosis caused by antibiotic treatment contributed to DPSCs dysfunction and impaired dentin formation is still not known. In this study, we aimed to clarify the role of microbiota or its metabolic products on dental mineralization and the function of DPSCs. Mice were treated with antibiotics to disrupt microbiota; then, the growth rate and histological characteristics of incisors as well as the biological characteristics of DPSCs in vitro were compared with specific pathogen-free (SPF) mice. In antibiotic-treated mice (AbT), we found a diminished quantity of microbiota and reduced growth rate of mechanical injured incisor, as well as decreased colony-forming rate and impaired ability of osteo-/odontogenic differentiation of DPSCs, in comparison to SPF mice. Colonization of AbT mice with SPF mice replanted the microbiota by cohousing (conventionalized (ConvD)) and normalized the growth rate of injured incisors and colony-forming and osteo-/odontogenic differentiation ability of DPSCs. Giving short-chain fatty acids (SCFAs) by oral gavage after antibiotic treatment also rescued the growth rate of incisors and the differentiation ability of DPSCs and enhanced proliferation ability of DPSCs. Collectively, gut microbiota could make contribution to maintain continuous growth of injured rodent incisor and differentiation capacity of DPSCs; SCFAs might play a crucial role in this process.

14.
Chemistry ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960997

RESUMO

A gram-scale synthesis of a series of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n=7-9) has been accomplished as well as the first synthesis of the next higher homologue 1,1,10,10-tetramethyl[10](2,11)teropyrenophane. The scale-up of the original small-scale synthesis required the development of several heavily modified synthetic methods, including a chlorination/Friedel-Crafts alkylation protocol and an iodination/Wurtz coupling protocol, which were performed on 25-30 g and 30-60 g scales, respectively. Two separate sets of conditions for the key teropyrene-forming cyclodehydrogenation reaction at the end of the synthetic pathway were developed, an acid-promoted one for the two less strained congeners and an acid-free method for the two more strained homologues.

15.
Front Physiol ; 11: 1077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973567

RESUMO

When pulp tissue is damaged by caries or trauma, vital pulp therapy (VPT) can help preserve the pulp tissue for long-term retention of teeth. However, the choice of pulp capping agent used in VPT is important for the successful preservation of the pulp tissue. Here we investigated the expression and biological function of human ß-defensin 4 (HBD4) in dental pulp stem cells (DPSC) and explored its potential as a pulp capping agent. We examined the expression of HBD4 in DPSC in vitro using qPCR and immunofluorescence staining. We also looked at the effect of HBD4 on inflammatory factors in lipopolysaccharide (LPS)-stimulated DPSC, and its effects on mineralizing cell phenotype differentiation, via qPCR and western blot. Finally, we examined the ability of HBD4 to promote the restoration of the pulp-dentin complex in vivo, using male Wistar rats with reversible pulpitis. We found HBD4 was highly expressed in DPSC stimulated by TNF-α and IL-1α. HBD4 down-regulated the expression of inflammatory mediators (i.e., IL-1α, IL-1ß, IL-6, TNF-α) in LPS-stimulated DPSC, and suppressed MAPK activity and the NF-κB pathway. HBD4 also enhanced the differentiation of DPSC into osteoblasts or odontoblasts, potentially by modulating the Notch pathway. Furthermore, HBD4 controlled the degree of pulp inflammation in a rat model of reversible pulpitis and induced the formation of restorative dentin. Together our findings indicate HBD4 may be a useful pulp capping agent for use in VPT.

16.
Neuroscience ; 448: 172-190, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-32976986

RESUMO

Caveolin-1 (Cav-1) is an important modulator for adult neurogenesis in post stroke brain repair but its underlying mechanisms are largely unknown. In the present study, we report that endothelial Cav-1 inhibits neuronal differentiation of neural stem/progenitor cells (NSCs/NPCs) in post ischemic brain via regulating vascular endothelial growth factor (VEGF) and NeuroD1 signaling pathway. We first investigated the dynamic change of Cav-1 and its impact on neuronal differentiation in rat and mouse models of 2 h transient middle cerebral artery occlusion (MCAO) plus 1, 7, 14, 21 and 28 day of reperfusion. We then studied the roles of endothelial Cav-1 in modulating the neuronal differentiation of NPCs which were co-cultured with brain microvascular endothelial cells (BMVECs) under 2 h oxygen-glucose deprivation plus 5 days reoxygenation (OGD/R). The major discoveries include: (1) Cav-1 expression in the hippocampal dentate gyrus (DG) was down-regulated on day 1 after 2 h cerebral ischemia, and gradually recovered with reperfusion time, accompanied with transient increased but gradually reduced neuronal differentiation of NPCs marked by doublecortin (DCX). (2) Cav-1 knockout mice exhibited the increased DCX and VEGF at the granular cell layers of hippocampal DG in post-ischemic brains. (3) Co-cultured with BMVECs, NPCs had remarkably decreased neuronal differentiation under OGD/R. Knockdown of Cav-1 in the BMVECs increased VEGF secretion into the medium and NeuroD1+ cells, and rescued the neuronal differentiation of NPCs without affecting astroglial and oligodendroglial differentiation. (4) Cav-1 exosomes released from BMVECs inhibited neuronal differentiation of NPCs via decreasing the expression of VEGF, p44/42MAPK phosphorylation and NeuronD1 upon OGD/R insults. Taken together, endothelial Cav-1 serves as a niche regulator to inhibit neuronal differentiation via negatively modulating VEGF, p44/42MAPK phosphorylation and NeuronD1 signaling pathway.

17.
Sci Rep ; 10(1): 15025, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929159

RESUMO

A detailed computational study of the atmospheric reaction of the simplest Criegee intermediate CH2OO with methane has been performed using the density functional theory (DFT) method and high-level calculations. Solvation models were utilized to address the effect of water molecules on prominent reaction steps and their associated energies. The structures of all proposed mechanisms were optimized using B3LYP functional with several basis sets: 6-31G(d), 6-31G (2df,p), 6-311++G(3df,3pd) and at M06-2X/6-31G(d) and APFD/6-31G(d) levels of theory. Furthermore, all structures were optimized at the B3LYP/6-311++G(3df,3pd) level of theory. The intrinsic reaction coordinate (IRC) analysis was performed for characterizing the transition states on the potential energy surfaces. Fifteen different mechanistic pathways were studied for the reaction of Criegee intermediate with methane. Both thermodynamic functions (ΔH and ΔG), and activation parameters (activation energies Ea, enthalpies of activation ΔHǂ, and Gibbs energies of activation ΔGǂ) were calculated for all pathways investigated. The individual mechanisms for pathways A1, A2, B1, and B2, comprise two key steps: (i) the formation of ethyl hydroperoxide (EHP) accompanying with the hydrogen transfer from the alkanes to the terminal oxygen atom of CIs, and (ii) a following unimolecular dissociation of EHP. Pathways from C1 → H1 involve the bimolecular reaction of EHP with different atmospheric species. The photochemical reaction of methane with EHP (pathway E1) was found to be the most plausible reaction mechanism, exhibiting an overall activation energy of 7 kJ mol-1, which was estimated in vacuum at the B3LYP/6-311++G(3df,3pd) level of theory. All of the reactions were found to be strongly exothermic, expect the case of the sulfur dioxide-involved pathway that is predicted to be endothermic. The solvent effect plays an important role in the reaction of EHP with ammonia (pathway F1). Compared with the gas phase reaction, the overall activation energy for the solution phase reaction is decreased by 162 and 140 kJ mol-1 according to calculations done with the SMD and PCM solvation models, respectively.

18.
J Org Chem ; 85(18): 11968-11974, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32803967

RESUMO

Previously, we have finished the total synthesis of lycojaponicumin A (2) via development of an efficient synthetic strategy using semipinacol rearrangement as a key step. In order to further demonstrate the generality of this synthetic route, herein, we report the total synthesis of another fawcettimine-type alkaloid sieboldine A (1) from the same intermediate, which possesses an A/B/D tricyclic ring system and vicinal quaternary centers of 1. The synthesis features late-stage site-selective redox reactions, Schmidt glycosylation cyclization, and highly selective transformations.

19.
Biomark Res ; 8: 30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817792

RESUMO

Background: Acute myeloid leukemia (AML) is a malignant hematological neoplasm of myeloid progenitor cells. Mutations of FLT3 in its tyrosine kinase domain (FLT3-TKD) are found in ~ 8% of patients with AML, with D835Y as the most common substitution. This mutation activates survival signals that drives the disease and is resistant to the first generation FLT3 inhibitors. Development of a highly sensitive method to detect FLT3D835Y is important to direct therapeutic options, predict prognosis, and monitor minimal residual disease in patients with AML. Methods and results: In the present study, we developed a highly sensitive FLT3D835Y detection method by using the restriction fragment nested allele-specific PCR technique. The method consists of three steps: 1) initial amplification of DNA samples with PCR primers surrounding the FLT3D835Y mutation site, 2) digestion of the PCR products with restriction enzyme EcoRV that only cleaves the wild type allele, and 3) detection of FLT3D835Y by allele-specific PCR with nested primers. We were able to detect FLT3D835Y with a sensitivity of 0.001% by using purified plasmid DNAs and blood cell DNAs containing known proportions of FLT3D835Y. We analyzed blood cell DNA samples from 64 patients with AML and found six FLT3D835Y-positive cases, two of which could not be detected by conventional DNA sequencing methods. Importantly, the method was able to detect FLT3D835Y in a sample collected from a relapsed patient while the patient was in complete remission with negative MRD determined by flow cytometry. Therefore, our RFN-AS-PCR detected MRD after treatment that was missed by flow cytometry and Sanger DNA sequencing, by conventional methods. Conclusions: We have developed a simple and highly sensitive method that will allow for detection of FLT3D835Y at a very low level. This method may have major clinical implications for treatment of AML.

20.
J Endod ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32771418

RESUMO

INTRODUCTION: The aim of this study was to establish an intrusive luxation model in rats and observe the pulpal and periodontal outcomes. METHODS: The intrusion was experimentally induced by an application of 20-N force on the occlusal surface of maxillary right second molar along the tooth axial using a striking instrument in 3-week-old male Sprague-Dawley rats. Thirty rats were divided into 6 groups (n = 5) and were sacrificed after 3, 7, 14, 30, 60, and 90 days of the surgery. The occurrence of pulpal and periodontal complications was observed by micro-computed tomographic scanning and hematoxylin-eosin staining. RESULTS: All experimental teeth were fully intruded into the alveolar bone with their occlusal surface located at the cervical level of the adjacent first molar. Spontaneous re-eruption initiated at 7 days. At 14 days, 4 teeth (80%, 4/5) partially re-erupted, whereas 2 (40%), 3 (75%), and 4 (100%) teeth completely re-erupted at 30, 60, and 90 days, respectively. Pulp degeneration and inflammation mainly occurred in 4 teeth at 3 days, 5 at 7 days, and 2 at 14 days; after 14 days, pulp calcification was observed in 8 teeth. Ankylosis and replacement root resorption mainly occurred in 1 tooth at 30 days, 2 teeth at 60 days, and 3 at 90 days. Marginal bone loss was observed in 3 teeth (60%) at 30 days, 3 (75%) at 60 days, and 2 (50%) at 90 days. CONCLUSIONS: An animal model of intrusive dentoalveolar trauma was successfully established in rats. Pulpal and periodontal complications similar to clinical tooth intrusion were observed, which provided a basis for exploring the mechanisms of complications in the future.

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