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1.
Int J Cancer ; 146(2): 400-412, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31271662

RESUMO

Histone demethylases are promising therapeutic targets as they play fundamental roles for survival of Mixed lineage leukemia rearranged acute leukemia (MLLr AL). Here we focused on the catalytic Jumonji domain of histone H3 lysine 9 (H3K9) demethylase JMJD1C to screen for potential small molecular modulators from 149,519 natural products and 33,765 Chinese medicine components via virtual screening. JMJD1C Jumonji domain inhibitor 4 (JDI-4) and JDI-12 that share a common structural backbone were detected within the top 15 compounds. Surface plasmon resonance analysis showed that JDI-4 and JDI-12 bind to JMJD1C and its family homolog KDM3B with modest affinity. In vitro demethylation assays showed that JDI-4 can reverse the H3K9 demethylation conferred by KDM3B. In vivo demethylation assays indicated that JDI-4 and JDI-12 could induce the global increase of H3K9 methylation. Cell proliferation and colony formation assays documented that JDI-4 and JDI-12 kill MLLr AL and other malignant hematopoietic cells, but not leukemia cells resistant to JMJD1C depletion or cord blood cells. Furthermore, JDI-16, among multiple compounds structurally akin to JDI-4/JDI-12, exhibits superior killing activities against malignant hematopoietic cells compared to JDI-4/JDI-12. Mechanistically, JDI-16 not only induces apoptosis but also differentiation of MLLr AL cells. RNA sequencing and quantitative PCR showed that JDI-16 induced gene expression associated with cell metabolism; targeted metabolomics revealed that JDI-16 downregulates lactic acids, NADP+ and other metabolites. Moreover, JDI-16 collaborates with all-trans retinoic acid to repress MLLr AML cells. In summary, we identified bona fide JMJD1C inhibitors that induce preferential death of MLLr AL cells.

2.
Neuroreport ; 31(1): 29-36, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31725061

RESUMO

Spinal cord injury (SCI) is a devastating disease with few effective treatments. This study mainly explored the mechanism of TRPC5 gene in the treatment of spinal cord ischemia reperfusion injury from the perspective of angiogenesis. Western blot, immunohistochemistry, hematoxylin and eosin, ELISA, and reverse transcription-PCR (RT-PCR) were used to detect the expression levels of related angiogenic proteins such as von Willebrend factor (vWF), vascular endothelial growth factor (VEGF), CD31, and HIF-1α. The results showed that compared with the IR group, the Basso, Beattie, and Bresnahan scores of IR + adeno-associated virus (AAV) + TRPC5 group were higher with significant difference. And compared with ischemia/reperfusion (I/R) group, RT-PCR and ELISA results showed that inflammatory factors such as IL-6, IL-1ß, and TNF-α were significantly reduced in IR + AAV + TRPC5 group. In addition, the expression of vascular related proteins such as vWF, VEGF, and CD31 in spinal cord tissue were all increased. Taken together the results, we suggest that TRPC5 could significantly increase the expression of angiogenic protein and slow down the occurrence of inflammatory response to repair the SCI.

3.
Gait Posture ; 75: 93-97, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639614

RESUMO

BACKGROUND: Scoliosis is accepted as a 3-dimensional deformity involving axial, sagittal and frontal planes. RESEARCH QUESTION: To evaluate the correlation between baropodometric parameters and coronal balance status for idiopathic scoliosis. METHODS: 44 patients (7 males and 37 females) of Adolescent Idiopathic Scoliosis (AIS) were recruited. All participants should have scoliosis confirmed by a spine X-ray performed less than one month ahead of the baropodometric study. Radiographic studies including Cobb angle, offset between Central Sacral Vertical Line (CSVL) and C7 Vertebra Plumb Line (C7PL) (considered as global coronal balance, GCB), Apical Translation of the major curve (AT, considered as regional coronal balance) as well as Lateral Pelvic Tilt (LPT) were examined. A static baropodometry was performed for each patient. The contact surface and load ratio (to the entire load of both feet) were measured. RESULTS: On both sides, the surface of the forefoot was significantly larger than that of the rearfoot (P < 0.001) and the load ratio of the forefoot was significantly smaller than that of the rearfoot (P < 0.001). On the major curve side, GCB showed a positive correlation with the contact surface of the forefoot (r = 0.36, P = 0.019), as well as the load ratio (r = 0.40, P = 0.008). AT also showed a positive correlation with the load ratio of the forefoot (r = 0.331, P = 0.03) but no correlation with contact surface. SIGNIFICANCE: In scoliosis, coronal balance is correlated to plantar pressure distribution. Apical translation of the major curve and offset between CSVL and C7PL are the best describers of coronal balance.

4.
Cell Signal ; 65: 109419, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31526829

RESUMO

Cancer cells with stem cell properties have been acknowledged to be responsible for cancer initiation and progression. Wnt/ß-catenin signalling is a major signal pathway promoting the stemness of cancer cells. Anterior gradient 3 (AGR3), a member of the protein disulfide isomerase (PDI) family, was found to be overexpressed in several cancers. However, the roles and mechanisms of AGR3 in colorectal cancer (CRC) have not been previously described. In our study, we find that AGR3 is highly expressed in CRC and associated with poor prognosis. Functional studies show that AGR3 promotes the stemness of CRC cells. Mechanically, AGR3 activates Wnt/ß-catenin signalling and promotes the nuclear translocation of ß-catenin to upregulate stemness related genes. Wnt/ß-catenin signalling inhibition counteracts the promoting effect of AGR3 on cancer stemness. Moreover, the effect of AGR3 on Wnt/ß-catenin signalling and cancer stemness depends on the presence of frizzled 4 (FZD4). Thus, our study first uncovers the stemness-promoting role and the oncogenic mechanism of AGR3 in CRC, which might provide a novel target for designing anti-CRC strategies.

5.
Respir Physiol Neurobiol ; 271: 103289, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31505275

RESUMO

Infection induced diaphragm weakness is a major contributor to death and prolonged mechanical ventilation in critically ill patients. Infection induced muscle dysfunction is associated with activation of muscle proteolytic enzymes, and taurine is known to suppress proteolysis. We therefore postulated that taurine administration may prevent infection induced diaphragm dysfunction. The purpose of this study was to test this hypothesis using a clinically relevant animal model of infection, i.e. cecal ligation puncture induced sepsis (CLP). Studies were performed on (n = 5-7 mice/group): (a) sham operated controls, (b) animals with sepsis induced by CLP, (c) sham operated animals given taurine (75 mg/kg/d, intraperitoneally), and (d) CLP animals given taurine. At intervals after surgery animals were euthanized, diaphragm force generation measured in vitro, and diaphragm calpain, caspase and proteasomal activity determined. CLP elicited a large reduction in diaphragm specific force generation at 24 h (1-150 Hz, p < 0.001) and taurine significantly attenuated CLP induced diaphragm weakness at all stimulation frequencies (p < 0.001). CLP induced significant increases in diaphragm calpain, caspase and proteasomal activity; taurine administration prevented increases in the activity of all three pathways. In additional time course experiments, diaphragm force generation remained at control levels over 72 h in CLP animals treated with daily taurine administration, while CLP animals demonstrated severe, sustained reductions in diaphragm strength (p < 0.01 for all time points). Our results indicate that taurine administration prevents infection induced diaphragm weakness and reduces activation of three major proteolytic pathways. Because this agent is has been shown to be safe, non-toxic when administered to humans, taurine may have a role in treating infection induced diaphragm weakness. Future clinical studies will be needed to assess this possibility.

6.
J Pediatr Orthop B ; 29(1): 1-8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31305364

RESUMO

Many surgical options have been proposed to improve the ambulatory status of children with spastic cerebral palsy (CP), but none have focused on addressing both spasticity and lower extremity tendon contractures. The purpose of this study is to evaluate the results of selective dorsal rhizotomy (SDR) followed by minimally invasive tendon lengthening allowing immediate return to ambulation. Two hundred fifty-five spastic CP patients (who received SDR procedure at an average age of 6.9±2.6 years and tendon lengthening procedure at an average age of 7.2±2.5 years) were retrospectively reviewed. Patients were grouped by the gross motor function classification system (GMFCS) 1-3 and 4-5. Kaplan-Meier analysis and Cox proportional hazard model using a requirement for additional tendon lengthening as an end point were conducted. Tendon lengthening followed SDR at an average of 4.3±10.7 months. On an average of 4.9±1.2 years after tendon lengthening, GMFCS was improved in 28 and maintained in 213 patients, respectively. There was no difference of variables and joint angles between the two GMFCS groups. A repeat tendon lengthening was required in 19 patients. The Kaplan-Meier analysis showed 81% success rate. Cox proportional hazard model identified age at tendon lengthening [hazards ratio (HR), 0.53; 95% confidence interval (CI), 0.37-0.76] and duration between SDR and tendon lengthening of more than 6 months (HR, 2.96; 95% CI, 1.05-8.33) associated with need for a repeat tendon lengthening procedure. Our novel approach of SDR/tendon lengthening results in improved joint angles as well as stable or improved GMFCS. Longer follow-up is necessary to determine if this approach could prolong ambulatory ability and reduced need for more invasive orthopedic surgeries.

7.
J Trace Elem Med Biol ; 57: 68-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568922

RESUMO

BACKGROUND AND AIM: Major and trace elements play an important role in human body, and it has been reported that ionomic distribution differ greatly in tumor patients. The aim of the present study was to investigate the effects of cisplatin-based neoadjuvant chemoradiotherapy on the ionomic profile in human plasma as a potential biomarker for the therapeutic effects of cervical cancer. METHOD: Thirty-seven patients with cervical cancer receiving neoadjuvant chemoradiotherapy were included in this study, pretherapy and post-treatment blood samples were collected and concentrations of 24 ions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The results showed that after cisplatin chemotherapy and radiotherapy, patients' plasma Pt level significantly increased, Na, Mg, P, K, Ca, Se, Cu, Zn, Se, Sr, Ba levels significantly decreased (P < 0.01), and Al, Cu ions were significantly correlated with the treatment effect (P < 0.05). In addition, the pattern of elemental correlations changed dramatically after the neoadjuvant chemoradiotherapy. CONCLUSION: The results indicated that the plasma ionomic profile may serve as a quick and convenient tool to reflect the therapeutic effect of cisplatin-based chemoradiotherapy in cervical cancer patients, and supplement of certain essential elements may be of great importance for the maintenance of ion homeostasis in human body and for the reduction of adverse effect of chemotherapy and radiotherapy.

8.
J Nanosci Nanotechnol ; 20(3): 1351-1357, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492294

RESUMO

Arginine-glycine-aspartic acid (RGD) peptide sequences exist in a variety of biological extracellular matrices and can specifically bind the cell-surface integrin αvß3, which is overexpressed in cancer cells and plays important roles in tumor growth and invasion. Quantum dots (QDs) have been applied in the field of cell biology and can be physically conjugated to the surface of cancer cells for imaging. In this research, we developed QDs-RGD nanoparticles and investigated its application in pancreatic cancer cell imaging and its influence on the biological behavior of pancreatic cancer cells. The results of flow cytometric analysis showed that the αvß3 receptor was markedly overexpressed on pancreatic cancer cells. In cellular uptake studies, the fluorescence signal of QDs-RGD nanoparticles in pancreatic cancer cells was higher than that of QDs without RGD conjugation, as determined by an inverted fluorescence microscope. Furthermore, the biological behavior of pancreatic cancer cells was affected by QDs-RGD nanoparticles, which inhibited proliferation, migration and invasion and induced G2-phase cell cycle arrest. With integrin αvß3 as a target, QDs-RGD nanoparticles can generate high-quality images of pancreatic cancer cells and have immense potential for use in the targeted diagnosis and therapy of pancreatic cancer.

9.
J Contemp Dent Pract ; 20(8): 994-999, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31797860

RESUMO

AIM: The contemporary article aims to review and compare various literatures concerning different conclusions regarding the correlation between tooth size discrepancy (TSD) and Angle's malocclusion groups. BACKGROUND: Acquiring the ideal occlusion plays one of the major roles while designing the treatment plan for an orthodontic patient, any alterations in the individual tooth sizes are called TSD and will hinder this prime requirement. By determining the correct tooth size ratio, it further helps in acquiring the accurate interdigitation, balanced occlusion, and also predicting the orthodontic treatment results. Various investigations were carried out to know the correlation between tooth size discrepancies and different malocclusion groups, of which, a few reported a statistically significant difference whereas others reported no significant difference. REVIEW RESULTS: A computerized database quest was operated utilizing the Medline database (Pubmed/Medline) for original research and review articles. Publications between 1946 and 2018 were included. Four hundred twenty-one articles were recovered from database search and, among them, 66 articles were selected to review the full-article. CONCLUSION: Although a comparison was done between the tooth-size ratios and malocclusion groups (classes I, II, and III), many investigators noted no significant difference but there is an inadequacy in the data particularly related to subgroups of Angle's classification of malocclusion among these investigations; therefore, further studies are required to interpret this correlation. CLINICAL SIGNIFICANCE: As there is high incidence of tooth size discrepancies noted in the previous literature orthodontist, Bolton's analysis regardless of malocclusion group, sex, and ethnicity is highly recommended.

10.
J Hazard Mater ; : 121663, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31784133

RESUMO

Exposure to polycyclic aromatic hydrocarbons and phthalates are linked to lung function decline and altered relative telomere length (RTL) accompanying with oxidative stress and inflammatory events in human body. However, limited data are available about impacts of co-exposure of PAHs and phthalates on lung function and RTL. We conducted a pilot study with repeated measures during the winter of 2014 and summer of 2015 in Wuhan city, China. Participants took part in the measures of lung function, RTL, urinary monohydroxylated-PAHs (OH-PAHs) and phthalate metabolites over three consecutive days in each season. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) were used to analyze the relations of OH-PAHs or phthalate metabolites with lung function or RTL. LME models showed the negative associations of 3-day average of hydroxyphenanthrene (2 + 3-, 4-OHPhe) or 1-hydroxypyrene with FEV1, 3-day average of 2 + 3-OHPhe with FVC. BKMR models revealed the negative relation of eight OH-PAHs with FEV1, FVC or RTL; nine phthalate metabolites may counteract an overall effect of eight OH-PAHs on FEV1, FVC or RTL. The findings indicated that urinary phthalate metabolites may counteract the negative association of urinary OH-PAHs on FEV1 or FVC, which may be partially linked to shorter RTL regarding biological aging.

11.
J Phys Chem Lett ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791124

RESUMO

Inspired by the superior optoelectronic performances of various 2D semiconductors, their new compositions and structures are being actively pursued in order to foster novel fundamental physics and device applications. As a layered semiconductor with a direct bandgap, few-layer PbI2 should have drawn much research attention due to their capability of emitting photons at short wavelengths of the visible spectrum. Here we chemically synthesize few-layer PbI2 flakes and nanoparticles, which demonstrate unique exciton properties that have rare counterparts in other 2D semiconductors. For three layers and more, the single PbI2 flakes can be utilized to show how the bandgap energy of a 2D semiconductor evolves with the changing layer thickness. The single PbI2 nanoparticles are associated with an ultranarrow photoluminescence linewidth of ~1 meV, thus reflecting the influence of lateral quantum confinement on the energy-level structures of a 2D semiconductor. The above findings mark the emergence of a potent 2D platform that is more than complementary to well-studied transition-metal dichalcogenide monolayers.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31792191

RESUMO

Strain describes the deformation of a material as a result of applied stress. It has been widely employed to probe transport properties of materials, ranging from semiconductors to correlated materials. In order to understand, and eventually control, transport behavior under strain, it is important to quantify the effects of strain on the electronic bandstructure, carrier density, and mobility. Here, we demonstrate that much information can be obtained by exploring magnetoelastoresistance (MER), which refers to magnetic field-driven changes of the elastoresistance. We use this powerful approach to study the combined effect of strain and magnetic fields on the semimetallic transition metal dichalcogenide [Formula: see text] We discover that WTe2 shows a large and temperature-nonmonotonic elastoresistance, driven by uniaxial stress, that can be tuned by magnetic field. Using first-principle and analytical low-energy model calculations, we provide a semiquantitative understanding of our experimental observations. We show that in [Formula: see text], the strain-induced change of the carrier density dominates the observed elastoresistance. In addition, the change of the mobilities can be directly accessed by using MER. Our analysis also reveals the importance of a heavy-hole band near the Fermi level on the elastoresistance at intermediate temperatures. Systematic understanding of strain effects in single crystals of correlated materials is important for future applications, such as strain tuning of bulk phases and fabrication of devices controlled by strain.

13.
Sci Rep ; 9(1): 18120, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792342

RESUMO

Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin+ cells, CD4+ cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin+ cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4+ cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4+ cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4+ lamina propria cells (placebo: median 30%; 0.1-1% Q-GRFT: median 36-39%). The resting time between sampling points were further associated with minor changes in the total and CD4+ rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.

14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 760-764, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762248

RESUMO

OBJECTIVE: To analyze of the minimum graft-to-recipient weight ratio (GRWR) required for living donor liver transplantation (LDLT) without middle hepatic vein branch (MHVT) reconstruction. METHODS: We retrospectively collected the clinical data and outcomes of 303 LDLT patients over 16 years from 2001 to 2017. The minimum GRWR of non-middle hepatic vein reconstruction was analyzed by propensity score (PSM). RESULTS: With PSM analysis, no significant differences were observed in postoperative complications, SFSS, inpatient time, liver function, and coagulation function, but significant differences in 1-year, 3-year and 5-year survival between MHVT reconstruction and non-reconstruction group. The patients with MHVT reconstruction had better short-term and long-term survival than those without reconstruction. CONCLUSION: For LDLT patients without HMVT reconstruction, GRWR should be greater than 0.86%; for patients with HMVT reconstruction, GRWR is acceptable between 0.5% and 0.6%.


Assuntos
Veias Hepáticas/cirurgia , Transplante de Fígado , Fígado/anatomia & histologia , Doadores Vivos , Sobrevivência de Enxerto , Humanos , Tamanho do Órgão , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida
15.
J Mech Behav Biomed Mater ; 103: 103529, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31783283

RESUMO

The cutting of tooth enamel using a high-speed air-turbine handpiece and carbide bur is a key procedure in oral surgeries, such as the minimally invasive extraction. However, presently little is known about the cutting mechanics and material removal mechanism related to tooth enamel machinability. In this study, the machinability of high-speed enamel cutting with carbide bur is studied by a computer-aided numerical control system. The dynamic cutting forces of enamel of the occlusal, buccal/lingual, and proximal surfaces were measured by the force measuring system. The force ratio, cutting torque, rotating speed, specific cutting energy, and bur wear were analyzed. The microstructure of enamel and carbide burs was observed by the scanning electron microscope, and the relationship between enamel microstructures and machinability was further analyzed. The results show that during the high-speed enamel cutting with carbide bur, the chip thickness is on the nano-scale, and the plastic deformation of the machined surface is obvious. With increased material removal rate, the cutting force, torque, specific cutting energy, and bur wear increases accordingly, whereas the rotating speed decelerates (p < 0.05). The different angles between the cutting direction and the axial direction of the enamel rods give rise to the large differences in the cutting mechanics and mechanism of the proximal, buccal/lingual, and occlusal surfaces of the teeth. When the cutting direction is parallel, vertical, and oblique 45° to the axial direction of the enamel rods, the force required for material fracture and crack propagation increases, and the cutting force increases as a consequence. Parallel and oblique 45° cutting are the main modes of tooth segmentation in the minimally invasive extraction. In comparison with the parallel cutting mode, the cutting force, torque, and cutting ratio of the oblique 45° cutting mode can be significantly increased, and the tool wear is obviously accelerated. This is the lowest priority in segmentation surgery, hence the problems of overload and temperature rise need to be considered. The cutting mechanics and cutting mechanism obtained in this study will provide scientific process guidance for dental cutting operations with the air-turbine handpiece driving bur.

16.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683708

RESUMO

As a novel monoterpenoid indole alkaloid, gardneramine has been confirmed to possess excellent nervous depressive effects. However, there have been no reports about the measurement of gardneramine in vitro and in vivo. The motivation of this study was to establish and validate a specific, sensitive, and robust analytical method based on UHPLC-MS/MS for quantification of gardneramine in rat plasma and various tissues after intravenous administration. The analyte was extracted from plasma and tissue samples by protein precipitation with methanol using theophylline as an internal standard (I.S.). The analytes were separated on an Agilent ZORBAX Eclipse Plus C18 column using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Gardneramine and I.S. were detected and quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 413.1→217.9 for gardneramine and m/z 181.2→124.1 for I.S.. Perfect linearity range was 1-2000 ng/mL with a correlation coefficient (r2) of ≥0.990. The lower limit of quantification (LLOQ) of 1.0 ng/mL was adequate for application to different preclinical studies. The method was successfully applied for determination of gardneramine in bio-samples.

17.
Food Chem ; : 125715, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31685368

RESUMO

Rhodomyrtus tomentosa (Aiton) is a flowering plant native to southern and southeastern Asia. Up to date, 106 chemical constituents have been isolated and identified from R. tomentosa. Among these compounds, triterpenoids, flavonoids, phenols and meroterpenoids are the major constituents. Investigations of pharmacological activities of R. tomentosa revealed that this edible medicinal herb exhibits a wide range of therapeutic potential including antibacterial, antitumor, anti-inflammatory and antioxidant activities both in vivo and in vitro. The purpose of this review is to provide an overview of R. tomentosa studies until 2019. This article also intends to review advances in the botanical, phytochemical, pharmacological studies and industrial applications of R. tomentosa, which will provide a useful bibliography for further investigations and applications of R. tomentosa in medicines and foods.

18.
Science ; 366(6467)2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31672918

RESUMO

Gastrulation is a key event in embryonic development when the germ layers are specified and the basic animal body plan is established. The complexities of primate gastrulation remain a mystery because of the difficulties in accessing primate embryos at this stage. Here, we report the establishment of an in vitro culture (IVC) system that supports the continuous development of cynomolgus monkey blastocysts beyond early gastrulation up to 20 days after fertilization. The IVC embryos highly recapitulated the key events of in vivo early postimplantation development, including segregation of the epiblast and hypoblast, formation of the amniotic and yolk sac cavities, appearance of the primordial germ cells, and establishment of the anterior-posterior axis. Single-cell RNA-sequencing analyses of the IVC embryos provide information about lineage specification during primate early postimplantation development. This system provides a platform with which to explore the characteristics and mechanisms of early postimplantation embryogenesis in primates with possible conservation of cell movements and lineages in human embryogenesis.

19.
Acta Pharmacol Sin ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685977

RESUMO

At present, few available drugs can be used to either improve pathological features or prevent the progression of Alzheimer's disease (AD). DL0410 ((1,1'-([1,1'-biphenyl]-4,4'-diyl) bis (3-(piperidin-1-yl) propan-1-one) dihydrochloride) is a multiple-target small molecule that has been found to reverse cognitive impairment in different animal models of AD. In this study we evaluated the cognition-improving effects of DL0410 in APP/PS1 transgenic mice and explored the underlying mechanisms. APP/PS1 transgenic mice were administered DL0410 (3, 10, 30 mg· kg-1· d-1, ig) for 2 months. We found that DL0410 administration significantly ameliorated cognitive deficits in both the nest-building and Morris water maze tests. In electrophysiological analysis of hippocampal slices, we showed that DL0410 administration significantly enhanced the field EPSP slope and HFS-induced LTP in CA1 area. Furthermore, we revealed that DL0410 administration significantly increased the phosphorylation of AKT and the activity of GSK-3ß in the hippocampus and cortex. Moreover, DL0410 administration dose-dependently increased the expression level of phosphorylated ERK1/2 in the hippocampus and cortex. In addition, DL0410 dose-dependently decreased the neuronal loss by decreasing the production of Aß deposition, inhibited glial overactivation, and the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. We conclude that DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission via activating the AKT/GSK-3ß and MAPK/ERK signaling pathway and reducing neuronal loss. DL0410 may be an effective agent for AD treatment in the future.

20.
Adv Healthc Mater ; : e1901301, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31763779

RESUMO

Due to their excellent size, designability, and outstanding targeted antibacterial effects, nanoparticles have become a potential option for controlling oral biofilm-related infections. However, the formation of an oral biofilm is a dynamic process, and factors affecting the performance of antibiofilm treatments are complex. As such, when examining the existing literature on the antibiofilm effects of nanoparticles, attention should be paid to the specific mechanisms of action at different stages of oral biofilm formation, as well as relevant influencing factors, in order to achieve an objective and comprehensive evaluation. This review is intended to detail the antibacterial mechanisms of nanoparticles during the four stages of the formation of oral biofilms: 1) acquired film formation; 2) bacterial adhesion; 3) early biofilm development; and 4) biofilm maturation. In addition, factors influencing the antibiofilm properties of nanoparticles are summarized from the aspects of nanoparticles themselves, biofilm models, and host factors. The limitations of current research and possible trends for future research are also discussed. In summary, nanoparticles are a promising antioral biofilm strategy. It is hoped that this review can serve as a reference and inspire ideas for further research on the application of nanoparticles for effectively targeting and treating oral biofilms.

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