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1.
Carbohydr Polym ; 231: 115695, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888803

RESUMO

Building blocks characterization is a significant approach for understanding the molecular structure of heparin and its derivatives. Nitrous acid (HONO) depolymerization of heparin generates oligosaccharides that maintain the epimerization conformation on C5 of the uronic acids, reflecting the authentic structure of the parental chain. HONO treatment at pH 1.5 selectively cleaves the bond between N-sulfated glucosamine and hexuronic acid, resulting mainly disaccharides, as well as tetra-, tri-, and mono-saccharides. The tetrasaccharides are derived from the structure of N-acetylated domains while tri-, and mono-saccharides are derived from the reducing or the non-reducing end of the heparin chain. The resulted oligosaccharides were separated and analyzed using a UHPLC-HILIC/WAX-MS method. We succeeded in the identification of 19 tetrasaccharides, 19 trisaccharides and 4 monosaccharides species, majority of which is structurally characterized. By comparing the theoretical possibilities and actual occurrence of the well-characterized tetrasaccharides, we demonstrated that the biosynthesis of heparin is a systematic process.

2.
J Agric Food Chem ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31899636

RESUMO

Theanine (thea) is the most abundant free amino acid in tea plant (Camellia sinensis) and one of the most important secondary metabolites conferring tea quality and health benefits. Great effort has recently been made to functionally dissect enzyme genes (e.g., GS, GDH, GOGAT) responsible for in vivo thea accumulation. However, the transcriptional regulation of its biosynthesis remains to be explored. Starting from publicly available (condition-independent) tea transcriptome data, we performed an exhaustive coexpression analysis between transcription factor (TF) genes and thea enzyme genes in tea plant. Our results showed that two typical plant-specialized (secondary) metabolites related TF families, such as MYB, bHLH, together with WD40 domain proteins, were prominently involved, suggesting a potential MYB-bHLH-WD40 (MBW) complex-mediated regulatory pattern in thea pathway. Aiming at the most involved MYB family, we screened seven MYB genes as thea candidate regulators through a stringent multistep selection (e.g., filtering with condition-specific nitrogen-treated transcriptome data). The control of MYB regulators in thea biosynthesis was further demonstrated using an integrated analysis of thea accumulation and MYB expression in several major tea tissues, including leave, bud, root, and stem. Our investigation aided tea researchers in having a comprehensive view of transcriptional regulatory landscape in thea biosynthesis, serving as the first platform for studying molecular regulation in thea pathway and a paradigm for understanding the characteristic components biosynthesis in nonmodel plants.

4.
Curr Microbiol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919672

RESUMO

Emcibacter congregatus ZYLT was isolated from a sediment sample cultured in situ in a coast located in the East China Sea. The genome of E. congregatus ZYLT was sequenced and assembled into one single circular chromosome with the size of 4,189,011 bp and G+C content of 52.6%. Genomic annotation showed that E. congregatus ZYLT had an intact Type II-C CRISPR-Cas system consists of three cas genes (cas 9, cas 1, and cas 2), 34 direct repeat sequences with the length of 36 bp, and 33 spacers. The predicted Cas 9 protein was smaller than most of existing genome editing tools. This structure might have potential in developing new gene editing system and uncovering the regulatory mechanisms of CRISPR-Cas system. Besides, the comparison between E. congregatus ZYLT and its relative species living in neritic environments unraveled some common traits of the defective strategies of these bacteria to face inshore challenges including the motility, multidrug resistance, and universal efflux pumps.

5.
Sci Adv ; 6(1): eaay0748, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31922006

RESUMO

Development of renewable energy is essential to mitigating the fossil fuel shortage and climate change issues. Here, we propose to produce a new type of energy, bio-coal, via a fast pyrolysis coupled with atmospheric distillation process. The high heating values of the as-prepared bio-coals from the representative biomass are within 25.4 to 28.2 MJ kg-1, which are comparable to that of the commercial coals. Life cycle assessment further shows that the bio-coal production process could achieve net positive energy, financial, and environmental benefits. By using available biomass wastes as feedstock, China is expected to have a total bio-coal production of 402 million tons of standard coal equivalent, which is equal to 13% of national coal consumption. It would grant China an opportunity to additionally cut 738 million tons of CO2 emission by substituting an equal amount of coal with bio-coal in 2030.

6.
Biol Pharm Bull ; 43(1): 102-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902913

RESUMO

Glycyrrhetinic acid (GA) is a natural product with certain antitumor activity. In order to enhance the cytotoxicity, a total of eighteen derivatives of GA were designed and synthesized. Their cytotoxicity against MDA-MB-231cells (human breast cancer cells) and HeLa cells (human cervical cancer cells), were evaluated by the MTT method (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide). The results indicated that these target compounds have a wide molar activity range and some of them show better activity than the commercial drugs gefitinib and doxorubicin. Compound 6g induces apoptosis of 7, 10 and 44% of MDA-MB-231 cells at 5, 10, and 20 µM, respectively.

7.
Theranostics ; 10(1): 62-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903106

RESUMO

Rationale: Nanoparticles (NPs) that are rapidly eliminated from the body offer great potential in clinical test. Renal excretion of small particles is preferable over other clearance pathways to minimize potential toxicity. Thus, there is a significant demand to prepare ultra-small theranostic agents with renal clearance behaviors. Method: In this work, we report a facile method to prepare NPs with ultra-small size that show renal clearable behavior for imaging-guided photodynamic therapy (PDT). Pyropheophorbide-a (Pa), a deep red photosensitizer was functionalized with polyethylene glycol (PEG) to obtain Pa-PEG. The prepared NPs formed ultra-small nanodots in aqueous solution and showed red-shifted absorbance that enabling efficient singlet oxygen generation upon light irradiation. Results: In vitro studies revealed good photodynamic therapy (PDT) effect of these Pa-PEG nanodots. Most of the cancer cells incubated with Pa-PEG nanodots were destroyed after being exposed to the irradiated light. Utilizing the optical properties of such Pa-PEG nanodots, in vivo photoacoustic (PA) and fluorescence (FL) imaging techniques were used to assess the optimal time for PDT treatment after intravenous (i.v.) injection of the nanodots. As monitored by the PA/FL dual-modal imaging, the nanodots could accumulate at the tumor site and reach the maximum concentration at 8 h post injection. Finally, the tumors on mice treated with Pa-PEG nanodots were effectively inhibited by PDT treatment. Moreover, Pa-PEG nanodots showed high PA/FL signals in kidneys implying these ultra-small nanodots could be excreted out of the body via renal clearance. Conclusion: We demonstrated the excellent properties of Pa-PEG nanodots that can be an in vivo imaging-guided PDT agent with renal clearable behavior for potential future clinical translation.

8.
Expert Opin Drug Saf ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914329

RESUMO

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. The propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61-3.18), coagulation disorders (aOR 1.81, 95% CI 1.43-2.30) and decreased PLT (aOR 1.46, 95% CI 1.25-1.72), but did not increase bleeding (aOR 1.05, 95% CI 0.79-1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11-2.10), coagulation disorders (aOR 1.53, 95% CI 1.21-1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81-1.07) or bleeding (aOR 1.11, 95% CI 0.87-1.42), compared with those receiving cefoperazone-tazobactam.Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.

9.
Philos Trans A Math Phys Eng Sci ; 378(2165): 20180425, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31902339

RESUMO

The subduction of seamounts and ridge features at convergent plate boundaries plays an important role in the deformation of the overriding plate and influences geochemical cycling and associated biological processes. Active serpentinization of forearc mantle and serpentinite mud volcanism on the Mariana forearc (between the trench and active volcanic arc) provides windows on subduction processes.  Here, we present (1) the first observation of an extensive exposure of an undeformed Cretaceous seamount currently being subducted at the Mariana Trench inner slope; (2) vertical deformation of the forearc region related to subduction of Pacific Plate seamounts and thickened crust; (3) recovered Ocean Drilling Program and International Ocean Discovery Program cores of serpentinite mudflows that confirm exhumation of various Pacific Plate lithologies, including subducted reef limestone; (4) petrologic, geochemical and paleontological data from the cores that show that Pacific Plate seamount exhumation covers greater spatial and temporal extents; (5) the inference that microbial communities associated with serpentinite mud volcanism may also be exhumed from the subducted plate seafloor and/or seamounts; and (6) the implications for effects of these processes with regard to evolution of life. This article is part of a discussion meeting issue 'Serpentine in the Earth system'.

10.
J Orthop Surg Res ; 15(1): 3, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900188

RESUMO

BACKGROUND: The relationship between spinal sagittal subtypes and lumbar disc degeneration is unclear. Thus, we aimed to investigate the relationship between lumbar intervertebral disc degeneration and age in asymptomatic healthy individuals with different sagittal alignments. METHODS: In this cross-sectional observational study, we examined 209 asymptomatic young and middle-aged volunteers (123 women and 86 men) who were divided into the following three groups according to age: groups A (20-30 years), B (31-40 years), and C (41-50 years). The volunteers underwent full-spine standing lateral radiography and magnetic resonance imaging (MRI, 3.0 T) of the lumbar spine. Based on panoramic radiography, two observers measured the spinopelvic parameters and classified the spine into Roussouly subtypes. The degree of disc degeneration was assessed based on T2-weighted images according to the Pfirrmann classification. RESULTS: There was a statistically significant difference in the degree of degeneration of type I spine between groups B and C at L4-L5 (P < 0.03) and L5-S1 (P < 0.01) and between groups A and C at L1-L2 (P < 0.04) and L4-L5 (P < 0.01). The degeneration degree of type II spine at all levels were significantly different between groups A and C. No statistically significant difference was found between groups A and B in all subtypes except for type II spine at L1-L2 (P < 0.04). A significant difference was found at four levels between groups B and C in type III spine (P < 0.05) and between groups A and C. For type IV spine, there was a significant difference in the degree of degeneration at L4-L5 (P < 0.02) between groups A and C. Moreover, almost all single parameters were not strongly correlated with the degree of disc degeneration. CONCLUSION: The different spinal subtypes have characteristics of lumbar disc degeneration at specific levels with age. We considered that spinal classification could be used as a predictor of lumbar disc degeneration. Our data may be helpful to increase awareness of the relationship between spinal subtypes and lumbar disc degeneration. LEVEL OF EVIDENCE: 3.

11.
Talanta ; 209: 120578, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892076

RESUMO

A direct on-line complexion combined with micelle to solvent stacking method was proposed for simultaneous determination of metal ions by capillary electrophoresis coupled diode array detector. During the experiment, a plug of complexing agent was first injected to the inlet of capillary, followed by introducing the micelle-bound metal ions. Then the metal ions produced a micelle-to-solvent stacking effect and interacted with the complexing agent under a positive voltage. Continued application of voltage, the analytes were effectively focused and separated in the capillary zone electrophoresis. Repeatability was ranged from 1.89% to 1.94% for the migration time. The detection limits were 2.66-27.9 ng mL-1 for Ni2+, Co2+, Cu2+, Hg2+ and Cd2+. Furthermore, the developed method showed a great potential for the determination of metal ions in the crayfish, beebread and Dendrobium officinale samples.

12.
Medicine (Baltimore) ; 99(1): e18503, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895784

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In clinical practice, we have observed that some HLH patients who have features of systemic autoinflammatory diseases (SAIDs) exhibit unique clinical manifestations and outcomes different from other HLH patients.We analyzed data from 25 HLH patients who were considered to have SAIDs; data were collected from patients of our center between January 1, 2015 and September 1, 2018.The median age of the patients was 1.75 years. In the early phase, all patients had a fever and 92% of patients had a rash; 96% of patients had high white blood cell count (WBC), C-reaction protein, and erythrocyte sedimentation rate. With progression, the above laboratory results decreased gradually. During the HLH period, we compared SAIDs-related HLH and Epstein-Barr virus (EBV)-related HLH and found that rash was more common (92%, P < .001) and splenomegaly was less common (64%, P = .023) in SAIDs-related HLH. Further, WBC, ferritin, and Interleukin-6 levels in SAIDs-related HLH patients were higher than those in EBV-related HLH patients. In contrast, hemoglobin, triglyceride, sCD25, Interleukin-10, and interferon-γ levels in SAIDs-related HLH patients were lower compared with those in EBV-related HLH patients. SAIDs-related HLH patients received a modified HLH-2004 protocol at our center. Most patients had a good prognosis.We provide a summary of the unique clinical and laboratory features, treatment protocols, and outcomes of SAIDs patients with HLH at onset. The findings indicate that these patients had a better response to corticosteroids and cyclosporin compared with EBV-related HLH patients.

13.
Huan Jing Ke Xue ; 41(1): 115-124, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854911

RESUMO

This study uses the national ambient air quality station data of Anyang City from 2014 to 2017 to analyze the characteristics and variation rules of ozone (O3) in different functional zones (urban, suburban, and industrial), and also studies meteorological influencing factors and potential source distributions of O3 pollution. The results showed that the O3 concentration in Anyang increased significantly between 2014 and 2017, whereby pollution started to advance from 2015 and the earliest occurrence of an O3 pollution episode was in April 2017. The 90th percentile and average concentrations of O3 in the industrial zone increased at faster rates (average annual growth of 16.0 µg·m-3 and 13.0 µg·m-3, respectively) than of those in the urban and suburban zones. The O3 concentrations at the suburban site showed the fastest increase of all zones at the 5th percentile (average annual growth of 13.2 µg·m-3). The monthly variation in O3 concentrations in Anyang showed an "M" pattern that varied spatially depending on the zone. Temperature played a leading role in O3 concentrations; air temperatures >23℃, relative humidity <58%, and a wind speed of 5 m·s-1 in a south-southwesterly direction were closely related to the occurrence of high O3 concentrations. Potential sources of O3 in different seasons were significantly different, and mainly distributed in southern Hebei, northern Hubei, and northern Shenyang in summer. The first heavy O3 pollution day in the studied period was in May 2017, at which time the highest O3 concentration was found in the industrial zone (up to 405 µg·m-3). This heavy O3 pollution episode was related to the continuous high temperature that was caused by the transfer of a dry, hot air mass in western China.

14.
Adv Sci (Weinh) ; 6(23): 1902043, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832326

RESUMO

Metal-containing polymer networks are ubiquitous in biological systems, and their unique structures enable a variety of fascinating biological behaviors. Cuticle of mussel byssal threads, containing Fe-catecholate complexes, shows remarkably high hardness, high extensibility, and self-healing capability. Understanding strengthening and self-healing mechanisms is essential for elucidating animal behaviors and rationally designing mussel-inspired materials. Here, direct evidence of Fe3+ and Fe2+ gradient distribution across the cuticle thickness is demonstrated, which shows more Fe2+ inside the inner cuticle, to support the hypothesis that the cuticle is a functionally graded material with high stiffness, extensibility, and self-healing capacity. The mechanical tests of the mussel threads show that both strength and extensibility of the threads decrease with increasing oxygen contents, but this property degradation can be restored upon removing the oxygen. The first-principles calculations explain the change in iron coordination, which plays a key role in strengthening, degradation, and self-healing of the polymer networks. The oxygen absorbs on metal ions, weakening the iron-catecholate bonds in the cuticle and collagen core, but this process can be reversed by sea water. These findings can have important implications in the design of next-generation bioinspired robust, highly extensible materials, and catalysis.

15.
Atherosclerosis ; 293: 42-48, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31835040

RESUMO

BACKGROUND AND AIMS: Endostatin is implicated in the atherosclerosis process and serves as a promising cardiovascular biomarker, while its clinical significance in ischemic stroke patients remains unclear. We aimed to examine the association between endostatin and mortality and disability after ischemic stroke. METHODS: A total of 3463 acute ischemic stroke patients with measured plasma endostatin from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this study. The primary outcome was death or severe disability (modified Rankin scale score of 4-6), and secondary outcomes included death and vascular events. RESULTS: After 3-month follow-up, 402 (11.61%) participants experienced severe disability or died. Compared with the lowest quartile of endostatin, odds ratios or hazard ratios (95% confidence intervals) for the highest quartile were 1.47 (1.04-2.09) for the primary outcome, and 2.36 (1.23-4.54) for death after adjustment for multiple covariates, including age, sex, admission NIH Stroke Scale score and systolic blood pressure. Each 1-SD higher log-transformed endostatin was associated with a 20% (6%-36%) increased risk for primary outcome. Adding plasma endostatin to the basic model constructed with conventional factors significantly improved risk stratification of primary outcome, as observed by the category-free net reclassification index of 20.5% (95% CI 10.1%-30.8%; p < 0.001) and integrated discrimination improvement of 0.3% (95% CI 0.01%-0.6%; p = 0.04). CONCLUSIONS: Increased baseline plasma endostatin levels in acute ischemic stroke were associated with increased risk of mortality and severe disability at 3 months. Plasma endostatin may serve as an important prognostic marker for risk stratification in patients with ischemic stroke.

16.
Materials (Basel) ; 12(24)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835697

RESUMO

In this study, two types of antibacterial montmorillonites (Mt) were prepared using a facile method. The Mt modified with ε-polylysine hydrochloride (ε-PL) was named PL-Mt, while the Mt dually modified with dioctadecyl dimethylammonium chloride (D1821) and ε-PL was named PL-OMt. The results of the X-ray diffraction, Fourier-transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA) of the PL-Mt indicated that 30% ε-PL was the most suitable amount for intercalating the Mt. The particle size and distribution of the ε-PL in the solution demonstrated that the Mt d-value could not be further increased owing to the increasing ε-PL diameter. The result of the X-ray diffraction of PL-OMt displayed that ultrasonic treatment at 600 W facilitated ε-PL to intercalate into the OMt interlayer space. The PL-OMt prepared with ultrasonic treatment at 600 W exhibited antibacterial activity against Escherichia coli and Bacillus subtilis superior to that of the PL-OMt prepared with higher-power ultrasonic treatment. Thus, the addition of 30% ε-PL based on the dry Mt mass is the most suitable ratio for preparing PL-Mt, while ultrasonic treatment at 600 W is the most suitable for preparing PL-OMt. These findings may expand the application fields of ε-PL.

17.
Chem Biol Interact ; : 108922, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837296

RESUMO

Homeodomain interacting protein kinase-2 (HIPK2) has emerged as a crucial stress-responsive kinase that plays a critical role in regulating cell survival and apoptosis. However, whether HIPK2 participates in regulating cardiomyocyte survival during myocardial ischemia/reperfusion injury remains unclear. Here, we investigated the regulatory effect of HIPK2 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its potential underlying molecular mechanism. We found that HIPK2 expression was induced in response to H/R exposure. HIPK2 depletion by small interfering RNA (siRNA)-mediated gene silencing significantly decreased the viability and exacerbated H/R-induced apoptosis and reactive oxygen species (ROS) production in cardiomyocytes. Comparatively, HIPK2 overexpression effectively rescued H/R-impaired viability and repressed H/R-induced apoptosis and ROS production in cardiomyocytes. HIPK2 overexpression significantly increased the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and enhanced Nrf2-mediated transcriptional activity. Moreover, HIPK2 overexpression significantly increased the transcription of Nrf2/ARE target genes. Additionally, Nrf2 inhibition partially reversed the HIPK2-mediated protective effect. Overall, these results demonstrate that HIPK2 overexpression protects cardiomyocytes from H/R-induced injury by enhancing Nrf2/ARE antioxidant signaling, data that suggest HIPK2 is a potential target for cardioprotection.

18.
Cancer Manag Res ; 11: 7231-7242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839714

RESUMO

Background: In recent years, statins have been frequently investigated in neoplasms. However, the potential roles of statins on prostate cancer cells and the underlying mechanisms have not been fully elucidated. In current study, we explored the effect and molecular mechanism of statins on cell proliferation and apoptosis in prostate cancer cells. Methods: Prostate cancer cell were treated with gradient doses of simvastatin and fluvastatin for 24-72 h. Cell proliferation was analyzed by using MTS assay and colony formation. Cell apoptosis was measured by Hoechst staining, flow cytometry and caspase-3 activity. Western blotting was used to evaluate the proteins levels. Results: Both simvastatin and fluvastatin produced a dose- and time-dependent inhibition of cell viability and colony formation while a promotion of cell apoptosis as evident with increases in caspase-3 activity, cleaved-caspase-3, cleaved-caspase-8 and cleaved-PARP levels in PC3 cells. Similar statin effects were observed in DU145 prostate cancer cells. Furthermore, statins produced a time- and dose-dependent reduction of phosphorylated-AKT and phosphorylated-FOXO1 levels in PC3 cells, and pretreatment of cells with an AKT phosphorylation inhibitor, MK2206, potentiated statins' effect. Conclusion: Statins decrease cell proliferation and induce cell apoptosis, probably mediated via a downregulation of AKT/FOXO1 phosphorylation in prostate cancer cells, which may have a potential benefit in prostate cancer prevention and therapy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31839998

RESUMO

Dysregulation of dickkopf-related protein 1 (DKK1) expression has been reported in a variety of human cancers. We previously reported that DKK1 was upregulated in hepatocellular carcinoma (HCC). However, the role of DKK1 in HCC remains unclear. This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC. The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). DKK1 was silenced or overexpressed in HCC cell lines, and in vitro and in vivo studies were performed. Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues (8/22, 36.4%) but upregulated in HCC tissues (48/53, 90.6%, cohort 1). Significant upregulation of DKK1 was observed in 57.6% (19/33, cohort 2) of HCC tissues by qRT-PCR, and the expression of DKK1 was associated with tumor size (P = 0.024) and tumor number (P = 0.019). Genetic depletion of DKK1 impaired the proliferation, colony-forming ability, invasion, and tumor formation of HCC cells (HepG2 and HUH-7). Conversely, forced expression of DKK1 increased the proliferation, colony-forming ability, and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo. Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/ß-catenin signaling pathway. These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/ß-catenin signaling pathway.

20.
J Cell Mol Med ; 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31840411

RESUMO

Meckel syndrome (MKS) is a pre- or perinatal multisystemic ciliopathic lethal disorder with an autosomal recessive mode of inheritance. Meckel syndrome is usually manifested with meningo-occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation. Germline variants in CEP290 cause MKS4. In this study, we investigated a 35-years-old Chinese female who was 17+1 weeks pregnant. She had a history of adverse pregnancy of having foetus with multiple malformations. We performed ultrasonography and identified the foetus with occipital meningoencephalocele and enlarged cystic dysplastic kidneys. So, she decided to terminate her pregnancy and further genetic molecular analysis was performed. We identified the aborted foetus without postaxial polydactyly. Histological examination of foetal kidney showed cysts in kidney and thinning of the renal cortex with glomerular atrophy. Whole exome sequencing identified a novel homozygous variant (c.2144T>G; p.L715* ) in exon 21 of the CEP290 in the foetus. Sanger sequencing confirmed that both the parents of the foetus were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters of the foetus as well as in the 100 healthy individuals. Western blot analysis showed that this variant leads to the formation of truncated CEP290 protein with the molecular weight of 84 KD compared with the wild-type CEP290 protein of 290 KD. Hence, it is a loss-of-function variant. We also found that the mutant cilium appears longer in length than the wild-type cilium. Our present study reported the first variant of CEP290 associated with MKS4 in Chinese population.

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