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1.
Cell Prolif ; : e13002, 2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33615584

RESUMEN

OBJECTIVES: Ex vivo engineered production of megakaryocytes (MKs) and platelets (PLTs) from human pluripotent stem cells is an alternative approach to solve shortage of donor-donated PLTs in clinics and to provide induced PLTs for transfusion. However, low production yields are observed and the generation of clinically applicable MKs and PLTs from human pluripotent stem cells without genetic modifications still needs to be improved. MATERIALS AND METHODS: We defined an optimal, stepwise and completely xeno-free culture protocol for the generation of MKs from human embryonic stem cells (hESCs). To generate MKs from hESCs on a large scale, we improved the monolayer induction manner to define three-dimensional (3D) and sphere-like differentiation systems for MKs by using a special polystyrene CellSTACK culture chamber. RESULTS: The 3D manufacturing system could efficiently generate large numbers of MKs from hESCs within 16-18 days of continuous culturing. Each CellSTACK culture chamber could collect on an average 3.4 × 108 CD41+ MKs after a three-stage orderly induction process. MKs obtained from hESCs via 3D induction showed significant secretion of IL-8, thrombospondin-1 and MMP9. The induced cells derived from hESCs in our culture system were shown to have the characteristics of MKs as well as the function to form proPLTs and release PLTs. Furthermore, we generated clinically applicable MKs from clinical-grade hESC lines and confirmed the biosafety of these cells. CONCLUSIONS: We developed a simple, stepwise, 3D and completely xeno-free/feeder-free/transgene-free induction system for the generation of MKs from hESCs. hESC-derived MKs were shown to have typical MK characteristics and PLT formation ability. This study further enhances the clinical applications of MKs or PLTs derived from pluripotent stem cells.

2.
Biomed Pharmacother ; 134: 111149, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33385683

RESUMEN

E. coli is associated with high rates of infection and resistance to drugs not only in China but also the rest of the world. In addition, the number of E. coli biofilm infections continue to increase with time. Notably, biofilms are attractive targets for the prevention of infections caused by multidrug-resistant bacteria. Moreover, the pgaABCD-encoded Poly-ß-1,6-N-acetyl-d-glucosamine (PNAG) plays an important role in biofilm formation. Therefore, this study aimed to explore the specific effect of the (R)-(+)-pulegone (PU) on growth and biofilm formation in multi-drug resistant E. coli. The molecular mechanisms involved were also examined. The results showed that PU had significant antibacterial and antibiofilm formation activity against E. coli K1, with MIC and MBC values of 23.68 and 47.35 mg/mL, respectively. On the other hand, the maximum inhibition rate for biofilm formation in the bacterium was 52.36 % at 94.70 mg/mL of PU. qRT-PCR data showed that PU significantly down-regulated expression of the pgaABCD genes (P < 0.05). PU was also broadly effective against biofilm formation in MG1655 and MG1655/ΔpgaABCD, exhibiting the maximum inhibition rates were 98.23 % and 93.35 %, respectively. In addition, PU destroyed pre-formed mature biofilm in both MG1655 and MG1655/ΔpgaABCD about 95.03 % and 92.4 %, respectively. The study therefore verified that pgaA was a potential and key target for PU in E. coli although it was not the only one. Overall, the findings indicated that PU is a potential and novel inhibitor of drug resistance, This therefore gives insights on new ways of preventing and treating biofilm-associated infections in the food industry as well as in clinical practice.


Asunto(s)
Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa/genética , Biopelículas/efectos de los fármacos , Monoterpenos Ciclohexánicos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli K12/efectos de los fármacos , Proteínas de Escherichia coli/genética , Amidohidrolasas/genética , Biopelículas/crecimiento & desarrollo , Escherichia coli K12/genética , Escherichia coli K12/crecimiento & desarrollo , Regulación Bacteriana de la Expresión Génica , Pruebas de Sensibilidad Microbiana
3.
Nat Commun ; 12(1): 60, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397900

RESUMEN

Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.


Asunto(s)
Nanoporos , Análisis de Secuencia de ADN , Línea Celular , Cromosomas Humanos/genética , Genoma Humano , Humanos , Retinoblastoma/genética , Programas Informáticos
4.
Pharm Biol ; 58(1): 1277-1289, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33355514

RESUMEN

CONTEXT: Chloranthus serratus (Thunb.) Roem. et Schult. (Chloranthaceae) is an herb widely used as a folk medicine treating inflammatory diseases, although it is toxic. OBJECTIVE: To investigate hepatotoxicity and related mechanisms induced by ethanol extracts of different parts of C. serratus in rats. MATERIALS AND METHODS: Sprague Dawley rats were divided into control (Con), ethanol extract of roots (ER), stems (ES), and leaves (EL) groups, and acute oral toxicity studies were conducted. The rats received doses of 4.14, 3.20, and 1.16 g/kg/d extracts for 14 days, respectively. Liver index, liver function and oxidative stress biomarkers, liver pathology, ultrastructure, TNF-α, ICAM-1, and Nrf2/HO-1 proteins expression levels were determined. RESULTS: The LD50 of ER, ES, and EL were higher than 10.35, 8.05, and 2.90 g/kg/p.o., respectively. The liver indexes in the extract groups increased significantly. EL dramatically increased TP, GLB, AST, ALT, ALP, TBA, MDA, ICAM-1, and TNF-α levels (p < 0.01), and induced the most obvious pathological and ultrastructural changes. ES and EL obviously decreased the T-SOD, GSH, CAT, and CHOL levels. Nrf2 and HO-1 proteins expression was reduced significantly in ES (0.77 ± 0.06, 2.33 ± 0.20) and EL (0.23 ± 0.04, 2.14 ± 0.16) groups, and reduced slightly in ER (1.08 ± 0.10; 3.39 ± 0.21) group. DISCUSSION AND CONCLUSION: ES and EL induce stronger hepatotoxicity than ER through oxidative stress and the Nrf2/HO-1 pathway, and the root is a better medicinal part, which provides a basis for clinical research, safe applications, and reasonable development of C. serratus.

5.
Materials (Basel) ; 13(21)2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33114066

RESUMEN

Low-density polyethylene (LDPE), as an excellent dielectric insulating material, is widely used in electrical equipment insulation, whereas its low thermal conductivity limits its further development and application. Hexagonal boron nitride (h-BN) filler was introduced into LDPE to tailor the properties of LDPE to make it more suitable for high-voltage direct current (HVDC) cable insulation application. We employed melt blending to prepare h-BN/LDPE thermally conductive composite insulation materials with different contents. We focused on investigating the micromorphology and structure, thermal properties, and electrical properties of h-BN/LDPE composites, and explained the space charge characteristics. The scanning electron microscope (SEM) results indicate that the h-BN filler has good dispersibility in the LDPE at a low loading (less than 3 phr (3 g of micron h-BN particles filled in 100g of LDPE)), as well as no heterogeneous phase formation. The results of thermal conductivity analysis show that the introduction of h-BN filler can significantly improve the thermal conductivity of composites. The thermal conductivity of the composite samples with 10 phr h-BN particles is as high as 0.51 W/(m·K), which is 57% higher than that of pure LDPE. The electrical performance illustrates that h-BN filler doping can significantly inhibit space charge injection and reduce space charge accumulation in LDPE. The interface effect between h-BN and the substrate reduces the carrier mobility, thereby suppressing the injection of charges of the same polarity and increasing the direct-current (DC) breakdown strength. h-BN/LDPE composite doped with 3 phr h-BN particles has excellent space charge suppression effect and high DC breakdown strength, which is 14.3% higher than that of pure LDPE.

6.
FEBS Lett ; 2020 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-33040326

RESUMEN

Hepatocellular carcinoma (HCC) is the most common liver cancer with high mortality. Here, we found that hnRNPU is overexpressed in HCC tissues and is correlated with the poor prognosis of HCC patients. Besides, hnRNPU is of high significance in regulating the proliferation, apoptosis, self-renewal, and tumorigenic potential of HCC cells. Mechanismly, c-Myc regulates hnRNPU expression at the transcriptional level, and meanwhile, hnRNPU stabilizes the mRNA of c-MYC. We found that the hnRNPU and c-Myc regulatory loop exerts a synergistic effect on the proliferation and self-renewal of HCC, and promotes the HCC progression. Taken together, hnRNPU functions as a novel transcriptional target of c-Myc and promotes HCC progression, which may become a promising target for the treatment of c-Myc-driven HCC.

7.
J Nat Prod ; 83(9): 2567-2577, 2020 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-32870000

RESUMEN

Trillium tschonoskii is a medicinal plant known to biosynthesize steroidal saponins. A phytochemical investigation of the rhizomes of T. tschonoskii led to the isolation of nine new furostanol saponins (1-9) and 11 known analogues (10-20). Five of these new compounds were shown to have hydroxy groups at the C-5 and C-6 positions, while two possess a rare aglycone containing carbonyl groups at the C-16 and C-22 positions as well as a Δ17(20) double bond, and the others have conjugated double bonds in the E-ring or have different sugar chains at the C-3 position. All the isolates were tested for their effect on the expansion of human cord blood (CB) CD34+ hematopoietic stem and progenitor cells. It was found that CB CD34+ cells treated with compounds 6, 7, 9, 10, 14, 15, and 19 showed increased numbers of rigorously phenotype-defined hematopoietic stem cells. Notably, compounds 9, 10, 13, and 14 demonstrated an enhanced ability to increase the percentages and numbers of CB CD34+CD38- cells and multipotential progenitors. The present study is the first to report that furostanol saponins from T. tschonoskii rhizomes can promote hematopoietic stem/progenitor cell (HSPC) expansion.

8.
Artículo en Inglés | MEDLINE | ID: mdl-32875820

RESUMEN

Accident statistics show that more than 80% of car-to-pedestrian collisions (CPC) occur when pedestrians cross the road. It is very important to establish a finite element model with natural walking posture to study the kinematics and injury mechanism of pedestrians. In this study, a finite element model of six-year-old child pedestrian is developed with detailed anatomical characteristics and posture parameters as specified in Euro NCAP Pedestrian Human Model Certification (TB024). The numerical human body model is validated in total twelve simulations in which the pedestrian is impacted against four generic vehicle models at speeds 30, 40, 50 km/h prescribed in TB024. The Head Impact Time (HIT), Contact Force and the Trajectories of HC, T12 and AC of all twelve simulations are compared with the reference corridors provided by Technical Bulletin 024. The results indicate that the numerical human body model of a six-year-old child can be used to demonstrate the suitability of the sensing system for the range of pedestrian sizes; the timing of system deployment, and the bonnet deflection due to body loading. Furthermore, the model could be a good tool for further research on pedestrian injury mechanism and the development of pedestrian protection devices.

9.
Adv Sci (Weinh) ; 7(17): 1903809, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32995116

RESUMEN

Stem cells have emerged as a potential therapy for a range of neural insults, but their application in Alzheimer's disease (AD) is still limited and the mechanisms underlying the cognitive benefits of stem cells remain to be elucidated. Here, the effects of clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on the recovery of cognitive ability in SAMP8 mice, a senescence-accelerated mouse model of AD is explored. A functional assay identifies that the core functional factor hepatocyte growth factor (HGF) secreted from hUC-MSCs plays critical roles in hUC-MSC-modulated recovery of damaged neural cells by down-regulating hyperphosphorylated tau, reversing spine loss, and promoting synaptic plasticity in an AD cell model. Mechanistically, structural and functional recovery, as well as cognitive enhancements elicited by exposure to hUC-MSCs, are at least partially mediated by HGF in the AD hippocampus through the activation of the cMet-AKT-GSK3ß signaling pathway. Taken together, these data strongly implicate HGF in mediating hUC-MSC-induced improvements in functional recovery in AD models.

10.
Theranostics ; 10(22): 10171-10185, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32929341

RESUMEN

Background: Acute gastrointestinal syndrome (AGS) is one of the most severe clinical manifestations after exposure to high doses of radiation, and is life-threatening in radiological emergency scenarios. However, an unmet challenge is lacking of an FDA-approved drug that can ameliorate the damage of radiation-exposed intestinal tissues and accelerate the regeneration of injured epithelia. In this study, we investigated whether the small molecule Me6TREN (Me6) can regulate intestinal stem cell (ISC) proliferation and promote crypt regeneration after irradiation. Methods: Lethally irradiated mice were administered with Me6 or PBS to study the survival rate, and sections of their small intestine were subjected to immunostaining to evaluate epithelial regeneration. An intestinal organoid culture system was employed to detect the role of Me6 in organoid growth and ISC proliferation. We further investigated the key signaling pathways associated with Me6 using microarray, western blotting, and RNA interference techniques. Results: We identified the small molecule Me6 as a potent intestinal radiation countermeasure. Systemic administration of Me6 significantly improved ISC and crypt cell regeneration and enhanced the survival of mice after high doses of radiation. Using an in vitro intestinal organoid culture system, we found that Me6 not only induced ISC proliferation but also increased the budding rate of intestinal organoids under unirradiated and irradiated conditions. Me6 remarkably activated the expression of ISC-associated and proliferation-promoting genes, such as Ascl2, Lgr5, Myc, and CyclinD1. Mechanistically, Me6 strongly stimulated the phosphorylation of ß-catenin at the S552 site and increased the transcriptional activity of ß-catenin, a key signaling pathway for ISC self-renewal and proliferation. This is further evidenced by the fact that knockdown of ß-catenin abolished the effect of Me6 on intestinal organoid growth in vitro and crypt regeneration in irradiated mice. Conclusion: The small molecule Me6TREN induced ISC proliferation, enhanced intestinal organoid growth in vitro, and promoted intestinal tissue regeneration after radiation injury by activating ß-catenin signaling.

11.
Stem Cell Res Ther ; 11(1): 358, 2020 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-32799928

RESUMEN

BACKGROUND: Although cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies. METHODS: In this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expresses E4ORF1 stably by using a retroviral system. RESULTS: Coculture of CD34+ hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34+CD38-, and CD34+CD38-CD90+ HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34+ hCB cells amplified on HuAECs-E4orf1-GFP. CONCLUSIONS: Collectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.

12.
FEBS Open Bio ; 10(9): 1737-1747, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32662250

RESUMEN

Liver cancer stem cells (L-CSCs) are considered to be an important therapeutic target for hepatocellular carcinoma (HCC). This study provides a new in vitro long-term culture model for a specific subpopulation of L-CSCs enriched by cell surface markers. We combined CD13, CD133 and EpCAM to selectively enrich L-CSCs, which we then cultured in modified chemically defined medium. The enriched L-CSCs exhibited enhanced proliferation, self-renewal and long-term clonal maintenance ability as compared with non-CSCs. Compared with wild-type hepatocellular carcinoma, the expression of stemness surface markers, oncogenes, drug resistance and tumorigenicity in enriched L-CSCs was significantly increased. In summary, the subpopulation of L-CSCs still maintains cancer stem cell-related phenotypes after 14 days of culture.

13.
J Affect Disord ; 273: 254-264, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32421611

RESUMEN

BACKGROUND: Antidepressants (ADs) are the main clinical therapy for depression, but approximately half of users do not get adequate response. The biallelic (5-HTTLPR) and triallelic (5-HTTLPR/rs25531) polymorphisms in SLC6A4 have been frequently investigated, but their associations with ADs response are in controversy. Here, we performed a meta-analysis to assess their modulation effect to ADs response in major depressive disorder (MDD). METHODS: We performed literature search in PubMed, Web of Science and EMBASE before June 2019. Pooled analysis of genetic associations with response and remission, meta-regression and sensitivity analysis were performed, and publication bias was assessed. RESULTS: Literature search yielded 49 eligible studies with 46 and 10 studies for biallelic and triallelic polymorphism, respectively. L allele of 5-HTTLPR was associated with both of response and remission rates. In the Caucasians using SSRIs only, carriers of LL/LS or LL genotype were more likely to be responders compared to SS carriers (LL/LS vs. SS: OR=1.55, 95%CI 1.20-2.00, p=0.001; LL vs. SS: OR=1.97, 95%CI 1.45-2.67, p<0.001). Similar associations were also found with remission rate. However, no effects on response or remission were found in the Asians or mixed/other antidepressant subgroups. Additionally, the 5-HTTLPR/rs25531 triallelic polymorphism may not associate with ADs response. Meta-regression showed that percent of female in participants, year of publication and treatment duration modulated the association in Caucasians. CONCLUSION: 5-HTTLPR, instead of 5-HTTLPR/rs25531 triallelic polymorphism, may exert as a marker for the prediction of response to SSRIs in Caucasians with MDD.

14.
Stem Cells Transl Med ; 9(6): 661-673, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32125099

RESUMEN

We reported a novel function of recombinant human thrombopoietin (TPO) in increasing hematopoietic stem and progenitor cell (HSPC) homing to the bone marrow (BM). Single doses of TPO treatment to the recipients immediately after BM transplantation showed significantly improved homing of HSPCs to the BM, which subsequently resulted in enhanced short- and long-term engraftment of HSPCs in mice. We found that TPO could downregulate the expression and secretion of matrix metalloproteinase 9 in BM cells. As a result, SDF-1α level was increased in the BM niche. Blocking the interaction of SDF-1α and CXCR4 on HSPCs by using AMD3100 could significantly reverse the TPO-enhanced HSPC homing effect. More importantly, a single dose of TPO remarkably promoted human HSPC homing and subsequent engraftment to the BM of nonobese diabetic/severe combined immunodeficiency mice. We then performed a clinical trial to evaluate the effect of TPO treatment in patients receiving haploidentical BM and mobilized peripheral blood transplantation. Surprisingly, single doses of TPO treatment to patients followed by hematopoietic stem cell transplantation significantly improved platelet engraftment in the cohort of patients with severe aplastic anemia (SAA). The mean volume of platelet and red blood cell transfusion was remarkably reduced in the cohort of patients with SAA or hematological malignancies receiving TPO treatment. Thus, our data provide a simple, feasible, and efficient approach to improve clinical outcomes in patients with allogenic hematopoietic stem cell transplantation. The clinical trial was registered in the Chinese Clinical Trial Registry website (www.chictr.org.cn) as ChiCTR-OIN-1701083.

15.
Mol Biotechnol ; 62(1): 56-66, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31749084

RESUMEN

DNA cloning is the basic step for different fields of life science, and many efforts have been made to simplify this procedure. In this study, we report two general purpose plasmids (pGP), pGP-XB2E and pGP-B2E, for rapid and cost-effective construct of basic clones. The BciVI and XcmI cleavage sites are designed in pGP-XB2E to test plasmid linearization efficiency. The plasmid has better linearization efficiency by using BciVI which could almost completely digest 2 µg plasmid in 10 min with only one-tenth the recommended enzyme concentration. In order to further optimize the pGP-XB2E, a new plasmid, pGP-B2E, which removed XcmI cleavage site was designed. This vector is highly efficient for cloning PCR products up to 1812 bp, and the number of colonies was about five times that of pGP-XB2E. In addition to TA cloning, blunt-end PCR products with T ended in the primer could be positively linked to the T-vector pGP-B2E without A-tailing treatment (TB cloning). Moreover, as an entry vector, pGP-B2E was also compatible for gateway recombination reaction without frameshift mutations. In general, this vector provides a universal, quick, and cost-efficient method for basic molecular cloning.


Asunto(s)
Clonación Molecular , Vectores Genéticos , Plásmidos/genética , Catalasa/genética , Catalasa/metabolismo , ADN Ligasas , Expresión Génica , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo
16.
Anat Rec (Hoboken) ; 303(11): 2801-2810, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31875354

RESUMEN

As a common subtype of malignant gliomas, glioblastoma multiforme (GBM) is associated with poor prognosis. This study is aimed to examine the anticancer activities of alpinumisoflavone (AIF) and its underlying mechanisms. Our results demonstrated that AIF inhibited the proliferation of GBM cells (U373 and T98G) in a time and dose-dependent manner. In addition, flow cytometry analysis not only confirmed AIF arrested cell cycle at the G0/G1 phase but also the induced apoptosis of U373 and T98G cells. Western blotting also confirmed that AIF altered the expression levels of cell cycle-related proteins. Further mechanism studies revealed that AIF inhibited cell proliferation, induced G0/G1 phase arrest and induced apoptosis of U373 and T98G cells through activating PPARγ, as evidenced by the fact that GW9662 (PPARγ inhibitor) could effectively reverse the effects of AIF on U373 and T98G cells. Furthermore, the in vivo study also revealed that AIF suppressed tumor growth and caused cell cycle arrest. Collectively, these results highlighted the potential use of AIF in the treatment of GBM.

17.
Front Oncol ; 9: 1072, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31681605

RESUMEN

Early-stage ovarian serous carcinoma is usually difficult to detect in clinical practice. The profiling of protein expression in high-grade serous carcinoma (HGSC) and low-grade serous carcinoma (LGSC) would provide important information for diagnoses and chemotherapy. Here, we performed proteomic profiling of specimens from 13 HGSC and 7 LGSC patients by iTRAQ. A total of 323 proteins that were differentially expressed were identified. After immunohistochemical confirmation of expressed proteins in 166 clinical tissues, asparagine synthetase (ASNS) and filamin A (FLNA) were selected for further functional study. Cisplatin-sensitive (CS; ASNShigh and FLNAlow) and cisplatin-resistant (CR; ASNSlow and FLNAhigh) SKOV3 and OVCAR3 ovarian cancer cell lines were used for subsequent in vitro and in vivo experiments. Notably, ASNS overexpression (ASNS+) or FLNA knockdown (shFLNA) enabled cisplatin-induced apoptosis and autophagy in CR cells. However, ASNS+ and shFLNA promoted and attenuated tumor growth, respectively. In CS cells, ASNS knockdown (shASNS) attenuated clonogenicity, cell proliferation, and the epithelial-mesenchymal transition, whereas FLNA overexpression (FLNA+) protected cells from cisplatin. In vivo, cisplatin resistance was attenuated in mice xenografted with ASNS+, shFLNA, or ASNS+-shFLNA CR cells, whereas xenografts of shASNS or FLNA+ CS cells exhibited resistance to cisplatin. Clinically, all HGSC patients (83/83) responded to cisplatin, while 6 in 41 LGSC patients exhibited cisplatin resistance. These findings identify ASNS and FLNA as distinct biomarkers for HGSC and LGSC, which may have potential value in the prognosis and clinical treatment of serous carcinoma.

18.
Chem Commun (Camb) ; 55(93): 14019-14022, 2019 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-31690921

RESUMEN

A series of siloxazanes were successfully prepared by a Piers-Rubinsztajn reaction between methoxydisilazanes and the corresponding hydrosilanes. Polysiloxazanes with narrow dispersion were also synthesized from methoxydisilazanes and Si-H terminated oligosiloxanes. The possible interaction mechanism between tris(pentafluorophenyl)borane and the methoxydisilazane was investigated.

19.
Cell Death Dis ; 10(6): 453, 2019 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-31186405

RESUMEN

Hepatocellular carcinoma (HCC) has a high mortality rate due to the lack of effective treatments and drugs. Arsenic trioxide (ATO), which has been proved to successfully treat acute promyelocytic leukemia (APL), was recently reported to show therapeutic potential in solid tumors including HCC. However, its anticancer mechanisms in HCC still need further investigation. In this study, we demonstrated that ATO inhibits tumorigenesis and distant metastasis in mouse models, corresponding with a prolonged mice survival time. Also, ATO was found to significantly decrease the cancer stem cell (CSC)-associated traits. Minichromosome maintenance protein (MCM) 7 was further identified to be a potential target suppressed dramatically by ATO, of which protein expression is increased in patients and significantly correlated with tumor size, cellular differentiation, portal venous emboli, and poor patient survival. Moreover, MCM7 knockdown recapitulates the effects of ATO on CSCs and metastasis, while ectopic expression of MCM7 abolishes them. Mechanistically, our results suggested that ATO suppresses MCM7 transcription by targeting serum response factor (SRF)/MCM7 complex, which functions as an important transcriptional regulator modulating MCM7 expression. Taken together, our findings highlight the importance of ATO in the treatment of solid tumors. The identification of SRF/MCM7 complex as a target of ATO provides new insights into ATO's mechanism, which may benefit the appropriate use of this agent in the treatment of HCC.


Asunto(s)
Antineoplásicos/farmacología , Trióxido de Arsénico/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Componente 7 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Células Madre Neoplásicas/metabolismo , Factor de Respuesta Sérica/metabolismo , Animales , Antineoplásicos/uso terapéutico , Trióxido de Arsénico/uso terapéutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Componente 7 del Complejo de Mantenimiento de Minicromosoma/genética , Células Madre Neoplásicas/efectos de los fármacos , Pronóstico , Factor de Respuesta Sérica/antagonistas & inhibidores , Factor de Respuesta Sérica/genética , Trasplante Heterólogo
20.
Materials (Basel) ; 12(11)2019 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-31146397

RESUMEN

In order to study the effects of the crystallinity of polyethylene with different densities on breakdown strength and conductance properties, this paper mainly tests the X-ray diffraction (XRD), different scanning calorimeter (DSC), direct current (DC) breakdown and conductance properties of low-density polyethylene (LDPE), linear low density polyethylene (LLDPE), medium density polyethylene (MDPE), and high-density polyethylene (HDPE), and further analyzes the experimental results separately. The results show that an increase in the density of polyethylene leads to the continuous improvement of crystallinity, and an increase in crystallinity causes a significant decrease in the conduction current at the same field strength. The field strength corresponding to the two turning points in the conductance characteristic curve increases simultaneously.

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