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1.
Sci Total Environ ; 734: 139443, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32454338

RESUMO

Due to the growing use and release of nanomaterials, their toxic impacts on aquatic ecosystems have drawn widespread attention in recent years. In this study, we exposed Microcystis aeruginosa to 5 mg/L titanium dioxide nanoparticles (nTiO2) under different culture conditions (pH 6, 7, 8, 9; 20 °C, 25 °C, 30 °C). The results showed that algae had the worst growth status with lowest biomass, lowest photosynthetic activity and highest reactive oxygen species (ROS) generation under 5 mg/L nTiO2 at pH 6 and 20 °C. Images by scanning electron microscopy (SEM) revealed that nTiO2 hindered light absorption by algal cells by wrapping the algal surface, which led to obvious cell surface deformation at pH 6 or 20 °C. In addition, microcystin-LR (MC-LR) production increased as temperature or pH decreased when exposed to nTiO2 at 5 mg/L, demonstrating that falling pH or temperature enhanced the adverse effects toward algal cells under nTiO2 stress and the potential risk of algae to the environment.

2.
J Cell Mol Med ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32420685

RESUMO

Long non-coding RNAs (lncRNAs) are key regulators or a range of diseases and chronic conditions such as cancers, but how they function in the context of ovarian cancer (OC) is poorly understood. The Coding-Potential Assessment Tool was used to assess the likely protein-coding potential of SNHG7. SNHG7 expression was elevated in ovarian tumour tissues measured by qRT-PCR. The online database JASPAR was used to predict the transcription factors binding to SNHG7. Twenty-four-well Transwell plates were used for invasion assays. RNA immunoprecipitation was performed to determine RNA-protein associations. EdU assay was introduced to detect cell proliferation. Chromatin immunoprecipitation was performed to confirm the directly interaction between DNA and protein. We discovered that in the context of OC there is a significant up-regulation of the lncRNA SNHG7. Knocking down this lncRNA disrupted both OC cell invasion and proliferation, while its overexpression had the opposite effect. SP1 binding sites were present in the SNHG7 promoter, and chromatin immunoprecipitation (ChIP) confirmed direct SP1 binding to this region, activating SNHG7 transcription. We found that at a mechanistic level in OC cells, KLF2 is a probable SNHG7 target, as we found that SHNCCC16 directly interacts with EZH2 and thus represses KLF2 expression. In summary, this research demonstrates that lncRNA SNHG7 is an SP1-activated molecule that contributes to OC progression by providing a scaffold whereby EZH2 can repress KLF2 expression.

3.
Drug Des Devel Ther ; 14: 1779-1798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440103

RESUMO

Background: Radiotherapy has an ameliorative effect on a wide variety of tumors, but hepatocellular carcinoma (HCC) is insensitive to this treatment. Overactivated mammalian target of rapamycin (mTOR) plays an important part in the resistance of HCC to radiotherapy; thus, mTOR inhibitors have potential as novel radiosensitizers to enhance the efficacy of radiotherapy for HCC. Methods: A lead compound was found based on pharmacophore modeling and molecular docking, and optimized according to the differences between the ATP-binding pockets of mTOR and PI3K. The radiosensitizing effect of the optimized compound (2a) was confirmed by colony formation assays and DNA double-strand break assays in vitro. The discovery and preclinical characteristics of this compound are described. Results: The key amino acid residues in mTOR were identified, and a precise virtual screening model was constructed. Compound 2a, with a 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine scaffold, exhibited promising potency against mTOR (mTOR IC50=7.1 nmol/L (nM)) with 126-fold selectivity over PI3Kα. Moreover, 2a significantly enhanced the sensitivity of HCC to radiotherapy in vitro in a dose-dependent manner. Conclusion: A new class of selective mTOR inhibitors was developed and their radiosensitization effects were confirmed. This study also provides a basis for developing mTOR-specific inhibitors for use as radiosensitizers for HCC radiotherapy.

4.
Oncol Nurs Forum ; 47(3): E58-E72, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32301933

RESUMO

PROBLEM IDENTIFICATION: Improving quality of life (QOL) is a key issue for patients with lung cancer. Exercise interventions could positively affect patients' QOL; however, there is no clear-cut understanding of the role of exercise in improving QOL in patients with lung cancer. LITERATURE SEARCH: The PubMed®, Embase®, Cochrane Library, and Web of Science electronic databases were searched from inception to September 6, 2019. DATA EVALUATION: 16 randomized controlled trials met the inclusion criteria. A qualitative synthesis method was used to identify the effect of exercise interventions on QOL in patients with lung cancer. SYNTHESIS: This review indicates that exercise interventions may have beneficial effects on the QOL of patients with lung cancer. The effectiveness seems to be affected by the duration of the intervention, as well as exercise frequency, intensity, and adherence. IMPLICATIONS FOR PRACTICE: Exercise interventions can be integrated into management plans for patients with lung cancer to improve their QOL. Healthcare providers should consider developing optimal exercise prescriptions to maximize the results for this population.

5.
Bull Environ Contam Toxicol ; 104(6): 834-839, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32306073

RESUMO

The interaction between metal oxide nanoparticles and toxin-producing cyanobacteria is relatively unknown. The present work exposed Microcystis sp.7806 to different concentrations of cerium oxide nanoparticles (CeO2 NPs) (1 mg/L, 10 mg/L and 50 mg/L), and evaluated the growth, photosynthetic activity, reactive oxygen species level, and the extra-(intra-) cellular microcystin-LR (MC-LR) contents. The particle size, zeta potential and cerium ions released into the medium were analyzed. Results showed 10 mg/L NP treatment promoted algae growth but slightly inhibited the photosynthetic yield of algae, and the 50 mg/L treatment reduced algae biomass. The algal cells remarkably responded to oxidative stress at higher concentrations (10 mg/L and 50 mg/L). CeO2 NPs largely increased the intracellular MC-LR content at 50 mg/L, and significantly reduced the extracellular MC-LR content at any concentration. This demonstrates CeO2 NPs may pose an ecological risk potential during harmful algal blooms by stimulating toxin production.

6.
Mol Pharm ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32347735

RESUMO

The diseases caused by Zika virus (ZIKV) have received widespread concerns. As a key viral element of ZIKV, E protein was an ideal antigen for vaccine development. However, the poor immunogenicity of E protein necessitated the formulation with adjuvants. Formulation of E protein by conjugation with ß-glucan was a strategy to improve the immunogenicity of E protein, where ß-glucan was a polysaccharide adjuvant that could activate macrophages and trigger intracellular processes. However, the antigenic epitopes of E protein and the immunomodulatory sites of ß-glucan were shielded in the conjugate. Moreover, the conjugate might elicit the undesired immune response to ß-glucan. Thus, the acidic-labile hydrazone and the thiol-sensitive disulfide bonds were used as the linkers between E protein and ß-glucan. Hydrazone hydrolysis and disulfide reduction could sufficiently detach the two components in the immune cells to overcome the two disadvantages. As compared with the conjugate without the two linkers, the conjugate with the two linkers (E-PS-4) elicited high E protein-specific IgG titers and low ß-glucan-specific IgG titers. E-PS-4 elicited high levels of IFN-γ, TNF-α, IL-2, and IL-10. Moreover, E-PS-4 greatly facilitated the activation of dendritic cells without significant toxicity to the organs. A pharmacokinetic study revealed that the serum duration of E-PS-4 was longer than that of E protein. Accordingly, conjugation of E protein with ß-glucan by the hydrazone and disulfide linkers could promote a potent cellular and humoral immune response to E protein. Thus, our study could facilitate the development of an effective vaccine against ZIKV.

7.
Viruses ; 12(4)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32340278

RESUMO

The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia-Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell's surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection.

8.
Biomed Pharmacother ; 127: 110141, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32334375

RESUMO

Osteosarcoma is a bone tumor prevalent in children and young adults. LncRNAs are a family of non-protein-coding transcripts longer than 200 nucleotides. The tumor-related pathological functions of lncRNAs include proliferation, migration, and chemotherapy resistance, all of which have been widely acknowledged in research on osteosarcoma. In addition, compelling evidence suggests that lncRNAs could serve as diagnostic indicators, prognostic biomarkers, and targets for disease treatment. In this review, we systematically summarize how lncRNAs regulate tumorigenesis, invasion and therapeutic resistance. By deepening our knowledge of the relationship between lncRNAs and osteosarcoma, we hope to translate research findings into clinical applications as soon as possible.

9.
Sci Total Environ ; 724: 138257, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32247119

RESUMO

A mechanistic understanding of perfluorooctanoic acid (PFOA) toxicity to plants is essential for future risk assessment of PFOA in agricultural soil. In this study, soil-grown cucumber (Cucumis sativus) was exposed to 0, 0.2, and 5 mg/kg of PFOA for 60 days. At harvest, contaminant accumulation, cucumber biomass, photosynthesis profiles and metabolites were measured. Results showed that PFOA depressed cucumber biomass and accumulated highest in leaves. Photosynthesis analysis revealed that PFOA at both doses reduced the chlorophyll contents and net photosynthesis rate of cucumber leaves. Gas chromatography-mass spectrometry-based non-targeted metabolomics revealed that PFOA induced metabolic reprogramming in cucumber leaves, including up-regulation of phenols (at 0.2 and 5 mg/kg) and down-regulation of amino acids (at 5 mg/kg), indicating disrupted nitrogen and carbon metabolism. Results revealed how PFOA represses plant growth by down-regulating photosynthetic pigments and disturbing the metabolism of carbohydroxides, phenols and amino acids. These findings provide valuable information for understanding the molecular mechanisms involved in plant responses to PFOA-induced stress.

10.
Chin Med Sci J ; 35(1): 85-91, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32299541

RESUMO

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 µmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 µmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

11.
Cell Cycle ; : 1-10, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32324084

RESUMO

Ring1 and Yin Yang 1-Binding Protein (RYBP) is a member of non-canonical polycomb repressive complex 1 to mediate monoubiquitination of histone H2A at lysine 119. It plays an important role in development, but its role in reproduction remains illusive. In this study, we used Rybp conditional knockout mouse model to genetically ablate Rybp in male germ cells. We found that Rybp deficiency during spermatogenesis led to smaller testes, loss of germline cells, disturbed meiosis, increased apoptosis of spermatocytes, decreased sperm motility, and reduced global H3K9me3, without impacting retrotransposon expression. Meanwhile, we depleted Rybp during oogenesis, but oocyte maturation and preimplantation development were normal. Our findings demonstrate that RYBP plays important roles in spermatogenesis through regulating meiosis and sperm motility.

12.
J Bioenerg Biomembr ; 52(2): 83-92, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32170604

RESUMO

The aim of this study was to explore the effect of miR-26a-5p targeting and regulating ADAM17 gene on myocardial cells in hypoxic model. Myocardial cells from 1 day old Sprague-Dawley rats were isolated and cultured for 3 days, and were used for experiment. The hypoxia model of myocardial cells was established after cell grouping transfection. The targeting relationship between miR-26a-5p and ADAM17 was verified by bioinformatics website prediction and double luciferase report experiment. The double luciferase report experiment showed that miR-26a-5p had a targeted relationship with ADAM17, and miR-26a-5p could target and bind ADAM17, down-regulate its expression, and the transfection efficiency of each group was good (P < 0.05). After overexpression of miR-26a-5p, cell activity was increased (P < 0.05), apoptosis was decreased (P < 0.05), and the expression levels of TNF-α, IL-1ß and IL-6 were significantly decreased (all P < 0.05). The release of creatine kinase-MB and the expression level of malondialdehyde were significantly decreased (both P < 0.05), and the expression level of superoxide dismutase was significantly increased (all P < 0.05). After overexpression of ADAM17, the results were reversed (all P < 0.05). MiR-26a-5p could target and regulate ADAM17, reduce the apoptosis of myocardial cells and the expression of inflammatory factors in acute myocardial infarction, and reduce the occurrence of oxidative stress.

13.
Clin Exp Pharmacol Physiol ; 47(6): 989-996, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32048308

RESUMO

Imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of myasthenia gravis with thymoma (MG-T). Long non-coding RNAs (lncRNAs) are implicated in the regulation of Th17/Treg balance. This study was designed to explore the role of XLOC_003810, a novel lncRNA, in regulating the Th17/Treg balance in MG-T. The thymic CD4+ T cells were isolated from control subjects and MG-T patients. The Th17/Treg balance was evaluated by determining proportions of Th17 and Treg cells and expression of Th17- and Treg- associated molecules. Lentivirus-mediated silencing and overexpression of XLOC_003810 in CD4+ T cells were performed. The results showed that XLOC_003810 expression was higher in MG-T thymic CD4+ T cells than that in the control group. Furthermore, the ratio of Th17/Treg cells, proportion of Th17 cells and levels of Th17-associated molecules were significantly increased, whereas the proportion of Treg cells and levels of Treg-associated molecules were decreased in MG-T thymic CD4+ T cells. Importantly, the Th17/Treg imbalance in MG-T thymic CD4+ T cells was aggravated by XLOC_003810 overexpression, whereas it was attenuated by XLOC_003810 silencing. Collectively, XLOC_003810 modulates thymic Th17/Treg balance in MG-T patients, providing the scientific basis for the clinical targeted therapy of MG-T.

14.
J Reprod Dev ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32051348

RESUMO

Changes in histone modifications always correlate with altered transcriptional activities of genes. Recent studies have shown that the mutation of certain lysine residues to methionine in the histone variant H3.3 can act as a valuable tool to reduce specific H3 methylation levels. In our study, we used the mouse spermatogenic cell line GC-2 as a model to generate cells stably expressing H3.3 K4, H3.3 K9, H3.3 K27, and H3.3 K36M. The expression of these H3.3 K-to-M mutants influenced the expression of different subsets of genes, and a total of 891 differentially expressed genes were identified through global gene expression profiling. Moreover, the H3.3 K-to-M transgenes, especially H3.3 K36M, impacted the expression of endogenous retrovirus ERVK. This study gives a global view of how different H3 modifications regulate transcriptomes in spermatogenic cell lines, and identifies potential targets of H3 modifications in male germ line.

15.
Cancer Gene Ther ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31902945

RESUMO

Chromosome translocation t(12;22)(p13;q12)/MN1-ETV6 and MN1 overexpression confer a subset of adverse prognostic AML but so far lack in-depth research. We focused on the clinical course and comprehensive genetic analysis of eight cases with t(12;22)(p13;q12) and one with t(12;17;22) (p13;q21;q13) to elucidate their molecular etiology and outcomes of allogeneic hemopoietic stem cell transplantation (allo-HSCT). The total incidence of t(12;22)(p13;q12) and related translocations was 0.32% in myeloid neoplasms. These patients were confirmed to have dismal prognosis when treated only with chemotherapy, and we firstly provided evidence that they can significantly benefit from timely allo-HSCT. Five cases were MN1-ETV6 positive, and a novel MN1-STAT3 fusion was identified in the patient with triadic translocation. Significant MN1 overexpression was observed in all three MN1-fusion-negative cases. Genetic analysis highlighted the evidence of an ectopic super-enhancer associated orchestrated mechanism of MN1 overexpression and ETV6 haploinsufficiency in t(12;22)(p13;q12) myeloid neoplasms, rather than the conventional thought of MN1-ETV6 fusion formation. We also disclosed the high concomitance of trisomy 8 and 531 Kbps focal 8q duplication in t(12;22)(p13;q12) cases. The new perspective about this entity of disease will enlighten further research to define the mechanism of tumorigenesis and discover effective treatments for MN1-driven malignancies.

16.
BMC Med ; 18(1): 2, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31902369

RESUMO

BACKGROUND: Heart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. METHODS: We generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression. RESULTS: Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort. The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content ≥ 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rank p value < 1.0 × 10- 4]. CONCLUSIONS: Our results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.

17.
Nanoscale ; 12(5): 2946-2960, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31994576

RESUMO

Effective treatment of glioma and other central nervous system (CNS) diseases is hindered by the presence of the blood-brain barrier (BBB). A novel nano-delivery vehicle system composed of PLGA-lysoGM1/DOX micelles was developed to cross the BBB for CNS treatment. We have shown that doxorubicin (DOX) as a model drug encapsulated in PLGA-lysoGM1 micelles can achieve up to 3.8% loading efficiency and 61.6% encapsulation efficiency by the orthogonal test design. Our in vitro experiments demonstrated that PLGA-lysoGM1/DOX micelles had a slow and sustainable drug release under physiological conditions and exhibited a high cellular uptake through the macropinocytosis and the autophagy/lysosomal pathways. In vivo experimental studies in zebrafish and mice confirmed that PLGA-lysoGM1/DOX micelles could cross the BBB and be specifically accumulated in the brain. Moreover, an excellent anti-glioma effect was observed in intracranial glioma-bearing rats. Therefore, PLGA-lysoGM1/DOX micelles not only effectively can cross the BBB, but our results also suggest that they have great potential for anti-glioma therapy and other central nervous system diseases.

18.
J Stroke Cerebrovasc Dis ; 29(3): 104591, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31899073

RESUMO

OBJECTIVE: The purpose of this meta-analysis was to assess the long-term effects of extracorporeal shock wave therapy (ESWT) on post-stroke spasticity. DATA SOURCES: An electronic search of EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) with hand search of relevant papers were performed on 20 June 2019. REVIEW METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature for randomized controlled trials of ESWT in stroke patients with spasticity. The primary outcome was the Modified Ashworth Scale (MAS) grade, and the second outcomes were the Visual Analogue Scale (VAS), range of motion (ROM) of joint, the Fugl-Meyer assessment (FMA) grade and adverse events. Two authors independently extracted data, assessed trial eligibility and risk of bias. Meta-analyses were performed using RevMan 5.3 software. RESULTS: We extracted data from 8 randomized controlled trials (301 participants). At long-term follow-up, ESWT significantly reduced MAS (Weighted Mean Difference (WMD) = -.36, 95% confidence interval (CI) = -.53 to -.19, I2 = 68%; P < .001) and VAS (WMD = -.94, 95% CI = -1.51 to -.37, I2 = 15%; P = .001), enhanced ROM (WMD = 5.97, 95% CI = 2.76 to 9.18, I2 = 0%; P < .001) and FMA (WMD = 1.26, 95% CI = .29 to 2.24, I2 = 96%; P = .01). CONCLUSIONS: ESWT showed long-term effects in relieving spasticity, while reducing pain, enhancing ROM and motor function in stroke patients.

19.
Aging (Albany NY) ; 12(2): 1591-1609, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969494

RESUMO

Islet ß cell mass reduction induced by glucose fluctuation is crucial for the development and progression of T2DM. Chikusetsu saponin IVa (CHS) had protective effects against DM and related injuries. Here we aimed to investigate the role of CHS in ß cell injuries and its possible mechanism involved. Isolated rat islets, ßTC3 cells and T2DM mice were used in this study. The results showed that CHS restored the secretion activity, promoted ß cell survival by increasing ß cell proliferation and decreasing apoptosis which induced by intermittent high glucose (IHG). In vivo, CHS protected ß cell apoptosis to normalize blood glucose and improve insulin sensitivity in DM mice. Further studies showed that CHS activated Wnt3a signaling, inhibited HBP1, promoted ß-catenin nuclear translocation, enhanced expressions of TCF7L2, GIPR and GLP-1R, inhibited p53, p27 and p21. The protective effect of CHS was remarkably suppressed by siRNAs against TCF7L2 or XAV-939 (a Wnt/ß-catenin antagonist) in vitro and in ß-catenin-/- mice. In conclusion, we identified a novel role of CHS in protecting ß cell survival and regeneration by mechanisms involving the activation of Wnt3a/ß-catenin/TCF7L2 signaling. Our results indicated the potential value of CHS as a possible intervention drug for T2DM.

20.
Small ; 16(4): e1906458, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31894633

RESUMO

Battery-type materials are promising candidates for achieving high specific capacity for supercapacitors. However, their slow reaction kinetics hinders the improvement in electrochemical performance. Herein, a hybrid structure of P-doped Co3 O4 (P-Co3 O4 ) ultrafine nanoparticles in situ encapsulated into P, N co-doped carbon (P, N-C) nanowires by a pyrolysis-oxidation-phosphorization of 1D metal-organic frameworks derived from Co-layered double hydroxide as self-template and reactant is reported. This hybrid structure prevents active material agglomeration and maintains a 1D oriented arrangement, which exhibits a large accessible surface area and hierarchically porous feature, enabling sufficient permeation and transfer of electrolyte ions. Theoretical calculations demonstrate that the P dopants in P-Co3 O4 @P, N-C could reduce the adsorption energy of OH- and regulate the electrical properties. Accordingly, the P-Co3 O4 @P, N-C delivers a high specific capacity of 669 mC cm-2 at 1 mA cm-2 and an ultralong cycle life with only 4.8% loss over 5000 cycles at 30 mA cm-2 . During the fabrication of P-Co3 O4 @P, N-C, Co@P, N-C is simultaneously developed, which can be integrated with P-Co3 O4 @P, N-C for the assembly of asymmetric supercapacitors. These devices achieve a high energy density of 47.6 W h kg-1 at 750 W kg-1 and impressive flexibility, exhibiting a great potential in practical applications.

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