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1.
Cell Death Dis ; 10(9): 662, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506423

RESUMO

Chronic pancreatitis (CP) is a progressive, recurrent inflammatory disorder of the pancreas. Initiation and progression of CP can result from serine protease 1 (PRSS1) overaccumulation and the ensuing endoplasmic reticulum (ER) stress. However, how ER stress pathways regulate the development and progression of CP remains poorly understood. In the present study we aimed to elucidate the ER stress pathway involved in CP. We found high expression of the ER stress marker genes ATF6, XBP1, and CHOP in human clinical specimens. A humanized PRSS1 transgenic mouse was established and treated with caerulein to mimic the development of CP, as evidenced by pathogenic alterations, collagen deposition, and increased expression of the inflammatory factors IL-6, IL-1ß, and TNF-α. ATF6, XBP1, and CHOP expression levels were also increased during CP development in this model. Acinar cell apoptosis was also significantly increased, accompanied by upregulated p53 expression. Inhibition of ATF6 or p53 suppressed the expression of inflammatory factors and progression of CP in the mouse model. Finally, we showed that p53 expression could be regulated by the ATF6/XBP1/CHOP axis to promote the development of CP. We therefore conclude that ATF6 signalling regulates CP progression by modulating pancreatic acinar cell apoptosis, which provides a target for ER stress-based diagnosis and treatment of CP.

2.
Nanoscale ; 11(37): 17216-17221, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31531444

RESUMO

In the last few years, all-inorganic cesium lead halide (CsPbX3) quantum dots have shown unprecedented radical progress for practical applications in the optoelectronic field, but they quickly decompose when exposed to air. The in situ growth of the CsPbX3 particles inside amorphous glass can significantly improve their stability. Unfortunately, it is formidably difficult to precipitate whole-family CsPbX3 from a glass matrix and their photoluminescence quantum yields require further improvement. Herein, fluoride additives were introduced into oxyhalide borosilicate glasses to break the tight glass network, which promoted the nucleation/growth of CsPbX3 (X = Cl, Cl/Br, Br, Br/I and I) inside the glass. Importantly, the quantum efficiencies of glass-stabilized CsPbBr3, CsPb(Br/I)3 and CsPbI3 reached 80%, 60% and 50%, respectively, which are the highest efficiencies reported so far. Benefiting from the effective protection of robust glass, CsPbX3 quantum dots exhibited superior water resistance with more than 90% luminescence remaining after immersing them in water for 30 days, and halogen anion exchange among different CsPbX3 materials was completely inhibited. Two prototype light-emitting diodes were constructed by coupling green/red and green/orange/red quantum dots with InGaN blue chips, yielding bright white light with optimal luminous efficiency of 93 lm W-1, tunable color temperature of 2000-5800 K and high color rendering index of 90.

3.
Reprod Biol Endocrinol ; 17(1): 64, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387587

RESUMO

BACKGROUND: Fluorochloridone (FLC) is a widely used herbicide, and its target organs are testes and epididymides. The Globally Harmonized System of Classification and Labelling of Chemicals classified FLC as Level 2-possibly cause fertility or fetal damage (no relevant data support). The maximum residue levels of FLC in processed crops have been reviewed in the latest European Food Safety Authority (EFSA) report in 2018. However, the toxic effect of FLC on fertility and early embryonic development is limited, and the health risk assessment of FLC needs further consideration. This study investigated the potential effects of FLC on fertility and early embryonic development in rats. METHODS: One hundred rats of each sex were divided into four groups including three FLC-treated groups at doses of 2 mg/kg, 5 mg/kg and 15 mg/kg, and a vehicle control group (0.5% (w/v) sodium carboxymethyl cellulose). Male and female rats were dosed for 9 and 2 consecutive weeks, intragastrically, prior to cohabitation and lasted throughout the mating period for males and continued until Gestation Day 7 (GD7) for females. Parameters such as weights and coefficients of reproductive organs, epididymal sperm number and motility, indexes of copulation, fecundity and fertility indexes, mating period, estrous cycle, corporalutea number, implantations, live, dead and resorbed fetuses, preimplantation loss rate, and postimplantation loss rate were observed in this study. RESULTS: Obvious toxicity of male reproductive system was found at the dose of 15 mg/kg including decreases in testicular and epididymal weight, also in sperm motility rate. Whereas the increase in sperm abnormality rate was observed. However, no significant effects of FLC were found on lutea count, implantations count, fetuses count and weight, live fetuses count (rate), dead fetuses count (rate), resorbed fetuses count (rate), placentas weight, fetuses gender, preimplantation loss (rate) and postimplantation loss (rate). Furthermore, FLC had no adverse effects on fertility and early embryonic development in rats. CONCLUSION: The no-observable-adverse-effect level (NOAEL) of FLC on fertility and early embryonic development in rats was considered to be 5 mg/kg/day.

4.
Dev Biol ; 454(2): 108-117, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31242446

RESUMO

Lung endoderm development occurs through a series of finely coordinated transcriptional processes that are regulated by epigenetic mechanisms. However, the role of DNA methylation in regulating lung endoderm development remains poorly understood. We demonstrate that DNA methyltransferase 1 (Dnmt1) is required for early branching morphogenesis of the lungs and for restraining epithelial fate specification. Loss of Dnmt1 leads to an early branching defect, a loss of epithelial polarity and proximal endodermal cell differentiation, and an expansion of the distal endoderm compartment. Dnmt1 deficiency also disrupts epithelial-mesenchymal crosstalk and leads to precocious distal endodermal cell differentiation with premature expression of alveolar type 2 cell restricted genes. These data reveal an important requirement for Dnmt1 mediated DNA methylation in early lung development to promote proper branching morphogenesis, maintain proximal endodermal cell fate, and suppress premature activation of the distal epithelial fate.

5.
Nanoscale ; 11(26): 12465-12470, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31219129

RESUMO

Effective Mn2+ doping in a CsPbCl3 lattice utilizing manganese acetate and trimethylchlorosilane is achieved via a one-pot hot-injection synthesis method. This strongly contrasts to the previous case, where only the MnCl2 precursor was suitable for Mn2+ doping by considering the matching of bond dissociation energies between Mn-Cl and Pb-Cl. The Mn doping concentration and luminescence quantum yield are highly dependent on trimethylchlorosilane content. A new doping mechanism is proposed, where the incorporation of Mn2+ into CsPbCl3 is achieved via directly inserting [MnCl6]4- octahedra into the perovskite structure during the nucleation/growth processes instead of Mn-to-Pb cation exchange. Accordingly, increasing Cl- content in the reaction solution indeed promotes the doping of other divalent transition metal ions such as Ni2+, Cu2+ and Zn2+ in CsPbCl3 and improve the quantum yield of CsPbCl3 nanocrystals up to ∼20% compared to the undoped counterparts (∼1%).

6.
Biomed Res Int ; 2019: 3842312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058188

RESUMO

There are about 1-2 million follicles presented in the ovary at birth, while only around 1000 primordial follicles are left at menopause. The ovarian function also decreases in parallel with aging. Folliculogenesis is vital for ovarian function, no matter the synthesis of female hormones or ovulation, yet the mechanisms for its changing with increasing age are not fully understood. Early follicle growth up to the large preantral stage is independent of gonadotropins in rodents and relies on intraovarian factors. To further understand the age-related molecular changes in the process of folliculogenesis, we performed microarray gene expression profile analysis using total RNA extracted from young (9 weeks old) and old (32 weeks old) mouse ovarian secondary follicles. The results of our current microarray study revealed that there were 371 (≥2-fold, q-value ≤0.05) genes differentially expressed in which 174 genes were upregulated and 197 genes were downregulated in old mouse ovarian secondary follicles compared to young mouse ovarian secondary follicles. The gene ontology and KEGG pathway analysis of differentially expressed genes uncovered critical biological functions such as immune system process, aging, transcription, DNA replication, DNA repair, protein stabilization, and apoptotic process were affected in the process of aging. The considerable changes in gene expression profile may have an adverse influence on follicle quality and folliculogenesis. Our study provided information on the processes that may contribute to age-related decline in ovarian function.


Assuntos
Envelhecimento/genética , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , RNA/genética , Animais , Reparo do DNA/genética , Replicação do DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Menopausa/genética , Camundongos , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Ovário/metabolismo , Ovulação/genética , RNA/biossíntese , Transcriptoma/genética
7.
Neurol Sci ; 40(9): 1873-1876, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31062190

RESUMO

PURPOSE: To explore the clinical and imaging characteristics and summarize the causes of missed diagnosis of reversible posterior leukoencephalopathy syndrome (RPLS) in eclampsia. METHODS: We collected the data of a total of 45 patients with RPLS who were misdiagnosed initially (27 cases were confirmed and 18 cases were suspicious) out of 804 patients with severe eclampsia who had presented themselves to the Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2016. We summarized the clinical and imaging characteristics of the patients and analyzed the possible causes of the misdiagnosis. RESULTS: Among the 804 patients with eclampsia, 45 were misdiagnosed the first time. Their clinical manifestations included headache (20 cases), epilepsy (13 cases), blurred vision (11 cases), disturbance of consciousness (2 cases), and drowsiness (3 cases). The parietal lobe was involved in 22 cases, the occipital lobe in 15 cases, the frontal lobe in 20 cases, basal ganglia in 9 cases, and the temporal lobe in 8 cases. Low-density lesions were observed on computed tomography (CT) scans. Head magnetic resonance (MR) scans showed hypo-intense lesions on T1-weighted image (T1WI), hyper-intense lesions on the T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR), iso-intense or slightly hyper-intense lesion on diffusion-weighted imaging (DWI), and slightly hyper-intense or hypo-intense lesion on apparent diffusion coefficient (ADC). CONCLUSION: The incidence of reversible posterior leukoencephalopathy syndrome is extremely high. The clinical features include headache, mental disturbance, seizures, blurred vision, and other neurological symptoms. The lesion area is mainly limited to the parietal and occipital lobes; however, the frontal lobe, basal ganglia, temporal lobe, corpus callosum, and cerebellum can also be involved. The prognosis is good with timely and appropriate treatments.

8.
J Cell Physiol ; 234(12): 22554-22564, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31111482

RESUMO

As a fundamental aging mechanism, cellular senescence causes chronic inflammation via the senescence-associated secretory phenotype (SASP). Theca-interstitial cells are an essential but little-studied component of follicle development in the ovarian microenvironment. In the present study, we observed significant cellular senescence in theca-interstitial cells and secretion of chemokine (C-C motif) ligand 5 (CCL5) by these cells during aging. Furthermore, we aimed to investigate whether and how senescence-associated secretory phenotype (SASP)-associated CCL5 may be involved in follicle development. Increased levels of CCL5 in the microenvironment of follicles attenuated preantral follicle growth, survival, and estradiol secretion. Oocyte maturation and the expression of zona pellucida 3 and differentiation factor 9 (GDF9) were also inhibited by CCL5. Granulosa cell apoptosis in follicles was promoted by CCL5, accompanied by the phosphorylation of nuclear factor-κB by CCL5 and inhibition of the PI3K/AKT pathway. These results suggest that SASP-associated CCL5 produced by senescent theca-interstitial cells may impair follicle development and maturation during ovarian aging by promoting granulosa cell apoptosis.

9.
Sci Transl Med ; 11(488)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996081

RESUMO

Monogenic lung diseases that are caused by mutations in surfactant genes of the pulmonary epithelium are marked by perinatal lethal respiratory failure or chronic diffuse parenchymal lung disease with few therapeutic options. Using a CRISPR fluorescent reporter system, we demonstrate that precisely timed in utero intra-amniotic delivery of CRISPR-Cas9 gene editing reagents during fetal development results in targeted and specific gene editing in fetal lungs. Pulmonary epithelial cells are predominantly targeted in this approach, with alveolar type 1, alveolar type 2, and airway secretory cells exhibiting high and persistent gene editing. We then used this in utero technique to evaluate a therapeutic approach to reduce the severity of the lethal interstitial lung disease observed in a mouse model of the human SFTPCI73T mutation. Embryonic expression of SftpcI73T alleles is characterized by severe diffuse parenchymal lung damage and rapid demise of mutant mice at birth. After in utero CRISPR-Cas9-mediated inactivation of the mutant SftpcI73T gene, fetuses and postnatal mice showed improved lung morphology and increased survival. These proof-of-concept studies demonstrate that in utero gene editing is a promising approach for treatment and rescue of monogenic lung diseases that are lethal at birth.

10.
Mol Genet Genomic Med ; 7(6): e697, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31033252

RESUMO

BACKGROUND: Trichilemmal cysts (TCs) are common intradermal or subcutaneous cysts, which are commonly sporadic and rarely autosomal dominantly inherited. However, little is known about the disease-determining genes in families with TCs exhibiting Mendelian inheritance. OBJECTIVE: The aim of this study was to identify the causative gene in a family with TCs. METHODS: Whole-exome sequencing was performed on a TCs family to identify the candidate gene. Sanger sequencing was conducted to validate the candidate variants and familial segregation. RESULTS: We identified the heterozygous variant c.3G>C (p.Met1?) within the BPIFC gene. Sanger sequencing confirmed the cosegregation of this variant with the TCs phenotype in the family by demonstrating the presence of the heterozygous variant in all the 12 affected and absence in all the seven unaffected individuals. This variant was found to be absent in dbSNP141, 1,000 Genomes database and 500 ethnicity matched controls. CONCLUSION: Our results imply that BPIFC is a causative gene in this Chinese family with hereditary TCs. Further studies should be performed to validate the role of BPIFC in the pathogenesis of this disease.

11.
Genes Dev ; 33(11-12): 656-668, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30923168

RESUMO

Transcription factors (TFs) are dosage-sensitive master regulators of gene expression, with haploinsufficiency frequently leading to life-threatening disease. Numerous mechanisms have evolved to tightly regulate the expression and activity of TFs at the transcriptional, translational, and posttranslational levels. A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors in the genome, but the regulatory relationship between these lncRNAs and their neighboring TFs is unclear. We identified a regulatory feedback loop between the TF Foxa2 and a downstream lncRNA, Falcor (Foxa2-adjacent long noncoding RNA). Foxa2 directly represses Falcor expression by binding to its promoter, while Falcor functions in cis to positively regulate the expression of Foxa2. In the lung, loss of Falcor is sufficient to lead to chronic inflammatory changes and defective repair after airway epithelial injury. Moreover, disruption of the Falcor-Foxa2 regulatory feedback loop leads to altered cell adhesion and migration, in turn resulting in chronic peribronchial airway inflammation and goblet cell metaplasia. These data reveal that the lncRNA Falcor functions within a regulatory feedback loop to fine-tune the expression of Foxa2, maintain airway epithelial homeostasis, and promote regeneration.


Assuntos
Células Epiteliais/metabolismo , Fator 3-beta Nuclear de Hepatócito/genética , Pulmão/citologia , Pulmão/metabolismo , RNA Longo não Codificante/genética , Animais , Adesão Celular , Linhagem Celular , Movimento Celular , Feminino , Regulação da Expressão Gênica , Fator 3-beta Nuclear de Hepatócito/metabolismo , Homeostase , Humanos , Masculino , Camundongos , Regiões Promotoras Genéticas , Regeneração , Transcrição Genética
12.
J Oleo Sci ; 68(3): 251-259, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760672

RESUMO

The nutritional components in oat and tartary buckwheat had been assessed to have cholesterollowering effects. However, The effect of oat and tartary buckwheat based-food (OF) on cholesterol-lowering and gut microbiota in hypercholesterole hamsters was still limited studied because they are usually consumed in whole gran as well as after being processed. In this study, normal diets, high fat diet (HFD) with/without OF were fed to hamsters for 30 days respectively and growth parameters, metabolic parameters, and gut microbiota were investigated, respectively. It was found that OF significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol), lowered liver TC, cholesterol ester (CE), and triglycerides (TG) concentrations, and increased fecal weight and bile acids (BA) concentrations, compared with HFD (p < 0.05). Moreover, the concentrations of acetate, propionate, butyrate and total short-chain fatty acids (SCFAs) were significantly increased in hamsters fed with OF, compared with HFD (p < 0.05). OF changed the overall structure of gut microbiota. The relative abundances of Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae were decreased and the relative abundance of Eubacteriaceae was increased, compared with HFD. These results suggested that OF could reduce the concentrations of plasma lipid by inhibiting cholesterol absorption in liver and promoting excretions of fecal lipid and BA. And it also increased SCFAs and modulated the gut microbiota effectively to exert the hypocholesterolemic effects.


Assuntos
Anticolesterolemiantes/uso terapêutico , Grão Comestível/química , Ácidos Graxos Voláteis/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/dietoterapia , Animais , Avena , Ésteres do Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae , Dieta Hiperlipídica , Fagopyrum , Fezes/química , Hipercolesterolemia/sangue , Masculino , Mesocricetus , Triglicerídeos/sangue
13.
Artigo em Inglês | MEDLINE | ID: mdl-30782824

RESUMO

During the stepwise specification and differentiation of tissue-specific multipotent progenitors, lineage-specific transcriptional networks are activated or repressed to orchestrate cell specification. The gas-exchange niche in the lung contains two major epithelial cell types, alveolar type 1 (AT1) and AT2 cells, and the timing of lineage specification of these cells is critical for the correct formation of this niche and postnatal survival. Integrating cell-specific lineage tracing studies, spatially specific mRNA transcript and protein expression, and single-cell RNA-sequencing analysis, we demonstrate that specification of alveolar epithelial cell fate begins concomitantly with the proximal-distal specification of epithelial progenitors and branching morphogenesis earlier than previously appreciated. By using a newly developed dual-lineage tracing system, we show that bipotent alveolar cells that give rise to AT1 and AT2 cells are a minor contributor to the alveolar epithelial population. Furthermore, single-cell assessment of the transcriptome identifies specified AT1 and AT2 progenitors rather than bipotent cells during sacculation. These data reveal a paradigm of organ formation whereby lineage specification occurs during the nascent stages of development coincident with broad tissue-patterning processes, including axial patterning of the endoderm and branching morphogenesis.

14.
Biomater Sci ; 7(4): 1607-1616, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30702089

RESUMO

Nitric oxide (NO) plays a pivotal role in the cutaneous healing process and a topical supplement of NO is beneficial for wound repair. In this work, a novel polyethylenimine (PEI) based diazeniumdiolate nitric oxide donor was prepared. The obtained polymer (PEI-PO-NONOate) was characterized by Fourier transform infrared (FTIR) spectroscopy, UV-vis absorption spectra, and nuclear magnetic resonance (NMR). The PEI-PO-NONOate polymer was stable under anhydrous conditions at different temperatures. A total of 0.57 µmol gaseous NO was released from 1.0 mg of the PEI-PO-NONOate polymer in PBS of pH 7.4 and it presented a proton-driven release pattern. Furthermore, the PEI-PO-NONOate polymer exhibited a controlled release profile sustained for over 30 hours within the polyethylene glycol (PEG) mixture system. Cytotoxicity evaluation was performed on L929 cells. Full-thickness excisional cutaneous wound models of mice were prepared and the PEI-PO-NONOate polymer was applied to investigate its effects on wound healing. The results revealed that the PEI-PO-NONOates exhibited good biocompatibility. It was also found that the PEI-PO-NONOate polymer promoted cutaneous wound healing and closure with enhanced granulation tissue formation, collagen deposition, and angiogenesis, as compared to the control. In summary, a novel nitric oxide releasing polymer with high loading efficiency and a controlled release profile was developed which presented the potential for application in the acceleration of cutaneous wound healing.


Assuntos
Compostos Azo/farmacologia , Doadores de Óxido Nítrico/farmacologia , Polietilenoimina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Compostos Azo/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/química , Polietilenoimina/química , Relação Estrutura-Atividade
15.
Artigo em Inglês | MEDLINE | ID: mdl-30769872

RESUMO

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.


Assuntos
Relação Dose-Resposta a Droga , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Pirrolidinonas/toxicidade , Testículo/efeitos dos fármacos , Administração Oral , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Testes de Toxicidade Subcrônica
16.
Aging (Albany NY) ; 11(2): 817-832, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674710

RESUMO

Aging has been regarded as a treatable condition, and delaying aging could prevent some diseases. Ovarian aging, a special type of organ senescence, is the earliest-aging organ, as ovaries exhibit an accelerated rate of aging with characteristics of gradual declines in ovarian follicle quantity and quality since birth, compared to other organs. Ovarian aging is considered as the pacemaker of female body aging, which drives the aging of multiple organs of the body. Hence, anti-ovarian aging has become a research topic broadly interesting to both biomedical scientists and pharmaceutical industry. A marked progress has been made in exploration of possible anti-ovarian agents or approaches, such as calorie restriction mimetics, antioxidants, autophagy inducers etc., over the past years. This review is attempted to discuss recent advances in the area of anti-ovarian aging pharmacology and to offer new insights into our better understanding of molecular mechanisms underlying ovarian aging, which might be informative for future prevention and treatment of ovarian aging and its related diseases.

17.
J Clin Invest ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30511962

RESUMO

The adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC), but remains a challenge for drug development. Long non-coding RNAs (lncRNAs) are invaluable in identifying cancer pathologies, and providing therapeutic options for cancer patients. Here, we identified a lncRNA (lncRNA-APC1) activated by APC through lncRNA microarray screening, and examined its expression among a large cohort of CRC tissues. A decrease in lncRNA-APC1 expression was positively associated with lymph node and/or distant metastasis, a more advanced clinical stage, as well as a poor prognosis of CRC patients. Additionally, APC can enhance lncRNA-APC1 expression by suppressing the enrichment of PPARα on the lncRNA-APC1 promoter. Furthermore, enforced lncRNA-APC1 expression was sufficient to inhibit CRC cell growth, metastasis and tumor angiogenesis by suppressing exosome production through directly binding Rab5b mRNA and reducing its stability. Importantly, exosomes derived from lncRNA-APC1-silenced CRC cells promoted angiogenesis by activating the MAPK pathway in endothelial cells, and moreover, exosomal Wnt1 largely enhanced CRC cell proliferation and migration through non-canonicial Wnt signaling. Collectively, lncRNA-APC1 is a critical lncRNA regulated by APC in the pathogenesis of CRC. Our findings suggest an APC-regulated lncRNA-APC1 program as an exploitable therapeutic maneuver for CRC patients.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30320562

RESUMO

Ultrasound elastography has been introduced into clinical practice for a decade and arisen continuous increasing attention worldwide. Shear wave elastography (SWE) is a further extension of ultrasound elastography on the basis of strain elastography, providing a two-dimensional distribution map of tissue stiffness and quantitative measurement of the tissue stiffness in Young's modulus (kPa) and/or shear wave speed (m/s). The Society of Ultrasound in Medicine, Chinese Medical Association (CMA) has recently released a series of guidelines for the use of SWE, including the technique and principle of SWE, and use of SWE in liver fibrosis, breast, thyroid, and musculoskeletal system. Herein, a part of SWE in thyroid nodules is presented. In this guideline, the background, classification and technology of SWE, examination methods, diagnostic performance, prognosis evaluation, reproducibility, and limitations are discussed and recommendations are given. The recommendations are based on the published literatures with regard to SWE with different levels of evidence, particularly a mid-term result of the prospective multi-center clinical trial of SWE in thyroid, as well as the Society of Ultrasound in Medicine, CMA expert's consensus. The document provides an overall analysis of SWE in thyroid from clinical perspective, which aimed to provide recommendations to the clinicians with regard to the management of thyroid nodules by the assistance of SWE.

19.
ACS Appl Mater Interfaces ; 10(46): 39872-39878, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30353721

RESUMO

Currently, it is of great challenge to achieve cation exchange in CsPbX3 (X = Cl, Br, I) perovskite nanocrystals (NCs) on account of rigid Pb2+ octahedral coordination protected by six halogen anions (PbX64-). Herein, we demonstrate that dynamic halogen exchange can effectively open up PbX64- octahedrons and enable fast Mn-to-Pb cation exchange at room temperature in a few seconds. Importantly, Cl concentration rather than Mn one is demonstrated to be a dominant factor for cation exchange, where different Mn2+/Cl- salts can be adopted as Mn/Cl sources and Cl-to-Cl or Cl-to-Br anion exchange is the necessary prerequisite. Such a facile synthesizing method can lead to the feasibility of tuning emissive colors for the Mn-doped CsPb(Cl/Br)3 NCs by controlling both cation and anion exchanges and open a new way to replace Pb2+ in CsPbX3 NCs by other nontoxic metal elements.

20.
J Cell Physiol ; 2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30256425

RESUMO

Mammalian oocytes go through a long and complex developmental process, while acquiring the competencies that are required for fertilization and embryogenesis. Recent studies revealed that the communication between oocytes and granulosa cells (GCs) is a critical process for female follicle development. In the current study, we aimed to study whether and how semaphorin 6C (Sema6c) regulated the cell junctions between oocytes and GCs in mice preantral follicles. The attenuation of SEMA6C expression by siRNA decreased the cell-cell junctions and accelerated follicle atresia in vitro. PI3K-AKT pathway was activated when SEMA6C expression was downregulated. And the LY294002, a PI3K inhibitor, could reverse the effect of low SEMA6C expression on cell junctions in preantral follicles. Our findings revealed that Sema6c was involved in follicle development, and the suppression of SEMA6C led to cell junction defection by activating the PI3K/AKT pathway, which might also provide valuable information for understanding premature ovarian failure and ovarian aging.

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