ABSTRACT
Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.
Subject(s)
Acute Lung Injury , Exosomes , Stem Cells , Animals , Exosomes/metabolism , Exosomes/transplantation , Acute Lung Injury/therapy , Humans , Mice , Stem Cells/cytology , Stem Cells/metabolism , Fibroblasts/metabolism , Male , Mice, Inbred C57BL , Cell Differentiation , Cells, Cultured , Lipopolysaccharides/pharmacology , Lung/metabolism , Lung/pathology , Disease Models, AnimalABSTRACT
The exploration of efficient bifunctional electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) under alkaline conditions is an importantway to promote the development of electrolytic water technology. Herein, the reduced graphene oxide-supported MoO42- modified amorphous cobalt metaphosphate cubes (a-Co(PO3)2/MoO4/rGO) as bifunctional OER/HER catalyst is prepared by anion exchange and phosphating, using the Prussian blue analogue (PBA) as a precursor. The resulting composite exhibits the low overpotentials (η) that of 290 and 50 mV for OER and HER in 1.0 M KOH solution at 10 mA cm-2, respectively. The electrochemical test and density functional theory (DFT) results reveal that the MoO42--modified optimizes the adsorption/desorption energy of H* of Co(PO3)2, thus enhance the HER activity. Benefiting from efficient HER and OER performances, an efficient and stable alkaline water electrolysis operation using a-Co(PO3)2/MoO4/rGO used as bifunctional catalyst can be carried out, which can deliver a current density (j) of 20 mA cm-2 at 1.65 V cell voltage and work continuously for 24 h.
ABSTRACT
A number of studies have verified the vital effects of long noncoding RNAs on the malignant behaviour of retinoblastoma (RB). The objective of the present study was to examine the specific role and mechanisms of HLA complex P5 (HCP5) in RB. For this purpose, reverse transcriptionquantitative polymerase chain reaction was used to determine the expression of HCP5, microRNA (miRNA/miR)36195p and histone deacetylase 9 (HDAC9). A 3(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was conducted to detect cell viability. Transwell assays were used to evaluate the abilities of cell migration and invasion. A mouse tumor model was established to explore the functions of HCP5 in RB in vivo. The interactions between HCP5, miR36195p and HDAC9 were confirmed by a dualluciferase reporter assay. The protein expression of HDAC9 was determined by western blot analysis. The results revealed that the expression levels of HCP5 and HDAC9 were upregulated, whereas those of miR36195p were downregulated in RB tissues and cell lines. The downregulation of HCP5 or the overexpression of miR36195p suppressed RB cell proliferation, migration and invasion in vitro. Simultaneously, the knockdown of HCP5 suppressed tumor growth in mice in vivo. In addition, HCP5 was directly bound to miR36195p and inversely correlated with miR36195p. HDAC9 was found to be a target gene of and negatively regulated by miR36195p. HCP5 expression also positively correlated with HDAC9 expression. Rescue experiments revealed that the overexpression of HDAC9 or the inhibition of miR36195p reversed the inhibition of RB cell viability, migration and invasion induced by the knockdown of HCP5. On the whole, the present study demonstrates that the silencing of HCP5 exerts an antitumor effect in RB by sponging miR36195p to target HDAC9.
Subject(s)
Histone Deacetylases/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Repressor Proteins/genetics , Retinal Neoplasms/pathology , Retinoblastoma/pathology , Animals , Cell Line, Tumor , Cell Movement/genetics , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Mice, Inbred BALB C , Retinal Neoplasms/genetics , Retinoblastoma/genetics , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: The purpose of our present study was to investigate the expression of cation transport regulator-like protein 1 (CHAC1) in uveal melanoma (UM) tissues and its function in UM progression. METHODS: The mRNA expression of CHAC1 in UM tissues and its prognostic value were investigated based on Gene Expression Omnibus database and The Cancer Genome Atlas database. SP6.5 and M23 UM cell lines with depleted CHAC1 were constructed using small interfering RNA. The viability and migration ability of SP6.5 and M23 UM cells were determined by MTT and wound healing assays, respectively. Western blot was conducted to test the influences of CHAC1 depletion on PI3K signaling pathway. RESULTS: Higher expression of CHAC1 was observed in the UM tissues from patients with liver metastases compared to that from patients without metastases. High CHAC1 expression was correlated with poor prognostic and was an independent predictor for UM patients. Depletion of CHAC1 remarkably inhibited the proliferation and motility of SP6.5 and M23 UM cells. Moreover, the ratios of p-AKT/AKT and p-mTOR/mTOR were reduced notably after silencing CHAC1. CONCLUSIONS: Our results suggested that CHAC1 functioned as a facilitator in UM cell proliferation and migration and possessed the potential to be a predictor as well as a therapeutic target for UM patients.
Subject(s)
Melanoma/metabolism , Uveal Neoplasms/metabolism , gamma-Glutamylcyclotransferase/metabolism , Cell Line , Cell Movement/physiology , Cell Proliferation/physiology , Humans , Predictive Value of Tests , RNA, Messenger/metabolismABSTRACT
For the sake of gaining a clear idea of the adsorption mechanism involved with an oil emulsion-membrane system, Daqing crude oil emulsion and two types of polyvinylidene fluoride (PVDF) ultrafiltration membranes made in our laboratory were used as the objects to pursue the adsorption characteristics in this system. Several isotherm and kinetics models were used here to simulate the adsorption process; the effect of variables such as time, initial concentration, temperature, as well as scanning electron microscopy (SEM) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra were investigated to assist in understanding the mechanism. The results show that the Redlich-Peterson model and the pseudo-first-order kinetic model are the best fitting models, with all of the models exhibiting correlation coefficient ( R2) values of >0.98, suggesting an endothermic adsorption process that involves a combination of chemical and physical mechanisms. Moreover, the thermodynamic parameters, such as Δr Gmθ, Δr Hmθ, and Δr Smθ were also calculated from the temperature dependence, indicating a nonspontaneous process, and increases in temperature had a negative effect on the oil-in-water (o/w) adsorption. Ultimately, further evidence is obtained from the microstructural and infrared spectral analyses.
ABSTRACT
Plant height is one of the most heritable traits in maize (Zea mays L.). Understanding the genetic control of plant height is important for elucidating the molecular mechanisms that regulate maize development. To investigate the genetic basis of the plant height response to density in maize, we evaluated the effects of two different plant densities (60,000 and 120,000 plant/hm(2)) on three plant height-related traits (plant height, ear height, and ear height-to-plant height ratio) using four sets of recombinant inbred line populations. The phenotypes observed under the two-plant density treatments indicated that high plant density increased the phenotypic performance values of the three measured traits. Twenty-three quantitative trait loci (QTLs) were detected under the two-plant density treatments, and five QTL clusters were located. Nine QTLs were detected under the low plant density treatment, and seven QTLs were detected under the high plant density treatment. Our results suggested that plant height may be controlled mainly by a common set of genes that could be influenced by additional genetic mechanisms when the plants were grown under high plant density. Fine mapping for genetic regions of the stable QTLs across different plant density environments may provide additional information about their different responses to density. The results presented here provide useful information for further research and will help to reveal the molecular mechanisms related to plant height in response to density.
Subject(s)
Chromosome Mapping/methods , Chromosomes, Plant/genetics , Quantitative Trait Loci/genetics , Quantitative Trait, Heritable , Zea mays/genetics , Genotype , Phenotype , Population Density , Reproducibility of Results , Zea mays/growth & developmentABSTRACT
The internode length above the uppermost ear (ILAU) is an important influencing factor for canopy architecture in maize. Analyzing the genetic characteristics of internode length is critical for improving plant population structure and increasing photosynthetic efficiency. However, the genetic control of ILAU has not been determined. In this study, quantitative trait loci (QTL) for internode length at five positions above the uppermost ear were identified using four sets of recombinant inbred line (RIL) populations in three environments. Genetic maps and initial QTL were integrated using meta-analyses across the four populations. Seventy QTL were identified: 16 in population 1; 14 in population 2; 25 in population 3; and 15 in population 4. Individual effects ranged from 5.36% to 26.85% of phenotypic variation, with 27 QTL >10%. In addition, the following common QTL were identified across two populations: one common QTL for the internode length of all five positions; one common QTL for the internode length of three positions; and one common QTL for the internode length of one position. In addition, four common QTL for the internode length of four positions were identified in one population. The results indicated that the ILAU at different positions above the uppermost ear could be affected by one or several of the same QTL. The traits may also be regulated by many different QTL. Of the 70 initial QTL, 46 were integrated in 14 meta-QTL (mQTLs) by meta-analysis, and 17 of the 27 initial QTL with R(2)â >10% were integrated in 7 mQTLs. Four of the key mQTLs (mQTL2-2, mQTL3-2, mQTL5-1, mQTL5-2, and mQTL9) in which the initial QTL displayed R(2) >10% included four to 11 initial QTL for an internode length of four to five positions from one or two populations. These results may provide useful information for marker-assisted selection to improve canopy architecture.
Subject(s)
Zea mays/growth & development , Zea mays/genetics , Genes, Plant , Phenotype , Plant Leaves/growth & development , Quantitative Trait LociABSTRACT
Tetramethylpyrazine (TMP), extracted from the Chinese herbal medicine Ligusticum wallichii franchat (chuan xiong in Chinese), is a potent anti-free radical and calcium antagonist. Correspondingly, two important hypotheses in the causation of cataracts are free radical toxicity and calcium ion overload. In this study we investigated the effect of TMP on lens opacification induced by sodium selenite in rats, addressing the potential of TMP eye drops to prevent and treat cataracts. Results showed that the extent of lens opacification in the untreated Normal Control group (NC group) was significantly less than that of selenite-injected untreated rats (MC group) on days 3, 5, 7 and 10 (p < 0.001), while TMP treated selenite-injected rats (TMP group) had less lens opacification than the MC group on days 3, 5, 7 and 10 (p < 0.05). Compared with the NC group, the MC group had significantly decreased activity of super-oxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) and significantly elevated malondialdehyde (MDA) and calcium ion content (p < 0.001). Compared with the MC group, the activity of (SOD), (GSH-PX) and (CAT) were significantly higher while (MDA) and calcium ion levels were significantly lower in the TMP group at all time points (p < 0.01). The findings demonstrate that the selenite-induced cataract rat models were successfully built and the TMP eye drops can delay lens opacification induced by sodium selenite in rats. The mechanism by which TMP preserves lens transparency from selenite treated animals is associated with the lenses' ability to maintain normal levels of activity of SOD, GSH-PX and CAT and normal concentrations of MDA and calcium ion.
Subject(s)
Calcium Channel Blockers/therapeutic use , Cataract/prevention & control , Drugs, Chinese Herbal/therapeutic use , Lens, Crystalline/drug effects , Ligusticum , Pyrazines/therapeutic use , Administration, Topical , Animals , Calcium/metabolism , Calcium Channel Blockers/administration & dosage , Catalase/metabolism , Cataract/chemically induced , Cataract/enzymology , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Glutathione Peroxidase/metabolism , Lens, Crystalline/metabolism , Malondialdehyde/metabolism , Photometry , Pyrazines/administration & dosage , Rats , Rats, Sprague-Dawley , Sodium Selenite/toxicity , Superoxide Dismutase/metabolismABSTRACT
OBJECTIVE: To construct a chick model of form-deprivation myopia (FDM) to investigate the effect of nitric oxide (NO) on FDM. METHODS: FDM was induced in 60 one-day white leghorn chicks. They were divided into group A and B. One eye was covered randomly, and the other served as control. In each week of the experimental period, the retinoscopic refraction was performed, and the axial length was measured with A-mode ultrasound. The NO concentration of retina and choroid from the control and the experimental eyes was measured using NO detection kit. Change in the expression of iNOS mRNA was measured by RT-PCR. The activity of iNOS was analyzed with immunohistochemistry. RESULTS: Form-deprivation eyes were significantly more myopic than the controls, and the axial length of occluded eyes was significantly longer than that of the controls. Unocclusion attenuated the development of myopia and inhibited the axial elongation. Form-deprivation reduced the NO concentration ,the immunoreactivity of iNOS, and the expression of iNOS mRNA. The gradual restoration of normal vision was found after uncovering the eyes. But the expression of iNOS mRNA was significantly higher than that of the controls at the first week after the unocclusion. CONCLUSION: Form-deprivation can construct an animal model of myopia. FDM is reversible before the chicks were mature. NO may be involved in the form of FDM.