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1.
Pathol Oncol Res ; 29: 1611343, 2023.
Article in English | MEDLINE | ID: mdl-38089646

ABSTRACT

Squamous differentiation of prostate cancer, which accounts for less than 1% of all cases, is typically associated with androgen deprivation treatment (ADT) or radiotherapy. This entity is aggressive and exhibits poor prognosis due to limited response to traditional treatment. However, the underlying molecular mechanisms and etiology are not fully understood. Previous findings suggest that squamous cell differentiation may potentially arise from prostate adenocarcinoma (AC), but further validation is required to confirm this hypothesis. This paper presents a case of advanced prostate cancer with a combined histologic pattern, including keratinizing SCC and AC. The study utilized whole-exome sequencing (WES) data to analyze both subtypes and identified a significant overlap in driver gene mutations between them. This suggests that the two components shared a common origin of clones. These findings emphasize the importance of personalized clinical management for prostate SCC, and specific molecular findings can help optimize treatment strategies.


Subject(s)
Carcinoma, Squamous Cell , Prostatic Neoplasms , Male , Humans , Prostate/pathology , Androgen Antagonists , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , Carcinoma, Squamous Cell/pathology , Genomics
2.
Environ Sci Pollut Res Int ; 30(54): 114920-114935, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37878178

ABSTRACT

With the mass production of coal-based solid waste, coal mine filling can effectively consume it. The coal gasification slag is modified and prepared as coal mine filling material to meet the relevant technical requirements, which can realize the recycling of coal mine → coal chemical industry → coal mine. In this paper, in order to explore the evolution law of the mechanical properties and pore structure characteristics of the modified coal gasification slag-cement cemented paste backfill (MCGS-CPB) prepared by sodium sulfate excitation coal gasification slag, a combined macro-meso-micro testing method is used. MCGS-CPB with different sodium sulfate contents (1~5%) were prepared and tested for uniaxial compressive strength (UCS), mercury intrusion (MIP) and microscopic tests. The results show that sodium sulfate has a significant effect on the UCS and pore structure characteristics of MCGS-CPB. The mechanical properties and pore structure characteristics of MCGS-CPB were best when sodium sulfate was doped at 3%; the mechanical properties and pore structure characteristics of MCGS-CPB were deteriorated when the addition of sodium sulfate is higher than 3%. On the meso-scale, when sodium sulfate was doped with 3%, the more harmful pores of MCGS-CPB gradually changed into harmless, less harmful, and harmful pores, and the macroscopic mechanical properties were gradually improved; when the addition of sodium sulfate is higher than 3%, the harmless, less harmful, and harmful pores of MCGS-CPB gradually changed into more harmful pores, and the macroscopic mechanical properties were deteriorated. On a microscopic scale, sodium sulfate can cause MCGS-CPB to form hydration products with expansion properties. The presence of a reasonable amount of sodium sulfate in the pores of MCGS-CPB is beneficial to the development of mechanical properties. However, excessive presence will lead to the formation of expansion stress, gradual formation of micro-expansion cracks, and deteriorate the macroscopic mechanical properties. Hence, the volcanic ash activity of coal gasification slag excited by external addition of sodium sulfate should not exceed 3%. This study provides a reference value for application ratio of sodium sulfate-stimulated MCGS-CPB used in coal mine filling design.


Subject(s)
Construction Materials , Sulfates , Compressive Strength , Charcoal , Coal Ash , Coal
3.
Sci Total Environ ; 880: 163209, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37001664

ABSTRACT

Applying solid waste resources as backfill material can reduce both the cost of backfill and the environmental problems caused by solid waste landfills. In this paper, the synergistic reaction effects of solid waste modified magnesia slag (MMS), coal gasification slag (CGS), and desulfurized gypsum (DG) as magnesium-coal slag based cementitious materials (MCC) and their preliminary feasibility as mining cementitious materials in synergy with coal gangue for the preparation of backfill materials are investigated. The results show that the order of the compressive strength of the cementitious systems is ternary system > binary system > monolithic system, which proves the existence of synergistic effect among MMS, CGS, and DG and determines the optimal dosing of each raw material in the ternary system. At early ages, the physical effect of CGS and the chemical effect of DG in the ternary system can promote the hydration reaction of MMS, but the synergistic effect between the three is weak; At later ages, a synergistic effect occurred among silica-aluminate depolymerization in CGS, dissolved sulfate from DG and hydration products from MMS, which promoted the production of more hydration products calcium-silicate(aluminum)-hydrate (C-S(A)-H) and AFt, and improved the compressive strength. In addition, the strength, fluidity and leaching of the backfill material prepared by MCC in collaboration with coal gangue can meet the preliminary feasibility for mine backfill. In the present work, the full solid waste MCC is developed to completely replace cement and use it to prepare backfill materials, which is of great importance to the comprehensive utilization of bulk solid waste, the reduction of backfill costs, and the enhancement of the economic and ecological interests of mines.

4.
J Environ Manage ; 329: 117016, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36586328

ABSTRACT

The environmental damage caused by surface subsidence and coal-based solid waste (CBSW) is a common problem in the process of coal mining. Backfill mining can control the mining-induced subsidence and solve the problem of bulk solid waste storage. In the present work, a magnesium-coal slag solid waste backfill material (MCB) with modified magnesium slag (MS) as binder and CBSW (fly ash (FA), flue gas desulfurization gypsum (FDG) and coal gasification slag (CGS)) as supplementary cementitious material/aggregate was proposed to meet the needs of coal mining in Northern Shaanxi, China, to realize the comprehensive treatment of goaf and CBSW. The results show that: (1) The rheological curve of the fresh MCB slurry is highly consistent with the Herschel-Bulkley (H-B) model, and its fluidity meets the basic requirements of mine backfill pumping. With the addition of FDG and MS, the yield stress, apparent viscosity and thixotropy of MCB slurry increase, while the pseudoplastic index and slump decrease. (2) The strength of MCB develops slowly in the early stage (0∼14 days) and increases rapidly in the later stage (14∼90 days). Except for the ratio of M20F1 and FDG = 0%, the strength of samples at other ratios (at 28 days) is between 6.06∼11.68 MPa, which meets the strength requirement of 6 MPa for coal mine backfill. The addition of MS and appropriate amount of FDG is beneficial to the development of strength. In contrast, MS exhibits a significant improvement in early strength, and FDG has a significant improvement in late-age strength. (3) Corresponding to the compressive strength, the hydration products C-S(A)-H and AFt of MCB are less in the early stage and greatly increased in the later stage. The active substance in FA/CGS will undergo pozzolanic reaction with the MS hydration product CH. The addition of FDG and MS can promote the reaction and increase the amount of hydration product, but in contrast, the promotion effect of FDG is more significant. (4) The amount of heavy metal leaching of MCB meets the requirements of national standards. The hardened MCB has a solidification/stabilization effect on heavy metal elements, which can significantly reduce the amount of heavy metal leaching. The results imply that MCB is a safe, reliable, and eco-friendly solid waste backfill material, and its application is conducive to the coordinated development of coal resource mining and environmental protection.


Subject(s)
Coal Mining , Metals, Heavy , Magnesium , Solid Waste , Coal/analysis , Fluorodeoxyglucose F18 , Coal Mining/methods , Coal Ash
5.
Materials (Basel) ; 15(24)2022 Dec 11.
Article in English | MEDLINE | ID: mdl-36556652

ABSTRACT

Spodumene tailing is the associated solid waste of extracting lithium from spodumene. With the increase in the global demand for lithium resources, its emissions increase yearly, which will become a key factor restricting the economic development of the mining area. Mechanical and hydration reactions, as well as the microstructure of early CSTB, are studied under different tailings-cement ratios (TCR) and solid mass concentration (SC) conditions. The results show that the uniaxial compressive strength of early CSTB has a negative exponential correlation with the decrease in TCR and a positive correlation with the increase in SC: when the age of CSTB increases to 7 days, the strength increases with the rise in SC in an exponential function, and the sensitivity of strength to TCR is higher than that of SC. Compared to other tailings cemented backfill materials, the addition of spodumene tailings reduces the sulfate ion concentration and leads to a new exothermic peak (i.e., the third exothermic peak) for the hydration exotherm of CSTB. Additionally, with the increase in TCR or decrease in SC, the height of the third exothermic peak decreases and the occurrence time is advanced. At the same time, the duration of induction phase was prolonged, the period of acceleration phase was shortened, and the total amount of heat released was significantly increased. The decrease in TCR or the increase in SC led to the rise in the number of hydration products which can effectively fill the internal pores of CSTB, enhance its structural compactness, and increase its compressive strength. The above study reveals the influence of TCR and SC on the early strength, hydration characteristics, and microstructure of CSTB and provides an essential reference for the mix design of underground backfill spodumene tailings.

6.
Materials (Basel) ; 15(17)2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36079414

ABSTRACT

Based on the test results of laser particle size analyzer, specific surface area analyzer and infrared spectrometer, the grinding kinetics of coal gasification slag (CGS) was systematically described by using Divas-Aliavden grinding kinetics, Rosin-Rammler-Bennet (RRB) distribution model and particle size fractal theory. The influence of grinding time and particle group of CGS on the strength activity index of mortar was studied by using the strength activity index of mortar and grey correlation analysis. The results show that the particles are gradually refined before mechanical grinding of CGS for 75 min. When the mechanical grinding time is greater than 75 min, the "agglomeration phenomenon" of fine CGS particles led to the decrease in various properties. Divas-Aliavden grinding kinetics, the RRB model and fractal dimension can characterize the change of CGS particle size in the grinding process quantitatively. The strength activity index of CGS at different curing ages is positively correlated with grinding time, and the influence on the later strength activity index is the most obvious. The relationship between CGS particle size distribution and strength activity index were probed using grey correlation analysis. The CGS particle groups with the particle size of 20~30 µm and 10~20 µm have the greatest impact on the early and late strength activity index, respectively. Therefore, the optimal grinding time of CGS as auxiliary cementing material is 75 min, considering factors, such as economy and performance, and the specific surface area (SSA) is 4.4874 m2·g-1.

7.
BMC Ophthalmol ; 22(1): 200, 2022 May 02.
Article in English | MEDLINE | ID: mdl-35501775

ABSTRACT

BACKGROUND: Inflammatory Myofibroblastoma Tumors (IMTs) are extremely tumour rare in the intraocular. CASE PRESENTATION: A ciliary body tumor was found under slit lamp biomicroscopy in a 55-year-old male first diagnosed with cataract. Then this patient underwent trans-sclera resection via partial lamellar sclerouvectomy and par plans vitrectomy to remove the mass. Hematoxylin and eosin (HE) staining and immunohistochemistry findings showed that the characteristics of the tumor were consistent with IMT. CONCLUSIONS: We reported a rare case of intraocular IMT, which is confirmed by H&E staining, and IHC positive staining for Vimentin, Desmin and ALK, while negative staining for SMA, S-100, ki-67, CK, CD68, and calponin.


Subject(s)
Neoplasms, Muscle Tissue , Uveal Neoplasms , Ciliary Body/surgery , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasms, Muscle Tissue/diagnosis , Neoplasms, Muscle Tissue/pathology , Neoplasms, Muscle Tissue/surgery , Uveal Neoplasms/diagnosis , Uveal Neoplasms/pathology
8.
Nat Commun ; 13(1): 594, 2022 02 01.
Article in English | MEDLINE | ID: mdl-35105871

ABSTRACT

In vivo electron transfer processes are closely related to the activation of signaling pathways, and, thus, affect various life processes. Indeed, the signaling pathway activation of key molecules may be associated with certain diseases. For example, epidermal growth factor receptor (EGFR) activation is related to the occurrence and development of tumors. Hence, monitoring the activation of EGFR-related signaling pathways can help reveal the progression of tumor development. However, it is challenging for current detection methods to monitor the activation of specific signaling pathways in complex biochemical reactions. Here we designed a highly sensitive and specific nanoprobe that enables in vivo imaging of electronic transfer over a broad range of spatial and temporal scales. By using the ferrocene-DNA polymer "wire", the electrons transferred in a biochemical reaction can flow to persistent luminescent nanoparticles and change their electron distribution, thereby altering the optical signal of the particles. This electron transfer-triggered imaging probe enables mapping the activation of EGFR-related signaling pathways in a temporally and spatially precise manner. By offering precise visualization of signaling activity, this approach may offer a general platform not only for understanding molecular mechanisms in various biological processes but also for promoting disease therapies and drug evaluation.


Subject(s)
Diagnostic Imaging , Electron Transport , Electrons , ErbB Receptors/metabolism , Signal Transduction , A549 Cells , Animals , Female , Ferrous Compounds , Humans , Intercellular Signaling Peptides and Proteins , Metallocenes , Mice , Mice, Inbred BALB C , Molecular Probes , Nanoparticles , Optical Imaging
9.
Angew Chem Int Ed Engl ; 60(32): 17564-17569, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34050591

ABSTRACT

Facet-selective nanostructures in living systems usually exhibit outstanding optical and enzymatic properties, playing important roles in photonics, matter exchange, and biocatalysis. Bioinspired construction of facet-selective nanostructures offers great opportunities for sophisticated nanomaterials, but remains a formidable task. We have developed a macromolecule-mediated strategy for the assembly of upconversion nanoparticles (UCNPs)/two-dimensional metal-organic frameworks (2DMOFs) heterostructures with facet selectivity. Both experimental and theoretical results demonstrate that polyvinylpyrrolidone (PVP) can be utilized as an interface-selective mediator to further promote the facet-selective assembly of MOFs onto the surface of UCNPs. The UCNPs/2DMOFs nanostructures with facet selectivity display specific optical properties and show great advantages in anti-counterfeiting. Our demonstration of UCNPs/2DMOFs provides a vivid example for the controlled fabrication of facet-selective nanostructures and can promote the development of advanced functional materials for applications in biosensing, energy conversion, and information assurance.

11.
Nat Commun ; 11(1): 4165, 2020 Aug 20.
Article in English | MEDLINE | ID: mdl-32820166

ABSTRACT

Perovskite light-emitting diodes (PeLEDs) have showed significant progress in recent years; the external quantum efficiency (EQE) of electroluminescence in green and red regions has exceeded 20%, but the efficiency in blue lags far behind. Here, a large cation CH3CH2NH2+ is added in PEA2(CsPbBr3)2PbBr4 perovskite to decrease the Pb-Br orbit coupling and increase the bandgap for blue emission. X-ray diffraction and nuclear magnetic resonance results confirmed that the EA has successfully replaced Cs+ cations to form PEA2(Cs1-xEAxPbBr3)2PbBr4. This method modulates the photoluminescence from the green region (508 nm) into blue (466 nm), and over 70% photoluminescence quantum yield in blue is obtained. In addition, the emission spectra is stable under light and thermal stress. With configuration of PeLEDs with 60% EABr, as high as 12.1% EQE of sky-blue electroluminescence located at 488 nm has been demonstrated, which will pave the way for the full color display for the PeLEDs.

12.
Ann Transl Med ; 8(3): 37, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32154282

ABSTRACT

BACKGROUND: The importance of HLA antigen matching is widely recognized and accepted worldwide. With the improvement of diagnostic methods, recent studies have shown that eplet mismatched for organ transplantation is essential. In the field of lung transplantation, eplet mismatch (MM) is closely related to chronic rejection after lung transplantation. To further investigate the relationship between early graft failure and acute rejection, we performed high-resolution HLA analysis on 59 patients in our center. METHODS: We conduct high-resolution HLA matching and Donor specific antibody (DSA) monitoring on 59 lung transplantation donors and recipients from April 1, 2018, to June 30, 2019. Baseline data were collected composed of both recipient characteristics and transplant-related features. Clinical outcomes were primary graft dysfunction (PGD) and acute rejection (AR). RESULTS: Overall, for these 59 patients, HLA antigen mismatch is 7.19±1.61, eplet mismatch is 8.31±1.75 (P=0.0005). As the number of mismatch sites increases, the severity of PGD increased significantly, especially when presented both eplet mismatch and HLA-DQ mismatch. In this group of patients, 2 cases of antibody-mediated rejection (AMR) occurred after transplantation, eplet MM 9 (HLA-DQ MM 2) and eplet MM 5 (HLA-DQ MM1). Both patients developed DSA after operation, and they are DQB1 06:01 and C07:02, respectively. There were 9 cases of death during the perioperative period. Five of them died of severe PGD, and 4 died of severe infection. All these 9 patients were with high-level eplet MM and HLA-DQ MM. CONCLUSIONS: Perioperative PGD and AR closely related to HLA mismatches, especially eplet and HLA-DQ MM. It might be noteworthy to do complementary detection of eplet matching and DSA in lung transplant donors and recipients, to predict the risk of early PGD and acute rejection after lung transplantation.

13.
Adv Mater ; 31(35): e1902618, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31293012

ABSTRACT

Optoelectronic devices based on metal halide perovskites, including solar cells and light-emitting diodes, have attracted tremendous research attention globally in the last decade. Due to their potential to achieve high carrier mobilities, organic-inorganic hybrid perovskite materials can enable high-performance, solution-processed field-effect transistors (FETs) for next-generation, low-cost, flexible electronic circuits and displays. However, the performance of perovskite FETs is hampered predominantly by device instabilities, whose origin remains poorly understood. Here, perovskite single-crystal FETs based on methylammonium lead bromide are studied and device instabilities due to electrochemical reactions at the interface between the perovskite and gold source-drain top contacts are investigated. Despite forming the contacts by a gentle, soft lamination method, evidence is found that even at such "ideal" interfaces, a defective, intermixed layer is formed at the interface upon biasing of the device. Using a bottom-contact, bottom-gate architecture, it is shown that it is possible to minimize such a reaction through a chemical modification of the electrodes, and this enables fabrication of perovskite single-crystal FETs with high mobility of up to ≈15 cm2 V-1 s-1 at 80 K. This work addresses one of the key challenges toward the realization of high-performance solution-processed perovskite FETs.

14.
Int J Biochem Cell Biol ; 113: 87-94, 2019 08.
Article in English | MEDLINE | ID: mdl-31200125

ABSTRACT

Pulmonary arterial hypertension (PAH) is characterized as pulmonary arterial endothelial dysfunction and endothelial cells over proliferation, therefore, the repair of pulmonary arterial endothelial cells has been a common goal in treating PAH. In the present study, human adipose derived mesenchymal stem cells (ASCs) were transfected with bFGF lentiviral vector and co-cultured with monocrotaline pyrrole treated human pulmonary arterial endothelial cells (HPAECs). The results showed that bFGF-ASCs improved the proliferation, viability and decreased the apoptosis of HPAECs, besides, improved PAH was observed in PAH rat models. Western blot analysis showed that the PI3k and p-Akt protein expression level increased in HPAECs, suggesting the activation of the PI3k/Akt signaling pathway. With the administration of LY294002, the bFGF induced HPAECs survival and PI3k/Akt signaling activation were successfully blocked. The present study demonstrated that bFGF transfected ASCs improved the survival of HPAECs by activating the PI3k/Akt pathway.


Subject(s)
Endothelial Cells/cytology , Fibroblast Growth Factor 2/biosynthesis , Mesenchymal Stem Cells/cytology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Artery/cytology , Adipose Tissue/cytology , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Cell Proliferation/physiology , Coculture Techniques , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Humans , Male , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Pulmonary Arterial Hypertension/metabolism , Pulmonary Arterial Hypertension/pathology , Pulmonary Arterial Hypertension/therapy , Pulmonary Artery/drug effects , Pulmonary Artery/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Transfection
15.
Biomed Res Int ; 2019: 2858750, 2019.
Article in English | MEDLINE | ID: mdl-31119161

ABSTRACT

Pulmonary arterial hypertension (PAH) is a serious condition. However, prevailing therapeutic strategies are not effective enough to treat PAH. Therefore, finding an effective therapy is clearly warranted. Adipose-derived mesenchymal stem cells (ASCs) and ASCs-derived exosomes (ASCs-Exos) exert protective effects in PAH, but the underlying mechanism remains unclear. Using a coculture of ASCs and monocrotaline pyrrole (MCTP)-treated human pulmonary artery endothelial cells (HPAECs), we demonstrated that ASCs increased cell proliferation in MCTP-treated HPAECs. Results showed that ASCs-Exos improved proliferation of both control HPAECs and MCTP-treated HPAECs. In addition, by transfecting ASCs with antagomir we observed that low exosomal miR-191 expression inhibited HPAECs proliferation whereas the agomir improved. Similar results were observed in vivo using a monocrotaline (MCT)-induced PAH rat model following ASCs transplantation. And ASCs transplantation attenuated MCT-induced PAH albeit less than the antagomir treated group. Finally, we found that miR-191 repressed the expression of bone morphogenetic protein receptor 2 (BMPR2) in HPAECs and PAH rats. Thus, we conjectured that miR-191, in ASCs and ASCs-Exos, plays an important role in PAH via regulation of BMPR2. These findings are expected to contribute to promising therapeutic strategies for treating PAH in the future.


Subject(s)
Bone Morphogenetic Protein Receptors, Type II/genetics , Hypertension, Pulmonary/genetics , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , Animals , Cell Line , Cell Proliferation/genetics , Endothelial Cells/metabolism , Exosomes/drug effects , Exosomes/genetics , Gene Expression Regulation/genetics , Humans , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/pathology , Monocrotaline/toxicity , Pulmonary Artery/drug effects , Pulmonary Artery/pathology , Rats , Rats, Sprague-Dawley
16.
Cytotherapy ; 21(4): 416-427, 2019 04.
Article in English | MEDLINE | ID: mdl-30904330

ABSTRACT

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial endothelial hyperproliferation and dysfunction. Restoration of endothelial function is a common goal of available treatments. In the present study, human adipose-derived mesenchymal stromal cells (ASCs) were co-cultured with monocrotaline pyrrole-treated human pulmonary arterial endothelial cells (HPAECs); increased proliferation of HPAECs and expression of vascular endothelial growth factor (VEGF) were observed. High throughput sequencing results showed that six microRNAs (miMNAs) of ASCs were significantly dysregulated. In monocrotaline-induced PAH rat models, ASC transplantation improved the right ventricle systolic pressure, right ventricle hypertrophy and pulmonary endothelium hyperproliferation, and four of the six miRNAs were validated in the lung tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these dysregulated miRNAs were involved in the regulation of transcription, signal transduction, negative regulation of cell proliferation through mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, VEGF signaling pathway, cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, transforming growth factor (TGF)-beta signaling pathway and P53 signaling pathway. Our data indicates that the unique six miRNA expression signature could be involved in the PAH endothelial repair by ASCs.


Subject(s)
Adipose Tissue/cytology , Endothelium/metabolism , Endothelium/physiopathology , Hemodynamics , Mesenchymal Stem Cells/cytology , MicroRNAs/genetics , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Arterial Hypertension/therapy , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cell Survival/drug effects , Coculture Techniques , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Gene Ontology , Hemodynamics/drug effects , Humans , Hypertrophy, Left Ventricular/genetics , Hypertrophy, Left Ventricular/physiopathology , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/drug effects , MicroRNAs/metabolism , Monocrotaline/analogs & derivatives , Monocrotaline/pharmacology , Pulmonary Arterial Hypertension/genetics , Pulmonary Artery/pathology , Rats, Sprague-Dawley , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism
17.
J Mol Med (Berl) ; 97(1): 127-140, 2019 01.
Article in English | MEDLINE | ID: mdl-30478628

ABSTRACT

KIAA1199 is often upregulated in cancer cells, including non-small-cell lung cancer (NSCLC). Although KIAA1199 is associated with aggressive tumor phenotype and poor survival in NSCLC, little is known about its functional role in NSCLC progression. Using archived clinical samples, we evaluated KIAA1199 messenger RNA (mRNA) and protein expression in NSCLC tissues and correlated with NSCLC clinicopathological characteristics as well as overall survival. Using NSCLC cell lines, KIAA1199 was either silenced using gene-specific shRNA or overexpressed to assess the impact on EMT signaling pathways. Finally, in a mouse xenograft NSCLC model, we determine the therapeutic potential of KIAA1199 repression. Our data showed that KIAA1199 was significantly upregulated in NSCLC tissues compared to adjacent normal tissues both at the mRNA (P < 0.001) and protein levels (P < 0.05). KIAA1199 overexpression is an independent prognostic marker for overall survival (HR = 1.833). In NSCLC cell lines, KIAA1199 expression directly influences the expression of EMT markers, EMT-inducing transcription factors (EMT-TFs), and EMT signaling molecules. Knocking down of KIAA1199 expression in the mouse NSCLC xenograft model significantly suppressed tumor growth and augmented the efficacy of chemotherapy (n = 5; P < 0.05). We conclude that KIAA1199 is not only a prognostic marker but a novel therapeutic target in NSCLC through regulating EMT signaling pathway. KEY MESSAGES: KIAA1199 overexpression is an independent prognostic marker in NSCLC. KIAA1199 expression directly influences the expression of EMT markers. KIAA1199 promotes invasion and migration in NSCLC via PI3K-Akt mediated EMT.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Epithelial-Mesenchymal Transition , Hyaluronoglucosaminidase/genetics , Lung Neoplasms/genetics , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement , Female , Gene Expression Regulation, Neoplastic , Humans , Hyaluronoglucosaminidase/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Mice, Nude , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
18.
Oncol Rep ; 41(2): 973-980, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30431103

ABSTRACT

Lysophospholipase1 (LYPLA1) also known as acyl­protein thioesterase1 (APT1) belongs to the superfamily of α/ß hydrolase. It has been found to have the properties of a homodimer by manifesting depalmitoylation as well as lysophospholipase activity. LYPLAs are under the control of both microRNAs, miR­138 and miR­424. They were observed to be significantly overexpressed in chronic lymphocytic leukemia cells. To date, LYPLAs are the sole enzymes recognized to activate depalmitoylation. In this study, we provide the expression pattern of LYPLA1 in non­small cell lung cancer (NSCLC) using four different NSCLC cell lines. Western blot analysis and RT­PCR were performed to detect the protein expression and mRNA expression of LYPLA1 in NSCLC cell lines. We detected the highest LYPLA1 protein expression level in SPC­A­1 cells followed by A549 cells, and the highest LYPLA1 mRNA expression level was detected in the SPC­A­1 cells followed by the H1299 cell line. We found that suppression of LYPLA1 expression using small­interfering RNA significantly inhibited proliferation, migration and invasion of the LYPLA1­transfected NSCLC cells. Furthermore, we explored the involvement of LYPLA1 in the regulation of epithelial­mesenchymal transition (EMT). The epithelial marker E­cadherin was significantly increased, while mesenchymal markers N­cadherin, vimentin and SNAIL were markedly decreased in the LYPLA1­silenced cells. Collectively the results of the present study suggest that the LYPLA1 gene plays a tumor­promotor role in NSCLC cells in vitro.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Thiolester Hydrolases/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Humans , Lipoylation/genetics , Lung Neoplasms/genetics , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Thiolester Hydrolases/genetics
19.
Tuberc Respir Dis (Seoul) ; 81(3): 167-174, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29926540

ABSTRACT

Despite recent clinical guidelines, the optimal therapeutic strategy for the management of refractory chronic cough is still a challenge. The present systematic review was designed to assess the evidence for efficacy and safety of gabapentin in the treatment of chronic cough. A systematic search of PubMed, Embase, Cochrane Library databases, and publications cited in bibliographies was performed. Articles were searched by two reviewers with a priori criteria for study selection. Seven relevant articles were identified, including two randomized controlled trials, one prospective case-series designed with consecutive patients, one retrospective case series of consecutive patients, one retrospective case series with unknown consecutive status, and two case reports comprising six and two patients, respectively. Improvements were detected in cough-specific quality of life (Leicester Cough Questionnaire score) and cough severity (visual analogue scale score) following gabapentin treatment in randomized controlled trials. The results of prospective case-series showed that the rate of overall improvement of cough and sensory neuropathy with gabapentin was 68%. Gabapentin treatment of patients with chronic cough showed superior efficacy and a good safety record compared with placebo or standard medications. Additional randomized and controlled trials are needed.

20.
Oncol Rep ; 39(3): 1505-1515, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29328462

ABSTRACT

The tumor suppressor gene p53 and its dynamic patterns have caused widespread attention in the field of cancer research. Serum and glucocorticoid-regulated kinase 1 (SGK1) with features of serine/threonine kinase activity, which also contributes to the structural and functional similarities with the AKT family of kinases, is a key enzyme in the regulation of immune responses in tumor cells, and SGK1 was noted to be expressed in close relation to p53 protein levels, and there exists a negative feedback pathway between intracellular SGK1 and p53. Noteworthy, SGK1 was detected to play a role in the development of resistance to cancer chemotherapy. In this study, we demonstrated that high SGK1 expression had strong prognostic value for reduced overall survival in NSCLC patients. Detection of SGK1 collectively was helpful to predict the prognosis of NSCLC. We also identified the expression level of SGK1 and the p53 pathway including downstream apoptotic proteins under the stimulation of γ-radiation and SGK1 inhibitor GSK650394, which presented a series of dynamic fluctuations. Our results suggest that SGK1 dynamics could play an important role in cell signaling, which is capable of directly influencing NSCLC cellular fate decisions.


Subject(s)
Adenocarcinoma/pathology , Benzoates/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Gamma Rays/adverse effects , Immediate-Early Proteins/antagonists & inhibitors , Lung Neoplasms/pathology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Adenocarcinoma/blood , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Apoptosis , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/therapy , Case-Control Studies , Cell Proliferation , Female , Follow-Up Studies , Humans , Lung Neoplasms/blood , Lung Neoplasms/therapy , Male , Middle Aged , Prognosis , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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