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1.
Cardiovasc Toxicol ; 24(6): 587-597, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38691303

ABSTRACT

Vascular lesions frequently arise as complication in patients diagnosed with diabetes mellitus (DM). Presently, percutaneous coronary intervention (PCI) and antithrombotic therapy serve as primary treatments. However, in-stent restenosis persists as a challenging clinical issue following PCI, lacking sustained and effective treatment. Linarin (LN) exhibits diverse pharmacological activities and is regarded as a potential drug for treating various diseases, including DM. But its specific role in restenosis after vascular injury in DM patients remains unclear. A rat model of diabetes-related restenosis was established to evaluate the role of LN on neointimal hyperplasia. Vascular smooth muscle cells (VSMCs) stimulated by high glucose (HG, 30 mM) underwent LN treatment. Additionally, an overexpression plasmid of A disintegrin and metalloproteinases (ADAM10) was constructed to transfect VSMCs. We employed CCK-8, Brdu, wound-healing scratch, and transwell migration assays to evaluate the proliferation and migration of VSMCs. Furthermore, western blot and immunofluorescence assays were utilized to investigate the expressions of ADAM10 and the downstream Notch signaling pathway in vivo and in vitro models. LN notably alleviated intimal hyperplasia after vascular injury in DM rats and reduced the protein expression of ADAM10, alongside its downstream Notch1 signaling pathway-related proteins (Notch1, NICD and Hes1) in rat carotid artery tissues. LN effectively suppressed the proliferation and migration of VSMCs induced by HG, downregulating the protein expression of ADAM10, Notch1, NICD and Hes1. Moreover, our findings indicated that ADAM10 overexpression significantly reversed LN's effects on proliferation, migration, and the expression of Notch1 signaling pathway-related proteins in HG-treated VSMCs. LN demonstrates potential therapeutic efficacy in addressing restenosis after diabetic-related vascular injury, with the ADAM10 mediated Notch signaling pathway playing a pivotal role.


Subject(s)
ADAM10 Protein , Amyloid Precursor Protein Secretases , Carotid Artery Injuries , Cell Movement , Cell Proliferation , Diabetes Mellitus, Experimental , Membrane Proteins , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Neointima , Rats, Sprague-Dawley , Signal Transduction , Animals , ADAM10 Protein/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/enzymology , Cell Movement/drug effects , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/enzymology , Cell Proliferation/drug effects , Male , Membrane Proteins/metabolism , Membrane Proteins/genetics , Amyloid Precursor Protein Secretases/metabolism , Cells, Cultured , Carotid Artery Injuries/pathology , Carotid Artery Injuries/metabolism , Carotid Artery Injuries/drug therapy , Carotid Artery Injuries/enzymology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Hyperplasia , Receptors, Notch/metabolism , Receptor, Notch1/metabolism , Transcription Factor HES-1/metabolism , Transcription Factor HES-1/genetics , Disease Models, Animal , Rats , Coronary Restenosis/pathology , Coronary Restenosis/etiology , Coronary Restenosis/metabolism , Coronary Restenosis/prevention & control
2.
Can J Infect Dis Med Microbiol ; 2024: 7547514, 2024.
Article in English | MEDLINE | ID: mdl-38283082

ABSTRACT

Background: The potential role of cell envelope integrity proteins in mediating antibiotic resistance is not well understood. In this study, we investigated whether the cell envelope integrity protein D0Y85_RS06240 from the multiantibiotic resistant strain Stenotrophomonas sp. G4 mediates antibiotic resistance. Methods: Bioinformatics analysis was conducted to identify proteins related to the D0Y85_RS06240 protein. The D0Y85_RS06240 gene was heterologously expressed in Escherichia coli, both antibiotic MICs and the effect of efflux pump inhibitors on antibiotic MICs were determined by the broth microdilution method. A combination of antibiotic and efflux pump inhibitor was used to investigate bacterial killing kinetics, and binding of D0Y85_RS06240 to antibiotic molecules was predicted by molecular docking analysis. Results: Sequence homology analysis revealed that D0Y85_RS06240 was related to cell envelope integrity proteins. The D0Y85_RS06240 heterologous expression strains were resistant to multiple antibiotics, including colistin, tetracycline, and cefixime. However, the efflux pump inhibitor N-methylpyrrolidone (NMP) reduced the antibiotic MICs of the D0Y85_RS06240 heterologous expression strain, and bacterial killing kinetics revealed that NMP enhanced the bactericidal rate of tetracycline to the drug-resistant bacteria. Molecular docking analysis indicated that D0Y85_RS06240 could bind colistin, tetracycline, and cefixime. Conclusion: The cell envelope integrity protein D0Y85_RS06240 in Stenotrophomonas sp. G4 mediates multiantibiotic resistance. This study lays the foundation for an in-depth analysis of D0Y85_RS06240-mediated antibiotic resistance mechanisms and the use of D0Y85_RS06240 as a target for the treatment of multiantibiotic-resistant bacterial infections.

3.
Life Sci ; 313: 121276, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36496032

ABSTRACT

AIM: LncRNAs are highly expressed in the CNS and regulate pathophysiological processes. However, the potential role of lncRNAs inischemic stroke (IS) remains unknown. In this study, we investigated the functions and possible molecular mechanism of lncRNA paternal expressed gene 11 antisense (PEG11as) in this process. METHODS: Middle cerebral artery occlusion/reperfusion (MCAO/R) mice model and N2a cells model from oxygen-glucose deprivation/reoxygenation (OGD/R) were used to simulate cerebral I/R in vivo and in vitro. High-throughput sequencing (RNA-Seq) was used todetect differential expression of lncRNAs in cerebral I/R. QRT-PCR was used to detect the expression of PEG11as and miR-342-5p. Bioinformatics analysis, FISH, luciferase reporter assay, RIP, Western blot, and immunofluorescence were used to detect the interaction between PEG11as, miR-342-5p and PFN1. The effect on neuronal apoptosis was analyzed using loss-of-function combined with TUNEL, Hoechst, and caspase3 activity assays. KEY FINDINGS: 254 lncRNAs were differentially expressed in MCAO1h/R6h mice. Among them, PEG11as was significantly up-regulated. PEG11as down-regulated could markedly attenuate the brain infarct volume, alleviate neurological deficit in vivo, and effectively promote neuron survival, attenuate neuronal apoptosis both in vivo and in vitro. FISH assay discovered that PEG11as was mainly located in the cytoplasm. Furthermore, we demonstrated that PEG11as was able to bind miR-342-5p to inhibit miR-342-5p activity, whereas the down-regulated of miR-342-5p resulted in profilin 1 (PFN1) overexpression and thus promoting apoptosis. SIGNIFICANCE: This study suggests that PEG11as regulates neuronal apoptosis by miR-342-5p/PFN1 axis, which may contribute to our understanding of pathogenesis and provide a potential therapeutic option for cerebral I/R.


Subject(s)
Brain Ischemia , Ischemic Stroke , MicroRNAs , RNA, Long Noncoding , Reperfusion Injury , Stroke , Mice , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Profilins , MicroRNAs/genetics , MicroRNAs/metabolism , Stroke/genetics , Reperfusion Injury/metabolism , Infarction, Middle Cerebral Artery/metabolism , Apoptosis/genetics , Glucose/metabolism , Brain Ischemia/genetics , Brain Ischemia/metabolism
4.
Int J Oncol ; 62(1)2023 01.
Article in English | MEDLINE | ID: mdl-36382667

ABSTRACT

Death associated protein­3 (DAP3) was identified as a responsive protein to interferon­gamma­induced cell death which possibly exerts this regulation by interacting with DAP3 binding cell Death enhancer­1 (DELE1), a newly discovered mitochondrial stress protein in response to cell stress signals. Whilst DAP3 has been shown to be aberrantly expressed in several cancer types (i.e. breast cancer), little is known about the relationship between DAP3 and DELE1 in cancers. The present study examined the expression levels of both DAP3 and DELE1 in clinical colorectal cancers (CRCs), as well as their implication on chemoresistance and mechanism behind the action. Firstly, transcript levels of both DAP3 and DELE1 were quantitatively assessed in a clinical cohort of CRC (n=94). Tumour tissues had significantly higher levels of DAP3, but not DELE1 compared with normal tissues. Levels of DAP3 and DELE1 had a significant association with patient's clinical outcomes and local recurrence. DAP3 and DELE1 significantly correlated in normal colorectal tissues but not in tumour tissues. Secondly, the protein levels of DAP3 and DELE1 were evaluated in both normal and tumour colon tissues which showed that both proteins were highly aberrant in CRC tissues. In addition, both DAP3 and DELE1 at transcript and protein levels were identified as prognostic factors for patient's clinical outcomes. Furthermore, in in vitro assays, knocking down DAP3 or DELE1, and in particular both DAP3 and DELE1 together rendered the CRC cells more sensitive to chemotherapy drugs, consistent with clinical findings of the TCGA­COAD datasets. The acquisition of drug sensitivity following the genetic knockdown was independent of the mitochondrial metabolism, as neither DAP3 knockdown nor DELE1 knockdown showed a significant change. In summary, DAP3 and DELE1 are highly aberrant in CRCs, and both molecules are prognostic factors for patient's clinical outcomes and local recurrence, and are indicators for chemoresistance.


Subject(s)
Apoptosis Regulatory Proteins , Colorectal Neoplasms , Humans , Apoptosis Regulatory Proteins/genetics , Cell Death , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , RNA-Binding Proteins
5.
Environ Sci Pollut Res Int ; 30(3): 6965-6985, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36008582

ABSTRACT

The aim of this study was to provide a new method for dynamic and continuous assessment of ecosystem service value (ESV) and reveal the impact of land use change on ESV in Dasi River Basin within Jinan's startup area from replacing old growth drivers with new ones. Based on four remote sensing images from 2002 to 2020, four ecological indicators were extracted, and the ecological environmental quality index (EEQI) was obtained through the approach of principal component analysis (PCA). Then, the traditional ESV evaluation method was modified by using the EEQI, grain yield, the biomass factor of cropland ecosystem, and the consumer price index (CPI). Finally, the impact of land use change on ESV was further analyzed based on the improved evaluation model. The result showed that (1) during 2002-2020, the area of forestland, grassland, and built-up land showed an increasing trend. The area of cropland and bare land showed a decreasing trend, and the water body area showed a slightly decreasing trend. (2) The total ESVS overall increased by 2.1759 × 107 yuan; the increased ESVS from air quality regulation, maintain biodiversity, and climate regulation were the main reasons for the increased of total ESVS, with contribution rates of 53.18%, 12.46%, and 11.29% respectively. (3) The sensitivity of ecosystem services to land use change showed a decreasing trend, and the order of elasticity index of different land use types was cropland > water body > forestland > grassland > bare land. The conversion of cropland and bare land to forestland was the main type of ESVs increase, with contribution rates of 18.35% and 10.13%, respectively. The cropland reclamation and built-up land expansion were the most significant land use changes that lead to the decline of ESVS, with contribution rates of 20.14% and 19.03% respectively. (4) The ESV showed a significant positive auto-correlation in terms of spatial distribution. The area of high-high region was mainly distributed in water body, forestland, and its surrounding areas. The area of low-low region was mainly distributed in built-up land and wasteland areas where human disturbance is relatively serious. The high-low and low-high regions were affected by landscape transition process and randomly distributed around the low-low and high-high regions, respectively. This study cannot only put forward a new method for the dynamic continuous evaluation of ESV, but also provide a reference for the rational allocation of land resources in the startup area to realize the balanced development of regional environment and economy.


Subject(s)
Ecosystem , Rivers , Humans , Conservation of Natural Resources , Forests , China , Water
6.
J Clin Neurosci ; 101: 244-251, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35653882

ABSTRACT

Evidence for effects of the dose of recombinant tissue plasminogen activator(rt-PA) in Asian populations is inconclusive. The standard dose may cause drug waste and increase economic burden in developing country. Therefore, we preliminarily describe the safety and efficacy of a new modified dose of rt-PA regimen(0.6 or 0.9 mg/kg, with a maximum dose of 50 mg) in real world settings. 265 consecutive patients with ischemic stroke were treated with intravenous(IV) rt-PA alone from all the 323 consecutive patients treated with reperfusion therapy between January 1, 2017 and March 31, 2020. Safety and Efficacy was assessed by early neurological improvement(ENI), early neurological deterioration(END), symptomatic intracranial hemorrhage(sICH) and 90-day outcome defined by modified Rankin scale(mRS). Subgroup analysis was conducted to draw comparisons between different dose groups ([0.5,0.6)mg/kg, [0.6,0.7)mg/kg, [0.7,0.8)mg/kg, [0.8,0.9]mg/kg). Among the 265 patients, 150(56.60%) had a favorable outcome at 3 months(3 M); Mortality occurred in 17(6.40%) in 3 M; sICH in 12(4.50%); ENI in 70(26.40%); END2 in 29(10.90%) and END4 in 18(6.80%). In subgroup analysis, there was a significant difference in sICH that more patients developed sICH in [0.8-0.9]mg/kg group(P = 0.044) in univariate analysis of different dose. After adjusting, there was no significant difference between 4 dosage groups. Significant differences were seen in gender, atrial fibrillation and baseline NIHSS in the multivariable model of favorable outcome at 3 M. Our study preliminarily shows a good safety and efficacy of our modified rt-PA regimen, indicating that this regimen should be worthy of further study especially in developing country to reduce the financial burden of patients and avoid drug waste.


Subject(s)
Brain Ischemia , Fibrinolytic Agents , Ischemic Stroke , Stroke , Tissue Plasminogen Activator , Brain Ischemia/drug therapy , China , Fibrinolytic Agents/adverse effects , Humans , Ischemic Stroke/drug therapy , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Retrospective Studies , Stroke/drug therapy , Stroke/etiology , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
7.
Oncol Lett ; 21(2): 140, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33552259

ABSTRACT

Anaesthetics have been implicated to influence cancer cells and progression. Similarly, crosstalk between cancer cells and stromal components within the microenvironment is also an important factor driving progression. Stromal cell-derived factor-1 (SDF-1) and hepatocyte growth factor (HGF) are key chemokines/cytokines produced by fibroblasts which have been established as influential factors in cancer progression. The present study explored the capacity of anaesthetics to influence the expression of these key molecules in fibroblasts. The anaesthetics rocuronium bromide (RB), vecuronium bromide (VB), suxamethonium chloride CRS (SCC), dexmedetomidine hydrochloride (DH) and lidocaine were used to treat MRC-5 fibroblasts over a range of concentrations. Following treatment, transcript expression of SDF-1 and HGF was quantified using quantitative PCR. Treatment of MRC-5 cells with RB brought about a reduction of SDF-1 expression which was found to be significant in the 45 µg/ml treatment group. Treatment with the other anaesthetics brought about some alterations in SDF-1 expression but these were not found to be statistically significant. Treatment with the tested anaesthetics did not have any significant effect on HGF transcript expression within MRC-5 cells, although again some alterations were observed. The results indicated that anaesthetics may have an impact on the fibroblast component of the tumour microenvironment, potentially influencing SDF-1 and HGF expression which in turn could influence tumour progression.

8.
Int J Mol Med ; 47(2): 435-443, 2021 02.
Article in English | MEDLINE | ID: mdl-33416125

ABSTRACT

Despite improvements in therapy and management, cancer represents and remains a major cause of mortality and morbidity worldwide. Although genetics serve an important role in tumorigenesis and tumour progression, the tumour microenvironment (TME) in solid tumours is also important and has been indicated to contribute to these processes. Stromal cell­derived factors (SDFs) represent an important family within the TME. The family includes SDF­1, SDF­2, SDF2­like 1 (SDF2L1), SDF­3, SDF­4 and SDF­5. SDF­1 has been demonstrated to act as a positive regulator in a number of types of tumour, such as oesophago­gastric, pancreatic, lung, breast, colorectal and ovarian cancer, while the biology and functions of other members of the SDF family, including SDF­2, SDF2L1, SDF­4 and SDF­5, in cancer are different, complex and controversial, and remain mainly unknown. Full identification and understanding of the SDFs across multiple types of cancer is required to elucidate their function and establish potential key targets in cancer.


Subject(s)
Intercellular Signaling Peptides and Proteins/metabolism , Neoplasm Proteins/metabolism , Neoplasms/metabolism , Tumor Microenvironment , Humans , Neoplasms/classification , Neoplasms/pathology
9.
Materials (Basel) ; 13(19)2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32998445

ABSTRACT

TiO2 possesses a wide forbidden band of about 3.2 eV, which severely limits its visible light absorption efficiency. In this work, copper nitride (Cu3N) films were prepared by magnetron sputtering at different gas flow ratios. The structure of the films was tested by scanning electron microscope, X-ray diffractometer, and X-ray photoelectron spectroscope. Optical properties were investigated by UV-vis spectrophotometer and fluorescence spectrometer. Results show that the Cu3N crystal possesses a typical anti-ReO3 crystal structure, and the ratio of nitrogen and Cu atoms of the Cu3N films was adjusted by changing the gas flow ratio. The Cu3N films possess an optical band gap of about 2.0 eV and energy gap of about 2.5 eV and exhibit excellent photocatalytic activity for degrading methyl orange (degradation ratio of 99.5% in 30 min). The photocatalytic activity of Cu3N mainly originates from vacancies in the crystal and Cu self-doping. This work provides a route to broaden the forbidden band width of photocatalytic materials and increase their photoresponse range.

10.
J Cell Biochem ; 121(12): 4908-4921, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32692884

ABSTRACT

Endometrial cancer (EC) is one of the most common malignancies in the female genital system, characterized by high mortality and recurrence rates. This study attempted to screen key genes and potential prognostic biomarkers for EC using bioinformatics analysis. Twenty-seven normal endometrial tissues and 135 EC samples were collected from four Gene Expression Omnibus (GEO) databases, then we identified the differentially expressed genes (DEGs) and conducted downstream analyses. Moreover, we screened hub genes by constructing a protein-protein interaction (PPI) network. Finally, we assessed the prognostic values and molecular mechanism of the potential prognostic genes using the Kaplan-Meier curve and Gene Set Enrichment Analysis (GSEA). As a result, 28 upregulated and 94 downregulated genes were determined after gene integration of these four GEO data sets. Gene Ontology analysis indicated that DEGs were mainly involved in transcriptional regulation and cell proliferation. The Kyoto Encyclopedia of Gene and Genome pathway analysis primarily related to transcriptional misregulation and apoptosis. Moreover, the PPI analysis revealed 10 hub genes (JUN, UBE2I, GATA2, WT1, PIAS1, FOXL2, RUNXI, EZR, TCF4, and NR2F2) with a high degree of connectivity, among them, the expression tendency of nine genes except UBE2I were consistent with messenger RNA level from The Cancer Genome Atlas data. Furthermore, only FOXL2, TCF4, and NR2F2 were significantly correlated with prognosis of EC patients, and their low expression associated biological pathways were enriched in the cell cycle and fatty acid metabolism. In conclusion, this study identified three key genes as biomarkers and potential therapeutic targets of EC on the basis of integrated bioinformatics analysis. The findings will improve our comprehension of the molecular mechanisms underlying the pathogenesis and prognosis of EC.

11.
Materials (Basel) ; 13(8)2020 Apr 16.
Article in English | MEDLINE | ID: mdl-32316301

ABSTRACT

Cu3N/MoS2 heterojunction was prepared through magnetron sputtering, and its optical band gap was investigated. Results showed that the prepared Cu3N/MoS2 heterojunction had a clear surface heterojunction structure, uniform surface grains, and no evident cracks. The optical band gap (1.98 eV) of Cu3N/MoS2 heterojunction was obtained by analyzing the ultraviolet-visible transmission spectrum. The valence and conduction band offsets of Cu3N/MoS2 heterojunction were 1.42 and 0.82 eV, respectively. The Cu3N film and multilayer MoS2 formed a type-II heterojunction. After the two materials adhered to form the heterojunction, the interface electrons flowed from MoS2 to Cu3N because the latter had higher Fermi level than the former. This behavior caused the formation of additional electrons in the Cu3N and MoS2 layers and the change in optical band gap, which was conducive to the charge separation of electrons in MoS2 or MoS2 holes. The prepared Cu3N/MoS2 heterojunction has potential application in various high-performance photoelectric devices, such as photocatalysts and photodetectors.

12.
Aging (Albany NY) ; 11(24): 12032-12042, 2019 12 18.
Article in English | MEDLINE | ID: mdl-31852839

ABSTRACT

Oxygen glucose deprivation-reoxygenation (OGD-R) causes the production of reactive oxygen species (ROS) and oxidative injury in neuronal cells. We tested the potential neuroprotective function of compound 13 (C13), a novel AMP-activated protein kinase (AMPK) activator, against OGD-R. We show that C13 pretreatment protected SH-SY5Y neuronal cells and primary hippocampal neurons from OGD-R. C13 activated AMPK signaling in SH-SY5Y cells and primary neurons. It significantly inhibited OGD-R-induced apoptosis activation in neuronal cells. Conversely, AMPKα1 shRNA or knockout reversed C13-mediated neuroprotection against OGD-R. C13 potently inhibited OGD-R-induced ROS production and oxidative stress in SH-SY5Y cells and primary neurons. Furthermore, C13 induced Keap1 downregulation and Nrf2 activation, causing Nrf2 stabilization, nuclear accumulation, and expression of Nrf2-dependent genes. Nrf2 silencing or knockout in SH-SY5Y cells abolished C13-mediated neuroprotection against OGD-R. In conclusion, C13 activates AMPK-Nrf2 signaling to protect neuronal cells from OGD-R.


Subject(s)
Adenylate Kinase/drug effects , NF-E2-Related Factor 2/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Reperfusion Injury/metabolism , Adenylate Kinase/metabolism , Animals , Cell Line , Humans , Mice , Neurons/metabolism , Neurons/pathology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Reperfusion Injury/pathology , Signal Transduction/drug effects
13.
Endocrine ; 63(1): 70-78, 2019 01.
Article in English | MEDLINE | ID: mdl-30128961

ABSTRACT

PURPOSE: Oxidative stress is an important mechanism for diabetic nephropathy. Studies showed that hemo oxygenase-1 (HO-1) expression in renal tissue of patients with diabetic nephropathy has upregulated, while the HO-1 can protect the body through anti-oxidative stress. The study aimed to preliminarily explore the molecular mechanism by observing the effect of Sitagliptin on HO-1 expression in renal tissue of rats with diabetic nephropathy. METHODS: The diabetic nephropathy rat model was established by STZ injection followed by intraperitoneal injection of sitagliptin with different concentrations. The mRNA expressions of HO-1 were detected by real-time PCR and Western blot and HO-1 enzyme activity change was detected by colorimetry. Human renal mesangial cell (HRMC) were cultured in vitro with high glucose concentration (30 µmol/L), phosphatidylinositol-3-kinase (PI3K) level and nuclear factor erythroid-2-related factor (Nrf2) content in cytoplasm and cell nucleus were observed before and after treatment with sitagliptin, as well as the action of in meditating HO-1 expression. RESULTS: HO-1 mRNA, protein level, and HO-1 enzyme activity in renal tissue of rats with diabetic nephropathy were significantly increased after treatment with sitagliptin (P < 0.05). As comparison, the 24 h urinary microalbumin, creatinine, and boold urea nitrogen were all decreased after treatment of sitagliptin (P < 0.05). Similar results were observed after CoPP (an agonist of HO-1) treatment (P < 0.05). In contrast, ZnPP, an inhibitor of HO-1, significantly abrogated the inhibitory effect of sitagliptin (P < 0.05). Phosphorylation of PI3K and Nrf2 nuclear translocation under high-glucose concentration condition was induced by sitagliptin in HRMC. HO-1 expression was suppressed by pretreating HRMC with PI3K inhibitor or RNA interference. CONCLUSIONS: Sitagliptin may induce HO-1 expression via activation of PI3K and Nrf2 in rats with diabetic nephropathy; HO-1 can improve the oxidative stress of diabetic nephropathy, eventually protect from diabetic nephropathy.


Subject(s)
Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/enzymology , Heme Oxygenase (Decyclizing)/biosynthesis , Hypoglycemic Agents/therapeutic use , Sitagliptin Phosphate/therapeutic use , Animals , Cells, Cultured , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/pathology , Glomerular Mesangium/cytology , Glomerular Mesangium/drug effects , Glucose/pharmacology , Heme Oxygenase (Decyclizing)/drug effects , Humans , Kidney/pathology , Kidney Function Tests , Male , NF-E2-Related Factor 2/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Sprague-Dawley , Up-Regulation/drug effects
14.
Front Chem ; 6: 222, 2018.
Article in English | MEDLINE | ID: mdl-29963549

ABSTRACT

To inhibit the polysulfide-diffusion in lithium sulfur (Li-S) batteries and improve the electrochemical properties, the commercial polypropylene (PP) was decorated by an active carbon (AC) coating with lots of electronegative oxygenic functional group of -OH. Owing to the strong adsorption of AC and the electrostatic repulsion between the -OH and negatively charged polysulfide ions, the Li-S batteries demonstrated a high initial discharge capacity of 1,656 mAh g-1 (approximately 99% utilization of sulfur) and the capacity can still remain at 830 mAh g-1 after 100 cycles at 0.2 C. Moreover, when the rate was increased to 1 C, the batteries could also possess a discharge capacity of 1,143 mAh g-1. The encouraging cycling stability make clear that this facile approach can successfully restrain the shuttle effect of polysulfides and make further progress to the practical application of Li-S batteries.

15.
Neuroreport ; 29(13): 1061-1067, 2018 09 05.
Article in English | MEDLINE | ID: mdl-29979260

ABSTRACT

BC200 is a long noncoding RNA expressed at high levels in the Alzheimer's disease (AD), and blocking of BC200 by siRNA is assumed to be an effective method for various disease therapy. We have established an AD cell model overexpressing amyloid ß-peptide (Aß)1-42 to observe the effects of BC200 on the cell viability and apoptosis, and to investigate the associated underlying mechanisms. Efficient knockdown and overexpression of BC200 were established using BC200 siRNA and BC200 mimics, respectively. Cell viability following BC200 knockdown and overexpression was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide assay, and cell apoptosis was monitored by flow cytometry. We successfully established an AD cell model overexpressing Aß1-42 gene, and reported the results of change of BC200 on Aß1-42 levels. Knockdown of BC200 significantly suppressed b-site amyloid precursor protein-cleaving enzyme 1 (BACE1) expression, and overexpression of BC200 increased BACE1 expression. Besides, inhibition of BC200 significantly increased cell viability and reduced cell apoptosis in the AD model via directly targeting BACE1, which can be increased by overexpression of BC200. BC200 regulated AD cell viability and apoptosis via targeting BACE1, and it may be one of the putative target in AD development and provides potential new insights into genetic therapy against AD.


Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Peptide Fragments/metabolism , RNA, Long Noncoding/metabolism , Amyloid Precursor Protein Secretases/metabolism , Apoptosis , Aspartic Acid Endopeptidases/metabolism , Cell Line, Tumor , Cell Survival , Humans , Up-Regulation
16.
Brain Behav ; 8(7): e01023, 2018 07.
Article in English | MEDLINE | ID: mdl-29888877

ABSTRACT

OBJECTIVE: Dehydration on admission is correlated with neurological deterioration (ND). The primary objective of our study was to use support vector machine (SVM) algorithms to identify an ND prognostic model, based on dehydration equations. METHODS: This study included a total of 382 patients hospitalized with acute ischemic stroke. The following parameters were recorded: age, sex, laboratory values (serum sodium, potassium, chlorinum, glucose, and urea), and vascular risk factor data. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative performance of the BUN/Cr ratio as well as each of 38 equations for predicting ND. We used the Boruta algorithm for feature selection. After optimizing the SVM kernel parameters, we built an SVM model to predict ND and used the test set to obtain predictive values for assessing model accuracy. RESULTS: In total, 102 of 382 patients (26.7%) with acute ischemic stroke developed ND. In all patients, the BUN/Cr ratio and each of 38 equations were significant predictors of ND. Equation 20 [1.86 × Na+ + glucose + urea + 9] yielded the maximum area under the ROC curve, and faired best in terms of prognostic performance (a cutoff value of 284.49 mM yielded a sensitivity of 94.12% and specificity of 61.43%). Equation 32 predicted ND poststroke across population groups, and worked well in older as well as young adults; (a cutoff value of 297.08 mM yielded a sensitivity of 93.14% and specificity of 60.00%). Feature selection by the Boruta algorithm was used to decrease the number of variables from 18 to 5 in the condition. The specificity of test samples for the SVM prediction model increased from 44.1% to 89.4%, and the AUC increased from 0.700 to 0.927. CONCLUSIONS: SVM algorithms can be used to establish a prediction model for dehydration-associated ND, with good classification results.


Subject(s)
Dehydration/complications , Neurodegenerative Diseases/etiology , Algorithms , Brain Ischemia/complications , Brain Ischemia/physiopathology , Dehydration/physiopathology , Female , Humans , Male , Models, Biological , Neurodegenerative Diseases/physiopathology , Osmolar Concentration , Prognosis , ROC Curve , Sensitivity and Specificity , Stroke/complications , Stroke/physiopathology , Support Vector Machine
17.
Anticancer Res ; 37(8): 4371-4378, 2017 08.
Article in English | MEDLINE | ID: mdl-28739730

ABSTRACT

BACKGROUND/AIM: Muscle relaxants, also known as neuromuscular blocking agents, can block nerve impulses to the muscles and are always used in surgery for general anesthesia. However, the effect of muscle-relaxant anesthetics on cell activity in gastric cancer is currently unknown. The present study aimed to examine and compare the role of three different muscle-relaxant anesthetics in gastric cancer cells. MATERIALS AND METHODS: Gastric cancer cells (SGC7901 and BGC 823) were treated with a different dose of muscle-relaxant anesthetics, Rocuronium bromide (Rb), Vecuronium bromide (Vb) and Cisatracurium Besilate (CB). Using in vitro models, the effects on gastric cancer cell invasion, growth and migration of various anesthetics were subsequently investigated. RESULTS: We found that Rb increased the growth, invasion and migration of gastric cancer cells SGC7901 and BGC823. However, Vb and CB, as relatively mitigative anesthetics, did not significantly affect gastric cancer cell malignant phenotype at their regular blood concentration. CONCLUSION: Our results are important in selecting the type and dose of anesthetic used for surgery of gastric cancer patients. An understanding of the effect of muscle-relaxant anesthetics and their impact on tumor metastasis is critical, since it provides insight into the appropriate anesthetic strategy that could improve long-term survival in some patients with gastric cancer.


Subject(s)
Androstanols/adverse effects , Atracurium/analogs & derivatives , Neuromuscular Blocking Agents/adverse effects , Stomach Neoplasms/pathology , Vecuronium Bromide/adverse effects , Androstanols/pharmacology , Atracurium/adverse effects , Atracurium/pharmacology , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Neoplasm Invasiveness , Neuromuscular Blocking Agents/pharmacology , Rocuronium , Vecuronium Bromide/pharmacology
18.
Anticancer Res ; 37(8): 4399-4403, 2017 08.
Article in English | MEDLINE | ID: mdl-28739733

ABSTRACT

AIM: To investigate the p53 and O6-methylguanine DNA methyltransferase (MGMT)5' upstream sequence gene promoter regions for single nucleotide polymorphisms and explore the p53 gene 5' upstream sequence consisting of two haplotypes to provide a genetic marker for the incidence of laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We included 96 cases of laryngeal squamous cell carcinoma and 102 controls. We used SNaPshot micro-sequencing analysis of the MGMT promoter region for four single nucleotide polymorphisms and p53 gene 5' upstream sequence loci (rs1625649, rs2287499, rs2287498, rs228749) genotypes. We calculated and compared two groups for genotypic and allelic frequencies, applied HaploView4.2 for computing rs2287499, rs2287498, rs228749 values and haplotype frequencies and tested control loci and Hardy-Weinberg equilibrium. All the experimental data were statistically evaluated using SPSS17.0. The Chi-square test was used for statistical analysis with p<0.05 indicating statistical significance. RESULTS: 5'Upstream single nucleotide polymorphisms rs1625649, rs2287499, rs2287498, rs228749 of p53 were polymorphic in both patient and control groups. There was no statistical significance in frequency distributions for the four loci genotypes when comparing patients and healthy controls (Chi-square values were 4.47, 0.98, 1.67, 4.68, respectively; p>0.05). However, allelic frequencies of the MGMT promoter region locus rs1625649 between patients and healthy control groups were statistically significantly different (chi-square value of 5.77; p<0.05). Differences between allelic frequencies for the p53 gene 5' upstream sequence loci rs2287499, rs2287498 and rs228749 between patients and the healthy control group were not statistically significant (Chi-square values were 1.11,1.56,3.36; p>0.05). Nor were those for the two haplotypes of rs2287499, rs2287498 and rs228749 between patients and the healthy control group were not statistically significant (Chi-square value 1.46, p>0.05). CONCLUSION: MGMT gene polymorphism appears to be associated with the incidence of laryngeal cancer.


Subject(s)
DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Laryngeal Neoplasms/genetics , Polymorphism, Single Nucleotide , Sequence Analysis, DNA/methods , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins/genetics , Adult , Aged , Female , Gene Expression Regulation, Neoplastic , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Promoter Regions, Genetic
19.
Anticancer Res ; 37(8): 4563-4567, 2017 08.
Article in English | MEDLINE | ID: mdl-28739753

ABSTRACT

AIM: To study the value of ultrasound-guided core needle biopsy (CNB) in the diagnosis of T3 or T4 stage laryngeal and hypopharyngeal cancer, which is difficult by routine methods. PATIENTS AND METHODS: Nineteen cases of T3 or T4 stage laryngeal or hypopharyngeal carcinoma with abnormal pharyngeal sensitivity, severe dyspnea, submucous cancer recurrence, cardiovascular and pulmonary dysfunction were reviewed retrospectively from October 2012 to October 2014 in the Yuhuangding Hospital of Qingdao University. Ultrasound-guided coarse needle biopsies were used on primary lesions after assessing the patients with neck-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scan(s). The clinical value of ultrasound-guided CNB in the diagnosis of laryngeal and hypopharyngeal cancer was analyzed. RESULTS: All patients underwent successful pathological diagnosis by ultrasound-guided CNB without any serious complications. Dyspnea, cardiovascular and pulmonary dysfunction did not deteriorate. CONCLUSION: Ultrasound-guided CNB is a highly safe and efficient method for the pathological diagnosis of T3 or T4 stage laryngeal and hypopharyngeal cancer. It should be used especially when the fiberoptic or laryngoscope biopsy are of high risk.


Subject(s)
Biopsy, Large-Core Needle , Hypopharyngeal Neoplasms/diagnosis , Image-Guided Biopsy , Laryngeal Neoplasms/diagnosis , Ultrasonography , Aged , Aged, 80 and over , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Staging , Risk Factors , Tomography, X-Ray Computed
20.
Oncol Rep ; 37(3): 1707-1715, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28112359

ABSTRACT

Phospholipase C (PLC) regulates a number of cellular behaviours including cell motility, cell transformation, differentiation and cell growth. PLC plays a regulatory role in cancer cells partly by acting as signalling intermediates for cytokines such as EGF and interleukins. The current study examined the expression of the PLC isozymes in human breast cancer and corresponding clinical relevance. Transcript levels of human PLC-α, -ß1, -δ, -ε, and -γ1 in human breast cancer tissues were quantitatively determined by real-time PCR. Immunochemical staining was performed for PLC-δ. The clinical relevance was analysed with clinic pathological information. Mammary tissues widely expressed PLC-α, -ß1, -δ, -ε, and -γ1. Significantly high levels of PLC -ß1 and -ε were seen in breast cancer tissues in comparison with normal mammary gland tissues. PLC-γ1 however, showed marginally low levels in tumour tissues. No significant difference was seen in the expression of the PLC isozymes in tumours with lymph node metastases. Moderately and poorly differentiated breast tumours (grade 2 and grade 3) had significantly higher levels of PLC-γ1, compared with well differentiated tumours. High levels of PLC-δ were significantly correlated with a shorter disease-free survival. The altered expression of other isozymes had no correlation with the survival. It is concluded that mammary tissues differentially expressed PLC isozymes. These isozymes have certain implications in the disease development and progression, with PLC-δ showing a significant correlation with shorter disease-free survival.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/enzymology , Gene Expression Regulation, Enzymologic , Phosphoinositide Phospholipase C/metabolism , Phospholipase C beta/metabolism , Phospholipase C delta/metabolism , Phospholipase C gamma/metabolism , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoenzyme Techniques , Isoenzymes , Neoplasm Grading , Phosphoinositide Phospholipase C/genetics , Phospholipase C beta/genetics , Phospholipase C delta/genetics , Phospholipase C gamma/genetics , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Tumor Cells, Cultured
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