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1.
Neurointervention ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32070088

RESUMO

Carotid blowout syndrome (CBS) is a fatal complication of head and neck cancer. Endovascular treatment, particularly deconstructive embolization, is effective for CBS, but it might result in thromboembolic events. We report the case of a 57-year-old man with underlying recurrent head and neck cancer who had CBS. The patient received endovascular embolization of the right internal, external, and common carotid arteries. Right internal carotid artery to middle cerebral artery embolic occlusion was noted immediately after the procedure, and left-sided weakness and facial palsy were found. Ipsilateral suprabulbar cervical internal carotid artery puncture was performed under fluoroscopic guidance, and rescue suction thrombectomy was successful. The patient had no significant neurological sequela. Transcarotid intraarterial thrombectomy is a reasonable method for managing postembolization large vessel occlusion, even in the neck, after irradiation.

2.
J Cell Biol ; 219(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31910261

RESUMO

Neuronal GABAergic responses switch from excitatory to inhibitory at an early postnatal period in rodents. The timing of this switch is controlled by intracellular Cl- concentrations, but factors determining local levels of cation-chloride cotransporters remain elusive. Here, we report that local abundance of the chloride importer NKCC1 and timely emergence of GABAergic inhibition are modulated by proteasome distribution, which is mediated through interactions of proteasomes with the adaptor Ecm29 and the axon initial segment (AIS) scaffold protein ankyrin G. Mechanistically, both the Ecm29 N-terminal domain and an intact AIS structure are required for transport and tethering of proteasomes in the AIS region. In mice, Ecm29 knockout (KO) in neurons increases the density of NKCC1 protein in the AIS region, a change that positively correlates with a delay in the GABAergic response switch. Phenotypically, Ecm29 KO mice showed increased firing frequency of action potentials at early postnatal ages and were hypersusceptible to chemically induced convulsive seizures. Finally, Ecm29 KO neurons exhibited accelerated AIS developmental positioning, reflecting a perturbed AIS morphological plastic response to hyperexcitability arising from proteasome inhibition, a phenotype rescued by ectopic Ecm29 expression or NKCC1 inhibition. Together, our findings support the idea that neuronal maturation requires regulation of proteasomal distribution controlled by Ecm29.

3.
Res Vet Sci ; 128: 99-106, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765842

RESUMO

Myxomatous mitral valve disease (MMVD) is the single most important acquired cardiovascular disease of the dog. Much is known about the cellular changes and the contribution of activated myofibroblasts (valve interstitial cells (aVICs) to the valve extra-cellular matrix remodelling characteristic of the disease. However, little is known on how aVIC survival might contribute to disease pathogenesis. This study examined the temporal (disease severity-dependent) and spatial distribution of aVICs in MMVD valves, the expression of a range of apoptosis-related genes in cultured VICs from both normal (quiescent VIC (qVIC) and diseased (aVIC) valves, and the differential effects of doxorubicin treatment, as a trigger of apoptosis, on expression of the same genes. Activated myofibroblasts were identified in normal valves at the valve base only (the area closest to the annulus), and then became more numerous and apparent along the valve length as the disease progressed, with evidence of cell survival at the valve base. There were no significant differences in basal gene expression comparing qVICs and aVICs for CASP3, FAS, BID, BAX, BCL2, CASP8, DDIAS, XIAP and BIRC5. After doxorubicin treatment (2 mM) for 8 h there was significant difference (P < .05) in the expression of BID, BCL2, DDIAS, and CASP8, but when assessed for interactions using a mixed model ANOVA only CASP8 was significantly different because of treatment (P < .05). These data suggest aVIC survival in MMVD valves may be a consequence of heightened resistance of aVICs to apoptosis, but would require confirmation examining expression of the relevant proteins.

4.
Food Sci Nutr ; 7(11): 3797-3807, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763029

RESUMO

Kalimeris indica (L.) Sch. Bip. is a traditional Chinese medicine (TCM) and a portion of food used for cooking in China. It has been demonstrated that an ethanol extract of K. indica has an anti-inflammatory effect by inhibition of nitric oxide (NO) production on murine macrophage RAW264.7 cells after lipopolysaccharide (LPS) induction. In this study, the hepatoprotective effects of the total phenolics of K. indica (TPK), the total triterpenes of K. indica (TTK), and the total flavones of K. indica (TFK) from ethanol extracts of K. indica were evaluated in Bacille Calmette-Guerin (BCG)/LPS-induced liver injury in vivo. The treatments of TPK, TTK, and TFK improved liver injury in mice. Additionally, all treatments significantly not only reduced the hepatic malondialdehyde (MDA) content and hepatic total nitric oxide synthase (tNOS) but also induced the hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. The treatments of TPK and TTK significantly reduced the hepatic inducible nitric oxide synthase (iNOS). The treatments of TPK, TTK, and TFK reduced the serum total bilirubin (T-Bil), and only TFK treatment reduced the serum alanine aminotransferase (ALT). Our results suggest that TPK, TTK, and TFK from ethanol extracts of K. indica might play an essential protective role against BCG/LPS-induced liver injury in vivo.

5.
J Food Drug Anal ; 27(4): 887-896, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31590760

RESUMO

The triggering of gemcitabine (GEM) drug resistance in pancreatic cancer by the receptor for advanced glycation end products (RAGE) has been demonstrated. Hence, finding a safe and effective adjuvant for preventing pancreatic cancer progression is imperative. Quercetin is a flavonoid that is abundant in apples, grapes, red raspberry, and onions and has been reported to inhibit RAGE. This research aimed to investigate the mechanisms of quercetin in regulating cell death and enhancing drug effects through RAGE reduction, especially in GEM-resistant pancreatic cancer cells. Our results showed that silencing RAGE expression by RAGE-specific siRNA transfection significantly increased cell death by apoptosis, autophagy and GEM-induced cytotoxicity by suppressing the PI3K/AKT/mTOR axis in MIA Paca-2 and MIA Paca-2 GEMR cells (GEM-resistant cells). Notably, quercetin showed a dramatic effect similar to RAGE silencing that effectively attenuated RAGE expression to facilitate cell cycle arrest, autophagy, apoptosis, and GEM chemosensitivity in MIA Paca-2 GEMR cells, suggesting that an additional reaction occurred under combined quercetin and GEM treatment. In conclusion, the results demonstrated that the molecular mechanisms of quercetin in regulating apoptosis and autophagy-related pathways and increasing GEM chemosensitivity in pancreatic cancer cells involved inhibition of RAGE expression.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31498944

RESUMO

RATIONALE: Understanding drug-drug interactions and predicting the side effects induced by polypharmacy is difficult because there are few suitable platforms that can predict drug-drug interactions and possible side effects. Hence, developing a platform to identify significant protein markers of drug-drug interactions and their associated side effects is necessary to avoid adverse effects. METHODS: Human liver cells were treated with ethosuximide in combination with cimetidine, ketotifen, metformin, metronidazole, or phenytoin. After sample preparation and extraction, mitochondrial proteins from liver cells were isolated and digested with trypsin. Then, peptide solutions were detected using a nano ultra-performance liquid chromatographic system combined with tandem mass spectrometry. The Ingenuity Pathway Analysis tool was used to simulate drug-drug interactions and identify protein markers associated with drug-induced adverse effects. RESULTS: Several protein markers were identified by the proposed method after liver cells were co-treated with ethosuximide and other drugs. Several of these protein markers have previously been reported in the literature, indicating that the proposed platform is workable. CONCLUSIONS: Using the proposed in vitro platform, significant protein markers of drug-drug interactions could be identified by mass spectrometry. This workflow can then help predict indicators of drug-drug interactions and associated adverse effects for increased safety in clinical prescriptions.

7.
Sci Rep ; 9(1): 10787, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346224

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for symptomatic relief from fever, inflammation, and chronic pain associated with a variety of human disorders. Long-term usage of these drugs can result in severe syndromes; hence, their dose should be controlled carefully and their side effects such as Stevens-Johnson syndrome, toxic epidermal necrolysis, phototoxicity, acute interstitial nephritis, gastrointestinal bleeding, cardiovascular diseases, and liver injury should be considered. Furthermore, the widely used combination of NSAIDs as over-the-counter (OTC) drugs with other drugs leads to adverse drug-drug interactions. Therefore, development of a throughput method to rapidly screen 20 NSAIDs in biological samples is necessary to safeguard human health. In this work, we selected a suitable fluorophore probe coupled with in situ micro-labeling (<2 min) on stainless plate for the fast detection of NSAIDs in plasma samples at the micro-liter level (5 µL) without complicated sample preparation and separation. Every step undertaken in the protocol was also at the micro-liter level; thus, a small amount of blood collected from the human finger will suffice to determine the drug concentration in blood using the proposed method. Furthermore, the proposed method we developed was also matched the modern trends of green analytical chemistry towards miniaturization of analytical methodologies.

9.
J Am Heart Assoc ; 8(13): e012272, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31240976

RESUMO

Background The angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin-converting enzyme inhibitor enalapril in terms of reducing cardiovascular mortality in the PARADIGM-HF (Prospective Comparison of ARNI with angiotensin-converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study. However, the impact of ARNI on cardiac reverse remodeling (CRR) has not been established. Methods and Results We conducted a meta-analysis to compare the effects of ARNI versus angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on CRR indices. We searched databases for studies published between 2010 and 2019 that reported CRR indices following ARNI administration. Effect size was expressed as mean difference (MD) with 95% CIs. Twenty studies enrolling 10 175 patients were included. ARNI improved functional capacity in patients with heart failure (HF) and a reduced ejection fraction (EF), including increasing New York Heart Association functional class (MD -0.79, 95% CI -0.86, -0.71) and 6-minute walking distance (MD 27.62 m, 95% CI 15.76, 39.48). ARNI outperformed angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in terms of CRR indices, with striking changes in left ventricular EF, diameter, and volume. However, there were no significant improvements in indices except left ventricular mass index (MD -3.25 g/m2, 95% CI -3.78, -2.72) and left atrial volume (MD -7.20 mL, 95% CI -14.11, -0.29) in HF patients with preserved EF treated with ARNI. Improvements in CRR indices were observed at 3 months and became more significant with longer follow-up to 12 months. The regression equation for the relationship between left ventricular EF and end-diastolic dimension was y=0.041+0.071x+0.045x2+0.006x3. Conclusions ARNI distinctly improved left ventricular size and hypertrophy compared with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in HF with reduced EF patients, even after short-term follow-up. Patients appeared to benefit more in terms of CRR treated with ARNI as early as possible and for at least 3 months. Further large sample trials are required to determine the effects of ARNI on CRR in HF with preserved EF patients.

10.
Sensors (Basel) ; 19(10)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137853

RESUMO

Cast fixation is a general clinical skill used for the treatment of fractures. However, it may cause many complications due to careless treatment procedures. Currently, swathing a cast for a patient can only be determined by a doctors' experience; however, this cannot be determined by the value of pressure, temperature, or humidity with objective and reliable equipment. When swathing a cast for a patient, the end result is often too tight or too loose. Hence, in this paper we developed a sensor for detecting pressure, temperature, and humidity, respectively. This could provide reliable reference cast data to help physicians to understand the tightness of cast swathing and to adjust the tightness of cast swathing instantly to alleviate a patient's complications caused by excessive pressure or overheating. In this paper, six pressure sensors and one temperature-humidity sensor are used to detect the pressure, temperature, and humidity in an arm swathed with a cast to confirm whether the tightness of the cast is fixing the fracture efficiently, while avoiding causing any damage by using excessive pressure. Currently, the variation in temperature and humidity can be detected by the inflammation of the wound, displaying secretions, and fever in the cast. Based on the experiments, the voltage and power conversion coefficients of the developed sensors could be compensated for by the nonlinear error of the sensor. The experimental results could be instantly displayed on a human interface, such as a smart mobile device. The average skin pressure in a swathed cast was 12.14 g and ranged from 5.0 g to 17.5 g. A few casts exceeded 37.50 g. The abnormal pressure of wrinkles produced during swathing a cast often ranged from 22.50 g to 38.75 g. This shows that cast wrinkles cause pressure on the skin. The pressure caused by cast wrinkles on bone protrusions ranged from 56.5 g to 84.4 g. Compared to other parts that lacked soft skin cushioning, the pressure of cast wrinkles that occurred in the ulna near the protrusion of the wrist bone increased averagely. The pressure error value was less than 2%, the temperature error was less than 1%, and the humidity error was less than 5%. Therefore, they were all in line with the specifications of commercially available products. The six pressure detection points and one temperature and humidity detection point in our newly designed system can accurately measure the pressure, temperature, and humidity inside the cast, and instantly display the corresponding information by mobile APP. Doctors receive reliable reference data and are instantly able to understand the tightness of the swathed cast and adjust it at any time to avoid complications caused by pressure or overheating due to excessive pressure.


Assuntos
Técnicas Biossensoriais , Umidade , Pele/fisiopatologia , Temperatura Ambiente , Humanos , Pressão , Pele/lesões , Smartphone
11.
J Agric Food Chem ; 67(12): 3323-3332, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30832473

RESUMO

High mobility group box 1 (HMGB1) is upregulated in nearly every tumor type. Importantly, clinical evidence also proposed that HMGB1 is particularly increased in metastatic prostate cancer patients. Besides, a growing number of studies highlighted that HMGB1 could be a successful therapeutic target for prostate cancer patients. Glycyrrhizin is a novel pharmacological inhibitor of HMGB1 that may repress prostate cancer metastasis. This research was aimed to investigate the effect of glycyrrhizin on inhibition of HMGB1-induced epithelial-to-mesenchymal transition (EMT), a key step of tumor metastasis, in prostate cancer cells. In this study, HMGB1 knock-downed DU145 prostate cancer cells were used. Silencing the HMGB1 gene expression triggered a change of cell morphology to a more epithelial-like shape, which was accompanied by a reduction of Cdc42/GSK-3ß/Snail and induction of E-cadherin levels estimated by immunoblotting. Furthermore, HMGB1 facilitated cell migration and invasion via downstream signaling, whereas HMGB1 targeting by 10 mM ethyl pyruvate effectively inhibited EMT characteristics. Interestingly, cell migration capacity induced by HMGB1 in DU145 cells was abolished in a dose-dependent effect of 25-200 µM glycyrrhizin treatment. In conclusion, glycyrrhizin successfully inhibited HMGB1-induced EMT phenomenon, which suggested that glycyrrhizin may serves as a therapeutic agent for metastatic prostate cancer.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Proteína HMGB1/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína HMGB1/genética , Humanos , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia , Caramujos/genética , Caramujos/metabolismo
12.
J Cardiovasc Transl Res ; 12(4): 366-377, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30790141

RESUMO

Desmogleins (Dsg2) are the major components of desmosomes. Dsg2 has five extracellular tandem cadherin domains (EC1-EC5) for cell-cell interaction. We had previously confirmed the Dsg2 antibody and its epitope (named KC21) derived from EC2 domain suppressing epithelial-mesenchymal transition and invasion in human cancer cell lines. Here, we screened six peptide fragments derived from EC2 domain and found that KR20, the parental peptide of KC21, was the most potent one on suppressing endothelial colony-forming cell (ECFC) tube-like structure formation. KC21 peptide also attenuated migration but did not disrupt viability and proliferation of ECFCs, consistent with the function to inhibit VEGF-mediated activation of p38 MAPK but not AKT and ERK. Animal studies showed that KC21 peptides suppressed capillary growth in Matrigel implant assay and inhibited oxygen-induced retinal neovascularization. The effects were comparable to bevacizumab (Bev). In conclusion, KC21 peptide is an angiogenic inhibitor potentially useful for treating angiogenesis-related diseases.

13.
Int J Oncol ; 54(4): 1271-1281, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720062

RESUMO

Metformin is commonly used to treat patients with type 2 diabetes and is associated with a decreased risk of cancer. Previous studies have demonstrated that metformin can act alone or in synergy with certain anticancer agents to achieve anti­neoplastic effects on various types of tumors via adenosine monophosphate­activated protein kinase (AMPK) signaling. However, the role of metformin in AMPK­mediated apoptosis of human gastric cancer cells is poorly understood. In the current study, metformin exhibited a potent anti­proliferative effect and induced apoptotic characteristics in human AGS gastric adenocarcinoma cells, as demonstrated by MTT assay, morphological observation method, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase­3/7 assay kits. Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k. Compound C (an AMPK inhibitor) suppressed AMPK phosphorylation and significantly abrogated the effects of metformin on AGS cell viability. Metformin also reduced the phosphorylation of mitogen­activated protein kinases (ERK, JNK and p38). Additionally, metformin significantly increased the cellular ROS level and included loss of mitochondrial membrane potential (ΔΨm). Metformin altered apoptosis­associated signaling to downregulate the BAD phosphorylation and Bcl­2, pro­caspase­9, pro­caspase­3 and pro­caspase­7 expression, and to upregulate BAD, cytochrome c, and Apaf­1 proteins levels in AGS cells. Furthermore, z­VAD­fmk (a pan­caspase inhibitor) was used to assess mitochondria­mediated caspase­dependent apoptosis in metformin­treated AGS cells. The findings demonstrated that metformin induced AMPK­mediated apoptosis, making it appealing for development as a novel anticancer drug for the treating gastric cancer.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Metformina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Oncol Rep ; 41(4): 2549-2557, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720102

RESUMO

Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti­angiogenesis, anti­human immunodeficiency virus (HIV), anti­hepatitis B virus, anti­microbial, anti­inflammatory, and neuro­protective bio­activities. However, the effect of P. cuspidatum extract (PCE) on drug­resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE­treated cisplatin­resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration­ and time­dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3­GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4',6­diamidino­2­phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick­end labeling (TUNEL) double staining. PCE significantly stimulated caspase­9 and ­3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin­1, LC3, Bax and cleaved caspase­3, while it decreased the protein expression of Bcl­2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin­resistant human oral cancer.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Fallopia japonica/química , Neoplasias Bucais/tratamento farmacológico , Extratos Vegetais/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Bucais/patologia , Extratos Vegetais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
15.
Nat Cell Biol ; 21(4): 531-532, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30643186

RESUMO

In the version of this Article originally published, Supplementary Fig. 6j showed incorrect values for the LS and AG4 glutathione samples, and Fig. 5c and Supplementary Fig. 6j did not include all n = 6 samples for the hESC, Y-hiPSC and AG4-ZSCAN10 groups as was stated in the legend. In addition, the bars for hESC, Y-hiPSC, AG4-ZCNAN10, AG4 and LS in Supplementary Fig. 6i and j have been reproduced from Fig. 5b and c, respectively. Fig. 6e was also reproduced in the lower panel of Supplementary Fig. 6h, to enable direct comparison of the data, however this was not explained in the original figure legends. The correct versions of these figures and their legends are shown below, and Supplementary Table 5 has been updated with the source data for all numerical data in the manuscript.

16.
Oncol Rep ; 41(2): 1324-1332, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535448

RESUMO

Gadolinium (Gd) compounds serve as magnetic resonance imaging contrast agents and exert certain anticancer activities. Yet, the molecular signaling underlying the antitumor effect of Gd chloride (GdCl3) on glioma remains unclear. In the present study, we aimed to ascertain the apoptotic mechanisms of GdCl3 on rat glioma C6 cells. Our results demonstrated that GdCl3 significantly reduced cell viability and shrunk cell morphology of C6 cells in a concentration­dependent manner. GdCl3 led to apoptotic C6 cell death as detected by TUNEL staining. An increase in cleaved caspase­3, cleaved caspase­8 and cleaved caspase­9 occurred in GdCl3­treated C6 cells as detected by immunoblotting analysis. The activities of caspase­3, caspase­8 and caspase­9 were increased, and the specific inhibitors of caspase­3/­8/­9 individually reversed cell viability, which caused apoptotic death in C6 cells prior to GdCl3 exposure. GdCl3 also caused an elevation in the cytoplasmic Ca2+ level and reactive oxygen species (ROS) production, as well as the loss of mitochondrial membrane potential (ΔΨm) as shown by flow cytometric analysis in C6 cells. The results from the immunoblotting analysis demonstrated that there were upregulated protein levels of cytochrome c and Bax but a downregulated protein level of Bcl­2 in C6 cells after GdCl3 treatment. Additionally, GdCl3 decreased the protein levels of phosphorylated­extracellular signal­regulated kinases, phosphorylated­c­Jun N­terminal kinase and phosphorylated­p38 mitogen­activated protein kinases in C6 cells. In conclusion, ROS production and MAPKs signaling pathways contribute to GdCl3­induced caspase cascade­mediated apoptosis in C6 cells. Our findings provide a better understanding of the molecular mechanisms underlying the role of GdCl3 in rat glioma C6 cells.

17.
Cancer Lett ; 442: 287-298, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439539

RESUMO

Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Exossomos/metabolismo , Proteínas do Olho/metabolismo , Neoplasias Pulmonares/metabolismo , Fatores de Crescimento Neural/metabolismo , Serpinas/metabolismo , Trombospondina 1/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Exossomos/genética , Exossomos/patologia , Proteínas do Olho/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos SCID , Invasividade Neoplásica , Fatores de Crescimento Neural/genética , Serpinas/genética , Transdução de Sinais , Trombospondina 1/genética , Carga Tumoral , Regulação para Cima
18.
J Cell Physiol ; 234(4): 5153-5162, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30362512

RESUMO

Overexpression of long noncoding RNA (lncRNA) H19 has been observed in various cancers, which indicates that H19 exert important roles in the progression of carcinogenesis. MiR-326 has been reported to play tumor suppressive roles in multiple tumors. Recently, the competing endogenous RNA (ceRNA) hypothesis has implied that lncRNAs might function as molecular sponges for microRNAs in various cancers. However, the roles of H19/miR-326 in human hepatocellular carcinoma (HCC) still remain unclear. The aim of our study was to determine H19/miR-326 expression in HCC cells and investigate their roles in HCC development. We found that H19 was significantly elevated and miR-326 was decreased in HCC cells including Hep3B, HepG2, MHCC-97L, SK-hep1, Hun7, SMCC-7721 compared with LO2 cells, respectively. In the subsequent experiments, we observed that inhibition of H19 can repress HCC cell growth, migration, and invasion in vitro. H19 downregulation can increase miR-326 expression in HCC cells. Meanwhile, miR-326 mimics can also inhibit HCC progression, whereas miR-326 inhibitors exhibited a reverse phenomenon by modulating H19 expression. In addition, a negative association between H19 and miR-326 was predicted and confirmed. Furthermore, the transcription factor TWIST1 has been recognized as a significant regulator in tumor progression. Here, by performing bioinformatics analysis, TWIST1 was identified as a downstream target of miR-326. The findings of our study implied that lncRNA H19 can serve as a ceRNA to sponge miR-326 and modulate TWIST1 levels in HCC pathogenesis. Taken these together, these findings indicated that H19/miR-326/TWIST1 axis was involved in HCC development and can indicate a novel HCC target.

19.
J Appl Gerontol ; 38(2): 207-231, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-28380728

RESUMO

Volunteering is beneficial not only for individuals' well-being but also for society's well-being; yet only a fraction of U.S. citizens regularly engage in volunteer activities. This study examined how underlying motivations are associated with interest in volunteering for individuals in three major life phases: early, middle, and later adulthood. Data were collected from 1,046 adults who volunteered through nonprofit organizations in Nevada (USA). Exploratory factor analysis revealed that community service, career advancement, and well-being were common underlying motivations for individuals across life stages. However, generativity among the later adulthood group, and social networking among the early and middle adulthood groups were unique motivations for volunteering. Regression analysis showed that the community service motivation was significantly associated with individuals' interest in volunteering among all life stages. Simultaneously, generativity for the later adulthood group, and career advancement for the early adulthood group were unique motivations linked to their actual interest in volunteering.

20.
PLoS One ; 13(12): e0208637, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521600

RESUMO

BACKGROUND: In this study, we assessed the association of SBRT (stereotactic body radiotherapy) dose and volume with radiation pneumonitis (RP) risk in lung tumor. METHODS: Relevant articles were identified up to April 2018, using following databases; Medline, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The pooled OR (odds ratio) with 95% CI (confidence interval) data [mean ± SD (standard deviation)] obtained from different studies was analyzed by statistical analysis using a fixed-effects model or a random-effects model when appropriate. RESULTS: The analysis was based on nine observational studies, which were identified based on the study selection criteria. Between RP and non-RP patients, no difference was observed based on age, but significant differences were observed based on planning target volume (PTV), mean ipsilateral lung dose (MLD), total MLD, and V5, V10, V20 and V40 (the percentage of lung volume exceeding 5, 10, 20 and 40 Gy). In addition, PTV >145 cm3, total MLD ≥4.7 Gy, V5 ≥26.8%, V10 >12% and V20 ≥5.8 were associated with RP risk. Overall, the grade assessments of V5 and V20 revealed moderate quality evidence. CONCLUSION: The present study indicated V5 and V20 as major risk factors for RP after SBRT treatment in lung tumor. In addition, it was observed that lung DVH (Dose Volume Histogram) patterns should be assessed more carefully, while predicting RP incidence after SBRT.


Assuntos
Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/epidemiologia , Radioterapia/efeitos adversos , Humanos , Estudos Observacionais como Assunto , Fatores de Risco
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