Norcantharidin induces G2/M arrest and apoptosis via activation of ERK and JNK, but not p38 signaling in human renal cell carcinoma ACHN cells

Renal cell carcinoma (RCC) is generally acknowledged as the most resistant primary malignancy unresponsive to conventional radiotherapy and chemotherapy treatments. Norcantharidin (NCTD), a therapeutic compound derived from medicinal plants, has been shown to trigger apoptosis, as well as antimetastatic and antioxidant activities in several tumor cells. However, NCTD’s mechanism of antitumor activity in the RCC cell line remains unclear. In this study, we report that NCTD led to a time- and dose-dependent inhibition of cell proliferation. It had also markedly induced apoptosis and G2/M phase cell cycle arrest in a dose-dependent manner by decreasing the expressions of pro-caspase-3, pro-caspase-9, cyclin B1, and pCDC25C while increasing active caspase-3, cleaved-PARP, P21, and pCDC2 levels. Interestingly, NCTD treatment provoked the phosphorylation of extracellular-regulated protein kinase (ERK) and c-Jun-N-terminal kinase (JNK), but not of p38 MAPK. Moreover, SCH772984 and SP600125, ERK and JNK inhibitors, respectively, could partially abolish NCTD-induced apoptosis and G2/M phase cell cycle arrest. Collectively, these findings suggest that NCTD might activate JNK and ERK signaling pathways, consequently inducing apoptosis and G2/M arrest through the modulation of related proteins. This study provided evidence that NCTD is a promising therapeutic drug for the treatment of RCC

The antitumor activity of umbelliferone in human renal cell carcinoma via regulation of the p110γ catalytic subunit of PI3Kγ

Umbelliferone exhibits extensive pharmacological activity, including anti-immunomodulatory, anti-inflammatory and antigenotoxicity activities. However, its antitumor properties still remain unclear in human renal cell carcinoma (RCC) cells. Our results have revealed that treatment of human RCC cells (786-O, OS-RC-2, and ACHN) with umbelliferone reduced cell proliferation in a concentration-dependent manner and induced dose-dependent apoptotic events. In addition, cell cycle analysis determined that umbelliferone treatment induced cell cycle arrest in the G1 phase in a dose-dependent manner. Furthermore, western blotting analysis showed a dose-dependent decrease in Ki67, MCM2, Bcl-2, CDK2, CyclinE1, CDK4, and CyclinD1 and a dose-dependent increase in Bax in RCC cells cultured with umbelliferone. Similarly, umbelliferone exhibited a dose-dependent reduction of p110γ when using western blotting analyses. Taken together, these results provide an insight into the pharmacology regarding the potential application of umbelliferone, which contributes to cell death by decreasing p110γ protein expression

The transcription factor CREB is involved in sorafenib-inhibited renal cancer cell proliferation, migration and invasion

Our previous reports showed that the cyclic-AMP-response element-binding protein (CREB) served as a proto-oncogene in the process of tumorigenesis and mediated the growth and metastatic activity of renal cancer cells. Our study, therefore, explored the role of CREB in sorafenib-inhibited cell proliferation, migration and invasion. Renal cancer cells were cultured in medium containing sorafenib for 12, 24, 48 and 72 h. The MTT assay was used to study the cytotoxic effects of sorafenib. Cell invasion and migration were assayed in wound healing and transwell experiments, respectively. Protein expression levels were evaluated by western blotting. The results show that sorafenib treatment decreased cell viability in a dose- and time-dependent manner. Sorafenib inhibited cell migration and invasion and decreased the expression of MMP-2 and MMP-9. Moreover, addition of the recombinant plasmid pCI-neo/CREB (PN) reversed the sorafenib-induced inhibition of cell proliferation, migration and invasion. These results show that CREB is associated with the sorafenib-induced inhibition of proliferation, migration and invasion

Electrical impedance performance of metal dry bioelectrode with different surface coatings

To improve the electrical impedance performance of bioelectrodes, a novel metal dry bioelectrodes with different coating layers are developed with laser micromilling and electroplating technology. Based on the analysis of the coating layer on the bioelectrode surface, the effect of different coating layers on the electrical impedance performance of bioelectrodes is investigated. The results show that the silver content increases with electroplating time when the silver layer is coated on the bioelectrode surface. However, the decrease of silver layer weight is observed with much longer electroplating time, and the optimal electroplating time is 20 min. Compared with the uncoated bioelectrode, the bioelectrode coated with silver layer exhibits much lower impedance value and better impedance stability. Especially, when the silver-coated bioelectrode is subsequently coated with silver-silver chloride layer, the lowest impedance value and best impedance stability are obtained

Effect of Clozapine on Anti-N-Methyl-D-Aspartate Receptor Encephalitis With Psychiatric Symptoms: A Series of Three Cases

The main clinical manifestations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are acute or subacute seizures, cognition impairment, and psychiatric symptoms. Nowadays, the scheme of antipsychotic therapy for this disease has not been established. This study reports three cases of anti-NMDAR encephalitis with psychiatric symptoms. The anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum were positive. The psychiatric symptoms still existed after intravenous immunoglobulin (IVIG) treatment; thus, clozapine was used for antipsychotic therapy. Case 1 was a 37-year-old man who suffered from bad mood and suicide behaviors for 1 month. Hallucination and delusion still existed after IVIG treatment and hormone therapy, and the symptoms were relieved when given clozapine for 12 months. Case 2 was a 28-year-old man who was admitted to our hospital due to injuring other people and destructive behaviors for 2 days. He showed irritability, bad temper, declined cognition, and severe delusion of persecution after IVIG treatment and hormone therapy, but the psychiatric symptoms disappeared when given clozapine for 3 months. Case 3 was a 23-year-old man who suffered from headache and babbing for 7 days. Symptoms such as irritability, bad temper, babbing, and injuring other people still existed after IVIG treatment and hormone therapy, but they disappeared when given clozapine for 2 months. Therefore, we suggest that during the treatment of anti-NMDAR encephalitis with psychiatric symptoms, if the anti-NMDAR antibodies in CSF and serum were positive, and psychiatric symptoms could not be controlled after IVIG and hormone therapy, clozapine may work

Genome sequences reveal global dispersal routes and suggest convergent genetic adaptations in seahorse evolution

Seahorses have a circum-global distribution in tropical to temperate coastal waters. Yet, seahorses show many adaptations for a sedentary, cryptic lifestyle: they require specific habitats, such as seagrass, kelp or coral reefs, lack pelvic and caudal fins, and give birth to directly developed offspring without pronounced pelagic larval stage, rendering long-range dispersal by conventional means inefficient. Here we investigate seahorses’ worldwide dispersal and biogeographic patterns based on a de novo genome assembly of Hippocampus erectus as well as 358 re-sequenced genomes from 21 species. Seahorses evolved in the late Oligocene and subsequent circum-global colonization routes are identified and linked to changing dynamics in ocean currents and paleo-temporal seaway openings. Furthermore, the genetic basis of the recurring “bony spines” adaptive phenotype is linked to independent substitutions in a key developmental gene. Analyses thus suggest that rafting via ocean currents compensates for poor dispersal and rapid adaptation facilitates colonizing new habitats.Fil: Chunyan, Li. Southern Marine Science and Engineering Guangdong Laboratory; China. Pilot National Laboratory for Marine Science and Technology; China. Chinese Academy of Sciences; República de ChinaFil: Olave, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina. University of Konstanz; AlemaniaFil: Hou, Yali. Chinese Academy of Sciences; República de ChinaFil: Geng, Qi. Chinese Academy of Sciences; República de China. Southern Marine Science and Engineering Guangdong Laboratory; ChinaFil: Schneider, Ralf. University Of Konstanz; Alemania. Helmholtz Centre for Ocean Research Kie; AlemaniaFil: Zeixa, Gao. Huazhong Agricultural University; ChinaFil: Xiaolong, Tu. Allwegene Technologies ; ChinaFil: Xin, Wang. Chinese Academy of Sciences; República de ChinaFil: Furong, Qi. China National Center for Bioinformation; China. University of Chinese Academy of Sciences; ChinaFil: Nater, Alexander. University of Konstanz; AlemaniaFil: Kautt, Andreas F.. University of Konstanz; Alemania. Harvard University; Estados UnidosFil: Wan, Shiming. Chinese Academy of Sciences; República de ChinaFil: Yanhong, Zhang. Chinese Academy of Sciences; República de ChinaFil: Yali, Liu. Chinese Academy of Sciences; República de ChinaFil: Huixian, Zhang. Chinese Academy of Sciences; República de ChinaFil: Bo, Zhang. Chinese Academy of Sciences; República de ChinaFil: Hao, Zhang. Chinese Academy of Sciences; República de ChinaFil: Meng, Qu ,. Chinese Academy of Sciences; República de ChinaFil: Shuaishuai, Liu. Chinese Academy of Sciences; República de ChinaFil: Zeyu, Chen. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Zhong, Jia. Chinese Academy of Sciences; República de ChinaFil: Zhang, He. BGI-Shenzhen; ChinaFil: Meng, Lingfeng. BGI-Shenzhen; ChinaFil: Wang, Kai. Ludong University; ChinaFil: Yin, Jianping. Chinese Academy of Sciences; República de ChinaFil: Huang, Liangmin. Chinese Academy of Sciences; República de China. University of Chinese Academy of Sciences; ChinaFil: Venkatesh, Byrappa. Institute of Molecular and Cell Biology; SingapurFil: Meyer, Axel. University of Konstanz; AlemaniaFil: Lu, Xuemei. Chinese Academy of Sciences; República de ChinaFil: Lin, Qiang. Chinese Academy of Sciences; República de China. Southern Marine Science and Engineering Guangdong Laboratory; China. Pilot National Laboratory for Marine Science and Technology; China. University of Chinese Academy of Sciences; Chin

Cleavage of a pathogen apoplastic protein by plant subtilases activates host immunity

The plant apoplast is a harsh environment in which hydrolytic enzymes, especially proteases, accumulate during pathogen infection. However, the defense functions of most apoplastic proteases remain largely elusive. We show that a newly identified small cysteine rich secreted protein PC2 from the potato late blight pathogen Phytophthora infestans induces immunity in Solanum plants only after cleavage by plant apoplastic subtilisin‐like proteases, such as tomato P69B. A minimal 61‐amino‐acid core peptide carrying two key cysteines, conserved widely in most oomycete species, is sufficient for PC2‐induced cell death. Furthermore, we showed that Kazal‐like protease inhibitors, such as EPI1 produced by P. infestans prevent PC2 cleavage and dampen PC2 elicited host immunity. This study reveals that cleavage of pathogen proteins to release immunogenic peptides is an important function of plant apoplastic proteases

Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop

Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central to the biogenesis, content, and function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes and EVs, the International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 in Baltimore, Maryland, USA, bringing together key opinion leaders and hands-on researchers who were selected on the basis of submitted applications. The workshop was accompanied by two scientific surveys and covered four broad topics: EV biogenesis and release; EV uptake and fusion; technologies and strategies used to study EV membranes; and EV transfer and functional assays. In this ISEV position paper, we synthesize the results of the workshop and the related surveys to outline important outstanding questions about EV membranes and describe areas of consensus. The workshop discussions and survey responses reveal that while much progress has been made in the field, there are still several concepts that divide opinion. Good consensus exists in some areas, including particular aspects of EV biogenesis, uptake and downstream signalling. Areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells. Further research is needed in these key areas, as a better understanding of membrane biology will contribute substantially towards advancing the field of extracellular vesicles.Fil: Russell, Ashley E.. University Johns Hopkins; Estados UnidosFil: Sneider, Alexandra. University Johns Hopkins; Estados UnidosFil: Witwer, Kenneth W.. University Johns Hopkins; Estados UnidosFil: Bergese, Paolo. Università Degli Studi Di Brescia; ItaliaFil: Bhattacharyya, Suvendra N.. Indian Institute of Chemical Biology; IndiaFil: Cocks, Alexander. Cardiff University; Reino UnidoFil: Cocucci, Emanuele. Ohio State University; Estados UnidosFil: Erdbrügger, Uta. University of Virginia; Estados UnidosFil: Falcon Perez, Juan M.. Ikerbasque Basque Foundation for Science; EspañaFil: Freeman, David W.. National Institute On Aging National Institute for Helth ; Estados UnidosFil: Gallagher, Thomas M.. Loyola University Of Chicago; Estados UnidosFil: Hu, Shuaishuai. Technological University Dublin; IrlandaFil: Huang, Yiyao. University Johns Hopkins; Estados Unidos. Southern Medical University; ChinaFil: Jay, Steven M.. University of Maryland; Estados UnidosFil: Kano, Shin-ichi. The University of Alabama at Birmingham School of Medicine; Estados UnidosFil: Lavieu, Gregory. Institut Curie; FranciaFil: Leszczynska, Aleksandra. University of California at San Diego; Estados UnidosFil: Llorente, Alicia M.. Oslo University Hospital; NoruegaFil: Lu, Quan. Harvard University. Harvard School of Public Health; Estados UnidosFil: Mahairaki, Vasiliki. University Johns Hopkins; Estados UnidosFil: Muth, Dillon C.. University Johns Hopkins; Estados UnidosFil: Noren Hooten, Nicole. National Institute On Aging National Institute for Helth ; Estados UnidosFil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Prada, Ilaria. Consiglio Nazionale delle Ricerche; ItaliaFil: Sahoo, Susmita. Icahn School of Medicine at Mount Sinai ; Estados UnidosFil: Schøyen, Tine Hiorth. Uit The Arctic University Of Norway; Noruega. University Johns Hopkins; Estados UnidosFil: Sheng, Lifuy. University of Washington. School of Medicine; Estados UnidosFil: Tesch, Deanna. Shaw University; Estados UnidosFil: Van Niel, Guillaume. No especifíca;Fil: Vandenbroucke, Roosmarijn E.. University of Ghent; BélgicaFil: Verweij, Frederik J.. No especifíca;Fil: Villar, Ana V.. Universidad de Cantabria; EspañaFil: Wauben, Marca. University of Utrecht; Países BajosFil: Wehman, Ann M.. Universität Würzburg; AlemaniaFil: Ardavan, Arzhang. Peking University; ; ChinaFil: Carter, David Raul Francisco. Oxford Brookes University; Reino UnidoFil: Vader, Pieter. University Medical Center Utrecht; Países Bajo

Numerical and experimental studies on a new variable stiffness and damping magnetorheological fluid damper

This article describes a new magnetorheological fluid damper; its damping and stiffness are variable and controllable through the compact structure of two damping units and a spring. The ability of variable stiffness and damping enables it to be used for more effective vibration control in wide-band excitation wave occasions. First, the effective stiffness and output damping force are calculated in theory. Then, the magnetic field is simulated by finite element analysis. After the prototype of the new magnetorheological fluid damper is developed and machined, the damper\u27s performances are tested in a hydraulic actuated MTS machine, including stiffness variability and damping variability in different current. The successful development, numerical calculation, and experimental testing shows that the new damper not only outputs a controllable damping force but also occurs as the great variable stiffness in a certain range, which makes the true design and implementation of the concept of variable stiffness and damping