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H-B Zheng, Y-T Fu, G Wang, L-H Sun, Y-Y Fan, T-W Yang
OBJECTIVE: We aimed to explore the effect of hyperphosphorylation of Tau on cognitive function of propofol-anesthetized rats. MATERIALS AND METHODS: Thirty 2-month-old male Wistar rats weighing 180-220 g were randomly divided into 3 groups (n=10): group of treating with saline (C group), group of treating with propofol for 1 hour (P1) and 24 h (P24 group). The cognitive function of rats was tested by Morris water maze before and 1 h or 24 h after drug administration...
June 2018: European Review for Medical and Pharmacological Sciences
Jae-Rim Heo, Soo-Min Kim, Kyung-A Hwang, Ji-Houn Kang, Kyung-Chul Choi
Resveratrol, a dietary product present in grapes, vegetables and berries, regulates several signaling pathways that control cell division, cell growth, apoptosis and metastasis. Malignant melanoma proliferates more readily in comparison with any other types of skin cancer. In the present study, the anti‑cancer effect of resveratrol on melanoma cell proliferation was evaluated. Treating A375SM cells with resveratrol resulted in a decrease in cell growth. The alteration in the levels of cell cycle‑associated proteins was also examined by western blot analysis...
June 15, 2018: International Journal of Molecular Medicine
Zhang-Ming Chen, Lei Huang, Miao-Miao Li, Lei Meng, Song-Cheng Ying, A-Man Xu
Gastric cancer (GC) is one of the most common digestive malignancies globally, and the prognosis of patients with advanced tumors remains poor. Isocryptotanshinone (ICTS), isolated from Salvia miltiorrhiza, was found to inhibit the proliferation of lung and breast cancer cells. However, whether ICTS has anticancer activities against GC is unknown. In the present study, we reported that the proliferation of GC cells was inhibited by ICTS in a dose- and time-dependent manner. After treatment with ICTS, GC cells were arrested in the G1/G0 phase of cell cycle and the apoptotic cells were induced in a dose-dependent manner...
June 18, 2018: Scientific Reports
Raj K Gopal, Sarah E Calvo, Angela R Shih, Frances L Chaves, Declan McGuone, Eran Mick, Kerry A Pierce, Yang Li, Andrea Garofalo, Eliezer M Van Allen, Clary B Clish, Esther Oliva, Vamsi K Mootha
Renal oncocytomas are benign tumors characterized by a marked accumulation of mitochondria. We report a combined exome, transcriptome, and metabolome analysis of these tumors. Joint analysis of the nuclear and mitochondrial (mtDNA) genomes reveals loss-of-function mtDNA mutations occurring at high variant allele fractions, consistent with positive selection, in genes encoding complex I as the most frequent genetic events. A subset of these tumors also exhibits chromosome 1 loss and/or cyclin D1 overexpression, suggesting they follow complex I loss...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jean Christopher Chamcheu, Islam Rady, Roxane-Cherille N Chamcheu, Abu Bakar Siddique, Melissa B Bloch, Sergette Banang Mbeumi, Abiola S Babatunde, Mohammad B Uddin, Felicite K Noubissi, Peter W Jurutka, Yong-Yu Liu, Vladimir S Spiegelman, G Kerr Whitfield, Khalid A El Sayed
Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola ( Annona muricata ), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431...
June 16, 2018: International Journal of Molecular Sciences
Naseruddin Höti, Tamara Jane Johnson, Wasim H Chowdhury, Ronald Rodriguez
We elucidate the role of p21/Waf-1, a cyclin-dependent kinase inhibitor, on the oncolytic infection and replication cycle of adenovirus by studying both mRNA and adenoviral proteins expression. We found that infection in the absence of p21 causes a significant increase in adenoviral genomes and late gene expression. Similarly, the oncolytic adenoviral infected p21−/− cells have earlier formation of replication foci and robust replication kinetics that were not observed in the wild type p21/Waf-1 intact cells...
June 15, 2018: Cancers
Lakshmi Dhevi Nagarajha Selvan, Ravikanth Danda, Anil K Madugundu, Vinuth N Puttamallesh, Gajanan J Sathe, Uma Maheswari Krishnan, Vikas Khetan, Pukhraj Rishi, Thottethodi Subrahmanya Keshava Prasad, Akhilesh Pandey, Subramanian Krishnakumar, Harsha Gowda, Sailaja V Elchuri
Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer...
June 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shakila Sabir, Ammara Saleem, Muhammad Furqan Akhtar, Muhammad Saleem, Moosa Raza
Finding a radical cure for diabetes has reached paramount importance in medicine due to the widespread prevalence of the disease. A substantial reduction in insulin-secreting beta cells is evident in diabetes. The failure of cyclin-dependent kinases (CDKs) and cyclins to access the nucleus is responsible for quiescence or senescence in human and rodent beta cells. The augmentation of beta cell proliferation is supposed to reverse diabetes. This concept has inspired the discovery of newer drugs that encourage the proliferation of beta cells...
June 18, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Fabienne Lampert, Diana Stafa, Algera Goga, Martin Varis Soste, Samuel Gilberto, Natacha Olieric, Paola Picotti, Markus Stoffel, Matthias Peter
In yeast, the glucose-induced degradation-deficient (GID) E3 ligase selectively degrades superfluous gluconeogenic enzymes. Here we identified all subunits of the mammalian GID/CTLH complex and provide a comprehensive map of its hierarchical organization and step-wise assembly. Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. Deletions of multiple GID subunits compromise cell proliferation, and this defect is accompanied by deregulation of critical cell cycle markers such as the retinoblastoma (Rb) tumor suppressor, phospho-Histone H3 and Cyclin A...
June 18, 2018: ELife
Junyan Sun, Ying Guo, Qiuwan Zhang, Shixia Bu, Boning Li, Qian Wang, Dongmei Lai
Psychological stress, which exerts detrimental effects on human reproduction, may compromise the meiotic competence of oocytes. Meiotic resumption, germinal vesicle breakdown (GVBD), is the first milestone to confer meiotic competence to oocytes. In the practice of assisted reproductive technology (ART), the timing for GVBD is associated with the rates of cleavage and blastocyst formation. However, whether chronic stress compromises oocyte competence by influencing GVBD and the underlying mechanisms are unclear...
June 18, 2018: Cell Cycle
Rongni He, Wei Huang, Yaowei Huang, Miaojing Xu, Pingping Song, Yinwei Huang, Huifang Xie, Yafang Hu
Parkinson's disease (PD) is one of the most affected neurodegenerative diseases in the world. Deregulation of cyclin-dependent kinase 5 (Cdk5) is believed to play an important role in neurodegenerative diseases including PD. p25 is a cleavage peptide of p35, a physiologic activator of Cdk5. p25 combines to Cdk5 and leads to the hyperactivity of Cdk5, which in turn hyperphosphorylates downstream substrates and leads to neuroinflammation and apoptosis of neurons. Previously, we have demonstrated that adeno-associated virus serotype-9 (AAV9) mediated Cdk5 inhibitory peptide (CIP) inhibits the activity of Cdk5/p25 complex and alleviates pathologic and behavioral changes in Alzheimer's disease mouse model...
2018: Frontiers in Aging Neuroscience
A AlFakeeh, C Brezden-Masley
Endocrine therapy, a major modality in the treatment of hormone receptor (hr)-positive breast cancer (bca), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in bca is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)-targeted therapy. The resistance pathways involve extensive cross-talk between er and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2 (her2), and insulin-like growth factor 1 receptor] and their downstream signalling pathways-most notably pi3k/akt/mtor and mapk...
June 2018: Current Oncology
Seung-Shick Shin, Dae-Hwa Noh, Byungdoo Hwang, Jo-Won Lee, Sung Lyea Park, Sung-Soo Park, Bokyung Moon, Wun-Jae Kim, Sung-Kwon Moon
Background: Although the diverse biological properties of nanoparticles have been studied intensively, research into their mechanism of action is relatively rare. In this study, we investigated the molecular mechanisms of the anticancer activity of heterometallic Au@Pt-nanoseeds (NSs) against bladder cancers. Materials and methods: Mode of action of Au@Pt-NSs was investigated through MTT assay, flow cytometry analysis, Western immunoblots, real-time qPCR, wound-healing migration and invasion assays, zymography, and electrophoretic mobility shift assay (EMSA)...
2018: International Journal of Nanomedicine
Qi Zhang, Ying Xu, Rong Chang, Dewen Tong, Xingang Xu
This essay focuses on transmissible gastroenteritis virus (TGEV), which is an enteropathogenic virus related to contagious and acute diseases in suckling piglets. Previous literature suggests that the TGEV nucleocapsid protein (N) plays a significant role in viral transcriptional process, however, there is a need to examine other functions of TGEV N protein in the porcine intestinal epithelial cell (IEC) which is the target cell of TGEV. In the present study, we investigated the degradation, subcellular localisation, and function of TGEV N protein by examining its effects on cycle progression, endoplasmic reticulum (ER) stress, interleukin-8 (IL-8) expression, and cell survival...
June 12, 2018: Research in Veterinary Science
Tingting Lv, Liang Xu, Guolin Wu, Cailong Li, Yibo Wen, Tao Zhang, Haijun Chen, Yu Gao
Chemotherapy is currently one of the promising therapeutic methods for non-small-cell lung cancer (NSCLC), but the emergence of multidrug resistance (MDR) is the greatest obstacle to efficient drug delivery for successful chemotherapy. Nanotechnology-based drug delivery holds great promise to promote intracellular drug delivery to reverse MDR. In this work, we used our previously synthesized ursolic acid (UA) derivative, FZU-03,010 (F3), to prepare nanodrugs of F3 with different architectures and study the role of the structure on the physiochemical properties and the biological effects against A549 and its PTX-resistant A549/PTX lung cancer cells...
June 13, 2018: European Journal of Pharmaceutical Sciences
Hung-Chuan Chiu, Wei-Ru Huang, Tsai-Ling Liao, Pei-I Chi, Brent L Nielsen, Jyung-Hurng Liu, Hung-Jen Liu
The avian reovirus (ARV) p17 protein is a nucleocytoplasmic shuttling protein. Although we have demonstrated that p17 causes cell growth retardation via activation of p53, the precise mechanisms remains unclear. This is the first report that ARV p17 possesses broad inhibitory effects on cell-cycle CDKs, cyclins, CDK/cyclin complexes, and CDK activating kinase (CAK) activity in various mammalian, avian, and cancer cell lines. Suppression of CDK activity by p17 occurs by direct binding to CDKs, cyclins, and CDK/cyclin complexes, transcriptional downregulation of CDKs, cytoplasmic retention of CDKs and cyclins, and inhibition of CAK activity by promoting p53/cyclin H interaction...
June 15, 2018: Journal of Biological Chemistry
Yingjie Xu, Jie Xu, Keli Ge, Qingwu Tian, Peng Zhao, Yunliang Guo
Atherosclerosis (AS) is the key cause of many cardiovascular and cerebrovascular diseases. The inflammatory response and lipid metabolism disorders contribute to the development and progression of AS. This work aims to study the anti-inflammatory effect and mechanism of low molecular weight fucoidan (LMWF) obtained from Saccharina japonica on atherosclerosis in apoE-knockout mice. The experimental results showed that LMWF statistically decreased the levels of triglyceride (TRIG) and oxidative low-density lipoproteins (ox-LDL) and stabilized established atherosclerotic lesions...
June 12, 2018: International Journal of Biological Macromolecules
Wang Jiashi, Qiu Chuang, Zhang Zhenjun, Wang Guangbin, Li Bin, He Ming
Osteosarcoma is an aggressive bone tumor primarily affecting children and adolescents. Its cause is not yet fully understood, and there is an urgent need for more effective treatment. In the present study we identified several miRNAs whose expression is altered in osteosarcoma compared to adjacent normal tissue. Moreover, expression levels of one of those miRNAs, miR-506-3p, correlated negatively with expression of RAB3D (a Ras-related protein). Suppression of miR-506-3p in osteosarcoma led to increased expression of RAB3D, which in turn led to increased CDK4 (cyclin-dependent kinase 4) and MMP9 (matrix metalloprotein 9) activities...
June 10, 2018: Aging
Eleonora Sementino, Craig W Menges, Yuwaraj Kadariya, Suraj Peri, Jinfei Xu, Zemin Liu, Richard G Wilkes, Kathy Q Cai, Frank J Rauscher, Andres J Klein-Szanto, Joseph R Testa
Malignant mesothelioma (MM) is a therapy-resistant cancer arising primarily from the lining of the pleural and peritoneal cavities. The most frequently altered genes in human MM are cyclin-dependent kinase inhibitor 2A (CDKN2A), which encodes components of the p53 (p14ARF) and RB (p16INK4A) pathways, BRCA1-associated protein 1 (BAP1), and neurofibromatosis 2 (NF2). Furthermore, the p53 gene (TP53) itself is mutated in ~15% of MMs. In many MMs, the PI3K-PTEN-AKT-mTOR signaling node is hyperactivated, which contributes to tumor cell survival and therapeutic resistance...
June 15, 2018: Journal of Cellular Physiology
Allison Shanks, Julia Choi, Vinit Karur
Neuroendocrine tumors are a rare subset of breast carcinomas. Commonly, platinum-based doublet is used as a systemic treatment option for high-grade neuroendocrine carcinomas from lung, gastrointestinal, and genitourinary origins. In comparison to other breast cancers, neuroendocrine carcinomas have unique genomic features and different treatment strategies. We present a patient with high-grade neuroendocrine carcinoma of the breast who had a successful and durable response to the cyclin D-dependent kinase (CDK) 4/6 inhibitor palbociclib in conjunction with endocrine therapy...
July 2018: Proceedings of the Baylor University Medical Center
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