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Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, Virginia L Scofield
Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson's disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells...
2016: Parkinson's Disease
Dan Wang, Yi-Ming Chen, Miao-Hua Ruan, Ai-Hua Zhou, Yan Qian, Chao Chen
Elevated plasma levels of homocysteine have been implicated in neurodevelopmental and neurodegenerative disorders in human studies. Although the molecular mechanisms underlying the effects of homocysteine (Hcy) cytotoxicity on the nervous system are not yet fully unknown, induction of DNA interstrand cross-links and inhibition of neural stem cells (NSCs) survival may be involved. The objective of our study was to investigate the effects of Hcy on DNA interstrand cross-links in NSCs, and to explore its possible mechanisms...
October 20, 2016: Neuroscience Letters
A D B Vliegenthart, R A Kimmitt, J H Seymour, N Z Homer, J I Clarke, M Eddleston, A Gray, D M Wood, P I Dargan, J G Cooper, D J Antoine, D J Webb, S C Lewis, D N Bateman, J W Dear
: Acetaminophen (paracetamol-APAP) is the commonest cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analysed from discovery (N=116) and validation (N=150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI...
October 22, 2016: Clinical Pharmacology and Therapeutics
Hye-Yeon Seok, Dong-Hyuk Woo, Linh Vu Nguyen, Huong T Tran, Vaishali N Tarte, Syed Muhammad Muntazir Mehdi, Sun-Young Lee, Yong-Hwan Moon
AtNAP , an Arabidopsis NAC transcription factor family gene, functions as a negative regulator via transcriptional repression of AREB1 in salt stress response. AtNAP is an NAC family transcription factor in Arabidopsis and is known to be a positive regulator of senescence. However, its exact function and underlying molecular mechanism in stress responses are not well known. Here, we investigated functional roles of AtNAP in salt stress response. AtNAP expression significantly increased at the seedling stage, with higher expression in both shoots and roots under NaCl, mannitol, and ABA treatments...
October 21, 2016: Planta
Alessandro Minarini, Silvia Ferrari, Martina Galletti, Nina Giambalvo, Daniela Perrone, Giulia Rioli, Gian Maria Galeazzi
N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder...
October 21, 2016: Expert Opinion on Drug Metabolism & Toxicology
Sophie Laguesse, Nadege Morisot, Khanhky Phamluong, Dorit Ron
We previously reported that the kinase AKT is activated in the nucleus accumbens (NAc) of rodents in response to excessive consumption of alcohol. One of the important downstream targets of AKT is the mammalian Target Of Rapamycin in Complex 1 (mTORC1), which was also activated by alcohol intake. mTORC1 controls dendritic protein translation, and we showed that the mTORC1-dependent translational machinery is activated in the NAc in response to alcohol intake. Importantly, systemic or intra-NAc inhibition of the AKT/mTORC1 pathway attenuated alcohol-drinking behaviors...
October 20, 2016: Addiction Biology
Thomas Martini, Christian Gilfrich, Roman Mayr, Maximilian Burger, Armin Pycha, Atiqullah Aziz, Michael Gierth, Christian G Stief, Stefan C Müller, Florian Wagenlehner, Jan Roigas, Oliver W Hakenberg, Florian Roghmann, Philipp Nuhn, Manfred Wirth, Vladimir Novotny, Boris Hadaschik, Marc-Oliver Grimm, Paul Schramek, Axel Haferkamp, Daniela Colleselli, Birgit Kloss, Edwin Herrmann, Margit Fisch, Matthias May, Christian Bolenz
INTRODUCTION: Guidelines recommend neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in patients with urothelial carcinoma of the bladder in clinical stages T2-T4a, cN0M0. We examined the frequency and current practice of NAC and sought to identify predictors for the use of NAC in a prospective contemporary cohort. MATERIALS AND METHODS: We analyzed prospective data from 679 patients in the PROMETRICS (PROspective MulticEnTer RadIcal Cystectomy Series 2011) database...
September 19, 2016: Clinical Genitourinary Cancer
Takaki Yoshikawa, Tsutomu Sato, Takanobu Yamada, Toru Aoyama, Takashi Ogata, Haruhiko Cho
Adjuvant chemotherapy aims to eradicate residual micro-metastatic tumor cells existing at distant sites outside the surgical field. The current standard adjuvant chemotherapy is S-1 for 1 year or capecitabine plus oxaliplatin for 6 months after D2 gastrectomy. However, there are some rooms in the overall survival of Stage III. Neoadjuvant chemotherapy(NAC)is a promising approach that combines intensive chemotherapy with high compliance; however, it is under development in Japan. Two JCOG phase II trials suggested that NAC was effective for bulky nodal disease...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Chihiro Oda-Yamamizo, Nobutaka Mitsuda, Shingo Sakamoto, Daisuke Ogawa, Masaru Ohme-Takagi, Akemi Ohmiya
No abstract text is available yet for this article.
October 19, 2016: Scientific Reports
Yue Yu, Ning Cui, Heng-Yu Li, Yan-Mei Wu, Lu Xu, Min Fang, Yuan Sheng
BACKGROUND: To evaluate the accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer patients with axillary lymph node (ALN) metastasis. METHODS: A total of 122 patients with operable breast cancer were enrolled in this single-center retrospective study. Eighty patients were clinically diagnosed with a positive axillary lymph node (ALN) via imaging or physical examination (including 66 patients with biopsy-proven metastasis)...
October 18, 2016: BMC Cancer
Hideaki Kaneko, Shuo Zhang, Miho Sekiguchi, Takuya Nikaido, Koshi Makita, Jiro Kurata, Shin-Ichi Konno
STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate activity of the nucleus accumbens (NAc) in response to lumbar mechanical stimulation in patients with chronic low back pain (cLBP) using functional magnetic resonance imaging (fMRI). SUMMARY OF BACKGROUND DATA: Although a modified activity of the NAc was characterized in cLBP patients, its pathological significance has yet to be determined. We hypothesized that NAc activation in response to pain might differ depending on the extent of psychiatric problems, which might be associated with the affective/motivational background of chronic pain...
October 17, 2016: Spine
Abhishek Srivastava, Vijender Panduga, Ramanatha Saralaya, Prabhakar Kr, Shahul Hameed, Suresh Solapure, Vinayak Hosagrahara
During the course of metabolic profiling of lead Compound 1, glutathione (GSH) conjugates were detected in rat bile, suggesting the formation of reactive intermediate precursor(s). This was confirmed by the identification of GSH and N-acetylcysteine (NAC) conjugates in microsomal incubations. It was proposed that bioactivation of Compound 1 occurs via the formation of a di-iminoquinone reactive intermediate through the involvement of the C-2 and C-5 nitrogens of the pyrimidine core. To further investigate this hypothesis, structural analogues with modifications at the C-5 nitrogen were studied for metabolic activation in human liver microsomes supplemented with GSH/NAC...
October 18, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Li Zhang, Si-Yuan Kong, Zhao-Qing Zheng, Xiao-Xiao Meng, Ji-Ling Feng, Hong-Sheng Tan, Yuan-Zhi Lao, Lian-Bo Xiao, Hong-Xi Xu
Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation...
October 12, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Takashi Ishida, Sachie Suzuki, Chen-Yi Lai, Satoshi Yamazaki, Shigeru Kakuta, Yoichiro Iwakura, Masanori Nojima, Yasuo Takeuchi, Masaaki Higashihara, Hiromitsu Nakauchi, Makoto Otsu
Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs)...
October 18, 2016: Stem Cells
Michael P Saddoris
Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggesting that the self-administration experience induces long-lasting neuroplastic alterations in the mesolimbic DA circuit. To understand these changes at the terminal level, rats were allowed to self-administer either cocaine intravenously (∼1 mg/kg per infusion) or water to a receptacle (control) in 2-h sessions over 14 days, followed by 30 days of enforced abstinence...
September 2016: ENeuro
Ruijun Su, Xiaoting Jin, Weifang Zhang, Zhuoyu Li, Xiaona Liu, Jie Ren
Many epidemiological investigations have consistently demonstrated the immunotoxicity of fine particulate matter (PM2.5), but the underlying molecular mechanism remains unclear and needs to be elucidated. In this work, the immune cells, including pulmonary macrophages of SD rats and Raw264.7 cells, were applied to further investigate the effect of PM2.5 on cell autophagy of macrophages, thus clarified the possible molecular mechanism of immunotoxicity caused by PM2.5. SD rats were exposed to summer (0.2, 0...
October 14, 2016: Chemosphere
Koichi Okamoto, Itasu Ninomiya, Yoshinao Ohbatake, Atsushi Hirose, Tomoya Tsukada, Shinichi Nakanuma, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Masafumi Inokuchi, Hisatoshi Nakagawara, Tomoharu Miyashita, Tajima Hidehiro, Hiroyuki Takamura, Sachio Fushida, Tetsuo Ohta
Cancer stem cells (CSCs) have self-renewal and pluripotency capabilities and contribute to cancer progression and chemoresistance. It has been proposed that the treatment resistance and heterogeneity of CSCs are deeply involved in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to identify the influence of the expression status of the CSC markers CD44 and CD133 on chemotherapeutic efficacy and prognosis in ESCC patients who underwent radical esophagectomy after neoadjuvant chemotherapy (NAC)...
September 28, 2016: Oncology Reports
Liying Guo, Kai Tan, Hao Wang, Xuan Zhang
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the second cause of cancer-related deaths around the world. Pterostilbene (PTE), is a natural analog of resveratrol, possessing diverse pharmacological activities. In the present study, we aimed to examine the effect of PTE on tumor growth in mouse models of HCC and to elucidate the possible molecular mechanism in vivo and in vitro. We showed that PTE dose-dependently suppressed tumor growth in mice induced by diethylnitrosamine plus carbon tetrachloride, as evidenced by a decrease in the number of tumors and in the maximum size of the tumors...
October 5, 2016: Oncology Reports
Guangyong Chen, Yangdong Han, Wang He, Feng Liang
In the present study, we evaluated the protective effects of amentoflavone (AMF) against high-fat (HF) diet-induced metabolic dysfunction and focused on the influence of AMF on adipogenic differentiation during 3T3-L1 adipocyte differentiation. For this purpose, male Wistar rats were fed a HF diet or a HF diet with AMF (10 or 50 mg/kg). We found that AMF protected against HF diet-induced metabolic dysfunction in a dose-dependent manner, as evidenced by a decrease in the fasting blood glucose levels, fasting insulin levels and the homeostatic model assessment-insulin resistance index (HOMA‑IR), as well as by a decrease in the glucose level, as shown by the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test...
October 14, 2016: International Journal of Molecular Medicine
Ali M Mokhtar, Ahmed I Elsakka, Hassan M Ali
BACKGROUND: Anxiety is a concern in obstetrics, especially in preeclamptic mothers. Sedation is not commonly used in parturients for fear of adverse neonatal effect. We investigated maternal and neonatal outcome of midazolam as an adjuvant to spinal anesthesia for elective cesarean delivery. METHODS: A prospective randomized controlled trial, in which eighty preeclamptic parturients received either an intravenous dose of 0.035 mg/kg of midazolam or an equal volume of normal saline, 30 min before spinal anesthesia...
September 2016: Anesthesia, Essays and Researches
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