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Yuichi Miura, Mizuho Morooka, Nicolas Sax, Rahul Roychoudhuri, Ari Itoh-Nakadai, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Susumu Satomi, Mitsuyo Matsumoto, Kazuhiko Igarashi, Akihiko Muto
BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yanpeng Ci, Xiaoning Li, Maorong Chen, Jiateng Zhong, Brian J North, Hiroyuki Inuzuka, Xi He, Yu Li, Jianping Guo, Xiangpeng Dai
Wnt signaling has emerged as a major regulator of tissue development by governing the self-renewal and maintenance of stem cells in most tissue types. As a key upstream regulator of the Wnt pathway, the transmembrane E3 ligase ZNRF3 has recently been established to play a role in negative regulation of Wnt signaling by targeting Frizzled (FZD) receptor for ubiquitination and degradation. However, the upstream regulation of ZNRF3, in particular the turnover of ZNRF3, is still unclear. Here we report that ZNRF3 is accumulated in the presence of proteasome inhibitor treatment independent of its E3-ubiquitin ligase activity...
March 1, 2018: Protein & Cell
Marieke Dubois, Katia Selden, Alexis Bediée, Gaëlle Rolland, Nicolas Baumberger, Sandra Noir, Lien Bach, Geneviève Lamy, Christine Granier, Pascal Genschik
The plant cell cycle is tightly regulated by factors that integrate endogenous cues and environmental signals to adapt plant growth to changing conditions. Under drought, cell division in young leaves is blocked by an active mechanism, reducing the evaporative surface and conserving energy resources. The molecular function of cyclin-dependent kinase-inhibitory proteins (CKIs) in regulating the cell cycle has already been well studied, but little is known about their involvement in cell cycle regulation under adverse growth conditions...
February 22, 2018: Plant Physiology
Li Gao, Ke-Xin Wang, Yu-Zhi Zhou, Jian-Song Fang, Xue-Mei Qin, Guan-Hua Du
Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of "main active compound-based network pharmacology" to explore the anti-cancer mechanism of CKI...
January 12, 2018: Scientific Reports
Yingshi Zhang, Fuhai Hui, Yue Yang, Haixiao Chu, Xiaochun Qin, Mingyi Zhao, Qingchun Zhao
Objective: To assess the comparative efficacy and safety of combination treatment with Compound Kushen Injection (CKI) and transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify the best conditions for using CKI. Materials and Methods: We performed a network meta-analysis based on randomized controlled trials. We searched databases for studies published by August 2017...
December 5, 2017: Oncotarget
Fabien Stucker, Belen Ponte, Victoria De la Fuente, Cyrielle Alves, Olivier Rutschmann, Sebastian Carballo, Nicolas Vuilleumier, Pierre-Yves Martin, Thomas Perneger, Patrick Saudan
BACKGROUND: We aimed to describe clinical characteristics of patients with community-acquired acute kidney injury (CA-AKI), the effectiveness of initial management of CA-AKI, its prognosis and the impact of medication on its occurrence in patients with previous chronic kidney injury (CKI). METHODS: We undertook a prospective observational study within the Emergency Department (ED) of a University Hospital, screening for any patient >16 years admitted with an eGFR <60 ml/mn/1...
December 29, 2017: BMC Nephrology
Lixiu Yu, Ying Zhou, Yu Yang, Furong Lu, Yeqin Fan
Objective: The efficacy and safety of Compound Kushen Injection (CKI) on advanced colon cancer remain controversial. We undertook a systematic meta-analysis of randomized controlled clinical studies on this issue. Methods: A comprehensive literature search was conducted by searching the following electronic databases: PubMed, Cochrane, Chinese Biological Medical disc, Chinese National Knowledge Infrastructure, and Wan-Fang Database in China by the end of January 31, 2017, without language restriction...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Hanan Mofty, Khaled Alzahrani, Fiona Carley, Sophie Harper, Arun Brahma, Leon Au, Debbie Morley, M Chantal Hillarby
Purpose: The purpose of this study was to assess UV corneal crosslinking (CXL) treatment outcomes for keratoconus by evaluating the corneal regularity in patients through follow-up using the Oculus Pentacam. Patients and methods: A total of 18 eyes from CXL patients with keratoconus were studied before and after CXL treatment, and six eyes from six patients who were not treated with CXL served as controls. Treated patients had Pentacam images taken before CXL treatment and regularly 3 months post treatment up to the 12th month...
2017: Clinical Ophthalmology
Taku Chibazakura, Yuichi Asano
Cyclin-cyclin dependent kinase (CDK) complex is negatively regulated by interaction with CDK inhibitors (CKIs). p27 protein is a major CKI in mammals and its down-regulation correlates with malignant transformation. However, some cancer cells express p27 at normal level, suggesting not only quantitative but qualitative control of p27, although little is known about such control. We analyzed the interaction between p27 and cyclin A (CycA)-CDK complex in living human cell lines, using a split yellow fluorescent protein (YFP) system in which the YFP fluorescence solely depends on p27-CycA binding...
December 2017: Bioscience, Biotechnology, and Biochemistry
Adelle A Vandersteen, Graeme W Howe, Barbara Sherwood Lollar, Ronald Kluger
The rate of decarboxylation of 2,4-dimethoxybenzoic acid (1) is accelerated in parallel to the extent that the carboxyl group acquires a second proton (1H(+)). However, the conjugate acid would resist C-C bond breaking as that would lead to formation of doubly protonated CO2. An alternative via formation of a higher-energy protonated phenyl tautomer (2H(+)) prior to C-C bond breaking would produce protonated CO2, an energetically inaccessible species that can be avoided by transfer of the carboxyl proton to water in the same step...
October 13, 2017: Journal of the American Chemical Society
Kazem Amanzadeh, Roghiyeh Elham, Ebrahim Jafarzadepur
PURPOSE: To assess the changes in visual acuity and topographic indices after implantation of single-segment Intacs. METHODS: Forty-two keratoconic eyes received Femtosecond-assisted single-segment Intacs. Uncorrected distance visual acuity (UDVA) and best spectacle corrected visual acuity (BSCVA), refractive error, keratometry (K1, K2, Km, and KMax.), and seven Pentacam measured topographical indices; index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), central keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration (IHD), and minimum radius of curvature (R Min) were assessed 4 months after surgery...
September 2017: Journal of Current Ophthalmology
Yuta Shinohara, Yohei M Koyama, Maki Ukai-Tadenuma, Takatsugu Hirokawa, Masaki Kikuchi, Rikuhiro G Yamada, Hideki Ukai, Hiroshi Fujishima, Takashi Umehara, Kazuki Tainaka, Hiroki R Ueda
Temperature compensation is a striking feature of the circadian clock. Here we investigate biochemical mechanisms underlying temperature-compensated, CKIδ-dependent multi-site phosphorylation in mammals. We identify two mechanisms for temperature-insensitive phosphorylation at higher temperature: lower substrate affinity to CKIδ-ATP complex and higher product affinity to CKIδ-ADP complex. Inhibitor screening of ADP-dependent phosphatase activity of CKIδ identified aurintricarboxylic acid (ATA) as a temperature-sensitive kinase activator...
September 7, 2017: Molecular Cell
Satya Prakash Yadav, Prashant Kumar Singh, Pradeep Sharma, Naseer Iqbal, Punit Kaur, Sujata Sharma, Tej P Singh
Proliferating cell nuclear antigen (PCNA) acts as a sliding clamp to support DNA replication and repair. The structure of PCNA from Leishmania donovani (LdPCNA) has been determined at 2.73Å resolution. Structure consists of six crystallographically independent molecules which form two trimeric rings. The pore diameter of the individual trimeric ring is of the order of 37Å. The two rings are stacked through their front to front faces. In order to gain a stable packing, the rings are rotated by 42° about the pore axis and shifted by 7Å and tilted by 16° along the perpendicular direction to pore axis...
August 24, 2017: Biochimica et Biophysica Acta
Ze Zhang, Ping Ren, Ajay A Vashisht, James A Wohlschlegel, David G Quintana, Fanli Zeng
In eukaryotic cells, a surveillance mechanism, the S phase checkpoint, detects and responds to insults that challenge chromosomal replication, arresting cell cycle progression and triggering appropriate events to prevent genomic instability. In the budding yeast Saccharomyces cerevisiae, Mec1/ATM/ATR, and its downstream kinase, Rad53/Chk2, mediate the response to genotoxic stress. In this study, we place Cip1, a recently identified Cdk1 inhibitor (CKI), under the regulation of Mec1 and Rad53 in response to genotoxic stress...
October 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Luis Cesar Bredt, Luis Alberto Batista Peres
AIM: To identify risk factors for the occurrence of acute kidney injury (AKI) in the postoperative period of partial hepatectomies. METHODS: Retrospective analysis of 446 consecutive resections in 405 patients, analyzing clinical characteristics, preoperative laboratory data, intraoperative data, and postoperative laboratory data and clinical evolution. Adopting the International Club of Ascites criteria for the definition of AKI, potential predictors of AKI by logistic regression were identified...
June 28, 2017: World Journal of Hepatology
Ya-Lan Chang, Shun-Fu Tseng, Yu-Ching Huang, Zih-Jie Shen, Pang-Hung Hsu, Meng-Hsun Hsieh, Chia-Wei Yang, Silvia Tognetti, Berta Canal, Laia Subirana, Chien-Wei Wang, Hsiao-Tan Chen, Chi-Ying Lin, Francesc Posas, Shu-Chun Teng
Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function and regulation of Cip1 are still poorly understood. Here we report that Cip1 expression is co-regulated by the cell-cycle-mediated factor Mcm1 and the stress-mediated factors Msn2/4. Overexpression of Cip1 arrests cell cycle through inhibition of Cdk1-G1 cyclin complexes at G1 stage and the stress-activated protein kinase-dependent Cip1 T65, T69, and T73 phosphorylation may strengthen the Cip1and Cdk1-G1 cyclin interaction...
July 4, 2017: Nature Communications
Julia Judd, Matthew Zibelman, Elizabeth Handorf, John O'Neill, Chethan Ramamurthy, Sasini Bentota, Jamie Doyle, Robert G Uzzo, Jessica Bauman, Hossein Borghaei, Elizabeth R Plimack, Ranee Mehra, Daniel M Geynisman
BACKGROUND: The programmed death 1 (PD-1) checkpoint inhibitors (CKIs) can lead to immune-related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with treatment response in non-melanoma malignancies. MATERIALS AND METHODS: We conducted a retrospective study of patients who received anti-PD-1 CKI monotherapy at Fox Chase Cancer Center. Endpoints included overall response rate (ORR), time to next therapy or death (TTNTD), and overall survival (OS)...
October 2017: Oncologist
Erin B Chapman, Alan Nasypany, Jim May, Timothy Henry, Chris Hummel, Hyung-Pil Jun
OBJECTIVE: The purpose of this study is to determine whether the Rosenbaum Concussion Knowledge and Attitudes Survey (RoCKAS) is an appropriate outcome measure to assess knowledge and attitudes toward concussion in collegiate student-athletes as determined through validity and reliability testing. STUDY DESIGN: Convenience study. SETTING: The researcher recruited all athletic teams at a Division III National Collegiate Athletic Association institution...
June 14, 2017: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
Yoshinari Okada, Shunsuke Kato, Yasuhiro Sakamoto, Takayuki Oishi, Chikashi Ishioka
Cell cycle control is a promising target in cancer treatments, and some small-molecule cyclin-dependent kinase (CDK) inhibitors have exhibited clinical effectiveness. However, no biomarkers predictive of efficacy have been developed. Recent studies have revealed that CDK inhibitor (CKI) proteins, such as p27 and p16, also induced cytoprotective autophagy in cancer cells. However, it is unclear whether small-molecule CKIs also induce autophagy in solid tumors, as induced autophagy promotes cancer cell survival...
July 2017: Oncology Reports
Xiaoge Gao, Jingjie Liu, Xiangye Liu, Liantao Li, Junnian Zheng
As the unique chimeric member of the β-galactoside-binding protein family, galectin-3 is a multivalent and multifunctional oncogenic protein involved in multiple physiological and pathological processes, including cell growth, cell differentiation, cell adhesion, RNA splicing, cell apoptosis, and malignant transformation. Post-translational modifications can effectively increase a protein's functional diversity, either by degradation or adding chemical modifications, thus regulating activity, localization, and ligand interaction...
June 2017: Cancer Metastasis Reviews
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