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Yuanzhi Zhao, Cong Zhou, Hang Yu, Wenwu Zhang, Fang Cheng, Haihang Yu, Dongsheng Zhou, Bin Li, Jing Liu, Jie Dai, Jie Zhong, Min Chen, Tianyi Huang, Ranran Pan, Shiwei Duan, Zhenyu Hu
Excessive apoptosis hinders the process of brain maturation and is regarded as one of the principal risk factors for the development of autism spectrum disorder (ASD). The aim of the present study was to investigate the association between the methylation of six apoptosis‑associated genes [transforming growth factor β 1 (TGFB1), BCL2 associated X, apoptosis regulator, insulin like growth factor binding protein 3, protein kinase C β 1, presenilin 2 and C‑C motif chemokine ligand 2] and ASD. Using quantitative methylation‑specific polymerase chain reaction technology, DNA methylation levels were detected in 42 autistic and 26 control subjects...
September 10, 2018: Molecular Medicine Reports
Xiaotong Wang, Xiaopeng Cui, Chuanwu Zhu, Ming Li, Juan Zhao, Zhongyi Shen, Xiaohang Shan, Liang Wang, Han Wu, Yanting Shen, You Ni, Dongmei Zhang, Guoxiong Zhou
Endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) has an important role in the pathogenesis of Crohn's disease (CD). FK506 binding protein 11 (FKBP11), a member of the peptidyl‑prolyl cis‑trans isomerase family, is involved in the unfolded protein response (UPR) and is closely associated with inflammation. Previous bioinformatics analysis revealed a potential association between FKBP11 and human CD. Thus, the present study aimed to investigate the potential significance of FKBP11 in IEC homeostasis and CD...
September 14, 2018: Molecular Medicine Reports
Zahra Shanesazzade, Maryam Peymani, Kamran Ghaedi, Mohammad Hossein Nasr Esfahani
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder which mainly affects the elderly population of various societies. The main hallmark of this disease is the loss of dopaminergic (DA) neurons. So far, numerous studies have implied the role of microRNAs in fine-tuning cellular processes including apoptosis. Studies have also shown that miR-34a is mainly involved in age-related disorders including Alzheimer's disease, and its expression is usually higher in the brain sample patients...
September 16, 2018: Molecular Genetics & Genomic Medicine
Michele Simbolo, Caterina Vicentini, Andrea Mafficini, Matteo Fassan, Serena Pedron, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Corrado Pedrazzani, Luca Landoni, Federica Grillo, Sara Cingarlini, Guido Rindi, Claudio Luchini, Aldo Scarpa, Rita T Lawlor
Small intestine neuroendocrine tumors (SI-NETs) represent the most common histotype among small intestine neoplasms, and metastatic disease is usually present at diagnosis. A retrospective series of 52 sporadic primary surgically resected SI-NETs, which were metastatic at diagnosis, was analyzed by high-coverage target sequencing (HCTS) for the mutational status of 57 genes and copy number status of 40 genes selected from recently published genome sequencing data. Seven genes were found to be recurrently mutated: CDKN1B (9...
September 16, 2018: Virchows Archiv: An International Journal of Pathology
Fengxia Yang, Li Guo, Yujing Cao, Shizhen Li, Jianhua Li, Min Liu
BACKGROUND Resistance to cisplatin results in recurrence or relapse of cervical cancer in women. An understanding of the mechanisms of cisplatin resistance will be important to improve the efficacy of cisplatin treatment. The aim of this study was to investigate the role of microRNA-7-5p (mir-7-5p) in cisplatin-resistant cervical cancer cells in vitro. MATERIAL AND METHODS The expression levels of miR-7-5p were detected in cisplatin-resistant cervical cancer cells, HeLa, and SiHa cells (HPV16-positive), and in clinical tissue samples, using miR-7-5p inhibition and a luciferase reporter assay...
September 16, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Behnaz Valipour, Seyede Momeneh Mohammadi, Ali Abedelahi, Behnaz Faramarzian Azimi Maragheh, Elahe Naderali, Alireza Dehnad, Hojjatollah Nozad Charoudeh
Despite the advances in the discovery of various types of anticancer drugs for curing acute lymphoblastic leukemia (ALL), their toxicity and unfavorable side effects remained as big limitations for therapeutical applications. In this regard, natural products such as Streptomyces -derived agents have shown potential applications as anticancer drugs. The present study deals with evaluating the anti-carcinogenic activity of the ether extracted metabolites derived from Streptomyces on nalm-6 and molt-4 ALL cell lines...
September 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bai-Sui Feng, Yong-Jin Wu, Xian-Hai Zeng, Dian Yu, Zhi-Qiang Liu, Cai-Jie Zhou, Zhi-Gang Liu, Peng-Yuan Zheng, Ping-Chang Yang
The immune dysregulation plays an important role in the pathogenesis of ulcerative colitis (UC). Bcl2 like protein-12 (Bcl2L12) and mast cells are involved in immune dysregulation of UC. This study aims to elucidate the role of Bcl2L12 in the contribution to the pathogenesis of T helper (Th)2-biased inflammation in UC patients. The results showed that Bcl2L12 was expressed by peripheral CD4+ T cells that was associated with Th2 polarization in UC patients. Bcl2L12 mediated the protease-activated receptor-2 (PAR2)-induced IL-4 expression in CD4+ cells...
September 11, 2018: Archives of Biochemistry and Biophysics
Yingyin Sun, Jingcao Shen, Lin Zeng, Dan Yang, Shuxin Shao, Jinglei Wang, Jie Wei, Junping Xiong, Jiaxiang Chen
Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry. DEHP can cause testicular atrophy, yet the exact mechanism remains unclear. In this study, male mice were intragastrically (i.g.) administered with 0, 100, 200 or 400 mg DEHP/kg/day for 21 days. We found that DEHP caused disintegration of the germinal epithelium and decreased sperm density in the epididymis. Furthermore, there was a significant increase in the levels of cleaved Caspase-8, cleaved Caspase-3 and Bax proteins and a decrease in Bcl2 protein...
September 5, 2018: Environmental Pollution
Beatrice Beck-Schimmer, Birgit Roth Z'graggen, Christa Booy, Sabrina Köppel, Donat R Spahn, Martin Schläpfer, Erik Schadde
BACKGROUND: Randomized controlled trials (RCTs) data demonstrate that sevoflurane postconditioning improves clinical outcomes of liver resection with inflow occlusion, presumably due to hepatocyte protection from ischemic injury. However, mechanisms remain unclear. This study examines liver biopsy samples obtained in an RCT of sevoflurane postconditioning to test the hypothesis that sevoflurane attenuates hepatocyte apoptosis. METHODS: Messenger ribonucleic acid (mRNA) of pro- and antiapoptotic regulators Bax and B-cell lymphoma 2 (Bcl2) was examined in hepatic biopsies obtained during the RCT...
October 2018: Anesthesia and Analgesia
Barbara Marengo, Paola Monti, Mariangela Miele, Paola Menichini, Laura Ottaggio, Giorgia Foggetti, Alessandra Pulliero, Alberto Izzotti, Andrea Speciale, Ombretta Garbarino, Nicola Traverso, Gilberto Fronza, Cinzia Domenicotti
Drug resistance is the major obstacle in successfully treating high-risk neuroblastoma. The aim of this study was to investigate the basis of etoposide-resistance in neuroblastoma. To this end, a MYCN-amplified neuroblastoma cell line (HTLA-230) was treated with increasing etoposide concentrations and an etoposide-resistant cell line (HTLA-ER) was obtained. HTLA-ER cells, following etoposide exposure, evaded apoptosis by altering Bax/Bcl2 ratio. While both cell populations shared a homozygous TP53 mutation encoding a partially-functioning protein, a mono-allelic deletion of 13q14...
September 13, 2018: Scientific Reports
James Godfrey, Michael J Leukam, Sonali M Smith
Indolent lymphomas typically have a prolonged course and favorable prognosis. Recent data support survival times that can reach several decades, even if periodic treatment is needed to manage symptoms or stabilize disease. However, all indolent lymphomas have the potential to undergo transformation to an aggressive phenotype, clinically characterized by a rapid progression of adenopathy, new-onset constitutional symptoms, or laboratory abnormalities, and the immediate need for therapeutic intervention. The most common scenario is transformation of follicular lymphoma to either diffuse large B-cell lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations; however, other indolent subtypes such as marginal zone lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or even nodular lymphocyte predominant Hodgkin lymphoma, can undergo similar histologic transformation...
September 2018: Best Practice & Research. Clinical Haematology
Brídgín Merron, Andrew Davies
Double/triple hit lymphoma is recognised as a distinct entity within the heterogeneous group of high grade B-cell lymphomas, accounting for between 5 and 10% of cases of diffuse large B-cell lymphoma. Under the WHO 2016 it is now known as high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6. When treated with standard chemotherapy it has a poor outcome. There is currently no standard of care for the management of this condition. Diagnosing double hit lymphoma requires identification of translocations of MYC and BCL2 and/or BCL6...
September 2018: Best Practice & Research. Clinical Haematology
Catherine Thieblemont, Sophie Bernard, Michel Meignan, Thierry Molina
Diffuse large B-cell lymphoma (DLBCL) is a group of lymphomas comprising heterogeneous molecular and biological subtypes, reflected in a broad range of clinical outcomes. With the standard R-CHOP regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab administered every 21 days, the treatment failure rate remains unacceptably high in certain DLBCL subsets. Here we review possible avenues for optimizing initial therapy. The role of functional imaging and biological features, such as double-hit lymphomas, defined by the dual translocation of MYC and BCL2, and dual protein-expresser lymphomas, defined by the overexpression of MYC and BCL2, activated B-cell (ABC)-like DLBCL, to better define these high-risk patient subsets, and their use to guide and personalize treatment decisions are discussed...
September 2018: Best Practice & Research. Clinical Haematology
David W Scott, Lisa M Rimsza
The aggressive B-cell lymphomas are a diverse collection of cancers grouped together based on clinical behavior and derivation from B lymphocytes. Genomic analyses on these tumours are now translating into improved classification systems and identification of underpinning targetable biology. Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme. Subsequently, gene expression profiling identified molecular subgroups within the most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell-like and germinal centre B-cell-like...
September 2018: Best Practice & Research. Clinical Haematology
Baharak Abdolhossein Zadeh, Kamal Yavari, Mehdi Banan, Ali Fallah, Leila Nasehi, Moloud Absalan, Gholamreza Tavoosidana
B-cell lymphoma 2 (BCL2) family proteins play a critical role in tuning cell death processes. Almost in half of all human cancers, a dysregulation in BCL2 family gene expression has been shown which made it an impressive target for human gene therapy as a novel approach in cancers. In this study we will optimize lentiviral-mediated RNA interference (RNAi), recombinant lentiviruses accommodating anti-BCL2 micro adaptive short hairpin RNAs (shRNAs), to downregulate BCL2 in human embryonic kidney 293T (HEK293T) cells to produce stable cell lines...
August 30, 2018: Cellular and Molecular Biology
Banudevi Sivanantham, UmaMaheswari Krishnan, Vignesh Rajendiran
Increasing studies have implicated superfluous production of reactive oxygen species (ROS) as a significant factor in the progress of neurodegenerative disorders ranging from ischemic stroke to amyotrophic lateral sclerosis. The possible mechanisms relating to oxidative stress and neurodegeneration are yet to be thoroughly understood. Rutin, a flavonoid, has been well documented for its beneficial and pharmacological activities against diverse targets. However, the mechanism involved in the beneficial effects of rutin against neurodegeneration still remains unclear...
September 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lixiang Zhai, Zi-Wan Ning, Tao Huang, Bo Wen, Cheng-Hui Liao, Cheng-Yuan Lin, Ling Zhao, Hai-Tao Xiao, Zhao-Xiang Bian
Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches...
2018: Frontiers in Pharmacology
Masaki Mitobe, Keisuke Kawamoto, Takaharu Suzuki, Maiko Kiryu, Suguru Tamura, Ayako Nanba, Tatsuya Suwabe, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Masayoshi Masuko, Hiroaki Miyoshi, Koichi Ohshima, Hirohito Sone, Jun Takizawa
A 61-year-old woman exhibited right inguinal lymphadenopathy and right lower limb edema approximately 1 month prior to hospitalization. She was diagnosed with high grade B-cell lymphoma, and a lymph node biopsy and fluorescence in situ hybridization indicated MYC, BCL2, and BCL6 rearrangements (triple-hit lymphoma). She had progressive disease that was CD20-negative after two courses of R-CODOX-M/IVAC therapy. Subsequent EPOCH therapy was not effective. However, after two cycles of gemcitabine, dexamethasone, and cisplatin (GDP) therapy, she achieved a complete response and was able to undergo autologous peripheral blood stem cell transplantation...
September 12, 2018: Internal Medicine
A Calva-Lopez, Carlos A Tirado
Chronic lymphocytic leukemia (CLL) is the most common type of hematological cancer diagnosed in human adults; however, it has been linked with a series of chromosomal abnormalities, the most common being deletion of 13q14. This chromosomal alteration leads to the deletion of the miR-15/16 cluster, as well as downregulation of DLEU7. Deletion of miR-15a and miR-16-1 causes overexpression of BCL2, an apoptosis suppressing protein, while the deletion of DLEU7 activates the NF-kB pathway. Both lead to the development of a pro-proliferative phenotype, an inhibition of apoptosis and prolonged cell life...
2018: Journal of the Association of Genetic Technologists
Saravana Babu Chidambaram, Abid Bhat, Bipul Ray, Mani Sugumar, Serva Peddha Muthukumar, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Gilles J Guillemin, Meena Kishore Sakharkar
Polyphenols are shown to protect from or delay the progression of chronic neurodegenerative diseases. Mitochondrial dysfunction plays a key role in the pathogenesis of Parkinson's disease (PD). This study was aims to gain insight into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma cells (SHSY5Y). The effects of cocoa on PPARγ, PGC1α, Nrf2 and TFAM protein expression and mitochondrial membrane potential were evaluated...
September 12, 2018: Nutritional Neuroscience
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