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Xin Hu, Jing Wang, Yu Xia, Mihereguli Simayi, Syed Ikramullah, Yuanbing He, Shihong Cui, Shuang Li, Qimanguli Wushouer
Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit‑8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double‑staining...
October 25, 2016: Molecular Medicine Reports
He Huang, Zhao-Tao Tian, Yong-Ming Yao, Tan-Shi Li
OBJECTIVE: To investigate the effect of tumor necrosis factor-α-induced protein 8 like-2 (TIPE2) on apoptosis of CD4(+) T lymphocytes in a murine model of severe burn injury. METHODS: A total of 140 male mice were randomly allocated into 6 groups. Small RNA interference technique was used to construct a siTIPE2-overexpressing lentivirus, and severe burn injury models were established in the mice. CD4(+) T cells were purified from spleen of the mice, and the expressions of TIPE2, Smad2/Smad3, P-Smad2/P-Smad3 and Bcl-2/Bimprotein in CD4(+) Tregs were detected...
October 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Koichi Miyamura, Toshihiro Miyamoto, Mitsune Tanimoto, Kazuhito Yamamoto, Shinya Kimura, Tatsuya Kawaguchi, Itaru Matsumura, Tomoko Hata, Hisashi Tsurumi, Shigeki Saito, Masayuki Hino, Seiji Tadokoro, Kuniaki Meguro, Hideo Hyodo, Masahide Yamamoto, Kohmei Kubo, Junichi Tsukada, Midori Kondo, Makoto Aoki, Hikaru Okada, Masamitsu Yanada, Kazuma Ohyashiki, Masafumi Taniwaki
Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months...
September 5, 2016: Leukemia Research
Cen Guo, Yang Geng, Feifei Song, Yajing Huo, Xuqing Wu, Jianing Lv, Anyan Ge, Wei Fan
BACKGROUND AND PURPOSE: Mild hypothermia has been proved to reduce global and focal cerebral ischemic injury in rodents by preventing cellular apoptosis through several pathways. However, whether hypothermia will be beneficial for intracerebral hemorrhage (ICH) and its underlying mechanisms haven't reached a consensus. It has been implicated that endoplasmic reticulum (ER) stress plays a role in the secondary injury after ICH in rats. In this study, we aimed to investigate whether mild hypothermia would attenuate ICH induced neuronal injury via regulating ER stress...
October 19, 2016: Neuroscience Letters
Yan Xu, Yawei Xing, Yanjie Xu, Chahua Huang, Huihui Bao, Kui Hong, Xiaoshu Cheng
We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis...
October 17, 2016: Environmental Toxicology and Pharmacology
Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K Dutta, Debabrata Mukhopadhyay, Frank A Sinicrope
Oncogenic BRAFV600E mutations activate MAP kinase signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer (CRC). In BRAFV600E mutant CRCs, treatment failure may be related to BRAFV600E -mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAFV600E can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using CRC cell lines isogenic for BRAF. BRAFV600E -induced MCL-1 upregulation was confirmed by ectopic BRAFV600E expression that activated MEK/ERK signaling to phosphorylate (MCL-1Thr163) and stabilize MCL-1...
October 7, 2016: Molecular Cancer Therapeutics
Bénazir Siddeek, Nadjem Lakhdari, Lilia Inoubli, Rachel Paul-Bellon, Véronique Isnard, Emmanuelle Thibault, André Bongain, Daniel Chevalier, Emanuela Repetto, Michele Trabucchi, Jean-François Michiels, Catherine Yzydorczyk, Umberto Simeoni, Michel Urtizberea, Claire Mauduit, Mohamed Benahmed
AIM: The Developmental Origin of Health and Disease refers to the concept that early exposure to toxicants or nutritional imbalances during perinatal life induces changes that enhance the risk of developing noncommunicable diseases in adulthood. Patients/materials & methods: An experimental model with an adult chronic germ cell phenotype resulting from exposure to a xenoestrogen was used. RESULTS: A reciprocal negative feedback loop involving decreased EZH2 protein level and increased miR-101 expression was identified...
October 20, 2016: Epigenomics
Vicente Andreu-Fernandez, Maria J García-Murria, Manuel Bañó-Polo, Juliette Martin, Luca Monticelli, Mar Orzáez, Ismael Mingarro
Changes in the equilibrium of pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family in the mitochondrial outer membrane (MOM) induce structural changes that commit cells to apoptosis. Bcl-2 homology-3 (BH3)-only proteins participate in this process by either activating pro-apoptotic effectors or inhibiting anti-apoptotic components and by promoting MOM permeabilization. The association of BH3-only proteins with MOMs is necessary for the activation and amplification of death signals; however, the nature of this association remains controversial, as these proteins lack a canonical transmembrane sequence...
October 7, 2016: Journal of Biological Chemistry
Lijia Chen, Steven Fletcher
The myeloid cell leukemia -1 (MCL-1) protein is one of the key anti-apoptotic protein members of the B-cell lymphoma-2 (BCL-2) protein family. Over-expression of MCL-1 has been closely related to tumor progression as well as resistance to not only traditional chemotherapies but also targeted therapeutics including BCL-2 inhibitors such as ABT-263. Therefore, extensive research and development in the last fifteen years in both academic and industrial settings to address this unmet medical need. Areas covered: This review covers research and patent literature of the past 10 years in the field of discovery and development of small-molecule inhibitors of the MCL-1 anti-apoptotic protein...
October 17, 2016: Expert Opinion on Therapeutic Patents
Jonathan Schwartz, Xiaojia Niu, Eric Walton, Laura Hurley, Hai Lin, Holly Edwards, Jeffrey W Taub, Zhihong Wang, Yubin Ge
Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus new treatment strategies are needed for this deadly disease. Poor clinical outcomes have been associated with overexpression of the anti-apoptotic Bcl-2 family proteins Bcl-2, Bcl-xL, and Mcl-1, which have garnered great interest as therapeutic targets. While the Bcl-2-selective inhibitor ABT-199 has demonstrated promising preclinical anti-leukemic activities, intrinsic drug resistance remains a problem. In our most recent study, we identified Mcl-1 sequestration of Bim as a mechanism of intrinsic resistance to ABT-199 in AML cells, thus upregulating Bim could overcome such resistance...
2016: American Journal of Translational Research
Mohamed Salah I Abaza, Mohammad Afzal, Raja'a J Al-Attiyah, Radhika Guleri
BACKGROUND: Natural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated...
October 1, 2016: BMC Complementary and Alternative Medicine
Aditi Bhattacherjee, Sanjay Wategaonkar
The imidazole group, characterized by an activated C(2)-H bond sandwiched between two N atoms, occurs in several biomolecules including alkaloids, amino acids, and nucleobases. The speculated role of this potential hydrogen bond donor in shaping the solvation shell around the neutral imidazole moiety, however, remains unidentified. In contrast, hydrogen bonding and electrostatic interactions are commonly observed in the imidazolium cation where the acidity of the C(2)-H bond is markedly enhanced. Here, we show direct evidence of the weakly activated C(2)-H bond in shaping the solvation shell of neutral imidazole, via spectroscopic characterization of the water clusters (Wn, n = 2-4) of two model compounds, benzimidazole (BIM) and N-methylbenzimidazole (MBIM)...
October 12, 2016: Physical Chemistry Chemical Physics: PCCP
Wenbin Zhou, Xingjie Bi, Guojun Gao, Lijiang Sun
Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In clear cell renal cell carcinoma (ccRCCs) expression of miR-133b and miR-135a is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-133b and miR-135a expression profiles in different RCC subtypes and the functional role of these miRNAs. Viability and apoptosis were examined in three different ccRCC cell lines (786-O, A498 and SN12-PM6) after over-expression of these miRNAs...
October 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jieyun Li, Hui Gao, Zhen Tian, Yi Wu, Yingzheng Wang, Yuan Fang, Lu Lin, Ying Han, Shuaishuai Wu, IhteshamUl Haq, Shenming Zeng
BACKGROUND: Heat stress is known to alter follicular dynamics and granulosa cell function and may contribute to the diminished reproductive efficiency commonly observed in mammals during the summer. Although several investigators have studied heat-induced ovarian injury, few reports have focused on the effects of chronic heat stress on ovarian function and the molecular mechanisms through which it induces ovarian injury. METHODS: In Exp. 1, 48 female mice were assigned to a control or heat-stressed treatment...
2016: Journal of Animal Science and Biotechnology
Marco Kramer, Diogo Ribeiro, Marie Arsenian-Henriksson, Thomas Deller, Hermann Rohrer
: Neuroblastoma (NB) is a childhood tumor that arises from the sympathoadrenal lineage. MYCN amplification is the most reliable marker for poor prognosis and MYCN overexpression in embryonic mouse sympathetic ganglia results in NB-like tumors. MYCN cooperates with mutational activation of anaplastic lymphoma kinase (ALK), which promotes progression to NB, but the role of MYCN and ALK in tumorigenesis is still poorly understood. Here, we use chick sympathetic neuroblasts to examine the normal function of MYCN and MYC in the control of neuroblast proliferation, as well as effects of overexpression of MYCN, MYC, and activated ALK, alone and in combination...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Juan Han, Runming Jin, Meiling Zhang, Qing Guo, Fen Zhou
Ikaros isoform 6 (Ik6) is associated with a poor prognosis for children with acute lymphoblastic leukemia (ALL). Our previous study demonstrated that overexpression of Ik6 enhances proliferation and chemoresistance of leukemia cells, with a possible underlying mechanism that involves antiapoptosis. In the present study, we investigated whether Ik6 protects against apoptosis by regulating the Akt-FoxO1 pathway. Bone marrow samples from children with ALL were collected and evaluated. In Ik6(+) patients, the Akt-FoxO1 pathway was activated such that expression of phosphorylated Akt and FoxO1 was significantly increased, but that of Bim and p27 decreased...
October 5, 2016: Journal of Leukocyte Biology
Ting Song, Ziqian Wang, Fangling Ji, Yingang Feng, Yudan Fan, Gaobo Chai, Xiangqian Li, Zhiqiang Li, Zhichao Zhang
By means of limited proteolysis assay, three-dimensional NMR, X-ray crystallography and alanine mutations, a dynamic region at the Q221R222N223 motif in the Bcl-2 homology 3 (BH3) domain of Mcl-1 has been identified as a conformational switch which controls Mcl-1 ubiquitination. Noxa(BH3) binding biases the QRN motif toward a helical conformation, thus leading to an enhanced in vitro ubiquitination of Mcl-1. In contrast, Bim(BH3) binding biases the QRN motif toward a nonhelical conformation, thus leading to the inhibition of ubiquitination...
October 4, 2016: Angewandte Chemie
Patricia Gomez-Bougie, Maxime Halliez, Philippe Moreau, Catherine Pellat-Deceunynck, Martine Amiot
As myeloma cells actively produce and secrete immunoglobulins, they are prone to ER stress, which if unresolved leads to apoptosis. We found that myeloma cell death induced by the ER stressor Thapsigargin was highly variable, ranging from 2 to 89%. Induction of ATF4 and CHOP was observed in myeloma cells under Thapsigargin independently of cell death. The decrease in Mcl-1 was associated with protein translation inhibition and identified as a crucial factor in Thapsigargin sensitivity, since it was the only Bcl-2 family protein differentially modified between sensitive and resistant myeloma cells...
September 30, 2016: Cancer Letters
Renato José Mendonça Natalino, Célia Beatriz Gianotti Antoneli, Karina de Cássia Braga Ribeiro, Antônio Hugo José Fróes Marques Campos, Fernando Augusto Soares
Retinoblastoma is the most common intraocular malignant neoplasia during childhood and results from the partial or total inactivity of the retinoblastoma protein (pRb). In the absence of pRb, the E2F transcription factors increase the levels of cell cycle proteins as well as some pro-apoptotic proteins. We intended to study the immunohistochemistry profile of apoptotic-related proteins in retinoblastoma. We also evaluated the association between the expression of apoptotic protein and stage of tumor or survivor after a 5year follow up...
September 22, 2016: Pathology, Research and Practice
Marcel Doerflinger, Jason Glab, Christina Nedeva, Irvin Jose, Ann Lin, Lorraine O'Reilly, Cody Allison, Marc Pellegrini, Richard S Hotchkiss, Hamsa Puthalakath
Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice...
October 3, 2016: Scientific Reports
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