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https://www.readbyqxmd.com/read/28429785/natriuretic-peptide-receptor-guanylyl-cyclase-a-pathway-counteracts-glomerular-injury-evoked-by-aldosterone-through-p38-mitogen-activated-protein-kinase-inhibition
#1
Yukiko Kato, Kiyoshi Mori, Masato Kasahara, Keisuke Osaki, Akira Ishii, Keita P Mori, Naohiro Toda, Shoko Ohno, Takashige Kuwabara, Takeshi Tokudome, Ichiro Kishimoto, Moin A Saleem, Taiji Matsusaka, Kazuwa Nakao, Masashi Mukoyama, Motoko Yanagita, Hideki Yokoi
Guanylyl cyclase-A (GC-A) signaling, a natriuretic peptide receptor, exerts renoprotective effects by stimulating natriuresis and reducing blood pressure. Previously we demonstrated massive albuminuria with hypertension in uninephrectomized, aldosterone-infused, and high salt-fed (ALDO) systemic GC-A KO mice with enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in podocytes. In the present study, we examined the interaction between p38 MAPK and GC-A signaling. The administration of FR167653, p38 MAPK inhibitor, reduced systolic blood pressure (SBP), urinary albumin excretion, segmental sclerosis, podocyte injury, and apoptosis...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428442/combination-of-ibrutinib-and-abt-199-in-diffuse-large-b-cell-lymphoma-and-follicular-lymphoma
#2
Hsu-Ping Kuo, Scott A Ezell, Karl J Schweighofer, Leo Wk Cheung, Sidney Hsieh, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Ssucheng J Hsu, Chun-Te Chen, Darrin M Beaupre, Matthias Versele, Betty Y Chang
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton's tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28426671/effect-of-mitochondrially-targeted-carboxy-proxyl-nitroxide-on-akt-mediated-survival-in-daudi-cells-significance-of-a-dual-mode-of-action
#3
Gokul Variar, Tarun Pant, Apoorva Singh, Abinaya Ravichandran, Sushant Swami, Balaraman Kalyanaraman, Anuradha Dhanasekaran
Vicious cycles of mutations and reactive oxygen species (ROS) generation contribute to cancer progression. The use of antioxidants to inhibit ROS generation promotes cytostasis by affecting the mutation cycle and ROS-dependent survival signaling. However, cancer cells select mutations to elevate ROS albeit maintaining mitochondrial hyperpolarization (Δψm), even under hypoxia. From this perspective, the use of drugs that disrupt both ROS generation and Δψm is a viable anticancer strategy. Hence, we studied the effects of mitochondrially targeted carboxy proxyl nitroxide (Mito-CP) and a control ten carbon TPP moiety (Dec-TPP+) in the human Burkitt lymphoma cell line (Daudi) and normal peripheral blood mononuclear cells under hypoxia and normoxia...
2017: PloS One
https://www.readbyqxmd.com/read/28426164/protease-activated-receptor-2-suppresses-interleukin-il-10-expression-in-b-cells-via-up-regulating-bcl2l12-in-patients-with-allergic-rhinitis
#4
Jin-Mei Xue, Li-Tao Yang, Gui Yang, Xiao-Rui Geng, Zhi-Qiang Liu, Shuai Wang, Hai-Liang Zhao, Zhi-Gang Liu, Chang-Qing Zhao, Ping-Chang Yang
BACKGROUND AND AIMS: The function of interleukin (IL)-10 producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immune regulatory functions. This study aims to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells. METHODS: Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2 like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed...
April 20, 2017: Allergy
https://www.readbyqxmd.com/read/28409693/tpt1-tumor-protein-translationally-controlled-1-negatively-regulates-autophagy-through-the-becn1-interactome-and-an-mtorc1-mediated-pathway
#5
Seong-Yeon Bae, Sanguine Byun, Soo Han Bae, Do Sik Min, Hyun Ae Woo, Kyunglim Lee
TPT1/TCTP (tumor protein, translationally-controlled 1) is highly expressed in tumor cells, known to participate in various cellular activities including protein synthesis, growth and cell survival. In addition, TPT1 was identified as a direct target of the tumor suppressor TP53/p53 although little is known about the mechanism underlying the anti-survival function of TPT1. Here, we describe a role of TPT1 in the regulation of the MTORC1 pathway through modulating the molecular machinery of macroautophagy/autophagy...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28408751/mmp9-integrates-multiple-immunoregulatory-pathways-that-discriminate-high-suppressive-activity-of-human-mesenchymal-stem-cells
#6
Carolina Lavini-Ramos, Hernandez Moura Silva, Alessandra Soares-Schanoski, Sandra Maria Monteiro, Ludmila Rodrigues Pinto Ferreira, Ana Paula Pacanaro, Samirah Gomes, Janaína Batista, Kellen Faé, Jorge Kalil, Verônica Coelho
The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73(+)Foxp3(+)Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#7
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a  subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). Hoever, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28400072/notch-signaling-pathway-promotes-the-development-of-ovine-ovarian-follicular-granulosa-cells
#8
Jiongjie Jing, Xiaolong Jiang, Jianwei Chen, Xiaolei Yao, Miaomiao Zhao, Pengfei Li, Yangyang Pan, Youshe Ren, Wenzhong Liu, Lihua Lyu
The Notch signaling pathway regulates cell proliferation, differentiation and apoptosis involved in development of the organs and tissues such as nervous system, cartilage, lungs, kidneys and prostate as well as the ovarian follicles. This study aimed to investigate the mRNA expression and localization of NOTCH2, as the key factor in Notch signaling pathway. This was determined by PCR, real-time PCR and immunohistochemistry. Additionally, the effects of inhibiting Notch signaling pathway with different concentrations (5μM, 10μM and 20μM) of N-[N-(3, 5-Difuorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling pathway, on ovine granulosa cells was determined in vitro by detecting estradiol production using enzyme linked immunosorbent assay and expressions of the genes related to the cell cycle and apoptosis using real-time polymerase chain reaction (PCR)...
March 28, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28396364/novel-indole-based-tambjamine-analogues-induce-apoptotic-lung-cancer-cell-death-through-p38-mitogen-activated-protein-kinase-activation
#9
Pilar Manuel-Manresa, Luís Korrodi-Gregório, Elsa Hernando, Alberto Villanueva, David Martínez-García, Ananda M Rodilla, Ricard Ramos, Margarida Fardilha, Juan Moya, Roberto Quesada, Vanessa Soto-Cerrato, Ricardo Perez-Tomas
Lung cancer has become the leading killer cancer worldwide, due to late diagnosis and lack of efficient anticancer drugs. We have recently described novel natural-derived tambjamine analogues that are potent anion transporters capable of disrupting cellular ion balance, inducing acidification of the cytosol and hyperpolarization of cellular plasma membranes. Although these tambjamine analogues were able to compromise cell survival, their molecular mechanism of action remains largely unknown. Herein we characterize the molecular cell responses induced by highly active indole-based tambjamine analogues treatment in lung cancer cells...
April 10, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28393197/effects-of-hylomecon-vernalis-ethanol-extracts-on-cell-cycle-and-apoptosis-of-colon-cancer-cells
#10
Jing Sun, Xin Zhang, Yang Sun, Zhi-Shu Tang, Dong-Yan Guo
Hylomecon vernalis Maxim. has traditionally been used to promote blood circulation, alleviate pain, dissipate stasis, and reduce swelling. The aim of the present study was to investigate the effect and potential mechanism of H. vernalis Maxim. ethanol extracts (HVMEE) on the growth and apoptosis of human colon cancer HT‑29 and SW620 cells. H. vernalis samples were extracted three times with ethanol, dried, and concentrated into powder. The components of HVMEE were investigated using high performance liquid chromatography in tandem with mass spectrometry analysis...
April 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28392886/amifostine-pretreatment-attenuates-myocardial-ischemia-reperfusion-injury-by-inhibiting-apoptosis-and-oxidative-stress
#11
Shao-Ze Wu, Lu-Yuan Tao, Jiao-Ni Wang, Zhi-Qiang Xu, Jie Wang, Yang-Jing Xue, Kai-Yu Huang, Jia-Feng Lin, Lei Li, Kang-Ting Ji
The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28391274/inhibition-of-brd4-suppresses-cell-proliferation-and-induces-apoptosis-in-renal-cell-carcinoma
#12
Xinchao Wu, Dong Liu, Xuemei Gao, Fei Xie, Dan Tao, Xingyuan Xiao, Liang Wang, Guosong Jiang, Fuqing Zeng
BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells...
April 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28386842/vitamin-k2-inhibits-rat-vascular-smooth-muscle-cell-calcification-by-restoring-the-gas6-axl-akt-anti-apoptotic-pathway
#13
Cuiting Qiu, Haijun Zheng, Huiren Tao, Wenjun Yu, Xiaoyu Jiang, Aiqin Li, Hui Jin, Anlin Lv, Huan Li
Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days...
April 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28386377/hypoxia-inducible-factor-1%C3%AE-promotes-survival-of-mesenchymal-stem-cells-under-hypoxia
#14
Bingke Lv, Feng Li, Jie Fang, Limin Xu, Chengmei Sun, Jianbang Han, Tian Hua, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Mesenchymal stem cells (MSCs) are ideal materials for cell therapy. Research has indicated that hypoxia benefits MSC survival, but little is known about the underlying mechanism. This study aims to uncover potential mechanisms involving hypoxia inducible factor 1α (HIF1A) to explain the promoted MSC survival under hypoxia. MSCs were obtained from Sprague-Dawley rats and cultured under normoxia or hypoxia condition. The overexpression vector or small interfering RNA of Hif1a gene was transfected to MSCs, after which cell viability, apoptosis and expression of HIF1A were analyzed by MTT assay, flow cytometry, qRT-PCR and Western blot...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28381544/modulation-of-bax-and-mtor-for-cancer-therapeutics
#15
Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam Marcus, Shi-Yong Sun, Zhuo Georgia Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew Magis, Haian Fu, Fadlo Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng
A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28380464/heat-stress-induces-intestinal-injury-through-lysosome-and-mitochondria-dependent-pathway-in-vivo-and-in-vitro
#16
Gao Yi, Li Li, Meijuan Luo, Xuan He, Zhimin Zou, Zhengtao Gu, Lei Su
Damage to the small intestine secondary to heat stroke is a major factor in heat stroke-related morbidity and mortality. However, the underlying mechanisms by which heat stroke causes small intestinal lesions and dysfunction remain unclear. To explore the pathogenesis of small intestinal tissue and epithelial cell injury, the SW480 cell heat stress model and the mice heat stroke model were established to mimic heat stroke. Morphologic changes in intestinal tissue and increased TUNEL-positive index were induced by heat stress in vivo...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379541/resistance-to-apoptosis-and-autophagy-leads-to-enhanced-survival-in-sertoli-cells
#17
Ferial Aslani, Tim Sebastian, Miguel Keidel, Suada Fröhlich, Hans-Peter Elsässer, Hans-Christian Schuppe, Jörg Klug, Poornima Mahavadi, Monika Fijak, Martin Bergmann, Andreas Meinhardt, Sudhanshu Bhushan
STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of pro-survival B cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. WHAT IS KNOWN ALREADY: In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of pro-survival mechanisms and inhibition of cell death pathways...
April 3, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28371137/proanthocyanidin-protects-against-cisplatin-induced-oxidative-liver-damage-through-inhibition-of-inflammation-and-nf-%C3%AE%C2%BA%C3%AE-tlr-4-pathway
#18
Nagla A El-Shitany, Basma Eid
Although cisplatin (CIS) is a highly effective anticancer drug, hepatotoxicity is one of the most common adverse effects associated with its use. Recently, reactive oxygen species (ROS) and inflammation are suggested to be key factors in the pathophysiology of CIS-induced acute liver damage. The aim of this study is to investigate the possible protective effect of proanthocyanidin (PRO) against CIS-induced acute hepatotoxicity. Rats were divided into four groups: 1, Control; 2, PRO; 3, CIS; and 4, PRO + CIS...
March 29, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28370166/mechanism-of-arsenite-toxicity-in-embryonic-stem-cells
#19
Naimisha Beeravolu, Christina McKee, G Rasul Chaudhry
Environmental arsenite exposure has been linked to cancer as well as other diseases, presenting an important and serious public health problem. Toxicity of inorganic arsenite (iAs) has been investigated using animal models and cell culture, yet its developmental effects are poorly understood. This study investigated the molecular mechanism of iAs toxicity to ascertain insight into development and differentiation processes using mouse embryonic stem cells (ESCs). The results showed that iAs exposure affected morphology and integrity of ESC colonies as well as inhibited cell growth in a concentration-dependent manner, excluding concentrations <1 μM iAs which stimulated ESC growth...
April 3, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28368400/interferon-%C3%AE-is-a-stat1-dependent-direct-inducer-of-bcl6-expression-in-imatinib-treated-chronic-myeloid-leukemia-cells
#20
H S Madapura, N Nagy, D Ujvari, T Kallas, M C L Kröhnke, S Amu, M Björkholm, L Stenke, P K Mandal, J S McMurray, M Keszei, L S Westerberg, H Cheng, F Xue, G Klein, E Klein, D Salamon
B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells...
April 3, 2017: Oncogene
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