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https://www.readbyqxmd.com/read/29687745/dual-pi3-k-mtor-inhibition-reduces-prostate-cancer-bone-engraftment-altering-tumor-induced-bone-remodeling
#1
Andrea Mancini, Alessandro Colapietro, Simona Pompili, Andrea Del Fattore, Simona Delle Monache, Leda Assunta Biordi, Adriano Angelucci, Vincenzo Mattei, Chris Liang, Giovanni Luca Gravina, Claudio Festuccia
Morbidity in advanced prostate cancer patients is largely associated with bone metastatic events. The development of novel therapeutic strategies is imperative in order to effectively treat this incurable stage of the malignancy. In this context, Akt signaling pathway represents a promising therapeutic target able to counteract biochemical recurrence and metastatic progression in prostate cancer. We explored the therapeutic potential of a novel dual PI3 K/mTOR inhibitor, X480, to inhibit tumor growth and bone colonization using different in vivo prostate cancer models including the subcutaneous injection of aggressive and bone metastatic (PC3) and non-bone metastatic (22rv1) cell lines and preclinical models known to generate bone lesions...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29684351/stat3-activation-by-il-6-from-adipose-derived-stem-cells-promotes-endometrial-carcinoma-proliferation-and-metastasis
#2
Yijing Chu, Yan Wang, Wei Peng, Lin Xu, Meixin Liu, Jing Li, Xiaoyu Hu, Yan Li, Jianxin Zuo, Yuanhua Ye
Endometrial cancer is the most common gynaecological cancer, and its incidence is increasing. Obesity is a well-recognized risk factor for endometrial cancer, and the mechanisms by which adipose tissue influences tumour development remain controversial. In this study, we examined the high IL-6 level in the ADSCs supernatant following treatment of endometrial cancer cell CM. Then, the activation of STAT3, a major tumourigenic IL-6 effector, was examined in endometrial cancer cells. Conditioned ADSC medium was used to stimulate endometrial cancer cell growth in vitro...
April 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29682889/fkbp12-6-protects-heart-from-angii-induced-hypertrophy-through-inhibiting-ca-2-calmodulin-mediated-signalling-pathways-in-vivo-and-in-vitro
#3
Yun-Fei Xiao, Zhi-Xiong Zeng, Xiao-Hui Guan, Ling-Fang Wang, Chan-Juan Wang, Huidong Shi, Weinian Shou, Ke-Yu Deng, Hong-Bo Xin
We previously observed that disruption of FK506-binding protein 12.6 (FKBP12.6) gene resulted in cardiac hypertrophy in male mice. Studies showed that overexpression of FKBP12.6 attenuated thoracic aortic constriction (TAC)-induced cardiac hypertrophy in mice, whereas the adenovirus-mediated overexpression of FKBP12.6 induced hypertrophy and apoptosis in cultured neonatal cardiomyocytes, indicating that the role of FKBP12.6 in cardiac hypertrophy is still controversial. In this study, we aimed to investigate the roles and mechanisms of FKBP12...
April 22, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29680477/yap1-tead1-signaling-controls-angiogenesis-and-mitochondrial-biogenesis-through-pgc1%C3%AE
#4
Akiko Mammoto, Megan Muyleart, Andrew Kadlec, David Gutterman, Tadanori Mammoto
Mitochondria contribute to key processes of cellular function, while mitochondrial dysfunction is implicated in metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, in which angiogenesis - the formation of new blood capillaries - is dysregulated. The Hippo signaling transducer, Yes-associated protein (YAP1) binds to the TEA domain (TEAD1) transcription factor and controls angiogenesis. YAP1 also regulates glucose metabolism through peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α), a major player controlling mitochondrial biogenesis...
April 19, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29678774/glial-cells-modulate-hippocampal-synaptic-plasticity-in-morphine-dependent-rats
#5
Azadeh Elahi-Mahani, Soomaayeh Heysieattalab, Narges Hosseinmardi, Mahyar Janahmadi, Fatemeh Sadat Seyedaghamiri, Habibeh Khoshbouei
Drugs of abuse mediate adaptive mechanisms leading to alterations in the synaptic plasticity that has been shown to underlie addictive behaviors. Glial cells play a critical role in modulation of synaptic strength and are potentially involved in drug addiction. Chronic administration of morphine has been shown to increase glial cell activation; therefore, it is possible that altered neuroplasticity induced by drugs of abuse is in part mediated by the activity of glial cells. We investigated the effect of hippocampal glial inhibition on synaptic plasticity in morphine treated rats...
April 17, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29674728/physiological-function-of-phospholipase-d2-in-anti-tumor-immunity-regulation-of-cd8-t-lymphocyte-proliferation
#6
Van Ngo Thai Bich, Tsunaki Hongu, Yuki Miura, Naohiro Katagiri, Norihiko Ohbayashi, Yumi Yamashita-Kanemaru, Akira Shibuya, Yuji Funakoshi, Yasunori Kanaho
Two major phospholipase D (PLD) isozymes in mammals, PLD1 and PLD2, hydrolyze the membrane phospholipid phosphatidylcholine to choline and the lipid messenger phosphatidic acid. Although their roles in cancer cells have been well studied, their functions in tumor microenvironment have not yet been clarified. Here, we demonstrate that PLD2 in cytotoxic CD8+ T cells plays a crucial role in anti-tumor immunity by regulating their cell proliferation. We found that growth of tumors formed by subcutaneously transplanted cancer cells is enhanced in Pld2-knockout mice...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29673329/comparison-of-electroencephalographic-changes-in-response-to-acute-electrical-and-thermal-stimuli-with-the-tail-flick-and-hot-plate-test-in-rats-administered-with-opiorphin
#7
Preet Singh, Kavitha Kongara, David Harding, Neil Ward, Venkata Sayoji Rao Dukkipati, Craig Johnson, Paul Chambers
BACKGROUND: The objective of this study was to compare the changes in the electroencephalogram (EEG) in response to noxious stimuli with tail flick and hot plate responses of rats administered opiorphin. METHODS: Female Sprague -Dawley rats (n = 8 per group) randomly received intravenous (IV) injection of morphine (1 mg/kg,) or opiorphin (2 mg/kg,) or saline (0.5 ml,) in each of the three testing methods (EEG, tail flick and hot plate). Each type of test (n = 24 per test) was conducted in different population of rats on separate occasions...
April 19, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29671280/efficacy-and-safety-of-subcutaneous-belimumab-in-anti-dsdna-positive-hypocomplementemic-patients-with-systemic-lupus-erythematosus
#8
A Doria, W Stohl, A Schwarting, M Okada, M Scheinberg, R van Vollenhoven, A E Hammer, J Groark, D Bass, N L Fox, D Roth, D Gordon
OBJECTIVE: To investigate the efficacy and safety of belimumab, a human immunoglobulin monoclonal antibody against B lymphocyte stimulator, in a subset of patients with systemic lupus erythematosus (SLE) who were hypocomplementemic (C3 [<90 mg/dL] and/or C4 [<10 mg/dL]) and anti-double-stranded(ds)DNA-positive (≥30 IU/mL) at baseline. METHODS: This Phase III, double-blind, placebo-controlled study (BEL112341; NCT01484496) randomized patients (2:1) with moderate-to-severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index ≥8) to weekly subcutaneous (SC) belimumab 200 mg or placebo, plus standard SLE therapy, for 52 weeks...
April 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29669585/endoplasmic-reticulum-stress-in-perivascular-adipose-tissue-promotes-destabilization-of-atherosclerotic-plaque-by-regulating-gm-csf-paracrine
#9
Ru Ying, Sheng-Wei Li, Jia-Yuan Chen, Hai-Feng Zhang, Ying Yang, Zhen-Jie Gu, Yang-Xin Chen, Jing-Feng Wang
BACKGROUND: Perivascular adipose tissue (PVAT) accelerates plaque progression and increases cardiovascular risk. We tested the hypothesis that PVAT contributed to plaque vulnerability and investigated whether endoplasmic reticulum stress (ER stress) in PVAT played an important role in vulnerable plaque. METHODS: We transplanted thoracic aortic PVAT or subcutaneous adipose tissue as a control, from donor mice to carotid arteries of recipient apolipoprotein E deficient (apoE-/- ) mice after removing carotid artery collar placed for 6 weeks...
April 18, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29668607/successful-treatment-of-high-risk-myelodysplastic-syndrome-with-decitabine-based-chemotherapy-followed-by-haploidentical-lymphocyte-infusion-a-case-report-and-literature-review
#10
Yuanyuan Ma, Jianliang Shen, Li-Xin Wang
RATIONALE: The current therapy for elderly patients with high-risk myelodysplastic syndromes (MDSs) remains unsatisfactory. Decitabine, which has been approved to treat MDS, cannot eliminate malignant clones of MDS. PATIENT CONCERNS: A 68-year-old woman presented with multiple divergent bleeding points in the subcutaneous tissue of the limb. Two years earlier, she had been diagnosed with invasive ductal carcinoma of the left breast and had undergone left modified radical mastectomy and local radiation therapy...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29665011/colony-stimulating-factor-1-receptor-blockade-improves-the-efficacy-of-chemotherapy-against-human-neuroblastoma-in-the-absence-of-t-lymphocytes
#11
Matthew W Webb, Jianping Sun, Michael A Sheard, Wei-Yao Liu, Hong-Wei Wu, Jeremy R Jackson, Jemily Malvar, Richard Sposto, Dylan Daniel, Robert C Seeger
Tumor-associated macrophages can promote growth of cancers. In neuroblastoma, tumor-associated macrophages have greater frequency in metastatic versus loco-regional tumors, and higher expression of genes associated with macrophages helps to predict poor prognosis in the 60% of high-risk patients who have MYCN-non-amplified disease. The contribution of cytotoxic T-lymphocytes to anti-neuroblastoma immune responses may be limited by low MHC class I expression and low exonic mutation frequency. Therefore, we modelled human neuroblastoma in T-cell deficient mice to examine whether depletion of monocytes/macrophages from the neuroblastoma microenvironment by blockade of CSF-1R can improve the response to chemotherapy...
April 17, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29664131/anti-fibrotic-actions-of-ghrelin-by-inhibition-of-the-nadph-oxidase-ros-signaling-pathway
#12
Qian Wang, Xin Sui, Rui Chen, Peiyong Ma, Tao Ding, Dianjun Sui, Ping Yang
This study aims to investigate whether the molecular mechanisms by which Ghrelin inhibits cardiac fibrosis are linked to the NADPH oxidase-ROS signaling pathway. Adult male Sprague Dawley (SD) rats were randomly divided into 4 groups: sham, myocardial infarction (MI), MI + Ghrelin (100 μg/kg, twice daily, subcutaneous for 4 weeks beginning 24 h post-MI), or Ghrelin alone. Adult rat cardiac fibroblasts (CFs) were isolated and pretreated with or without Ghrelin for 24 h, followed by stimulation with or without angiotensin II (Ang II) for another 24 h...
April 17, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29659105/lyso-dgts-lipid-isolated-from-microalgae-enhances-pon1-activities-in-vitro-and-in-vivo-increases-pon1-penetration-into-macrophages-and-decreases-cellular-lipid-accumulation
#13
Loureen Dahli, Dana Atrahimovich, Jacob Vaya, Soliman Khatib
High-density lipoprotein (HDL) plays an important role in preventing atherosclerosis. The antioxidant effect of HDL is mostly associated with paraoxonase 1 (PON1) activity. Increasing PON1 activity using nutrients might improve HDL function and quality and thus, decrease atherosclerotic risk. We previously isolated and identified a novel active compound, lyso-DGTS (C20:5,0) from Nannochloropsis sp. ethanol extract. In the present study, its effect on PON1 activities was examined and the mechanism by which the compound affects PON1 activity was explored...
April 16, 2018: BioFactors
https://www.readbyqxmd.com/read/29658074/injection-of-multipotent-mesenchymal-stromal-cells-as-a-cause-of-hemorrhages-in-the-regional-lymph-nodes-experimental-study
#14
I V Maiborodin, V V Morozov, A A Anikeev, N F Figurenko, R V Maslov, V A Matveeva, V I Maiborodina
Hemorrhagic changes after subcutaneous injection of autologous bone marrow multipotent mesenchymal cells with transfected GFP gene and additionally stained cell membranes to WAG rats in the projection of ligated femoral vein were studied by fluorescent microscopy. Hemorrhages in tissues with experimental acute local venous occlusion were caused by a combination of venous hypertension with inflammation around the foreign body - the ligature used for ligation of the vein. Fibrin found in tissues together with erythrocytes in the hemorrhages could stimulate the formation of granulations and new vessels instead of damaged or thrombosed ones...
April 16, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29656250/exposure-to-environmental-level-phenanthrene-induces-a-nash-like-phenotype-in-new-born-rat
#15
Jiaojiao Guo, Chonggang Wang, Zhizhun Guo, Zhenghong Zuo
More and more evidence indicates that persistent organic pollutants (POPs) are a risk factor for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Phenanthrene (Phe) is a kind of POP which existed extensively in the environment, but whose toxicity on mammals has so far received less focus. Subcutaneously injection of Phe (0.5, 5, 50 μg/kg) for 21 days induced significant NAFLD/NASH symptoms in new born rats. Exposure to environmental levels of Phe decreased body weight and liver-somatic index; impaired histology of liver; influenced the peroxisome proliferator-activated receptor gamma (PPARγ) signaling and lipid metabolism in liver; stimulated oxidative stress in the rats' liver; induced the variation of NFκB pathway and liver inflammatory response; and caused liver fibrosis via transforming growth factor β1 (tgfβ1)...
April 12, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29651017/effects-of-different-doses-of-granulocyte-colony-stimulating-factor-mobilization-therapy-on-ischemic-cardiomyopathy
#16
Rongchong Huang, Haichen Lv, Kang Yao, Lei Ge, Zhishuai Ye, Huaiyu Ding, Yiqi Zhang, Hao Lu, Zheyong Huang, Shuning Zhang, Yunzeng Zou, Junbo Ge
G-CSF mobilization might be beneficial to ICM, but the relationship between effect/safety and the dosage of G-CSF remains unclear. In this study, 24 pigs were used to build ICM models and were randomized into four groups. Four weeks later, different dosages of G-CSF were given daily by subcutaneous injection for 5 days. Another 4 weeks later, all the animals were sacrificed. Electrocardiography, coronary arteriography, left ventriculography, transthoracic echocardiography, cardiac MRI, and SPECT, histopathologic analysis, and immunohistochemistry techniques were used to evaluate left ventricular function and myocardial infarct size...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29649772/enhancement-of-th1-immune-response-against-leishmania-cysteine-peptidase-a-b-by-plga-nanoparticle
#17
H Noormehr, A Zavaran Hosseini, S Soudi, F Beyzay
Recombinant cysteine peptidase vaccine can induce protective immunity against cutaneous leishmaniasis. However, the antigenic diversity and variable immunogenicity prevents them from being approved for general vaccination. Different approaches like adjuvant application and antigen delivery systems are studied to increase their efficacy. Nanoparticles can both stimulated antigen uptakes and affect direction of immune response. In this study the effect of PLGA nanoparticles were considered to enhance the immune response against recombinant CPA (CPA) and CPB (CPB)...
April 9, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29628021/regulation-by-3-5-3-tri-iodothyronine-and-fsh-of-cytochrome-p450-family-19-cyp19-expression-in-mouse-granulosa-cells
#18
Juan Liu, Yingying Han, Ye Tian, Xuechun Weng, Xusong Hu, Wenbo Liu, Dai Heng, Kaili Xu, Yanzhou Yang, Cheng Zhang
Cytochrome P450 family 19 (CYP19) plays an important role in follicular development, which is regulated by FSH. Although 3,5,3'-tri-iodothyronine (T3) combines with FSH to induce preantral follicle growth and granulosa cell development, the mechanism involved remains unclear. The aim of the present study was to determine the cellular and molecular mechanisms by which thyroid hormone (TH) and FSH regulate CYP19 expression and sterol biosynthesis during preantral follicle growth. Mice were injected subcutaneously (s...
April 9, 2018: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29626484/neuroestradiol-in-regulation-of-gnrh-release
#19
REVIEW
Ei Terasawa
The concept that the positive feedback effect of ovarian estradiol (E2 ) results in GnRH and gonadotropin surges is a well-established principle. However, a series of studies investigating the rapid action of E2 in female rhesus monkeys has led to a new concept that neuroestradiol, synthesized and released in the hypothalamus, also contributes to regulation of the preovulatory GnRH surge. This unexpected finding started from our surprising observation that E2 induces rapid stimulatory action in GnRH neurons in vitro...
April 4, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29623491/the-complex-alteration-in-the-network-of-il-17-type-cytokines-in-patients-with-hereditary-angioedema
#20
Francesco Arcoleo, Mariangela Lo Pizzo, Gabriella Misiano, Salvatore Milano, Giuseppina Colonna Romano, Vito Muggeo, Enrico Cillari
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes...
April 6, 2018: Clinical and Experimental Medicine
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