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https://www.readbyqxmd.com/read/28531963/mir-19b-and-mir-16-cooperatively-signaling-target-the-regulator-adra1a-in-hypertensive-heart-disease
#1
Liping He, Congxin Huang
BACKGROUND: Hypertensive heart disease (HHD) is one of the most important causes of disease-related deaths worldwide and brings great painful for patients. In recent years, increasingly evidences support the role of miRNAs in various physiology processes and human diseases. In the present study, we investigated whether ADRA1A regulated by miR-19b and miR-16 was involved in the pathogenic mechanism of HHD. METHODS: HHD mice models were established with injection of Deoxycorticosterone acetate (Doca)...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531921/hesperetin-post-treatment-prevents-rat-cardiomyocytes-from-hypoxia-reoxygenation-injury-in-vitro-via-activating-pi3k-akt-signaling-pathway
#2
Shangfei He, Xianbao Wang, Yongkang Zhong, Lu Tang, Ya Zhang, Yuanna Ling, Zhipeng Tan, Pingzhen Yang, Aihua Chen
Hesperidin (HES), a citrus fruit extract, has beneficial effects on various ischemia/reperfusion (I/R) models. Here, we investigated the possible positive effect of hesperetin (HPT), an active metabolite of HES, and identified the potential molecular mechanisms involved in cardiomyocytes H/R-induced injury. To construct the cardiomyocyte model of hypoxia/reoxygenation (H/R) injury, cultured neonatal rat cardiomyocytes were subjected to 3h of hypoxia followed by 3h of reoxygenation. Cell viability and apoptosis were detected...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531812/macrophages-produce-il-33-by-activating-mapk-signaling-pathway-during-rsv-infection
#3
Feifei Qi, Song Bai, Dandan Wang, Lei Xu, Haiyan Hu, Sheng Zeng, Ruonan Chai, Beixing Liu
It has been reported that RSV infection can enhance IL-33 production in lung macrophages. However, little is known about specific signaling pathways for activation of macrophages during RSV infection. In the present study, by using real-time RT-PCR as well as western blot assay, it became clear that RSV infection can enhance not only the expression of mRNAs for MAPK molecules (including p38, JNK1/2, and ERK1/2), but also the levels of MAPK proteins in lung macrophages as well as RAW264.7 cells. Furthermore, infection with RSV resulted in an increased level of phosphorylated MAPK proteins in RAW264...
May 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28531804/protective-effect-and-mechanism-of-lycopene-on-endothelial-progenitor-cells-epcs-from-type-2-diabetes-mellitus-rats
#4
Yao-Chi Zeng, Li-Sheng Peng, Liyuan Zou, Shu-Fen Huang, Yi Xie, Gui-Ping Mu, Xue-Hui Zeng, Xi-Lin Zhou, Ya-Chi Zeng
Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531803/isofraxidin-inhibited-proliferation-and-induced-apoptosis-via-blockage-of-akt-pathway-in-human-colorectal-cancer-cells
#5
Peng Shen, Hong-Gang Wang, Miao-Miao Li, Qian-Yun Ma, Chuan-Wen Zhou, Feng Pan, Rui Xie
BACKGROUND: Isofraxidin (IF), a natural coumarin compound, has been reported to possess anti-cancer activity in human liver cancer. However, whether IF is involved in the regulation of colorectal cancer tumorigenesis and development has been not well elucidated. METHODS: The cell proliferation were assessed by Cell Counting Kit-8 (CCK-8) and colony formation test, respectively. The transwell assays were conducted to estimate cell migration and invasion abilities...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531794/binding-of-the-anticancer-drug-bi-2536-to-human-serum-albumin-a-spectroscopic-and-theoretical-study
#6
Jesús Fernández-Sainz, Pedro J Pacheco-Liñán, José M Granadino-Roldán, Iván Bravo, Andrés Garzón, Jaime Rubio-Martínez, José Albaladejo
BI-2536 is a potent Polo-like kinase inhibitor which induces apoptosis in diverse human cancer cell lines. The binding affinity of BI-2536 for human serum albumin (HSA) protein may define its pharmacokinetic and pharmacodynamic profile. We have studied the binding of BI-2536 to HSA by means of different spectroscopic techniques and docking calculations. We have experimentally observed that the affinity of BI-2536 for HSA is higher than that of other common HSA binding drugs. Therefore, it can be postulated that the drug dose should be increased to achieve a certain concentration of free drug in plasma, although BI-2536 could also reach tumour tissues by uptaking HSA/BI-2536 complex...
May 12, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28531660/carbon-black-aggregates-cause-endothelial-dysfunction-by-activating-rock
#7
Junyan Yan, Chia-Hsiang Lai, Shih-Chun Candice Lung, Wen-Cheng Wang, Chih-Ching Huang, Guan-Wen Chen, Guangli Suo, Cheng-Tai Choug, Chia-Hua Lin
Carbon black nanoparticles (CBNs) have been associated with the progression of atherosclerosis. CBNs normally enter the bloodstream and crosslink together to form agglomerates. However, most studies have used nano-sized CB particles to clarify the involvement of CBN exposure in CBN-induced endothelial dysfunction. Herein, we studied endothelial toxicity of CBN aggregates (CBA) to human EA.hy926 vascular cells. Cell viability, lactate dehydrogenase leakage, and oxidative stress were affected by the highest concentration of CBA...
May 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28531263/in-vivo-dynamics-of-the-cortical-actin-network-revealed-by-fast-scanning-atomic-force-microscopy
#8
Yanshu Zhang, Aiko Yoshida, Nobuaki Sakai, Yoshitsugu Uekusa, Masahiro Kumeta, Shige H Yoshimura
Together with lamellipodia and stress fibers, a dynamic network of actin filaments in the cell cortex plays a major role in the maintenance of cell morphology and motility. In contrast to lamellipodia, which have been well studied in various motile cells, the dynamics of actin filaments in the cell cortex have not yet been clarified due to a lack of proper imaging techniques. Here, we utilized high-speed atomic force microscopy for live-cell imaging and analyzed cortical actin dynamics in living cells. We successfully measured the polymerization rate and the frequency of filament synthesis in living COS-7 cells, and examined the associated effects of various inhibitors and actin-binding proteins...
May 20, 2017: Microscopy
https://www.readbyqxmd.com/read/28531229/protein-kinase-c-theta-is-dispensable-for-suppression-mediated-by-cd25-cd4-regulatory-t-cells
#9
Kerstin Siegmund, Nikolaus Thuille, Katarzyna Wachowicz, Natascha Hermann-Kleiter, Gottfried Baier
The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay...
2017: PloS One
https://www.readbyqxmd.com/read/28531218/autophagy-inhibitor-facilitates-gefitinib-sensitivity-in-vitro-and-in-vivo-by-activating-mitochondrial-apoptosis-in-triple-negative-breast-cancer
#10
Zhaoyun Liu, Kewen He, Qinghua Ma, Qian Yu, Chenyu Liu, Isabella Ndege, Xinzhao Wang, Zhiyong Yu
Epidermal growth factor receptor (EGFR) is over-expressed in about 50% of Triple negative breast cancers (TNBCs), but EGFR inhibitors have not been effective in treating TNBC patients. Increasing evidence supports that autophagy was related to drug resistance at present. However, the role and the mechanism of autophagy to the treatment of TNBC remain unknown. In the current study, we investigated the effect of autophagy inhibitor to gefitinib (Ge) in TNBC cells in vitro and in nude mice vivo. Our study demonstrated that inhibition of autophagy by 3-Methyladenine or bafilomycin A1 improved Ge's sensitivity to MDA-MB-231 and MDA-MB-468 cells, as evidence from stronger inhibition of cell vitality and colony formation, higher level of G0/G1 arrest and DNA damage, and these effects were verified in nude mice vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28531217/store-operated-ca2-entry-supports-contractile-function-in-hearts-of-hibernators
#11
Olga V Nakipova, Alexey S Averin, Edward V Evdokimovskii, Oleg Yu Pimenov, Leonid Kosarski, Dmitriy Ignat'ev, Andrey Anufriev, Yuri M Kokoz, Santiago Reyes, Andre Terzic, Alexey E Alekseev
Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase (SERCA)...
2017: PloS One
https://www.readbyqxmd.com/read/28531207/benzo-a-pyrene-activates-interleukin-6-induction-and-suppresses-nitric-oxide-induced-apoptosis-in-rat-vascular-smooth-muscle-cells
#12
Huei-Ping Tzeng, Kuo-Cheng Lan, Ting-Hua Yang, Min-Ni Chung, Shing Hwa Liu
Benzo[a]pyrene, a ubiquitous environmental pollutant, has been suggested to be capable of initiating and/or accelerating atherosclerosis. Accumulation of vascular smooth muscle cells (VSMCs) in vessel intima is a hallmark of atherosclerosis. Nitric oxide (NO) can suppress VSMCs proliferation and induce VSMCs apoptosis. NO plays a compensatory role in the vascular lesions to reduce proliferation and/or accelerate apoptosis of VSMCs. The aim of this study was to investigate whether benzo[a]pyrene can affect VSMCs growth and apoptosis induced by NO...
2017: PloS One
https://www.readbyqxmd.com/read/28531199/mir-145-mediates-zebrafish-hepatic-outgrowth-through-progranulin-a-signaling
#13
Ya-Wen Li, Keng-Yu Chiang, Yen-Hsing Li, Sung-Yu Wu, Wangta Liu, Chia-Ray Lin, Jen-Leih Wu
MicroRNAs (miRs) are mRNA-regulatory molecules that fine-tune gene expression and modulate both processes of development and tumorigenesis. Our previous studies identified progranulin A (GrnA) as a growth factor which induces zebrafish hepatic outgrowth through MET signaling. We also found that miR-145 is one of potential fine-tuning regulators of GrnA involved in embryonic hepatic outgrowth. The low level of miR-145 seen in hepatocarinogenesis has been shown to promote pathological liver growth. However, little is known about the regulatory mechanism of miR-145 in embryonic liver development...
2017: PloS One
https://www.readbyqxmd.com/read/28531161/development-of-optimized-inhibitor-rnas-allowing-multisite-targeting-of-the-hcv-genome
#14
Cristina Romero-López, Thomas Lahlali, Beatriz Berzal-Herranz, Alfredo Berzal-Herranz
Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs...
May 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28531143/a-4-phenoxyphenol-derivative-exerts-inhibitory-effects-on-human-hepatocellular-carcinoma-cells-through-regulating-autophagy-and-apoptosis-accompanied-by-downregulating-%C3%AE-tubulin-expression
#15
Wen-Tsan Chang, Wangta Liu, Yi-Han Chiu, Bing-Hung Chen, Shih-Chang Chuang, Yen-Chun Chen, Yun-Tzh Hsu, Mei-Jei Lu, Shean-Jaw Chiou, Chon-Kit Chou, Chien-Chih Chiu
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines...
May 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28531105/high-mobility-group-box-1-disrupts-metabolic-function-with-cigarette-smoke-exposure-in-a-ceramide-dependent-manner
#16
Oliver J Taylor, Mikayla O Thatcher, Sheryl T Carr, Jonathan L Gibbs, Annie M Trumbull, Mitchell E Harrison, Duane R Winden, Mackenzie J Pearson, Trevor S Tippetts, William L Holland, Paul R Reynolds, Benjamin T Bikman
We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1), which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28530791/farnesyltransferase-mediated-delivery-of-a-covalent-inhibitor-overcomes-alternative-prenylation-to-mislocalize-k-ras
#17
Christopher J Novotny, Gregory L Hamilton, Frank McCormick, Kevan Shokat
Mutationally activated Ras is one of the most common oncogenic drivers found across all malignancies, and its selective inhibition has long been a goal in both pharma and academia. One of the oldest and most validated methods to inhibit overactive Ras signaling is by interfering with its post-translational processing and subsequent cellular localization. Previous attempts to target Ras processing led to the development of farnesyltransferase inhibitors, which can inhibit H-Ras localization but not K-Ras due to its ability to bypass farnesyltransterase inhibition though alternative prenylation by geranylgeranyltransferase...
May 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28530706/akt-is-indispensable-for-coordinating-par-4-jnk-cross-talk-in-p21-downmodulation-during-er-stress
#18
R U Rasool, D Nayak, S Chakraborty, M M Faheem, B Rah, P Mahajan, V Gopinath, A Katoch, Z Iqra, S K Yousuf, D Mukherjee, L D Kumar, A Nargotra, A Goswami
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#19
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28530127/an-oncolytic-adenovirus-expressing-snord44-and-gas5-exhibits-anti-tumor-effect-in-colorectal-cancer-cells
#20
Sujing Yuan, Yu Wu, Yigang Wang, Jianhua Chen, Liang Chu
SNORD44 is a C/D box small nucleolar RNA, and low expresses in breast cancer and head and neck squamous cell carcinoma tissues. Its host gene is growth arrest specific transcript 5 (GAS5), which is a long noncoding RNA. GAS5 is down-regulated in colorectal cancer (CRC), and overexpression of GAS5 suppresses cell proliferation. However, the function of SNORD44 in CRC remains largely unknown, and the application of SNORD44 combined with GAS5 in CRC treatment has not been reported. In this study, the expression levels of SNORD44 and GAS5 were measured in CRC tissues by qRT-PCR...
May 20, 2017: Human Gene Therapy
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