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https://www.readbyqxmd.com/read/29783282/sustained-conduction-of-vasomotor-responses-in-rat-mesenteric-arteries-in-a-two-compartment-in-vitro-setup
#1
Teresa Palao, Angela van Weert, Anne de Leeuw, Judith de Vos, Erik N T P Bakker, Ed van Bavel
AIM: Conduction of vasomotor responses may contribute to long-term regulation of resistance artery function and structure. Most previous studies have addressed conduction of vasoactivity only during very brief stimulations. We developed a novel setup that allows the local pharmacological stimulation of arteries in vitro for extended periods of time, and studied the conduction of vasomotor responses in rat mesenteric arteries under those conditions. METHODS: The new in vitro set up was based on the pressure myograph...
May 21, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#2
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29783120/canine-mesenchymal-stem-cells-treated-with-tnf-%C3%AE-and-ifn-%C3%AE-enhance-anti-inflammatory-effects-through-the-cox-2-pge-2-pathway
#3
Hye-Mi Yang, Woo-Jin Song, Qiang Li, Su-Yeon Kim, Hyeon-Jin Kim, Min-Ok Ryu, Jin-Ok Ahn, Hwa-Young Youn
Mesenchymal stem cells (MSCs) have been used in studies on treatment of various diseases, and their application to immune-mediated diseases has garnered interest. Various methods for enhancing the immunomodulation effect of human MSCs have been used; however, similar approaches for canine MSCs are relatively unexplored. Accordingly, we evaluated immunomodulatory effects and mechanisms in canine MSCs treated with TNF-α and IFN-γ. Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were incubated with the conditioned media (CM) from canine MSCs for 48 h...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29783099/leveraging-the-cruzain-s3-subsite-to-increase-affinity-for-reversible-covalent-inhibitors
#4
Lorenzo Cianni, Geraldo Sartori, Fabiana Rosini, Daniela De Vita, Gabriel Pires, Bianca Rebelo Lopes, Andrei Leitão, Antonio C B Burtoloso, Carlos A Montanari
Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiological agent of Chagas disease. Reversible covalent cruzain inhibitors can block the steps of cell differentiation in the parasite and kill the organism. To this end, the description of how inhibitors modified at the P2/P3 positions lead to analogs with greater cruzain affinity to the S2/S3 subsites is of fundamental importance. Albeit many efforts are being employed in the characterization of the interaction processes with S2 subsite, little is known about the cruzain S3 subsite...
April 26, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29783098/design-and-synthesis-of-aminocoumarin-derivatives-as-dpp-iv-inhibitors-and-anticancer-agents
#5
Rina Soni, Shubhangi S Soman
DPP-IV "a moonlighting protein" has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay...
May 17, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29782989/nadph-oxidase-2-deletion-enhances-neurogenesis-following-traumatic-brain-injury
#6
Jing Wang, Merry W Ma, Krishnan M Dhandapani, Darrell W Brann
The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions...
May 18, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29782975/roles-of-germline-jak2-activation-mutation-jak2-v625f-in-the-pathology-of-myeloproliferative-neoplasms
#7
Qing-Yun Wu, Meng-Meng Ma, Lin Fu, Yuan-Yuan Zhu, Yang Liu, Jiang Cao, Ping Zhou, Zhen-Yu Li, Ling-Yu Zeng, Feng Li, Xiao-Yun Wang, Kai-Lin Xu
Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations play key roles in the pathology of myeloproliferative neoplasms (MPNs). Recently, germline JAK2 mutations are also associated with triple-negative MPNs. A novel germline mutation JAK2 V625F is reported to be involved in a subset of MPNs patients. However, the pathogenesis of this mutation caused MPN is still unclear. In this study, the homology models of JAK2 V625F showed that the newly formed interaction between F625 and Y613 disrupted the JAK2 JH1-JH2 domain interactions was responsible for its activation, when F625 and Y613 interaction was disrupted, its activity significantly decreased...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#8
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29782889/development-of-robust-genotype-1a-hepatitis-c-replicons-harboring-adaptive-mutations-for-facilitating-the-antiviral-drug-discovery-and-study-of-virus-replication
#9
Hui-Mei Lin, Pei-Shan Wu, Han-Shu Hu, Wan-Chun Chang, Ren-Huang Wu, Jia-Ni Tian, Jyh-Haur Chern, Andrew Yueh
The hepatitis C virus (HCV) subgenomic replicon is a valuable tool for studying virus replication and HCV drug development. Despite the fact that HCV genotype 1a (HCV1a) is the most prevalent genotype in the United States, few HCV1a reporter replicon constructs have been reported, and their replication capacities are not as efficient as those of HCV1b or 2a, especially in transient expression. In this study, we selected efficient HCV1a replicons and characterized the novel adaptive mutations derived from stable HCV1a (strain H77) replicon cells after G418 selection...
May 18, 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29782855/role-of-statins-and-mevalonate-pathway-on-impaired-hdac2-activity-induced-by-oxidative-stress-in-human-airway-epithelial-cells
#10
Maria Gabriella Matera, Luigino Calzetta, Giulia Gritti, Laura Gallo, Brunella Perfetto, Giovanna Donnarumma, Mario Cazzola, Paola Rogliani, Maria Donniacuo, Barbara Rinaldi
In patients with chronic obstructive pulmonary disease (COPD) the inflammatory response is often steroid-resistant, likely since oxidative stress and cigarette smoking impair histone deacetylase 2 (HDAC2) activity. Since it has been demonstrated that statins may restore the HDAC2 activity in cultured human endothelial cells, the aim of this study was to investigate the effects of statins in reversing the steroid-resistance induced by oxidative stress. We evaluated the effects of simvastatin and dexamethasone on HDAC2 expression and activity, and the role of mevalonate and Rho/ROCK pathways in A549 cells, a human lung type II epithelial cell line stressed with H2 O2 ...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782840/docosahexaenoic-acid-induces-ppar%C3%AE-dependent-preadipocytes-apoptosis-in-grass-carp-ctenopharyngodon-idella
#11
Ai Jin, Xiao-Chen Shi, Yangyang Liu, Jian Sun, Hong Ji
Our previous study showed that docosahexaenoic acid (DHA) plays an important role in decreasing lipid accumulation by inducing apoptosis of the adipocytes in grass carp. However, the mechanism involved remains unclear. DHA has been reported as the natural ligand of PPARγ. The present study aimed to assess whether PPARγ mediates the pro-apoptotic effects by DHA. Adipocytes of grass carp were cultured until 2 days post-confluence and were treated with DHA at various concentrations-0, 25, 50, 100, 200, and 400 μmol/L for 24 h and at 200 μmol/L for various time periods (0, 12, 24, and 48 h, respectively)...
May 18, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29782572/patient-related-outcomes-with-the-use-of-checkpoint-inhibitors-for-the-treatment-of-metastatic-non-small-cell-lung-cancer
#12
EDITORIAL
Jyoti Malhotra, Salma K Jabbour
No abstract text is available yet for this article.
April 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29782563/repurposing-established-cyclic-adenosine-monophosphate-reducing-agents-for-the-prevention-and-therapy-of-epidermal-growth-factor-receptor-inhibitor-resistance-in-non-small-cell-lung-cancer
#13
EDITORIAL
https://www.readbyqxmd.com/read/29782545/rosmarinic-acid-is-a-novel-inhibitor-for-hepatitis-b-virus-replication-targeting-viral-epsilon-rna-polymerase-interaction
#14
Yuta Tsukamoto, Sotaro Ikeda, Koji Uwai, Riho Taguchi, Kazuaki Chayama, Takemasa Sakaguchi, Ryo Narita, Wan-Ling Yao, Fumihiko Takeuchi, Yukie Otakaki, Koichi Watashi, Takaji Wakita, Hiroki Kato, Takashi Fujita
Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (ε) sequence of HBV pregenomic RNA and viral polymerase (Pol) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of ε-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited ε-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent...
2018: PloS One
https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#15
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29782303/clindamycin-induced-maculopapular-exanthema-with-preferential-involvement-of-striae-distensae-a-koebner-phenomenon
#16
Benigno Monteagudo, Miguel Cabanillas, Pilar Iriarte, Aquilina Ramírez-Santos, Elvira León-Muinos, Daniel González-Vilas, Óscar Suárez-Amor
Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier...
April 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29782192/the-histone-deacetylase-inhibitor-ci994-improves-nuclear-reprogramming-and-in-vitro-developmental-potential-of-cloned-pig-embryos
#17
Long Jin, Qing Guo, Guang-Lei Zhang, Xiao-Xu Xing, Mei-Fu Xuan, Qi-Rong Luo, Zhao-Bo Luo, Jun-Xia Wang, Xi-Jun Yin, Jin-Dan Kang
Epigenetic reprogramming and somatic cell nuclear transfer (SCNT) cloning efficiency were recently enhanced using histone deacetylase inhibitors (HDACis). In this study, we investigated the time effect of CI994, an HDACi, on the blastocyst formation rate, acetylation levels of H3K9 and H4K12, DNA methylation levels of anti-5-methylcytosine (5mC), and some mRNA expression of pluripotency-related genes in pig SCNT embryos. Treatment with 10 μM CI994 for 24 hours significantly improved the blastocyst formation rate of SCNT embryos in comparison with the untreated group (p < 0...
May 21, 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29782188/an-evaluation-of-nivolumab-for-the-treatment-of-metastatic-renal-cell-carcinoma
#18
Kevin Zarrabi, Shenhong Wu
The treatment paradigm for metastatic renal cell carcinoma (mRCC) has undergone a revolution with the rapid market approval of multiple agents over a three-year period. The immunogenicity of RCC provided the biological rationale to assess the clinical efficacy of nivolumab, an immune checkpoint inhibitor. Nivolumab is approved for second-line treatment after failure of angiogenesis targeted therapy and in combination therapy with ipilimumab for previously untreated intermediate or poor-risk advanced renal cell carcinoma...
May 21, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29782174/expression-of-concentrative-nucleoside-transporters-slc28a-in-the-human-placenta-effects-of-gestation-age-and-prototype-differentiation-affecting-agents
#19
Lucie Jiraskova, Lukas Cerveny, Sara Karbanova, Zuzana Ptackova, Frantisek Staud
Equilibrative ( SLC29A) and concentrative ( SLC28A) nucleoside transporters contribute to proper placental development and mediate uptake of nucleosides/nucleoside-derived drugs. We analyzed placental expression of SLC28A mRNA during gestation. Moreover, we studied in choriocarcinoma-derived BeWo cells whether SLC29A and SLC28A mRNA levels can be modulated by activity of adenylyl cyclase, retinoic acid receptor activation, CpG islands methylation, or histone acetylation, using forskolin, all- trans-retinoic acid, and 5-azacytidine, and sodium butyrate/sodium valproate, respectively...
May 21, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29782069/efficacy-and-safety-of-nivolumab-in-non-small-cell-lung-cancer-with-preexisting-interstitial-lung-disease
#20
Osamu Kanai, Young Hak Kim, Yoshiki Demura, Makiko Kanai, Tsuyoshi Ito, Kohei Fujita, Hironori Yoshida, Masaya Akai, Tadashi Mio, Toyohiro Hirai
BACKGROUND: The risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non-small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI-related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD. METHODS: We retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy...
May 21, 2018: Thoracic Cancer
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